Textbook of Female Urology and Urogynecology - Clinical Perspectives, 5e (Jul 28, 2023)_(036770014X)_(CRC Press) 9780367700140, 9780367700157, 9781003144236, 9780367700164, 9780367700171, 9781003144243

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Textbook of Female Urology and Urogynecology Volume 1: Clinical Perspectives EDITORS - IN - CHIEF

Linda Cardozo and David Staskin CRC Press

Textbook of Female Urology and Urogynecology Featuring contributions by an international team of the world’s experts in urology and urogynecology, this fifth edition reinforces its status as the classic comprehensive resource on female urology and urogynecology and an essential clinical reference in the field, with new chapters throughout.

Volume 1 (Clinical Perspectives) – available separately or as part of the set – covers background issues; role of patient-reported outcome measures and health economics; structure and function of the lower urinary tract and anorectal tract in women; diagnostic evaluation of incontinence and urogenital prolapse; conservative and minimally invasive therapies; and associated disorders.

Volume 2 (Surgical Perspectives) – available separately or as part of the set – covers surgery for urinary incontinence; surgery for urogenital prolapse; laparoscopy and robotics; complex problems; and appendix on standardized terminology for incontinence and pelvic floor dysfunction.

Volume One

Textbook of Female Urology and Urogynecology Clinical Perspectives Fifth Edition Edited by

Linda Cardozo O.B.E., M.D., F.R.C.O.G

Professor of Urogynaecology, King’s College Hospital, London, UK

David Staskin M.D.

Director, Male and Female Pelvic Surgery, Division of Urology, Steward Health – St. Elizabeth’s Medical Center and Associate Professor of Urology, Boston University School of Medicine, Boston, Massachusetts, USA Section Editors

Lori A. Birder Ph.D. Rufus Cartwright M.D., M.R.C.O.G. Nikki Cotterill Ph.D. Roger R. Dmochowski M.D., M.M.H.C., F.A.C.S. Ian Milsom M.D., Ph.D. Victor W. Nitti M.D. Christian Phillips M.D. Dudley Robinson M.B.B.S., M.D., F.R.C.O.G. Eric S. Rovner M.D. Peter K. Sand M.D. Philip Toozs-Hobson M.B.B.S., A.S.M., F.R.C.O.G, M.D.

Fifth edition published 2023 by CRC Press 6000 Broken Sound Parkway NW, Suite 300, Boca Raton, FL 33487-2742 and by CRC Press 4 Park Square, Milton Park, Abingdon, Oxon, OX14 4RN CRC Press is an imprint of Taylor & Francis Group, LLC © 2023 selection and editorial matter, Linda Cardozo and David Staskin individual chapters, the contributors First edition published by CRC Press 2001 Fifth edition published by CRC Press 2023 The right of Linda Cardozo and David Staskin to be identified as the authors of the editorial material, and of the authors for their individual chapters, has been asserted in accordance with sections 77 and 78 of the Copyright, Designs and Patents Act 1988. This book contains information obtained from authentic and highly regarded sources. While all reasonable efforts have been made to publish reliable data and information, neither the author[s] nor the publisher can accept any legal responsibility or liability for any errors or omissions that may be made. The publishers wish to make clear that any views or opinions expressed in this book by individual editors, authors or contributors are personal to them and do not necessarily reflect the views/opinions of the publishers. The information or guidance contained in this book is intended for use by medical, scientific or health-care professionals and is provided strictly as a supplement to the medical or other professional’s own judgement, their knowledge of the patient’s medical history, relevant manufacturer’s instructions and the appropriate best practice guidelines. Because of the rapid advances in medical science, any information or advice on dosages, procedures or diagnoses should be independently verified. The reader is strongly urged to consult the relevant national drug formulary and the drug companies’ and device or material manufacturers’ printed instructions, and their websites, before administering or utilizing any of the drugs, devices or materials mentioned in this book. This book does not indicate whether a particular treatment is appropriate or suitable for a particular individual. Ultimately it is the sole responsibility of the medical professional to make his or her own professional judgements, so as to advise and treat patients appropriately. The authors and publishers have also attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, access www.copyright.com or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. For works that are not available on CCC please contact [email protected] Trademark notice: Product or corporate names may be trademarks or registered trademarks and are used only for identification and explanation without intent to infringe. Library of Congress Cataloging‑in‑Publication Data Names: Cardozo, Linda, editor. | Staskin, David, editor. Title: Textbook of female urology and urogynecology. Clinical perspectives / edited by Linda Cardozo, David Staskin. Other titles: Clinical perspectives | Textbook of female urology and urogynecology. Description: Fifth edition. | Boca Raton : CRC Press, 2022. | Replacement in part of Textbook of female urology and urogynecology / editors in chief, Linda Cardozo and David R. Staskin. Fourth edition. 2017. | Includes bibliographical references and index. Identifiers: LCCN 2022025410 (print) | LCCN 2022025411 (ebook) | ISBN 9780367700140 (v. 1 ; hardback) | ISBN 9780367700157 (v. 1 ; paperback) | ISBN 9781003144236 (v. 1 ; ebook) Subjects: MESH: Urinary Incontinence--diagnosis | Urinary Incontinence--therapy | Pelvic Organ Prolapse--diagnosis | Pelvic Organ Prolapse--therapy | Urogenital System--physiology Classification: LCC RC921.I5 (print) | LCC RC921.I5 (ebook) | NLM WJ 146 | DDC 616.6/2--dc23/eng/20220817 LC record available at https://lccn.loc.gov/2022025410 LC ebook record available at https://lccn.loc.gov/2022025411 ISBN: 9780367700140 (hbk1) ISBN: 9780367700157 (pbk1) ISBN: 9781003144236 (ebk1) ISBN: 9780367700164 (hbk2) ISBN: 9780367700171 (pbk2) ISBN: 9781003144243 (ebk2) DOI: 10.1201/9781003144236 Typeset in Warnock Pro by KnowledgeWorks Global Ltd. Access the companion website: https://resourcecentre.routledge.com/books/9780367700140

CONTENTS Preface.....................................................................................................................................................................................................................................ix Editors-in-Chief..................................................................................................................................................................................................................... x Section Editors......................................................................................................................................................................................................................xi Current Contributors........................................................................................................................................................................................................ xii

VOLUME ONE: CLINICAL PERSPECTIVES SECTION I: BACKGROUND ISSUES

Section Editor: Ian Milsom

1 History of Urogynecology and Female Urology.....................................................................................................................................................2 Jane A. Schulz and Harold P. Drutz 2 Tackling the Stigma of Incontinence.....................................................................................................................................................................10 Angie Rantell 3 The Epidemiology of Urinary Incontinence, Other Lower Urinary Tract Symptoms, and Pelvic Organ Prolapse..............................17 Maria Gyhagen and Ian Milsom 4 Natural History and Prevention of Urinary Incontinence and Urogenital Prolapse...................................................................................26 Ifeoma Offiah, Chendrimada K. Madhu, Ruben Trochez, and Robert M. Freeman 5 A Short History of Surgery for Stress Urinary Incontinence............................................................................................................................43 Dudley Robinson and Linda Cardozo 6 The History of Surgery for Pelvic Organ Prolapse...............................................................................................................................................47 Sören Lange and Heinz Kölbl 7 Medical Error and Patient Safety in Surgery........................................................................................................................................................55 Roxane Gardner 8 Medicolegal Issues in Urogynaecology..................................................................................................................................................................72 Swati Jha

SECTION II: ROLE OF PATIENT REPORTED OUTCOME MEASURES AND HEALTH ECONOMICS

Section Editor: Nikki Cotterill

9 Patient-Reported Outcomes: From Development to Utilization.....................................................................................................................80 Karin Coyne, Chris Sexton, and Alan Uren 10 Patient-Reported Outcome Questionnaires to Assess Health-Related Quality of Life and Symptom Impact.....................................89 Victoria Kershaw, Thomas Gray, Swati Jha, and Stephen Radley 11 Patient-Reported Outcome Questionnaires to Screen and Measure Satisfaction, Expectations, and Goal Achievement..............................................................................................................................................................................................99 Zoe S. Kopp, Christopher J. Evans, and Nathan A. Johnson 12 Questionnaires to Assess Sexual Function.........................................................................................................................................................111 Claudine Domoney, Tara Symonds, and Raman Basra 13 Questionnaires to Assess Bowel Function..........................................................................................................................................................119 Alison Hainsworth and Andrew Williams 14 International Consultation on Incontinence Modular Questionnaire.........................................................................................................129 Alan Uren, Nikki Cotterill, and Paul Abrams 15 Electronic Personal Assessment Questionnaire (EPAQ) for Pelvic Floor....................................................................................................135 Thomas Gray, Victoria Kershaw, and Stephen Radley 16 Questionnaires to Assess Pelvic Organ Prolapse..............................................................................................................................................145 Alka A. Bhide and Alex Digesu 17 Economic Aspects of Urinary Incontinence.......................................................................................................................................................152 Marie-Aimée Perrouin Verbe v

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Contents

SECTION III: STRUCTURE AND FUNCTION OF THE LOWER URINARY TRACT AND ANORECTAL TRACT IN WOMEN

Section Editor: Lori A. Birder

18 Anatomy......................................................................................................................................................................................................................164 John O.L. DeLancey 19 Embryology of the Female Urogenital System and Clinical Applications...................................................................................................179 Dana Weiss and Stephen A. Zderic 20 Tissue Engineering and Regenerative Medicine for the Female Genitourinary System..........................................................................197 Sara Anis and Anthony Atala 21 Physiology of Micturition...................................................................................................................................................................................... 207 Naoki Yoshimura, Pradeep Tyagi, and Michael B. Chancellor 22 Pharmacology of the Bladder and Emerging Treatments................................................................................................................................218 Karl-Erik Andersson 23 Classification of Lower Urinary Tract Dysfunction in the Female Patient................................................................................................ 238 David Staskin, Márcio A. Averbeck, and Alan J. Wein 24 Research Horizons: Translational and in Development..................................................................................................................................247 Christopher Fry and Lori A. Birder

SECTION IV: DIAGNOSTIC EVALUATION OF INCONTINENCE AND UROGENITAL PROLAPSE

Section Editor: Dudley Robinson

25 History and Examination....................................................................................................................................................................................... 256 Vik Khullar and Visha Tailor 26 Bladder Diary and Symptom Scores.................................................................................................................................................................... 266 Nikki Cotterill and Alan Uren 27 Pad Tests.....................................................................................................................................................................................................................272 Marie-Andrée Harvey 28 Basic Urodynamic Tests: Uroflowmetry............................................................................................................................................................. 280 Matthias Oelke 29 Basic Urodynamic Tests: Filling and Voiding Cystometry............................................................................................................................. 288 Hashim Hashim and Andrew Gammie 30 Tests of Urethral Function......................................................................................................................................................................................298 Niels Klarskov 31 Videourodynamics.................................................................................................................................................................................................. 306 Ilias Giarenis 32 Special Urodynamic Tests: Ambulatory Urodynamics....................................................................................................................................313 Kevin L.J. Rademakers, Desiree M.J. Vrijens, and Gommert A. van Koeveringe 33 Basic Neurological Evaluation and Referral........................................................................................................................................................325 Melita Rotar, Jalesh N. Panicker, and David B. Vodušek 34 Imaging of the Upper and Lower Urinary Tract: Radiology.......................................................................................................................... 342 Andrea Tubaro, Riccardo Lombardo, Antonio Pastore, and Antonio Carbone 35 Ultrasound in Urogynaecology: Lower Genitourinary Tract.........................................................................................................................352 Kamil Svabik 36 Magnetic Resonance Imaging in Urogynecology..............................................................................................................................................362 Elisabetta Costantini, Francesco Trama, and Ester Illiano 37 Cystoscopy and Vesicoscopy..................................................................................................................................................................................373 Paul A. Moran, Jennifer Cole, and Tamsin Greenwell 38 Urinalysis and Urine Culture.................................................................................................................................................................................387 Rajvinder Khasriya, Kiren Gill, and Alexandros Fanourgiakis

Contents

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39 The Urinary Microbiome........................................................................................................................................................................................394 Visha Tailor, Alka Bhide, and Vik Khullar

SECTION V: CONSERVATIVE AND MINIMALLY INVASIVE THERAPIES

Section Editor: Eric S. Rovner

40 The Role of the Continence Nurse....................................................................................................................................................................... 400 Angie Rantell 41 Behavioral Therapies and Management of Urinary Incontinence in Women............................................................................................410 Kathryn L. Burgio 42 Physiotherapy for Urinary Incontinence............................................................................................................................................................ 420 Enrico Finazzi-Agrò, Donatella Giraudo, Simone Pletto, and Gianfranco Lamberti 43 Pessaries and Devices: Nonsurgical Treatment of Pelvic Organ Prolapse and Stress Urinary Incontinence.............................................................................................................................................................................................. 433 Joseph T. Kowalski and Catherine S. Bradley 44 Catheters, Pads, and Pants..................................................................................................................................................................................... 441 Kevin Cwach and Eric S. Rovner 45 Drug Treatment of Lower Urinary Tract Dysfunction in Women............................................................................................................... 457 Ariana L. Smith and Alan J. Wein 46 Botulinum Toxin Treatment of Neurogenic Detrusor Overactivity and Overactive Bladder............................................................... 490 David Ginsberg, Rita Jen, and Unwanaobong Nseyo 47 Electrical Stimulation and Magnetic Stimulation.............................................................................................................................................501 Bary Berghmans 48 Peripheral Neuromodulation................................................................................................................................................................................ 509 John Heesakkers and Frank Martens 49 Sacral Neuromodulation in the Treatment of Female Overactive Bladder Syndrome and Nonobstructive Urinary Retention.....................................................................................................................................................................................................517 Dora K. Jericevic, Benjamin Brucker, and Benoit Peyronnet 50 Nonsurgical Transurethral Radiofrequency Therapy, Laser and Other Interventions for the Treatment of Stress Urinary Incontinence..............................................................................................................................................................................525 Elizabeth A. Rourke and Roger R. Dmochowski 51 Injectable Bulking Agents in the Treatment of Female Stress Urinary Incontinence..............................................................................531 Elisabeth M. Sebesta, Brian J. Linder, Philip Wanzek, Deborah J. Lightner, and Roger R. Dmochowski

SECTION VI: ASSOCIATED DISORDERS

Section Editor: Philip Toozs-Hobson

52 The Overactive Bladder.......................................................................................................................................................................................... 542 Pedro Abreu Mendes and Francisco Cruz 53 Neurological Disorders............................................................................................................................................................................................551 Claire Hentzen and Jalesh N. Panicker 54 Nonneurogenic Voiding Dysfunction and Urinary Retention...................................................................................................................... 567 Felicity Reeves and Jeremy Ockrim 55 Pathophysiology of Chronic Pelvic Pain..............................................................................................................................................................578 Athanasios E. Dellis, Athanasios G. Papatsoris, and Lazaros Tzelves 56 Bladder Pain Syndrome/Interstitial Cystitis...................................................................................................................................................... 585 Ilias Liapis and Matthew Parsons 57 The Urinary and Vaginal Microbiomes...............................................................................................................................................................598 Niels Frimodt-Møller, Karen Leth Nielsen, and Frederik Boetius Hertz 58 Bacterial Cystitis in Urogynaecology: An Update............................................................................................................................................ 609 Kate H. Moore, Zhuoran Chen, Nevine I.D. te West

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Contents

59 Vaginitis......................................................................................................................................................................................................................628 Jack D. Sobel 60 The Impact of Pregnancy and Childbirth on the Pelvic Floor........................................................................................................................638 Martino Maria Zacchè and Philip Toozs-Hobson 61 Problems Associated with Sexual Activity........................................................................................................................................................ 650 Anna Padoa, Tal Fligelman, and Roni Tomashev 62 Menopause................................................................................................................................................................................................................ 665 Elizabeth Stephenson and Timothy C. Hillard 63 Sports and Fitness Activities................................................................................................................................................................................. 680 Kari BØ 64 Anal Incontinence................................................................................................................................................................................................... 685 Alison Hainsworth and Andrew Williams 65 Constipation...............................................................................................................................................................................................................698 Yvette Perston, Anil Bagul, Sarah Addison, and Simon Radley 66 Female Sexual Dysfunction....................................................................................................................................................................................713 Maria Uloko and Irwin Goldstein 67 Multidisciplinary Clinics: Urogynaecology, Colorectal, and Urology......................................................................................................... 730 Hayser Medina Lucena, Ivilina Pandeva, and Ashish Pradhan Index........................................................................................................................................................................................................................................I1

PREFACE … we would like to thank our patients, who place their trust in us each and every day. We hope that this textbook contributes to the quality of their care and to the ability of those who will care for them in the future. (from the Preface of the first edition, 2001) The success of the first four editions of the Textbook of Female Urology and Urogynecology (2001, 2006, 2010, 2017) and our desire to continue to provide a timely and relevant reference textbook in an evolving field stimulated us to produce another contribution, this fifth edition. We hope, as we did with all previous editions, that we have continued to fulfil our mission to present a book that serves as a foundation for established ideas, a review of the current state of the art and a platform for introducing the dynamic concepts of the future. Over 20 years, the textbook has evolved from a single volume of seven sections and approximately 1000 pages – to a two volume, ten section, 1300-page version. We are grateful to those who have served as section editors – introduced in the second edition. These section editors are an invaluable part of the process. We

specifically selected the section editors and authors to represent an international approach to the numerous female urogenital health disorders to produce a good balance of knowledge, and expertise, despite the polarization of ideas that can occur as a natural product of geography, training, and interests. We recognize that there is a significant overlap between female urology and urogynecology. However, there are also important differences, and we hope that these are reflected by having a balance between the healthcare professionals who have edited and authored the chapters. Please allow us to take pride in the fact that many of the authors who contributed as co-authors in the early editions are now distinguished clinicians, department chairs, or editors of their own textbooks. We are humbled by their efforts. Similarly, we are indebted to the publishers, who have expertly facilitated the organization and production of all five editions. Thank you for choosing this textbook for your education and reference, and for your practice and library. Linda Cardozo David Staskin

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EDITORS-IN-CHIEF Linda Cardozo O.B.E., M.D., F.R.C.O.G., is Professor of Urogynaecology, King’s College Hospital, London, U.K.

x

David Staskin M.D., is Director of the Male and Female Pelvic Surgery, Division of Urology, Steward Health – St. Elizabeth’s Medical Center, and Associate Professor of Urology, Tufts University School of Medicine, Boston, Massachusetts, U.S.A.

SECTION EDITORS Lori A. Birder Ph.D. is with Departments of Medicine and Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A. Rufus Cartwright M.D., M.R.C.O.G., is with the Faculty of Medicine, School of Public Health, Imperial College London, London, U.K. Nikki Cotterill Ph.D., is with the Faculty of Health and Applied Sciences, University of the West of England, Bristol, U.K. Roger R. Dmochowski M.D., M.M.H.C., F.A.C.S., is with the Departments of Urology and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee, U.S.A. Ian Milsom M.D., Ph.D., is with the Department of Obstetrics and Gynecology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. Victor W. Nitti M.D., is with the Division of Female Pelvic Medicine and Reconstructive Surgery, Departments of Urology and Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A.

Christian Phillips M.D., is with the Department of Obstetrics and Gynaecology, Hampshire Hospitals NHS Foundation Trust, Basingstoke, and Health and Wellbeing Research Group, University of Winchester, Winchester, U.K. Dudley Robinson M.B.B.S., M.D., F.R.C.O.G., is with the Department of Urogynaecology, King’s College Hospital, London, U.K. Eric S. Rovner M.D., is with the Department of Urology, Medical University of South Carolina, Charleston, South Carolina, U.S.A. Peter K. Sand M.D., is with the Obstetrics and Gynecology, Pritzker School of Medicine, University of Chicago, and Evanston Continence Center, NorthShore University Health System, Chicago, Illinois, U.S.A. Philip Toozs-Hobson M.B.B.S., A.S.M., F.R.C.O.G, M.D., is with the Urogynaecology and Pelvic Floor Medicine, Birmingham Women’s N.H.S. Foundation Trust, University of Birmingham, Birmingham, U.K.

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CURRENT CONTRIBUTORS Paul Abrams Bristol Urological Institute Southmead Hospital Bristol, U.K. Sarah Addison Surgery Queen Elizabeth Hospital Birmingham Birmingham, U.K. Karl-Erik Andersson Wake Forest Institute for Regenerative Medicine Wake Forest University School of Medicine Winston-Salem, North Carolina, U.S.A. and University of Lund Lund, Sweden Sara Anis Wake Forest Institute for Regenerative Medicine Wake Forest University School of Medicine Winston-Salem, North Carolina, U.S.A. Anthony Atala Wake Forest Institute for Regenerative Medicine Wake Forest University School of Medicine Winston-Salem, North Carolina, U.S.A. Márcio A. Averbeck Video-Urodynamics Unit Moinhos de Vento Hospital Porto Alegre, Brazil

Frederik Boetius Hertz Clinical Microbiology Rigshospitalet, Copenhagen, Denmark Kari Bø Sports Medicine Norwegian School of Sport Sciences Oslo, Norway Catherine S. Bradley Urogynecology and Reconstructive Pelvic Surgery Obstetrics and Gynecology Carver College of Medicine University of Iowa Health Care Iowa City, Iowa, U.S.A. Benjamin Brucker Urology New York University New York, New York, U.S.A. Kathryn L. Burgio Continence Program and Genitourinary Disorders Center University of Alabama at Birmingham Birmingham, Alabama, U.S.A and Gerontology and Geriatric Medicine Birmingham, U.K. Atlanta Geriatric Research Education, and Clinical Center (GRECC) Birmingham VA Medical Center Birmingham, Alabama, U.S.A.

Karin Coyne Patient-Centered Research Evidera Bethesda, Maryland, U.S.A. Francisco Cruz Urology Faculty of Medicine of Porto and Hospital de S. Joao i3S Instituto para Investigação e Inovação em Saúde Porto, Portugal Kevin Cwach Urology The Iowa Clinic West Des Moines, Iowa, U.S.A. John O.L. DeLancey Pelvic Floor Research Obstetrics and Gynecology University of Michigan Medical School Ann Arbor, Michigan, U.S.A. Athanasios E. Dellis Urology and Surgery National and Kapodistrian University of Athens Athens, Greece Alex Digesu Obstetrics and Gynaecology St. Mary’s Hospital Imperial College NHS Trust London, U.K.

Antonio Carbone Urology Ospedale di Latina Latina, Italy

Claudine Domoney Urogynaecology Chelsea & Westminster Hospital London, U.K.

Anil Bagul Surgery Queen Elizabeth Hospital Birmingham Birmingham, U.K.

Michael B. Chancellor Urology William Beaumont Hospital Royal Oak, Michigan, U.S.A.

Harold P. Drutz Urogynecology University of Toronto Toronto, Canada

Raman Basra Urogynaecology Chelsea and Westminster Hospital London, U.K.

Zhuoran Chen Pelvic Floor Unit, Urogynaecology St. George Hospital Sydney, Australia

Christopher J. Evans Endpoint Outcomes Boston, Massachusetts, U.S.A.

Bary Berghmans Pelvic Care Center Maastricht Maastricht University Medical Centre Maastricht, The Netherlands Alka A. Bhide Obstetrics and Gynaecology St. Mary’s Hospital Imperial College NHS Trust London, U.K. xii

Jennifer Cole Obstetrics and Gynaecology Warwick Hospital Warwick, U.K. Elisabetta Costantini Andrological and Urogynecological Clinic AOU Terni and Perugia and Department of Medicine and Surgery University of Perugia Perugia, Italy

Alexandros Fanourgiakis Urogynaecology Whittington Hospital London, U.K. Enrico Finazzi-Agrò Surgical Sciences University of Rome Tor Vergata and Urology Policlinico Tor Vergata University Hospital Rome, Italy

Current Contributors

xiii

Tal Fligelman Urogynecology and Pelvic Floor Service Assaf Harofe Medical Center Tsrifin and Sackler School of Medicine Tel Aviv University Tel Aviv, Israel

Irwin Goldstein San Diego Sexual Medicine Sexual Medicine Alvarado Hospital San Diego, California, U.S.A. and Surgery University of California at San Diego San Diego, California, U.S.A.

Robert M. Freeman Obstetrics and Gynaecology University Hospitals Plymouth NHS Trust Plymouth, U.K.

Thomas Gray Urogynaecology and Pelvic Reconstructive Surgery Norfolk and Norwich University Hospitals NHS Foundation Trust Norwich, U.K.

Niels Frimodt-Møller Clinical Microbiology Rigshospitalet Copenhagen. Denmark

Tamsin Greenwell Urology University College London London, U.K.

Christopher Fry School of Physiology Pharmacology and Neuroscience University of Bristol Bristol, U.K.

Maria Gyhagen Obstetrics and Gynaecology Sahlgrenska Academy at Gothenburg University Gothenburg, Sweden

Andrew Gammie Bristol Urological Institute Southmead Hospital Bristol, U.K.

Alison Hainsworth Surgery, Guys’ and St Thomas’ Hospital London, U.K.

Roxane Gardner Gynecology Boston Children’s Hospital Boston, Massachusetts, U.S.A. Ilias Giarenis Obstetrics and Gynaecology Norfolk and Norwich University Hospitals NHS Foundation Trust Norwich, U.K. Kiren Gill Urogynaecology Whittington Hospital London, U.K. David Ginsberg Urology Keck School of Medicine University of Southern California Los Angeles, California, U.S.A. Donatella Giraudo Urology San Raffaele Hospital Ville Turro Milan, Italy

Marie-Andrée Harvey Obstetrics and Gynaecology and Urology Queen’s University Kingston, Ontario, Canada Hashim Hashim Bristol Urological Institute Southmead Hospital Bristol, U.K. John Heesakkers Urology MUMC+ Maastricht Maastricht, The Netherlands Claire Hentzen Uro-Neurology The National Hospital for Neurology and Neurosurgery and Brain Repair and Rehabilitation UCL Queen Square Institute of Neurology Faculty of Brain Sciences University College London London, U.K. and GRC 01 GREEN Group of Clinical REsEarch in Neurourology Sorbonne University and Hôpital Tenon Paris, France

Timothy C. Hillard Urogynaecology, Obstetrics & Gynaecology University Hospitals Dorset Poole, U.K. Ester Illiano Andrological and Urogynecological Clinic Santa Maria Terni Hospital University of Perugia Terni, Italy Rita Jen Female Pelvic Medicine & Reconstructive Surgery Department of Urology Keck School of Medicine University of Southern California Los Angeles, California, U.S.A. Dora K. Jericevic Urology New York University New York, New York, U.S.A. Swati Jha Gynaecology and Urogynaecology Sheffield University and Sheffield Teaching Hospitals NHS Foundation Trust Sheffield, U.K. Nathan A. Johnson Endpoint Outcomes Long Beach, California, U.S.A. Victoria Kershaw Urogynaecology Sheffield Teaching Hospitals Sheffield, U.K. Rajvinder Khasriya Urogynaecology Whittington Hospital and University College London Hospital London, U.K. Vik Khullar Urogynaecology St Mary’s Hospital Imperial College London, U.K. Niels Klarskov Obstetrics and Gynecology Herlev and Gentofte Hospital Herlev and University of Copenhagen Copenhagen, Denmark

Current Contributors

xiv Heinz Kölbl Gynecology and Gynecologic Oncology Medizinische Universität Wien Vienna, Austria Zoe S. Kopp Endpoint Outcomes Boston, Massachusetts, U.S.A.

Frank Martens Urology Radboud UMC Nijmegen Nijmegen, The Netherlands Hayser Medina Lucena Urogynaecology Cambridge University Hospital NHS Foundation Trust Cambridge, U.K.

Joseph T. Kowalski Urogynecology and Reconstructive Pelvic Surgery, Obstetrics and Gynecology Carver College of Medicine University of Iowa Health Care Iowa City, Iowa, U.S.A.

Pedro Abreu Mendes Urology, Faculty of Medicine of Porto and Hospital de S. Joao i3S Instituto para Investigação e Inovação em Saúde Porto, Portugal

Gianfranco Lamberti Rehabilitative Medicine Fiorenzuola Hospital Piacenza, Italy

Kate H. Moore Urogynaecology Obstetrics and Gynaecology University of New South Wales Sydney, Australia

Sören Lange Urogynecology Medizinische Universität Wien Vienna, Austria Karen Leth Nielsen Clinical Microbiology Rigshospitalet Copenhagen, Denmark Ilias Liapis Birmingham Women’s and Children’s Hospital Birmingham, U.K. Deborah J. Lightner Urology Mayo Clinic Rochester, Minnesota, U.S.A. Brian J. Linder Urology Mayo Clinic Rochester, Minnesota, U.S.A. Riccardo Lombardo Urology Sant’Andrea Hospital Sapienza University Rome, Italy Chendrimada K. Madhu Department of Women’s Health Bristol Urological Institute and Southmead Hospital Bristol, U.K.

Paul A. Moran Gynaecology Worcestershire Acute Hospitals Worcester, U.K. Unwanaobong Nseyo Female Pelvic Medicine & Reconstructive Surgery, Department of Urology, Keck School of Medicine University of Southern California Los Angeles, California, U.S.A. Jeremy Ockrim Urology University College London Hospitals London, U.K. Matthias Oelke Urology Hannover Medical School, Hannover, and Urology, Paediatric Urology and Urological Oncology St. Antonius-Hospital Gronau, Germany Ifeoma Offiah University Hospital Plymouth NHS Trust Plymouth and Southmead Hospital Bristol, U.K.

Anna Padoa Urogynecology and Pelvic Floor Service Assaf Harofe Medical Center Tsrifin and Sackler School of Medicine Tel Aviv University Tel Aviv, Israel Ivilina Pandeva Gynaecology Cambridge University Hospital NHS Foundation Trust Cambridge, U.K. Jalesh N. Panicker Uro-Neurology The National Hospital for Neurology and Neurosurgery and UCL Queen Square Institute of Neurology London, U.K. Athanasios G. Papatsoris Urology National and Kapodistrian University of Athens Athens, Greece Matthew Parsons Urogynaecology Birmingham Women’s NHS Foundation Trust Birmingham, U.K. Antonio Pastore Urology, Sapienza University, Rome, Italy Marie-Aimée Perrouin Verbe Bristol Urological Institute Southmead Hospital Bristol, U.K. Yvette Perston Functional Bowel Service, Nursing Queen Elizabeth Hospital Birmingham Birmingham, U.K. Benoit Peyronnet Urology University of Rennes Rennes, France Simone Pletto Residency Program in Urology University of Rome ‘Tor Vergata’ and Urology Policlinico Tor Vergata University Hospital Rome, Italy

Current Contributors Ashish Pradhan Urology Cambridge University Hospital NHS Foundation Trust Cambridge, U.K. Kevin L.J. Rademakers Urology Zuyderland Medical Centre Heerlen, The Netherlands Simon Radley Colorectal Surgery Queen Elizabeth Hospital Birmingham Birmingham, U.K. Stephen Radley Urogynaecology Sheffield Teaching Hospitals Sheffield, U.K. Angie Rantell Urogynaecology King’s College Hospital NHS Foundation Trust London, U.K. Felicity Reeves Urology University College London Hospitals London, U.K. Melita Rotar Division of Neurology, Institute of Clinical Neurophysiology University Medical Centre Ljubljana Ljubljana, Slovenia Elizabeth A. Rourke Urology Lousiana State University New Orleans, Louisiana, U.S.A. Jane A. Schulz Obstetrics and Gynecology University of Alberta Edmonton, Alberta, Canada Elisabeth M. Sebesta Urology Vanderbilt University Medical Center Nashville Nashville, Tennessee, U.S.A. Chris Sexton Obstetrics and Gynaecology South Coast District Hospital Adelaide, Australia

xv Ariana L. Smith Pelvic Medicine & Reconstructive Surgery, Urology University of Pennsylvania Health System Philadelphia, Pennsylvania, U.S.A.

Andrea Tubaro Urology Sant’Andrea Hospital and Sapienza University Rome, Italy

Jack D. Sobel Internal Medicine, Immunology and Microbiology, and Obstetrics and Gynecology Wayne State University School of Medicine Detroit, Michigan, U.S.A.

Pradeep Tyagi Urology University of Pittsburgh Pittsburgh, Pennsylvania, U.S.A.

Elizabeth Stephenson Obstetrics & Gynaecology University Hospitals Dorset Poole, U.K. Kamil Svabik Obstetrics and Gynecology, First Faculty of Medicine Charles University and Obstetrics and Gynecology General University Hospital Prague, Czech Republic Tara Symonds Clinical Outcomes Solutions Folkestone, U.K. Visha Tailor Urogynaecology St Mary’s Hospital, Imperial College London, U.K. Nèvine I.D. te West Pelvic Floor Unit, Urogynaecology St. George Hospital Sydney, Australia Roni Tomashev Urogynecology and Pelvic Floor Service Assaf Harofe Medical Center Tsrifin and Sackler School of Medicine Tel Aviv University Tel Aviv, Israel Francesco Trama Andrological and Urogynecological Clinic Santa Maria Terni Hospital University of Perugia Terni, Italy Ruben Trochez Spire Liverpool Hospital Liverpool, U.K.

Lazaros Tzelves Urology National and Kapodistrian University of Athens Athens, Greece Maria Uloko San Diego Sexual Medicine, and Surgery University of California at San Diego San Diego, California, U.S.A. Alan Uren Bristol Urological Institute Southmead Hospital Bristol, U.K. Gommert A. van Koeveringe Urology Maastricht University Medical Centre Maastricht, The Netherlands David B. Vodušek Division of Neurology, Institute of Clinical Neurophysiology, University Medical Centre Ljubljana Ljubljana, Slovenia Desiree M.J. Vrijens Urology Maastricht University Medical Centre Maastricht, The Netherlands Philip Wanzek Urology Essentia Health Fargo, North Dakota, U.S.A. Alan J. Wein Surgery and Urology University of Pennsylvania School of Medicine and Hospital of the University of Pennsylvania Philadelphia, Pennsylvania, U.S.A.

Current Contributors

xvi Dana Weiss Urology, Surgery Perelman School of Medicine University of Pennsylvania School of Medicine and Children’s Hospital of Philadelphia Philadelphia, Pennsylvania, U.S.A. Andrew Williams Colorectal and Pelvic Floor Surgery Guy’s and St. Thomas’ NHS Foundation Trust London, U.K.

Naoki Yoshimura Urology, Pharmacology, and Cell Biology University of Pittsburgh Pittsburgh, Pennsylvania, U.S.A. Martino Maria Zacchè Urogynaecology, Department of Gynaecology Birmingham Women’s and Children’s NHS Foundation Trust Birmingham, U.K.

Stephen A. Zderic Pediatric Urology Perelman School of Medicine University of Pennsylvania School of Medicine and Children’s Hospital of Philadelphia Philadelphia, Pennsylvania, U.S.A.

VOLUME ONE: CLINICAL PERSPECTIVES Section I Background Issues Section Editor: Ian Milsom

1

HISTORY OF UROGYNECOLOGY AND FEMALE UROLOGY Jane A. Schulz and Harold P. Drutz*

Introduction Having moved into the new millennium, accompanied by many new advances in the field of urogynecology and reconstructive pelvic surgery, it is appropriate to take time to reflect on the events of the last century and to make suggestions for future directions. With the significant increase in our postmenopausal female population, there is a growing demand for improved quality of life and management of pelvic floor dysfunction. No longer do we contemplate whether women will grow older but, rather, how they will grow older. The life expectancy for women has almost doubled through the twentieth century. In 1923, Professor Sir Arthur Keith, in his Hunterian lecture on “Man’s Posture: Its Evolution and Disorders” [1], stated: Every movement of the arms, cough or strain sets going a multitude of “water hammers” within the abdominal and pelvic cavities. Every impulse sets the bladder knocking at the vaginal exit … it is the continual repetition of small forces, more frequently than the sudden application of a great effort which wear down the vaginal defense. Although it has long been recognized that factors such as childbearing and chronic increases in intra-abdominal pressure contributed to pelvic floor prolapse, only recently has there been growing demand to manage all of the resulting problems. Urinary incontinence is now the most common reason for admission to long-term institutionalized centers in Canada and the United States. Billions of dollars are spent every year on nappy (diaper) and pad products, but this does nothing to correct the underlying problem of incontinence. Since the inception of medical writing, gynecological and urological conditions have been reported. The Kahun papyrus, circa 2000 BC, described diseases of women including diseases of the urinary bladder. The Ebers papyrus, 1550 BC, classified diseases by systems and organs. Section VI includes a prescription for the cure of a woman suffering from the disease in her urine, as well as her womb. Urinary fistula is an example of the intimate relationship between the urinary and genital systems in women. Henhenit lived in the court of Mentuhotep II, about 2050 BC. Her mummy, found in 1935, revealed by radiography an extensive urinary fistula [2]. Reviewing the last century of progress in the new subspecialty of urogynecology and reconstructive pelvic surgery proved to be a tremendous and somewhat daunting task. Perhaps, the quotation that best summarizes the events that have occurred is the opening sentence from Charles Dickens’ A Tale of Two Cities: “It was the best of times, it was the worst of times.” Undoubtedly, *

2

We gratefully acknowledge the involvement of Jack R. Robertson for his contribution to the previous editions of this chapter. Jack, who was a founding father of IUGA, sadly passed away on April 1, 2015, and we dedicate this updated chapter in his memory.

we have made tremendous progress in this burgeoning new field; however, a political battlefield was perpetuated with the division of the female pelvic floor between urologists, urogynecologists, gynecologists, and colorectal surgeons. This political feud is cleverly illustrated in the article of Louis Wall and John DeLancey with its well-known drawing of the competing urologist, gynecologist, and colorectal surgeon [3]. This is one of the many challenges that must be overcome in providing overall women’s health care as we move further into the twenty-first century. A multidisciplinary approach to managing female pelvic floor dysfunction must be advocated to provide women with appropriate care in the areas of urinary and fecal incontinence, urogenital aging, conservative management, and reconstructive pelvic surgery [4]. Voltaire, the French philosopher of the “Age of Enlightenment” said, “these truths are not for all men nor for all times.” From this, we must humbly accept the concept that the truths we believe in today regarding our management of women with pelvic floor disorders must be constantly reassessed and modified with scientific advancements and research. Similarly, the epigram by Alphonse Karr (1849) “plus ça change plus c’est la même chose” (the more things change, the more they stay the same) also reflects the changes during the past century especially in the field of surgical intervention, where in many cases we have continued to reinvent the wheel. Now, we will review the significant events in this field over the last century.

History of the International Urogynecology Association At the Federation International of Gynecology and Obstetrics (FIGO) meeting in Mexico City in 1976, two medical friends, Professor Axel Ingelman-Sundberg, of Stockholm, Sweden, and Jack Rodney Robertson, of California, USA, met. It was time to form a new society. The objective was to further the urinary health of females. Both physicians were deeply involved in this work. Axel Ingelman-Sundberg, renowned for his research, his pioneering in gynecologic surgery, and his teaching at the Karolinska Institute in Stockholm, Sweden, was the catalyst. Sweden had been a founding member of FIGO. Axel tried to persuade FIGO to make International Urinary Incontinence a subcommittee, but they declined. In his capacity as vice president of FIGO, Axel reserved a special room for the formation of the International Urogynecological Association (IUGA). He was elected the first president, to serve 5 years, 1976–1980, by the colleagues who registered as members. They were Abbo Hassan Abbo, MD, Sudan; Wolfgang Fisher, MD, East Germany; Bozo Kralj, MD, Yugoslavia; Oscar Contreras Ortiz, MD, Argentina; Donald R. Ostergard, MD, USA; Eckard Petrie, MD, West Germany; Jack R. Robertson, MD, USA; Mr. Stuart Stanton, MD, UK; Ulf Ulmsten, MD, Sweden; and David W. Waller, MD, UK. Ulf Ulmsten, then professor of obstetrics and gynecology in Aarhus, Denmark, was chosen as secretary.

DOI: 10.1201/9781003144236-2

History of Urogynecology and Female Urology The next meeting followed in Sheffield, UK, in July 1977, in connection with the local gynecological meeting. At Bergen, Norway, in 1978, members of IUGA met along with the Scandinavian Congress of Obstetrics and Gynecology. In 1979, in Tokyo, they met again with FIGO; this time, IUGA was a special section of the program. In October 1980, members of IUGA met in New Orleans, organized by Jack Robertson, in connection with the newly formed Gynecological Urology Society (GUS), later to become the American Urogynecologic Society (AUGS). The fifth IUGA meeting was held in Stockholm, September 1981, at the Wenner-Gren Center, famous for Nobel Prize presentations. The banquet was at the Royal Opera House, with a special program by the famous Swedish opera singer, Kerstin Dellert. Jack Robertson was elected president and served until 1985. Peter Sand, of Chicago, Illinois, became the general secretary. During this time, the association was growing in membership. In the United States, Jack Robertson found that women were being treated as second-class citizens, being examined with male instruments for their incontinence problems. An alarming number of women were incontinent after their hysterectomy surgery. Robertson devised a system of viewing the bladder using carbon dioxide instead of water. In 1968, he went to Germany and convinced the famous endoscope maker, Karl Storz, who had recently acquired the technique of fiber optics, to produce a female urethroscope to Robertson’s specifications. Storz immediately liked the idea of not using water and made the first Robertson female urethroscope. Instead of just resting their instruments upon it, this was the first time doctors could view the female urethra and its pathology. This was the beginning of a pioneering path with Robertson giving seminars to physicians anxious to learn about the female urinary tract, which had not been included in their gynecological training. An immediate result was a sharp rise in the diagnoses of urethral diverticula. The meeting was held in Santa Barbara, California, in 1982, organized by Jack Robertson and combined with the GUS, organized by Don Ostergard. In 1983, members of IUGA met in Mainz, Germany, and in 1984, they met at the famous Breakers Hotel in West Palm Beach, Florida. At the meeting in Budapest, Hungary, in 1985, physicians came from behind the Iron Curtain. It was vital for them to present their work at the meeting as they would rise in professional and, most importantly, pay level as a result. When one group from Poland presented a problem, the audience asked why ultrasound had not been used, which at that time would have been the obvious method of treatment. The physicians from Poland replied simply: “We do not have ultrasound.” Donald Ostergard was elected the third president and presided at the 1986 meeting at Yale University, organized by Ernest Kohorn. Don’s memories include “a lot of work organizing individuals to take the financial risks to hold a meeting.” An important event occurred at the 1986 Yale meeting. The International Urogynecology Journal was born. Oscar Contreras Ortiz was nominated editor-in-chief. Donald Ostergard became the first managing editor and, later, the editor in chief. He was followed by Linda Brubaker, Peter Dwyer, Paul Riss, Gunner Lose, and now Rebecca Rogers and Steven Swift. The first issue, Volume I, was printed in September 1989 and contained the abstracts of the Riva del Garda meeting. The associate editors, section editors, and editorial board represent countries all around the world. The 1987 meeting was in Ljubljana, Yugoslavia, organized by Bozo Kralj, of Slovenia, with 200 members worldwide. Bozo became the fourth president at the 1988 memorable meeting

3 in Iguazu Falls, Argentina, hosted by Oscar Contreras Ortiz, where Hans Van Geelen says, “made every effort, and succeeded in strengthening social ties.” In 1989, Rodolfo Milani hosted the meeting in Riva Del Garda, Italy. Next elected was Eckhard Petri of Germany, from 1990 to 1992, inaugurated at the Stockholm, Sweden, meeting organized by Ulf Ulmsten. Peter Dwyer says of this meeting: “One of the most low key of all the meetings, it was possibly one of the most enjoyable. It was basic but had good science. The chairman’s dinner was held in Ulf’s department at the Uppsala University cafeteria.” The 16th annual IUGA meeting was held in Sydney, Australia, in 1991, and the host and hostess were Jim and Peggy Gibson. They had a fabulous chairman’s reception that was held at the farm they owned at the time called “Stanton Hall.” In 1992, IUGA combined with AUGS, in Boston, Massachusetts, with a lobster bake party at the famous aquarium. James Gibson, Australia, was elected the sixth president. He presided over the 1993 meeting in Nimes, France, which was coordinated with ICS in Rome. Gibson organized Organon to give IUGA $10,000 each year for 5 years for the best presentation at each meeting. In 1994, Harold Drutz hosted the meeting in Toronto, Canada, at which he was elected the seventh president. He presided at the Kuala Lumpur meeting in 1995 as well, hosted by Jim Gibson, which, he says, was one of the first meetings to make a profit. On September 2–5, 1996, the meeting was held in Vienna, Austria, organized by Paul Riss. This was a glorious site at which Oscar Contreras Ortiz, Buenos Aires, Argentina, was elected the eighth president. The 1997 meeting occurred in Amsterdam, arranged with the combined efforts of Hans Van Geelen, Harry Vervest, and Mark Vierhout. The meeting location was planned in Europe as FIGO was in Copenhagen. In 1998, Buenos Aires, Argentina, was the venue for IUGA, hosted by Oscar Contreras Ortiz. Linda Cardozo, London, UK, was the ninth president. In 1999, in Denver, Colorado, Willy Davila organized IUGA with Rick Schmidt of ICS to allow the first combined meeting of the two societies. The 2000 IUGA meeting in Rome, Italy, organized by Mauro Cervini, chose Hans Van Geelen, from the Netherlands, as president. The largely attended meeting was enlivened by an audience with Pope John Paul II, celebrating the millennium year. The Pope blessed the International Urogynecology Association in his Papal address during the meeting. Hans Van Geelen recalls that at an early IUGA meeting, the attendance was so small that the members could sit around one round table, discussing the clinical relevance of urodynamics. He, too, says, “in the beginning, hosting a meeting was a delicate task.” In 2001, the IUGA meeting moved to the southern hemisphere again with Peter Dwyer as the host in Melbourne, Australia, combined with the Australian Continence Foundation. Axel Ingelman-Sundberg was awarded a lifetime achievement award, via a live television connection, at the 2001 meeting. The 2002 meeting was held in Prague, with Michael Halaska as the organizer. The river Moldau flooded the inner town, and Professor Halaska had to change the venue of the gala dinner and take out new insurance. In Prague, Peter Dwyer of Melbourne, Australia, was elected president. Peter comments that IUGA became not only a scientific society but developed a true camaraderie of friendship. He says that the young urogynecologists appreciated the emphasis on the clinic rather than the basic science (rats). Peter writes: “Presenting our own research internationally and getting ideas for our next projects was also very important, and the meetings were great fun.”

4 In 2003, IUGA was back in Buenos Aires, again organized by Oscar Contreras Ortiz. August 24–27, 2004, saw a spectacular meeting of IUGA in Paris, France, combined for the second time with the ICS. The chairman’s dinner, held at Maxim’s Restaurant, honored Jack R. Robertson with a lifetime achievement award. The Palais Versailles was the unbelievable site of the gala dinner, hosted by Bernard Jacquetin for IUGA and Francois Haab for ICS. Paul Riss of Moedling, Austria, was elected to serve as president from 2004 to 2006. Copenhagen, Denmark, August 9–12, was the site of the 2005 IUGA meeting, organized by Gunnar Lose. The two old friends, Axel Ingelman-Sundberg and Jack R. Robertson, met in Munich, Germany, in August of 2004. The meeting in Copenhagen in 2005 was an exciting meeting at a unique venue with the first discussion of some of the newer mesh kits. In 2006, the annual IUGA meeting was in the beautiful historic city of Athens, with many social events being held at some of the ancient historic sites. Professor Oscar Contreras Ortiz received a prestigious lifetime achievement award. The year 2007 found us back across the Atlantic in Cancun, Mexico, with a stunning gala dinner at sunset on the beach. At the Cancun meeting, Professor Donald Ostergard received a lifetime achievement award. Despite difficult weather caused by a number of typhoons, many were still able to attend the 2008 meeting in Taipei, where Professor Harold Drutz received a lifetime achievement award from the IUGA for his ongoing contributions to the society (including the only Canadian to become president of the society, in 1994–1996). The stunning venue of Lake Como, Italy, was the site for the 2009 meeting, where Professor Jim Gibson received a lifetime achievement award. The year 2010 saw another joint meeting of the ICS and IUGA hosted by Professors Drutz and Herschorn in Toronto, Canada. The 2011 IUGA meeting moved back to Europe and was held in Lisbon, Portugal. The year 2012 led the IUGA meeting back to beautiful Brisbane, Australia. In 2013, Dublin hosted a wonderfully successful meeting and Linda Cardozo received a lifetime achievement award. In 2014, IUGA joined with AUGS in Washington, DC, to host a great meeting where 61 countries were represented. In June 2015, the 40th ACM was held in Nice, France, in conjunction with the Second World Congress on Abdominal and Pelvic Pain. The meeting chairs were Emmanuel Chartier-Kastler (Urologist) and Brigitte Fatton (Gynecologist). The Ulf Ulmsten Lecture was given by Professor Ian Milsom (Sweden) whose topic was “Can We Predict and Prevent Pelvic Floor Dysfunction.” The meeting was well attended, and the very successful Gala was held at the Hyatt Regency Nice Palais de la Méditerranée. The 41st ACM moved IUGA for the first time to Cape Town, South Africa, in August 2016. The meeting hosts were Peter de Jong and Stephen Jeffery. One of the many highlights of the meeting was the Live Surgical Day at Groote Schuur Hospital. The Ulf Ulmsten Lecture was presented by Professor Jan Deprest (Belgium) who spoke on “From the Bench to the Bedside in Pelvic Floor Surgery.” Lynsey Hayward took over as the incoming IUGA president. A lifetime achievement award was presented to Professor Gustav Nilsson (Finland). The concluding dinner and dance were held at the unusual venue of the Cape Town Fish Market. June 2017 found IUGA back in Canada for a meeting in Vancouver, chaired by Professor Geoff Cundiff. At this meeting, the inaugural international meeting of the new Canadian Society

Textbook of Female Urology and Urogynecology for Pelvic Medicine (CSPM) took place. This fledgling group has now become an affiliate society of IUGA and is managed by Status Plus. Status Plus, under the leadership of David Casalod, became the managerial force for IUGA as of January 1, 2017. The Ulf Ulmsten Lecture was given by Professor Bary Berghmanns (The Netherlands) on “Physiotherapy for Pelvic Pain and Sexual Dysfunction: An Untapped Resource.” A distinguished service award was presented to G. Willy Davila (USA). The IUGA/FIUGA Gala Dinner was held at the Pinnacle Hotel. IUGA went back to Vienna, Austria, in June 2018 for the 43rd ACM. The meeting chairs were Heinz Kolbl and Karl Tomassino; Paul Riss was the Honorary Chairman. Professor Don Wilson (New Zealand) gave the Ulf Ulmsten Lecture on “The Ideal Birth (in the developed world) in 2018 – is UR-Choice.” A lifetime achievement award was presented to Professor Paul Riss (Austria). The Gala was held at the magnificent Festive Hall of the Vienna City Hall. The 44th ACM meeting was combined with AUGS in September 2019 and held in Nashville, Tennessee (USA). The meeting chairs were Roy Ng (IUGA) and Emily Lukacz (AUGS). Ranee Thaker became the IUGA president-elect. Professor Rebecca Rogers gave the Ulf Ulmsten Lecture on “Curing Pelvic Floor Disorders in 2040: Measuring Sex and Other Aspects of Pelvic Floor Function.” A lifetime achievement award was presented to Professor Peter Dwyer (Australia). The first Oscar Contreras Ortiz Award was presented for the best original paper in the IUJ for the past year. The Gala Friday Night Party was held at the Nashville Underground. In early 2020, the world was forever changed by the COVID-19 pandemic. This unprecedented situation has impacted everyone personally and professionally. The 2020 IUGA ACM was scheduled for The Hague (The Netherlands) but was canceled because of COVID-19. The IUGA Board and Status Plus organized an amazing Virtual Meeting from August 29 to September 1, 2020. Suzie Bailey presented the Ulf Ulmsten Lecture on “Let the Light Come Streaming In – Leading With Compassion.” Despite the chaos created by the pandemic, the virtual meeting remained a huge success and a celebration of scholarly international activity in urogynecology. The year 2021 was planned for Singapore (Chairman Professor Roy Ng), but because the world was still plagued with COVID and global travel remained uncertain, it was switched to a Hybrid Meeting (both face-to-face and virtual). IUGA remains strong, vibrant, and under excellent leadership. As we evolve from COVID-19, your “IUGA Family” will meet again. Stay healthy, keep up your hard work, and look forward to future annual IUGA meetings. We look forward to when we can gather together again to network, share our achievements, and celebrate the amazing work being done to enhance the pelvic floor health of women.

Urogynecology training programs Urogynecology training programs have grown internationally with support from the IUGA. Recognition and accreditation of urogynecology and pelvic floor reconstruction have also progressed significantly with formal subspecialty certification programs now in many countries. The detailed progress and trainees of some of the larger subspecialty training programs are given in the appendix.

History of Urogynecology and Female Urology

Progress in the twentieth and twenty-first centuries Treatment

Marion Sims, in the United States, was one of the first to establish the relationship between urology and gynecology. Determined to cure vesicovaginal fistulas, he finally used silver wire and announced in 1852 the cure of 252 out of 320 attempts. Howard A. Kelly, the first professor of gynecology at the Johns Hopkins Medical School, believed that gynecology and urology were so closely related that a physician could not be trained in either field and ignore the other. In 1893, he invented a cystoscope and was the first person to insert ureteral catheters under direct vision. Kelly’s successor, Guy Hunner, described Hunner’s ulcer, which today is called interstitial cystitis. Succeeding Hunner was Houston Everett, whose contribution was the relationship of the urinary tract to cervical cancer. In 1914, Latzko perfected the cure of posthysterectomy vesical vaginal fistula. Next, Richard TeLinde added water endoscopy to the Hopkins female urology program. Most teaching programs at the time gave little or no exposure to female urology [2]. In 1892, Poussan proposed the concept of urethral advancement for the management of urinary incontinence [5]. He suggested, “introducing a bougie into the urethra, resecting the external meatus and portion of the urethra, and then after torsion of the canal to one hundred and eighty degrees, it is transplanted to a point just below the clitoris.” By the turn of the century, four main treatments for stress urinary incontinence were outlined: 1. Injection of paraffin into the region of the urethra 2. Massage and electricity 3. Torsion of the urethra 4. Advancement of the external urethral meatus A century later, we are still trying to identify the best urethral bulking agent. Although it is no longer paraffin, research with Teflon (poly [tetrafluoroethylene]), silicone, collagen, autologous fat, hyaluronic acid, carbon particles, and various copolymers has failed to identify an ideal medium. In his landmark paper in 1913, Kelly outlined operations for managing urinary incontinence in women [6]. These included the following: • • • • • •

Puncture of the bladder and insertion of a catheter Closing the urethra and creating a vesicoabdominal fistula Closing the vagina and creating a rectovaginal fistula Compression of the urethra with an anterior colporrhaphy Periurethral injection of paraffin Advancement of the urethral meatus to the clitoris

Kelly suggested that “the torn or relaxed tissues of the vesical neck should be sutured together using two or three vertical mattress sutures of fine silk linen passed from side to side.” In his first publication, he described 16 patients as being well and four patients in whom the procedure was not successful, giving a success rate of 80%. However, further evaluation has revealed that the long-term success, using only these sutures to correct stress incontinence, falls to roughly 60% [7]. This decline is possibly related to gradual postoperative elongation of the smooth muscle in which the sutures were placed [8]. With coincident suburethral plication of the pubourethro-vaginal ligaments of the urogenital

5 diaphragm, the long-term results of a Kelly plication are significantly better [9]. Sling procedures were pioneered in the early 1900s by three European physicians. Goebell first suggested transplantation of the pyramidalis muscle in 1910 [10]. This was followed by Frankenheim who, in 1914, recommended using the pyramidalis or strips of rectus muscle as a suburethral sling by attaching the muscle to the overlying fascia [11]. In 1917, Stoeckel suggested combining the techniques of Goebell and Frankenheim and adding plication of the vesical neck [12]. Throughout the twentieth century, there have been many variations of sling procedures described in the literature. In 1907, Giordano suggested the use of the gracilis muscle by wrapping it around the urethra [13]. Shortly thereafter, in 1911, Squier described the use of the levator ani muscles by placing them between the vagina and urethra [14], and, in 1923, Thompson recommended the use of strips of the rectus muscle, surrounded by fascia, to be passed in front of the pubic bones and around the urethra [15]. The next key event in the development of surgery to the anterior compartment was the development of the bulbocavernosus muscle fat pad graft by Martius in 1929 [16]. This has found wide use in fistula repairs and reconstruction of the anterior vaginal wall. In 1968, John Chasser Moir [17] introduced the concept of the gauze hammock operation as a modification of the original Aldridge [18] sling procedure described in 1942. Chasser Moir recognized that “operations of this type do no more than support the bladder neck and urethrovesical junction and so prevent the undue descent of parts when the woman strains or coughs.” Victor Bonney, in 1923, stated, “incontinence depends in some way upon a sudden and abnormal displacement of the urethra and urethrovesical junction immediately behind the symphysis” [19]. This was followed in 1924 by a description from B.P. Watson of “the muscle sheet that normally supports the base and neck of the bladder” and his statement that “so far as the incontinence of urine is concerned, the important sutures are those which overlap the fascia at the neck of the bladder and so restore it to its normal position.” In reviewing Watson’s work with anterior colporrhaphy, he was able to obtain “perfect control” in 65.7% of cases, “improvement” in 21.9%, and “no success” in 12.4% [20]. These figures are in keeping with others that have been reported for anterior colporrhaphy. Therefore, it was apparent that hypermobility of the bladder neck was an issue and that the anterior colporrhaphy was not a satisfactory operation for stress incontinence. The next landmark in genitourinary surgery occurred in 1949 with the publishing of the paper of Marshall, Marchetti, and Krantz on “The correction of stress incontinence by simple vesicourethral suspension.” They suggested that this operation was “particularly valuable for patients whose first procedure failed.” In their first 44 patients, they described 82% of patients with excellent results, 7% with improvement, and an 11% failure rate [21]. Shortly thereafter, in 1950, H.H. Fouracre Barns described the “round ligament sling operation for stress incontinence”; this technique was popularized by Paul Hodgkinson [22]. In 1961, John Burch first described his modification of the Marshall– Marchetti–Krantz procedure, which involved a retropubic colpourethropexy that took the anterolateral aspects of the vault of the vagina and attached them to Cooper’s ligament [23]. Burch recognized the potential complications of this procedure if done alone including the creation of an enterocele or rectocele, the development of ventral/incisional hernias, and even the possibility of a vesicovaginal fistula.

6 Diagnosis and investigation

As the number of procedures offered for the treatment of stress incontinence increased, there were also significant advances in the urogynecological diagnostic procedures available. In 1882, Mosso and Pellacani described cystometry using a smoked drum and a water manometer [24]. An aneroid barometer for cystometric evaluation was developed by Lewis in 1939 [25]. Jeffcoate and Roberts, in 1952, introduced the concept of radiographic changes in the posterior urethrovesical angle [26]. These changes were further modified in 1956 by Bailey in England, who described seven variations in the urethrovesical angle in radiographic studies [27]. Later modifications were performed by Tom Green in the United States in 1962 when he described Green types 1 and 2 incontinence [28]. Identification of the posterior urethrovesical angle by lateral bead chain cystography was introduced by Hodgkinson in 1953 [29]. By 1956, Von Garrelts had introduced the concept of uroflowmetry [30]. In 1964, Enhorning, Miller, and Hinman combined cystometry with radiographic screening of the bladder [31]; this was followed a few years later in 1969 by Brown and Wickham’s introduction of urethral pressure profilometry [32]. Another landmark occurred in 1971, when Patrick Bates, Sir Richard Turner-Warwick, and Graham Whiteside introduced synchronous cine pressure-flow cystography, with pressure and flow studies [33]. This was the beginning of the field of video urodynamics. Equipment was further expanded with the introduction of the microtip transducer in 1975 by Asmussen and Ulmsten, for measuring urethral closure pressure [34]. Further investigational advances occurred in the latter part of the twentieth century. These included the introduction of the Urilos monitor in 1974 by James et al. [35]. This device allowed evaluation of the symptom of dampness for whether the fluid lost was urine. In 1981, Sutherst et al. developed the padweighing test as an objective measure of the severity of urinary incontinence [36]. In 1961, Enhorning suggested that “surgical treatment for stress incontinence is probably mainly beneficial because it restores the neck of the bladder and the upper part of the urethra to the influence of intra-abdominal pressure” [37]. This introduced the concept of pressure transmission ratios and the idea that successful operations for stress urinary incontinence worked by restoring the urethrovesical junction to an intra-abdominal position. In 1956, Jeffcoate added further interpretation of our investigative techniques when he attempted to caution gynecologists by stating “the absence of the posterior urethrovesical angle is merely a sign of incompetence of the internal sphincter. The presence of an angle is a function of the involuntary muscle at the urethrovesical junction, not of the muscle of the pelvic floor” [38]. And so the simplistic approach of static cystourethrograms began to be questioned. Green had suggested that if one saw a radiographic diagnosis of type 1 incontinence, this could readily be repaired with an anterior colporrhaphy; the type 2 stress incontinence required a retropubic urethropexy. A number of authors, including Drutz in 1978 [39], have confirmed the limited accuracy of static cystourethrograms. By 1953, Paul Hodgkinson had recommended that “if on anteroposterior straining radiograph, the urethrovesical junction is depressed 4 cm below the lower border of the symphysis, I believe the objective of the operation can be accomplished through anterior colporrhaphy” [28]. A decade later, Hodgkinson commented on the frequency of detrusor dyssynergia, with grade 1 defined as a detrusor contraction in response to coughing

Textbook of Female Urology and Urogynecology and heel jouncing and grade 2 a spontaneous automatic detrusor contractility when recumbent. Hodgkinson recognized the importance of discovering this condition prior to performing any surgery for stress urinary incontinence [40].

Success rates

As we approached the 1970s, we began to recognize that operative failures in the treatment of stress urinary incontinence involve three areas [41] as follows: 1. Incorrect diagnosis and the fact that bladder instability (and not just simple stress incontinence) may have been the cause of the incontinence. 2. The wrong operation may have been chosen and some operations probably give better long-term results. 3. The concept of technical failure. We recognized that the vaginal approach to primary stress incontinence probably only gave a 50–60% success rate, whereas the suprapubic approach gave success rates of at least 80%. Morgan, in 1973, discussed indications for primary retropubic urethropexy: These included minimal pelvic floor relaxation, chronic chest disease, occupations involving heavy lifting patients who were heavily involved in athletics, and obesity [42]. In 1970, Hodgkinson stated that “the most durable operation for stress incontinence is a retropubic urethropexy and the least durable is a vaginal repair.” Hodgkinson quoted a 92.1% success rate with his own 404 patients that had retropubic urethropexy [40]. The other movement in the 1970s was of the urologists and gynecologists toward endoscopic bladder-neck suspensions such as the Pereyra, Raz, and Stamey suspensions; numerous variations including the Gittes and Cobb-Raagde were described in the literature. In the 1990s, we have now realized that the long-term results of these needle suspension procedures are also not as good as the retropubic procedures. The 1990s saw the advent of minimally invasive sling procedures for stress urinary incontinence. The first of these, the tension-free vaginal tape and the concomitant integral theory of the pathophysiology of incontinence were described by Ulmsten and Petros in the early 1990s [43, 44]. There are now multiple variations of this procedure including the transobturator approach. Success rates are reported to be similar to that of the Burch repair [45]. More recently, single-incision midurethral slings have been advocated. The long-term success of these new procedures is yet to be established. The great champion of pelvic floor exercises, Arnold Kegel, reported pre- and postoperative benefits of the properly performed exercises [46]. Unfortunately, many patients are placed on this regimen only after an unsuccessful surgical procedure. Robertson, with Bergman and Elia, in 2004, described an enhancement of Kegel exercises, when done in a magnetic field, combined with DeLancey’s “knack procedure,” to give support to the urethra when it is most needed [47].

COVID-19 and the impact of a global pandemic

In early 2020, the world was presented with the profound challenge of a global pandemic; nothing like this has been experienced for over a century. Since vaccines were not immediately available, in attempts to prevent the viral spread and “flatten the curve,” different health jurisdictions responded to protect patients and reduce stress on the hospital systems. This was accomplished by canceling non-urgent surgeries and ambulatory clinic visits. As much of

History of Urogynecology and Female Urology urogynecology care falls into this category, our subspecialty group and the patients we serve, have been profoundly impacted. In an attempt to navigate these changes, and the unpredictable restrictions posed by the pandemic, a rapid change to care delivery occurred with the implementation of virtual care. Under normal circumstances, changes to models of care are studied in a more measured, methodical, and graduated fashion. Since this was not possible, a group of our colleagues conducted an expedited literature review on four topics (telemedicine in FPMRS, pessary management, urinary tract infections, urinary retention); they also completed a review of guidelines on urinary and fecal incontinence, pelvic organ prolapse, and defecatory dysfunction to guide care [48]. Key findings from this review include the fact that thanks to advances in technology, telemedicine is more widely accessible with good patient satisfaction and serves as a reasonable option for assessment, postoperative follow-up, physiotherapy, and conservative management. Intervals for pessary follow-up and care can likely be safely extended. Urinary tract infections can be treated empirically with resulting lowering of costs, but there is a risk of overprescribing and increased antibiotic resistance [48]. Conservative, behavioral, and pharmacologic first-line options for care can easily be navigated virtually. As vaccines become more available and we look toward the reduction of restrictions imposed by the pandemic, consideration must occur for managing the backlog of patients awaiting care. In most countries, emergent, urgent, and oncology care were prioritized. In urogynecology, while we were able to move to virtual patient assessments and education, electronic patient-reported outcome measures, increased intervals for pessary care, and telephysiotherapy, there will be a significant waitlist of patients requiring physical examination with prolapse assessment, urodynamics, cystoscopy, and pelvic reconstructive surgery [49–51]. Methods to triage these patients, with consideration of symptom worsening during the wait, must be developed. In a subspecialty where much of our work is non-urgent, preoperative evaluation, risk assessment tools, and optimization of medical conditions to minimize perioperative complications are an integral part of patient management. Emerging data is indicating worse surgical outcomes in patients who test positive for COVID-19, with increased postoperative complications and mortality [52]. Consideration of ongoing pre-operative COVID screening and management of patients with long-haul COVID symptoms will have to occur. From an educational perspective, consideration will be required regarding training of our fellows, taking into account the impact on our trainees of reduced surgical time and clinical exposure due to the pandemic restrictions. In this current time of uncertainty, we must also consider potential impacts of COVID-19 on pelvic floor symptoms whether it be direct or indirect. Looking forward, some innovations such as components of virtual care and education will likely persist and be a part of new care pathways beyond the pandemic.

The way ahead Now in the twenty-first century, we must consider what lies ahead. The main fields of responsibility as urogynecologists and reconstructive pelvic surgeons include the following: • Education • Surgery • Uropharmacology

7 • • • • • •

Neurophysiology Behavior modification Collagen Ultrasonography/magnetic resonance imaging (MRI) Stem cells Graft materials

Regarding education, we need to focus on education of our colleagues in obstetrics and gynecology, family practice, geriatrics, and community health care of allied health professionals such as nursing and physiotherapy and of the public. The awareness must be increased that incontinence is not a normal effect of aging; the many myths including “everyone gets it” and “it can’t be treated” must be dispelled. Urogenital aging must be stressed as part of menopause management, and conservative management in the community should be promoted. The other aspect of education is the training of new subspecialists in the field of urogynecology and reconstructive pelvic surgery. Board certification is now available in Australia and in the United States. IUGA is now establishing international standards for training in conjunction with FIGO and WHO. Within the field of surgery for pelvic floor problems, we need to reevaluate what we do. Over 200 operations have been described for stress incontinence. Randomized controlled trials, with adequate patient numbers and follow-up of at least 2 years, are required for evaluation of new and existing procedures. The role of bulking agents is still controversial and the ideal medium has yet to be discovered. A variety of fascia and mesh is available for use in pelvic floor reconstructive procedures; however, the longterm durability and consequences of these are still unknown. This includes many new mesh devices and kits for pelvic floor reconstruction. Concerns have been raised about the ethics of some of these newer mesh devices [52]. New pharmacologic agents continue to be produced; well-designed, placebo-controlled trials are mandatory for their evaluation. Neurophysiology is another developing area; work is being done to determine if there are certain factors in labor that lead to irreversible changes to the pelvic floor. Other questions that have been raised include whether abnormalities in the electromyographic patterns predict the success or failure of different treatments. We continue to develop new modes of conservative management including behavior modification and devices; further studies are needed to clarify the specific areas of use for these therapies. The role of collagen in pelvic floor disorders is a fascinating area. We need effective, qualitative, and quantitative assays to determine whether there are certain defects of collagen in patients with pelvic floor dysfunction. Also, we need to establish whether there may be potential genetic markers that may be screened for to determine certain “at-risk” patients. Perhaps there exists a select group of patients that should be counseled to have delivery by cesarean section; this group may also require the use of synthetic materials in reconstruction of their pelvic floor. We need to look at the relationship of collagen to estrogen and the general effects of urogenital aging to see if they are independent factors. Research into genetic components of pelvic floor prolapse is exciting. At Mount Sinai Hospital in Toronto, Dr. May Alarab and her associates have shown that genes that both promote the buildup of extracellular matrix and cause its degradation are different in premenopausal women with prolapse compared to controls. We are in the midst of a revolution in imaging and diagnostic technology. The development of 3D ultrasound [53] and the

Textbook of Female Urology and Urogynecology

8 progress with MRI have allowed a new approach to evaluating defects associated with stress urinary incontinence and pelvic floor disorders. Progress in the field of ultrasound has been hampered by a lack of standardization of terminology; this was recognized by the German Association of Urogynecology that attempted to make recommendations for standardization of methodology [54]. The fact that different methods are used (such as abdominal, perineal, introital, vaginal, and rectal) has further impeded progress in this field. Recent papers have investigated the urethra and surrounding tissues with intra-urethral ultrasonography; the authors have proposed that sphincter measurements can be a prognostic factor in patients who underwent operations for stress urinary incontinence [55]. Beco stated that “Doppler and colour studies will play an increasing role in the evaluation of urethrovesical disorders” (J. Beco, personal communication, November 1996). With new developments in MRI and especially dynamic MRI, these techniques will also play a growing role in investigation and research. New ways of investigating urethral function are also appearing with the introduction of the MoniTorr device and measurement of urethral retro-resistance [56]. The difficulties of introducing new graft materials into pelvic floor reconstructive surgery have highlighted the need for careful research and long-term follow-up with all innovative technologies. Stem cell research may introduce a natural type of treatment for stress urinary incontinence that replaces bulking agents. There is an increasing focus on quality of life tools as a research outcome. National and international societies must continue to promote and support research in the field to advance pelvic floor health for women.

Conclusions At the International Continence Society meeting in 1986, Sir Richard Turner-Warwick gave an address in which he defined the urogynecologist as “neither the general urologist nor the general obstetrician and gynecologist, but someone who has special training and expertise in genitourinary problems in women” [57]. Today, we should expand this definition to include urogynecology and reconstructive pelvic surgery. Such a physician implies a surgeon with specialized training in the conservative and surgical management of women with urinary and/or fecal incontinence, persistent genitourinary complaints, and disorders of pelvic floor supports. As Marcel Proust said, “We must never be afraid to go too far, for the truth lies beyond.” We must humbly accept that the “truths” that we identify today certainly will have to be changed in the future. However, if we work collaboratively to produce welldesigned scientific research, we should be able to establish truths that stand the test of time in our ongoing quest to improve the quality of life for women with pelvic floor problems.

Acknowledgments This chapter includes major segments of text adapted from the IUGA presidential address given by Professor Harold Drutz at the 21st Annual Meeting of the International Urogynecological Association held in Vienna in 1996. The text was later published: Drutz HP. The first century of urogynecology and reconstructive pelvic surgery: Where do we go from here? Int Urogynecol J 1996;7:348–353.

We thank Professors Stanton, Cardozo, Ostergard, Drutz, and Dwyer for providing information on their trainees, included in the appendix on the text’s companion website.

References 1. Keith A. Man’s posture: Its evolution and disorders. Br Med J 1923;II:451–454. 2. Robertson JR. Genitourinary Problems in Women. Springfield, IL: Charles C Thomas, 1978, pp. 6–12. 3. Wall LL, DeLancey JOL. The politics of prolapse: A revisionist approach to disorders of the pelvic floor in women. Perspect Biol Med 1991;34:486–496. 4. Nager CW, Kumar D, Kahn M, Stanton SL. Management of pelvic floor dysfunction. Lancet 1997;350:1751. 5. Poussan. Arch Clin Bord 1892;(1). 6. Kelly HA. Incontinence of urine in women. Urol Cutan Rev 1913;17:291. 7. Bergman A, Elia G. Three surgical procedures for genuine stress urinary incontinence: Five year follow-up of a prospective randomized study. Am J Obstet Gynecol 1995;173(1):66–71. 8. Wall LL, Norton PA, DeLancey JOL. Practical Urogynecology. Baltimore, MD: Williams and Wilkins, 1993, pp. 153–190. 9. Nichols DH, Randall CL. Vaginal Surgery. Baltimore, MD: Williams and Wilkins, 1996, pp. 218–256. 10. Goebell R. Zur operativen Besierigung der angeborenen Incontinentia vesical. Z Gynäk Urol 1910;2:187. 11. Frankenheim P. Zentral Verhandl. d. Deutsch. Geseusch Chir 1914;43:149. 12. Stoeckel W. Über die Verwändung der Musculi Pyramidales bei der opeutinen Behandlung der Incontinentia Urinae. Zentralbl Gynäkol 1917;41:11. 13. Giordano D. Twentieth Congress. Franc de Chir 1907;20:506. 14. Squier JB. Postoperative urinary incontinence. Med Rec 1911;79:868. 15. Thompson R. A case of epispadias associated with complete incontinence treated with rectus transplantation. Br J Dis Child 1923;20:146–151. 16. Martius H. Sphincter und Harndöurenplastic aus dem Musicailus Bulbocavernosus Chirurgie 1929;1:769. 17. Chasser Moir J. The gauze-hammock operation (a modified Aldridge sling procedure). J Obstet Gynaecol Br Commonw 1968;75:1–9. 18. Aldridge AH. Transplantation of fascia for relief of urinary stress incontinence. Am J Obstet Gynecol 1942;44:398–411. 19. Bonney V. On diurnal incontinence of urine in women. J Obstet Gynecol Br Emp 1923;30:358–365. 20. Watson BP. Imperfect urinary control following childbirth and its surgical treatment. Br Med J 1924;11:566. 21. Marshall VF, Marchetti AA, Krantz KE. The correction of stress incontinence by simple vesicourethral suspension. Surg Gynecol Obstet 1949;88:509–518. 22. Fouracre Barns HH. Round ligament sling operation for stress incontinence. J Obstet Gynaecol Br Emp 1950;57:404–407. 23. Burch JC. Urethrovaginal fixation to Cooper’s ligament for correction of stress incontinence, cystocele and prolapse. Am J Obstet Gynecol 1961;81:281–290. 24. Mosso A, Pallacani P. Sur les fonctions de la vessie. Arch Ital Biol 1882;1:97. 25. Lewis LG. New clinical recording cystometer. J Urol 1939;41:638–645. 26. Jeffcoate TNA, Roberts H. Stress incontinence. J Obstet Gynaecol Br Emp 1952;59:681–720. 27. Bailey KV. A clinical investigation into uterine prolapse with stress incontinence: Treatment by modified Manchester colporrhaphy. Part II. J Obstet Gynaecol Br Emp 1956;63:663. 28. Green TH Jr. Development of a plan for the diagnosis and treatment of urinary stress incontinence. Am J Obstet Gynecol 1962;83:632–648. 29. Hodgkinson CP. Relationship of female urethra and bladder in urinary stress incontinence. Am J Obstet Gynecol 1953;65(3):560–573. 30. Von Garrelts B. Analysis of micturition: A new method of recording the voiding of the bladder. Acta Chir Scand 1956;112:326–340. 31. Enhorning G, Miller E, Hinman F Jr. Urethral closure studied with cine roentgenography and simultaneous bladder-urethral pressure recording. Surg Gynaecol Obstet 1964;118:507–516. 32. Brown W, Wickham JEA. The urethral pressure profile. Br J Urol 1969;41:211–217. 33. Bates CP, Whiteside CG, Turner-Warwick R. Synchronous cine/pressure/flow cystography: A method of routine urodynamic investigation. Br J Radiol 1971;44:44–50. 34. Asmussen M, Ulmsten U. Simultaneous urethrocystometry and urethral pressure profile measurements with a new technique. Acta Obstet Gynaecol 1975;54:385–386.

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35. James ED, Flack F, Caldwell KP, Smith M. Urine loss in incontinence patients: How often, how much? Clin Med 1974;4:13–17. 36. Sutherst JL, Brown M, Shawer M. Assessing the severity of urinary incontinence in women by weighing perineal pads. Lancet 1981;1:1128–1130. 37. Enhorning G. Simultaneous recording of intravesical and intraurethral pressure: A study of urethral closure pressures in normal and incontinent women. Acta Chir Scand 1961;276(Suppl):1. 38. Jeffcoate TNA. Bladder control in the female. Proc Roy Soc Med 1956;49:652–660. 39. Drutz HP, Shapiro BJ, Mandel F. Do static cystourethrograms have a role in the investigation of female incontinence? Am J Obstet Gynecol 1978;130:516–520. 40. Hodgkinson CP, Ayers MA, Drukker BH. Dyssynergic detrusor dysfunction in the apparently normal female. Am J Obstet Gynecol 1963;87:717–730. 41. Hodgkinson CP. Stress urinary incontinence. Am J Obstet Gynecol 1970;1:1141–1168. 42. Morgan JE. The suprapubic approach to primary stress incontinence. Am J Obstet Gynecol 1973;49:37–42. 43. Petros PE, Ulmsten UI. An integral theory and its method for the diagnosis and management of female urinary incontinence. Scand J Urol Nephrol Suppl 1993;153:1–93. 44. Ulmsten U, Petros P. Intravaginal slingplasty (IVS): An ambulatory surgical procedure for treatment of female urinary incontinence. Scand J Urol Nephrol March 1995;29(1):75–82. 45. Ward KL, Hilton P. UK and Ireland TVT Trial Group. A prospective multicenter randomized trial of tension-free vaginal tape and colpo-suspension for primary urodynamic stress incontinence: Two-year follow-up. Am J Obstet Gynecol February 2004;190(2):324–331. 46. Kegel AH, Powell TH. The physiologic treatment of stress incontinence. J Urol 1950;63:808. 47. Bergman J, Robertson JR, Elia G. Effects of a magnetic field on pelvic floor muscle function in women with stress urinary incontinence. Altern Ther Health Med May–June 2004;10(3):70–72.

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48. Grimes CL, Balk EM, Crisp CC et al. A guide for urogynecologic patient care utilizing telemedicine during the COVID-19 pandemic: Review of existing evidence. Int Urogynecol J April 2020;31(6):1–27. 49. Gray T, Mukopadhay S, Giarinis I. What effect will the COVID-19 pandemic have on urogynecology services in the United Kingdom? Neurourol Urodyn November 2020;39(8):2544–2545. 50. Agro EF, Farullo G, Balzarro M et al. Triage of functional, female and neuro-urology patients during and immediately after the Covid-19 outbreak. Minerva Urol Nefrol August 2020;72(4):513–515. 51. Ferreira CHJ, Driusso P, Haddad JM et al. A guide to physiotherapy in urogynecology patient care during the COVID-19 pandemic. Int Urogynecol J January 2021;32(1):203–210. 52. Ross S, Robert M, Harvey MA et al. Ethical issues associated with the introduction of new surgical devices, or just because we can, doesn’t mean we should. J Obstet Gynaecol Can June 2008;30(6):508–513. 53. Khullar V, Salvatore S, Cardozo LD, Hill S, Kelleher CJ. Three dimensional ultrasound of the urethra and urethral sphincter: A new diagnostic technique. Neurourol Urodyn 1994;13:352–353. 54. Shaer G, Koelbl H, Voigt R et al. Recommendations of the German Association of Urogynecology on functional sonography of the lower female urinary tract. Int Urogynecol J 1996;7:105–108. 55. Hermans RK, Klein HM, Muller U, Schafer W, Jakse G. Intraurethral ultrasound in women with stress incontinence. Br JUrol 1994;74: 315–318. 56. Slack M, Culligan P, Tracey M, Hunsicker K, Patel B, Sumeray M. Relationship of urethral retro-resistance pressure to urodynamic measurements and incontinence severity. Neurourol Urodyn 2004;23(2):109–114. 57. Turner-Warwick R. International Continence Society Proceedings, Boston, MA, 1986.

2

TACKLING THE STIGMA OF INCONTINENCE Angie Rantell*

Introduction More than half a billion people worldwide suffer from urinary incontinence (UI) of varying degrees with the burden of this condition being greater in developing countries (in locations such as Asia, South America, and Africa), making it a global health problem. The prevalence of fecal incontinence (FI) is near 10% in the general population [1]. Brown and colleagues [2] reported that one-fifth of mature U.S. women suffer from bothersome leakage of stool in the absence of acute diarrheal illness at least once a year. Despite the considerable impact of UI and FI (referred to as “incontinence”) on quality of life (QoL), many people never seek help for either UI or FI and thus remain unaccounted [3–6]. There has been extensive research documenting the success of various forms of conservative treatment, but the reality is that less than 50% of persons with UI seek help [7, 8], and even less inform a health-care provider that they have FI. Many more, especially in less developed countries, do not have help available [8, 9]. The psychological consequences of incontinence are well documented, and barriers to seeking help have been frequently identified in the literature. Barriers include embarrassment, social stigma, and the mistaken belief that the incontinence is either inevitable, untreatable, or a normal part of aging [10]. Public awareness and community-based continence promotion programs are ways to destigmatize UI and to promote understanding about this widespread condition [8]. This chapter will discuss the stigmatization of UI and FI and provide examples of what is currently being done worldwide to increase awareness and understanding.

The basis of stigma The word stigma has been defined in different ways including “as a mark of disgrace or reproach” and as “a moral or physical blemish that serves to identify a disease or condition.” These are negative attributes as they discredit an individual, reduce the person from a whole and normal person to a tainted, discounted one. Gartley’s [11] definition of stigma is the “recognition of difference based on some distinguishing characteristic or ‘mark’ and a consequence of devaluation for the person.” Garcia and colleagues [12] noted that persons who are stigmatized are discredited thus reducing the person to a tainted human being. Stigmatization is characterized by chronic social and physical avoidance of a person(s) by other people. The key feature associated with stigma is that the stigmatized person and society often represent extreme positions of the condition. These definitions and attributes of stigmatization are closely aligned with incontinence. Gartley [13] noted that stigma in health care is a subset of stigmatization in society and is costly for all. Heinz [14] noted that stigma associated with UI signifies something lost or abnormal. There are several types of stigma (see Table 2.1), and each addresses an aspect of incontinence behavior. Oaten and *

With thanks to Diane K. Newman.

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colleagues [15] propose that many forms of stigmatization reflect the activation of this disease-avoidance system, which is prone to respond to visible signs and labels that connote disease, irrespective of their accuracy. Joachim and Acorn [16] developed a framework that would explain how people respond to stigmas. They found that the visibility or invisibility of the condition was crucial. If it could be kept invisible (e.g., urine or stool leakage), individuals had options about whether/when to disclose information about their condition. When it was more visible, they had to focus on whether the condition could be hidden. When it could not be concealed, more stigma was likely.

Stigma and its association with incontinence Being stigmatized because of a chronic disabling illness means being responded to differently by the general public [17]. Three strategies are used to manage stigma: avoid hurtful situations, pass as normal, and appropriate a philosophy to help cope with the stigma. This is demonstrated in Figure 2.1. When an individual develops a continence concern, they may feel stigmatized due to loss of control and invasion of their privacy [18]. The stigma, shame, and humiliation of wetting episodes in public are major fear factors, resulting in feelings of isolation from a person’s family, peers, communities, and activities [19]. This is not surprising as bladder and bowel continence is an adjustment to the social norm, especially in Western cultures, which have developed acceptable rules and behavior for bladder and bowel emptying [20–22]. UI has frequently been linked with incompetence because control and self-restraint is important to notions of adulthood in Western society. Many feel humiliated with their condition and find it uncomfortable and distressing to discuss with health-care providers [8, 23]. Yuan et al. [24] found that many patients considered UI as shameful and their own fault and were unwilling to talk about incontinence with their families, friends, or doctors. In a survey undertaken by the National Association for Continence in 2019, 90% of respondents reported feeling depressed, isolated, or hopeless due to incontinence [25]. The stigma, level of shame, and embarrassment attached to incontinence is higher than that for depression and cancer [26]. Individuals who reduce their social interaction with peers and limit consultation with health-care professionals due to incontinence are at an increased risk of mental health problems [27]. Our society places a significant emphasis on sanitation and personal hygiene [28]. Discussions about personal hygiene and/ or elimination are not part of social conversations, especially in Western cultures. During toilet training, children are inoculated with all the cultural norms and expectations concerning elimination of urine and stool [29]. If incontinence occurs in adulthood, persons revive those childhood beliefs and begin to internalize their condition causing a decrease in self-esteem and feelings of shame and of not being “normal” [10]. These barriers are shared by the public as well as by many health-care providers and may contribute to the burden of caregiving [30].

DOI: 10.1201/9781003144236-3

Tackling the Stigma of Incontinence

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TABLE 2.1: Types of Stigma Type

Definition

Behavior Related to Incontinence

Felt or perceived stigma

Internalize negative perceptions regarding oneself

Self-stigma

Harsh or unjustified beliefs about oneself

Enacted stigma

Discrimination that takes place at an institution or from a group

Avoidance of incontinence is a strategy many use and is a worldwide coping measure. Seshan and Muliira [5] conducted a study by going door to door in Coimbatore, South India, to interview women about the presence of UI and attitudes on the condition. Of the 598 participants recruited in the study, a total of 202 (33.8%) reported that they had UI and 396 (66%) denied having UI. The attitudes of these women about UI were negative whether they experienced the problem or not. More than 80% of all respondents stated they agreed with the following statements: • Accidental loss of urine is a common problem that every woman faces. • Women should not go to social events if they have UI.

• Denial of the problem. • Embarrassment resulting in lack of disclosure to family members, friends, or providers. • Feels “dirty,” contaminated. • Discomfort with disclosing symptoms. • Concerned about odor. • Belief that they are the only person with the problem. • Self-isolation. • Avoids intimacy, feels sexually undesirable. • Mistaken beliefs such as “art of being a women,” “part of growing old.” • Disgust expressed by others because of odor, frequent trips to the bathroom, etc. • Long-term care staff avoid or ignore UI complaints. • Fear of institutionalization. • Media subtle messages to “keep UI in the closet” or comparisons to “plumbing” that can be fixed.

• There is no treatment available for UI. • UI cannot be prevented or cured. The embarrassment associated with UI was evident as 65% of women who reported UI had not revealed their problem to anyone, professional or not. There is no question that the stigma of UI prevents help-seeking in women [31]. Persons with incontinence experience insensitive language and loss of freedom and endure questions of a sensitive nature. The experience of UI generally includes the subthemes of fear, stigmatization, and shame. Siddiqui and colleagues [32] systematically reviewed perceptions regarding UI in women of different racial and ethnic backgrounds. Dominant themes fell into two

Incontinence impairment and disability

Restriction of activities and social roles

Lack of confidence and skills Negative labeling

Isolation and withdrawal from social life

Diminished self-esteem and "felt" stigma

Negative social views and stereotypes transmitted in mass media and everyday life

FIGURE 2.1  Cycle of incontinence stigma: negative feedback between incontinence stigmatization, self-esteem, and participation in social activities.

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Bl ac

te hi W

k

12

• Self-blame for UI

• Self-blame for UI • Secrecy

ic an sp

ab Ar

• Self-blame for UI • Disruptions to religious observance (Muslim)

Hi

• Self-blame for UI • Disruptions to religious observance (Muslim)

• Pre-emptive voiding • Limit activities in public • Difficulty understanding terminology • Feeling that Ul not taken seriously by health-care provider • Preference to discuss Ul with other women

Asian

FIGURE 2.2  Similarities and differences in perceptions about UI in different ethnic groups. categories, UI management and UI experience, and were similar across racial/ethnic groups. Women reported a preference for discussing UI with other women, even if this was not a physician. Nonwhite women expressed self-blame and perceived UI as a negative outcome from childbirth or prior sexual experiences. Latina women maintained more secrecy around this issue, even among family members. Figure 2.2 depicts the themes among these women. Similar perceptions are reported by persons who experience fecal or anal incontinence. Olsson and Berterö [33] conducted a qualitative interpretative study based on interviews conducted with five women living with FI. The analysis resulted in four different themes: self-affirmation, guilt and shame, limitations in life, and personal approach. They found that living with FI had a lot in common with living with a stoma, including associated taboo, guilt and shame, and a persistent need for control. The Boston Area Community Health population-based random epidemiological survey of urologic symptoms (n = 5503) indicated that the stigma of UI also includes other lower urinary tract symptoms (LUTS) [34]. Overactive bladder (OAB) symptoms of urgency and frequency were linked to social interruption, loss of socially expected control of the body, not understanding the nature of the bladder problem, and the need to mix private behavior and public space. The stigma of OAB and UI was correlated to whether the problem was perceptible (i.e., odor or observation of trips to the bathroom or soiled clothes) or concealed. Men reported feeling stigmatized for being seen making frequent trips to the bathroom and feared being viewed as impotent. Women feared being stigmatized based on having an unclean body and a compromised social identity.

Ignorance and lack of tolerance by and of others is common, leading frequently to anger and withdrawal. Whether the condition is visible or apparent to others (e.g., disfigurement) or concealed (e.g., colostomy or incontinence) does not change the way the person with the condition feels or reacts. The stigma associated with incontinence is similar to the stigma in other conditions and is associated with public ignorance and lack of awareness. The traditional medical model of care is very much focused on “treatment” but does not empower the sufferer to actually develop strategies to cope with what is often a lifelong condition. The topic of stigma associated with both UI and FI have received scant attention in the research literature. Questions have also been raised as to whether the patient reported outcome measures used to assess incontinence and treatment outcomes adequately address the impact of stigma and how it may affect health-care interventions [35].

Social “taboo” surrounding the lack of bladder and bowel control Bladder and bowel problems are often ignored, considered taboos, and are subjects not talked about because the truth is too unpleasant for people to acknowledge [36]. When society also ignores the presence of a taboo by refusing to acknowledge or address it, the taboo is stigmatized [37]. It is possible to understand the longstanding stigma surrounding unexpected loss of urine and feces by considering the potential health consequence of incontinence on society [9]. Epidemiological and clinical studies of individuals with incontinence indicate that the condition has a considerable impact on overall QoL and well-being. The inability to control

Tackling the Stigma of Incontinence urine or feces is one of the most unpleasant and distressing symptoms a person can experience, causing stigmatization and denial of the condition [12]. Emotional well-being is impaired, probably as a result of social isolation and feelings of stigmatization produced by the incontinence. Society does not know how to respond to persons with incontinence, so avoidance is the norm. This public stigma affects treatment-seeking attitudes through internationalization of messages [38].

Stigma and its effect on care-seeking A common phenomenon seen in conditions that have greater stigma (and often are less life-threatening) is that they tend to take a much longer time to be reported to a health-care provider (e.g., physician) and even longer to family, friends, and others. Urologic and gastrointestinal symptoms are associated with feelings of stigmatization, making it challenging for individuals to talk with doctors about their condition [33, 39]. To avoid embarrassment, persons with incontinence turn to “self-management” rather than “seeking help” from a doctor or nurse. With increasing access to the Internet, many people are now looking to selfdiagnose and treat through information gained on the Internet, social media, and through advertising. However, this poses its own challenges due to variations in the quality and validity of information provided on some websites [40]. It can also lead to a considerable delay in seeking help as it has been reported that 40% of people with incontinence waited two or more years after symptoms first appeared before mentioning it to their doctor [25]. Unfortunately, factors that promote care-seeking behavior for incontinence issues remain less researched and are complex and multifactorial [8]. Triggers for help-seeking are important for health-care professions to understand. Older adults may be keen to seek help if they are concerned that a health issue such as how incontinence impacts on their ability to remain independent and living in the community [22]. In certain parts of the world, the gender of the person with incontinence may be a factor in helpseeking behavior and the gender of the health-care provider may be a barrier. Barriers to seeking help for continence issues that have been frequently identified in the literature include embarrassment, social stigma, and the mistaken belief that incontinence is inevitable, untreatable, and/or a normal part of aging. The authors of a Swedish study suspected that lack of knowledge, worries about different procedures, and negative expectations may be important factors in reducing the desire to seek treatment among even those most severely affected [41]. Among women with gynecological cancers who experience concomitant LUT, failure to seek help for the latter symptoms has been attributed to a perception that the LUTS were not serious enough symptoms to warrant attention and lack of awareness of treatment options [42]. In a Canadian study by Shaw et al. those who held the belief that incontinence was a normal part of aging were less likely to seek help, regardless of the impact it may have on their QoL [43]. Vethanayagam et al. performed interviews to explore the views of older people with incontinence on the process of seeking help and identified three themes [44]: • Being Brushed Aside: Where participants expressed the feeling that their health provider did not prioritize or recognize their concerns.

13 • Putting Up with It: In which participants delayed seeking help for reasons including embarrassment, development of coping mechanisms, perceiving UI as a normal part of aging, or due to being unaware that help was available. • Something Has to Be Done: Where help-seeking was prompted by the recognition that their UI was a serious problem (e.g., as a result of experiencing incontinence in public, the remark of a relative, or the belief that they had a serious illness). A known barrier is terminology for incontinence as how patients relate their condition may not match health-care professional’s medical assessment. In an Internet-based survey of mature women who reported FI, they preferred the term “accidental bowel leakage” (n = 667, 71.1%) as opposed to “bowel incontinence” (n = 211, 22.5%) and FI (n = 60, 6.4%) [2]. Patel et al. found that many patients had a significant emotional component to their experience of FI and that knowledge about the terms used to describe the condition was often limited [45].

Incontinence, attitudes, and beliefs The way people react to a person with incontinence is influenced by many factors. The further the person is connected from the sufferer, the more negative attitudes become. As the condition becomes more severe, the more obvious it becomes to others, and often, therefore, the more the person is likely to be stigmatized [12, 22]. In addition, attitudes and reactions of both the person with incontinence and those in society who interact with that person may vary according to the age of the person. At the extreme is the newborn child, where incontinence is regarded as a norm, through to childhood bedwetting, all the way to a frail older person in a nursing home. Depending on the age, sex, and social situation of the person, the reaction may well be different. It is important to understand how attitudes and stigma can change for these conditions. An important component is breaking the cycle of public and personal ignorance through education and public awareness programs [8]. For this to be successful, there needs to be a partnership between health-care professionals, governments, and industry groups with a vested interest to work together to break the cycle of ignorance and negative attitudes. Central to this is the availability of funds, either in allocated dollars or “in kind” (e.g., access to advertisements), which represents an ongoing funding source. A group of experts [9] conducted a systematic review of existing evidence, collated qualitative data, and used expert consensus to develop an internationally applicable service specification for continence care around the world. This service can be tackled locally and internationally in order to raise awareness of incontinence, bring a greater opportunity to incontinence management, and improve the plight of hundreds of millions of people around the world. The good news about stigma is that individuals and society as a whole continue to change their views on what is or is not a stigmatizing condition. One reason is technology as consumers now have immediate access to information about incontinence via the Internet and social media (e.g., YouTube). In light of the reluctance of those affected by stigmatized illnesses such as incontinence to seek treatment or to ask health-care professionals for information, the Internet may prove to be a useful tool for patient education, public health outreach, and improving QoL in those with incontinence [46]. In a national survey of Internet users in

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14 the United States, Berger and colleagues found a trend among people with a stigmatized illness such as UI to more likely report that using the Internet increased their health-care utilization and communication with a health-care provider [47].

Patient-centered care According to the World Health Organization (WHO; [48]), patient-centered care is defined as “an approach to care that consciously adopts the perspectives of individuals, families, and communities and sees them as participants as well as beneficiaries of trusted health systems that respond to their needs and preferences in a humane and holistic way.” Peoplecentered care also requires that patients have the education and support they need to make decisions and participate in their own care and that carers are able to attain maximal function within a supportive working environment [48]. It has been shown to improve quality outcomes and patient satisfaction [49]. Patient-centered health care is based on five core principles [50]: 1. Patients have individual needs and preferences. 2. Patients have the right and responsibility to be involved in making decisions that affect their lives. 3. Governments and health-care organizations should involve patients when designing new health-care policies. 4. Patients must have access to safe, quality, and appropriate health services, treatments, and preventive care (e.g., vaccinations). 5. Patients should be given the information needed to make decisions about health care, treatment, and living with their condition. This model of health care has been suggested as the ideal model to improve continence care as it does not focus on standard objective outcome measures seen in clinical research but identifies individuals’ expectations, knowledge levels, and knowledge gaps and allows care to be tailored to their needs. There is also a significant focus on education of the patients, their family, caregivers, and other health-care professionals. It has been demonstrated that a lack of public knowledge can lead to delays in help-seeking [51, 52]. Paid caregivers have reported that they feel they do not have enough training and knowledge to adequately manage incontinence (not only in urban long-term care settings but also in rural community populations with geographical and language barriers) [53, 54] and family carers have reported even less knowledge, confidence, and competence in helping their family member manage their condition [55]. By educating and improving the knowledge of all those involved in continence care, it will help to de-stigmatize incontinence, improve understanding, and lead to more proactive care and improved QoL of those living with incontinence and those who care for them [51]. In order to achieve this, health-care professionals must ensure the protection of an individual’s privacy and develop clear, effective communication between patient and caregivers, creating a collaborative, secure, and sensitive environment for dialogue [56]. Respect, dignity, kindness, and consideration shown on a personal level will have an extraordinarily positive impact on the experience of patients and carers [57]. A multidimensional and multidisciplinary team approach is essential to reduce embarrassment and social isolation [58].

Role of national organizations As previously mentioned, the stigma associated with incontinence is similar to other conditions and is associated with public ignorance and lack of awareness. An important component is breaking the cycle of public and personal ignorance through education and public awareness programs. As the stigma associated with incontinence is similar to other conditions and is associated with public ignorance and lack of awareness, educating the public will increase their awareness of the condition. Therefore, it is important to understand how attitudes and stigma have changed for these conditions. There have been some advances in breaking the cycle of public and personal ignorance through education and public awareness programs [59]. Patient advocacy organizations for UI have been formed worldwide to promote awareness (www. icsoffice.org). Continence promotion involves informing and educating the public that incontinence is not inevitable or shameful, but is treatable or at least manageable [8]. The International Continence Society, a professional organization, has supported the work of organizations that promote incontinence awareness and education, and promotion. Although the ratio between affected patient populations and continence national organization funding has not been formally studied, anecdotal information suggests that continence promotion is among the most difficult of medical problems for which to obtain funding. In view of all these challenges, the proliferation of new national continence organizations, especially in Asia and South America, is a validation of both the need for continence promotion and the dedication of those who have recognized and are addressing this need. There are also many charities and patient organizations that have been developed with the aim of providing advocacy services, information to the public and to health-care professionals but also to provide patients with access to support from people with lived experience of a condition. This may be in the form of a telephone support line or through such mechanism as social media groups, and online forums.

Summary In order to improve health care for those men and women with incontinence, the social stigma must be removed, public education about resources and treatment must be increased, and health-care professionals need to be trained in incontinence management. The good news is that there is a growing international awareness about the need to “destigmatize” incontinence by promoting awareness through partnerships of health-care professionals, governments, and industry. This process must continue in order for incontinence to be removed from the list of conditions associated with stigma so that people can and will seek help.

References

1. Shamliyan T, Wyman JF, Bliss, DZ et al. Prevention of urinary and fecal incontinence in adults. Evid Rep Technol Assess 2007;161:1–379. 2. Brown HW, Wexner SD, Segall MM, Brezoczky KL, Lukacz ES. Accidental bowel leakage in the mature women’s health study: Prevalence and predictors. Int J Clin Pract November 2012;66(11):1101–1108. 3. Pedersen LS, Lose G, Høybye MT, Jürgensen M, Waldmann A, Rudnicki M. Predictors and reasons for help-seeking behavior among women with urinary incontinence. Int Urogynecol J 2018;29(4):521–530.

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4. Ribas Y, Coll M, Espina A et al. Initiative to improve detection of faecal incontinence in primary care: The GIFT Project. Fam Pract 2017;34(2): 175–179. 5. Seshan V, Muliira JK. Self-reported urinary incontinence and factors associated with symptom severity in community dwelling adult women: Implications for women’s health promotion. BMC Womens Health April 8, 2013;13:16. 6. Bliss DZ, Norton C, Vodusek DB. Raising awareness about fecal incontinence. Neurourol Urodyn April 2010, 2013;29(4):612–615. 7. Moore K, Bradley C, Burgio B et al. Adult conservative management. In P Abrams, L Cardozo, S Khoury, and A Wein, eds. Incontinence: Proceedings from the Fifth International Consultation on Incontinence. Plymouth, U.K.: Health Publications, 2013, pp. 1101–1228. 8. Newman DK, Buckley B, Gordon D, Griebling TL, Petty LE, Wang K. Continence promotion, education & primary prevention. In P Abrams, L Cardozo, S Khoury, and A Wein, eds. Incontinence: Proceedings from the Fifth International Consultation on Incontinence. Plymouth, U.K.: Health Publications, 2013, pp. 1787–1828. 9. Wagg AS, Newman DK, Leichsenring K, van Houten P. Developing an internationally-applicable service specification for continence care: Systematic review, evidence synthesis and expert consensus. PLOS ONE August 14, 2014;9(8):e104129. 10. Newman DK, Wein AJ. Managing and Treating Urinary Incontinence, 2nd ed. Baltimore, MD: Health Professions Press, 2009, pp. 565–584. 11. Gartley CB. Bringing Mohammed to the mountain: Educating the community for continence. Urol Nurs October 2006a;26(5):387–393. 12. Garcia JA, Crocker J, Wyman JF. Breaking the cycle of stigmatization. J Wound Ostomy Continence Nurs 2005;32(1):38–52. 13. Gartley C. Life with incontinence. Lancet January 7, 2006;367(9504):68. 14. Heinz PA, DeMucha CM, Deguzman MM, Softa R. Stigma and micro aggressions experienced by older women with urinary incontinence: A literature review. Urol Nurs November–December 2013;33(6):299–305. 15. Oaten M, Stevenson RJ, Case TI. Disease avoidance as a functional basis for stigmatization. Philos Trans R Soc Lond B Biol Sci December 12, 2011;366(1583):3433–3452. 16. Joachim G, Acorn S. Stigma of visible and invisible conditions. J Adv Nurs 2000;32(1):243–248. 17. Earnshaw VA, Quinn DM. The impact of stigma in healthcare on people living with chronic illnesses. J Health Psychol March 2012;17(2):157–168. 18. Whitehead J, Wheeler H. Patients’ experience of privacy and dignity. Part 2: An empirical study. Br J Nurs 2008;17(7):458–464. 19. Sinclair AJ, Ramsay IN. The psychosocial impact of urinary incontinence in women. Obstet Gynaecol 2011;13(3):143–148. 20. Herschorn S, Gajewski J, Schutz J, Corcos J. A population-based study of urinary symptoms and incontinence: The Canadian Urinary Bladder Survey. Br J Urol Int 2007;101:52–58. 21. Newman D. Double taboos: Urinary and fecal incontinence: The state of the science. Ostomy Wound Manage 2007;53(12):6–7. 22. Norton C. Nurses, bowel continence, stigma, and taboos. J Wound Ostomy Continence Nurs March–April 2004;31(2):85–94. 23. Wagg A. Improving continence care around the world. Nurs Times 2015;111(22):22–24. 24. Yuan HB, Williams BA, Liu M. Attitudes toward urinary incontinence among community nurses and community-dwelling older people. J Wound Ostomy Continence Nurs 2011;38:184–189. 25. NAFC, 2019, The State of Incontinence. https://www.nafc.org/bhealthblog/overcoming-the-stigma-of-incontinence (accessed March 30, 2021). 26. Elenskaia K, Haidvogel K, Heidinger C, Doerfler D, Umek W, Hanzal E. The greatest taboo: Urinary incontinence as a source of shame and embarrassment. Wien Klin Wochenschr October 2011;123(19–20):607–610. 27. Kwak Y, Kwon H, Kim Y. Health-related quality of life and mental health in older women with urinary incontinence. Aging Ment Health 2016;20(7):719–726. 28. Rozensky RH, Tovian SM, Dubyak P. How we view our bodies. In CB Gartley, MR Klein, C Norton, and A Saltmarche, eds. Managing Life with Incontinence. Wilmette, IL: Simon Foundation, 2012, pp. 71–84. 29. Paterson J. Stigma associated with postprostatectomy urinary incontinence. J Wound Ostomy Continence Nurs May 2000;27(3):168–173. 30. Brittain K, Shaw C. The social consequences of living with and dealing with incontinence—A carer’s perspective. Soc Sci Med 2007;65(6): 1274–1283. 31. Wan X, Wang C, Wang K, Li J, Sun T, Guan X. Disease stigma and intentions to seek care for stress urinary incontinence among community-dwelling women. Maturitas April 2014;77(4):351–355.

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32. Siddiqui NY, Levin PJ, Phadtare A, Pietrobon R, Ammarell N. Perceptions about female urinary incontinence: A systematic review. Int Urogynecol J 2014;25(7):863–871. 33. Olsson F, Berterö C. Living with faecal incontinence: Trying to control the daily life that is out of control. J Clin Nurs June 3, 2014;24:141–150. 34. Elstad EA, Taubenberger SP, Botelho EM, Tennstedt SL. Beyond incontinence: The stigma of other urinary symptoms. J Adv Nurs November 2010;66(11):2460–2470. 35. Southall K, Tuazon JR, Djokhdem AH, van den Heuvel EA, Wittich W, Jutai JW. Assessing the stigma content of urinary incontinence intervention outcome measures. J Rehabil Assist Technol Eng 2017;4, 2055668317738943. 36. Norton C, Dibley L. Understanding the taboos about bladders and bowels. In CB Gartley, MR Klein, C Norton, and A Saltmarche, eds. Managing Life with Incontinence. Wilmette, IL: Simon Foundation, 2012, pp. 1–8. 37. Drennan VM, Cole L, Iliffe S. A taboo within a stigma? A qualitative study of managing incontinence with people with dementia living at home. BMC Geriatr November 14, 2011;11:75. 38. Jackson CB, Botelho EM, Welch LC, Joseph J, Tennstedt SL. Talking with others about stigmatized health conditions: Implications for managing symptoms. Qual Health Res November 2012;22(11):1468–1475. 39. Wang C, Li J, Wan X, Wang X, Kane RL, Wang K. Effects of stigma on Chinese women’s attitudes towards seeking treatment for urinary incontinence. J Clin Nurs April 2015;24(7–8):1112–1122. 40. Saraswat I, Abouassaly R, Dwyer P, Bolton DM, Lawrentschuk N. Female urinary incontinence health information quality on the Internet: A multilingual evaluation. Int Urogynecol J 2016;27(1):69–76. 41. Andersson G, Johansson JE, Garpenholt O, Nilsson K. Urinary incontinence—Prevalence, impact on daily living and desire for treatment: A population-based study. Scand J Urol Nephrol 2004;38:125–130. 42. Hazewinkel MH, Sprangers MA, Taminiau-Bloem EF, van der Velden J, Burger MP, Roovers JP. Reasons for not seeking medical help for severe pelvic floor symptoms: A qualitative study in survivors of gynaecological cancer. Br J Obstet Gynaecol January 2010;117(1):39–46. 43. Shaw C, Rajabali S, Tannenbaum C, Wagg A. Is the belief that urinary incontinence is normal for ageing related to older Canadian women’s experience of urinary incontinence?. Int Urogynecol J 2019;30(12):2157–2160. 44. Vethanayagam N, Orrell A, Dahlberg L et al. Understanding help-seeking in older people with urinary incontinence: An interview study. Health Soc Care Community 2017;25(3):1061–1069. 45. Patel K, Bliss DZ, Savik K. Health literacy and emotional responses related to fecal incontinence. J Wound Ostomy Continence Nurs 2010;37: 73–79. 46. Rosensky RH, Tovian SM, Gartley CB, Nichols TR, Layton M. A quality of life survey of individuals with urinary incontinence who visit a selfhelp website: Implications for those seeking healthcare information. J Clin Psychol Med Settings 2013:20:275–283. 47. Berger M, Wagner TH, Baker LC. Internet use and stigmatized illness. Soc Sci Med October 2005;61(8):1821–1827. 48. World Health Organization, 2016, Framework on Integrated People Centered Health Services. https://apps.who.int/gb/ebwha/pdf_files/ WHA69/A69_39-en.pdf?ua=1&ua=1 (accessed March 2021). 49. Taylor DW, Cahill JJ. From stigma to the spotlight: A need for patientcentred incontinence care. In Healthcare Management Forum. Los Angeles, CA: Sage Publications, November 2018, Vol. 31, No. 6, pp. 261–264. 50. International Alliance of Patients’ Organisations, June 2007, What Is Patient-Centred Healthcare? A Review of Definitions and Principles. 2nd ed. http://iapo.org.uk/sites/default/files/files/IAPO%20Patient-Centred%20 Healthcare%20Review%202nd%20edition.pdf (accessed March 2021). 51. Taylor DW, Weir M, Cahill JJ, Rizk DE. The self-reported prevalence and knowledge of urinary incontinence and barriers to health careseeking in a community sample of Canadian women. Am J Med Sci 2013;3(5):97–102. 52. Taylor DW, Cahill JJ, Rizk DE. Denial, shame and acceptance: Generating base-line knowledge and understanding of fecal incontinence amongst long-term care residents and care providers. Public Health Res 2014;4:13–18. 53. Taylor DW, Cahill JJ. Continence training needs assessment of residential long-term care personal support workers. ARC J Nurs Healthc 2017;3(1):12–17. 54. Saiki LS, Morales ML. Incontinence care needs in a US rural border region: Perspectives of promotoras. Online J Rural Nurs Health Care 2019;19(1)179–196.

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55. Taylor DW, Cahill JJ. Continence home care: A qualitative study of family carers and community-based continence care providers. J Health Sci 2018;8(2):19–25. 56. Kadivar M, Mardani-Hamooleh M, Kouhnavard M. Concept analysis of human dignity in patient care: Rodgers’ evolutionary approach. J Med Ethics Hist Med 2018;11. 57. Ellins J, Glasby J, Tanner D et al. Understanding and improving transitions of older people: A user and carer centred approach. Final report. NIHR Service Delivery and Organisation Programme, 2012.



58. Stickley A, Santini ZI, Koyanagi A. Urinary incontinence, mental health and loneliness among community-dwelling older adults in Ireland. BMC Urology 2017;17(1):1–9. 59. Newman DK. Community awareness and education. In GH Badlani, GW Davila, MC Michel, and JJMCH de la Rosette, eds. Continence: Current Concepts and Treatment Strategies. London, U.K.: Springer-Verlag, 2009, pp. 521–532.

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THE EPIDEMIOLOGY OF URINARY INCONTINENCE, OTHER LOWER URINARY TRACT SYMPTOMS, AND PELVIC ORGAN PROLAPSE Maria Gyhagen and Ian Milsom Urinary incontinence (UI) and other lower urinary tract symptoms (LUTS) as well as other forms of pelvic floor dysfunction such as pelvic organ prolapse (POP) are highly prevalent conditions with a profound influence on well-being and quality of life.1–3 Millions of women throughout the world are afflicted1,2 and there has been a growing interest in these symptoms in recent years as a consequence of the increased awareness of the human and social implications for the individual sufferer. Population studies have demonstrated that UI is more common in women than men and that approximately 10% of all women suffer from UI.1,2 Prevalence increases with age and in women aged ≥70 years more than 20% of the female population are affected. Urinary leakage is perceived by many women but is not always reported to the doctor. However, an increasing awareness of the problem has in recent years attracted more patients to seek advice. In older women UI may lead to possible rejection on the part of a relative and may be an important factor in the decision whether or not to institutionalize an elderly person. The prevalence of POP based on a sensation of a mass bulging into the vagina is consistent, ranging between 10% and 20%.1 A number of specific obstetrical events and interventions have been implicated as risk factors for the development of POP.1 POP is an uncommon finding in women who have not undergone a vaginal delivery.1 UI, other LUTS and POP not only cause considerable personal suffering for the afflicted individual but are also of immense economic importance for the health service.4 The lifetime risk of undergoing surgery for UI or POP has been reported to vary between 5% and 20%.5–8 In Sweden, the annual cost of UI alone has been reported to account for approximately 2% of the total health-care budget. 3

Urinary incontinence The reported prevalence of UI among women varies widely in different studies due to the use of different definitions, the heterogenicity of different study populations, and population sampling procedures. In addition, different definitions of UI have been applied. UI has been defined in the joint report from the International Urogynecological Association (IUGA)/ International Continence Society (ICS) as any involuntary leakage of urine.9 However, some authors have chosen to restrict prevalence figures according to the frequency of involuntary urinary leakage – for example, based only on daily, weekly, monthly, or annual urinary leakage. Thus, for the reasons given above, it is difficult to compare the results of different population studies. However, when reviewing the literature, there is considerable evidence to support the theory that the prevalence of UI in women increases with age, but there are divergent opinions regarding the pattern of this increase.1,10–38

DOI: 10.1201/9781003144236-4

In a review1 of population studies from numerous countries, the prevalence of UI ranged from approximately 5% to 70%, with most studies reporting a prevalence of any UI in the range of 25–45%. For daily incontinence, prevalence estimates typically range between 5% and 15% for middle-aged and older women. Thomas et al.10 investigated the prevalence of UI in two London boroughs by a postal survey (Fig. 3.1a). The reported prevalence of UI increased from 5.1% in girls aged 5–14 years to 16.2% in 85-year-old women. There was, however, little or no change in prevalence rates up to 35 years of age. The prevalence rates then increased to approximately 10% in the 35–44 years age group. There was no significant increase at the time of the menopause but a further increase to approximately 16% occurred in women ≥75 years. On the other hand, Iosif et al.11 and Jolleys18 (Fig. 3.1b) reported a maximum prevalence of UI at the time of the menopause. Hannestad et al., 31 in a large Norwegian study, demonstrated an increased prevalence during the perimenopausal years, with prevalence rates being lower both before and after the time of the menopause (Fig. 3.2a). There are several large population-based studies from Sweden describing the prevalence of UI in women and men. Figure 3.3(a) illustrates the results from two independent studies of UI in women. In both studies, prevalence was restricted to women who had urinary leakage at least once per week. Although the study performed by Samuelsson and co-workers29 was undertaken in a rural area and that by Simeonova et al. 30 was carried out in an inner city, there are strong similarities between the results of the two studies, with a linear increase in the prevalence of UI which continues over the perimenopausal years. In contrast, another Swedish population study27 (Fig. 3.4a) failed to demonstrate any increase in the prevalence of UI between women aged 46 and 56 years of age (prevalence 12% for both cohorts). The majority of 46-year-old women were premenopausal whereas the majority of 56-year-old women were postmenopausal. There were no differences in prevalence rates between pre- and postmenopausal women within the respective birth cohorts (Fig. 3.4a). Thus, there was no evidence to suggest that the prevalence of UI increased at the time of the last menstrual period. The Fifth International Consultation on Incontinence after an evaluation of the available literature came to the conclusion that the menopause per se did not influence the prevalence of UI. However, this is not necessarily synonymous with the fact that the reduction in circulating estrogens is not associated with an increase in the prevalence of UI in women after the menopause. The prevalence of UI in women has been compared with the prevalence in men of the same age in two large Swedish studies.27,39 As can be seen from the results illustrated in Figure 3.3(b), there is a higher prevalence of UI in women than in men in all the age groups studied. In general, the prevalence of UI is approximately three times more common in women than in men. 17

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FIGURE 3.1  Comparison of the prevalence of female UI in two British studies. (a) The study by Thomas et al. (ref. 10) was performed in 9323 British women and (b) the study by Jolleys et al. (ref. 18) was performed in 833 British women.

FIGURE 3.2  Prevalence of UI in Norwegian women grouped (a) by age and (b) type of incontinence (MUI, mixed urinary incontinence; SUI, stress urinary incontinence; UUI, urge urinary incontinence; based on data from ref. 31).

FIGURE 3.3  Comparison of the prevalence of UI: (a) in two population-based studies of Swedish women in a rural area (Samuelsson et al., ref. 29) and in an inner city (Simeonova et al., ref. 30); (b) in two population-based Swedish studies in women (n = 7459, ref. 27) and men (n = 7763, ref. 39) of the same ages.

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FIGURE 3.4  Prevalence of UI: (a) in a random sample of 46- and 56-year-old women grouped according to menopausal (MP) status; (b) in a random sample of 46- (n = 1530) and 56-year-old (n = 1638) women grouped according to parity; and (c) in a random sample of 66-, 71-, 76-, 81-, and 86-year-old women grouped according to history of hysterectomy (data from ref. 27). The majority of the population studies referred to in this chapter have been performed by means of postal questionnaires. In several of the studies, attempts have been made to determine the proportion of women suffering from the different types of urinary leakage, i.e. stress urinary leakage (SUI), urge urinary leakage (UUI), and mixed urinary leakage (MUI). The distribution of the various types of incontinence in the large Norwegian study by Hannestad et al. 31 is shown in Figure 3.2(b). In the literature, isolated stress urinary leakage tends to dominate among younger women while the number of women with urge incontinence and mixed incontinence increases with age. Further studies27,30–35 have added important information on the prevalence of incontinence in women younger than 30 and older than 80 years of age, particularly for the prevalence of incontinence by type. These studies are consistent with previous studies reporting that older women are more likely to have mixed and urge incontinence while young- and middle-aged women generally report stress incontinence. Overall, approximately half of all incontinent women are classified as stress incontinent. A smaller proportion is classified as mixed incontinent and the smallest fraction as urge incontinent. A recent study which included the entire adult age range by Hannested et al. 31 demonstrated a fairly regular increase in prevalence of mixed incontinence across the age range, and a decrease in prevalence of stress incontinence from the 40–49 years old age group through the 60–69 years old group. There is no hard evidence for different prevalences of UI among Western countries. However, comparing prevalence between countries based on separate studies is difficult due to differences in methods and definitions, as well as language, cultural, and social differences. One of the few studies to estimate the prevalence of UI in more than one country found similar prevalences of any UI (41–44%) in three of the four countries examined (France, Germany, and UK), but a lower prevalence

(23%) in the fourth country (Spain). 32 There was no apparent reason for the lower prevalence in Spain. UI is, however, not static but dynamic and many factors may contribute to incidence, progression, or remission. There are only a few studies describing progression as well as remission, in the short term, of UI in the general population as well as in selected groups of the population. The mean annual incidence of UI seems to range from 1% to 9% while estimates of remission are more varying, 4–30%.40–42 Wennberg et al.40 studied the prevalence of UI in the same women (aged ≥20 years) over time in order to assess possible progression or regression. A self-administered postal questionnaire with questions regarding UI, OAB, and other LUTS was sent to a random sample of the total population of women in 1991. The same women who responded to the questionnaire in 1991 and who were still alive and available in the population register 16 years later were re-assessed using a similar self-administered postal questionnaire. The overall prevalence of UI increased from 15% to 28% (p < 0.001) from 1991 to 2007 and the incidence rate of UI was 21% while the corresponding remission rate was 34% (Fig. 3.5). Thus, in summary, when reviewing the literature, there is considerable evidence to support the theory that the prevalence of UI increases in a linear fashion with age as shown in Figure 3.6 which includes pooled data from 19 epidemiologic studies where UI was reported to occur at least once per week.

Factors influencing the prevalence of UI Risk factors described in the literature are shown in Table 3.1.1,31–34,43–49 For the majority of these risk factors, there are at present no controlled trials demonstrating that intervention reduces the incidence, prevalence, or degree of severity of UI.

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20

FIGURE 3.5  The incidence and regression of UI in the same women assessed in 1991 and 2007 (from ref. 40, with permission).

FIGURE 3.6  Prevalence of female UI (≥1/week) which affected the woman’s way of life (summary of 19 population studies, based on ref. 1). TABLE 3.1: Risk Factors for Urinary Incontinence in Women Age Sex Smoking Chronic bronchitis, asthma Ethnic group Obesity Pregnancy Vaginal delivery Collagen defect Hysterectomy Dementia Stroke, Parkinson’s disease, etc. Physical activity Medication Constipation Diuretics Enuresis Chronic illness

The influence of various factors on the prevalence of UI was evaluated by means of a postal questionnaire in women aged 46–86 years resident in the city of Gothenburg, Sweden.27 Age, parity, and a history of hysterectomy were all correlated to the prevalence of UI which increased in a linear fashion from 12.1% in women 46 years of age to 24.6% in women aged 86 years of age. The prevalence of UI was greater in parous women compared to nulliparous women, and prevalence increased with increasing parity (Fig. 3.4b). UI was more prevalent in women who had undergone a hysterectomy (Fig. 3.4c). The prevalence of UI was unaffected by the duration of previous oral contraceptive usage and there was no evidence to suggest that the prevalence of UI increased at the time of the last menstrual period (Fig. 3.4a). Several studies suggest that the risk of UI “runs in the family.”1,33,43–45 Family history studies have found a two- to threefold greater prevalence of stress UI among first degree relatives of women with stress UI compared to first degree relatives of continent women. In the Norwegian Nord-Trøndelag health survey (EPINCONT), daughters of mothers with UI had an increased risk of stress incontinence, mixed incontinence, and urgency incontinence. 33 In general the risk was somewhat higher for sisters of a woman with UI than for daughters. Studies from the Swedish twin register indicated that heritability contributes to the liability of developing UI. The authors presented evidence that for both disorders, genetic and non-shared environmental factors equally contributed 40% of the variation in liability.44,45 Although study methodology and the magnitude of the risk estimates vary, studies on familial transmission of incontinence are in agreement33,44,45 having a first degree female family member with SUI increases the risk for an individual becoming afflicted by the same disorder. Many studies have assessed the influence of pregnancy and in particular vaginal delivery on the risk of developing UI. The prevalence of UI in nulliparous women of childbearing age has been reported to be 10–15%.46–48 UI preceding pregnancy in nulliparous has been shown to be a strong indicator for increased prevalence of UI 4–12 years postpartum.49,50 Pregnancy in itself, independent of labor and delivery practices, seems to be a risk factor for postpartum UI51,52 especially if the incontinence started during the first trimester.53 During pregnancy, the prevalence of UI increases with gestational age1 so that more than half of all women report UI during the third trimester.51–53 Stress UI and mixed UI increased the most during pregnancy compared to before pregnancy, whereas urge UI did not change during the same period.54 During the first 3 months postpartum, UI prevalence was 30% and most women had stress UI.55 In uncomplicated courses of pregnancy and labor, UI usually declines rapidly during the first 3 months following childbirth, indicating that most symptoms are part of a normal pregnancy and delivery.47 Several studies have also demonstrated that postpartum UI is a risk factor for UI after longer (7 months to 6 years) terms of follow-up.48,56–58 The first delivery is considered to increase the prevalence of UI the most, and recent studies have demonstrated a further increase for each delivery.23,59–62 Many cross-sectional and several longitudinal studies show a protective effect of CS for UI.63–71 BMI is considered to be an established risk factor for UI,61 whereas the association between UI and age is complicated by confounders.67,68

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OAB and other LUTS In recent years, several epidemiological studies have also been conducted in order to better understand the prevalence and the impact of overactive bladder (OAB) and other LUTS. OAB is defined as the presence of urgency and frequency (either daytime or nighttime), with or without UI.9 OAB is often divided into OAB without UI (OABdry) and those with OAB and UI (OABwet). The reported prevalence of OAB in females varied between 7.7% and 31.3% and in general prevalence rates increased with age.72–77 OAB has been shown to be associated with other chronic debilitating illnesses such as depression, constipation, and diabetes as well as neurological illnesses. OAB is commonly associated with other LUTS which was well illustrated by the cluster analysis performed by Coyne et al.77 The prevalence of the overactive bladder symptoms was estimated in a large European study involving more than 16,000 individuals.72 Data were collected using a population-based survey (conducted by telephone or face-to-face interview) of men and women aged ≥40 years, selected from the general population in France, Germany, Italy, Spain, Sweden, and the United Kingdom using a random, stratified approach. The main outcome measures were: prevalence of urinary frequency (>8 micturitions/24 hours), urgency, and urge incontinence; proportion of participants who had sought medical advice for overactive bladder symptoms; and current or previous therapy received for these symptoms. The main results of this study are illustrated in Figure 3.7(a) with the prevalence of overactive bladder symptoms grouped according to age and sex, and in Figure 3.7(b) grouped according to age, sex, and nationality. The progression or regression of OAB and other LUTS was studied by Wennberg et al.40 in the same women (aged ≥20 years) followed over a period of 16 years (from 1991 to 2007). The overall prevalence of OAB, nocturia, and daytime micturition frequency

FIGURE 3.8  The percentage distribution of overactive bladder (OAB) symptoms in the same women assessed in 1991 and 2007 (from ref. 40, with permission).

of eight or more times per day increased by 9%, 20% (p < 0.001) and 3% (p < 0.05), respectively from 1991 to 2007. The incidence of OAB was 20% and the corresponding remission rate was 43%. Women with OAB symptoms were classified as OAB dry or wet depending on the presence or absence of concomitant UI. The prevalence of OAB dry did not differ between the two assessment occasions (11% and 10%, respectively), but the prevalence of OAB wet increased from 6% to 16% (p < 0.001). Among women with no OAB in 1991, the prevalence in 2007 was 8% and 12% for OAB dry and wet, respectively. There was a progression from OAB dry to wet in 28%. Remission from OAB dry or wet to no OAB occurred in 50% and 26%, respectively (Fig. 3.8). Irwin and coworkers2 published data estimating the global prevalence of LUTS. The objective of the study was to estimate the number of women with LUTS, including overactive bladder (OAB) and UI utilizing current ICS definitions. It was estimated that more than 500 million women worldwide had UI, and other individual LUTS were also reported by more than half a billion women.

Pelvic organ prolapse

FIGURE 3.7  Prevalence of overactive bladder symptoms: (a) grouped according to age and sex; (b) in a random sample of the total population aged ≥40 years from six European countries (adapted from ref. 29).

POP refers to the loss of support for the uterus, bladder, colon, or rectum leading to prolapse of one or more of these organs into the vagina.1 In addition to mechanical discomfort, POP may negatively affect sexuality, body image, and quality of life and is one of the most common reasons for gynecologic surgery peeking in upper midlife.1,5–8 Today the lifetime risk of POP surgery is reported to be 11–19% in welfare states.5–8 For clinical purposes, the degree of POP is commonly described as above the introitus, at the introitus, or beyond the introitus with or without valsalva. The International Continence Society first developed a standardized definition for the condition of POP in 1996.78 The ICS Pelvic Organ Prolapse Quantification (POPQ) examination defines prolapse by measuring the descent of specific segments of the reproductive tract during valsalva strain relative to a fixed point, the hymen. The POPQ system describes the

Textbook of Female Urology and Urogynecology

22 anatomic findings of POP without consideration for symptoms and bother perceived by the woman. Globally up to half of all parous women have some degree of clinical prolapse and 10–20% are symptomatic.1,79–95 One of these studies examined prolapse by race and found that the Afro-American women had the lowest prevalence and Hispanic women the highest after controlling for multiple other factors in a multivariate analysis.86 Many of the risk factors described for UI (Table 3.1) are also relevant for POP. POP is a rare condition in nulliparous women and in women after one or several cesarean sections indicating that mode of delivery is more important than pregnancy alone. Obstetric trauma resulting from the passage of the fetus through the pelvic floor during vaginal delivery and increasing parity have been implicated as important risk factors for the development of POP. For ethical and practical reasons, randomized controlled trials to study the causal effects of vaginal and cesarean delivery on the pelvic floor will never be performed. Observational studies will, therefore, remain the main source of knowledge on this subject. Nonetheless, it is widely accepted that childbirth is a significant risk factor for POP, presumably due to overt or occult pelvic floor tissue trauma. A large number of studies identify childbirth as one of the strongest predictors for developing POP later in life.1,80,81,83,85,86,92,95 It is also a recurrent observation that the number of childbirths is associated with the risk for prolapse. In the prospective Oxford Family Planning Association study,96 childbirth was the single strongest risk factor for developing prolapse in women under 59 years of age and the risk increased for every childbirth. Similar findings were reported from the Womens Health Initiative (WHI) study86 where a parity of one conveyed an overall two-fold risk increase for prolapse compared to having no children, after which each additional childbirth added a 10–20% risk increase. Leijonhufvud et al.97 found that women having only vaginal deliveries had a significantly increased overall risk of subsequent prolapse surgery (hazard ratio, 9.2; 95% CI 7.0–12.1) compared with women only having caesarean deliveries. In a case-control study, Tegerstedt et al.98 found that the risk for symptomatic POP increased with the number of childbirths and was 3.3-times higher among mothers of four children than among mothers of one child. Similarly, Rortveit et al.91 found that the risk for prolapse increased in women with one (OR 2.8, 95% CI 1.1–7.2), two (OR 4.1, 95% CI 1.8–9.5), and three or more

(OR 5.3, 95% CI 2.3–12.3) vaginal deliveries compared with nulliparous women. Numerous long-term longitudinal studies published in recent years, with follow-up times ranging between 10 and 23 years, commonly show that caesarean section provides a significant reduction in risk for POP.1,67,99–101 Gyhagen et al.99 reported that 20 years after birth singleton primiparae with no further births (n = 5236) had a significantly higher prevalence of POP after vaginal delivery compared with caesarean section (14.6 versus 6.3%, OR 2.55, 95% CI 1.98–3.28) but was not increased after acute compared with elective caesarean section. The rate of POP surgery in relation to mode of delivery and time from first childbirth was studied by Leijonhufvud et al.97 The incidence of POP increased over time after a vaginal delivery. There was in comparison to a vaginal delivery only a minimal increase in POP over time in women who had undergone a caesarean delivery (Fig. 3.9). Several somatic risk factors for POP have been identified. Generalized connective tissue disorders such as the EhlersDanlos disease and Marfans syndrome have been linked to an increased risk of POP.102,103 Risk factors for pelvic floor disorders including POP among women in developing countries were similar to those in industrialized countries (increased age and parity). In a review study across 16 low-income and lower middle-income countries, the mean prevalence for POP was 19.7% (range 3.4– 56.4%) but risk factors were similar to those described in studies from more affluent countries.104

Global health economic consequences

UI and other lower urinary tract conditions as well as POP have enormous public health consequences as well as being a huge economic burden for society. It has been reported that 20% of the female population will undergo surgery for either UI or POP. UI alone puts a huge economic burden on health-care services in particular with regard to the growing elderly population. The economic consequences of UI, other LUTS and POP have recently been reviewed4 and there are now numerous reports to support the statement that these common conditions have a huge bearing on health-care costs. 3,4,105–109 Prevalence rates vary throughout the world but a recent review indicated that urge UI rates were particularly high in the Nordic countries77 and in particular Sweden (Fig. 3.9). The economic consequences of UI in Sweden in 1990 were assessed by Ekelund et al. 3 The estimated annual

Rate per 10,000 person-years

30

20

10

0

10 20 Time since first delivery (yrs)

30

Cesarean section Vaginal delivery

FIGURE 3.9  The rate of POP surgery in relation to mode of delivery and time from first childbirth (from ref. 97, with permission).

The Epidemiology of Urinary Incontinence cost for UI in Sweden at that time was 1.8 billion Swedish crowns. The Swedish Health Care budget for 1990 amounted to 93 billion Swedish crowns. Based on the results of this evaluation, the annual costs of UI in Sweden accounted for approximately 2% of the total health-care costs. Ten years later, the annual estimated costs had increased from 1.8 billion Swedish crowns to 2.8–4.4 billion Swedish crowns.109 Mean life expectancy in the industrialized world is increasing and in some countries 25% of all persons are at present ≥65 years of age. Thus, the number of women requiring treatment for UI is expected to increase in the future. Another important factor to consider, apart from the numerical increase in the number of older women, is the fact that many older women of today suffer in silence, accepting these symptoms as a normal part of the ageing process. Women who are at present 30 and 40 years of age have other demands on their physical condition and will undoubtedly not accept what their older counterparts accepted later in life.

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References









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45. Wennberg AL, Altman D, Lundholm C, et al. Genetic influences are important for most but not all lower urinary tract symptoms: a population based survey in a cohort of adult Swedish twins. Eur Urol 2011;59:1032–8. 46. Alnaif B, Drutz HP. The prevalence of urinary and fecal incontinence in Canadian secondary school teenage girls: questionnaire study and review of the literature. Int Urogynecol J Pelvic Floor Dysfunct 2001;12(2):134–7. 47. Brown SJ, Donath S, MacArthur C, et al. Urinary incontinence in nulliparous women before and during pregnancy: prevalence, incidence, and associated risk factors. Int Urogynecol J Pelvic Floor Dysfunct 2010 February;21(2):193–202. 48. Peyrat L, Haillot O, Bruyere F, et al. Prevalence and risk factors of urinary incontinence in young and middle-aged women. BJU Int 2002 January;89(1):61–6. 49. Hvidman L, Foldspang A, Mommsen S, et al. Postpartum urinary incontinence. Acta Obstet Gynecol Scand 2003 June;82(6):556–63. 50. Fritel X, Fauconnier A, Levet C, et al. Stress urinary incontinence 4 years after the first delivery: a retrospective cohort survey. Acta Obstet Gynecol Scand 2004 October;83(10):941–5. 51. Foldspang A, Hvidman L, Mommsen S, et al. Risk of postpartum urinary incontinence associated with pregnancy and mode of delivery. Acta Obstet Gynecol Scand 2004 October;83(10):923–7. 52. Schytt E, Lindmark G, Waldenstrom U. Symptoms of stress incontinence 1 year after childbirth: prevalence and predictors in a national Swedish sample. Acta Obstet Gynecol Scand 2004 October;83(10):928–36. 53. Van Brummen HJ, Bruinse HW, Van de Pol G, et al. What is the effect of overactive bladder symptoms on woman’s quality of life during and after first pregnancy? BJU Int 2006 February;97(2):296–300. 54. van Brummen HJ, Bruinse HW, van de Pol G, et al. The effect of vaginal and cesarean delivery on lower urinary tract symptoms: what makes the difference? Int Urogynecol J Pelvic Floor Dysfunct 2007 February;18(2):133–9. 55. Dimpfl T, Hesse U, Schussler B. Incidence and cause of postpartum urinary stress incontinence. Eur J Obstet Gynecol Reprod Biol 1992;43(1):29–33. 56. Burgio KL, Zyczynski H, Locher JL, et al. Urinary incontinence in the 12-month postpartum period. Obstet Gynecol 2003 December;102(6):1291–8. 57. Eason E, Labrecque M, Marcoux S, et al. Effects of carrying a pregnancy and of method of delivery on urinary incontinence: a prospective cohort study. BMC Pregnancy Childbirth 2004 February 19;4(1):4. 58. Morkved S, Bo K. Prevalence of urinary incontinence during pregnancy and postpartum. Int Urogynecol J Pelvic Floor Dysfunct 1999;10(6):394–8. 59. Thom DH, Rortveit G. Prevalence of postpartum urinary incontinence: a systematic review. Acta Obstet Gynecol Scand 2010 December;89(12):1511–22. 60. Casey BM, Schaffer JI, Bloom SL, et al. Obstetric antecedents for postpartum pelvic floor dysfunction. Am J Obstet Gynecol 2005 May;192(5):1655–62. 61. Viktrup L, Lose G, Rolff M, et al. The symptom of stress incontinence caused by pregnancy or delivery in primiparas. Obstet Gynecol 1992 June;79(6):945–9. 62. MacArthur C, Glazener CM, Wilson PD, et al. Persistent urinary incontinence and delivery mode history: a six-year longitudinal study. BJOG 2006 February;113(2):218–24. 63. Waetjen LE, Liao S, Johnson WO, et al. Factors associated with prevalent and incident urinary incontinence in a cohort of midlife women: a longitudinal analysis of data: study of women’s health across the nation. Am J Epidemiol 2007;165:309–18. 64. Grodstein F, Fretts R, Lifford K, et al. Association of age, race, and obstetric history with urinary symptoms among women in the Nurses’ Health Study. Am J Obstet Gynecol 2003 August;189(2):428–34. 65. Danforth KN, Townsend MK, Lifford K, et al. Risk factors for urinary incontinence among middle-aged women. Am J Obstet Gynecol 2006 February;194(2):339–45. 66. Rortveit G, Hannestad YS, Daltveit AK, et al. Age- and type-dependent effects of parity on urinary incontinence: the Norwegian EPINCONT study. Obstet Gynecol 2001 December;98(6):1004–10. 67. Rortveit G, Daltveit AK, Hannestad YS, et al. Urinary incontinence after vaginal delivery or cesarean section. N Engl J Med 2003;348:900–7. 68. Press JZ, Klein MC, Kaczorowski J, et al. Does cesarean section reduce postpartum urinary incontinence? A systematic review. Birth 2007 September;34(3):228–37. 69. Gyhagen M, Bullarbo M, Nielsen T, et al. The prevalence of urinary incontinence 20 years after childbirth: a national cohort study in singleton primiparae after vaginal or caesarean delivery. BJOG 2013;120:144–51. 70. Gyhagen M, Bullarbo M, Nielsen TF, et al. A comparison of the long-term consequences of vaginal delivery versus caesarean section on the prevalence, severity and bothersomeness of urinary incontinence subtypes: a national cohort study in primiparous women. BJOG 2013;120:1548–55.









71. Tennstedt SL, Link CL, Steers WD, et al. Prevalence of and risk factors for urine leakage in a racially and ethnically diverse population of adults: the Boston Area Community Health (BACH) Survey. Am J Epidemiol 2008 February 15;167(4):390–9. 72. Milsom I, Abrams P, Cardozo L, et al. How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study. BJU Int 2001;87:760–6. 73. Irwin DE, Milsom I, Hunskaar S, et al. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol 2006;50:1306–15. 74. Coyne KS, Sexton CC, Thompson CL, et al. The prevalence of lower urinary tract symptoms (LUTS) in the USA, the UK and Sweden: results from the Epidemiology of LUTS (EpiLUTS) study. BJU Int 2009 August;104(3):352–60. 75. McGrother CW, Donaldson MMK, Hatward T, et al. Urinary storage symptoms and comorbidities: a prospective population cohort study in middleaged and older women. Age Ageing 2006;35:16–24. 76. Wagg AS, Cardozo L, Chapple C, et al. Overactive bladder in older people. BJU Int 2007;99:502–9. 77. Coyne K, Matza L, Kopp Z, et al. Examining lower urinary tract symptom constellations using cluster analysis. BJU Int 2008;101:1267–73. 78. Bump RC, Mattiasson A, Bø K, et al. The standardization of terminology of female pelvic organ prolapse and pelvic floor dysfunction. Am J Obstet Gynecol 1996;175:10. 79. Miedel A, Tegerstedt G, Maehle-Schmidt M, Nyren O, Hammarstrom M. Symptoms and pelvic support defects in specific compartments. Obstet Gynecol 2008 October;112(4):851–8. 80. Tegerstedt G, Maehle-Schmidt M, Nyren O, Hammarstrom M. Prevalence of symptomatic pelvic organ prolapse in a Swedish population. Int Urogynecol J Pelvic Floor Dysfunct 2005 November–December;16(6):497–503. 81. Fritel X, Varnoux N, Zins M, Breart G, Ringa V. Symptomatic pelvic organ prolapse at midlife, quality of life, and risk factors. Obstet Gynecol 2009 March;113(3):609–16. 82. Ellerkmann RM, Cundiff GW, Melick CF, et al. Correlation of symptoms with location and severity of pelvic organ prolapse. Am J Obstet Gynecol 2001;185:1332. 83. Lukacz ES, Lawrence JM, Buckwalter JG, et al. Epidemiology of prolapse and incontinence questionnaire: validation of a new epidemiologic survey. Int Urogynecol J Pelvic Floor Dysfunct 2005;16:272. 84. Ghetti C, Gregory WT, Edwards SR, et al. Pelvic organ descent and symptoms of pelvic floor disorders. Am J Obstet Gynecol 2005;193:53. 85. Swift SE. The distribution of pelvic organ support in a population of female subjects seen for routine gynecologic health care. Am J Obstet Gynecol 2000;183:277. 86. Hendrix SL, Clark A, Nygaard I, et al. Pelvic organ prolapse in the Women’s Health Initiative: gravity and gravidity. Am J Obstet Gynecol 2002;186:1160. 87. Handa VL, Garrett E, Hendrix S, et al. Progression and remission of pelvic organ prolapse: a longitudinal study of menopausal women. Am J Obstet Gynecol 2004;190:27. 88. Lawrence JM, Lukacz ES, Nager CW, et al. Prevalence and co-occurrence of pelvic floor disorders in community-dwelling women. Obstet Gynecol 2008;111:678. 89. Bradley CS, Zimmerman MB, Qi Y, et al. Natural history of pelvic organ prolapse in postmenopausal women. Obstet Gynecol 2007;109:848. 90. Nygaard I, Bradley C, Brandt D. Pelvic organ prolapse in older women: prevalence and risk factors. Obstet Gynecol 2004;104:489. 91. Rortveit G, Brown JS, Thom DH, et al. Symptomatic pelvic organ prolapse: prevalence and risk factors in a population-based, racially diverse cohort. Obstet Gynecol 2007;109:1396. 92. Uustal Fornell E, Wingren G,  Kjølhede P. Factors associated with pelvic floor dysfunction with emphasis on urinary and fecal incontinence and genital prolapse: an epidemiological study. Acta Obstet Gynecol Scand 2004 April;83(4):383–9. 93. Samuelsson EC, Victor FT, Tibblin G, et al. Signs of genital prolapse in a Swedish population of women 20 to 59 years of age and possible related factors. Am J Obstet Gynecol 1999;180:299. 94. Kumari S, Walia I, Singh A. Self-reported uterine prolapse in a resettlement colony of north India. J Midwifery Womens Health 2000;45:343. 95. MacLennan AH, Taylor AW, Wilson DH, et al. The prevalence of pelvic floor disorders and their relationship to gender, age, parity and mode of delivery. BJOG 2000;107:1460. 96. Mant J, Painter R, Vessey M. Epidemiology of genital prolapse: observations from the Oxford Family Planning Association Study. BJOG 1997;104:579–85.

The Epidemiology of Urinary Incontinence

97. Leijonhufvud A, Lundholm C, Cnattingius S, Granath F, Andolf E, Altman D. Risks of stress urinary incontinence and pelvic organ prolapse surgery in relation to mode of childbirth. Am J Obstet Gynecol 2011 January;204(1):70. 98. Tegerstedt G, Miedel A, Maehle-Schmidt M, Nyren O, Hammarstrom M. Obstetric risk factors for symptomatic prolapse: a population-based approach. Am J Obstet Gynecol 2006;194:75–81. 99. Gyhagen M, Bullarbo M, Nielsen TF, Milsom I. Prevalence and risk factors for pelvic organ prolapse 20 years after childbirth: a national cohort study in singleton primiparae after vaginal or caesarean delivery. BJOG 2013 January;120(2):152–60. 100. Glazener C, Elders A, MacArthur C, et al; ProLong Study Group. Childbirth and prolapse: long-term associations with the symptoms and objective measurement of pelvic organ prolapse. BJOG 2013 January;120(2):161–8. 101. Volløyhaug I, Mørkved S, Salvesen Ø, Salvesen K. Pelvic organ prolapse and incontinence 15-23 years after first delivery: a cross-sectional study. BJOG 2015 June;122(7):964–71. 102. Carley ME, Schaffer J. Urinary incontinence and pelvic organ prolapse in women with Marfan or Ehlers Danlos syndrome. Am J Obstet Gynecol 2000;182:1021–3.

25 103. McIntosh LJ, Mallett VT, Frahm JD, Richardson DA, Evans MI. Gynecologic disorders in women with Ehlers-Danlos syndrome. J Soc Gynecol Investig 1995;2:559–64. 104. Walker GJ, Gunasekera P. Pelvic organ prolapse and incontinence in developing countries: review of prevalence and risk factors. Int Urogynecol J 2011 February;22(2):127–35. 105. Hu T, Wagner T, Bentkover J, et al. Costs of urinary incontinence and overactive bladder in the United States: a comparative study. Urology 2004;63:461–5. 106. Reeves P, Irwin D, Kelleher C, et al. The current and future burden and cost of overactive bladder in five European countries. Eur Urol 2006;50:1050–7. 107. Irwin DE, Mungapen L, Milsom I, et al. The economic impact of overactive bladder syndrome in six Western countries. BJU Int 2008;103:202–9. 108. Milsom I, Coyne KS, Nicholson S, et al. Global prevalence and economic burden of urgency urinary incontinence: a systematic review. Eur Urol 2014;651:79–95. 109. Hellström AL, Kinn AC, Lindehall B, et al. Health economics. In: Treatment of urinary incontinence. The Swedish Council on Technology Assessment in Health Report on Urinary Incontinence. Stockholm, SBU, 2000.

4

NATURAL HISTORY AND PREVENTION OF URINARY INCONTINENCE AND UROGENITAL PROLAPSE Ifeoma Offiah, Chendrimada K. Madhu, Ruben Trochez, and Robert M. Freeman

Introduction Pelvic floor dysfunction such as urinary incontinence (UI) and pelvic organ prolapse (POP), though rarely spoken of in society are common health problems, with the ability to adversely affect the quality of life of affected patients. Few studies have prospectively evaluated the natural history of UI, POP, and fecal incontinence (FI). A hypothesis for the natural history is presented with possible preventative strategies.

Natural history of urinary incontinence The natural history of both stress urinary incontinence (SUI) and urgency urinary incontinence (UUI) is reviewed.

Hypothesis for the genesis of SUI

Pregnancy and childbirth and factors such as age, body mass index (BMI), chronic cough, and genetic factors influence the prevalence of UI (1, 2). During pregnancy, the endopelvic fascial attachments of the bladder neck and distal urethral sphincter are weakened due to hormonal influences (3). Progesterone reduces urethral closure pressures and promotes connective tissue changes (4, 5) that contribute to the high incidence of antenatal incontinence. In most cases, however, incontinence improves after delivery (6). Why stress urinary incontinence (SUI) should persist postpartum in some women is unclear, but vaginal delivery is implicated. If the endopelvic fascial attachments and sphincter function are not damaged at delivery, then the changes seen antenatally are likely to revert to the nonpregnant state with the return of urethral function and continence. However, if these structures are damaged or are inherently weak in the nonpregnant state, then recovery might not occur. Support for this hypothesis comes from studies suggesting the presence of a constitutional factor, e.g. weak connective tissue/fascia in women with SUI (7, 8). For example, there is a known association between connective tissue disorders and UI, e.g. in Marfans and Ehlers– Danlos syndromes (9). Should such individuals suffer pelvic floor trauma at delivery, then recovery might not be complete resulting in postpartum SUI. This, along with further deliveries, aging, menopause, and muscle weakness, seems to increase the risk of long-term incontinence (10). Further support for the hypothesis comes from evidence suggesting that antenatal SUI and, in particular, incontinence before a first pregnancy are important risk factors for the development of incontinence in later years (11). Based on the available evidence, the following hypothesis regarding the genesis of SUI can be made (Fig. 4.1).

Hypothesis for the genesis of overactive bladder (OAB) and urgency urinary incontinence (UUI)

In contrast to SUI, our understanding of OAB or UUI is less clear. The etiology of OAB and UUI is presumed to be multifactorial 26

including aging, abnormal neurotransmission, outlet obstruction, neuropathy and psychological factors. With aging, there is a significant reduction of the endopelvic fascial supports. Bladder emptying is not as efficient and residual urine can cause irritation of the urothelium via an inflammatory response (12). Resident and recruited immune cells penetrate the urothelial barrier causing depolarization of the underlying sensory afferents. A combination of abnormalities in the regulatory neural reflexes located in the brain, spinal cord and peripheral ganglia, and depolarization of bladder afferents induces involuntary detrusor contractions and hence the syndrome of OAB (13, 14). With reduced endopelvic fascial support, these involuntary bladder contractions can proceed to UUI. The most significant risk factors for the development of UUI are raised BMI and aging (15). Other risk factors associated with this condition are race (black women are at higher risk of developing UUI than white women), diabetes, Chronic Obstructive Pulmonary Disease, smoking and surgery for SUI (16). Parity appears to have no effect on the development of UUI.

Natural history of urinary incontinence The natural history of the progression and remission of both SUI and UUI has attracted much consideration. Once present, the symptom of UI is reported to vary over time with reports of remission and progression. A population-based prospective longitudinal study with 16 years follow-up of over a thousand women found considerable rates of both incidence and remission of UI, overactive bladder (OAB), and other lower urinary tract symptoms (LUTS) (17). They reported cumulative incidences of UI and OAB of 21% and 20%, respectively, with corresponding regressions of 34% and 43%, respectively. However, regression was more frequent in women with mild symptoms, suggesting that clinically relevant UI infrequently improves spontaneously. UUI certainly increased in prevalence, where OAB dry rates did not differ between the assessment years (17). This finding is echoed by a systematic review of longitudinal studies of OAB and UI which suggests that there is a dynamic progression of symptom severity in OAB, with 28% of women progressing from OAB dry to OAB wet over 16 years, and that symptoms persist over a long period of time (18). A more recent study of the natural history of UI in over 16,500 middle-aged and older women, followed over 10 years, reported either persistence or progression of symptoms over the study period. Remission was seen in 3–11% of cases when all symptom severity levels were included (19). Remission was more often reported in younger women or women with less severe symptoms. Raised BMI, older age at first presentation and reduced physical activity were reported as significant risk factors for progression to severe UI (19). The association between SUI and parity is well known. The mean prevalence of antenatal SUI is 41% (range 9–75%) (20, 21).

DOI: 10.1201/9781003144236-5

Natural History and Prevention of Urinary Incontinence

3 months postpartum, the pooled prevalence of any postpartum incontinence is between 29% and 33% (6, 22). Review of women 6 years after childbirth reveals a prevalence of persistent UI of 24% (23). This is echoed by a more recent study which reported that 80% of those with UI at 3 months still had UI at a 12-year follow-up (24). However, in 27% who were incontinent at 3 months, there was spontaneous remission at 6 years. Of particular interest were those women who were incontinent prior to pregnancy; there was a markedly increased risk for leakage at 6 years. These interesting findings suggest that there is a specific group of women who are at increased risk of postpartum incontinence, while in others there is spontaneous remission. Identification of such individuals might help in prevention of SUI if they can be identified at an early stage (see section “Childbirth”).

Pregnancy Pressure effects

Hormonal effects fascial support bladder neck mobility urethral resistance

abdominal pressure

Antenatal stress incontinence Delivery Congenital weakness

No Trauma

Remission of UI

UI can be considered as a dynamic condition. Prevalence rates differ depending on the criteria used for diagnosis of the affected patients. Review of the literature reveals a yearly incidence of between 2.5% and 20% and a corresponding yearly remission rate of between 2.9% and 27.9% (Table 4.1). Remission is more likely in younger women, and women with mild to moderate UI at diagnosis (25–32).

Recovery

Trauma

Continence

Fascial weakness Failure to recover Stress incontinence (mild)

Natural history of POP

Levator weakness Further parity Age Menopause

27

Stress incontinence (bothersome)

FIGURE 4.1  Hypothesis for the genesis and natural history of stress urinary incontinence. (Reproduced from Maclean AB and Cardozo L eds., Incontinence in Women, RCOG Press, London, U.K., 2002. With permission of the Royal College of Obstetricians and Gynaecologists.)

Reported risk factors for UI in pregnancy in a European population were maternal age greater than 35, BMI, a family history of UI and parity (2). Although multiple risk factors can be present antenatally and postnatally, many women do not go on to develop UI until later in life. Unless, significant harm is sustained during childbirth, remission is expected for the majority. In the first

Increasing age and vaginal delivery are the most common factors associated with POP. As with SUI, endopelvic fascial and connective tissue laxity are implicated in disease pathogenesis, and the contribution of genetic factors to the genesis of POP is widely recognized (33). There is limited knowledge on the natural history of POP. The reported incidence for cystocele is around 9 per 100 woman-years, 6 per 100 woman-years for rectocele, and 1.5 per 100 womanyears for uterine prolapse (34). A 4-year observational study in postmenopausal women showed an overall 1- and 3-year prolapse incidence of 26% and 40%, respectively, and a 1- and 3-year resolution risk of 21% and 19%, respectively (35). The study also showed that over 3 years, the maximum vaginal descent increased by at least 2 cm in 11% of the women and decreased by at least 2 cm in 2.7%. Obesity and grand multiparty increased the risk of vaginal descent progression (35). The ProLong study, which was a longitudinal study of women following childbirth, showed a 24% objective POP rate (20% of the study group) at 12 years following the index birth (36). The SWEPOP (Swedish Pregnancy, Obesity and Pelvic Floor) study

TABLE 4.1: 1 Year Incidence and Remission Rates of Urinary Incontinence. There Is Higher Overall Mean Yearly Remission of UI Compared to Yearly Incidence Rates Publication Date

Population

199025 200026 200027 200428 200629 200730 201531 201732

Michigan, US Denmark Sweden Sweden Austria Boston, US France Spain

*

2 year incidence and remission rates.

No. of Women

Age

1,956 2,860 382 248 441 64,650 4,127 1,188

>60 years 40–60 years 20–59 years 20–50 years 20–84 years 36–55 years 47–52 years 18–91 years

Incidence 20% 10% 2.5% 4% 3.9% 13.7%* 3.3% 5.3%

Remission 12% 27.8% 5.9% 4% 2.9% 13.9%* 6.2% 27.9%

Follow-up Duration 2 years 1 years 5 years 4 years 6.5 years 2 years 18 years 1 years

Textbook of Female Urology and Urogynecology

28 showed a 12.8% prevalence of symptomatic POP 20 years following one childbirth (37). Previously published prevalence studies, which might have been helpful in identifying the natural history of POP, have been hampered by selection bias (e.g. hospital-based populations in developed countries). For example, in such groups, 30–50% of women seen for other gynecological problems have signs of POP (38, 39), but most will be asymptomatic. In older age groups (>70 years), many are symptomatic and approximately 11% will undergo surgery, but there are few data on the numbers treated conservatively, e.g. with pessaries (40). The natural history of untreated POP was assessed in menopausal women as part of the estrogen, progestin trial of the Women’s Health Initiative (University of California) (34). Annual pelvic examinations for POP were performed on 412 women (mean follow-up 5.7 years) using a non-validated classification system. At baseline 31.8% had POP. The annual incidences of new-onset POP were 9, 5, and 7 per 100 woman-years for anterior vaginal wall prolapse, posterior vaginal wall prolapse, and uterine prolapse, respectively. Of interest were the rates of progression and regression. For progression, the rates were 9.5, 13.5, and 1.9 per 100 woman-years, respectively. Corresponding figures for spontaneous regression, especially Grade 1 POP, were 23.5, 22, and 48, suggesting that spontaneous regression is common. Only 3 women (0.7%) required surgery. These findings have been supported by a study (29) of 64 women with POP, who chose no treatment (observation only) and were followed up with sequential POP-Q examinations (median follow-up 16 months; range 6–91 months) (41). The majority (78%) demonstrated no change in the leading edge of the prolapse between the first and the last visit, following which 63% still continued observation (41). Risk factors for progression of untreated POP include age greater than 60 years of age and the baseline status of the leading edge of the prolapse (42). These data suggest that POP is common, and that spontaneous regression occurs in many cases. The symptom of vaginal bulge is specific to prolapse, and the leading edge at or beyond the hymenal remnants helps define symptomatic POP (43, 44). Treatment might be unnecessary unless the symptoms are bothersome. In developing countries, untreated POP is more prevalent with an average prevalence of 18% (range 3.4–56.4%) (45–47). This is because in addition to age and parity, women in low- and middleincome countries are exposed to other risk factors for POP, such as heavy load carrying (45, 48). For example, in rural Gambia, an epidemiological study showed a prevalence of 46%. Only 8 of 152 with “severe POP” (i.e. subjective and objective) accepted the offer of treatment (49). There are no data on the outcome for these untreated women. If severe and left untreated, POP can result in obstructed voiding and recurrent urinary infection. This could progress to obstruction of the upper tracts and renal failure. In a small case series of women with untreated severe POP (i.e. beyond the introitus), all had evidence of bilateral upper tract dilatation, and three had obstructive renal failure. Treatment of POP is shown to result in resolution of renal failure or hydronephrosis (50, 51). These findings highlight the need for prevention of upper tract changes by early treatment of advanced POP.

Natural history of fecal incontinence Fecal incontinence (FI) (i.e. loss of liquid, solid feces) and anal incontinence (AI) (i.e. including flatus incontinence) are

debilitating conditions that cause significant public health and social problems. Obstetric anal sphincter injury (OASI) is the most common factor associated with FI and AI. Other common causes of FI include irritable bowel syndrome, high BMI, increasing age, dementia, stroke and constipation (52, 53). The median prevalence of FI is 7.7% (range 1.4–20.7%) (54, 55). This is higher following childbirth due to injury to the pelvic floor and anal sphincters. The prevalence of FI at 3-months postpartum was 9.6% in one study (56). The authors from the same study group showed a 3.6% prevalence of persistent FI at 6 years following childbirth (90% of these women were asymptomatic before their first birth) (57). At 12 years follow-up, 43% of women who complained of FI at 3 months complained of persistent FI (overall prevalence rate of FI was 6%) (58). There are few data on the prevalence of AI, which includes flatus incontinence, but it is likely to be much higher than FI alone. A prospective cohort study on AI reported a prevalence of nearly 10% 6 years following childbirth. However, those women who had an instrumental vaginal delivery, with or without an OASI, had a higher prevalence of AI compared to women who delivered by caesarean section or had normal vaginal delivery: prevalence rates were 23%, 8%, and 12%, respectively (59).

Risk groups There are known predisposing factors such as age, obesity, family history, parity/vaginal childbirth, and surgery. Identification of individuals at risk might help with implementing preventative measures.

Age

POP is a common condition in older women, and advancing age has a strong correlation with the prevalence of prolapse (60, 61). With advancing age, a progressive and age-dependent decrease of the density of striated muscle cells can be observed in the rhabdosphincter of the urethral sphincter (due to apoptosis), which may contribute to UI (62). Although the prevalence of incontinence is increased in the elderly, the two do not necessarily have a cause-and-effect relationship; other pathological processes associated with aging might be responsible. Resnick has created the mnemonic “DIAPPERS” to describe these: Delirium, Infection, Atrophic change, Pharmacological, Psychological, Excess urine output, Restricted mobility, and Stool impaction (63). There is a known association between constipation and POP (64), and attention to regular bowel habit, avoiding straining, a high-fiber diet and, if necessary, laxatives might have a positive effect on prevention. Likewise, management of other risk factors such as chronic cough, smoking, and adjusting medication that has an adverse effect on the bladder could help incontinence (e.g. diuretics, calcium channel antagonists [that can cause polyuria], nonsteroidal anti-inflammatory drugs [that can lead to fluid retention], ACE inhibitors [leading to chronic cough], and sedatives) (65).

Menopause and hormone replacement therapy

There is a definite aging process in the lower urinary tract, resulting in atrophic change and poor urethral function. Hormone replacement therapy (HRT) should in theory prevent LUTS. A Cochrane review concluded that local estrogen treatment for incontinence may improve or cure it; however, systemic hormone replacement therapy (HRT), using conjugated equine estrogen,

Natural History and Prevention of Urinary Incontinence might make incontinence worse (66). There is limited evidence from randomized controlled trials (RCTs) regarding the use of estrogens for the prevention and management of POP (67). However, a retrospective observational study to evaluate the effect of hormone therapy on pelvic organ prolapse quantification revealed that the use of hormone therapy may have a negative effect on pelvic organ support, though this effect is too small to be clinically significant (68). The results of this were echoed by a more recent study which indicated that women with uterine prolapse had used HRT more often than women without, and the longer the duration of use, the higher the risk of POP (69).

Overactive bladder and urgency

Urgency is a distressing symptom due to the fear of incontinence. Often, patients void more frequently to prevent this, which can have the opposite effect by reducing bladder capacity and worsening the symptoms. In those with restricted mobility, urgency can cause panic and anxiety on the sensation of bladder fullness. There is a strong association between mobility impairment and urgency urinary incontinence (UUI), which is proportional to the severity of UUI (70). As a result, there is an increased risk of falls and bone fracture (71). These might be preventable with improved access to toilets, the use of bedside commodes and/or hand-held urinals (see chapter on OAB).

Raised BMI

Obesity is also strongly associated with an increased prevalence of both stress and urgency UI (72) and epidemiological evidence lends further support to this view (73). Increasing BMI is associated with progression of POP for all three compartments, but weight loss was not associated with a significant regression of POP, which might suggest an irreversible damage to the pelvic floor with obesity (74). In pregnancy, an increased BMI has been shown to be an important risk factor for persistent UI postpartum although the quality of the evidence is low (75, 76). In theory weight loss should be preventative. However, studies are often hampered by the failure of subjects to lose weight. Following bariatric surgery approximately half report improvement or resolution of UI, but the quality of the evidence is low (77). In a larger case series of women (BMI > 30) with UI undergoing weight loss with diet and exercise, reduced incontinence loss and improved quality of life have been demonstrated in women losing more than 5% body weight (78). A randomized trial in 338 overweight and obese women found that a mean weight loss of 8% in the intervention group (vs. 1.6% in controls) led to a significant decrease in weekly episodes of incontinence (47% vs. 28%) (79). Results from a systematic review and meta-analysis of studies on weight loss in UI including 2,352 women showed that nonsurgical weight loss can improve UI and should be considered part of the standard practice in the management of UI in overweight women (80).

Familial and genetic factors

Identification of risk groups is important and family history might be relevant. Daughters of women with UI are more likely to develop incontinence themselves (8, 81). A genetic predisposition to abnormal extracellular matrix remodeling, influenced by reproductive hormones, trauma, mechanical stress, and aging could alter normal tissue architecture and mechanical properties leading to SUI and POP (82). Studies also suggest increased collagenolysis due to genetic polymorphisms playing a key role in extracellular protein turnover, resulting in decreased collagen and development of POP and SUI (83). However, a lack of

29 association between DNA polymorphisms with advanced POP has also been recently reported (84). A linkage to chromosome 9 has been demonstrated in families with POP and SUI (85). A large twin registry study from Sweden concluded that genetic effects do contribute to the occurrence of SUI and POP, but there was a substantial effect of environmental factors providing some hope for preventative strategies (86). A small study in four pairs of postmenopausal identical twins with different parity status, i.e. nulliparous/parous for each set of twins, found identical continence status in all four pairs, and a difference greater than one stage on the Pelvic Organ Prolapse Quantification (POPQ) assessment in only one set of twins (87), which seems to support a genetic predisposition for both UI and POP rather than parity. Racial differences have also been demonstrated, with white Caucasian women having an increased risk of SUI (88, 89) and POP (90) compared to African American women. However, a direct comparison of pelvic floor morphology revealed that black women had a greater hiatal area on Valsalva and lower point Ba and C on POP quantification, and greater pelvic organ mobility than white or South Asian women (91). This discrepancy between anatomic examination findings and prevalence reports may in fact be because of differential reporting of health problems and access to healthcare among different ethnic groups. Finally, childhood symptoms, e.g. nocturnal enuresis and OAB might predispose to incontinence in adulthood (92). Identifying and treating these children, e.g. by pelvic floor muscle training (PFMT) and behavioural modification, might help to prevent symptoms in adulthood.

Childbirth

The understanding of the pathophysiology of pelvic floor dysfunction as a result of childbirth has grown in recent years, especially with imaging techniques. Levator avulsion/trauma, a high-risk factor for short- and long-term pelvic floor dysfunction, is seen in ultrasound and MRI studies (93, 94) with incidences of 66% with forceps delivery compared with 10.7% after spontaneous vaginal delivery and 25% with vacuum extraction (94). Women who are older at first delivery and those requiring instrumental delivery, particularly forceps are at highest risk, as seen in subsequent studies (93, 95, 96). Such trauma results in symptoms of UI and prolapse in 35% with severe injuries compared to 15% with minor injuries (94). With regard to anal and fecal incontinence Obstetric Anal Sphincter Injury (OASI) is a major cause with rates rising in many countries. For example, in the UK, OASI rates rose over a ten-year period from 1.8% to 5.9%, i.e. approximately 70,000 women (97). The following risk factors for OASI have been identified: first childbirth, older age at first childbirth, South Asian ethnicity (possibly due to a shorter perineal body in some South Asian women), induction of labour, Birthweight > 4 kg, persistent occiptio-posterior position, prolonged second stage, waterbirth, vaginal birth after caesarean section, and instrumental birth (98–102). Likewise in a study on AI and mode of delivery, the strongest risk factors after vaginal delivery were high maternal age, larger birthweight, and instrumental delivery (see in subsequent texts) (103). For any type of pelvic floor dysfunction (UI, POP, or FI) the ProLong, SWEPOP (36, 37) and other studies have identified additional risk factors including urinary incontinence before and during pregnancy (104, 105) persistent postnatal incontinence (106), race/ethnicity, maternal height, BMI (76), and family history (36, 37). As mentioned, age at first pregnancy is a risk factor

Textbook of Female Urology and Urogynecology

30 for OASI with an increased risk in those ≥35 years (99). In addition, maternal age has also been shown to be a risk factor for longterm pelvic organ prolapse (36), prolapse surgery (107), urinary incontinence (95, 108), and pelvic floor weakness (109). Pre-pregnancy BMI (76) (see “raised BMI” above), and maternal height are other risk factors that increase the risk of pelvic floor dysfunction following childbirth (37, 110). For example, symptomatic POP has been shown to increase by 3% for every unit increase in BMI which is also a risk factor for several urinary symptoms 6–18 months postpartum (76). In addition, there is also an increased risk of shoulder dystocia in women with prepregnancy obesity which increases the risk of pelvic floor dysfunction further (111). Women with a short stature (i.e. height ≤160 cm) and who deliver a baby ≥4000 g are also at risk for pelvic floor dysfunction and shoulder dystocia (112), as well as in-labour caesarean section (113). Compared with taller women, a doubled prevalence of symptomatic POP 20 years following one vaginal childbirth has been reported (24.2% vs. 13.4%) (37). A further risk group for postpartum stress urinary incontinence (itself a risk factor for long-term incontinence) are those primigravidae with bladder-neck mobility antenatally (a possible marker for weak pelvic floor collagen) (114, 115). As mentioned above, high prevalences of UI, POP, and AI have been reported long-term (36, 37). In a study of 1,528 women assessed 5–10 years after delivery, the 15-year cumulative incidences of pelvic floor disorders after first vaginal delivery were: SUI, 34.3% (95% CI, 29.9–38.6%); OAB, 21.8% (95% CI, 17.8– 25.7%); AI, 30.6% (95% CI, 26.4–34.9%); and POP, 30.0% (95% CI, 25.1–34.9%). Compared with spontaneous vaginal delivery, caesarean delivery was associated with significantly lower hazard of SUI (adjusted hazard ratio [aHR], 0.46 [95% CI, 0.32–0.67]); OAB (aHR, 0.51 [95% CI, 0.34–0.76]); and POP (aHR, 0.28 [95% CI, 0.19–0.42]), while operative vaginal delivery was associated with significantly higher hazard of AI (aHR, 1.75 [95% CI, 1.14–2.68]) and POP (aHR, 1.88 [95% CI, 1.28–2.78]) (116).

While many women are asymptomatic after childbirth trauma the evidence suggests that symptoms can arise in the long-term. In some countries there is now a higher risk for birth trauma and pelvic floor dysfunction due to older age at first delivery, higher BMI and larger birthweights along with an increasing rate of instrumental delivery, particularly forceps (Fig. 4.2).

Choice of instrumental delivery

As mentioned, a major risk factor for levator avulsion/trauma and OASI is forceps delivery (93, 94). There is robust evidence suggested in a Cochrane review of an increased association of maternal perineal trauma with forceps delivery (117). This review also suggested significantly more third- or fourth-degree tears (with or without episiotomy), vaginal trauma, and flatus incontinence with forceps compared with ventouse (117). In an analysis of 13,694 women following vaginal birth, the risk of SUI after forceps delivery was reported as significantly greater than that after spontaneous delivery (odds ratio [OR], 1.42; 95% CI, 1.09–1.86). This risk was not seen after vacuum/ventouse delivery (OR, 0.80; 95% CI, 0.59–1.09) (118). Anal incontinence following forceps has been reported in up to 16% compared to 12% in non-forceps births, presumably due to OASI (58). This increased risk of forceps use has to be borne in mind during decision-making for mode of delivery, especially for women who may already have the risk factors above. Forceps and vacuum extraction have different benefits and risks, and the choice of instrument should be based on clinical circumstances such as the urgency of delivery (e.g. fetal distress) and the level of skill of the operator (119).

Preventative measures Identifying women with risk factors before or early in a first pregnancy might enable preventative measures to be introduced. It was suggested that the moderately robust epidemiological data at 12 and 20 years after delivery (36, 37) could be used to predict

14% 12% 10% 8% 6% 4% 2%

19

8 19 0 8 19 2 83 19 8 19 4 19 85 8 19 9-9 9 0 19 0-9 9 1 19 1-9 9 2 19 2-9 9 3 19 3-9 9 4 19 4-9 9 5 19 5-9 9 6 19 6-9 9 7 19 7-9 9 8 19 8-9 9 9 20 9-0 0 0 20 0-0 0 1 20 1-0 0 2 20 2-0 0 3 20 3-0 0 4 20 4-0 0 5 20 5-0 0 6 20 6-0 0 7 20 7-0 0 8 20 8-0 0 9 20 9-1 1 0 20 0-1 1 1 20 1-1 1 2 20 2-1 1 3 20 3-1 1 4 20 4-1 1 5 20 5-1 16 6 -1 7

0%

Forceps %

Ventouse %

--lnstumental (total) %

FIGURE 4.2  Instrumental delivery rates UK. (By permission of Hannah Knight).

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FIGURE 4.3  UR-CHOICE risk calculator. this, based on the major risk factors that have been identified, i.e. UI before pregnancy, ethnicity, age at birth of first child, BMI, family history (mother and sister) of PFD, and baby’s weight and maternal height (if 4 kg) (120). Using these (36, 37) a UR-CHOICE scoring system has been developed which compares the individual woman’s risk against the average risk of PFD following both vaginal and CS deliveries (121). This has similar concordance indices to the tools used for heart disease and breast cancer and has the potential to help counsel women regarding PFD prevention (Fig. 4.3). While further clinical trials are required, nonetheless this risk assessment tool has the potential to provide individual risk and so reassure women at lower risk, whereas those at higher risk can be referred to a physiotherapist or continence advisor for supervised pelvic floor muscle training (PFMT). In those at very high-risk caesarean section can be discussed with the woman as well as the risks and benefits (see in subsequent texts). Informing women of their risk score has been assessed in a qualitative study of women, midwives and obstetricians (122). The data showed that all the women interviewed wanted to know their risk of developing PFD to help make informed decisions. They also reported that knowing their risk would motivate them to undertake preventative strategies such as PFMT. However, midwives and obstetricians were concerned that providing such information would result in more maternal requests for caesarean section (CS). This might be an incorrect assumption as most women did not mention CS. Likewise, in the OASI Care Bundle study of over 55,000 women, even after explaining the risk of FI due to OASI, there was no increase in CS rates (123). Such prediction models, by providing individual risk, including one on the risk of levator trauma/avulsion, might help with

patient counselling, improved compliance with PFMT and enable choice regarding mode of delivery (96).

Prevention with pelvic floor muscle training (PFMT)

There is Level 1 evidence that supervised antenatal PFMT in continent women can prevent UI in late pregnancy and postpartum (124), and also reduce prolapse symptoms and the need for further treatment (125). It is also recommended that women with OASI receive supervised PFMT as a form of secondary prevention. However, as with SUI, a randomized trial showed that the significant improvement in FI following PFMT compared to controls at 1 year (4% vs. 11%) did not persist at 6 years (12% vs. 13%) irrespective of subsequent deliveries (126). This might be due to poor long-term adherence and might be improved by providing individual risk, e.g. UR-CHOICE. Postpartum PFMT also seems to be preventative both in the short and medium term (127). A Cochrane review of 22 studies involving over 8,000 patients found evidence that PFMT can prevent UI in pregnancy (relative risk [RR] 0.71; 95% confidence interval [CI], 0.54–0.95) and postpartum (RR, 0.60; 95% CI, 0.35–1.03). The review indicated a greater treatment effect with a more intensive program (124). However, the level of intervention, i.e. the PFMT regimen, varied greatly in the studies, and it remains unclear whether PFMT should be targeted to women at risk or should be a population-based intervention. In one study of at-risk women, i.e. with bladder neck mobility (128) an RCT of supervised antenatal PFMT showed a reduced incidence of SUI at 3 months postnatally suggesting that targeting those at-risk might be a better use of physiotherapy resources.

32 In France, all women are offered postnatal physiotherapy after delivery (La rééducation) paid for by French Social Security since 1985. In the UK by 2023, the same should be available via the NHS Long-Term Plan and data for its effectiveness will be reported. These promising reports are valid only in the short or medium term. Longer-term studies with 6- and 8-years follow-up (126, 129) and one review (130) have shown that the initial beneficial effect do not persist, probably due to poor compliance. This lack of long-term effect may be due to lack of adherence to a structured exercise regimen, small sample sizes, and loss to follow up. However, if the report from the qualitative study above (122) shows that those identified to be at-risk are more likely to adhere to PFMT then there is the potential for better long-term outcomes. For the secondary prevention of POP, PFMT has been shown to be effective in prevention of prolapse progression as well as resolution of prolapse symptoms (125). PFMT is safe and other than a few reports of pelvic floor pain, has no known harmful effects (131). As PFMT antenatally and postnatally can be preventative in the short and medium term, Caesarean section might not be necessary except possibly for those women at the highest risk, e.g. with severe incontinence before and/or during the first pregnancy or in those with early-stage symptomatic POP or a high UR-CHOICE score.

Caesarean section Does caesarean section prevent PFD?

For those women at highest risk of UI, POP, and FI, should planned CS be offered as a form of prevention?

Urinary incontinence

CS provides partial protection for UI but the prevalence is still high. For example, by 12 years the prevalence of UI was 55% after vaginal delivery (VD) and 40% after CS (132). Likewise, in a national cohort study investigating UI prevalence 20 years after one delivery only, the corresponding prevalence were 40% VD and 29% CS (37). Interestingly there was no difference between planned and in-labour CS suggesting that the trauma probably occurs at the time of delivery. Overall there appears to be a reduced risk of pelvic floor dysfunction 5–10 years after caesarean section compared with vaginal delivery (133). A review on the role of caesarean section in preventing UI concluded that the short-term occurrence of any degree of postpartum SUI is reduced with caesarean section though severe symptoms are equivalent by mode of birth (134). These findings are echoed by a more recent systematic review, which reported a reduction in the risk of UI after caesarean section (OR, 0.56; 95% CI, 0.47–0.66; n = 58,900) (135). Vaginal delivery by comparison is associated with an almost twofold increase in the risk of long-term SUI, with an absolute increase of 8%, an effect that is largest in younger women. There is also an increased risk of UUI, with an absolute increase of approximately 3% (118). It would seem therefore that while caesarean section (planned or in-labour) is not completely protective for UI nonetheless the risk is less than with vaginal delivery.

Anal/Fecal incontinence

A Cochrane review failed to demonstrate any benefit of caesarean section in the prevention of AI and recommended that prevention of anal continence should not be used as a criterion for choosing elective primary caesarean delivery (136).

Textbook of Female Urology and Urogynecology However, two large population-based cohort studies have shown an increased risk of FI in primiparous women after one vaginal birth compared to one caesarean section (OR, 1.65; 95% CI, 1.49–1.82; p < 0.0001) (103, 137). Of 185, 219 women who had a cesarean delivery only, and 1,400,935 delivered vaginally followed up 30 years later 416 (0·22%) in the caesarean delivery group were diagnosed with AI compared with 5171 (0·37%) in the vaginal delivery group. The odds ratio (OR) for being diagnosed with AI after vaginal delivery compared with caesarean delivery was 1·65 (95% CI, 1·49–1·82; p < 0·0001) (103). A possible explanation for the difference between studies might be that the causes of anal/faecal incontinence are multifactorial including irritable bowel syndrome, constipation with overflow which is unlikely to be affected by planned CS. This might also be an explanation for the inconsistent effect of CS on urinary incontinence, i.e. other aetiologies such as recurrent UTI and overactive bladder.

Pelvic organ prolapse

The evidence suggests that patients delivered exclusively by caesarean section have a significantly reduced risk of objectively demonstrable POP 12 years after delivery (36) and symptomatic POP by 20 years after childbirth (prevalence of POP 6.3% caesarean section versus 14.6% vaginal delivery, OR = 2.3 (37). There is a reduction in the risk of POP following caesarean section compared to vaginal delivery (OR, 0.29; 95% CI, 0.17–9.51; n = 39,208) (135). In addition, a reduction in POP surgery long-term has been reported lending further support to a protective effect of CS for POP (VD vs. CS Hazard Ratio 9.2 and Forceps vs. CS Hazard Ratio 20.9 (107). The evidence would suggest that particularly for POP, planned CS can be preventative for those at higher risk. However, what are the numbers needed to treat (NNT)? For all women, to prevent one case of UI or POP the NNT would be 12 and 10, respectively (37) but in an analysis of short stature women with a clinically large baby (a higher risk group as mentioned above), the corresponding numbers are 4 and 6 only (Gyhagen M personal communication). Concerns exist about the potential for rising CS rates and risks. However, the evidence that informing women of their risk will result in more CS’s does not exist (123). Nonetheless with regard morbidity from planned CS the following should be considered: • Usually, the risks cited are for all CS’s i.e. planned/elective and in-labour, including in the second stage where the risk of complications is different (138). However, for planned as opposed to in-labour CS: the incidence of surgical complications is low. Placenta accreta is known to occur following multiple CS’s but World Population statistics (2015) (139) show that in developed countries the fertility rate is 2–3 babies per woman. Should they all be delivered by planned CS, the risk of accreta with the 2nd and 3rd is 0.24%, 0.31%, respectively (140). • Associations have been reported for CS and childhood illnesses, and stillbirth in the next pregnancy (135, 141). However, these are statistical associations with no evidence of causality proven. One theory to explain these associations is the fetal microbiome. However, there is much conflicting evidence with few large studies of CS vs. vaginal delivery matched for BMI, intrapartum antibiotic use, and breastfeeding patterns (142). Again, while an association has been found no studies have confirmed causality.

Natural History and Prevention of Urinary Incontinence Therefore, for women at highest risk of PFD, the benefits and risks and careful planning of mode of delivery to prevent pelvic floor dysfunction should be discussed.

Prevention of obstetric anal sphincter injury (OASI)

OASI is a high-risk factor for AI (143). The rate among primiparous women increases over time and is affected by further childbirth (44% at 9 months and 53% at 5 years) (144, 145). Rates of OASI have increased in many countries (146–148) with a threefold increase of up to 5.9% over a 10-year period in the UK (97). According to a 2019 clinical report (UK National Maternity Perinatal Audit [NMPA 2019]), the overall incidence of detected OASI was 3.5% (range 1.6–7.5%) (149). This results in significant physical and psychosocial trauma with a systematic review showing a significant risk (OR, 2.66; 95% CI, 1.77–3.98; Q = 27.9; p = .002; I2 = 64.1) after vaginal delivery (150). This is likely to result in long-term financial consequences to the woman, her family and healthcare providers with perineal trauma/OASI being the 4th most common cause for litigation in obstetrics in the UK (151). Nearly one-third of primiparous women (29.2%) have unidentified/“occult” OASI following vaginal childbirth with assisted vaginal delivery being a high-risk factor (ventouse less traumatic than forceps) (152). Despite repair, 30–50% of affected women suffer from AI (144, 145, 153), and many will opt for a future elective caesarean section to avoid worsening of symptoms from a further vaginal birth (154, 155). In women with recognized OASI, 85% of them have been shown to have residual sphincter damage despite repair at delivery (156). In primiparous women with persistent FI following an OASI, the risk of deterioration appears to increase after the second vaginal delivery (145, 157). For example, a fivefold increase in recurrent OASI (7.2% vs. 1.3%) has been reported in women who had a third- or fourthdegree tear in their first delivery (158). For these women, prevention might be achieved by elective caesarean section. While there are no systematic reviews or randomized controlled trials to suggest the best method of delivery following OASI nonetheless it is recommended that women should be investigated and counselled. For example, if symptomatic or abnormally low anorectal manometric pressures and/or endoanal ultrasonographic defects are present, an elective caesarean section may be considered (159). These research findings have focused the attention of obstetricians and midwives to the potential risk of anal sphincter injury and the possible association with long-term FI. This should result in improved awareness, training, and prevention. We recommend that obstetricians and midwives are adequately trained in the identification and treatment as well as methods of prevention.

Intrapartum prevention of OASI

The UK “OASI Care Bundle” (i.e. a set of interventions likely to improve outcomes when implemented together) and which includes good communication, manual perineal protection, episiotomy at a 60-degree angle (only when indicated) and perineal and rectal examinations to check for sphincter integrity has been shown in a multicenter RCT of 55,060 women to reduce the incidence of OASI from 3.3% to 3.0%, i.e. 16,518 women (adjusted OR, 0.80; 95% CI, 0.65–0.98; p = 0.03) (123). When analyzing the individual elements of a care bundle in Denmark, Rasmussen et al. found that the hands on/manual perineal protection technique was the most effective component and significantly reduced the risk of OASI (OR, 0.28; 95% CI, 0.14–0.58) (160).

33 Manual perineal protection (MPP)

While RCT’s have failed to show a consistent benefit with MPP, most of the studies did not have OASI as the primary outcome. In addition, unlike the non-randomized studies, the techniques of MPP and “hands poised” are not standardized, unlike the UK Care Bundle which used the Finnish Grip for MPP (see below). This might explain the lack of effect seen in systematic reviews (161–163). It should be noted however that: “no evidence of an effect” does not equate to “evidence of no effect.” For example, in studies from Scandinavia using “real world data” a consistent reduction in OASI rates with the use of manual perineal protection using the “Finnish Grip” has been reported in several studies (164–166). While in the UK National Institute for Health and Care Excellence (NICE) states that on the basis of RCT evidence that either the “hands on (MPP) or hands off/poised” can be used, new evidence suggests that MPP should be used as part of a package of preventative measures, i.e. a Care Bundle (123, 167). While not used in the Care Bundle (for practical reasons), a systematic review of the use of warm compresses in the second stage of labour has shown a reduced risk of OASI further (1.9% vs. 5.8%; RR, 0.34; 95% CI, 0.20–0.56) and can be considered in addition to the existing components of the Care Bundle (168).

Episiotomy

Again, this should be considered as part of a Care Bundle rather than a method of prevention alone. In isolation there is conflicting evidence regarding prevention of OASI or other pelvic floor disorders, e.g. UI and POP. In a Cochrane review, restrictive episiotomy compared with routine use, resulted in less severe perineal trauma, less suturing (RR = 0.71), and fewer healing complications, but with more anterior perineal trauma. There was no difference in UI or several pain measures (169). However, as with all studies assessing episiotomy, the technique and angle are poorly described. A more recent systematic review which was focused on the long-term effects of episiotomy on UI and POP reported that use of episiotomy resulted in an increase in UI symptoms. However, they found no increase in POP development and that episiotomy may in fact be protective in respect to POP severity and prevalence (170). While several studies have shown no preventative effect of episiotomy (169), others have shown mediolateral episiotomy to be preventive following SVD’s and instrumental deliveries (97, 171, 172) with a 23–27% reduction in OASI being reported (173). The reason for the difference might be the angle at which the episiotomy is performed with evidence suggesting that the closer the cut is to the midline the higher the risk of extension causing OASI (174). The angle further away from the midline has been shown to be important in reducing the incidence of OASI (174–176). As a result, national recommendations in the UK are that the angle should be 45–60 degrees from the midline (177, 178). To cut an episiotomy at this angle during crowning of the fetal head might be difficult to achieve by visualization alone (179, 180), And so episcissors (Fig. 4.4) have been designed to enable a 60-degree episiotomy at crowning which will achieve a 45-degree angle at suturing, i.e. well away from the anal sphincter (181). Studies have suggested a protective effect (182, 183). Episiotomy is recommended with instrumental delivery as the highest rate of OASI has been reported in women delivered with forceps without an episiotomy (97). Although clinical guidelines do not “mandate” episiotomy with forceps (119), nonetheless evidence shows the lowest rate of OASI is with an episiotomy (97).

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FIGURE 4.4  Episcissors. As per the OASI Care Bundle (above) episiotomy is more likely to provide a protective effect as part of a prevention “package” rather than as a single intervention with the benefits and risks explained preferably before labour and delivery so the woman can make an informed choice.

Recommendations

Prevention of PFD should ideally be discussed with every pregnant woman as part of her antenatal care. Identifying those at risk and providing information can help with counselling and prevention strategies such as pelvic floor muscle training, weight control and delivery management, e.g. ventouse rather than forceps, OASI Care Bundle, caesarean section for women at high risk. In an increasingly higher risk population for birth trauma and PFD (e.g. older age at first delivery, increased BMI and larger birthweights) women should be informed of the benefits and risks of both vaginal delivery and planned CS and have choice in their mode of delivery.

Prevention of incontinence and prolapse following gynecological surgery Hysterectomy and urinary incontinence

Hysterectomy, performed either vaginal, open, or laparoscopic, is one of the most common procedures performed by gynecologist. Overall, the estimates suggest a 60% increased risk of developing incontinence after hysterectomy. Younger women are at a lower risk of developing post-hysterectomy UI than older women (184). A systematic review of UI post hysterectomy revealed that the vaginal route results in significantly more UI than the abdominal or laparoscopic routes (OR, 2.3; 95% CI 1.0–5.2) (185). Consideration might be given to concomitant continence surgery as secondary prevention for women with preexisting urodynamic stress incontinence, requiring hysterectomy. This has been shown to improve the chances of continence at 1 year postoperatively (186). However, there is no evidence that this is indicated for primary prevention. It has been suggested that subtotal hysterectomy might reduce the incidence of UI (187), as the cervix might act as a posterior support for the sphincter mechanism. However, RCT’s have failed to show any benefit of subtotal over total hysterectomy with regards the onset of UI (188) with a more recent systematic review actually showing a higher risk of UI following subtotal hysterectomy compared to total hysterectomy (OR for total hysterectomy 0.74; 95% CI 0.58–0.94) (185).

Likewise, a Cochrane systematic review of 9 trials with 1,553 participants has not shown improved outcomes for sexual, urinary or bowel function with subtotal hysterectomy compared to total hysterectomy either in the short or long-term (189). It would appear therefore that there is little benefit in preserving the cervix for primary prevention of pelvic floor dysfunction after hysterectomy. Nonetheless, there is an association with UI in the long term (190) and so, preventative measures need to be investigated. With regards to visceral injury at the time of hysterectomy, results from a population-based cohort study of almost 300,000 women showed the risk of ureteric, bladder and genitourinary fistula following hysterectomy for benign indications were 1.0%, 0.7%, and 0.3%, respectively (191). In an effort to prevent fistulae, identification of urologic injury and repair at the time of surgery was shown to significantly lower the risk of subsequent fistula development (191). In addition, the vaginal (OR, 0.56; 95% CI 0.53–0.64) and laparoscopic (OR, 0.80; 95% CI, 0.75–0.86) approaches, had lower risks of genitourinary injury compared to the abdominal approach (191). Preoperative intravenous urography, intraoperative cystoscopy, and the use of ureteric catheters in potentially difficult cases might help prevent trauma to the urinary tract.

Pelvic reconstructive surgery and pelvic organ prolapse

The risk of vaginal vault/apical prolapse and enterocele following hysterectomy has been reported to occur in up to 5% (at 15 years) (40). Recurrence rate for POP following prolapse procedures is 36% (192). This same review identified predictors for recurrence of POP. These included levator avulsion (OR 2.76; p < 0.01), preoperative POP stage of 3–4 (OR, 2.11; p < 0.001) and family history of POP (odds ratio 1.84, p = 0.006) (192). However, the definitions of “recurrence” in most of the studies were based on anatomical outcomes (i.e. POPQ stage > 2) rather than symptoms. Other possible causes of postsurgical POP might include reduced and weakened collagen (193–195), failure to support the vault at hysterectomy or “anteversion” of the anterior vaginal wall following colposuspension. The incidence of a new-onset enterocele has been reported to be 18–30% following culposuspension (196). This might also be due to a worsening of preexisting posterior compartment POP. One year after colposuspension prolapse was reported to be significantly associated with the presence of posterior vaginal descent before colposuspension (OR, 3.07; 95% CI, 1.10–8.60; p = 0.03) (197). Similarly, “retroversion” of the vaginal vault after sacrospinous ligament fixation can result in a high incidence of cystocele (see chapter on “Laparoscopic Sacrocolpopexy”). In a population cohort study of over 178,000 women, vaginal hysterectomy was reported to have a threefold increased risk of subsequent POP development compared to abdominal hysterectomy (198). However, in a large series of over 300,000 patients, only 4.4% of those with POP recurrence required further POP surgery (199) suggesting that while there might be anatomical recurrence the symptoms are not severe or bothersome enough to warrant another POP procedure. Prevention will depend on the surgical procedure, the technique, and the strength of the supporting structures. It is generally accepted that apical support is the key to preventing recurrence of vault prolapse following hysterectomy (200). For example, laparoscopic and robot-assisted sacrocervicopexy with supracervical hysterectomy and sacrohysteropexy have been reported to have good success rates (201). However, the results

Natural History and Prevention of Urinary Incontinence of the randomized controlled trial which compared uterine preservation with vaginal hysterectomy, and abdominal procedures with vaginal procedures revealed that there was no difference identified between the groups in term of clinical effectiveness, quality of life, or adverse events (202).

Surgery for stress urinary incontinence and de novo urgency urinary incontinence Midurethral tapes

The midurethral tape procedures, have been shown to result in de novo urgency symptoms/idiopathic detrusor overactivity (IDO). A systematic review of outcomes following midurethral tape procedures reported an overall incidence of de novo OAB of 11.5% in non-randomized studies and 6.4% in randomized studies (203). There was no difference in the rate of de novo OAB symptoms between the different types of midurethral tapes used (203). Risk factors for development of OAB and UUI following midurethral tape procedures include preoperative mixed incontinence with predominant OAB component and older age (204).

Colposuspension

OAB (± DO) with urgency urinary incontinence has been reported to occur in 15–18.5% following colposuspension, (196). Overelevation of the bladder neck (>2.6 cm on MRI) with obstruction has been implicated (205), but no reliable intraoperative method has been found to reproduce the 2.6 cm measurement of elevation; it can only be done subjectively. It is recommended that excessive elevation be avoided by whatever surgical technique.

Midurethral tapes versus colposuspension

In a large RCT comparing these two procedures, the incidence of new-onset urgency and urgency urinary incontinence was less than 2% for TVT and less than 5% for colposuspension at 5 years (206), although this might be an underestimate given the high incidence (over 90%) of preoperative OAB symptoms in both groups in this study. A 13-year follow-up study of outcomes in 1,344 women following either TVT or Colposuspension revealed a nonsignificant difference in de novo OAB symptoms between the two groups: 3% colposuspension and 4.1% TVT, p = 0.41 (207). In a follow-up of patients 7 years after TVT, 22.5% had “urge symptoms.” In a further 6.3%, this was “de novo” (208), similar to the 9.1% incidence reported by other authors (209). In those with preoperative OAB symptoms, 57% resolved after surgery (210). From these case series, it would appear that the incidence of urgency incontinence and OAB after TVT is similar to that reported after colposuspension. Likewise, the rate of de novo urgency and urgency incontinence after transobturator tape (TOT) seems to be comparable to that of TVT (210, 211) and Burch colposuspension (212, 213).

Prolapse surgery and concomitant SUI surgery

The presence of preoperative SUI or UUI is the most important predictor of SUI and UUI postoperatively (214). However, new onset/de novo urinary incontinence is a particularly worrying complication following surgery for POP with an incidence of 15% reported in a national database study of 1198 women. This was irrespective of the prolapsed compartment but strongly associated with BMI (215). Predictive factors include preoperative positive pessary testing, age >50 years, and MUCP 0.7 in all domains tested, indicating adequate internal consistency. Convergent validity was

Questionnaires to Assess Bowel Function assessed by comparison with responses in the SF-36, which showed significant correlations between domains of the two instruments. It was concluded that the questionnaire was both valid and reliable and given the good response rates could be a successful part of a postal survey (26).

Faecal Incontinence and Constipation Assessment (FICA) (Grade B)

The pelvic floor consortium found this tool to be the most comprehensive, validated instrument for faecal incontinence (10). It was the only instrument to capture the volume of stool leakage (deemed essential for characterizing severity of faecal incontinence by the National Institute of Health (27)) and to incorporate the Bristol Stool Scale (a useful marker for colonic transit). It is a modification of other existing tools that the Mayo Clinic developed (28) and is a 98-item questionnaire that assesses the frequency and type of incontinence, number of pads used daily and the severity of urgency. It was validated in an outpatient clinic involving 83 patients; 20 of the patients re-tested 6 months later in order to assess the validity. Although the sample was small, the reproducibility was acceptable. However, the length of the instrument has limited its’ use. The severity of faecal incontinence can be captured with 5 of the 98 questions but the instrument has not been validated in its’ component parts (10).

EQ-5D (Grade B)

This is a generic quality of life tool, applicable across many disease states, translated into most languages. The EQ-5D (developed by the EuroQol group with five dimensions), is a descriptive system that has five dimensions/questions related to mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. In tandem with this addition, there is also a vertical visual analogue scale EQ-VAS, 20 cm (0–100) for self-rated health. It is an HRQL instrument, and one recommended by the National Institute for Health and Care Excellence particularly for the use of health economic analysis in calculations of quality-adjusted life-years (QUALYs). It has been featuring more in clinical trials for faecal incontinence. Its simplicity and ease of analysis is likely to see this gaining popularity over the more complex SF-36 (29).

Elderly Bowel Symptoms Questionnaire (ESBQ) (Grade B)

Another questionnaire developed by the Mayo Clinic group which looks at the elderly (aged 65–93) with bowel symptoms (30). It was a postal questionnaire sent to 424 independently living elderly persons with a 77% response rate. Test–retest reliability was acceptable, and the questionnaire was easy to understand and well accepted.

Wexner score (The Cleveland clinical incontinence score) (Grade C)

The Wexner Score was developed in the Cleveland clinic in 1990 to objectively assess patients with incontinence (31). It was originally published as a clinical tool for physicians but has since been filled in by patients and has also been validated for its’ sensitivity to change following treatment interventions (32). It consists of tables for entry of clinical details and a grading system for the frequency and consistency (solid, liquid, gas) of incontinence and its’ effect on lifestyle (pad usage, lifestyle alteration). The scores are added to generate a figure from 0 (fully continent) to 20 (severely incontinent).

123 This is the most widely used severity index score in Europe and America, its psychometric credentials have been evaluated and it is simple to use and easily understood by patients (28, 29). The ICI evaluated the attributes construct and criterion validity, internal consistency, test–retest reliability and responsiveness to be partly or adequately validated (25). However, the committee has not recommended a higher grade of recommendation due to the lack of more stringent validation.

St. Mark’s incontinence score (Grade C)

This is a tool designed to assess the severity of faecal incontinence and is an adapted version of the Wexner Score with the additional assessment of bowel urgency and the use of anti-diarrhoea medication (maximum score 24) (32). Urgency is defined as less than 15 minutes warning to reach a toilet which may be too long given that healthy women can only defer defaecation for an average of 9 minutes (10, 33). Initial validation involved comparing this tool with the Wexner score in a small group of patients (34). The results were encouraging and showed good inter-instrument correlation and good relationship with a diary card and objective clinical impression. However, another large study of 390 patients that looked at patients with faecal incontinence and compared subjective visual analogue scale score to the St. Mark’s rescore showed only moderate correlation regardless of the severity of the incontinence (35). The St. Mark’s Incontinence Score is validated and reliable, but lack of robust validity leads the ICI panel to state that the tool had potential although more data are required before it can be fully recommended.

Pescatori incontinence score (Grade C)

This tool is hardly used in clinical practice. It was developed in 1992 and uses a number to letter system to the type of incontinence (letter A: flatus/mucus; letter B: liquid; letter C: solid; number 1: occasionally; number 2: weekly; number 3: daily) (34). No comparison has been made with other tools.

Mayo faecal incontinence survey (Grade C)

This is a tool that is used not only for the assessment of faecal incontinence but also its associated symptoms and the risk factors for developing the symptoms [24]. It is a 13-item questionnaire that has been extensively studied [25–27]. It has a good reliability and validity, but very little data exist on responsiveness to clinical change.

The pelvic floor consortium

The consortium concluded that measurement of mucus discharge was not essential because leakage of mucus is seen most commonly with prolapse and haemorrhoids rather than true incontinence. Subsequently, the Faecal Incontinence Severity Index and Faecal Incontinence and Constipation Assessment were excluded from their recommended assessment. Assessment of urgency was considered essential but given that the St Mark’s Incontinence Score paradoxically worsens with fibre supplementation this tool could not be recommended in isolation. The Wexner score was favoured due to its’ logical and clear layout, but it was thought that the lack of assessment of urgency was a major drawback. Consequently, the group reached a more than 70% consensus that a combination of both the St Mark’s Incontinence Score and The Wexner Score provides the best level of quantifying symptoms, treatment outcomes, and impact upon lifestyle whilst also being a practical tool for clinical use (10).

124

Questionnaires to assess symptoms and quality of life in patients with constipation/ bowel evacuation difficulties (Table 13.2) Constipation is a problem that affects a significant proportion of the world’s population and is responsible for symptoms and disorders that create discomfort and morbidity, with consequent high social and economic costs for health care systems. Constipation is a subjective symptom that can be related to a multitude of factors, including dietary, psychological, cultural, anatomic, and functional aspects. In addition, constipation is still surrounded by misconceptions and taboos that hamper an objective evaluation and encourage self-medication that is not always innocuous to the patient care.

Rome IV diagnostic questionnaire

The absence of firm criteria for the diagnosis of digestive functional disorders includes dietary, psychological, cultural, anatomic, and functional aspects. In addition, ecological and clinical research led a group of experts in the 1980s to create committees for establishing consensus on the criteria used to diagnose these problems (36). These were known as the Rome criteria. These have been subject to continual expert review, revision, and modification. In 2016, the Rome IV criteria were published (37). According to the Rome IV committee, the following must be fulfilled for three months (symptom onset at least 6 months prior) for the diagnosis of functional defaecation disorder: 1. Two or more of the following for at least 25% of defaecations: a. straining, b. lumpy or hard stools, c. sensation of incomplete evacuation, d. sensation of anorectal obstruction/blockage, e. manual manoeuvres to facilitate defecations (e.g., digital evacuation, support of the pelvic floor), or f. fewer than three defecations per week. 2. Loose stools are rarely present without the use of laxatives. 3. Insufficient criteria for irritable bowel syndrome (abdominal pain and bloating may be present but are not predominant) (37, 38). The Rome IV diagnostic questionnaires have been developed to screen for functional gastrointestinal disorders, were formulated and verified by clinical experts and their diagnostic sensitivity tested in 843 patients (39). The constipation module consists of 10 questions, its’ validity and reliability has been tested and it should be used to screen for inclusion into clinical trials and for epidemiological studies.

Patient assessment of constipation symptoms and quality of life (Grade B)

These are self-reported questionnaires used to measure symptoms severity of constipations (PAC-SYM) and their impact upon health-related quality of life (PAC-QOL) (40, 41). The PAC-SYM consists of 12 questions, 3 domains (stool, rectal, and abdominal symptoms) and a Likert scale (0–4) for each symptom. It has been partly validated with good internal consistency and test–retest reliability. It has been used across multiple treatment sites and multiple populations with responsiveness over time and the ability to distinguish between treatment responders and non-responders showing its response to change as discriminant validity (10). The validated PAC-QOL is composed of 28 items grouped into four subscales: physical discomfort, psychosocial discomfort,

Textbook of Female Urology and Urogynecology worries and concerns, and satisfaction, with a Likert scale (0–5) for each. The first three subscales are used to assess the patient dissatisfaction index, with an overall score ranging from 0 to 96 (where lower scores correspond to better quality of life). The satisfaction subscale includes four items with a global score ranging from 0 to 6, so that each patient’s self-reported definitive outcome is defined as either poor [0–4], fairly good [5–8], good [9–12], or excellent [13–16]. This questionnaire has been validated in Europe, North America, and Australia [34].

The PROMIS constipation module (Grade B)

The NIH-sponsored Patient Reported Outcomes Measurement Information System (PROMIS) Gastrointestinal Symptom scales have been developed to assess gastrointestinal symptoms across populations in clinical practice and clinical research (42). The PROMIS constipation module is the newest instrument available and is a nine-point questionnaire which has been validated across multiple practices. However, assessment of abdominal pain and bloating, both commonly seen with constipation, require different modules and the PROMIS constipation scale is not responsive to change (42).

Wexner constipation score (The Cleveland constipation scoring system) (Grade C)

This is the most widely used scoring system in the assessment of constipation [30]. It aims to stratify the severity of constipation based on a set of subjective symptomatic complaints. There are eight questions in this score (frequency, painful evacuation, completeness of evacuation, abdominal pain, time on lavatory, assistance, unsuccessful attempts to evacuate, and duration of constipation) and a global scale of (0–30). Constipation is defined if the score is greater than 15. It was developed based on interviews with patients and correlates well with physiological findings (it has been found to differentiate between colonic inertia and pelvic outlet obstruction) (36). This score has been widely accepted because it has a good predictive validity but does not address quality of life.

Knowles Eccersley Scott symptoms (KESS) Score (Grade C)

This is an 11-point tool with Likert Scales (4, 5) and is a modified version of the Wexner Constipation Score with the advantage of including different subtypes of constipation (43). However, no definition of constipation is given which makes it difficult to assess its’ validity.

The Chinese constipation questionnaire (Grade C)

The Chinese Constipation Questionnaire (44) is a six-item selfreport measure designed to diagnose functional constipation in Chinese participants. This scale consists of six items with four subscales: bowel function, stool rectal symptoms, laxative use, and abdominal symptoms. A composite score is generated by principal component analysis with a cut-off score of more than 5 being able to discriminate between controls and constipated patients with both a sensitivity and specificity of 91%. This scoring system is a simple validated tool more commonly used in oriental countries in outcome measures.

The constipation severity instrument (Grade C)

Varma et al. developed this self-assessment tool that consists of 16 questions under 3 subscales: colonic inertia (slow transit), pain (irritable bowel syndrome C symptoms), and incomplete bowel movements (45). It was developed based on literature review

Questionnaire

Aspects Examined

Quality of life

Who

Structure

Validation

Advantages

Disadvantages

Rome IV Constipation Module

Diagnosis of constipation.

No.

Men and women.

10 questions.

Validity and reliability tested.

Does not assess severity.

Patient Assessment of Constipation Symptoms (PAC-SYM)

Symptom severity (stool, rectal and abdominal symptoms).

No.

Men and women.

12 questions, 3 domains, Likert scale (0–4) for each symptom.

Patient Assessment of Constipation Quality of Life (PAC-QOL)

Impact of constipation upon health-related quality of life (physical discomfort, psychosocial discomfort, worries and concerns, satisfaction). Symptom severity.

Yes.

Men and women.

28 items, 4 subscales, Likert scale (0–5) for each symptom.

Partly validated with good internal consistency, test–retest reliability and discriminant validity. Validity and reliability tested.

Used for inclusion for clinical studies and epidemiological research. Ability to distinguish between treatment responders and non-responders. Each domain can be scored independently.

No.

Men and women.

9-point questionnaire.

Wexner Constipation Score (The Cleveland Constipation Scoring System)

Symptom severity.

No.

Men and women.

8 questions.

Knowles Eccersley Scott Symptoms (KESS) Score

Symptom severity (modified version of the Wexner Score).

No.

Men and women.

11 questions (Likert scales 4–5).

Validity tested; reliability not tested.

Correlates well with physiological findings (differentiates between colonic inertia and pelvic outlet obstruction). Includes different subtypes of constipation.

The Chinese Constipation Questionnaire

Diagnosis of functional constipation in Chinese patients (bowel function, stool rectal symptoms, laxative use, abdominal symptoms).

No.

Men and women.

6 item self-report measure.

Validated.

Simple tool.

The PROMIS Constipation Module

Validated across multiple practices. Not responsive to change. Reliability tested. Good predictive validity.

Lack of evidence supporting division of symptoms into the three domains.

Each domain can be scored independently.

Can be used across populations in clinical practice and research.

Questionnaires to Assess Bowel Function

TABLE 13.2: Questionnaires to Assess Symptoms and Quality of Life in Patients with Constipation/Bowel Evacuation Difficulties

Assessment of abdominal pain and bloating require different modules.

Validation is limited as does not give definition of constipation.

(Continued)

125

Questionnaire

Aspects Examined

Quality of life

Who

Structure

Validation

The Constipation Severity Instrument (CSI)

Symptom severity (colonic inertia, pain and incomplete bowel movements).

No.

Men and women.

Self-assessment tool, 16 questions, 3 subscales.

Gastrointestinal Quality of Life Index

Quality of life related to all gastrointestinal symptoms. Effects of constipation on quality of life (social impact, distress, diet, defaecation features). Symptom severity for obstructed defaecation.

Yes.

Men and women.

36 items.

Good discriminatory validity, good convergent validity, high test–retest reliability, reliability tested. Statistically validated.

Yes.

Men and women.

18 questions, 4 domains, 37 items.

Validity tested; reliability tested.

No.

Men and women.

8-point scale with a Likert scale for each.

Still to be validated.

Top two troublesome symptoms and impact upon activities of daily living.

Yes.

Men and women.

Self-reported tool, bespoke questionnaire.

More sensitive to change that SF-36.

Constipation-Related Quality of Life

Obstructive Defecation Syndrome (ODS) Score Measure Yourself Medical Outcome Profile

Advantages

Disadvantages

126

TABLE 13.2 (Continued): Questionnaires to Assess Symptoms and Quality of Life in Patients with Constipation/Bowel Evacuation Difficulties Each domain cannot be scored independently.

Not specific to constipation.

Designed specifically for symptoms of obstructed defaecation. May discriminate between clustering of symptoms. Simple to use.

Recommended for research only.

Textbook of Female Urology and Urogynecology

Individualized so difficult to compare different patients and therefore difficult to use in research.

Questionnaires to Assess Bowel Function and then focus groups of patients and health care providers and has been validated using 191 patients with constipation symptoms and 103 controls. The instrument has good discriminatory validity, good convergent validity when compared with other established questionnaires and high test–retest reliability for all subscales. This instrument is quickly gaining use in both clinical and research settings, especially when patients present with subtypes of constipation syndromes.

Gastrointestinal quality of life index (Grade C)

The gastrointestinal quality of life (QoL) questionnaire (46) was designed to address all gastrointestinal symptoms and therefore is not specific for constipation. It includes 36 items with 5 possible answers, and it has a maximum possible score of 180. Another statistically validated QoL questionnaire, the Constipation-Related Quality of Life (47), has been developed. This includes four domains: social impact (11 items), distress (11 items), usual diet (11 items), and defecation features (4 items). It appears to be an invaluable tool for assessing the effects of constipation on the quality of life.

Obstructive Defecation Syndrome (ODS) score (Grade C)

Given that it may be difficult to identify patients with obstructed defaecation, Longo et al. developed a questionnaire to correlate symptoms with objective physiological findings, grade symptom severity and monitor treatment outcomes (48, 49). It was based on items from the Cleveland Clinic Constipation Scoring System and KESS Score. The original Longo score (0–40) is an 8-point scale (defecation frequency, straining, sensation of incomplete evacuation, recto/perineal pain/discomfort, activity reduction per week, laxatives, enemas, and digitations) with a Likert scale for each symptom (maximum score 31). A modified Longo score is now in use and a lifestyle change parameter has been added to the seven symptom-based parameters. Currently, the modified score is the most commonly used scoring system to decide treatment strategy for ODS patients as well as an outcome measure. The authors suggest that the score may discriminate between clustering of symptoms associated with dyssynergia (rectal digitation) and fragmented defaecation (rectocele, intussusception or prolapse) (50). However, it has no quality-of-life items and is still to be validated, though is recommended for research (1).

Measure yourself medical outcome profile (Grade C)

This is a bespoke questionnaire and is evolving as one of the selfreported tools with potential clinical impact. Patients are asked for their top two troublesome symptoms and the impact of these on their activities of daily living and on general well-being, with both being scored using a 7-point (51) Likert scale. It is simple to use and will apply to all bowel disorders. As it involves generic questions, it allows the patient to self-report symptoms that are important to them. These types of self-reported scoring systems are particularly useful in the follow up assessment of patients and are more sensitive to change than the SF-36. This questionnaire is individualized, thus making it difficult to compare different patients, thus making it less of a research tool, and more of a clinical tool for individual outcome.

The pelvic floor consortium

Although members of the consortium were familiar and comfortable with the PAC-SYM questionnaire, criticisms included weak correlation between symptom scores and diaries (probably due to recall bias), the lack of evidence supporting the division

127 of symptoms into the three domains (rectal symptoms, stool symptoms, abdominal symptoms) and the absence of a threshold value. It was also noted that manoeuvres for manual evacuation were not included. The group found that The Constipation Severity Instrument had been validated against the SF-36 and PAC-SYM scores and that the three domains (obstructed defaecation, colonic inertia, and pain) were useful for placing patients into categories according to the potential cause for their symptoms. Consequently, there was a more than 70% consensus that both the PAC-SYM and Constipation Severity Instrument should both be used to obtain the greatest breadth of information in the most practical way possible (10).

Conclusion A wide range of questionnaires and scoring systems are in existence in order to evaluate bowel function. The mere fact of the bewildering array of different tools is an indication of the generally low quality of the tools. Very few of the questionnaires have been rigorously assessed despite their widespread use. Organizations such as the ICI, the Rome Criteria, and The Pelvic Floor Consortium have recognized this problem. Currently, recommendations from The Pelvic Floor Consortium, endorsed by the ICI, provides the most practical advice for clinical assessment of bowel function and is the result of a more than 70% consensus from international experts. However, continual review and research is needed to optimize the quality of tools available.

Acknowledgement The authors would like to acknowledge Said Mohamed and David Chatoor, the authors of the previous version of this book chapter.

References





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30. O’Keefe EA, Talley NJ, Tangalos EG, Zinsmeister AR. A bowel symptom questionnaire for the elderly. J Gerontol. 1992 July;47(4):M116–21. 31. Jorge JM, Wexner SD. Etiology and management of fecal incontinence. Dis Colon Rectum. 1993 Jan;36(1):77–97. 32. Vaizey CJ, Carapeti E, Cahill JA, Kamm MA. Prospective comparison of faecal incontinence grading systems. Gut. 1999 January;44(1):77–80. 33. Bharucha AE, Seide BM, Zinsmeister AR, Melton LJ. Relation of bowel habits to fecal incontinence in women. Am J Gastroenterol. 2008 June;103(6):1470–5. 34. Pescatori M, Anastasio G, Bottini C, Mentasti A. New grading and scoring for anal incontinence. Evaluation of 335 patients. Dis Colon Rectum. 1992 May;35(5):482–7. 35. Maeda Y, Parés D, Norton C, Vaizey CJ, Kamm MA. Does the St. Mark’s incontinence score reflect patients’ perceptions? A review of 390 patients. Dis Colon Rectum. 2008 April;51(4):436–42. 36. Agachan F, Chen T, Pfeifer J, Reissman P, Wexner SD. A constipation scoring system to simplify evaluation and management of constipated patients. Dis Colon Rectum. 1996 June;39(6):681–5. 37. Schmulson MJ, Drossman DA. What Is New in Rome IV. J Neurogastroenterol Motil. 2017 April 30;23(2):151–63. 38. Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology. 2006 April;130(5):1377–90. 39. Palsson OS, Whitehead WE, van Tilburg MAL, Chang L, Chey W, Crowell MD, et al. Rome IV Diagnostic Questionnaires and Tables for Investigators and Clinicians. Gastroenterology. 2016 February 13; 40. Marquis P, De La Loge C, Dubois D, McDermott A, Chassany O. Development and validation of the Patient Assessment of Constipation Quality of Life questionnaire. Scand J Gastroenterol. 2005 May;40(5):540–51. 41. Frank L, Kleinman L, Farup C, Taylor L, Miner P. Psychometric validation of a constipation symptom assessment questionnaire. Scand J Gastroenterol. 1999 September;34(9):870–7. 42. Khanna D, Hays RD, Shreiner AB, Melmed GY, Chang L, Khanna PP, et al. Responsiveness to change and minimally important differences of the patient-reported outcomes measurement information system gastrointestinal symptoms scales. Dig Dis Sci. 2017 May;62(5):1186–92. 43. Knowles CH, Eccersley AJ, Scott SM, Walker SM, Reeves B, Lunniss PJ. Linear discriminant analysis of symptoms in patients with chronic constipation: validation of a new scoring system (KESS). Dis Colon Rectum. 2000 October;43(10):1419–26. 44. Chan AOO, Lam KF, Hui WM, Hu WH, Li J, Lai KC, et al. Validated questionnaire on diagnosis and symptom severity for functional constipation in the Chinese population. Aliment Pharmacol Ther. 2005 September 1;22(5):483–8. 45. Varma MG, Wang JY, Berian JR, Patterson TR, McCrea GL, Hart SL. The constipation severity instrument: a validated measure. Dis Colon Rectum. 2008 February;51(2):162–72. 46. Eypasch E, Williams JI, Wood-Dauphinee S, Ure BM, Schmülling C, Neugebauer E, et al. Gastrointestinal Quality of Life Index: development, validation and application of a new instrument. Br J Surg. 1995 February;82(2):216–22. 47. Wang JY, Hart SL, Lee J, Berian JR, McCrea GL, Varma MG. A valid and reliable measure of constipation-related quality of life. Dis Colon Rectum. 2009 August;52(8):1434–42. 48. Renzi A, Izzo D, Di Sarno G, Izzo G, Di Martino N. Stapled transanal rectal resection to treat obstructed defecation caused by rectal intussusception and rectocele. Int J Colorectal Dis. 2006 October 1;21(7):661–7. 49. Schwandner O, Stuto A, Jayne D, Lenisa L, Pigot F, Tuech J-J, et al. Decisionmaking algorithm for the STARR procedure in obstructed defecation syndrome: position statement of the group of STARR Pioneers. Surg Innov. 2008 June;15(2):105–9. 50. Altomare DF, Spazzafumo L, Rinaldi M, Dodi G, Ghiselli R, Piloni V. Set-up and statistical validation of a new scoring system for obstructed defaecation syndrome. Colorectal Dis Off J Assoc Coloproctology G B Irel. 2008 January;10(1):84–8. 51. Paterson C. Measuring outcomes in primary care: a patient generated measure, MYMOP, compared with the SF-36 health survey. BMJ. 1996 April 20;312(7037):1016–20.

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INTERNATIONAL CONSULTATION ON INCONTINENCE MODULAR QUESTIONNAIRE Alan Uren, Nikki Cotterill, and Paul Abrams

What is the ICIQ? The first International Consultation on Incontinence was held in 1998 to provide evidence-based recommendations regarding all aspects of incontinence care and research. Committees of experts were convened to encompass all the relevant subject areas. These individuals were from multidisciplinary backgrounds and represented the worldwide scientific community and the range of specialities involved. Each committee was tasked with performing a systematic review of the relevant medical literature in order to make recommendations for clinical practice and research. One such committee responsible for the review of symptom and quality of life assessment identified numerous published questionnaires for the assessment of urinary incontinence (UI). Grades of recommendation regarding their use were applied based on their degree of validation in the published literature [1]. The use of questionnaires with the highest levels of validation was encouraged in clinical practice and research to enable robust evaluation of symptoms and their impact on quality of life and to facilitate the comparison of results across studies. It was also suggested that there was a need for a universally applicable, brief and simple UI questionnaire to be developed and used widely across the population in clinical practice and research—the International Consultation on Incontinence Modular Questionnaire (ICIQ)-UI Short Form [2]. Such an instrument would facilitate comparisons between findings in different settings and studies and was supported by the ICI Scientific Committee [3]. An advisory board was convened to steer development of this questionnaire, and while not included in the review at the first consultation, the lack of questionnaires available for bowel symptoms and incontinence, and vaginal symptoms such as prolapse, was recognized. The decision was taken to expand the project to enable the recommendation and development of, where required, high-quality, fully validated questionnaires for all lower pelvic dysfunction related to incontinence. Since the modular structure was finalized, the ICIQ has expanded to offer 19 psychometrically validated patient reported outcome measures (PROMs) for lower pelvic dysfunction including incontinence, which includes amongst others, a bladder diary, male and female lower urinary tract symptoms (LUTS), long-term catheter use, pad use and bowel symptom questionnaires [4].

Aims and objectives The ICIQ’s objectives are to provide consensus on the use of published questionnaires for the assessment of lower pelvic symptoms and their impact on quality of life. Four aims underpin the ICIQ in order to achieve clarity over questionnaire use [4]: 1. To develop psychometrically validated questionnaires to evaluate symptoms and impact of dysfunction of the lower urinary tract, lower bowel and pelvic organ prolapse.

DOI: 10.1201/9781003144236-16

2. The adoption of existing questionnaires that are psychometrically valid and complement the existing ICIQ. 3. To increase the use of patient reported questionnaires to standardize the assessment of lower urinary tract, lower bowel and pelvic organ prolapse and their impact on patients’ lives. 4. To use the questionnaire to facilitate communication in different patient settings and patient groups, both in clinical practice and wider clinical research.

How is the ICIQ developed? Development of the ICIQ is achieved in two ways: 1. Inclusion of existing high-quality questionnaires with the author’s permission. 2. Production of new questionnaires. Inclusion into the ICIQ is based on a principal factor: evidence of a questionnaire’s robust validation. Psychometric testing of questionnaires for use in clinical practice and research is considered essential to afford confidence in the results obtained [5]. This is of particular importance where decisions regarding treatment or research outcomes are made. There are three main components to standard psychometric evaluation: 1. Validity: Indicates that the instrument is a valid measure of the concept in question. 2. Reliability: Indicates that the instrument can measure the concept in a reproducible and consistent manner. 3. Sensitivity to Change: Indicates that the instrument is able to detect real change in the concept under evaluation [5–10]. To achieve these standards requires considerable time and effort. Production of a new questionnaire, therefore, is only undertaken when there is a specific requirement for the new instrument and when available instruments are inadequate.

ICIQ development protocol The ICIQ follows a standard protocol incorporating qualitative and quantitative methodology. Qualitative studies are undertaken to achieve the aims of including the items of relevance to patients and to maximize clinical utility. There is a particular emphasis on including patients in the item generation process, usually through in-depth interviews (concept elicitation interviews). Patients are essential to provide insight regarding the lived experience of their symptoms and describe the impact on their quality of life [11]. Issues required for clinical evaluation may be more readily identified by the input of clinical experts, particularly where specific clinical manifestations are required to 129

130 infer diagnosis. For example, the symptoms of urinary urgency and frequency described by patients are symptoms characteristic of overactive bladder (OAB) [12]. This process of sourcing the views of patients, those of expert clinical panel and the known literature documenting the patient experience of the condition ensures that the most pertinent issues for evaluation are identified. The value of conducting qualitative enquiry is also in establishing the most appropriate phraseology and terminology for self-report questionnaires [13] and refining the tool to ensure it is understood by the user as intended and completed easily. This approach is considered essential in producing a credible patientreported tool [14] and provides a sound evidence base for questionnaires to go on and be evaluated using rigorous quantitative methods. The quantitative evaluation of the resulting tool has the aim of establishing the extent to which the tool displays the properties of validity (accuracy), reliability (stability) and sensitivity to change (ability to measure change when it occurs). Following the collection of questionnaire data in the target population, numerous statistical analyses are undertaken in order to make decisions regarding the most robust measurement question items to retain in the final version of the questionnaire. Further consultations with clinicians and potential respondents are conducted to ensure the final version of the questionnaire reflects clinical and patient relevance while displaying the most robust psychometric properties.

Textbook of Female Urology and Urogynecology The ICIQ continues to update its protocols in-line with current scientific standards of questionnaire development [4], including when appropriate the adherence with guidelines as set out by the United States FDA “Guidance for Industry: Patient Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims” [14]. This is particularly relevant if an instrument is to be approved by regulatory authorities as an outcome measure in clinical drug trials to support labeling claims. The publication in scientific journals of the development process for new modules, showing evidence of the content validity and subsequent psychometric testing is an important part of demonstrating their validity and to allow the rigor of their development to be assessed. A summary of the current ICIQ process for the development of a questionnaire is given in Figure 14.1 [4].

How to use the ICIQ Nineteen ICIQ modules/questionnaires are currently available for use. Clinicians or researchers are able to select modules to compile a tailored questionnaire set that meets their study/ clinical practice requirements to achieve complete evaluation. In order to simplify this, modules have been categorized to aid selection (Table 14.1). The ICIQ recommends the use of a “core” or “symptom-specific” module and an “add-on” quality of life measure in all patient evaluations for both clinical practice and research. Symptom alleviation may not indicate a difference

FIGURE 14.1  The six main stages of questionnaire development as per the ICIQ protocol. (From ref [4], with permission.)

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TABLE 14.1: The ICIQ Modular Structure Core Questionnaires Condition

Symptoms

Optional

HRQoL

Sexual Matters

Post Treatment

Urinary symptoms

Males: ICIQ-MLUTS [17] Females: ICIQ-FLUTS [18]

Males: ICIQ-MLUTS Long Form Females: ICIQ-FLUTS Long Form

ICIQ-LUTSqol [19]

Males: ICIQ-MLUTSsex Females: ICIQ-FLUTSsex

ICIQSatisfaction

Vaginal symptoms Bowel symptoms Urinary incontinence

ICIQ-VS [20] ICIQ-B [13, 21] ICIQ-UI Short Form [2]

ICIQ-VS ICIQ-B ICIQ-LUTSqol ICIQ-UI SF

ICIQ-VS ICIQ-B Males: ICIQ-MLUTSsex Females: ICIQ-FLUTSsex

Prospective bladder events

ICIQ-Bladder diary [22, 23]

Condition Nocturia

Symptoms ICIQ-N

HRQoL ICIQ-Nqol [24]

Overactive bladder

ICIQ-OAB

ICIQ-OABqol [25]

Underactive bladder Long-Term catheter Children Absorbent pads Inflammatory bowel disease Cognitively impaired adults

ICIQ-UABa [26, 27]

Specific Patient Groups Sexual Matters Males: ICIQ-MLUTSsex Females: ICIQ-FLUTSsex Males: ICIQ-MLUTSsex Females: ICIQ-FLUTSsex

ICIQ-LTCqol [28] ICIQ-CLUTS [29] ICIQ-PadPROM [30] ICIQ-IBD ICIQ-Coga, [31]

Source:  Adapted from Uren et al. [4] Note:  The following modules were adopted as ICIQ modules with author’s permission: ICIQ-Nqol, ICIQ-OABqol, ICIQ-LUTSqol. a These questionnaires are currently in development.

in impact on quality of life and so the evaluation of both is recommended to encompass all relevant aspects to the individual [15, 16]. This approach can also target treatment to the most bothersome component of a symptom complex. The following text describes the available modules to inform initial decisions regarding questionnaire selection.

impact on quality of life. These may be used as an indicator by clinicians to target treatment to the most bothersome symptoms (Fig. 14.2). The bladder diary provides the first validated diary for the collection of bladder-related events. Qualitative studies were conducted to derive the parameters for inclusion followed by quantitative studies to evaluate the robustness of the tool [3, 5].

Recommended modules for the assessment of symptoms Core modules

Specific patient groups

The questionnaire modules provide assessment of core symptoms of lower pelvic dysfunction: • Lower urinary tract symptoms (LUTSs) (male and female specific versions): ICIQ-MLUTS/ICIQ-FLUTS • Diary of urinary events: ICIQ-Bladder Diary • Vaginal symptoms (female version only): ICIQ-VS • Bowel symptoms focusing on anal incontinence (male and female applicable version): ICIQ-B • UI (male and female applicable version): ICIQ-UI Short Form Each questionnaire provides a comprehensive yet brief instrument for measurement of the stated symptoms and associated “bother.” The bother items attached to individual symptoms enable the individual to indicate symptoms that causing the most

This group of questionnaires provides assessment of some specific conditions or symptom complexes such as nocturia and OAB. This category also includes specific patient groups (e.g., children, individuals with long-term catheters). These instruments contain only question items associated with the symptom complex or have been developed specifically for use in a specific group. These questionnaires therefore are only utilizable in the stated populations and would need further evaluation for use in other groups. Bother items are included for all except the children’s questionnaire: • • • • • •

Nocturia (male and female applicable version): ICIQ-N OAB (male and female applicable version): ICIQ-OAB Patients using long-term catheters: ICIQ-LTCqol LUTS in children: ICIQ-CLUTS Underactive bladder: ICIQ-UAB Inflammatory Bowel Disease: ICIQ-IBD

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5b.

Do you have to rush to the toilet to urinate?

Never

0

Occasionally

1

Sometimes

2

Most of the time

3

All of the time

4

How much does this bother you? Please ring a number between 0 (not at all) and 10 (a great deal) 0

1

2

3

4

5

6

7

8

9

10

Not at all

A great deal

FIGURE 14.2  Example of an International Consultation on Incontinence Modular Questionnaire question item.

Recommended modules for the assessment of quality of life and sexual matters Core modules

This group of questionnaires incorporates quality of life and sexual matters modules. They are recommended to be completed as stand-alone questionnaires or alongside other core or specific symptom evaluations. The core symptom modules described earlier contain bother items indicating impact on quality of life directly related to symptoms. Quality of life questionnaires cover more specific issues that are a consequence of symptoms (e.g., limiting activities and affecting relationships). The combination of symptom assessment with associated bother and a quality of life assessment provides a more complete evaluation of the patient’s experience [16, 32]. In addition, given the nature of lower pelvic dysfunction, sexual matters can also be affected and questionnaires are available for this further evaluation where appropriate. Bother associated with impact items is included as this can be very personal and quite unrelated to the frequency of the issue alone: • Quality of life associated with LUTSs (male and female applicable version): ICIQ-LUTSqol. • Quality of life associated with bowel symptoms (male and female applicable version): ICIQ-B. • Sexual matters associated with LUTSs (male and female specific versions): ICIQ-MLUTSsex/ICIQ-FLUTSsex. • Sexual matters associated with vaginal symptoms are included in the symptom questionnaire (ICIQ-VS) as the issues were considered too intrinsically linked to separate for evaluation. • Sexual matters associated with bowel symptoms are included in the symptom and quality of life questionnaire (ICIQ-B) as the issues were considered too intrinsically linked to separate for evaluation.

Specific patient groups

In the same manner as the symptom modules, quality of life modules are available for specific symptom complexes: • Quality of life associated with nocturia (male and female applicable version): ICIQ-Nqol • Quality of life associated with OAB (male and female applicable version): ICIQ-OABqol • Quality of life associated with long-term catheter use: ICIQ-LTCqol • Quality of life associated with the use of absorbant continence products: ICIQ-PadPROM

Optional modules

This category includes lengthier questionnaires for more exploratory evaluation of the core symptoms of lower pelvic dysfunction. There is the long form for the assessment of LUTS in men (ICIQ-MLUTS LF) and the long form for the assessment of LUTS in women (ICIQ-FLUTS LF). While these questionnaires are suitable for use in clinical practice, they have not been shortened for clinical efficiency and are therefore more widely used in research studies where exploration of a broader range of symptoms may be desired and more feasible.

Post-treatment module

The ICIQ-Satisfaction was developed to allow the assessment of patient satisfaction with experience, expectations and outcomes after urological surgery. The questionnaire was developed using a post-surgical population of men after prostatectomy [33]. After further testing in different patient populations, the ICIQ-S is intended to be more generally used after any urological or gynecological surgical procedure. A further questionnaire to assess patient satisfaction and perceived value of urological investigations (such as urodynamics) is also under development.

Scoring of the ICIQ

The scoring of the ICIQ modules are derived using standard factor analytic methods to group items that are related to one another [34]. For example, in the ICIQ-FLUTS there are “Filling” (F), “Voiding” (V) and “Incontinence” (I) domains. The F domain contains items that ask about the frequency of nocturia, urgency, bladder pain and daytime urinary frequency. The sum of the items within the domain gives a score that is more reliable than the individual items, and more sensitive to change if compared over multiple administrations. The associated part “b” of the items asks “how much does this bother you?” on a scale of 0–10 and is not included in the summed domain score but can be used by the clinician to indicate which of the symptoms may be of most concern to the patient and to target treatment accordingly. For some of the modules, the interpretation of the scores can be helped by categories of severity, or minimally clinically important differences. For example, the ICIQ-UI SF has had scoring categories derived as follows: light (1–5), moderate (6–12), severe (13–18), very severe (19–21) [35]. For the ICIQ-LUTSqol, a change of six points is deemed a clinically significant effect for women with SUI [36]. The ICIQ does not routinely develop MIDs or scoring interpretation categories for its questionnaires within its standard development protocols but encourages further research and collaborations in order to aid their interpretation. Further

International Consultation on Incontinence Modular Questionnaire scoring instructions can be found on the ICIQ website or by contacting the ICIQ group.

ICIQ translations

The ICIQ’s international nature requires that translations are available, which is also conducted according to an established protocol involving structured translation process. In brief, the new translation is first produced by a bilingual speaker of the target language, which is then back-translated by a native English speaker. The back translation is then reviewed for any semantic differences between the original English version and any discrepancies are reconciled. This new version is then tested for its equivalence to the original version. At the minimum, cognitive interviews are carried out with a number of patients in the target language population and full psychometric testing in some cases. Over 300 translations of the modules are now available through the ICIQ website. However, if a translation is not already available then the ICIQ encourages external collaborators to produce translations and the team are happy to support developers with the process. The ICIQ retains copyright of any translations produced.

Uptake of the ICIQ

Use of the ICIQ in clinical practice and research has been encouraging in achieving the aims of standardized, high-quality assessment for symptoms of lower pelvic dysfunction and their impact on quality of life. As of October 2020 there have been over 3700 publications that mention the “ICIQ” or the modules [4]. The most widely applied module is the ICIQ-UI Short Form (ICIQ), which is closely followed by the ICIQ-FLUTS reflecting the fact that most applications relate to the evaluation of female urinary symptoms. The ICIQ has most commonly been applied to clinical and general practice settings, alongside its considerable uptake in the research setting.

The ICIQ licensing, website and online library

The website was first available in 2004 and since then has been achieving its aim of providing information and the dissemination of the ICIQ modules. The new website, launched in 2019 has a semi-automated request form which allows a user to request access and to be given permission for use of their specified modules. More information about each module, including lists of the items, sample copies, scoring systems and links to the validation publications can be found here. Access to the online library of modules and translations is given after the user has completed this brief user access form. The ICIQ modules remain free for use in small grant funded research and clinical practice. However, a license fee is required for use in large grant funded research (users are requested to include a recommended fee in their grant funding applications) and for commercial users. Any funds raised are used to pay for the not-for-profit running costs and ongoing research and development activities of the ICIQ. Additional updates on new modules that are in development are also included in the website and also announced on the ICIQ twitter account (@ICIQ_PROMs).

Electronic adaptation of the ICIQ

The need for innovative digital solutions to remotely support patient management is advancing at pace. The advantages of electronic administration include the automatic administration and collection of PROM data for ongoing assessment and research, reducing the need for costly paper administration and data entry.

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Urology lags behind other healthcare fields in the adoption of digital health technology, despite its potential to improve patient care [37]. Studies have been conducted to evaluate the acceptability and equivalence of the psychometric robustness of electronic versions of the ICIQ. Qualitative studies were undertaken to evaluate the acceptability to the population of interest and to identify modifications required to enable the ICIQ to be completed in an electronic format. Quantitative studies were also undertaken to evaluate the psychometric properties of the ICIQ modules in electronic format to ensure their equivalence to paper versions [38]. A new project in collaboration with an existing eHealth platform provider is to adapt an existing digital platform/mobile application for patients presenting with LUTS symptoms. The platform is also expected to offer an electronic option for the routine clinical and research administration of the ICIQ questionnaires.

Conclusion The ICIQ modular questionnaire project provides an expanding series of standardized questionnaires for the assessment of lower pelvic dysfunction and its impact on quality of life. The ICIQ provides clarity over which questionnaires to use by recommending only those with evidence of high quality and robust psychometric validation data. This assurance provides the user with confidence in the results obtained. This is particularly important in clinical practice and research where treatment decisions or trial outcomes increasingly rely on this source of evidence. The ICIQ continues to have international usage, and facilitates dissemination through its website, online library and a social media presence. The future use of the ICIQ is anticipated to be increasingly electronic as there is a greater focus on their electronic integration into clinical practice by various digital means.

References





1. Donovan J, Naughton M, Gotoh M, et al. Symptom and quality of life assessment. In P Abrams, S Khoury, and A Wein, eds. Proceedings of the First International Consultation on Incontinence, 1st ed., June 28–July 1, 1998. Plymouth, U.K.: Health Publication Limited, 1999, pp. 295–331. 2. Avery K, Donovan J, Peters T, Shaw C, Gotoh M, Abrams P. ICIQ: A brief and robust measure for evaluating symptoms and impact of urinary incontinence. Neurourol Urodyn. 2004;23:322–330. 3. Abrams P, Avery K, Gardener N, Donovan J. The international consultation on incontinence modular questionnaire: www.iciq.net. J Urol. 2003;175:1063–1066. 4. Uren AD, Cotterill N, Pardoe M, Abrams P. The International Consultation on Incontinence Questionnaires (ICIQ): An update on status and direction. Neurourol Urodyn. 2020;39(6):1889–1896. 5. Streiner DL, Norman GR. Health Measurement Scales: A Practical Guide to Their Development and Use, 3rd ed. New York: Oxford University Press, 2004. 6. Oppenheim AN. Questionnaire Design, Interviewing and Attitude Measurement, 2nd ed. London, U.K.: Continuum, 1992. 7. Bowling A. Research Methods in Health: Investigating Health in Health Services, 2nd ed. Maidenhead, U.K.: Open University Press, 2002. 8. Boynton PM, Greenhalgh T. Selecting, designing, and developing your questionnaire. Br Med J. 2004;328:1312–1315. 9. Saw SM, Ng TP. The design and assessment of questionnaires in clinical research. Singapore Med J. 2001;42:131–135. 10. Donovan J, Bosch JLHR, Gotoh M, et al. Symptom and quality of life assessment. In P Abrams, L Cardozo, S Khoury, and A Wein, eds. Proceedings of the Third International Consultation on Incontinence, 3rd ed., June 26–29, 2004. Plymouth, U.K.: Health Publication Limited, 2005, pp. 519–584. 11. Rapley M. Quality of Life Research: A Critical Introduction, 1st ed. London, U.K.: Sage Publications Limited, 2003. 12. Peat J. Health Science Research: A Handbook of Quantitative Methods. London, U.K.: Sage Publications Limited, 2002.

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13. Cotterill N, Norton C, Avery KNL, Abrams P, Donovan JL. A patient centered approach to developing a comprehensive symptom and quality of life assessment of anal incontinence. Dis Colon Rectum. 2008;51:82–87. 14. Food and Drug Administration (FDA). Guidance for Industry: PatientReported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. Silver Spring, MD: FDA, 2009. 15. Weber AM, Abrams P, Brubaker L, et al. The standardization of terminology for researchers in female pelvic floor disorders. Int Urogynecol J. 2001;12:178–186. 16. Fairclough DL. Patient reported outcomes as endpoints in medical research. Stat Methods Med Res. 2004;13:115–138. 17. Donovan JL, Peters TJ, Abrams P, Brookes ST, De La Rosette J, Schäfer W. Scoring the short form ICSmaleSF questionnaire. J Urol. 2000;164(6):1948–1955. 18. Brookes ST, Donovan JL, Wright M, Jackson S, Abrams P. A scored form of the Bristol Female Lower Urinary Tract Symptoms questionnaire: Data from a randomized controlled trial of surgery for women with stress incontinence. Am J Obstet Gynecol. 2004;191(1):73–82. 19. Kelleher CJ, Cardozo LD, Khullar V, Salvatore S. A new questionnaire to assess the quality of life of urinary incontinent women. BJOG Int J Obstet Gynaecol. 1997;104(12):1374–1379. 20. Price N, Jackson S, Avery K, Brookes S, Abrams P. Development and psychometric evaluation of the ICIQ Vaginal Symptoms Questionnaire: The ICIQ-VS. BJOG Int J Obstet Gynaecol. 2006;113(6):700–712. 21. Cotterill N, Norton C, Avery KNL, Abrams P, Donovan JL. Psychometric evaluation of a new patient-completed questionnaire for evaluating anal incontinence symptoms and impact on quality of life: The ICIQ-B. Dis Colon Rectum. 2011;54(10):1235–1250. 22. Bright E, Cotterill N, Drake M, Abrams P. Developing a validated urinary diary: Phase 1. Neurourol Urodyn. 2012;31(5):625–633. 23. Bright E, Cotterill N, Drake M, Abrams P. Developing and validating the International Consultation on Incontinence Questionnaire bladder diary. Eur Urol. 2014;66(2):294–300. 24. Abraham L, Hareendran A, Mills IW, et al. Development and validation of a quality-of-life measure for men with nocturia. Urology. 2004;63(3):481–486. 25. Coyne K, Revicki D, Hunt T, et al. Psychometric validation of an overactive bladder symptom and health-related quality of life questionnaire: The OAB-q. Qual Life Res. 2002;11(6):563–574. 26. Uren AD, Cotterill N, Harding C, et al. Qualitative exploration of the patient experience of underactive bladder. Eur Urol. 2017;72(3):402–407. 27. Uren AD, Cotterill N, Harding C, et al. The development of the ICIQ-UAB: A patient reported outcome measure for underactive bladder. Neurourol Urodyn. Published online February 22, 2019. doi:10.1002/nau.23947



28. Cotterill N, Fowler S, Avery M, et al. Development and psychometric evaluation of the ICIQ-LTCqol: A self-report quality of life questionnaire for long-term indwelling catheter users: Quality of life evaluation for long term indwelling catheter users. Neurourol Urodyn. Published online February 2015:n/a-n/a. doi:10.1002/nau.22729 29. De Gennaro M, Niero M, Capitanucci ML, et al. Validity of the international consultation on incontinence questionnaire-pediatric lower urinary tract symptoms: A screening questionnaire for children. J Urol. 2010;184(4 Suppl.):1662–1667. 30. Yearwood Martin C, Murphy C, Cotterill N, Williams S, Cottenden A, Fader M. Development and psychometric evaluation of ICIQ-PadPROM: A quality of life questionnaire to assess the treatment effect of absorbent continence products. Neurourol Urodyn. 2018;37(5):1650–1657. 31. Volz-Sidiropoulou E, Rings T, Wagg AS, Leistner N, Gauggel S, KirschnerHermanns R. Development and initial psychometric properties of the “ICIQ-Cog”: A new assessment tool to measure the disease-related impact and care effort associated with incontinence in cognitively impaired adults. BJU Int. 2018;122(2):309–316. 32. Abrams P, Artibani W, Gajewski JB, Hussain I. Assessment of treatment outcomes in patients with overactive bladder: Importance of objective and subjective measures. Urology. 2006;68(Suppl. 2a):17–28. 33. Uren AD, Cotterill N, Hashim H, Worthington J, Kapoor D, Abrams P. International Consultation on Incontinence Questionnaire-Satisfaction: Psychometric testing of a new patient-reported outcome measure for the evaluation of satisfaction after urological surgery. BJU Int. Published online April 22, 2020. doi:10.1111/bju.15091 34. Yong AG, Pearce S. A beginner’s guide to factor analysis: Focusing on exploratory factor analysis. Tutor Quant Methods Psychol. 2013;9(2):79–94. 35. Klovning A, Avery K, Sandvik H, Hunskaar S. Comparison of two questionnaires for assessing the severity of urinary incontinence: The ICIQ-UI SF versus the incontinence severity index. Neurourol Urodyn. 2009;28(5):411–415. 36. Lim R, Liong ML, Lim KK, Leong WS, Yuen KH. The Minimum Clinically Important Difference of the International Consultation on Incontinence Questionnaires (ICIQ-UI SF and ICIQ-LUTSqol). Urology. 2019;133:91–95. 37. Pereira Azevedo N, Gravas S, de la Rosette J. Mobile health in urology: The good, the bad and the ugly. J Clin Med. 2020;9(4). doi:10.3390/jcm9041016 38. Uren AD, Cotterill N, Parke SE, Abrams P. Psychometric equivalence of electronic and telephone completion of the ICIQ modules. Neurourol Urodyn. 2017;36(5):1342–1349.

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ELECTRONIC PERSONAL ASSESSMENT QUESTIONNAIRE (EPAQ) FOR PELVIC FLOOR Thomas Gray, Victoria Kershaw, and Stephen Radley

Background Interest in questionnaire use in healthcare has been driven largely by the need for reliable and valid instruments for outcomes research. More recently, however, their use has become a desirable, if not essential element in routine clinical practice [1]. This chapter explores the concept, development, and introduction of electronic patient-reported outcome measures (ePROM) for use in urogynaecology, aiming to bridge the divide between research and day-to-day patient care. There is growing enthusiasm for reducing the resource burden of patient-reported outcome measures using information technology (IT). Electronic data collection compares favourably with paper-based systems in terms of reliability and validity, with lower levels of missing data [2]. Patients have found them relatively easy and even enjoyable to complete, offering efficiency advantages for large surveys [3, 4]. When collecting sensitive data, computerassisted interviewing results in greater openness and disclosure than paper-based questionnaires or face-to-face interviews [5–7]. These findings have implications for questionnaire use in urogynaecology, both in research and clinical practice. Web-based and paper versions of the Pelvic Floor Distress Inventory-20 (PFDI-20), Pelvic Floor Impact Questionnaire-7 (PFIQ-7), and Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12) have been compared and found to be reliable and with high correlations between the different formats [8, 9]. The sample sizes in these studies were relatively small (n = 52), and although correlations were strong, differences were observed between different formats and not all patients were willing or able to use the electronic questionnaire. In the select sample of those using both formats, the majority expressed a preference for web-based completion.

Pelvic floor patient-reported outcome measures A range of questionnaires have been developed to measure and record symptomatology, conditions, health, and health-related quality of life in urogynaecology [10]. Such instruments have often been designed for a specific purpose or setting, the more established patient-reported outcome measures (PROMs) having been developed for research. However, using questionnaires in direct clinical care presents substantially different challenges. In order for a questionnaire to be clinically useful, it must be accessible, meaningful, and easy-to-use (both for patients and clinicians) as well as possessing demonstrable reliability, validity, and responsiveness. In order to inform clinical assessment, an instrument should ideally be completed prior to clinical consultation, reducing the risk of influence by the clinician and informing the consultation itself. Most condition-specific questionnaires are, however, too narrow in their scope to be used in this way. Women with pelvic floor disorders commonly have interrelated problems,

DOI: 10.1201/9781003144236-17

for example, bowel and urinary incontinence, incontinence and prolapse, prolapse and sexual dysfunction. This has driven the development of more generic urogynaecology/pelvic floor questionnaires, covering a range of disorders. For these broader and potentially longer instruments, there is then a tension between the burden of providing sufficient detail and the lack of depth afforded by brevity. One of the key disadvantages of paper-based PROMs is their inability to process, store, and analyse the data easily. In order to achieve this with paper-based PROMs, the data need to be entered by hand into a database which is time consuming and costly. ePROMs offer patients the opportunity to complete the assessment when it is convenient for them and in their own home. This may mean that responses to questions are more honest and open as the patient may feel more comfortable in a non-medical setting and have a better opportunity to reflect on their symptoms [5, 6] and the impact of these on function and health-related quality of life (HRQoL), compared to completing the PROM on paper in an outpatient clinic waiting room. ePROMs also offer the opportunity to assess patients remotely, via a virtual clinic. This has considerable benefits for follow-up patients who may be able to have a telephone consultation after completion of an ePROM at home to assess progress, rather than having to re-attend the outpatient department [11]. ePROM data could also be utilised to give tailored advice to patients on selfmanagement, as well as providing healthcare professionals with detailed symptom and HRQoL data between scheduled appointments. Previous research has found that electronic systems can gain better response rates and patients may find them easier and more satisfying to complete [12].

Development of electronic Personal Assessment Questionnaire: Pelvic Floor The original concept for the electronic Personal Assessment Questionnaire (ePAQ) arose from a desire to harness the accuracy and reliability of well-designed questionnaires in clinical practice, enhance communication, and provide in-depth, objective understanding of patients’ conditions. The aim was to utilise computer technology to provide an efficient, interactive, single instrument, addressing issues of feasibility faced with the use of paper questionnaires such as compliance, burden, and cost associated with entering, processing, and storing large volumes of clinical data (Fig. 15.1) [13]. Electronic Personal Assessment Questionnaire-Pelvic Floor (ePAQ-PF) was initially created as a web-based software application, using Microsoft Access® combined with Structured Query Language (SQL) server and dotNet programming to produce an interactive system for use on touch-screen computer terminals. The purpose-built Microsoft Access® “Q-Builder” software incorporated all the technical elements: physical layout and 135

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FIGURE 15.1  Touch-screen PC used in gynaecology outpatient department. ePAQ was initially deployed in outpatient clinics using touch-screen terminals. The majority of patients now complete the questionnaire via the Internet prior to clinic attendance. Women who are unable to complete online are invited to attend early in order to complete the questionnaire using a touchscreen terminal, prior to their clinical consultation. This takes approximately 20–25 minutes. display (e.g., colours, buttons, and font sizes), item content, and response data. Active Server Pages provide dynamic and interactive elements, supporting a database interface via SQL server that allowed data management on a single database. The system is forward-compatible with electronic data management software systems, allowing integration with other modalities such as new electronic results reporting and electronic patient records. The initial prototype for ePAQ-PF was based on existing paper-based questionnaires; Birmingham Bowel and Urinary Symptoms, Sheffield Prolapse Symptoms Questionnaires, and Female Sexual Function Index (FSFI) were adapted and combined in a single instrument. Consultation with specialists in urology, gynaecology, colorectal surgery, and sexual medicine identified additional items, whose format was unified to achieve consistency throughout. Sub-questions on impact (as used in the ICS-Male and Bristol Female Lower Urinary Tract Symptoms Questionnaires) were included. Paper and electronic versions were reviewed by the local maternity research user group, who provided critical structured feedback. Psychometric testing was carried out in 432 patients in primary and secondary care [13]. Test–retest indicated good stability over time and patient acceptability was high. This was evaluated in terms of value and burden using a 10-item questionnaire (QQ10), specifically designed for this purpose, and administered to patients immediately following their clinical episode [14]. ePAQ showed high value and low burden; most women find it relevant, valuable, and easy-to-use. Secondary factor analysis was carried out in a further 247 patients, to confirm the item content and 19-domain structure of the instrument now in clinical use, which was subsequently found to be responsive to change in women undergoing surgical intervention for incontinence and prolapse [15, 16]. Assessment of construct validity by comparing ePAQ-PF domain scores with urodynamic diagnosis was also undertaken [17]. Subsequently, a further domain was

Textbook of Female Urology and Urogynecology developed to assess “Body image” in urogynaecology patients, having identified an unmet need during an analysis of free-text data from ePAQ-PF [18]. The content of this new domain was developed using free-text data from patients completing ePAQPF who reported body image concerns, feedback from a patient user group, and review of existing PROMs to assess body image in urogynaecological patients in a systematic review [19]. This new domain underwent psychometric testing with factor analysis to determine item structure, assessment of internal consistency reliability with Cronbach’s alpha, criterion validity assessment compared to an established body image PROM, and assessment of convergent construct validity by evaluating seven hypotheses regarding body image in urogynaecology patients based on outcomes from studies identified in the previous systematic review [19]. Face validity was assessed using the QQ-10 questionnaire [15]. The new body image domain consisted of five questions and demonstrated good reliability, validity, acceptability, and functionality [20]. Table 15.1 provides a summary of all the studies undertaken evaluating the psychometric properties of ePAQ-PF, and Table 15.2 summarises the populations of these studies.

Questionnaire structure and content The main section of ePAQ-PF is preceded by introductory pages, which provide information about the system and instructions for unsupervised completion. The standard format presents one question per page, each of which includes its own “Help Page.” Navigation through the questionnaire uses “Next” and “Back” buttons, with a “Skip” button allowing subjects not to answer a question, thereby eliminating accidental nonresponse, a fundamental problem with paper-based instruments. The questionnaire automatically adapts responses to screening questions enabling skipping of non-relevant items or sections, whilst more probing questions are presented when appropriate. Responses to key screening questions determine whether or not subsequent items are skipped, thereby minimising burden. When subjects are asymptomatic, the number of questions is reduced, minimising respondent burden. Conversely, symptomatic individuals undergo more detailed and relevant assessment. The full questionnaire comprises up to 137 items, distributed across four dimensions: (1) Urinary, (2) Bowel, (3) Vaginal, and (4) Sexual (Table 15.3). Within each dimension are five scored domains (20 in total), each comprising of three to seven items (questions). All items included in these domains are scored between 0 and 3. Domains themselves are scored by dividing the sum total of item response values by the maximum possible score and transforming this value onto a scale of 0 to 100 (0 indicating “Best” and 100 “Worst” health status). The 20 domains of ePAQ and a summary of their constituent items are shown in Table 15.3. ePAQ is interactive on a number of levels. The standard item format includes a question on how often a symptom occurs (symptom frequency) and a sub-question on how much of a problem this is (symptom impact). These sub-questions are also hidden if subjects are asymptomatic (screen negative) (Fig. 15.2). The “friends and family test” has recently been incorporated, giving patients the opportunity to provide feedback on the care that they have received. The final item records patients’ willingness for their data to be used for non-clinical purposes, such as service evaluation and audit; 95% of patients agree to this (Fig. 15.3).

Electronic Personal Assessment Questionnaire (ePAQ) For Pelvic Floor

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TABLE 15.1: Summary of Results of Psychometric Evaluations of ePAQ-PF Reliability

Validity

Study

Cronbach’s Alpha Interclass Correlation/ Pearson’s R

Radley et al, 2006 [13]

Cronbach’s alpha: 0.82–0.97 ICC 0.73–0.91, all p < 0.001

Patients in secondary care had higher domain scores than those in primary care

Jones et al, 2008 [16]

Cronbach’s alpha 50% reduction in symptoms) compared to placebo [66]. In a randomised, prospective, double-blind, placebo-controlled trial conducted by CL Parsons [66], 32% of 148 patients treated with PPS reported significant improvement in symptoms, compared with 16% in the placebo group (p = 0.01). A recent large multicentre randomised controlled trial of 368 patients randomised to receive either 100 mg of PPS once per day, three times per day or placebo, reported no significant difference between any group (success defined as a 30% reduction in baseline interstitial cystitis symptom index [ICSI] score) [67]. PPS remains the medication of choice for most patients. Patients should be advised that it may take up to 6–9 months for the full effect of the drug to be attained. There have been increasing recent reports of pigmentary maculopathy leading to visual disturbance with long-term use (median 186 months) in up to 16% of patients, and this is likely to reduce the use of PPS for BPS/IC in the future [68, 69]. The use of PPS simultaneously as an intravesical and oral agent, has also been studied in a small randomized double blinded clinical trial with evidence suggesting short term reduction in BPS symptomatology by a median of 46% when compared to placebo [70].

Intravesical treatments

Intravesical treatments involve direct administration of the drug into the bladder. They are usually used alone as second-line treatment or in conjunction with oral therapy and other forms of conservative management. The available intravesical drug treatments include the following:

592 Dimethyl sulfoxide

Dimethyl sulfoxide (DMSO) was first synthesised as a byproduct of the wood industry. It is the most widely used and remains the sole intravesical agent approved by the Food and Drug Administration for treatment of BPS/IC. Its mechanism of action is not clearly understood but it is hypothesised to exert its clinical action by decreasing inflammation, triggering relaxation of bladder muscles, and influencing inflammatory mast cells [71]. It has been shown to be an effective treatment of BPS/IC. Objective improvement was noted in 93% of patients with cystoscopy-positive IC treated with DMSO versus 35% in the placebo group [72]. A common side effect of the drug is garlic-like odour to the breath. Treatment is usually performed on a weekly basis for 6–8 weeks after which treatment is discontinued until symptoms recur. A more recent study aiming to assess the long term efficacy of intravesical DMSO/heparin/hydrocortisone and bupivacaine combined therapy in patients with BPS concluded that at a median follow-up of 60 months, intravesical DMSO combined therapy appeared moderately effective for the treatment of IC/BPS. Treatment failure was more frequent in patients with pretreatment symptoms of reduced bladder capacity [73]. DMSO has also been compared with intravesical chondroitin sulphate 2% (CS) in a randomised controlled multicentre trial including 36 patients diagnosed with BPS, with CS demonstrating superior effects in terms of withdrawal rate due to side effects, reported moderate or marked improvement (72.7% vs. 14%, P = 0.002) and reduction in VAS scores (20% vs. 8.3%). CS groups performed significantly better in pain reduction (−1.2 vs. −0.6) and nocturia (−2.4 vs. −0.7) [74]. However due to lack of larger scale randomised controlled trials with sufficient follow up, DMSO remains unlicensed in the UK [75].

Heparin

It is thought that instillation with heparin, a glycosaminoglycan (GAG), may also afford protection to the urothelium by replacing the GAG layer. It has not been associated with coagulation abnormalities when administered intravesically and has been reported to be useful in the treatment of IC. In a study by Parsons et al., 56% of patients reported improvements in their symptoms within 3 months of treatment [76].

Hyaluronic acid and chondroitin sulphate

Intravesical Hyaluronic Acid (HA) has been proven to provide symptomatic relief to patients with BPS in observational trials [77]. In the largest of those studies [78], more than 80% of patients with positive potassium testing – indicating an urothelial defect – reported improved outcome. The efficacy of intravesical Chondroitin Sulphate (CS) as monotherapy has been studied in two small, multicenter randomized trials [79, 80]. These revealed that intravesical CS resulted only in minor improvement of IC/BPS related symptoms and hence its use as monotherapy is not supported. Dual therapy with use of both HA and CS has been proven beneficial [81] and equally effective when compared to DMSO but with less side effects [82]. Further well-powered randomized trials are required to assess the clinical significance of these two treatments when compared to placebo. The EAU guidelines, therefore, provide a weak recommendation for the use of intravesical HA or CS prior to initiation of more invasive treatment options.

Textbook of Female Urology and Urogynecology Bacillus Calmette-Guerin

Bacillus Calmette-Guerin (BCG) is an attenuated strain of Mycobacterium bovis. Its precise mechanism of action is unknown. Studies have reported it to be effective in the symptomatic management of BPS/IC. Peters et al. [83] reported improvement in symptoms in 60% of patients treated with BCG compared to 27% in the placebo group. A larger randomised trial, however, did not show a significant response in patients treated with BCG compared to those treated with DMSO [84]. The clinical benefit of this treatment remains unclear and the American Urological Association does not recommend its use outside of an investigational study setting [85].

Botulinum toxin A

This is a potent neurotoxin derived from the bacterium Clostridium botulinum. The presence of afferent nerve fibres in the suborothelial layer of the bladder which are hypersensitised by increased levels of neurotransmitters is thought to play a predominant part in the pathogenesis of BPS. Botulinum toxin type A has been suggested to act by inhibiting neurotransmitter release from afferent nerve fibres and thus decreasing the sensitivity experienced in BPS/IC [86]. There is emerging evidence that suggests botulinum toxin is beneficial in the treatment of BPS/IC [87, 88]. However, many of these studies are small with short-term follow-up only. The treatment regime and dose of botulinum toxin has also not been standardised. As a recent systematic review and meta-analysis of controlled studies concluded [89], until further evidence from larger scale randomised control trials become available, botulinum toxin should be offered only in patients with refractory BPS/IC after thorough consultation, who are willing to accept the risk of voiding dysfunction requiring clean intermittent self-catheterisation. Other intravesical treatments that have been used include resiniferatoxin, capsaicin, lignocaine, and oxybutynin. Evidence of their clinical efficacy however is lacking.

Neuromodulation

Sacral nerve stimulation is often used in the management of patients with detrusor overactivity. It is a minimally invasive procedure that involves stimulation of the S3 or S4 nerve root, and its afferent sacral nerves as they exit the sacral foramina, by a mild electric current. As a recent systematic review and meta-analysis suggested, there is emerging evidence suggesting that it may be beneficial in the treatment of refractory BPS/IC [90]. However, there is a lack of large scale randomised control trials and hence definitive conclusions cannot be drawn due to the small sample size, short follow up period of 6 months and lack of confirmation of outcomes from multiple centres.

Surgery

Surgery is reserved for severe cases that are refractory to all other treatment options. Available surgical treatments include bladder augmentation cystoplasty, cystectomy, and urinary diversion, with total cystectomy being associated with higher rates of improvement [91]. Current data suggests that BPS patients with the presence of Hunner’s ulcers are more suitable for radical surgery than those with non-Hunner’s ulcers [92] and that longer preoperative symptoms were a predictor for persisting

Bladder Pain Syndrome/Interstitial Cystitis post-operative pain [93]. A recent systematic review of 20 studies including 450 BPS patients highlighted a 23% risk of failure to improve symptoms. As such, a multidisciplinary joint urologicalurogynaecological approach should be pursued. Consequently, due to the significant morbidity and mortality associated with this level of intervention large scale prospective studies need to be conducted.

Emerging treatments

The exact pathophysiology of BPS remains elusive. Its complexity coupled with its non-specific clinical manifestation make it a diagnosis of exclusion that can be challenging to treat. A number of emerging novel therapies have shed a glimpse of hope in the treatment of BPS, however more robust evidence from large scale randomized trials is needed to support those treatment options [94].

Monoclonal antibodies

Monoclonal antibodies such as Adalimumab have been investigated in a phase III, randomized, double-blind, placebocontrolled clinical trial in which treatment resulted in a statistically significant improvement in the O’Leary-Sant Interstitial Cystitis Symptom and Problem Indexes, Interstitial Cystitis Symptom Index, Interstitial Cystitis Problem Index and Pelvic Pain, Urgency, Frequency Symptom Scale at 12 weeks compared to baseline in patients with moderate to severe bladder pain syndrome [95]. However it failed to demonstrate a statistically significant improvement when compared to placebo.

Cannabinoids

The endocannabinoid system has been identified as a key regulator of immune function, with experimental evidence for the involvement of cannabinoid receptors in bladder inflammation. A study evaluating experimental cannabinoid 2 receptor activation by phyto-derived and synthetic cannabinoid ligands in LPS-induced Interstitial cystitis in mice revealed that intravesical instillation of those phyto-derived ligands, such as beta-caryophyllene (BCP), significantly reduces the number of adhering leukocytes in submucosal bladder venules and improves bladder capillary perfusion. The effects of BCP were found to be comparable to that of the selective CB2R synthetic cannabinoid, HU308, and superior to intravesical DMSO treatment. Oral treatment with BCP was also able to reduce bladder inflammation and significantly reduced mechanical allodynia in experimental IC [96].

Phosphodiesterase-5 inhibitors

Phosphodiesterase-5 inhibitors (PDE5-i) act by inhibiting potassium release and thus preventing mast cell degranulation and subsequent smooth muscle contraction. A randomized control trial evaluating the efficacy of daily low-dose sildenafil for the treatment of non-ulcer interstitial cystitis in 48 women with BPS revealed statistically significant improvement in symptom and problem indices scores and urodynamic index at 3 month follow up when compared with placebo [97].

Enhanced intravesical drug delivery systems

Enhanced intravesical drug delivery systems, although in their infantile steps of development, represent a promising solution towards the effective management of BPS in the future. Liposomes, spherical phospholipid vesicles, are thought to repair the urothelial lining and reduce its permeability to irritant

593 substances in the urine. Sphingomyelin liposome instillations, in subjects with BPS, were shown to improve urgency, pain, and overall symptom scores by an open label study [98] The therapeutic effects of intravesical instillation of liposomal formulated botulinum toxin A (lipotoxin) were assessed in a 2-center, doubleblind, randomized, placebo controlled, study of 31 patients with refractory BPS. Lipotoxin instillation was associated with a statistically significant improvement in O’Leary-Sant symptom scores, GRA, and VAS pain scale [99]. Semi-synthetic glycosaminoglycan ethers (SAGE) are an emerging class of therapeutic GAG with intrinsic antiinflammatory and analgesic properties. A silk-elastin like protein polymer (SELP) intravesical drug delivery system has been developed to enhance SAGE intravesical drug delivery by reducing its clearance and thus enhancing its accumulation in the bladder mucosa with evidence of sustained analgesic effect 24 hours after administration, and reduced inflammation as demonstrated by one study [100] A continuous lidocaine-releasing intravesical system (LiRIS) was designed to be retained in the bladder and release therapeutic amounts of the drug into urine over a period of 2 weeks with promising shortterm efficacy in pain and urinary symptoms as well as clinical improvement on cystoscopic examination as demonstrated in a trial involving 16 patients with BPS and presence of bladder haemorrhages/Hunner’s ulcers [101].

Extracorporeal shockwave therapy

The use of extracorporeal shockwave therapy (ESWT) has been shown to reduce BPS related pain in a randomized sham-controlled trial including 54 patients with BPS who received the therapy once a week for 4 weeks however there was no change in O’Leary Sant symptom scores [102]. This modality requires further studies to determine its efficacy in the treatment of this condition.

Conclusion BPS/IC remains a clinical challenge as a refractory chronic debilitating disorder. The aetiology of the disease is unknown and it continues to be a diagnosis of exclusion. Patients typically complain of pain in the bladder or pelvic area associated with urinary frequency or urgency. The diagnosis is heavily dependent on the history and physical examination as there is currently no specific diagnostic test for BPS/IC. Diagnostic adjuncts such as urinary analysis, urodynamics, and cystoscopy aid the diagnosis and exclusion of other confusable diseases. Treatment is multimodal and often multidisciplinary. It includes patient education, which is fundamental. Management should commence with conservative measures such as behavioural modification and dietary modification followed by medical management with oral or intravesical therapy, which aims to provide symptomatic relief for pain and irritable bladder symptoms. More invasive treatments such as surgery should be reserved for refractory cases as they are associated with more morbidity. There is a limited role currently in clinical practice for neuromodulation and botulinum toxin. Although the results of available studies are promising, larger trials are required on the efficacy of these therapies. Further research into the aetiology of the disease is required in order to correctly define a diagnostic criterion and management plan of the disease (Fig. 56.6).

Textbook of Female Urology and Urogynecology

594 IC/BPS An unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than six week duration, in the absence of infection or other identifiable causes

BASIC ASSESSMENT – History – Frequency/Volume Chart – Post-void residual – Physical examination

Signs/Symptoms of Complicated IC/BPS

– Incontinence/OAB – GI signs/symptoms Microscopic/gross hematuria/sterile pyuria – Gynecologic signs/symptoms

CONSIDER: – Urine cytology – Imaging – Cystoscopy – Urodynamics – Laparoscopy – Specialist referral (urologic or non-urologic as appropriate)

– Urinalysis, culture – Cytology if smoking hx – Symptom questionnaire – Pain evaluation

FIRST-LINE TREATMENTS – General Relaxation/Stress Management – Pain Management – Patient Education – Self-care/Behavioral Modification

Confirmed or Uncomplicated IC/BPS

RESEARCH TRIALS Patient enrollment as appropriate at any point in treatment process

SECOND-LINE TREATMENTS – Appropriate manual physical therapy techniques – Oral: amitriptyline, cimetidine, hydroxyzine, PPS – Intravesical: DMSO, Heparin, Lidocaine – Pain Management

Dx Urinary Tract Infection

TREAT & REASSESS THIRD-LINE TREATMENTS – Cystoscopy under anesthesia w/hydradistention – Pain Management – Tx of Hunner’s lesions if found

CLINICAL MANAGEMENT PRINCIPLES – Treatments are ordered from most to least conservative; surgical treatment is appropriate only after other treatment options have been found to be ineffective (except for treatment of Hunner’s lesions if detected) – Initial treatment level depends on symptom severity, clinician judgment, and patient preferences – Multiple, simultaneous treatments may be considered if in best interests of patient – Ineffective treatments should be stopped – Pain management should be considered throughout course of therapy with goal of maximizing function and minimizing pain and side effects – Diagnosis should be reconsidered if no improvement within clinically-meaningful time-frame

FOURTH-LINE TREATMENTS – Intradetrusor botulinum toxin A – Neuromodulation – Pain Management

FIFTH-LINE TREATMENTS – Cyclosporine A – Pain Management

The evidence supporting the use of Neuromodulation, Cyclosporine A, and BTX for IC/BPS is limited by many factors including study quality, small sample size, and lack of durable follow up. None of these therapies have been approved by the U.S. Food and Drug Administration for this indication. The panel believes that none of these interventions can be recommended for generalized use for this disorder, but rather should be limited to practitioners with experience managing this syndrome and willingness to provide long term care of these patients post intervention. Copyright © 2014 American Urological Association Education and Research, Inc.

SIXTH-LINE TREATMENTS – Diversion w/ or w/out cystectomy – Pain Management – Substitution cystoplasty Note: For patients with end-stage structurally small bladders, diversion is indicated at any time clinician and patient believe appropriate.

FIGURE 56.6  American Urological Association suggested approach for treatment of interstitial cystitis/bladder pain syndrome. (From ref [85] with permission.)

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597 102. Chuang YC, Meng E, Chancellor M, Kuo HC. Pain reduction realized with extracorporeal shock wave therapy for the treatment of symptoms associated with interstitial cystitis/bladder pain syndrome—a prospective, multicenter, randomized, double-blind, placebo-controlled study. Neurourology and Urodynamics [Internet]. 2020 June 1 [cited 2021 March 30];39(5):1505–14.

57

THE URINARY AND VAGINAL MICROBIOMES Niels Frimodt-Møller, Karen Leth Nielsen, and Frederik Boetius Hertz

Introduction The exposed inner and outer surfaces of the human body are coated with bacteria and, to some degree, with fungi and viruses which have been termed normal flora or the indigenous microbiota. With the introduction of molecular biological methods, such as DNA sequencing, it has now become possible to describe this microbiota in more detail, than possible with the standard culturing methods. The term “microbiota” is commonly used to describe the community of microorganisms (bacteria, yeasts and viruses) that colonizes a body area (e.g. the skin, nasal passages, throat, vagina and gastrointestinal tract). Furthermore, “microbiome” defines the total collective of microbial genes located at a specific part of a person’s body and the proteins, etc. produced by the host. Here, we will use the term microbiome, as we describe bacteria, fungi and virus compositions in the urinary and vaginal microbiome (VM), and discuss the challenges and barriers for studying these. Although the microbiome should in principle include all microorganisms, there are also terms indicating specific microorganisms, such as the mycobiome (defined as the fungal microbiota within a host environment and their collective genome) and the virome (defined as the viral microbiota within a host environment and their collective genome). Although not as intense as the intestinal or gut microbiome, vaginal and urinary microbiomes have been the foci of rapidly increasing interest during the last decade. We will discuss it in the following review literature concerning the microbiome of the urinary tract and the vagina, which will include topics, where the microbiome has been shown or indicated to have importance for the course, pathogenesis or possible treatment. Although the literature is vast and expanding rapidly, there are still major gaps in our understanding of the microbiomes, their development and changes over time, their possible importance for the healthy state of the respective organs and the possibility of therapeutic interventions, e.g. probiotics, to reinstate an indigenous microbiota.

The urinary microbiome It has been known since the birth of diagnostic bacteriology that bacteria are present as indigenous microbiota on the skin – and in the urethral orifice, which in women appeared like the microbiota of the vagina. Until the seminal studies by Edward Kass in the mid-1950s, it was difficult to discern between urinary pathogens and constituents of the indigenous microbiota (1). Kass (1) introduced the quantitative urine culture as a method to distinguish asymptomatic bacteriuria (ABU) from the urinary tract infection (UTI) as represented by pyelonephritis; colonization of the bladder without typical symptoms of UTI with typical urinary pathogens, such as Escherichia coli, did exist as ABU if it was found in numbers higher than 105 bacteria/ml of urine in two consecutive 598

midstream urine (MSU) samples taken at least 24 hours apart. The diagnosis of an actual UTI was proven with just one MSU sample containing increased numbers of leukocytes (leukocyturia) and ≥ 105 bacteria/ml of a typical urinary pathogen if the patient had typical symptoms (pain at voiding or over the symphysis, symptomatic increased urinary frequency (pollakisuria) and general discomfort perhaps with low-grade fever). Later investigators (2, 3) used suprapubic puncture to demonstrate that even low numbers, i.e. from 10 to 100 colony forming units (CFU)/ml, of E. coli or Staphylococcus saprophyticus in the urine could be diagnostic of UTI in women. In all these studies, contamination with other bacteria was noted but not described in detail. It was generally assumed that the urinary tract from 1 to 2 cm above the urethral orifice was normally sterile and that the presence of bacteriuria indicated a disease state although not necessarily requiring antibiotic therapy. The first published studies utilizing PCR, 16S rRNA or wholegenome sequencing (WGS) of urine specimens appeared around 2010 (4), and a myriad of publications have since repeated the original studies or investigated the urine microbiome in a number of disease states including UTI, ABU, lower urinary tract symptoms (LUTS), renal stones and various cancer diseases of the bladder, prostate and kidney. It is now generally believed that urine is normally not sterile, as hitherto assumed, and albeit present in relatively low numbers (around 101–103 bacteria per ml of urine), there are differences in the microbiome between men and women, with increasing age and among different diseases. The urinary microbiome studies have not changed the notion of UTI being mostly caused by the classical urinary pathogens; the majority still encompass E. coli, and with a lower prevalence of S. saprophyticus, Klebsiella spp., Citrobacter spp., Proteus spp., Enterococcus faecalis, Aerococcus spp., Actinobaculum schaalii and certain Corynebacterium spp.. In comparison Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella spp. and Candida spp. are generally not considered primary urinary pathogens but occur after urethral instrumentation including bladder catheterization or as filtered through the kidneys during bacteremia. To which degree the urinary microbiome is present in the bladder as a flora, which protects against ascending pathogens, is still under debate. Before further discussion of the composition and role of the urine microbiome, it is pertinent to discuss some technical issues.

Sampling of urine

It is impossible to obtain an MSU sample without contamination from bacteria residing at the urethral orifice, both in men and women, and even after cleaning or disinfection of the area (5). The optimal method to obtain urine without contamination is by bypassing the urethral orifice with suprapubic puncture, although a small risk of contamination from skin cannot completely be ruled out. So far, only one study of the urinary

DOI: 10.1201/9781003144236-63

The Urinary and Vaginal Microbiomes microbiome investigated this sampling method (4). Wolfe et al. (4) studied urine sampled from 23 women which consisted of a control group of 12 patients without urinary symptoms undergoing surgery for benign gynecologic conditions and 11 patients with at least one urinary symptom undergoing surgery for conditions, such as pelvic organ prolapse or urinary incontinence. The study used several techniques to sample urine, including MSU, transurethral catheter urine (TUC), suprapubic aspiration (SPA) of urine including samples from the skin over the puncture site and a needle aspirate from the same skin without penetrating the bladder. A vaginal swab was also included in some cases. Urine samples underwent various microscopy procedures and cultivation aero- and anaerobically, and microbiome analysis was performed by 16S PCR amplification for quantification by fluorescent double-stranded DNA (dsDNA) assay. From women in the control group/disease group, they found 165/150, 226/191, 205/185 and 181/179 genera in TUC, SPA, skin and needle samples, respectively. The most abundant genera found via TUC were also present in urine obtained via SPA, while genera detected in skin and needle samples were different from the catheter and suprapubic samples. Voided urine (MSU) samples contained mixtures of urinary and genital tract bacteria. The study concluded that urine obtained via SPA is optimal for microbiome studies, but for practical reasons, the TUC sampling method may suffice. This advice has been followed in several later studies (6, 7), while other publications have relied on the less recommendable sampling method of MSU (8, 9).

Culture or DNA sequencing

Although microbiome studies using DNA-sequencing methods (PCR, 16S RNA, WGS or combinations of these) have been considered most reliable by many authors for detecting most different genera including “unculturable” genera (10), several studies using so-called enhanced urine culture techniques or expanded quantitative urine culture (EQUC) have been able to detect many of the same genera and even some, which were not found by DNA methods (6, 11). Hilt et al. (6) studied 65 urine samples from 41 patients with overactive bladder (OAB) and 24 healthy controls by EQUC including larger volumes of urine and incubation under various and prolonged atmospheric conditions and compared with 16S RNA sequencing in four urines; they grew bacterial species in 80% of the samples, of which 92% were not reported by standard culture methods. The most likely explanation for this was that the majority of these genera were present in lower quantities in the urine, i.e. ≤ 103 CFU/ml urine. Most species found by EQUC were confirmed by 16S RNA sequencing. In a later similar, but larger study, Dubourg and coworkers (11) compared EQUC with 16S rRNA gene analysis and found that by culture, they could identify 457 microorganisms, including seven fungi, in 435 urine samples from 279 patients; interestingly, however, 165 bacterial species were not identified by DNA sequencing. Also of note, 256 of the cultured species had never previously been described in urine, 18 of which were entirely newly described species. The quality of DNA sequencing methods for microbiome studies is dependent on a number of factors, including the volume of urine sampled and freezing urine samples to −80°C within 4 hours. More technical issues involving the method of lysis of the bacterial content, sequencing methods and the subsequent bioinformatic analyses employed (12) are also relevant. The discussion of these issues is beyond the scope of this book, and the interested reader is referred to an excellent review on this matter (12).

599 Table 57.1 summarizes some of the factors and methodology involved in the study of the urine microbiome. Species richness of a microbiome essentially refers to how many different species could be detected in a sample while species diversity describes how evenly microbes are distributed in a sample. Often microbiomes are described by “Alpha diversity”, which is the variation of microbes in a single sample. As an example, the “Shannon diversity index” combines richness and diversity. It measures both the number of species and the inequality between species abundances. A large value is given by the presence of many species with well-balanced abundances. On the other hand, “beta diversity” describes the variation of microbial communities between samples – either between samples from one individual or between samples from different individuals: How different is the microbial composition in one environment compared to another? Here, an example could be the “Bray–Curtis dissimilarity”, explaining the differences in microbial abundances between two samples (e.g. at species level), that is values from 0 to 1; 0 means that both samples share the same species at exactly the same abundances as opposed to values of 1, which means the two samples do not share any species.

The normal microbiome of urine and adjacent anatomical sites

Microbiome studies published in the scientific literature report their findings in several different ways, either bacteria stratified into phylae, families or single species. Table 57.2 illustrates the most important phylae and examples of the corresponding species. Table 57.3 describes some of the findings from studies, where the microbiota results from both urine and vagina were reported as bacterial species (quantities as percent of total species) (13–16). It is obvious from the table that there is general agreement regarding the major species such as Lactobacilli in the female urine or vagina, while there are some differences with respect to those species found in lower numbers, i.e. < 1% of the total number of species. These differences are in major part due to technical issues related to the DNA methods used, but age and geography probably also play a role. Curtiss et al. (9) studied 79 healthy women of different age and menopausal status and found no differences in urine microbiome composure in relation to age, but Lactobacilli were common in premenopausal women and Mobiluncus spp. more common in postmenopausal women. In some studies, α-diversity of the urine microbiome in healthy women has been shown to increase with age (17), increasing prevalence with increasing age of E. coli but Gardnerella spp. with younger age (18), while other studies in women have found that the microbiome did not change with age (19). Dong et al. (13) compared the microbiome in male first catch urine with that in paired urethral swabs and found them to be remarkably similar (see Table 57.2). The near-repeat study was performed by Nelson et al. (20), who expanded microbiome studies in repeated cultures over 3 months from 18 adolescent males including first catch urine, urethral swab and swabs from the coronal sulcus (CS) and related the findings to sexual activity. CS microbiotas of most males were more stable than their urine microbiotas, and the composition of CS microbiotas was strongly influenced by circumcision. Lactobacillus and Streptococcus accounted for the majority in urine, while Sneathia, Mycoplasma and Ureaplasma were only found in urine from sexually active participants (20).

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TABLE 57.1: Important Factors Involved in the Study of the Urine Microbiome Comments/Relevance for Microbiome Studies

Factor

Characteristics/Issues

Sample collection method

Contamination: Suprapubic puncture Minimal – skin microbiota Transurethral catheter Minimal – urethral microbiota Midstream urine   Women: Major – urethral (vaginal) microbiota   Men: Minimal – skin microbiota Due to low bacterial content, larger volume is needed to extract sufficient amount of DNA Frozen to at least −20°C within 4 h Time of day/season Diseases of urogenital system Underlying disease Previous antibiotic treatment

Urine volume Specimen storage Clinical data

Identification of microbial content Culture

DNA methods

Quality control Data analysis

Expanded quantitative urine culture: media, atmosphere, duration of incubation, identification by 16SrRNA, matrix-assisted laser desorption ionization–time of flight, etc. DNA extraction:   Heat/mechanical lysis, proteases, RNases   DNA purification PCR amplification, 16S rRNA sequencing Whole-genome sequencing Handling contamination Negative and positive controls Alpha diversity   Inverse Simpson index   Shannon index Beta diversity   Principal Coordinate Analysis Plot   Non-metric multidimensional scaling Differential abundance testing

Ok Ok Not optimal Ok Optimal volume: 30–50 ml Optimal −80°C Stratify according to aim of study Exclusion/inclusion criteria

Time-consuming

Phylae, families and species are usually reported – the latter (species) is easiest to understand for medical laypersons

TABLE 57.2: Examples of Bacterial Phyla

Phylum/ Genus

Note:

Firmicutes (Most Are Gram-positive Bacteria)

Fusobacteria (Anaerobic, Gramnegative, Non-sporeforming Bacteria)

Lactobacillus Veillonella Streptococcus Anaerococcus Aerococcus Staphylococcus Finegoldia Gemella Enterococcus Shuttleworthia Clostridium Megasphaera Peptoniphilus Finegoldia Dialister Parvimonas

Sneathia Fusobacterium

Bacteroidetes (Aerobic and Anaerobic, Gram-negative, Non-spore-forming Bacteria) Prevotella Flavobacterium Bacteroides

Actinobacteria (Most Are Gram-positive Bacteria) Corynebacterium Atopobium Gardnerella Bifidobacterium Alloscardovia Rhodococcus Adlercreutzia

Tenericutes (Absence of a Cell Wall) Ureaplasma Mycoplasma

Proteobacteria (A Major Phylum of Gram-negative Bacteria) Tepidimonas Escherichia Enterobacter Acidovorax Sphingobium Proteus Trabulsiella Klebsiella Shigella Ralstonia

The largest phylae shown are most often included in studies describing the microbiome. Even though debated, a bacterial phylum is defined as the lineage of bacteria whose 16S rRNA genes share a pairwise sequence identity and share 75% or less with members of other phyla.

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TABLE 57.3: Examples of Species Distribution in Microbiomes in Urine, Urethral Swab and Vagina According to Gender and Age Male, Urine

Male, Urethral Swab

Female, Urine

Female, Vagina

Female, Vagina

Female, Vagina

Dong et al. (13) American men, no STI (>18y (m.28y)

Dong et al. (13) American men, no STI (>18y (m.28y)

Komesu et al. (14) American women, (53 ± 11 y)

Komesu et al. (14) American women, UTI (53 ± 11 y)

Geng et al. (15) Chinese women, menopause (>45 y)

Kawahara et al. (16) Japanese women, observation for cervical neoplasia (24–48 y)

10%

Lactobacillus Veillonella

Lactobacillus

Lactobacillus Gardnerella

Sneathia Prevotella Streptococcus Corynebacterium Ureaplasma Anaerococcus Aerococcus Mycoplasma Atobium Staphylococcus Finegoldia Gemella

Lactobacillus Streptococcus Prevotella Escherichia Ureaplasma Shuttleworthia

Lactobacillus Gardnerella

1–10%

Lactobacillus Sneathia Corynebacterium Veillonella Prevotella Streptococcus Mycoplasma Ureaplasma Anaerococcus Atobium Aerococcus Staphylococcus Enterococcus Gemella

Prevotella Streptococcus EscherichiaShigella Atopobium Sneathia Bifidobacterium Aerococcus Ralstonia Anaerococcus Chlamydia Alloscardovia Rhodococcus Peptoniphilus Finegoldia

Atobium Bifidobacterium Megasphaera Sneathia Prevotella Streptococcus Clostridium Anaerococcus

Proportion of species in specimen

4.5, the presence of adherent white discharge, detection of “clue cells” and the presence of an amine odor after the addition of potassium hydroxide. Nugent and colleagues proposed a score system, originally Nugent score 0–4 (later more detailed score 1–10 (60)), based on the composition of the vaginal secretion based on Gram-stain, especially Lactobacillus morphotypes, Gardnerella and Bacteroides morphotypes and curved Gram-variable rods (60), so that score 0 represents none of the morphotypes present, while score 4 denoted > 30 morphotypes present. Ravel et al. (58), later validated by Gajer et al. (59), have found a correlation between CSTs and Nugent score, in that high Nugent scores were most often associated with CST IV, while low Nugent scores correlated with CST I, II, III and V. There is a relationship with the VM and ethnicity. Ravel et al. included a number of ethnical groups in their study of the VM in 394 women (58) and found that vaginal bacterial communities dominated by species of Lactobacillus (groups I, II, III, and V) were found in 80% and 90% of Asian and white women, respectively, while these species were found in only 60% and 62% of Hispanic and black women, respectively, in the two latter groups corresponding to an overrepresentation of CST IV. Since women of these two ethnical groups are not considered to normally have BV, it was speculated that vaginal bacterial communities are governed by genetically determined differences between hosts (58). The VM changes in composition over time. Gajer et al. (59) followed 32 healthy reproductive-age women with twice-weekly mid-vaginal swabs over 16 weeks. Although women could be generally divided in all CSTs, in many women, the bacterial species composition and rank abundances of bacterial species changed markedly over short periods of time, and the communities of some women seemed resilient and showed simple and predictable changes between community states that occurred only during menses (59). Of all the metadata evaluated in the model, sexual activity was the only one that had a significant (negative) effect on constancy independent of time in the menstrual cycle, but its effect was rather weak in comparison to that of CST. This fluctuation in the composition of VM over time brings into question the validity of studies comparing only single-sample strategies of the VM relative to ethnicity or various disease states. Of note, women with menses in the prior 2 days as compared with those without recent menses have a higher level of dysbiosis, which is why timing of testing is important (61). VM also changes during a woman’s lifetime (62). Initial colonization of microbes takes place from the mother’s vagina. Before puberty, the VM of the child corresponds to CST-IV, while increasing estrogen production at puberty leads to increased glycogen production, the breakdown of which causes selection of Lactobacilli, which by fermenting glycogen and byproducts to lactic acid results in vaginal acidification and further dominance of Lactobacillus spp. in the VM of the different CSTs (I, II, III and V) (62).

The Urinary and Vaginal Microbiomes In general, studies of the VM have illustrated that colonization and dominance of Lactobacilli are essential for a healthy vaginal microbiota, commonly by species such as L. crispatus, L. gasseri, L. iners, and L. jensenii. Lactobacillus rhamnosus and Lactobacillus reuteri, and common ingredients of oral probiotics are more prone to colonize the gut and are seldom found in the VM. L. crispatus-dominated vaginal microbiota (CST I) is almost always associated with healthy vagina, while L. iners-dominated vaginal milieu (CST III) is more prone to vaginal dysbiosis (63). The protective effect of L. crispatus is associated with the ability to produce lactic acid maintaining a low pH and the production of bacteriocins that maintain a healthy vagina. In contrast to the vaginal bacterial microbiome, the human vaginal mycobiome has been less studied. According to Drell et al. (64) who were among the first to investigate the vaginal mycobiome, 196 fungal operational taxonomic units could be detected in healthy women, and the most dominant phyla was Ascomycota represented by the genus Candida (37.0%), mainly Candida albicans (34.1%), Candida krusei (2.3%), Candida alimentaria (reported as Candida sp. VI04616 in this study) (0.3%), Candida parapsilosis (0.3%), and Candida dubliniensis (0.04%). Obviously, Candida spp. can colonize the vagina without causing infection. On the other hand, vulvovaginal candidiasis may ensue as shown for risk factors such as hormones, diabetes, oral sex, intravaginal douching, treatment with antibiotics, intrauterine devices and perineal trauma (65).

The vaginal microbiome and disease states Bacterial vaginosis (BV)

BV is a vaginal dysbiosis with a VM similar to CST-IV, i.e. displacement of lactic acid-producing Lactobacillus spp. with increased concentrations of facultative and strict anaerobic bacteria including Gardnerella vaginalis, Prevotella spp., Atopobium vaginae, Sneathia spp. and other BV-associated bacteria. Further, there is an appearance of a polymicrobial biofilm on vaginal epithelial cells (66). This biofilm formation may be related to G. vaginalis, which can adhere to vaginal epithelial cells and has a certain propensity for biofilm formation (67). G. vaginalis has for many years been thought of as the main etiology of BV, and many microbiology laboratories searched for and reported this organism solely as diagnostic for BV. Its resistance toward metronidazole which has an effect on this condition, however, always puzzled clinicians, and the effect is now better understood with the importance of the preponderance of anaerobic flora, which is susceptible to metronidazole. Prevalence of BV varies internationally and ranges from 20 to 60%, which is high in many African countries and relatively moderate in regions such as South and Southeast Asia and South and North America, while the lowest prevalence is reported in Europe, Australia and New Zealand (68). Diagnosis of BV is based on the clinical appearance using either Amsel’s criteria or the Nugent score as described above (60). Multiplex PCR tests are appearing, which search for a combination of Lactobacillus spp., G. vaginalis, A. vaginae, Prevotella bivia and Megasphaera-1 and Megasphaera-2 (69, 70). Metronidazole or clindamycin is still recommended for the treatment of symptomatic BV and is usually effective in 80–90% of cases, but relapse rates from 30 to 50% have been reported (71, 72). The woman may be reinfected via her male partner, but the need for concomitant treatment of the partner is still discussed (73).

605 Treatment should include possible change in conduct related to numerous risk factors: sexual activity, intravaginal practices, contraceptive use, vaginal cleansing or washing, antibiotic use, race, education, age and menstrual cycle (74). BV increases the risk of various sexually transmitted diseases including HIV, gonorrhea, Trichomonas vaginalis vaginitis and herpes simplex virus-2 (74). This is most probably related to the lack of Lactobacillus spp., especially L. crispatus.

Urinary tract infection (UTI)

It is well known for many years that the vagina plays a role in the pathogenesis of both acute uncomplicated UTI as well as for rUTI (75). In a treatment study with ofloxacin versus trimethoprim– sulfamethoxazole for acute cystitis, Hooton et al. studied vaginal swabs of the patients and found E. coli in the vaginal swabs in 47–50% of the patients before treatment, which was reduced to 3–40% at the early follow-up but returned to 18–65% 5 weeks after the treatment (76). Further, vaginal microbiota affects the woman’s susceptibility to UTI, e.g. as mentioned above, the presence of BV increases the risk of UTI (76). Replacement of the vaginal flora via vagitoria containing L. crispatus protects against rUTI (28), and there are several reports of fecal transplantation for recurrent C. difficile infection protecting against rUTI most probably due to concomitant change in the vaginal flora. Many of the bacteria found in the VM are also found in urine as part of the urinary microbiome; to which degree this microflora interacts with urinary pathogens or themselves being pathogenic in the urinary tract is under debate and needs further study (77). Vaginal estrogen plays a key role in restoring a normal vaginal flora that protects against colonization with urinary pathogens (78). The vagina plays a specific role regarding Streptococcus agalactiae (Group B streptococcus [GBS]), the contamination of which during labor can cause serious infections in the newborn child, e.g. septicemia and meningitis. GBS colonization of the vagina occurs in 30–40% of women in the western world and stems from the gut. The vaginal colonization is asymptomatic, but the bacteria can in rare cases spread to the urinary tract and cause UTI and pyelonephritis. MSU cultures in pregnant women are often positive for GBS in women with vaginal colonization, while urine sampled via urethral catheter will most often be negative (79). Treatment of GBS bacteriuria during pregnancy is still common in many countries, but it is difficult to remove GBS colonization in the gut and vagina with antibiotics, and this strategy leads to overuse of antibiotics with the risk of development of resistance and unwanted change in the vaginal flora (80). In order to prevent infection of the newborn child, it is now considered wiser to screen the pregnant women just before labor with a PCR test for GBS and let the results of this together with other risk factors for the woman in labor decide the use of antibiotic prophylactic coverage during labor (80).

Vulvovaginitis

Apart from BV, dysbiosis of the vagina can lead to infection with other microorganisms such as Candida spp. or T. vaginalis. Both can cause infection of the vagina with pain or irritation, pruritus, increased discharge containing neutrophils, wounds and scars, and sometimes bleeding, which surmounts to a highly unpleasant and debilitating condition for the woman. For Candida, the pathogenesis involves adherence to epithelial cells triggered by hyphae formation, biofilm formation and secretion of virulence factors and proliferation of yeast cells (62). Risk factors include antibiotic therapy, e.g. treatment of UTI has this condition as an

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606 adverse effect in up to 10% of treated women (62). Gram-stain or wet mount microscopy reveals abundant yeast cells, which can easily be cultured for further diagnosis and susceptibility testing. Candida vulvovaginitis is treated with antifungals either locally in the vagina or systemically, e.g. oral treatment with fluconazole. T. vaginalis is an anaerobic flagellated parasite normally existing as trophozoite, easily recognized by microscopy of the wet mount. It can be transmitted sexually (62). T. vaginalis also adheres to the vaginal epithelium with the degradation of the mucosal layer, phagocytosis of Lactobacilli leading to increase in vaginal pH further promoting survival and propagation of the parasite. The diagnosis rests upon microscopic detection in the wet mount of vaginal discharge, and the organism is highly susceptible to metronidazole.

VM and genital cancer

Emerging evidence shows that genital dysbiosis and/or specific bacteria might have an active role in the development and/or progression and metastasis of gynecological malignancies, such as cervical, endometrial and ovarian cancers, through direct and indirect mechanisms, including the modulation of estrogen metabolism (80). The proven connection between cervical cancer and human papilloma virus (HPV) has spurned the interest in the possible contribution of other virus, fungi or bacteria to the etiology, severity of disease or interaction with the treatment of gynecological cancers (77). A vast amount of scientific literature has already appeared on this subject, which is out of scope with this chapter, and the interested reader is referred to a recent excellent review (81). Leave it to say, that epidemiological studies suggest that urogenital microbiota is linked to malignancies, but apart from HPV, no game-changing results have so far appeared. Much is left to future research, which should be based on robust clinical data sets, e.g. the change over even short time in the VM, as shown by Gajer et al. (59) and others, stresses the importance of following patients and controls over time with repeated sampling in order to fully appreciate the composition and possible pathogenic role of the VM. In summary, the VM consists of numerous different bacteria, fungi and virus. So-called community structures (CSTs) of the bacterial composition occur in at least five different versions which relate to ethnicity and even over time in the individual woman and are also related to dysbiosis, e.g. BV. Lactobacilli dominate the normal microbiome, especially L. crispatus, and are the focus for possible probiotic interventions. A relationship between the VM and various disease states including gynecological malignancies is being intensely investigated but so far without results that have been translated into relevant interventions.

Summary In contrast to earlier beliefs, urine even from healthy individuals contains up to a wide range of different species of bacteria, fungi and viruses although in small quantities, i.e. < 103 microorganisms/ml of urine. This is now termed the urinary microbiome. Sophisticated culture methods including culture for strict anaerobes can identify most of the bacterial taxa and species identified by DNA methods. Suprapubic bladder puncture or urethral catheterization avoids contamination from the urethral orifice, which is a problem for urine sampled by the usual midstream voiding sampling method. The urinary microbiome in women contains up to 60% of the taxa found in the vagina. The most prevalent species in women at both sites are Lactobacilli, and it is the same

in men together with Streptococci. The male urinary microbiome simulates the VM in sex partners, which can explain the dysbiosis seen in the female partners’ BV. Five different bacterial communities, which can shift over time, are identified in women. L. crispatus dominance indicates a normal vaginal flora and forms the basis for the probiotic treatment of dysbiosis. The relationship between various urogenital diseases and the urinary and VMs has been identified and is the focus of major research attention, so far without major breakthroughs, but this will most probably change in the near future.

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49. Bresler L, Price TK, Hilt EE et al. Female lower urinary tract microbiota do not associate with IC/PBS symptoms: a case-controlled study. Int Urogynecol J. 2019; 30: 1835–42. 50. Mehta M, Goldfarb DS, Nazzal L. The role of the microbiome in kidney stone formation. Int J Surg. 2016; 36: 607–12. 51. Kelly JP, Curhan GC, Cave DR et al. Factors related to colonization with Oxalobacter formigenes in U.S. adults. J Endourol. 2011; 25: 673–9. 52. Dornbier RA, Bajic P, Van Kuiken M et al. The microbiome of calcium-based stones. Urolithiasis. 2020; 48: 191–9. 53. Honeycutt J, Hammam O, Fu C-L et al. Controversies and challenges in research on urogenital schistosomiasis-associated bladder cancer. Trends Parasitol. 2014; 30: 324–32. 54. Xu W, Yang L, Lee P et al. Mini-review: perspective of the microbiome in the pathogenesis of urothelial carcinoma. Am J Clin Exp Urol. 2014; 2: 57–61. 55. Popović VB, Situm M, Chow CT et al. The urinary microbiome associated with bladder cancer. Sci Rep. 2018; 8: 12157. 56. Wu P, Zhang G, Zhao J et al. Profiling the urinary microbiota in male patients with bladder cancer in China. Front Cell Infect Microbiol. 2018; 8: 167. 57. Mai G, Chen L, Li R et al. Common core bacterial biomarkers of bladder cancer based on multiple datasets. BioMed Res Int. 2019; 2019: 1–8 (ID 4824909). 58. Ravel J, Gajer P, Abdo Z et al. Vaginal micrbiome of reproductive-age women. Proc Natl Acad Sci U S A. 2011; 108, suppl. 1: 4680–87. 59. Gajer P, Brotman RM, Bai G et al. Temporal dynamics of the human vaginal microbiota. Sci Transl Med. 2012; 4: 132ra52. 60. Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of Gram stain interpretation. J Clin Microbiol. 1991; 29: 297–301. 61. Muzny CA, Lensing SY, Aaron KJ et al. Incubation period and risk factors support sexual transmission of bacterial vaginosis in women who have sex with women. Sex Transm Infect. 2019; 95: 511–5. 62. Kalia N, Singh J, Kaur M. Microbiota in vaginal health and pathogenesis of recurrent vulvovaginal infections: a critical review. Ann Clin Microbiol Antimicrob. 2020; 19: 5. 63. Chee WJY, Chew SY, Than LTL. Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health. Microb Cell Fact. 2020; 19: 203. 64. Drell T, Lillsaar T, Tummeleht L et al. Characterization of the vaginal micro- and mycobiome in asymptomatic reproductive-age Estonian women. PLoS ONE. 2013; 8: e54379. 65. Guzel AB, Ilkit M, Akar T et al. Evaluation of risk factors in patients with vulvovaginal candidiasis and the value of chromID Candida agar versus CHROMagar Candida for recovery and presumptive identification of vaginal yeast species. Med Mycol. 2011; 49: 16–25. 66. Muzny CA, Łaniewski P, Schwebke JR et al. Host-vaginal microbiota interactions in the pathogenesis of bacterial vaginosis. Curr Opin Infect Dis. 2020; 33: 59–65. 67. Alves P, Castro J, Sousa C et al. Gardnerella vaginalis outcompetes 29 other bacterial species isolated from patients with bacterial vaginosis, using in an in vitro biofilm formation model. J Infect Dis. 2014; 210: 593–6. 68. Kenyon C, Colebunders R, Crucitti T. The global epidemiology of bacterial vaginosis: a systematic review. Am J Obstet Gynecol. 2013; 209: 505–23. 69. Gaydos CA, Beqaj S, Schwebke JR et al. Clinical validation of a test for the diagnosis of vaginitis. Obstet Gynecol. 2017; 130: 181–9. 70. Cartwright CP, Lembke BD, Ramachandran K et al. Development and validation of a semiquantitative, multitarget PCR assay for diagnosis of bacterial vaginosis. J Clin Microbiol. 2012; 50: 2321–9. 71. Bradshaw CS, Morton AN, Hocking J et al. High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence. J Infect Dis. 2006; 193: 1478–86. 72. Cook RL, Redondo-Lopez V, Shmitt C et al. Clinical, microbiological, and biochemical factors in recurrent bacterial vaginosis. J Clin Microbiol. 1992; 30: 870–7. 73. Mehta SD. Systematic review of randomized trials of treatment of male sexual partners for improved bacterial vaginosis outcomes in women. Sex Transm Dis. 2012; 39: 822–30 74. Coudray MS, Madhivanan P. Bacterial vaginosis – a brief synopsis of literature. Eur J Obstet Gynecol Reprod Biol. 2020; 245: 143–8. 75. Lewis AL, Gilbert NM. Roles of the vagina and the vaginal microbiota in urinary tract infection: evidence from clinical correlations and experimental models. GMS Infect Dis. 2020; 8: Doc02 (ISSN 2195-8831).

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76. Hoooton TM, Johnson C, Winter C et al. Single-dose and three-day regimens of ofloxacin versus trimethoprim-sulfamethoxazole for acute cystitis in women. Antimicrob Agents Chemother. 1991; 35: 1479–83. 77. Stapleton AE. The vaginal microbiota and urinary tract infection. Microbiol Spectr. 2016; 4. doi: 10.1128/microbiolspec.UTI-0025-2016 78. Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med. 1993; 329: 753–6.



79. Hooton TM, Roberts PL, Cox ME et al. Voided midstream urine culture and acute cystitis in premenopausal women. N Engl J Med. 2013; 369: 1883–91. 80. Rosenberg LR. Normann AK, Henriksen B et al. Risk-based screening and intrapartum group streptococcus polymerase chain reaction results reduce use of antibiotics during labor. Dan Med J. 2020; 67: A06200460. 81. Łaniewski P, Ilhan ZE, Herbst-Kravoletz MM. The microbiome and gynecological cancer development, prevention and therapy. Nat Rev Urol. 2020; 17: 232–50.

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BACTERIAL CYSTITIS IN UROGYNAECOLOGY An Update Kate H. Moore, Zhuoran Chen, Nevine I.D. te West

Introduction Since the publication of the previous chapter on bacterial cystitis in this textbook, there has been a dramatic increase in international concern about MultiResistant Bacteria. Partly this arises because of the administration of low-dose antibiotics to livestock animals to promote growth and prevent infection (which increases yields and profits). Hence, multidrug-resistant organisms find their way into the human food chain. Also, the overuse of antibiotics for viral conditions such as respiratory infections, or inappropriate use of prophylactic antibiotics in the hospital, has led to the development of “super-bugs”, which are becoming difficult or near-impossible to treat (1). Further data regarding this recent concern are provided in the Emerging Antibiotic Resistance section. As a result, patients and urogynaecologists are becoming increasingly interested in nonantibiotic prevention strategies for women suffering from recurrent urinary tract infections (UTIs), which are updated in this chapter.

Background UTIs are traditionally divided into infections of the upper tract (pyelonephritis) and of the lower tract (bacterial cystitis). This chapter does not discuss upper tract infections, as knowledge on this subject is normally obtained during training in obstetrics. Untreated lower UTI may ascend to the kidneys and even be associated with septicaemia; however, such events are beyond the remit of this chapter, which focuses on bacterial cystitis. Cystitis is the general term used to describe inflammation of the urinary bladder. The subjects of interstitial cystitis (IC), cyclophosphamide cystitis or rare parasitic infestations are not covered herein (but see Chapter 56 regarding bladder pain syndrome/IC). Bacterial cystitis is an inflammatory response to bacterial infection of the lower urinary tract. The hallmark symptoms and signs include dysuria and discoloured, foul-smelling urine, suprapubic tenderness, urinary frequency, urgency ± nocturia, which may be associated with microscopic or macroscopic haematuria and pyuria. Bacterial cystitis may be acute, chronic or recurrent as well as simple or complex. The natural history is dependent on the type and virulence of the urinary pathogen, resistance to antimicrobial agents and host defences. Diagnosis in most simple cases is based on clinical symptoms, urine dipstick testing (which is controversial), preferably with laboratory confirmation by microscopy and culture. Management comprises identification of the causative organism and, based on the results of urine culture and sensitivity, prescribing an appropriate antimicrobial agent for a suitable length of time. In those women with recurrent or complex infections, more detailed strategies may be needed. This chapter examines the definition, epidemiology and pathogenesis of bacterial cystitis and reviews the management of women presenting

DOI: 10.1201/9781003144236-64

with both simple and complex lower UTI. Current controversies regarding low-grade bacterial cystitis in refractory detrusor overactivity (DO) are also summarised.

Definitions Bacteriuria

The term bacteriuria indicates the presence of bacteria in urine because traditionally, urine is thought to be sterile in normal individuals. When assessing the results of urine cultures, the clinician must distinguish between true bacteriuria and contamination of the urine as it passes through the distal urethral and introitus. The term “Significant bacteriuria” was first defined in the late 1950s by Kass, a Harvard nephrologist. His goal was to determine a quantitative threshold that would accurately distinguish true bacteriuria (which he defined as ‘actual residence of bacteria within the urine of the urinary tract’) from bacterial contamination (‘the entry of bacteria into the urine during the collection of the specimen’) (2). In 335 asymptomatic female outpatients, he identified two populations based on catheter specimens of urine: those with low bacterial counts (0–105 colony forming unit (CFU)/mL) and those with high counts (>105 CFU/mL). Bacteria cultured from the ‘low count’ group frequently showed commensal organisms, and a repeat urine sample taken from them rarely matched the original specimen. In contrast, counts of >105 were more consistent on repeat testing, and known urinary pathogens were commonly isolated. The relative degrees of pyuria were not reported. He concluded that ‘patients with more than 105 bacteria per mL of urine may be regarded as having true bacteriuria’ (2, 3). Kass was mainly interested in preventing pyelonephritis. He compared asymptomatic women (2, 4) with those having overt upper UTI (5, 6). It is worth remembering that in the 1940s and 1950s, pyelonephritis/infected shrunken kidney was found in 15–20% of autopsy specimens and was a major cause of death in one-third of these cases (5). Although Kass defined >105 CFU/mL as ‘significant’ bacteriuria (i.e., likely to result in morbidity), he did acknowledge that pyelonephritis may be associated with lesser degrees of bacteriuria in some situations. Sixty years later, despite the fact that Kass’ threshold was not tested systematically on women with frequency/urgency/nocturia, his criterion of 105 CFU/mL of urine is still widely accepted as the definition of significant bacteriuria (i.e., infection) among symptomatic women (3, 7). Reevaluation in the 1980s by Stamm et al. later found that these criteria would in fact miss approximately half of patients with clinical symptoms of bacterial cystitis (8). Therefore, he favoured a diagnostic cut off of ≥102 CFU per mL. Tapsall et al. also demonstrated that patients with symptoms, but without significant bacteriuria, responded just as well to antibiotics as the group with significant bacteriuria (9). In 1993, Kunin et al. reinforced the importance of low-count bacteriuria in a study assessing 609

610 639 women with and without symptoms of cystitis (10). Of the symptomatic patients, 46% were found to have low-count bacteriuria (102–104 CFU/mL) compared to only 10% of the asymptomatic women. This study rejected the old hypothesis that urinary dilution contributes to low-count bacteriuria and concluded that lowcount bacteriuria is actually just an early phase of infection (3). The Infectious Diseases Society of America has since revised its guidelines accordingly (11), as has the European Association of Urology (12), recommending a threshold of 103 CFU/mL, as this improves the sensitivity without a significant loss of specificity. However, to date, most laboratories in UK and Australia persist with the original diagnostic cut off of 105 CFU per mL (unlike the USA and Europe, which now employ the more stringent cut off). Interestingly, the 2010 ICS/IUGA report on terminology defines UTI as “the finding of microbiological evidence of significant bacteriuria and pyuria usually accompanied by symptoms such as increased bladder sensation, urgency, frequency, dysuria, urgency urinary incontinence and/or pain in the lower urinary tract” with suggested criteria of (i) bacteriuria >100,000 (105) CFU/mL on voided specimen or >1,000 (103) CFU/mL on catheter specimen and (ii) pyuria >10 WBC/mm3 (13). This “traditional” threshold for significant bacteriuria on voided specimens now appears controversial.

Sterile urine? – Recent evidence

Historically, the urine in the bladder is normally considered to be completely sterile, in that uropathogens are not detected using routine cultivation techniques. Older studies comparing suprapubic puncture specimens versus midstream urine samples revealed that incidences of significant bacteriuria on suprapubic catheter stab samples from asymptomatic women were less than 1% (14). However, very recent studies in Europe and America using sophisticated techniques demonstrate that up to 35 genera of bacteria do in fact reside in the bladder of some women (15–18). This research uses deep 16S rRNA gene sequencing and polymerase chain reaction (PCR) to identify various species of uncultivated bacteria in the urine (16). Such specimens taken via transurethral catheters, suprapubic catheters and voided samples from both symptomatic and asymptomatic women found bacterial DNA in urine from all three sampling methods. The microbial genera detected by PCR amplification in the transurethral catheter specimens corresponded to those obtained from suprapubic catheters. They appeared to be the true colonies of the bladder, as they differed greatly from the mixture of urinary and genital tract bacteria DNA found in the voided samples (which suggested contamination). The same researchers went on to evaluate whether or not the bacteria found in the preliminary study could be grown in the lab (18). Although 92% of samples showed no growth when cultivated at 103 CFU/mL using routine urine culture protocol, 80% grew bacteria when an expanded quantitative urine culture (EQUC) protocol was used (i.e., different types of agars in various aerobic and anaerobic conditions). Bacteria of 35 different genera and 85 species were present at levels below the cutoff used in standard culture protocols, which correlated with the 16S rRNA gene sequencing results. Thus, DNA studies show that viable bacteria inhabit the normal adult female bladder, in contrast with previous beliefs that the normal bladder is “sterile”. For further detail, see Chapter 57 on the microbiome.

Pyuria

Traditionally, infection is distinguished from colonisation by evidence of tissue injury/inflammation, normally indicated by the finding of pyuria (19), which is present in most women with

Textbook of Female Urology and Urogynecology high-count UTIs (19, 20). However, the relationship between lowcount bacteriuria 102–105 CFU/mL and pyuria is less clear (3). Levels more than 10 leucocytes/mm3 are considered pathological. However, the prevalence of pyuria increases with the concentration of bacteriuria, so that low-count bacteriuria is not always associated with pyuria (10, 21). For example, Stamm et al. (21) reported that incorporating pyuria into the diagnostic standard for acute infection (i.e., insisting on >102 CFU/mL plus pyuria) made little difference compared to quantification of bacteria alone (8). The large case-control study by Kunin et al. established that the prevalence of pyuria (>20 WBC/mm3) rises with the level of bacteriuria. This again supports the notion that low-count bacteriuria is just an early phase of classical bacterial cystitis in which pyuria has not yet appeared (10).

Asymptomatic bacteriuria

Asymptomatic bacteriuria (ABU) (i.e., absence of dysuria, foul smell, discoloured urine, loin pain, fever) is found in 1–9% of young women and increases with age, reaching a prevalence of 14–75% in the elderly/institutionalised (22), with doubled risk in pregnant women (2–15%) and 3-fold risk in diabetics (1–30%). Recently, ABU has received greater attention, partly because chronic infection in the elderly may be asymptomatic until it leads to fever. Long-term ABU is defined as persistent colonisation of >3 weeks (to several years) duration (22). In general, treatment of ABU is not recommended, as routine antibiotics contribute to resistance as well as causing other adverse events and ABU may even be protective against recurrent UTI (23). However, ABU requires treatment in the circumstances such as pregnancy, instrumentation of the lower urinary tract and renal transplant patients. Escherichia coli (E. coli) is the most commonly detected bacteria in ABU (22). ABU with Streptococcus agalactiae (Group B streptococcus) is common in pregnancy and requires treatment as it is associated with chorioamnionitis (24) and neonatal sepsis (25). Note that Group B streptococcus bacteria are increasingly recognised as a uropathogen (see later section).

Recurrent bacterial cystitis

This term describes symptomatic infections, which recur after a previous UTI, usually after treatment. It may be due to bacterial persistence or due to a new infection with the same or different bacteria. Traditionally cited risk factors for recurrent infection are shown in Table 58.1. However, the evidence for the increased risk of UTI in women with cystocoele is actually quite limited. Although voiding dysfunction, diagnosed on urodynamic testing, and a postvoid bladder residual of >30 mL on ultrasound, is associated with recurrent UTI, no data could be found to show that TABLE 58.1: Risk Factors for Recurrent Urinary Tract Infection Lower urinary tract obstruction and chronic retention of urine Bladder stones or intravesical foreign bodies Mesh erosion into bladder/urethra Enterovesical and vesicovaginal fistulae Urethral diverticulae Malformations of the urinary tract, i.e., vesicoureteric reflux Cystocele – weak evidence Short urethra-vaginal distance Infected paraurethral glands Contraceptive diaphragm use

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(a)

611

(b)

(c)

FIGURE 58.1  Relationship between urethral orifice and external genital with (b) and (c) showing a more external urethral meatus that is associated with increased risk of postcoital UTI. (Reprinted from International Journal of Urogynaecology, 30:1351–1357, Gyftopoulos et al, Copyright (2021) with permission from Springer.)

cystocoele per se is significantly associated with recurrent cystitis (26, 27). As regards the risk of recurrent postcoital UTI, an anatomical variation whereby the urethra sits very close to the introitus has anecdotally been considered to promote UTI. Recently, a study employing careful measurements of the distance between the urethra and the vaginal introitus showed that this distance was significantly shorter in 61 women with proven recurrent UTI versus 56 controls (see Fig. 58.1) (28). A family history of recurrent UTI is not widely cited as a risk factor for recurrent cystitis. However, a study featuring 43 women with documented recurrent cystitis versus 400 women with no such history revealed that in women with one or two affected first-degree relatives, the odds ratio for recurrent cystitis was 3.1 for one affected relative (95% CI 2.1–4.7) and 5.0 for two affected relatives (95% CI 3.1–8.1) (29). Bacterial persistence often leads to frequent recurrence within days or weeks. The infection is usually by the original organism from a focus inside the urinary tract and is associated with an underlying anatomical problem (30). Bacterial persistence may also occur if empirical treatment was given without proper urine culture and checking of the bacterial antibiotic sensitivity, or if the patient did not complete the antibiotic course, or if the bacteria developed resistance after the original (correct) treatment was started. In urogynaecology patients (who often have coexisting incontinence, prolapse, voiding dysfunction, recent surgery, diverticula, etc.), the economically expedient practice of performing a simple dipstick and treating empirically cannot be recommended, as these patients are, by definition, prone to recurrence. Reinfection occurs after a prolonged interval (months) from the original infection and is often caused by a different organism (30). Older studies found that about 80–90% of recurrent cystitis is due to reinfection (31), of which 50% are due to the same organism (32). A recent study of severely recurrent UTI patients followed up for 4 years using culture-independent analysis showed that such chronic cases with cultures of “mixed growth” are often harbouring 2–3 bacteria in the bladder wall, which emerge at different times (33).

Clinical classification of cystitis

In summary, UTIs as a whole are classified according to their location, clinical symptoms, laboratory and microbiological findings, as shown in Table 58.2 modified from EUA guidelines (12).

Complicated UTI

Although this chapter primarily concerns bacterial cystitis, the urogynaecologist must be constantly vigilant for what are described as “complicated” UTIs. As seen in Table 58.3, many “complicated” UTIs involve upper urinary tract, e.g., renal calculi and cysts, ureteric stricture, vesicoureteric reflux, ureteric stents, nephrostomy tubes and renal transplants. However, the urogynaecologist should be mindful that lower tract anomalies, e.g., bladder cancer, urethral stricture/diverticulae, urogenital fistula, incomplete emptying and indwelling catheter commonly feature TABLE 58.2: Definitions of Cystitis Terminology Description Acute Cystitis - “Classical” uncomplicated bacterial cystitis - Low-count/“Occult” bacterial cystitis Recurrent UTI Complicated UTI

Symptomatic UTI

Asymptomatic bacteriuria

Clinical Features - Significant bacteriuria > 105 CFU/mL with pyuria (>10 white blood cells (WBC) per high-power field (HPF)) - Bacteriuria 103–105 CFU/mL ± pyuria Classical bacterial cystitis that reoccurs >3 times a year UTIs associated with a condition that increases the risk of infection or of therapy failing (see Table 58.3) Significant bacteriuria with dysuria, frequency, urgency, nocturia: foulsmelling urine, ± loin pain, febrile symptoms Bacteriuria >105 CFU/mL of urine, without pyuria or symptoms

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612 TABLE 58.3: Conditions Associated with Complicated Lower Urinary Tract Infection Structural

Functional

Foreign Bodies

Other

Urolithiasis Malignancy Ureteric stricture Urethral stricture Bladder diverticulae Renal cysts Fistulae Urinary diversions Neurogenic bladder Vesicoureteric reflux Voiding difficulties (incomplete bladder emptying) Indwelling catheter Ureteric stent Nephrostomy tube Diabetes mellitus Pregnancy Renal failure Renal transplant Immunosuppression Multidrug resistance Hospital-acquired (nosocomial) infection

sessile, non-E. coli organisms such as pseudomonas, which are frequently multiresistant organisms.

Prevalence Lower UTI is a common clinical diagnosis in developed countries and the most prevalent bacterial infection. Very little epidemiological data is available for bacterial cystitis alone; most prevalence data refers to “UTI” as a whole. Approximately, half of all women will experience a UTI sometime during their life, with an estimation of 150 million cases occurring a year worldwide (34). Other than in the elderly, UTI is more common in women than in men and account for 1–3% of all general practitioner consultations in the UK (35). Over the last two decades in the US, there has also been a 52% increase in hospital admissions associated with acute UTIs with an estimated cost of $3.5 billion in 2015 (36). Furthermore, recurrent cystitis is becoming a major problem, as 20–30% of females with an acute UTI will have a recurrence within 3–4 months (37), and recurrence occurs in 48% of women who have had more than one episode (38). Besides being distressing for patients, UTIs cause enormous health care expenses, mainly due to the high incidence. The costs of community-acquired UTI were totalled at 2.5 billion dollars in the year 2000 in the US (39). With the increasing resistance to antibiotics, the costs are likely to rise.

Pathogenesis As discussed above, urine is not “sterile”, contradictory to what was originally thought. However, pathogenic bacteria must gain access to the bladder, generally from neighbouring sites. The faecal–perineal–urethral route of infection is well documented. E. coli is the main causative organism, with the rectal flora serving

as the main reservoir (40), explaining why faecal incontinence is associated with a higher risk of UTI (41). Other colonisation sites include the perineum, vaginal vestibule, urethra and paraurethral tissues. How bacteria ascend the urethra is still poorly understood. It may be facilitated by sexual intercourse or catheterisation. The periurethral area is heavily colonised with bacteria. Urinary incontinence generally predisposes healthy postmenopausal women to develop recurrent cystitis (42). The use of incontinence pads is associated with a significant increase in the incidence of symptomatic cystitis in the elderly (43). However, just because bacteria gain access to the bladder, cystitis does not necessarily result. The bacteria must attach to the urothelial cells to begin the inflammatory process (see below for more detail). Even virulent organisms require some degree of host susceptibility (44). Patients with symptomatic bacteriuria are more likely to be neutropenic compared to those with ABU (45).

Host defences The bladder has several mechanisms to resist infection. Most important is the hydrokinetic or “washout” effect, in which diuresis and voiding act to dilute the bacterial load and wash away infecting organisms. In a 1969 study, 40% of women with bacteriuria became free of infection spontaneously within 12 months (46), while a 1971 study demonstrated that the urine of 80% of women with simple infections became sterile on placebo alone (47). Thus, the risk of infection will depend on the size of the bacterial load, the multiplication rate of the organism, the urinary residual, the frequency of voiding and the volume of fluid intake.

Antimicrobial factors

The composition of urine may inhibit bacterial growth. Extremes of urine pH, high osmolality and high urea concentration tend to be protective (48), which is why historically urine has been used as an antiseptic. Urea is the principal antibacterial electrolyte in urine, and its effect is also modulated by concentration and the pH (49). The acquisition of iron is also an important requirement for bacterial virulence because bacteria need iron to grow. The E. coli bacteria are most studied in this regard (50), as they have been shown to upregulate the genes that control iron acquisition systems (51). Urothelial cells that are invaded by E. coli respond by upregulating their own production of the transferrin receptor so as to prevent bacterial acquisition of iron (52).

Epithelial factors

The inner (luminal) surface of the urothelium is lined by uroplakin membrane proteins that lie within the plasma membrane of the superficial urothelial cells (also known as umbrella cells). These uroplakin plaques are composed of four proteins (UPIa, UPIb, UPII and UPIIIa) (53). They form a permeability barrier not only to prevent the resorption of urine solutes across the urothelium but also to limit the availability of receptors for bacterial adherence factors (54). The urothelium is also coated by a proteoglycan mucin layer that further reduces permeability. This acts to oppose bacterial colonisation, partly due to the high negative charge of the sulfated and carboxylated glycosaminoglycans (55). Unfortunately, uropathogens that express certain kinds of type 1 pili (mannose-binding) can block this adherence barrier by binding to the UPIa protein (as it contains a high mannose content) using an adhesion protein called FimH (56). Soluble factors normally found in the urine,

Bacterial Cystitis in Urogynaecology such as Tamm–Horsfall protein, also protect the bladder. This mucoprotein is shed from the renal tubular cells and is excreted in the urine. It can bind and trap E. coli, partly by competing for the binding sites on the type 1 pili (57). However, if uropathogens are able to adhere to urothelium, then the acute pathogenic cycle of bladder infection can begin.

Immunologic factors

The fact that recurrent cystitis affects 20–30% of women suggests that some women do not develop long-lasting protective adaptive immunity following their initial infection (58). The reasons for this are unknown. The T helper (CD4+) cell adaptive responses to uropathogen infection are unknown, though CD8+ T cells are reportedly recruited to uropathogenic E. coli (UPEC) infected bladders (59). Secretory immunoglobulin A (IgA) is synthesised by plasma cells within the lamina propria of the bladder wall and hence provides a degree of humoral immunity. In addition, a significant proportion of IgA originates in the urethra, and this may help prevent ascending infection (60). Secretory IgA has also been shown to prevent microbial invasion by disrupting bacterial adherence (61) and production of IgA can be deficient in women with recurrent UTI (62). When uropathogens bind to urothelium during the process of cystitis initiation, the bacteria induce the production of C-reactive protein (CRP), leading to leukocyte influx, IgA production and cytokine release, such as IL-6 and IL-8. These cytokines promote activation of CRP and mucosal IgA.

Toll-like receptors (TLRs)

If the initial defence mechanisms are resisted and the pathogen continues to attach itself to the epithelial cells, TLRs are activated. These TLRs play an important role in the pathogenic cascade of UTI by the host (63). This inhibits further invasion of the microorganism, induces the production of antimicrobial peptides, initiates apoptotic pathways, so that infected cells are exfoliated, and proinflammatory chemokines are released, triggering neutrophil accumulation (48). Defects in TLR pathway genes are associated with bacteriuria (63).

Role of the bacterial pathogen

613 Uropathogens: Structure and function

UPEC are the commonest cause of UTI in the US and abroad; they are responsible for about 80% of community-acquired cystitis and 25% of hospital-acquired infection. These are followed in prevalence by Staphylococcus saprophyticus (10–15% of community infections), then Klebsiella, Enterobacter, Proteus and Enterococcus species (40). UPEC possess a number of structural factors that enhance their ability to adhere to and colonise the urothelium. Most important are adhesive fibres known as pili, or fimbriae, which live on the bacterial outer membrane (40, 65). Different types of UPEC strains are able to assemble different types of fimbriae, which recognise specific receptors on the urothelium and enable strong adherence to the cell. For example, FimH (on Type I pili) binds to uroplakin 1a, which has mannose as one of its components (this is relevant to cranberry and D-Mannose treatment, discussed later in this chapter). Type 1 pili also binds to the TLR 4. The presence of the FimH adhesive molecule is very important for triggering acute inflammation (and symptoms of pain, etc.); E. coli that do not have FimH tend to be nonadherent, and they are often found in ABU (40, 66, 67).

Risk factors for UTI Host factors are certainly of equal importance with bacterial virulence in terms of the risk of developing cystitis. Host factors are considered in terms of congenital anomalies (such as vesicoureteric reflux, ectopic ureter, megaureter, or meningomyelocele) and acquired causes (Table 58.4). Other risk factors include a history of childhood UTI and a maternal history of UTI (40).

Age

Among children, the incidence of UTI is highest in the first year of life, with a gradual decrease to low rates at 11–15 years. TABLE 58.4: Acquired Risk Factors for Urinary Tract Infection Traumatic

Uropathogens have the ability to survive and multiply in the bladder as well as being able to adhere to the bladder epithelium. These unique qualities make them particularly virulent.

Adherence

The ability of bacteria to adhere to the urothelium of the lower urinary tract is an important initial step in the pathogenesis of lower UTI. The E. coli uropathogen has been the most widely studied because it possesses Type-I fimbriae, which are essential for invasion of the E. coli into the bladder epithelial cells (Fig. 58.2) (48). E. coli, which do not have these type-1 fimbriae are unable to infect the urothelium. These fimbriae receptors bind to the surface uroplakins and other cellular proteins, thus preventing washout by the shear forces of the urine cascading across them. In animal models and one human study (64), the E. coli are then shown to actually live inside the urothelial cells, forming intracellular bacterial communities (IBCs), unless the release of cytokines can provoke shedding of the urothelium and washout. Once the IBCs become established in the superficial umbrella cells, they can invade the lower layers of the urothelium and can become impervious to antibiotic treatment.

Inflammatory

Metabolic Drugs Anatomic Functional

Malignancy

Surgery (urinary diversion, clam cystoplasty) Sexual intercourse Sexual abuse Foreign bodies (catheters, stents, mesh) Contraceptive diaphragm Vulvourethritis Chronic inflammation (tuberculosis, syphilis, schistosomiasis) Radiotherapy Fistula Calculi Diabetes mellitus Cyclophosphamide Tiaprofenic acid Cystocele – nonemptying Urethral diverticulum Detrusor hypotonia/DHIC (spell out) Detrusor dyssynergia Constipation Bladder tumours Other disseminated pelvic tumours (cervix, uterus)

Textbook of Female Urology and Urogynecology

614 Bacterial life cycle (1) Attachment

(2) Invasion

(3) Replication IL-6 IL-8

Tissue

Killing

(4) Exfoliation & Quiescent reservoir

Blood vessel Neutrophils

· Cathelicidin · Defensins - Killing - Exfoliation - Immunopatholgy?

UPEC Urine Host defense (1) - Inhibition of binding - Direct killing slgA Tamm-Horsfall protein Lactoferrin, Lipocalin

(2) Cell activation: Production of inflammatory mediators - Antimicrobial peptides - Chemokines

(3) Immune cell recruitment

(4) - Killing - Exfoliation

- Neutrophils - (Macrophages) - (Dendritic Cells)

FIGURE 58.2  Multilayered effector mechanisms to combat urinary tract infections (UTI). Soluble factors like lactoferrin, Tamm– Horsfall protein (THP) or secretory IgA inhibit attachment of uropathogenic E. coli (UPEC) to the epithelium. Despite these defence mechanisms, some bacteria are able to attach and invade the epithelium, which in turn releases antimicrobial molecules like cathelicidin or defensins. Moreover, the uroepithelium produces interleukin (IL)-6 and IL-8 to attract additional immunocompetent cells like neutrophils, which help to eliminate the pathogens. (Reprinted from European Journal of Clinical Investigation, 38 Suppl 2, Weichhart T, Haidinger M, Horl WH et al., Current concepts of molecular defense mechanisms operative during urinary tract infection, 29–38, Copyright (2008), with permission from John Wiley and Sons.)

Low-grade vesicoureteric reflux is an important factor. During a voiding detrusor contraction, if the vesicoureteric valves are incompetent, reflux of bladder urine up into the ureters/renal pelvis may occur. When the detrusor relaxes again, stagnant urine drains back from the upper renal tracts into the bladder, which predisposes to infection. In a review of 200 girls with recurrent lower UTI, 43% demonstrated vesicoureteric reflux, whereas in those with only one episode of infection, the corresponding rate was 36% (68). Young girls with recurrent UTI and day wetting (likely due to Detrusor Overactivity) are known to adopt a posture of kneeling down on their heel (“the curtsy sign”) to stop urgency incontinence, which is thought to promote reflux of nonsterile urine from the lower urethra back up into the bladder (69). This may be associated with irregular or “staccato” voiding patterns and incomplete emptying, which promotes UTI. The incidence of UTI increases in young adult women, where sexual activity is an important contributory factor, and increases again in old age. Reduced oestrogen levels following menopause are associated with vaginal flora changes. Lactobacilli that belong to the normal microflora of the vagina decline, which is associated

with a rise in pH, allowing growth of Gram-negative bacteria increasing the risk of UTI (70). UTIs in the elderly are common, accounting for approximately 25% of all infections (37), 30% of those found in nursing homes (71). The increasing prevalence of lower UTI in old age is most likely to be multifactorial in nature and is associated with a history of UTI, the presence of concomitant systemic disease, diabetes, increasing immobility, faecal and urinary dysfunction, the presence of a cystocele, instrumentation of the urinary tract and sexual activity (although the association is less strong than in younger women) (72). Persistent bacteriuria is not associated with significant morbidity (41), and it has a low predictive value for identifying febrile UTIs (73). In part, this is because bacteriuria with low virulence Gram-positive bacteria such as enterococci, coagulase-negative staphylococci and group B streptococci is more common in this age group (22). ABU is very common in the elderly with up to 75% of institutionalised women found to be bacteriuric (22) and treatment is not proven to be generally helpful (74). However, UTI in the elderly can provoke fever, confusion, nausea, vomiting, dehydration and delerium without bladder symptoms (75). Predictive factors include severe cognitive impairment, disability in daily

Bacterial Cystitis in Urogynaecology living and self-reported urinary incontinence. Antibiotics must be used with particular care in the elderly because of the risk of C. difficile.

Obesity

Studies on the association between obesity and UTI have shown contradicting results. In a large study of the factors influencing the rate of first referral for urinary infection in 17,032 women, the risk of the first infection was higher in the nonobese compared to the obese (76). A larger study of insurance claims for UTI treatment in 95,598 patients found obese women likely to be diagnosed with UTI (77). Several studies have shown that obese patients are more at risk of developing UTIs after surgery than nonobese patients (78).

Behavioural factors

Factors such as adequate fluid intake, voiding habits, diet, synthetic underwear and use of perfumed soaps and bubble baths may be associated with the development of UTIs (79). Sexual intercourse increases the risk of UTI by 90%, which increases even more with the use of condoms (80). Furthermore, the frequency of intercourse has also been shown to be a significant risk factor (81), and certain strains of E. coli may be transmitted between partners (82, 83). Theoretically, anal sex may be associated with an increased risk of UTI; however, there is no literature to support this.

Instrumentation of the urinary tract

The incidence of bacteriuria associated with an indwelling urinary catheter (known as catheter-associated UTI or CAUTI) is 3–10% per day. Duration of catheterisation and failure to maintain a closed draining system are the most important risk factors for infection (84). Following catheter removal, the bacteriuria will resolve spontaneously in around a third of cases (85). While fewer than 5% of CAUTIs result in bacteraemia, they are nevertheless a significant cause of morbidity, and they are also an important reservoir of antibiotic-resistant bacteria in hospitals and nursing homes. Consequently, it is not uncommon that infections with multiple organisms occur in women with long-term indwelling catheters. The prevalence of CAUTI in the literature ranges from 9 to 100% (22). Klebsiella, Pseudomonas and Enterobacter are more prevalent as well as Morganella morganii, which is rarely found in other subgroups. U.K. and American evidence-based guidelines for preventing infections and treating CAUTIs have been published (35, 86). Using interventions such as topical antimicrobials, disinfectants added to the urinary drainage bag, antimicrobial coatings for catheters or antimicrobial irrigation does not decrease the incidence of catheter-associated infections (86). Various types of catheters (nitrofurazone-impregnated silicone catheter, standard PTFE-coated latex catheters and silver alloycoated hydrogel latex) do not affect the UTI rate (87). Bacteriuria should be expected in women with long-term catheterisation and, if asymptomatic, treatment is generally not justified as it is unlikely to give a microbiological cure, and risks selecting for antibiotic-resistant microorganisms (86). Catheters should be removed at the earliest opportunity and changed on a regular basis, as microbial colonisation is inevitable over time. As an alternative to long-term catheterisation, the technique of clean intermittent self-catheterisation (CISC) may be considered in women who are able to learn the technique, as it significantly reduces bacteriuria (88). Evidence shows that the use of

615 prophylactic antibiotics does not improve the outcome in women performing CISC and should not be used. Catheters can be kept sterile at home and reused for up to 1 week with no change in bacteriuria rates (89). Suprapubic catheterisation (SPC) as an alternative method of long or short-term bladder drainage is associated with lower infection rates. A study of post urogynaecology surgery studied the insertion of indwelling urethral catheters for 24 and 90 hours versus SPC for 90 hours and found no significant difference between the three groups in the incidence of symptomatic UTI, but ABU was significantly less in the SPC group (90). The suprapubic route has the added advantage of allowing women to void with the catheter in situ and have postvoid residuals checked without the need for repeated urethral catheterisation. The rate of bacteriuria in the literature following cystoscopy ranges from 2.8 to 21% (91). Bacteriuria can be lowered by a single dose of antibiotic prophylaxis such as gentamycin, but the risk of side effects should be considered, as the majority will not develop UTI symptoms.

Voiding dysfunction

Incomplete emptying of the bladder is an important cause of UTI (69). It is usually secondary to detrusor underactivity but can be associated with detrusor–sphincter dyssynergia or outflow obstruction secondary to a pelvic mass, significant cystocele, surgery or urethral stricture. As regards to detrusor underactivity, urodynamic studies have shown that, with increasing age, there is a significant increase in postvoid residual and a decrease in urinary flow rates, voided volume, and bladder capacity (92). This would suggest that voiding function deteriorates with age and may be partly responsible for the increased incidence of UTI in the elderly. Postpartum bladder hypotonia following unrecognised over distension is a major problem that can affect UTI risk long term.

Causative organisms and antibiotic resistance Gram-negative coliform bacilli of the family Enterobacteriaceae account for over 70% of cases, and E. coli (Fig. 58.3) remains the predominant species in both primary care (approximately 70%)

FIGURE 58.3  Urothelial cells associated Escherichia coli (wright stain).

616 (93, 94) and hospital practice (56%) (95). Proteus mirabilis, Enterococcus faecalis and Klebsiella pneumonia are the most prevalent hereafter (3–8%) and are found twice as often in hospital-acquired UTIs and in patients over 65 years of the age (95). Antibiotic-resistant noncoliform Gram-negative bacilli such as Pseudomonas aeruginosa and Acinetobacter species occur almost exclusively in hospital-acquired infections. Among Grampositive bacteria, Staphylococcus saprophyticus is an important cause of UTI in sexually active women. Although mainly known for its association with neonatal disease, Streptococcus agalactiae (group B streptococcus) is also a known uropathogen that is increasingly being reported (96), particularly in the elderly with chronic diseases (97). The other coagulase-negative staphylococci and S. aureus are more commonly hospital associated, apart from contaminated collections. Fastidious bacteria that can only be isolated on enriched culture media, including Streptococcus pneumoniae and Haemophilus influenzae, occasionally cause UTI in primary care. Bacteria that require special detection techniques, such as the cell wall-deficient mycoplasma (including Ureaplasma urealyticum) and the obligate intracellular pathogen Chlamydia trachomatis, are also recognised causes of cystitis. UTI can also be caused by microorganisms other than bacteria. Lower UTI due to Candida species is most common in patients with urinary catheters and usually reflects colonisation of the catheter. However, florid refractory vaginal candidiasis can colonise the urethra and be cultured in the urine.

Emerging antibiotic resistance

The global threat from increasing prevalence of resistance to antimicrobials among uropathogens was reported by the World Health Organisation in 2014 (98). However, the problem of increasing bacterial resistance has wide-ranging implications, which the urogynaecologist needs to be aware of. In a landmark 2017 paper from the Lancet, the opening paragraph reads as follows: “Antimicrobial resistance represents arguably the greatest current public health threat. If the increase in drug resistance is not slowed, modelling suggests that from the current 700,000 deaths annually, deaths attributed to drug-resistant infections by 2050 will surpass 10 million – i.e. one person dying every three seconds” (1). Another Lancet article describing the mechanisms of antimicrobial resistance points out that “more antimicrobials are used in food production than in human beings, with marked national difference” varying from 4 mg to 400 mg of antimicrobial per kg of meat produced in European countries (99). As regards to bacterial cystitis, rates of resistance to the commonly used oral antimicrobial agents vary between countries depending on the availability and usage of different medicines. Until recently, cystitis has been a relatively simple condition to treat with the available antibacterial drugs, although increasing resistance is a major concern (40, 100). The susceptibility of E. coli to nitrofurantoin is still high (96–100%) (101). A study in a general practice setting in France showed high levels of susceptibility to fosfomycin (99%), norfloxacin (97%), trimethoprimsulfamethoxazole (87%) and amoxicillin/clavulanic acid (91%) (94). However, increasing resistance to the traditional first-line therapy, trimethoprim-sulfamethoxazole, has led to wider use of fluoroquinolones with resultant increasing bacterial resistance against norfloxacin and ciprofloxacin. An Australian study on acute pyelonephritis, which spanned 12 years, demonstrated increasing resistance of E. coli strains to a variety of antibiotics, with a stable prevalence of resistance to ampicillin/

Textbook of Female Urology and Urogynecology amoxicillin between 40 and 50% (93). Although resistance to 1st and 3rd generation cephalosporins in E.coli is low, it is rising, particularly in those elderly, who have been admitted to hospital, require indwelling catheters or are residents of nursing homes. Most community-derived urinary isolates remain susceptible to cephalosporins and co-amoxiclav, although this is not the case in hospitals. The emergence and spread of plasmid-borne extended-spectrum beta-lactamase genes (ESBL) that confer resistance to penicillin combined with clavulanate or sulbactam and 3rd generation cephalosporins in Enterobacteriaceae and other Gram-negative bacteria present a growing problem. The mobile plasmids containing these genes may also carry genes that confer resistance to other classes of antibiotics including aminoglycosides, folate antagonists and quinolones, so their spread may be influenced by antibiotics prescribed for any condition, including UTI. The genes encoding these enzymes are readily transferred between species, so that cross-infection is not recognised simply by a rising rate of antibiotic resistance within one species. Communityacquired UTIs with ESBL-producing bacteria that are resistant to all oral antibiotics are already being encountered and pose real therapeutic difficulties. Nonsusceptibilities and resistances are demonstrated in Table 58.5 (102).

Hospital- versus community-acquired infections

Community-acquired infections differ from those originating within the hospital environment where Klebsiella, Staphylococcus and Pseudomonas are more prevalent (95). The frequency of various species causing community and hospital-acquired UTIs cultured in the UK are demonstrated in Table 58.6 (95).

Investigations Microbiologic investigations

In primary care, the diagnosis of UTI is often made on clinical grounds, possibly supported by dipstick urinalysis. This is not generally appropriate in a urogynaecology service, partly because bacterial toxins are known to enhance detrusor contractility (103, 104), and inflammation can weaken urethral sphincter strength (105), thus incontinence is worsened, but also because accurate treatment is required before placing urodynamic catheters or commencing urogynaecology surgery. Furthermore, Khasriya et al. have highlighted the low sensitivity and specificity of dipstick urinalysis as well as microscopic examination for pyuria (106). They compare both these tests to the urine culture of both mid-stream and catheter specimens. The sensitivity of leukocyte esterase (LE) and microscopic pyuria was 56% compared to that of nitrite 10%. Moreover, in patients with urinary symptoms associated with low bacterial counts, the sensitivity of combined LE and nitrite testing may be as low as 25% (79).

Microscopy and culture

Phase-contrast microscopy is mainly used to quantify leukocytes and erythrocytes and detect squamous epithelial cells (urethral) and bacteria. Gram staining can be a useful alternative; the presence of bacteria can be confirmed and indicative of the causative microorganism. Selective media used to culture urine routinely (e.g., cysteine lactose electrolyte deficient (CLED), MacConkey and chromogenic agars) are selected to enhance colonial morphology and distinguish mixed from pure growth of common uropathogens. Blood agar will support the growth of

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TABLE 58.5: Nonsusceptibility and Resistance Rates for the Main Species Tested Antimicrobial

Category*

Ampicillin Ampicillin Amoxycillin-clavulanate Amoxycillin-clavulanate Ticarcillin-clavulanate Piperacillin-tazobactam Cefazolin Cefoxitin Ceftriaxone Ceftazidime Cefepime Meropenem Ciprofloxacin Norfloxacin Gentamicin Trimethoprim Nitrofurantoin

I R I R R R R R NS NS NS NS NS NS NS R NS

Escherichia Coli (%)

Klebsiella Pneumonia (%)

Klebsiella Oxytoca (%)

Enterobacter Cloacae (%)

Enterobacter Aerogenes (%)

†

†

†

†

†

†

†

†

†

†

†

†

16.8 8.8

19.8 11.4

†

†

†

†

27.3 19.5 0.8 1.6 0.8 0.0 5.5 17.2

21.5 18.7 0.0 0.0 1.9 1.9 0.0 1.9

†

†

1.9 44.3 11.3 5.3 5.7 1.7 14.3 1.5 4.2 2.2 0.7 0.0 6.9 6.8 4.5 22.7 5.4

2.8 2.1 1.8 0.7 6.9 1.4 4.6 3.0 0.5 0.0 3.5 2.3 3.0 9.9 †

1.0 9.9 12.5 9.2 75.8 0.0 6.9 0.0 0.0 0.0 0.0 0.0 0.0 3.0 †

Source: * †

Reprinted with permission from Communicable Diseases Intelligence, 37 (3), Turnidge JD, Gottlieb T, Mitchell DH, et al., Australian Group on Antimicrobial Resistance Community-onset Gram-negative Surveillance Program annual report 2012. Commun Dis Intell 2014;38(1):E54–E58 Copyright (2014). R = resistant, I = intermediate, NS = nonsusceptible (intermediate + resistant) Considered largely intrinsically resistant due to natural β-lactamases

more fastidious organisms that may not otherwise be recognised. Liaison between the requesting clinician and the laboratory is essential to ensure optimal investigation.

Further investigations

In the majority of women with a single episode of simple acute cystitis there is no need for further investigation. However, women with proven recurrent cystitis, those with a childhood history of UTI, persistent infection that does not respond to therapy or persistent haematuria warrant further investigation. TABLE 58.6: Relative Frequency (% of Total) of Isolation of Species Causing Various Types of UTI CommunityAcquired UTI (Patients < 65 years) (N = 397) Organism % E. coli 77.3 P. mirabilis 4.3 E. faecalis 3.8 K. pneumoniae 3.5 S. saprophyticus 2.0 P. aeruginosa 1.8 S. aggalactiae 1.5 Other species 5.8

Source:

CommunityAcquired UTI (Patients > 65 years) (N = 392) Organism % E. coli 66.6 E. faecalis 5.9 K. pneumoniae 5.9 P. mirabilis 4.3 P. aeruginosa 3.1 E. cloacae 2.8 K. oxytoca 1.8 Other species 9.7

Hospital Patient UTI (Excluding Pyelonephritis)

(N = 394) Organism % E. coli 56.3 E. faecalis 8.4 K. pneumoniae 6.9 P. mirabilis 6.3 P. aeruginosa 3.8 E. cloacae 2.5 S. aureus 2.5 E. faecium 2.0 K. oxytoca 2.0 Other species 9.1

Reprinted with permission from Farrell DJ, Morrissey I, De Rubeis D, et al., A UK Multicentre Study of the Antimicrobial Susceptibility of Bacterial Pathogens Causing Urinary Tract Infection, Journal of Infection, 46(2), 94–100, Copyright (2003), Elsevier.

Renal function should be assessed with serum creatinine, urea and electrolytes. In specific cases, it may be helpful to exclude atypical infections (Mycoplasma hominis, Ureaplasma urolyticum and Chlamydia trachomatis). The usual history is of a woman suffering repeated cystitis episodes, which improve with antibiotics, but symptoms return as soon as antibiotics are stopped. Often there have been repeated MSUs which demonstrate a sterile pyuria, but no growth on culture. One study found a positive culture for ureaplasma in 26% of the specimens tested for atypical organisms and 7.6% revealed ureaplasma and mycoplasma (107). They were cultured in 4.3% of patients with sterile pyuria. Although the numbers are small, an improvement rate of 71% was found with 3 months of antibiotics (Norfloxacin in most patients). Ultrasound of the entire renal tract to eliminate hydronephrosis or calculi, with postmicturition scan to exclude residual >100 mL, is important. Pelvic ultrasound to rule out pelvic mass is worthwhile at the same time. The upper tracts can be imaged using CT urography, which has largely replaced intravenous pyelograms (108). Renal imaging on dimercaptosuccinic acid (DMSA) scan may be needed in protracted or recurrent upper tract infection. Technetium-labelled diethyltriaminepentaacetic acid may also exclude both upper urinary tract obstruction and renal scarring. Women with recurrent UTI not responding to simple prophylactic measures (see below) or those with haematuria should undergo cystoscopy (although if urine cytology is positive, this should be done by a urologist). Follicular cystitis (Fig. 58.4a and b), which may indicate intracellular bacterial colonies (IBC’s) can benefit clinically from diathermy to these lesions. A prospective cohort study of 47 patients showed a fourfold reduction in UTI after diathermy to follicular cystitis (109). Evidence of mesh erosion in the bladder (Fig. 58.4c) or urethra (Fig. 58.4d) in the context of a continence procedure (i.e., mid urethral sling) or prolapse mesh needs scrutiny with a 70-degree telescope, as this may

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618 (a)

(b)

(c)

(d)

FIGURE 58.4  Cystoscopy findings of potential causes of recurrent UTI nonresponsive to oral therapy. (a) Diffuse follicular cystitis on posterior bladder wall, (b) focal follicular cystitis at bladder neck, (c) intravesical or (d) transurethral mesh from previous continence surgery. cause recurrent UTI that is resistant to any therapy. Search for the lumen of a urethral diverticulum requires meticulous examination with a cystourethroscope (after MRI scan).

Treatment Management of bacterial cystitis is aimed at treating the current infection, with eradication of clinical symptoms and microbiologically significant bacteriuria/pyuria, and preventing further recurrences, by correcting risk factors and instigating a prophylactic regime where needed.

General measures

Patients with acute cystitis should be encouraged to increase their fluid intake (2–2.5 L) in order to achieve a short voiding interval and a high flow rate, which will help to dilute and flush out the infecting organism (110). Symptomatic relief may be provided by alkalinisation of the urine, drinking a large teaspoon of bicarbonate of soda (or commercial preparations, e.g., ural) in a glass of water every 3–4 hours for 2–3 days. With such measures, spontaneous remission of symptoms may occur in up to 40% of women (111). However, in the urogynaecology patient with associated pelvic dysfunction, a urine culture should be performed and appropriate antibiotics should be given if symptoms are not greatly resolved when the culture result is known. The common practice of patients simply alkalinising and diluting the urine is fraught with difficulty in those with coexistent incontinence.

Antimicrobial therapy Ideally, drugs should be reliably absorbed after oral administration, safe, and well tolerated. Where the pathogen is known, the most precise antibiotic should be used. When treating an acute episode of cystitis encountered in the urogynaecology clinic, the antibiotic with the greatest likelihood of eradicating the most common organism (E. coli) appears to be nitrofurantoin (98–100% susceptibility) (101). Because it is highly concentrated in the urine but serum and tissue levels are subtherapeutic, it does not generally cause vaginal monilia; however, it cannot be used to treat pyelonephritis (112). It has a complex mode of action, so that the acquired resistance is uncommon (112, 113). Importantly, nitrofurantoin is one of few oral antibiotics for cystitis due to ESBL-producing organisms alongside fosfomycin and pivmecillinam with susceptibilities of 94, 97 and 85%, respectively (114). Adverse effects other than nausea are rare, and this can be contained by taking the drug with food, which also increases the absorption of nitrofurantoin and the duration of therapeutic levels (112). The macrocrystilline formation, such as in nitrofurantoin, slows absorption, which reduces nausea and vomiting. Many of the antibiotics that were most commonly used to treat UTIs now have to be used with caution, either because resistance rates among uropathogens are high (as in the case of amoxicillin and trimethoprim) or because of the association with C. difficile (as in the case of cephalosporins and quinolones).

Bacterial Cystitis in Urogynaecology Undue emphasis is often placed on the distinction between bactericidal and bacteriostatic antibiotics. In most cases, it makes no difference to the outcome. However, bactericidal antibiotics are preferred on theoretical grounds for patients with immunodeficiencies. Of the antibiotics commonly used to treat UTIs, the β-lactam antibiotics and aminoglycosides and fluoroquinolones are the most reliably bactericidal.

Individual antibiotics Nitrofurantoin

Nitrofurantoin is excreted in urine in high concentrations and has little action systemically. It is converted by bacterial nitrofuran reductase to active forms that attack ribosomal proteins, DNA and other macromolecules. Resistance to this agent is uncommon and may be chromosomal or plasmid mediated. There may be antagonism with quinolones if taken in combination. This agent is generally regarded as a urinary antiseptic because of its negligible tissue penetration and low blood levels. Although nitrofurantoin is highly effective against E. coli, Klebsiella and Enterobacter sp. and Streptococci in acid urine, it has no effect at all against Proteus or Pseudomonas species as these organisms split urea producing ammonia and alkaline urine. Nitrofurantoin is safe during pregnancy but is contraindicated at term because of the risk of causing neonatal haemolysis. Nitrofurantoin is used in caution in the elderly, due to it being contraindicated in patients with renal insufficiency. Data have proven its use to be both effective and safe in those with a creatinine clearance greater than 40 mL/min (72).

Amoxicillin

Amoxicillin is a derivative of ampicillin that has a similar antibacterial spectrum but is better and more reliably absorbed. Both antibiotics contain a β-lactam ring and are effective against Gram-negative and Gram-positive organisms, targeting the cross-linkages of the bacterial cell wall and are destroyed by bacterial beta-lactamase. These drugs are no longer recommended as first-line empiric therapy for UTIs because of the high prevalence of resistance among Enterobacteriaceae. Augmentin (Co-amoxiclav) is a combination of amoxicillin and clavulanic acid that inhibits the β-lactamase enzymes produced by many amoxicillin-resistant bacteria. Augmentin has a spectrum of antibacterial activity suitable for treating UTIs as it is also effective against Gram-positive pathogens. Although coamoxiclav use has been associated with C. difficile, the association may be less strong than with cephalosporins. Co-amoxiclav has therefore superseded second-generation cephalosporins in many hospitals, but it should still be used with caution, especially in the elderly (115).

Cephalosporins

Cephalosporins act in a similar fashion to penicillin by targeting the cross-linkages of the bacterial cell wall to prevent replication and weaken the rigid structure allowing cell death by lysis. First-generation cephalosporins are effective against most community-associated uropathogens, but they are not active against enterococci, Enterobacter and Pseudomonas. Although serum levels of first-generation cephalosporins are poor after oral administration, they appear in high concentrations in urine, so they are useful for cystitis but not pyelonephritis. For treating UTIs, the newer and more expensive second-generation oral cephalosporins offer little or no benefits over the earlier (and

619 cheaper) cephalosporins. The third-generation cephalosporins are resistant to the effects of simple beta-lactamases and have found widespread use in empiric therapy for acute uro-sepsis often in combination with an aminoglycoside.

Trimethoprim

Trimethoprim blocks the folic acid metabolic pathway in bacteria and was widely used as first-line empiric therapy for UTIs; however, resistance is increasing, even in the community. Trimethoprim is best avoided in pregnancy (especially the first trimester) because of the theoretical risk of teratogenicity. Co-trimoxazole (Bactrim) is a mixture of trimethoprim and sulfamethoxazole, which rarely offers any benefits over trimethoprim but has a higher risk of side effects. The U.K. Committee for Safety of Medicines recommends that co-trimoxazole should be used only where there is good bacteriologic evidence of benefit over trimethoprim.

Tetracyclines

Tetracyclines cover 50–90% of most uropathogens, including atypical microorganisms. They are bacteriostatic and act on the bacterial ribosome to block protein synthesis. Other than doxycycline and minocycline, they are excreted mainly in the urine. However, they are little used for treating UTIs, and they are deposited in growing bones and teeth and are contraindicated in pregnancy, breastfeeding women, and children aged 4.5. 4. Presence of clue cells on light microscopy. These Amsel features are simple and reliable, and tests for them are easy to perform. The presence of clue cells is the single most reliable predictor of BV. Clue cells are exfoliated vaginal squamous epithelial cells covered with G. vaginalis, giving the cells a granular or stippled appearance with characteristic loss of clear cell borders. The offensive fishy odor may be apparent during the physical examination or may become apparent only during the amine test. Gram stain of vaginal secretions, expressed as Nugent score, is extremely valuable in diagnosis, with a sensitivity of 93% and specificity of 70%. Although cultures for G. vaginalis are positive in almost all cases of BV, G. vaginalis may be detected in 50–60% of women who do not meet the diagnostic criteria for BV. Accordingly, vaginal culture has no part in the diagnosis of BV. PCR-based molecular tests are both sensitive (95%) and specific (99%) and are now widely used by practitioners.

Management

The most widely used oral therapy remains to be metronidazole or tinidazole [35]. Most studies using multiple divided dose metronidazole regimens of 800–1200 mg/day for 1 week achieved clinical cure rates in excess of 90% immediately and of approximately 80% at 4 weeks. Although single-dose therapy with 2 g metronidazole achieves comparable immediate clinical response rates, higher recurrence rates have been reported. CDC-recommended regimen is metronidazole 500 mg twice daily for 7 days [35]. The beneficial effect of metronidazole results predominantly from its antianaerobic activity and because G. vaginalis is susceptible to the hydroxymetabolites of metronidazole. Although Mycoplasma hominis and Mobiluncus curtisii are resistant to metronidazole, the organisms are usually not detected at follow-up visits of successfully treated patients. Similarly, metronidazole and tinidazole are considered therapeutic equivalents.

633 Topical therapy with 2% clindamycin cream once daily for 7 days, clindamycin ovules for 3 days, or metronidazole gel 0.75% administered daily for 5 days has been shown to be as effective as oral metronidazole, without any of the side effects of the latter [35]. In the past, asymptomatic BV was not treated, especially because patients often improve spontaneously over several months. However, the growing evidence linking asymptomatic BV with numerous obstetric and gynecologic upper tract complications has caused reassessment of this policy, especially with additional convenient topical therapies. Asymptomatic BV should be treated before pregnancy, in women with cervical abnormalities, and before elective gynecologic surgery. Routine screening for and treatment of asymptomatic BV in pregnancy remain controversial [35, 36]. Despite indirect evidence of sexual transmission, no study has documented reduced recurrent rates of BV in women whose partners have been treated with a variety of regimens, including metronidazole. Accordingly, most clinicians do not routinely treat male partners [37]. After therapy with oral metronidazole, approximately 30% of patients initially respond experiencing recurrence of symptoms within 3 months. Reasons for recurrence are unclear, including the possibility of reinfection, but recurrence more likely reflects vaginal relapse, with failure to eradicate the offending organisms and reestablish the normal protective Lactobacillus sp.–dominant vaginal flora. Management of BV relapse includes switching from one drug class to the other, e.g., metronidazole to clindamycin. Newer regimens include using higher doses of vaginal metronidazole, combination therapy with boric acid, or a maintenance dose of twice-weekly metronidazole gel 0.75% [38, 39]. Probiotic use consisting of exogenous Lactobacillus sp. containing highly selected bacteria-containing suppositories has been encouraging, but they are not yet available commercially [40].

Trichomoniasis Epidemiology

Studies estimate that 3–5 million American women contract trichomoniasis annually, with a worldwide distribution of approximately 180 million annual cases [41]. The prevalence of trichomoniasis correlates with the overall level of sexual activity of the specific group of women under study, being diagnosed in about 5% of women in family planning clinics, in 13–25% of women attending gynecology clinics, in 50–75% of prostitutes, and in 7–35% of women in STD clinics [41].

Pathogenesis and pathology

Sexual transmission is the dominant method of introduction of Trichomonas vaginalis into the vagina. T. vaginalis was identified in the urethra of 70% of men who had had sexual contact with infected women within the previous 48 hours. There is also a high prevalence of gonorrhea in women with trichomoniasis, and both of these are significantly associated with the use of nonbarrier methods of contraception. Recurrent trichomoniasis is common, but rarely it is indicative of lack of significant protective immunity. Nevertheless, an immune response to Trichomonas spp. does develop, as indicated by low titers of serum antibody, but this is insufficient for diagnostic serology. Antitrichomonal IgA has been detected in vaginal secretions, but a protective role is not defined. The predominant host defense response is provided by the numerous PMNs, which

634 respond to chemotactic substances released by trichomonads and are capable of killing T. vaginalis without ingesting trichomonads. T. vaginalis destroys epithelial cells by direct cell contact and cytotoxicity. The urethral, paraurethral, Bartholin’s, and Skene’s glands are infected in the majority of patients, and organisms are occasionally isolated from bladder urine. Most recurrences are due to reinfection or lack of treatment compliance.

Prevention

Sexual transmission of trichomonads is efficiently prevented by the use of barrier contraception. Spermicidal agents such as nonoxynol-9 also reduce transmission. Reinfection of women is common and hence the mandatory requirement of treatment, preferably simultaneously, of all sexual partners with metronidazole. Women can acquire the disease from other women, but men do not usually transmit infection to other men.

Clinical features

Infection with Trichomonas spp. in women ranges from an asymptomatic carrier state to severe acute inflammatory disease [42]. Vaginal discharge is reported by 50–75% of women diagnosed with trichomoniasis; however, the discharge is not always described as malodorous. Pruritus occurs in 25–50% of patients and is often severe. Other infrequent symptoms include dyspareunia, dysuria, and, rarely, frequency of micturition. Lower abdominal pain occurs in fewer than 10% of patients and should alert the physician to the possibility of concomitant salpingitis caused by other organisms. Symptoms of acute trichomoniasis often appear during or immediately after menstruation. Although controversial, the incubation period has been estimated to range from 3 to 28 days [42]. Physical findings represent a spectrum depending on the severity of the disease. Vulvar findings may be absent but are typically characterized in severe cases by diffuse vulvar erythema (10–33%), edema, and a copious, profuse, and malodorous vaginal discharge, which is often described as being yellow-green and frothy but is frequently grayish-white [32]. Frothiness is seen in a minority of patients and is more commonly seen in BV. The vaginal walls are erythematous and in severe cases may be granular in appearance. Punctate hemorrhages (colpitis macularis) of the cervix may result in a strawberry-like appearance that, although apparent to the naked eye in only 1–2% of patients, is present in 45% of cases on colposcopy. The clinical course of trichomoniasis in pregnancy is identical to that seen in the nonpregnant state, and when untreated, it is associated with premature rupture of membranes and prematurity. Trichomoniasis is reported to facilitate HIV transmission. Trichomoniasis is a risk factor for the development of posthysterectomy cellulitis, tubal infertility, cervical neoplasma, and pelvic inflammatory disease [43].

Diagnosis

None of the clinical features of vaginitis caused by Trichomonas spp. are sufficiently specific to allow a diagnosis of trichomonal infection based on signs and symptoms alone. Definitive diagnosis requires the demonstration of the organism. Vaginal pH is markedly elevated, almost always above 5.0, and not infrequently 6.0. On saline microscopy, an increase in the number of PMNs is almost invariably present. The ovoid parasites are slightly larger than PMNs and are best recognized by their motility. The wet mount is positive in only 40–80% of cases (low sensitivity). Gram stain is of little value because of its inability to differentiate PMNs

Textbook of Female Urology and Urogynecology from non-motile trichomonads, and the use of Giemsa, acridine orange, and other stains has no advantage over saline preparations. Although trichomonads are often seen on Papanicolaou smears, this method has a sensitivity of only 60–70% when compared with saline preparation microscopy, and false-positive results are not infrequently reported. Several equivalent culture medium methods are available, and growth is usually detected within 48 hours. However, culture, including “InPouch,” has now been replaced by PCR molecular detection of Trichomonas DNA and should be considered in all patients with unexplained vaginitis, especially in whom an elevated pH is found together with PMN excess and absence of motile trichomonads [44].

Management

Therapy is indicated in all nonpregnant women diagnosed with Trichomonas vaginitis even if asymptomatic and consists of administering the 5-nitroimidazole group of drugs—metronidazole, tinidazole, secnidazole, and ornidazole—which are all of similar efficacy [35]. Oral therapy as opposed to topical vaginal therapy is preferred because of the frequency of infection of the urethra and periurethral glands, which provide sources for endogenous recurrence [35]. Treatment of all sexual partners is mandatory. Treatment consists of oral metronidazole, 500 mg/12h for 7 days, which has a cure rate of 95%. Comparable results have been obtained with a single oral dose of 2 g metronidazole, achieving cure rates of 82–88%. The latter cure rate increases to greater than 90% when sexual partners are treated simultaneously. In spite of some advantages of single-dose therapy including better patient compliance, lower total dose, and possibly decreased incidence of subsequent vaginitis caused by Candida spp., however, recurrence rates of trichomoniasis are high with single-dose therapy and multidose regimes are preferred [35]. A disadvantage of single-dose therapy is the need to insist on simultaneous treatment of sexual partners. The 5-nitroimidazoles are not in themselves trichomonacidal, but low-redox proteins reduce the nitro group, resulting in the formation of highly cytotoxic products within the organisms. Aerobic conditions interfere with this reduction process and decrease the antianaerobic activity of the 5-nitroimidazoles. Most strains of T. vaginalis are highly susceptible to metronidazole, with minimum inhibitory concentrations of 1 mg/L. Similar efficacy results are reported with tinidazole, but the latter has superior activity against metronidazole-resistant isolates. Patients not responding to an initial course often respond to an additional standard course of 7 day therapy. Some patients are refractory to repeated courses of therapy even when compliance is assured, and sexual partners are known to have been treated. If reinfection is excluded, these rare patients may have strains of T. vaginalis that are resistant to metronidazole, which can be confirmed in vitro. Increased doses of metronidazole and longer duration of therapy are necessary to cure these refractory patients. The patients should be given maximal tolerated dosages of oral metronidazole of 2–4 g/day for 10–14 days. Considerable success has been observed in treating resistant infections with oral tinidazole [45]. Most investigators use high-dose tinidazole 1–4 g/day for 14 days [45]. Rare patients not responding to nitroimidazoles can be treated with topical paromomycin. Side effects of metronidazole include an unpleasant or metallic taste. Other common side effects include nausea (10%) and transient neutropenia (7.5%). Caution should be taken when

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5-nitroimidazoles are used in patients taking warfarin. Longterm and high-dose therapy increase the risk of neutropenia and peripheral neuropathy. Treatment of symptomatic trichomoniasis in pregnancy is identical [35]. Metronidazole readily crosses the placenta, and previously because of concern for teratogenicity, some considered it prudent to avoid its use in the first trimester of pregnancy. More recently, investigators have become reassured with the use of metronidazole throughout pregnancy.

Atrophic vaginitis Atrophic vaginitis, also called urogenital atrophy, refers to the extremely common condition that is characterized by atrophy of the vagina, vestibule, and vulva as a consequence of estrogen deficiency [1]. The dominant target of estrogen deficiency is the vaginal epithelium, which loses its rugosity and undergoes progressive thinning and atrophy. Simultaneously but often less conspicuous is progressive thinning of the vestibular epithelium. Atrophy of the vaginal epithelial lining is accompanied by reduced glycogen synthesis, which serves as a critical substrate for resident bacteria that break down glycogen to produce organic acid most importantly lactic acid, further resulting in the loss of Lactobacillus species, the dominant component of vaginal microbiota. Accordingly, a consistent consequence of estrogen deficiency is the elevation of vaginal pH, usually above 5.0. Low estrogen levels reduce vaginal secretions that result in vaginal dryness, but not infrequently and paradoxically, a vaginal discharge is perceived to exist or may in fact present as a watery discharge. Atrophic vaginitis typically occurs in menopausal women, but it can also occur in women at any age who have a decrease in estrogenic stimulation to this area of the genitalia. In premenopausal women, hypoestrogenic settings include postpartum, lactation, and during the administration of antiestrogenic drugs. Vaginal atrophy that follows the gradual decline of estrogen production is often associated with manifestations at other sites including the bladder floor and urethra. Accordingly, urethral and bladder symptoms may be a manifestation of estrogen deficiency including dysuria. The loss of estrogen also has an effect on the bladder lining facilitating the development of bacterial cystitis in aging women. Another impact of estrogen deficiency relates to the loss of muscle tone and dilatation of the vaginal introitus as well as contributing to the development of prolapse of bladder, uterus, and rectum.

Clinical manifestations

The earliest effects of estrogen deficiency are progressive atrophy and diminished vaginal secretions manifesting as vaginal dryness experienced during intercourse. While early symptoms may be relieved in part by the use of vaginal lubricants, invariably, progressive estrogen deficiency will not be compensated for by the use of such lubricants. Ultimately, adequate vaginal lubrication for pain-free intercourse will require adequate estrogenic effect on the vaginal epithelium. Vaginal dryness is often experienced by women long before the onset of amenorrhea or the development of systemic vasomotor symptoms and is followed by dyspareunia. Dyspareunia is initially superficial or entry in nature, but with the progression of the vaginal atrophy, the discomfort and pain will be experienced throughout and following intercourse with discomfort and irritation and even itching, lasting for several days after intercourse. With advanced atrophy, patients may complain of postcoital bleeding as a result of the susceptibility

of the thinned vaginal epithelium to the effects of local friction and trauma.

Diagnosis

Vaginal atrophy and estrogen deficiency can be easily diagnosed without the use of sophisticated testing. The vaginal pH becomes elevated in excess of 4.5 and may reach levels in excess of 6. The vaginal pH is an excellent marker of estrogen deficiency. The elevated pH is a consequence of the loss of the lactic and other organic acid–producing bacteria. Lactic acid–producing bacteria are replaced in part by Gram-negative organisms, usually coliform, which in their own right are not pathogenic. On wet mount microscopy, the paucity of the typical rod-shaped bacterial morphotypes is apparent. Another important diagnostic feature is the appearance of parabasal epithelial cells reflecting a lack of maturation of basal and parabasal cells in the absence of adequate estrogen stimulation to achieve full maturation effect. Increase in the number of parabasal cells will confirm the diagnosis in the presence of elevated pH and altered bacterial flora. It is also unnecessary and often misleading to measure serum estradiol levels. The latter test is redundant and does not parallel vaginal findings. Neither does receipt of oral nor transcutaneous estrogen products preclude the development of vaginal atrophy.

Treatment

One of the most remarkable biological miracles is the reversible nature of vaginal atrophy. Following adequate estrogen replacement, especially by the vaginal route, a rapid transformation can be anticipated with the reversal of the vaginal thinning together with reconstitution of healthy, protective bacterial flora with a dominant lactobacillus morphotype as well as the return to normal vaginal pH and accompanied by the disappearance of parabasal cells [46]. This dramatic change can be expected within 4–6 weeks of adequate estrogen replacement therapy. A number of local vaginal treatments may be used to rectify atrophic vaginitis. These include intravaginal estradiol as creams, vaginal suppositories of estradiol, or removable ring releasing estradiol. Alternatively, intravaginal estriol may be used. Not infrequently, vaginal atrophy continues and progresses in the presence of systemic estrogen therapy. Accordingly, one should always insist on local intravaginal therapy. A more recent alternative is the use of the estrogen-releasing vaginal rings of which several varieties are available. One can anticipate a return to vaginal health within 1–2 months although the use of lubricants during intercourse may still be required.

Noninfectious vaginitis and vulvitis Women often present with acute or chronic vulvovaginal symptoms of noninfectious etiology. These symptoms are indistinguishable from those of infectious syndromes but are most commonly confused with those of acute Candida vaginitis (e.g., pruritus, irritation, burning, soreness, and variable discharge). Noninfectious causes of vaginitis and vulvitis include physical irritants (e.g., minipads), chemical irritants (e.g., spermicides, Betadine, topical antimycotics, soaps and perfumes, and topical 5-fluorouracil), and allergens responsible for immunologic acute and chronic hypersensitivity reactions, including contact dermatitis (e.g., latex condoms and antimycotic creams). There is an enormous list of topical factors that are responsible for local inflammatory reactions and symptoms, and many more are yet to

Textbook of Female Urology and Urogynecology

636 be defined. Depending on the site of contact, symptoms may be vaginal or vulvar. A noninfectious mechanism may coexist with or follow an infectious process and should be considered when (1) the three common infectious causes of vulvovaginal symptoms, as well as hormone deficiency, are excluded, (2) the vaginal pH and saline content are normal, and (3) KOH microscopy and a yeast culture are negative. Unfortunately, given the anticipated 20% colonization rates in normal asymptomatic women, a positive yeast culture sometimes reflects the presence of an “innocent bystander” organism rather than the cause of a patient’s vulvovaginal symptoms. The only logical way of establishing the role of Candida in this context is to treat the patient with an oral antifungal agent and assess the clinical response. Once a local chemical, irritant, or allergic reaction is suspected as the cause of vaginitis and/or vulvitis, a detailed inquiry into possible causal factors is essential. Offending agents or behaviors should be eliminated whenever possible, including the avoidance of chemical irritants and allergens (e.g., soaps and detergents). The immediate management of severe vulvovaginal symptoms of noninfectious etiology should not rely on topical corticosteroids, which are rarely the solution to such symptoms; moreover, highpotency steroid creams often cause intense burning. Local relief measures include sodium bicarbonate sitz baths and oral antihistamines. Finally, an uncommon cause of purulent vaginitis called desquamative inflammatory vaginitis may cause chronic vulvovaginal symptoms and requires referral to vaginitis specialists [47].

References 1. Eckert LO. Clinical practice. Acute vulvovaginitis. N Engl J Med 2006;355:1244–1252. 2. Berg AO, Heidrich FE, Fihn SD et al. Establishing the cause of genitourinary symptoms in women in a family practice. Comparison of clinical examination and comprehensive microbiology. JAMA 1984;251:620–625. 3. Sobel JD. Vulvovaginal candidosis. Lancet 2007;369:1961–1971. 4. Foxman B. Epidemiology of vulvovaginal candidiasis: Risk factors. Am J Public Health 1990;80:329–331. 5. Spinillo A, Capuzzo E, Egbe TO, Baltaro F, Nicola S, Piazzi G. Torulopsis glabrata vaginitis. Obstet Gynecol 1995;85:993–998. 6. Pirotta M, Gunn J, Chondros P et al. Effect of lactobacillus in preventing post-antibiotic vulvovaginal candidiasis: A randomised controlled trial. BMJ 2004;329:548. 7. Fidel PL Jr, Sobel JD. Immunopathogenesis of recurrent vulvovaginal candidiasis. Clin Microbiol Rev 1996;9:335–348. 8. Smeekens SP, van de Veerdonk FL, Kullberg BJ, Netea MG. Genetic susceptibility to Candida infections. EMBO Mol Med 2013;5:805–813. 9. Wang X, van de Veerdonk FL, Netea MG. Basic genetics and immunology of Candida infections. Infect Dis Clin North Am 2016 Mar;30(1):85–102. doi: 10.1016/j.idc.2015.10.010. PMID: 26897063. 10. Giraldo PC, Bubula O, Gomcalves AK et al. Mannose-binding lectin gene polymorphism, vulvovaginal candidiasis and bacterial vaginosis. Obstet Gynecol 2007;109:1123–1128. 11. Babula O, Lazdāne G, Kroica J, Linhares IM, Ledger WJ, Witkin SS. Frequency of interleukin-4 (IL-4)-589 gene polymorphism and vaginal concentrations of IL-4, nitric oxide, and mannose-binding lectin in women with recurrent vulvovaginal candidiasis. Clin Infect Dis 2005;40:1258–1262. 12. Hooton TM, Roberts PL, Stamm WF. Effects of recent sexual activity and use of a diaphragm on the vaginal microflora. Clin Infect Dis 1994;19:274–278. 13. Spinillo A, Carrato L, Pizzoli G et al. Recurrent vulvovaginal candidiasis: Results of a cohort study of sexual transmission and intestinal reservoir. J Reprod Med 1992;37:353–447. 14. Richardson JP, Willems HME, Moyes DL et al. Candidalysin drives epithelial signaling, neutrophil recruitment, and immunopathology at the vaginal mucosa. Infect Immun 2018;86: e00645–17. 15. Swidsinski A, Guschin A, Tang Q et al. Vulvovaginal candidiasis: histologic lesions are primarily polymicrobial and invasive and do not contain biofilms. Am J Obstet Gynecol 2019;220(1):91.e1–91.e8. PubMed: 30595144.



















16. Nurbhai M, Grimshaw J, Watson M, Bond Cm, Mollison J, Ludbrook A. Oral versus intravaginal imidazole and triazole anti-fungal treatment of uncomplicated vulvovaginal candidiasis (thrush). Cochrane Database Syst Rev 2007;(4): CD002845 doi: 10.1002/14651858.CD002845.pub2. PMID: 17943774. 17. Pappas PG, Kauffman CA, Andes D et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009;48:503–535. 18. Sobel JD, Brooker D, Stein GE et al. Single oral dose fluconazole compared with conventional clotrimazole topical therapy of Candida vaginitis. Fluconazole Vaginitis Study Group. Am J Obstet Gynecol 1995;172 (4 Pt 1):1263–1268. 19. Sobel JD, Kapernick PS, Zervos M et al. Treatment of complicated Candida vaginitis: Comparison of single and sequential doses of fluconazole. Am J Obstet Gynecol 2001;185:363–369. 20. Sobel JD, Chaim W. Treatment of Candida glabrata vaginitis: A retrospective review of boric acid therapy. Am J Obstet Gynecol 1997;24:649–652. 21. Ray D, Goswami R, Banerjee U et al. Prevalence of Candida glabrata and its response to boric acid vaginal suppositories in comparison with oral fluconazole in patients with diabetes and vulvovaginal candidiasis. Diabetes Care 2007;30:312–317. 22. Marchaim D, Lemanek L, Bheemreddy S, Kaye KS, Sobel JD. Fluconazole-resistant Candida albicans vulvovaginitis. Obstet Gynecol 2012 Dec;120(6):1407–1414. doi: 10.1097/aog.0b013e31827307b2. PMID: 23168767. 23. Sobel JD, Wiesenfeld HC, Martens M et al. Maintenance fluconazole therapy for recurrent vulvovaginal candidiasis. N Engl J Med 2004;351:876–883. 24. Donders G, Bellen G, Byttebier G et al. Individualized decreasing-dose maintenance fluconazole regimen for recurrent vulvovaginal candidiasis (ReCiDiF trial). Am J Obstet Gynecol 2008;199:613.e1–613.e9. 25. Collins LM, Moore R, Sobel JD. Prognosis and long-term outcome of women with idiopathic recurrent vulvovaginal candidiasis caused by Candida albicans. J Low Genit Tract Dis 2020;24:48–52. 26. Eschenbach DA, Davick PR, Williams BL et al: Prevalence of hydrogen peroxide-producing Lactobacillus species in normal women and women with bacterial vaginosis. J Clin Microbiol 1989;27:251–256. 27. Peebles K, Velloza J, Balkus JE, McClleland RS, Barnabas RV. High global burden and costs of bacterial vaginosis: A systematic review and meta-analysis. Sex Transm Dis 2019;46:304–311. 28. Fredricks DN, Fiedler TL, Marrazzo JM. Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med 2005;353:1899–1911. 29. Ling Z, Kong J, Liu F et al. Molecular analysis of the diversity of vaginal microbiota associated with bacterial vaginosis. BMC Genomics 2010;11:488. 30. Swidsinski A, Mendling W, Loening-Baucke V et al. Adherent biofilms in bacterial vaginosis. Obstet Gynecol 2005;106:1013–1023. 31. Hillier SL, Krohn MA, Cassen E, Easterling TR, Rabe LK, Eschenbach DA. The role of bacterial vaginosis and vaginal bacteria in amniotic fluid infection in women in preterm labor with intact fetal membranes. Clin Infect Dis 1995;20(Suppl 2): S276–S278. 32. Platz-Christensen JJ, Sundström E, Larsson PG. Bacterial vaginosis and cervical intraepithelial neoplasia. Acta Obstet Gynecol Scand 1994;73:586–588. 33. Martin HL, Richardson BA, Nyange PM et al. Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition. J Infect Dis 1999;180:1863–1869. 34. Cherpes TL, Meyn LA, Krohn MA, Lurie JG, Hillier SL. Association between acquisition of herpes simplex virus type 2 in women and bacterial vaginosis. Clin Infect Dis 2003;37:319–325. 35. Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted disease treatment guidelines, 2015. MMWR Recomm Rep 2015;64:1–137. 36. Hauth JC, Goldenberg RL, Andrews WW, DuBard MB, Copper RL. Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis. N Engl J Med 1995;333:1732–1736. 37. Schwebke JR, Lensing SY, Lee J et al. Treatment of male sexual partners of women with bacterial vaginosis: A randomized, double-blind, placebocontrolled trial. Clin Infect Dis 2021;73: e672–e679. 38. Sobel JD, Sobel R. Current and emerging pharmacotherapy for recurrent bacterial vaginosis. Expert Opin Pharmacother. 2021 Aug;22(12):1593– 1600. doi: 10.1080/14656566.2021.1904890. Epub 2021 Mar 29. PMID: 33750246 39. Reichman O, Akins R, Sobel JD. Boric acid addition to suppressive antimicrobial therapy for recurrent bacterial vaginosis. Sex Transm Dis 2009;36:732–734. 40. Cohen CR, Wierzbicki MR, French AL et al. Randomized trial of Lactin-V to prevent recurrence of bacterial vaginosis. N Engl J Med 2020;382:1906–1915.

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41. Sutton M, Sternberg M, Koumans EH, McQuillan G, Berman S, Markowitz L. The prevalence of Trichomonas vaginalis infection among reproductive-age women in the United States, 2001–2004. Clin Infect Dis 2007;45:1319–1326. 42. Wølner-Hanssen P, Krieger JN, Stevens CE et al. Clinical manifestations of vaginal trichomoniasis. JAMA 1989 Jan 27;261:571–576. 43. Moodley P, Wilkinson D, Connolly C, Moodley J, Sturm AW. Trichomonas vaginalis is associated with pelvic inflammatory disease in women infected with human immunodeficiency virus. Clin Infect Dis 2002;34:519–522.

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44. Schwebke JR, Hobbs MM, Taylor SN et al. Molecular testing for Trichomonas vaginalis in women: Results from a prospective U.S. clinical trial. J Clin Microbiol 2011;49:4106–4111. 45. Sobel JD, Nyirjesy P, Brown W. Tinidazole therapy for metronidazole-resistant vaginal trichomoniasis. Clin Infect Dis 2001;33:1341–1346. 46. North American Menopause Society. The role of local vaginal estrogen for treatment of vaginal atrophy in postmenopausal women: 2007 position statement of The North American Menopause Society. Menopause 2007;14:355–369. 47. Reichman O, Sobel JD. Desquamative inflammatory vaginitis. Best Pract Res Clin Obstet Gynaecol 2014;28:1042–1050. PMID: 25132275.

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THE IMPACT OF PREGNANCY AND CHILDBIRTH ON THE PELVIC FLOOR Martino Maria Zacchè and Philip Toozs-Hobson Bladder, bowel and vaginal symptoms are often considered to be inevitable sequelae of vaginal delivery (VD). Blomquist et al. reported on a cohort of 1,528 parous women, who were recruited 5 to 10 years after their first delivery and evaluated annually for up to 9 years [1]. The cumulative incidence of each pelvic floor disorder (PFD) was described using each woman’s first delivery as the time of origin. Temporal distinctions among PFDs were evident, with pelvic organ prolapse (POP) having a much longer latency, while stress urinary incontinence (SUI) had a high incidence in the first few years after delivery. VD is known to have a detrimental effect on the pelvic floor, although other factors may play a role, such as genetics, ethnicity, age, hormonal status and obesity [2]. In the last decade, biomechanics of childbirth have also been studied and computational models have been introduced to gain greater insight into the relationship between VD and pelvic floor trauma. Maternal adaptations in preparation for parturition have been documented in the pelvic floor musculature. It is an astonishing feature of the pelvic floor muscles that, during birth, they can stretch to over three times their original length without injury [3]. This chapter will initially focus on the impact of pregnancy on the pelvic floor anatomy and function. Then, we will consider the pathophysiology of childbirth-related injuries. Finally, we will discuss the main PFDs.

Pregnancy – effect on the pelvic floor function Muscle/ligaments

The pelvic floor consists of muscle fibres and connective tissue, which provide support for the bladder, vagina, uterus and bowel. The levator ani muscle (LAM) is the main pelvic floor muscle and consists of five parts: the pubovaginal, puboperineal and puboanal portions, which form the pubovisceral complex, the puborectalis and iliococcygeus muscles. Historically, PFDs have been associated with VD and pelvic floor injuries. However, there is good evidence suggesting that women delivered by Caesarean Section (CS) only may also be affected. This suggests that there is an interaction between childbearing and the pelvic floor. In the last decade, pregnancy-driven pelvic floor adaptations in morphology and function have been the focus of research in animal models. Alperin et al. studied pregnancy-driven remodelling mechanisms in rats [4]. During pregnancy, hormones affected the intrinsic structure of coccygeus, iliocaudalis and pubocaudalis muscles. The architectural changes consisted of an increase in the number of sarcomeres in series (sarcomerogenesis) and elongation of the muscle fibres by 21–37%. Changes in the quantity of intramuscular extracellular matrix were also documented, resulting in increased stiffness of the pelvic floor muscles [5]. These changes did not occur in the tibialis anterior muscle, which was used as a control. Catanzarite et al. showed that these structural and functional adaptations 638

protect from pelvic floor trauma, attenuating delivery-related strains and sarcomere hyperelongation [6]. Pregnancy-induced adaptations have also been studied at the molecular level, showing a difference in the protein expression between pelvic floor and limb muscles in the rat model [7]. Pregnancy can also affect the properties of human pelvic floor tissues, through remodelling mechanisms and biochemical changes. A case-control study found a higher incidence of mild POP in nulliparous pregnant vs. non-pregnant women [8]. Protective changes appear to occur at a greater extent in younger women. As such, increased maternal age at first delivery has been associated with obstetric trauma and explains why age may be a risk factor [9]. Anatomical and biochemical adaptations have been prospectively evaluated in 173 nulliparous women using Pelvic Organ Prolapse Quantification (POP-Q) and vaginal elastase activity, respectively [10]. Higher first-trimester elastase activity was associated with an uncomplicated spontaneous VD. Positive predictor factors for VD were a lower body mass index (BMI) in the first trimester and a younger age and a greater vaginal relaxation on third-trimester POP-Q points. Further data supporting an association between the remodelling of the vaginal matrix and uncomplicated VD derive from a study evaluating the activity of metalloproteinase 9 (MMP-9), a key vaginal elastase [11]. Women with a higher postpartum MMP-9 activity were more likely to achieve an uncomplicated VD. Interestingly, this study also showed that women with higher MMP-9 activity are more likely to recover an acute vaginal angle, which results from the joint action of the LAM (pulling the distal vagina towards the pubic bone) and the utero-sacral ligaments (pulling the proximal vagina towards the sacrum). The significance of these findings is not fully understood. However, remodelling may explain why some women experience a better recovery after a VD and may be less likely to develop PFDs in the long term.

Urinary tract in pregnancy

The urinary tract undergoes both structural and functional changes during pregnancy and after delivery. The kidneys grow by 1 cm in length, while their volume increases up to 30%. This is attributed to increased kidney vascular interstitial volume. Dilation of the ureters is noted in approximately 90% of women by the third trimester. This change is usually more marked on the right, and it results mainly from mechanical compression. The left side is protected by the loaded sigmoid colon. Also, the right ureter crosses the iliac and ovarian vessels at an angle before entering the pelvis, while this is less pronounced on the left side [12]. The dilated collecting system can hold up to 300 mL of urine, leading to urinary stasis and explaining the increased risk of pyelonephritis in pregnant women. There is a 40–50% increase in glomerular filtration rate and a 60–80% increase in the effective renal plasma flow. As a result, serum creatinine, urea and urate levels are lower than the normal range for non-pregnant women [13].

DOI: 10.1201/9781003144236-66

The Impact of Pregnancy and Childbirth on the Pelvic Floor The bladder is passively drawn upwards and anteriorly as the uterus enlarges, resulting in the lengthening of the urethra. The urethral mucosa becomes more hyperaemic and congested, and the detrusor muscle hypertrophies in pregnancy in response to the increase in circulating oestrogen levels. After delivery, cystoscopy of the bladder shows changes such as mucosal congestion, submucosal haemorrhage and capillary oozing, especially around the bladder neck, trigone and ureteric orifices. These changes have been seen in association with a decrease in bladder sensation and tone and are mostly marked in those who have a VD [14]. Studies assessing bladder capacity have revealed conflicting results, with most early studies using simple cystometry only. Muellner [15] reported an increase in bladder capacity to an average of 1,300 mL in the third trimester due to bladder hypotonia, with a return to normal values postpartum. However, other investigators found no change in bladder capacity in the first trimester and a reduced bladder capacity in the third trimester in association with increased detrusor irritability rather than bladder hypotonia [16]. Dual-channel cystometry studies have found that all urodynamic variables, such as first sensation and maximum bladder capacity, are lower in pregnancy and postpartum compared to a non-pregnant population, and this may account for symptoms of frequency, nocturia and urgency [17]. An analysis of normative bladder diaries also showed a reduction in bladder capacity during pregnancy [18]. Changes in the urethra have been considered an important element of maternal adaptation. Urodynamic studies showed an increase in both absolute and functional length of the urethra in pregnant women by respective median values of 6.7 and 4.8 mm [19]. Also, the maximum urethral closure pressure increased to 93 cmH2O at 38 weeks’ gestation and then dropped to prepregnancy values of 69 cmH2O postpartum. These changes were not seen in women complaining of UI and are postulated to be a mechanism whereby continence is maintained despite an increase in intravesical pressure.

Lower urinary tract symptoms in pregnancy Frequency and nocturia

These are the commonest and earliest symptoms to develop, as outlined in a prospective cohort study of nulliparous pregnant women [20]. Using a definition of frequency as at least seven daytime voids and one night-time void, Francis studied the voiding habits in 400 healthy women during and after an uncomplicated pregnancy and compared them with 50 healthy non-pregnant patients of similar age [16]. Frequency was reported by 59% in early pregnancy, 61% in midpregnancy and 81% in late pregnancy. Parboosingh and Doig defined nocturia as at least three night-time voids and, following the questioning of 873 healthy antenatal patients, found that nearly 66% experienced nocturia by the third trimester [21]. They also measured mean urine flow and solute excretion in 24 h and overnight collections in 100 normal and non-pregnant women. An increase in sodium excretion was the major reason for increased night-time voiding as well as the mobilisation of dependent oedema at night in the recumbent position. Cutner et al. assessed lower urinary tract symptoms in 47 women undergoing termination of pregnancy at 6–15 weeks’ gestation and found that 40% complained of frequency and 23% of nocturia [22]. The cause of frequency was not related to bladder capacity or the effect of posture but to the polydipsia and polyuria of pregnancy. Both fluid intake and output rise rapidly in the first trimester, remaining constant until the third trimester, when a decrease in sodium excretion leads to a decrease in

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output. Despite this, frequency persists related to the pressure on the bladder by the uterus.

Voiding difficulties

Urinary hesitancy may be found in up to 27% of patients in the first two trimesters [23]. Fischer and Kittel assessed flow rates in 290 women during pregnancy and found that there was a significant increase in peak flow rates in the second and third trimesters compared to controls and early pregnancy, but these higher flow rates were associated with larger voided volumes [24]. Cutner et al. assessed flow rates in pregnancy, adjusting for volume voided, and found no difference in women complaining of hesitancy or incomplete emptying, compared to pregnant women with normal voiding [22]. Urinary retention can be associated with the enlargement of a retroverted uterus with subsequent entrapment of the fundus below the sacral promontory [25]. This retention usually resolves by 16 weeks’ gestation as the uterus grows out of the pelvis and can be managed in the interim with either bladder drainage or clean intermittent self-catheterisation (CISC). Alternatively, manual reduction of the uterus can be performed or a Hodge pessary may be inserted to maintain uterine position and relieve the obstruction on the bladder neck. Clinicians should also be aware that a urethral diverticulum represents a possible, although rare, cause for new-onset voiding difficulties in pregnancy [26]. More sporadic causes for urinary retention include an enlarged fibroid uterus or a pelvic mass. Postpartum urinary retention is common, with a reported incidence of 1.7–17.9% [27]. It is more common in nulliparous women, and risk factors include anything that can disrupt sensation such as trauma associated with instrumental delivery, epidural analgesia and a longer duration of labour (≥800 minutes) [28]. The bladder can take up to 8 hours to regain normal sensation after the last top-up of an epidural [29]. Overdistension of the bladder may occur during this period, leading to permanent detrusor dysfunction, urinary tract infections, hydronephrosis and kidney failure [30]. A randomised-controlled trial highlighted that CISC is well-tolerated in 85% of women developing overt urinary retention after VD [31]. Also, CISC resulted in a significantly lower duration of catheterisation when compared to the transurethral indwelling catheter, with a median time of 12 h and 24 h, respectively.

Urinary incontinence

UI is frequently reported in pregnancy, in particular with advancing gestation. SUI is the most common form, followed by mixed urinary incontinence (MUI) and urgency urinary incontinence (UUI). Prevalence studies have shown a variety of rates according to the population. An interesting study evaluated the prevalence of UI in a multi-ethnic group of 761 women in Norway [32]. UI rates ranged from 25.5% to 45.4% according to different ethnicity. Overall, the prevalence of SUI, MUI and UUI was 71.0%, 11.7% and 9.1%, respectively. In a large cohort of 43,279 from the Norwegian Mother and Child Cohort Study, SUI was reported by 31% of nulliparous and 42% of parous women at 30 weeks’ gestation [33]. A similar prevalence was found also in other reports from Europe [34], while SUI was experienced by up to 59% of parous women in UK studies [35, 36]. A lower prevalence has been documented in China, with 18.6% of women experiencing SUI symptoms between 37- and 42-week gestation [37]. A cross-sectional study from a low-resourced setting in Nigeria has been recently published [38]. It involved 442 pregnant women

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640 receiving antenatal care in a hospital. Overall, UI was reported by 28.1% of women, with comparable rates in nulliparae (28.7%) and multiparae (27.7%). The prevalence of SUI was 17.4%, while UUI and MUI were found in 6.8% and 3.9% of the population, respectively. The aetiology of UI in pregnancy is multifactorial. In a cohort study of 12,679 primiparous women, a high weight gain (>4 kg) until 15 weeks’ gestation was associated with an increased incidence of UI at 30 weeks’ gestation [39]. Interestingly, women with high weight gain between 15 and 30 weeks’ gestations did not show such association. Reproductive hormones have also been considered. Reduction of relaxin concentrations in the third trimester has been associated with increased rates of UI; however, its mechanism is uncertain [40]. The peak of progesterone levels in late pregnancy may also cause relaxation of the smooth muscles in the urinary tract, including ureteric, bladder and urethral tone [41]. Other factors involved in the development of UI are changes in collagen properties [42], age >35 years, raised BMI and leaking less than once per month pre-pregnancy [43]. This is discussed further later in the chapter. Treatment of UI in pregnancy typically consists of pelvic floor muscle training (PFMT) [44]. Alongside conservative management, including bladder retraining and fluid modification, oxybutynin (pregnancy Category B drug) may be considered in women suffering from urgency symptoms or pre-existing detrusor overactivity.

Bowel symptoms in pregnancy

Defecatory disorders are common during pregnancy, with up to 25% of women experiencing symptoms of constipation [45]. In a prospective cohort study of 487 nulliparous pregnant women, constipation was more prevalent at 12 weeks than at 36 weeks’ gestation (8.9% vs. 4.5%), while symptoms of incomplete evacuation remained stable (10%) [46]. Similar trends were also found by Derbyshire et al., with constipation rates decreasing from the first to the third trimester, while sensations of incomplete defecation and time spent defecating were increased during all the three trimesters [47]. These changes are thought to be multifactorial

Dorsal border of pubic bone

with the contribution of both hormonal and mechanical aspects. Increased levels of progesterone have been related to prolonged gastrointestinal transit times. This may be exacerbated by nausea, poor fluid intake and increased absorption of sodium and water from the colon in response to the raised levels of aldosterone during the second trimester [48]. Compression from the gravid uterus may contribute to constipation. However, data highlighting a reduced prevalence in the third trimester do not support this “mechanical hypothesis” [49]. Increased rectal mobility, assessed through pelvic floor ultrasound and magnetic resonance (MR) defecography, has been associated with obstructed defecation syndrome (ODS) in a population of non-pregnant women [50]. Dysfunction of the LAM and neuropathy of the pudendal nerve may play a role in the development of postpartum ODS. However, its aetiology is still uncertain.

Childbirth – mechanisms of pelvic floor injury The impact of childbirth on the anatomy and physiology of the pelvic floor has been studied in depth with the implementation of advanced imaging techniques such as MR and 3D/4D ultrasound (Fig. 60.1). Revolutionary computer models have also enabled researchers to study pelvic floor changes with loading, allowing individual components of the support system to be altered in a way not possible in human subjects. There are two major mechanisms by which VD causes pelvic floor trauma: muscle trauma and nerve injury. This section will not include trauma associated with episiotomy, as this is extensively discussed in a separate chapter (“Episiotomy and perineal reconstruction”).

Muscle trauma

Lien et al. performed a simulation of VD through biomechanical modelling, evaluating changes to the LAM [51]. A stretch ratio, defined as tissue length under stretch/original tissue length, was calculated at different LAM levels. The pubococcygeus muscle, the shortest, most medial and ventral portion of LAM, was at

Hypoechogenic horseshoe of rhabdosphincter

Ventral border of pubic bone Right anterior vaginal sulci

Probe artefact

Hyperechogeni core of urethra Pubococcygeus

Rectum

FIGURE 60.1  Ultrasound of the pelvic floor. (From Chaliha C, Pregnancy and childbirth and the effect on the pelvic floor, in: Cardozo L and Staskin D, eds., Textbook of Urogynaecology and Female Urology, 3rd ed., Informa Healthcare, London, U.K., 2010, pp. 554–566. With permission.)

The Impact of Pregnancy and Childbirth on the Pelvic Floor greatest risk of strain-related injury, with a stretch ratio of 3.26. This was proportional to foetal head size. In fact, if its diameter increased by 9%, there was a subsequent 9% increase in pubococcygeus stretch. In an MR-simulated model of vaginal birth, a maximum stretch ratio of 3.5 was seen in the posteromedial aspect of the puborectalis muscle [52]. Simulated decrease in stiffness of the lateral attachments of the LAM (iliococcygeus to arcus tendineus levator ani attachments) resulted in decrease in the maximal levator stretch. Authors hypothesised that a more rigid levator in nulliparous women could be subjected to higher stretch during childbirth than multiparous. Thus, the first VD may predominantly contribute to PFDs, such as UI development, which is associated with bladder neck mobility. Subsequent research has examined the shear forces applied to the pelvic floor. Ashton-Miller et al. assessed the biomechanics of the pelvic floor muscles, demonstrating the pelvic floor sustains a pressure of 37N while standing and 19N in supine position [53]. Straining to pass a stool increases the pressure to 92N. However, these pressures rise dramatically in active second stage of labour to 120N during each contraction with active pushing. An additional traction force is applied during instrumental delivery, which can reach 113N with ventouse and 200N with forceps. A further study demonstrated that contracting pelvic floor muscles become stiffer and may be an obstacle to the descending foetal head and suggested that pelvic floor muscle exercises may improve muscle control and flexibility [54]. This may result in a higher risk of muscle stretch injury near the levator hiatus with a tearing direction perpendicular to the hiatal edge. In a subjectspecific pelvic floor model, the muscle stretch bordering the levator hiatus was inhomogeneous, with an average hiatal stretch ratio of 3.55 [55]. Areas at highest risk for stretch-related injury were the pubovisceral muscle enthesis and the muscle near the perineal body, with a peak stretch ratio of 4.64 and 4.15, respectively. More recently, the stretch in LAM has been estimated using MR images during a live birth of a 2.585 kg baby in a woman with one previous VD [56]. A maximum stretch ratio of 2.5 was found on the posterior-medial portion of the LAM. This was lower than previous estimates. This may be related to the parity, as the genital hiatus is often larger and less susceptible to stretchrelated injuries, and the baby’s weight, which was smaller than average. However, the location of the maximum stretch region matched with previous simulations.

US

MRI

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The prevalence of LAM injuries is 13–36% after VD [57]. Both micro- and macro-trauma have been reported, as a result of stretch (overdistension) or avulsion (disruption) of the muscle. MR was introduced to assess LAM by Strohbehn et al. in 1996 [58]. Subsequently, 3D/4D perineal ultrasound has been used as it is more widely available, cheaper, repeatable and accurate [59] (Figs. 60.2 and 60.3). Different obstetric factors have been associated with the occurrence of LAM injuries. Valsky et al. evaluated risk factors for LAM avulsion in a group of 210 primiparous women [60]. A large head circumference in the newborn (≥ 35.5cm) and a prolonged second stage (≥ 110 min) increased the odds of LAM trauma by a factor of 5.32. A systematic review aimed to provide high-quality evidence regarding the contribution of delivery mode to LAM trauma [61]. Three meta-analyses were carried out: forceps vs. ventouse (9 studies), forceps vs. normal VD (12 studies) and ventouse vs. normal VD (12 studies). Forceps was a strong risk factor for LAM trauma, with an OR of 6.94 and 4.57, when compared with normal VD and ventouse, respectively. Although a trend towards an association with LAM trauma was seen, ventouse did not reach statistical significance as a risk factor when compared to normal VD. A recent study used an in vitro simulation model to assess the spatial requirements of forceps delivery and its impact on LAM trauma [62]. The mean increase in circumference of the foetal head model was 1.64 cm for Neville-Barnes forceps. This resulted in an OR of 1.19 for LAM avulsion, which was considerably lower than expected. Thus, there are other elements that may play a role during forceps delivery, such as increased speed of distension and application of greater forces. It is therefore likely that a change in obstetric practice, with an increase in ventouse over forceps rate, will reduce the burden of pelvic floor trauma [63]. Clinicians aiming to predict pelvic floor trauma should also take into consideration maternal characteristics. For example, increased maternal age has been associated with LAM avulsion [64, 65]. Histopathological changes and subsequent loss of elasticity have been implicated. Other relevant antenatal factors are a lower BMI and decreasing bladder neck descent (marker of hiatal distensibility). In fact, obesity seems to be protective against trauma by modifying biochemical properties of the muscle and connective tissue (also known as the “marbled steak” effect), while a larger genital hiatus is more prone to stretch, therefore reducing the risk of LAM avulsion [65].

TUI

FIGURE 60.2  Unilateral avulsion on ultrasound, MRI and tomographic ultrasound. (Courtesy of H.P. Dietz.)

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FIGURE 60.3  Typical bilateral avulsion injury seen in primiparous patient (forceps) as seen in the axial plane (right image). The defects are indicated by*. (Reproduced from Gamble JA and Creedy DK, Birth, 27, 256, 2000. With permission and courtesy of H.P. Dietz.)

Researchers have been trying to build accurate prediction models for LAM avulsion in order to target women at risk and offer them timely treatment, such as PFMT. Delft et al. reported on a model and nomogram for postnatal women to estimate the individual risk of having sustained LAM avulsion [66]. This was related to childbirth only and identified obstetric anal sphincter injury (OASI), prolonged second stage of labour and forceps delivery as risk factors. Alternative measures to predict trauma have been subsequently described by Rostaminia et al. [67], who used ultrasound to measure the pelvic floor biometry at 36 weeks’ gestation. Foetal head circumference (FHC) and minimal levator hiatus circumference (MLHC) were obtained. LAM stretch ratio (calculated by multiplying the ratio FHC/MLHC × baby’s weight in kg) was found to be associated with severe LAM trauma. More recently, “capacity-to-demand” geometric ratio has been calculated through biomechanical analysis [68]. Bony and soft tissue factors, respectively, the pelvis and the pelvic floor, were the maternal “capacity,” while foetal “demand” consisted of variations in foetal head and size. This new framework aims to predict whether a mother is likely to deliver a head of given size without LAM trauma.

Nerve injury

The pelvic floor is innervated by the pudendal and levator ani nerves. There is evidence suggesting that labour and VD are major risk factors for neurologic injury. This was first documented by Snooks et al. who studied 71 women after delivery with pudendal nerve terminal motor latency (PNTML) and electromyography (EMG) and 51 women before and after delivery with EMG [69]. The study showed an increase in anal sphincter striated muscle fibre density at 2 months following VD, which was suggestive of reinnervation following denervation. This was associated with an increased risk of anal incontinence (AI). Stretch and ischemic compression are considered the two pathophysiological mechanisms for trauma to motor fibres. The pudendal nerve is particularly susceptible to compression and damage at the point where it curves around the ischial spine and enters the pudendal canal enclosed in a tight fibrous sheath. Sensory function can also be concomitantly affected and play a role in the development of PFDs

[70]. In a 3D computer model of VD, pudendal nerve strain was evaluated [71]. There was a direct correlation between the degree of strain and perineal descent, with the maximum strain of 35% exhibited at the inferior rectal branch of the pudendal nerve. The strain in the perineal branches innervating the anal sphincter, the posterior labia and the urethral sphincter reached values of 33%, 15% and 13%, respectively. Neurologic injury results in demyelination of the fibres. In rat models of birth trauma, there was evidence of injury in L6–S1 spinal cord segments as well as a decrease in ganglion cells in the neural plexuses posterolateral to the vagina [72]. Allen et al. prospectively evaluated 96 nulliparous women using concentric needle single-fibre EMG and PNTML [73]. Electrophysiologic tests were performed within 5 days and 2 months postpartum. Evidence of reinnervation in the pelvic floor muscles was found in 80% of primiparous women 2 months after VD. Obstetric factors associated with EMG evidence of nerve damage were high birth weight and long second active stage of labour. Sultan et al. [74] investigated the pudendal nerve function before and after the delivery and found that PNTML was significantly prolonged at 8 weeks’ postpartum, especially on the left side, which the authors postulated could be due to the unequal traction from the foetal head on the two sides of the pelvic floor during the descent down the birth canal. When restudied after 6 months, PNTML returned within the normal range in two out of three cases. Interestingly, there was a correlation between the degree of perineal descent and the incremental change in PNTML. However, no relationship between abnormal neurophysiology and symptoms of AI was shown. Subsequently, Tetzschner et al. demonstrated an increase in PNTML after VD and after CS during labour, in particular in women with UI [75]. Patients with SUI have been shown to have abnormal conduction in the perineal branch of the pudendal nerve, which innervates the periurethral striated muscle and pubococcygeus muscle [76]. The degree of pudendal nerve damage was greater in multiparous women and was associated with the use of forceps and a longer second stage of labour. Five years after delivery, Snooks et al. found manometric and neurophysiological evidence of partial denervation of the pelvic floor striated sphincter musculature

The Impact of Pregnancy and Childbirth on the Pelvic Floor [77]. This suggests that denervation may progress with future deliveries and ageing, therefore predisposing women to develop PFDs. In fact, in the same group of women, pudendal neuropathy was more marked in those with SUI symptoms. Also, sphincter weakness can be attributed not only to the loss of motor units but also to the asynchronous activity in those units that remain [78]. Thus, VD can induce both quantitative and qualitative changes, while an elective CS appears to be protective against these changes [74, 75]. Sensory nerve function may also be affected by nerve damage. The anal canal has a greater variety of afferent nerve endings than the rectum. These allow the detection of differences in touch, temperature and pain in the anal canal. The rectum has a configuration of nerve plexuses that serves as specialised sensory receptors for distension, perception of fullness, urgency to defecate and pain. It is believed that the sensory information is critical to the preservation of continence, and in patients with faecal incontinence, there is a significant reduction in the ability to perceive electrical and other forms of stimulation [79]. In pregnancy, however, the role of anal sensation is unclear as deficits in anal canal sensation appear to be transient and unrelated to the development of incontinence [80].

Childbirth – impact on pelvic floor disorders Approximately 45% of the female population suffer from PFDs. Of these, UI is the most common, with an estimated prevalence of 30–60%, followed by AI with 11–15% and POP with 5–10%. PFDs have a negative effect on the quality of life, including working ability, sporting activity and sexual activity. Women are more likely to experience PFDs either immediately after delivery or years later. As such, with the increase in life expectancy, the burden of PFDs is projected to increase further over the coming years [81]. Approximately 20% of women undergo POP or SUI surgery before 85 years of age [82]. Parity and VD are well-documented risk factors, and their impact is maintained over time. The evidence suggests that not only the first VD but also subsequent VDs play an important role with regard to the risk of developing PFDs, with POP having the strongest association with delivery mode [83].

Urinary incontinence

UI is common during pregnancy and increases with advancing gestation. In a cohort of 515 nulliparous pregnant women, the prevalence of SUI and UUI was 18.6% and 6.4% at 12 weeks’ gestation. In the third trimester, 42.1% and 19.2% of women reported SUI and UUI, respectively [20]. In a prospective study, Viktrup et al. [34] interviewed 305 primiparae and found that 32% developed SUI during pregnancy and 7% after delivery. Only 3% had SUI at 1 year. However, in a subsequent follow-up study of the same women, they reported a prevalence of SUI of 30% at 5 years [84]. In those without symptoms after the first delivery, the incidence was 19%. However, in those who reported SUI 3 months after the first delivery, 92% had SUI 5 years later. A prospective cohort study of 949 women, which was undertaken to find risk factors for postpartum SUI at 3 months, found that SUI was experienced by 22.3% before pregnancy, 65.1% during the third trimester and 31.1% after delivery [85]. Regardless of the mode of delivery, women with SUI during pregnancy had a two-fold risk of postpartum SUI. The largest community-based epidemiological study of UI (EPINCONT) assessed 15,307 women who were younger than 65 years and were grouped according to obstetric performance

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as “had not delivered,” “delivered only by CS” or “only VDs” [86]. The authors reported that the prevalence of any UI was 10.1% in nulliparous women, 15.9% in the CS-only group and 21.0% in the VD-only group. Prevalences did not differ significantly according to whether the CS was elective or non-elective. Therefore, pregnancy itself may also be an etiological factor in the development of any UI. As compared with nulliparous women, women who had a CS had an OR for any UI of 1.5 (95% CI 1.2–1.9). The OR for any UI and moderate-to-severe UI with VD as compared to CS was 1.7 (95% CI 1.3–2.1) and 2.2 (95% CI 1.5–3.1), respectively. A recent large population-based study aimed to compare the effects of different kinds of operative deliveries on SUI and UUI. In women aged younger than 50 years, forceps delivery had a higher risk of SUI when compared to either VD (OR 1.42, 95% CI 1.09–1.86) and vacuum (OR 1.76, 95% CI 1.20–2.60) [87]. The exact aetiological mechanism of UI following childbirth is unclear and probably multifactorial. The external urethral sphincter may become hypoxic during vaginal distension [88]. Also, the pudendal nerve can be compressed and stretched during VD in Alcock’s canal proximal to where it innervates the external urethral sphincter [71]. Finally, other pelvic floor trauma may be implicated. For example, the vagina itself may be torn away from its intrapelvic attachment, with the loss of anterior vaginal wall support and increase in the mobility of the bladder neck and proximal urethra. Trauma of childbirth has been simulated in a rat model. The combination of pudendal nerve crush and vaginal distension results in a more severe and durable dysfunction than either pudendal nerve crush or vaginal distension alone [89]. In a recent cross-sectional study, defects in the pelvic floor anatomy were evaluated in women with cystocele [90]. Both apical support and LAM were found to be predisposing factors, and their injury may be correlated with the later development of SUI. However, it is less clear whether the continence mechanism depends more on a normal anatomy or a functioning urethra. A case-control study evaluated both urethral function and bladder neck mobility in 80 primiparous women with de novo SUI 9–12 months after VD [91]. These were compared to 80 primiparous continent and 80 nulliparous continent women. Maximal urethral closure pressure was the variable most strongly associated with de novo SUI in primiparae, and it was identified as the dominant factor in the pathophysiology of SUI. Women with SUI were also found to have a shorter urethral functional length. The association between pubovisceral muscle tear and urethral function has been recently studied during the first year postpartum in a cohort of 56 women [92]. During an attempted pelvic floor contraction, women with a pubovisceral muscle tear (n = 21) had a significantly lower urethral closure pressure. Interestingly, urethral pressures at rest did not differ between the two groups. It is therefore plausible that symptoms of SUI in women with pubovisceral muscle tear may have a suboptimal response to PFMT. Trauma to pelvic floor structures (nerves, muscles and connective tissue) during pregnancy and VD does not always lead to overt SUI, but it certainly represents a risk factor for later development of SUI. Transient antenatal or postnatal SUI symptoms are strongly associated with recurrent SUI. This suggests that, although functional recovery from postpartum SUI often occurs, there are latent pathophysiologic changes, which could predispose to develop SUI later in life [93].

Pelvic organ prolapse

Data from a large Swedish cohort study suggest that VD significantly increases the lifetime risk of needing POP surgery [83].

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FIGURE 60.4  Comparison between posterior compartment imaging (midsagittal plane) in the third trimester (left) and 3 months postpartum (right) on maximal Valsalva manoeuvre. The anorectal junction appears normal on the left. On the right, there is a rectocele, with a depth of about 2 cm, filled with stool. (Reproduced from Dietz HP and Steensma AB, Br J Obstet Gynecol, 113, 264, 2006. With permission and by courtesy of H.P. Dietz.) When compared with CS, the risk increased 9-fold both after non-instrumental VD and after vacuum extraction and 20-fold after forceps. The pathogenetic link between POP and childbirth is unclear. MR and 3D/4D ultrasound have provided new knowledge regarding the levator ani complex. Detachment of LAM from the pelvic sidewall, avulsion, is only found in VD parous women. LAM avulsion increases two-fold the risk of significant POP. Also, its prevalence is about four times greater in women with POP-Q stage II or higher [94]. Avulsion causes alterations in the pelvic floor anatomy, including an increase in the levator hiatus size and a reduction in pelvic muscle strength. These factors may explain to a large extent the effect of avulsion on POP [95]. The association

between avulsion and POP is especially strong for the anterior and central compartments. A cystocele with an intact retrovesical angle is more likely to be associated with avulsion injury [96]. A longitudinal study of parous women annually assessed the prevalence of PFDs and found that POP had the strongest association with LAM avulsion [97]. Childbirth has also been implicated in the aetiology of rectocele, and in particular, vaginal parity has been associated with the descent of rectal ampulla and rectocele depth [98]. The herniation of the rectocele occurs through a defect of the rectovaginal septum (or Denonviller’s fascia). It is plausible that the foetal head may displace the septum downwards, and the disruption may worsen with each delivery (Figs. 60.4 and 60.5).

FIGURE 60.5  Comparison between posterior compartment imaging (midsagittal plane) in the third trimester (left) and 3 months postpartum (right), on maximal Valsalva. The anorectal junction is normal on the left. The right image shows increased bladder descent and perineal mobility, resulting in the displacement of the rectal ampulla below the symphysis pubis. There is no actual rectocele, that is, no defect of the rectovaginal septum shown in Figure 60.4. (Reproduced from Dietz HP and Steensma AB, Br J Obstet Gynecol, 113, 264, 2006. With permission and by courtesy of H.P. Dietz.)

The Impact of Pregnancy and Childbirth on the Pelvic Floor Another potential mechanism for developing POP is covert damage to connective tissue or pelvic floor muscles. This may result from either stretching or avulsion of structures. Notably, different pathogenic factors may coexist in one individual. However, it is still unclear why it may take many years until women develop POP symptoms. This may be explained by the effect of lesser injuries, biological ageing or other external components (i.e. BMI).

Anal incontinence

In a large national population-based study, women following VD were found to be at higher risk for developing AI compared with CS, with an OR of 1.65 (95% CI 1.49–1.82) [99]. For the CS group compared to the nulliparous control group, the OR of being diagnosed with AI was 1.31 (95% CI 1.16–1.46). This study suggests that there are other factors associated with pregnancy that may play a role, such as pregnancy-related mechanical and hormonal changes. OASI, defined as a partial or complete disruption of the anal sphincter muscles following childbirth, is believed to be a major risk factor for AI in adult women (Figs. 60.6, 60.7 and 60.8). Operative VD, and in particular forceps delivery, is associated with OASI. Maternal and obstetric characteristics associated with AI 12 months postpartum have been evaluated in a prospective cohort study including a total of 603 primiparous women [100]. A major OASI (3c and 4) was associated with AI, with a prevalence of 33–35% and a four-fold higher risk compared to women with no, labia or first-degree rupture. Obesity was also

found to increase the development of AI, probably as a result of raised abdominal pressure and subsequent straining and damage of the pelvic floor. Finally, this study confirmed that an accurate identification and repair of an OASI are essential as the prevalence of AI increased up to 60% in women with residual sonographic defects in the anal sphincter complex. However, postpartum AI is not only explained by OASI, but also other pathophysiological mechanisms may play a role, such as trauma to pelvic nerves, pelvic fascia and pelvic floor musculature. Patton et al. evaluated 181 primiparous women with OASI, and 46% reported some degree of AI at 6 months postpartum [101]. This study confirms that a higher degree OASI correlates with more severe AI. However, approximately one third of women with normal external anal sphincter tone experienced AI. Also, there was no increased likelihood of AI with reduced anal squeeze pressure. The authors suggest that OASI alone does not fully explain the later development of AI and conclude that investigating rectal and colonic motor function may provide further insight into the relationship between pelvic floor damage and AI. AI occurs in approximately 50% of women at long-term followup after the first delivery with OASI [102]. The mode of the second delivery does not seem to influence the risk of AI. A secondary analysis of a national questionnaire study evaluated 245 women who sustained a fourth-degree tear in their first delivery, with a median follow-up time of 11.6 years [103]. Out of 245, 124 women had a CS and 121 had a VD in the second delivery, and longterm AI symptoms were, respectively, found in 83 (66.9%) and 61 (50.4%) cases, with a median follow-up of 8.5 years. The mode of second delivery did not influence the risk of long-term AI (OR 0.97; 95% CI 0.41–1.84; P = 0.71). Factors that may be implicated in the development of long-term symptoms include increasing age, parity, pudendal nerve damage or weakening of pelvic floor muscles.

Is a Caesarean Section protective?

FIGURE 60.6  Two-dimensional image of the anal sphincter, demonstrating an external sphincter defect (arrows). The external sphincter appears hyperechoic surrounding the hypoechoic external sphincter. (From Chaliha, C., Pregnancy and childbirth and the effect on the pelvic floor, in: Cardozo, L. and Staskin, D., eds., Textbook of Urogynaecology and Female Urology, 3rd ed., Informa Healthcare, London, U.K., 2010, pp. 554–566. With permission.)

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Epidemiologic studies suggest that PFDs are more common in multiparous women, in particular following VD. In order to prevent childbirth-related trauma, women may opt for an elective CS. However, there is conflicting evidence to support this practice, as pregnancy itself is a risk factor for PFDs. When discussing the pros and cons, it must be considered that a CS may be associated with increased maternal morbidity and mortality particularly when viewed longitudinally with the potential effect on the outcomes of future pregnancies. A study randomising women to either VD or elective CS is clearly not possible for ethical and practical reasons. With regard to UI, Wilson et al. showed that the protective effect of CS is completely lost after three CS [104]. In a longitudinal study, 3,763 women, from the United Kingdom and New Zealand, were followed up at 12 years after birth [105]. When compared with VD, women delivered by CS only had a lower risk of UI. As one would expect, any protective effect of CS for UI disappears if VD subsequently occurs. A subgroup of 762 women was examined using POP-Q system [106]. A POP at the hymen or beyond was found to be less common in women who delivered exclusively by CS. Of note, despite OASI is a major risk factor for AI, there is not enough evidence to support the protective effect of routine CS for AI. Also, it is acknowledged that the potential benefits of CS to the pelvic floor may reduce with time, as factors such as ageing and menopause may become more relevant.

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FIGURE 60.7  Three-dimensional image of an intact anal sphincter. (From Chaliha C, Pregnancy and childbirth and the effect on the pelvic floor, in: Cardozo L and Staskin D, eds., Textbook of Urogynaecology and Female Urology, 3rd ed., Informa Healthcare, London, U.K., 2010, pp. 554–566. With permission.)

FIGURE 60.8  Three-dimensional image of internal and external sphincter trauma. (From Chaliha C, Pregnancy and childbirth and the effect on the pelvic floor, in: Cardozo L and Staskin D, eds., Textbook of Urogynaecology and Female Urology, 3rd ed., Informa Healthcare, London, U.K., 2010, pp. 554–566. With permission.)

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Conclusions



Epidemiological studies suggest that PFDs are strongly associated with childbirth, although the underlying biological mechanisms are still not fully understood. Identification of women at risk is a key element to target prevention programmes. New prognostic models have been developed in order to individualise risk estimates for the development of PFDs 12 and 20 years after delivery [107]. A risk calculator is now freely available online (https://riskcalc.org/UR_CHOICE). Future research should focus on how do women and providers interpret and use prediction tools. Clinicians should pay attention on modifiable risk factors that may impact on pelvic floor trauma. Adequate training of birth attendants is essential as well as accurate recognition of perineal trauma and repair. When relevant, women should be advised to address concomitant comorbidities such as constipation and obesity. Immediate postpartum recognition of high-risk women can allow early implementation of treatment strategies and follow-up. PFMT showed promising results in the short term; however, its efficacy many years after delivery has not been demonstrated yet [108].



Acknowledgements We acknowledge the contribution of Charlotte Chaliha, who is the author of previous editions.

References



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PROBLEMS ASSOCIATED WITH SEXUAL ACTIVITY Anna Padoa, Tal Fligelman, and Roni Tomashev

Introduction The World Health Organization (WHO) has defined sexual health as “a state of physical, emotional, mental and social wellbeing related to sexuality; it is not merely the absence of disease, dysfunction or infirmity. Sexual health requires a positive and respectful approach to sexuality and sexual relationships, as well as the possibility of having pleasurable and safe sexual experiences, free of coercion, discrimination, and violence. For sexual health to be attained and maintained, the sexual rights of all persons must be respected, protected and fulfilled” (1). The ways in which healthy sexual function (SF) is achieved can vary significantly between women and depend on factors such as sexual orientation, interpersonal and emotional factors, body image, physical well-being and response, and partner SF. The American Psychiatric Association defines female sexual dysfunction (FSD) as “a group of disorders that are typically characterized by a clinically significant disturbance in a person’s ability to respond sexually or to experience sexual pleasure” (2). According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), FSD is categorized as sexual interest/arousal disorder, genito-pelvic pain penetration disorder (GPPPD), and female orgasmic disorder (3). According to cross-sectional studies, sexual problems and distress in adult women with and without pelvic floor dysfunction (PFD) is 43.1% and 22–26% (4, 5), respectively. Women’s sexuality is complex, strongly modulated by psychosocial situations and life events; therefore, a bio-psychosocial approach must be adopted. The interaction of reproductive and gynecological conditions with SF needs to be understood to deal effectively with sexual well-being as a whole. In this chapter, we review the evidence on SF in women with PFD. Specific sections explore the relationship between common urogynecological conditions, their treatment, and female SF and dysfunction.

Sexual function in women with pelvic floor dysfunction

Cross-sectional studies have shown that PFD is associated with a large FSD burden: the prevalence of sexual dysfunction in women attending urogynecological clinics has been reported to be 37–71% (6–9). Some studies on women with PFD have shown overactive bladder (OAB) (7, 10, 11) and pelvic organ prolapse (POP) (6, 7, 10–12) to have a negative impact on sexual activity (SA), while other studies have reported that PFD is not an independent predictor of sexual distress (5), and rates of SA are similar in women with or without PFD (13, 14). This discrepancy may be explained by the fact that some studies assessed not only for the presence of FSD but also for related distress/bother and found the latter to be low (8). Furthermore, when controlling for potential confounders such as age, menopausal status, atrophy, and partner issues, in some studies, this association has been noted to disappear (9, 15). Conflicting results of studies on the 650

impact of PFD on SF may result both from the complex nature of SF and from the utilization of different assessment tools. Moreover, the frequent association between POP and lower urinary tract symptoms (LUTS) may be a confounding factor when assessing the specific impact of each of those disorders. Lastly, many studies on urogynecologic patients have failed to distinguish between low-tone PFD and disorders associated with an overactive pelvic floor (OPF) (16). In their study on a sample of patients referred to pelvic floor muscle training (PFMT), Bortolami et al. (17) identified that patients with low-tone PFD had better SF when compared to patients with OPF. Some authors (18, 19) have observed a correlation between poor PFM activity and FSD. It seems safe to conclude that a relaxed pelvic floor and mindful attention to sexual sensations are the key elements allowing good SF (16).

Sexual health assessment in women with pelvic floor dysfunction

Practitioners report obstacles when approaching SF: common barriers include fear to offend the patient, low recognition that healthy SA is important, time constraints, inadequate reimbursement, lack of privacy, cultural barriers, and personal discomfort (20). A survey among members of the Dutch Urology Association revealed that only 5.5% of respondents ask female patients about SF and 91% underestimate the frequency of FSD (21). Patient barriers include lack of perception or bothersomeness, not thinking FSD is a medical problem, and embarrassment (22). In a webbased survey (23), 40% of participants reported not seeking help from a physician for FSD, while 54% would have liked to. Less than half of the women felt their physician thoroughly addressed their sexual complaint (23). Clinicians may choose one of the available validated instruments for SF assessment. The routine administration of a sexuality questionnaire is important, as it conveys the message that a sexual history forms part of the routine assessment. Furthermore, self-administered questionnaires allow women to express their concerns in private, before exploring SF during the clinical interview. A cohort study (8) on urogynecological patients has shown that less than one in five women overtly disclosed their sexual concerns, while 37% reported sexual complaints through a selfadministered questionnaire. In a cross-sectional study on urogynecologic patients (7), 94% stated that completing the survey did not make them uncomfortable. In 2012, the joint Terminology and Standardization Committees of the International Urogynecological Association (IUGA) and the International Continence Society (ICS) published guidelines (24) on recommended reporting of the surgical outcomes for POP, including minimum required pre- and postoperative sexual information. In 2018, IUGA and ICS issued a new consensus-based terminology report for sexual health in women with PFD (25), extending and further detailing previous recommendations (for more details, see Appendix 4 in [25]).

DOI: 10.1201/9781003144236-67

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TABLE 61.1: Sexual Function Questionnaires Instrument

Description

ICIQ-FLUTSsex (BFLUTS) GRISS

Female sexual matters associated with urinary symptoms and related bother Anorgasmia, vaginismus, impotence and premature ejaculation, avoidance, dissatisfaction and non-sensuality, infrequency, and no communication about sex Effects of vaginal symptoms on sexual quality of life Sexual function in women with urinary and anal incontinence and prolapse Sexual function in women with urinary and anal incontinence and prolapse Sexual function in women with urinary and anal incontinence and prolapse includes evaluation of women who do not report sexual activity Multiple dimensions of sexual function Impact of OAB on sexual function in the male and female population Impact of female sexual dysfunction on quality of life

ICIQ-VS PISQ PISQ-12 PISQ-IR FSFI SFQ SQOL-F *

ConditionSpecific

No. of Items

ICI* Grade

4

A

Yes

28

A

No

14 31 12 33

B B NR NR

Yes Yes Yes Yes

19 31 18

A C B

No Yes Yes

International Consultation on Incontinence (25).

International urogynecological societies recommend using validated questionnaires (23). Instrument selection depends on the specific clinical or research setting. These questionnaires can be “condition-specific” questionnaires or “generic” SF questionnaires (Table 61.1) (26). The most commonly used condition-specific questionnaire, the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ) (27), and its short form, the PISQ-12 (28), have been used extensively in the past decade despite a significant shortcoming: they can be completed only by partnered, heterosexual, and sexually active women. To fill this gap, in 2013, the IUGA published the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire IUGA-Revised (PISQ-IR) (29). This questionnaire has been validated in women with POP and/or urinary and/or fecal incontinence (FI) and is suitable for both sexually active and non-sexually active women. The process of translation and validation that will enable its use in other languages besides English is currently underway.

Urinary incontinence Epidemiological studies suggest urinary incontinence (UI) affects up to 41% of adult women (30). Women suffering from LUTS or UI complain of deteriorating quality of life (QoL) and also of FSD significantly more than the general population (31), creating a major burden on social, psychological, occupational, domestic, physical, and sexual well-being (32–36). Bekker et al. (37) observed that male partners of women with UI have significantly impaired SF compared to men with partners without UI. UI and FSD often go undiagnosed, untreated, or addressed as separate issues (38) due to patient and/or clinician barriers, as discussed above. All types of UI, stress urinary incontinence (SUI), urgency urinary incontinence (UUI), mixed urinary incontinence (MUI) along with LUTS without UI, are associated with FSD. Patients with more severe UI, regardless of subtypes, and those with more than one PFD have increased risk of FSD (31, 39, 40). The most common sexual complaints in women with UI are low desire, vaginal dryness, and dyspareunia (12). Studies provide conflicting results as to which type of UI has the greatest impact on SF. Munaganuru et al. (40) observed that women with, predominantly, SUI or MUI were more likely to suffer from FSD,

whereas Gomes et al. (36) found similar FSD rates in all incontinence types. A prospective study from the Lower Urinary Tract Dysfunction Research Network in the US (41) found higher UI severity and worse SF scores in women with MUI, compared to the other subtypes. These newer studies seem to be in conflict with earlier studies (42–44), which observed OAB/UUI to have the highest association with FSD.

Coital incontinence

Coital incontinence (CI) is defined as the involuntary loss of urine with sexual intercourse. In women with SUI, the prevalence of CI ranges from 11% to 70% (45–49). Traditional teaching has been that urodynamic SUI is associated with penetration incontinence and detrusor overactivity with orgasm incontinence (47). However, subsequent studies (48) have failed to confirm this association and found SUI to be associated with high rates of penetration incontinence (80%), orgasm incontinence (93%), and a combination of the two (92%). Jha et al. (49) correlated different urodynamic diagnoses to orgasm or penetration incontinence and found no association.

The effect of UI treatment on sexual function

Systematic reviews report the efficacy of PFMT for UI, specifically for SUI (50–54). Little is known regarding whether PFMT concomitantly improves SF (55), though some studies demonstrate a beneficial effect (56, 57). In a randomized controlled study on SUI patients versus controls, Bø et al. (58) observed a statistically significant reduction in FSD in the study group. Serati et al. (59) reported improved Female Sexual Function Index (FSFI) scores in 34 SUI patients after a 3-month PFMT course. Data on the impact of SUI surgery on SF is conflicting. Moran et al. assessed the impact of colposuspension on SF (48) on 55 women with SUI and CI. Sixty-five percent of women reported CI with penetration, 16% with orgasm, and 18% with both. After surgery, 81% reported resolution of CI. Baessler and Stanton (45) later confirmed those findings; however, neither study used validated SF questionnaires. A meta-analysis (60) could not reach conclusions due to the paucity of data on Burch colposuspension. Cayan et al. (61) found worsened FSFI scores following both Burch colposuspension and pubovaginal sling, with Burch ranking worse for the domains of desire, arousal, lubrication, and orgasm.

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652 Following tension-free vaginal tape (TVT), different studies have shown different outcomes: some suggesting deterioration (62, 63) of SF, some an improvement (46, 64–66), whereas others are equivocal (67–70). Deterioration in SF may be associated with dyspareunia (63), loss of libido, or partner-associated discomfort. However, there seemed to be a consensus that TVT reduces CI rates by between three- and sixfold (63, 67, 71). The transobturator TVT approach appears to have an overall beneficial effect (68, 72) on SF compared to the retropubic approach (73). Upon comparison of the outside-in and the insideout technique, reports on SF are conflicting: one study suggests the inside-out technique (TVT-O) is better (72), and another study shows the outside-in technique (TOT) is superior (74). There have been anecdotal reports of anorgasmia after TVT-O, possibly related to trocar passage and subsequent injury to the dorsal nerve of the clitoris (74). In a meta-analysis on the impact of anti-incontinence procedures on SF, Jha et al. found that CI was significantly reduced following surgery (75). However, though the pooled results suggest between two and three times greater likelihood of improvement compared to deterioration, at least half of all women undergoing the surgery for SUI are likely to experience no change in SF. The authors found no difference in SF following the two most common procedures for SUI, i.e., the TVT and TOT/TVT-O. Glass Clark et al. (76) conducted a combined secondary analysis of Stress Incontinence Surgical Treatment Efficacy Trial (SISTEr) and Trial of Mid-Urethral Slings study (TOMUS). Women in the original trials were randomized to either autologous fascial sling or Burch colposuspension (SISTEr) or a retropubic versus transobturator MUS (TOMUS). There was a clinically important improvement in PISQ-12 scores over 24 months, with no differences between the four treatment groups. In sexually active women with OAB, sexual QoL and PISQ scores were improved with the corresponding improvement in OAB scores following anticholinergics (77, 78). Miotla et al. (79) and Balzarro et al. (80) observed that intravesical injections with onabotulinum toxin A for OAB resulted in significant improvement in SF. Treatment of OAB has also been shown to improve with both percutaneous tibial nerve stimulation (81) and sacral nerve neuromodulation (SNM) (82). See Table 61.2.

Pelvic organ prolapse In the US, 2.9–7% of women seek treatment for POP (106, 107). Not all women with POP experience symptoms, and in many cases, no treatment is warranted, as pelvic symptoms and SF are highly variable (26, 106). Studies exploring the relationship between POP and SF have yielded conflicting results. Some authors suggest the presence and stage of POP are unrelated to SF. Handa et al. (12) interviewed 1299 participants, and 38.1% had evidence of PFD. Sexual complaints were more common among women with PFD than controls (53.2% vs. 40.4%, p < 0.01), but while women with UI had FSD, POP patients did not. Weber et al. (13) observed no difference between women with POP and controls in global SF score, dryness, dyspareunia, interest in SA, and sexual satisfaction. They found that age is the main predictor of SF. Additional studies (108, 109) concluded that POP severity does not affect SF. Other studies reached opposite conclusions. Barber et al. (10) found that POP was more likely to influence SF than UI; however, POP treatment was less likely to impact SF than UI treatment. Athanasiou et al. (110) observed POP status, and years of

menopause significantly impair SF. Pauls et al. (7) found advanced POP is related to lack of SA, while mild POP is an independent factor predicting SA. The relationship between vaginal topography and SF has been addressed. Karabulut et al. (111) assessed women with stage 1–2 POP using the FSFI: no difference was detected in terms of POP-Q measurements between women with and those without FSD, except for shorter vaginal length in the FSD group. An additional study (112) identified greater vaginal length in sexually active POP patients, who were less symptomatic and had less severe POP. Mechanisms through which POP may affect SF have been investigated. Novi et al. (39) showed POP to be related to vaginal discomfort, CI, obstruction, dryness, UI, and FI during SA, dyspareunia, and fewer orgasms. Studies comparing SF in women with and without POP (39, 113) observed worse scores of sexual desire and excitement, CI, fear of incontinence, avoidance due to embarrassment, and negative emotional reactions. Partners of women with POP had worse scores of erection problems and premature ejaculation. However, the mean scores of orgasm, sexual satisfaction, and pain during intercourse were similar between groups (113). Presence of both POP and UI has a cumulative negative effect on SF, with libido, sexual excitement, and orgasm mostly affected (114). Studies suggest pain with SA may be attributable to POP: in a retrospective analysis of preoperative sexual symptoms in POP and SUI patients, 53% of the POP group complained of dryness, 60% of lack of sensation, 56% had vaginal discomfort, 18% reported tightness, and 59% reported obstruction (6). Body image and perceived attractiveness seem to play an important role in SF in POP patients. A multicenter, cross-sectional study from the US including 384 POP patients (115) has shown SF is related to women’s self-perceived body image and degree of bother from POP, regardless of vaginal topography. Genital body image and SF have been found to be related in women with POP stage 2 or greater (25, 116, 117), particularly in the domains of sexual desire and satisfaction. Moroni et al. (109) identified a correlation between body image scores and FSFI scores in POP (109). In a qualitative study, many women with POP claimed to abstain from SA because of fear that the prolapse represents an infection or tumor or because of shame (118). In summary, POP seems to impact SF mainly through its effect on body image, genito-urinary syndrome of menopause, and comorbidity with UI and FI. The role of POP stage and vaginal topography is currently unclear: larger epidemiological studies are required to substantiate available evidence.

The effect of POP treatment on sexual function

Current treatment options for POP include physiotherapy, vaginal pessaries, and surgery. The impact of each treatment modality on SF is discussed here.

Physiotherapy

A Cochrane review by Hagen et al. (119), assessing the efficacy of PFMT in POP prevention and management, could not reach conclusions regarding SF, as the four selected studies did not include SF assessment. The POPPY RCT, assessing the impact of PFMT on SF in women with POP (120), identified improved SF scores at 6 months, but not at 12 months. Another RCT (121) assessed the effect of PFMT versus lifestyle changes advice in POP: 39% of the study group experienced improved SF versus 5% of controls (p < 0.01). Women reported increased control, pelvic floor strength and awareness, improved self-confidence, sensation of

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TABLE 61.2: The Effect of Urinary Incontinence on Sexual Function Study

Study Population (n)

Control Group

Tools and Main Findings

All Incontinence Types – Population and Community Samples, Stress urinary incontinence, Overactive bladder/Urgency Urinary Incontinence Temml et al., 2000 (83) 1262 women None BFLUTS: 25.1% reported UI had impaired their sexual function. Sako et al., 2011 (84) 576 women None FSFI score was similar between women with LUTS and without LUTS. Mean FSFI score of women with SUI was lower than that of women without SUI. Coyne et al., 2011 (44) 6326 men, 8085 women None OAB: worse SF, diminished sexual activity, and enjoyment of sex. Shindel et al., 2012 (85) 1566 women None Women with OAB had an OR = 2.1 for FSD. Su et al., 2015 (86) 883 women None UI patients: OR = 1.6–1.8 for FSD. All Incontinence Types – Clinical Samples Sutherst, 1979 (87) 103 women None 46% of women maintained that their urinary disorder had adversely affected sexual relations. Berglund et al., 1991 (88) 421 women None Sexual problems (dyspareunia) registered in 15%. FSD unrelated to UI type/treatment. Gordon et al., 1999 (89) 100 women None Lower SF score in DO as compared to SUI, sensory urgency, and MUI. Bodden-Heidrich et al., 1999 (90) 72 women 34 women FSD correlated with depression and unrelated to LUTS. Yip et al., 2003 (91) 93 women None DAS, DSFI: women with SUI had poorer marital relationship and less sexual satisfaction. Handa at al., 2004 (12) 495 women 804 women UI: lower libido (OR = 1.96), vaginal dryness (OR = 2.11), and dyspareunia (OR = 2.4). Salonia et al., 2004 (31) 216 women None According to FSFI: 46% sexual dysfunction. Aslan et al., 2005 (32) 21 women 18 women All FSFI scores were significantly lower in the UI patients, except for pain. Urwitz-Lane et al., 2006 (92) 148 women None PISQ-12 scores did not differ significantly among groups with or without UI. Coksuer et al., 2011 (93) 170 women None SUI: better PISQ-12 scores than women with UUI. MUI: worst PISQ-12 scores. Asoglu et al., 2014 (94) 111 women None Patients with SUI had significantly lower PISQ-12 scores than those with UUI. Felippe et al., 2017 (95) 243 women 113 women More sexual abstinence in incontinent women. Increased UI severity: worst SQ-F score. Caruso et al., 2017 (96) 93 women None MUI: worst FSFI. MUI/UUI has more orgasmic disorders, and MUI/SUI has more desire problems. Doğan et al., 2017 (97) 153 women 72 women Infrequency, dissatisfaction, avoidance, and anorgasmia: higher in UI than control. Dissatisfaction subscale of the GRISS was significantly higher in MUI. Stress Urinary Incontinence Tennstedt et al., 2007 (98) 655 women None Worse UI scores are correlated with worse PISQ scores. Grzybowska and Wydra, 2018 (99) 130 women 126 women Worse PISQ-score in women with moderate and severe SUI. Mild SUI: better SF than moderate SUI.  Lim et al., 2018 (100) 66 couples 95 couples GRISS scores and SF of men and women were strongly correlated. The correlation coefficient was higher in couples with SUI partners. Poorer female SF, increasing age, and lower frequency of sexual intercourse were predictors of poorer GRISS score in couples. Overactive Bladder/Urgency Urinary Incontinence Sen et al., 2007 (101) 40 women 40 women FSFI: desire domain was found lower in women with OAB. Coyne et al., 2008 (102) 1434 women 1434 women Women with OAB: higher rates of depression and decreased enjoyment of sexual activity. Zahariou et al., 2010 (103) 112 women 165 women FSFI < 26.5, indicating FSD, in 47% of women with OAB and 22% of controls. Nilsson et al., 2011 (104) 147 women None 1/3 of women had coital UI. 1/2 of women reported SA was spoiled due to UI or urgency. Juliato et al., 2017 (105) 267 women None Low FSFI score: 19.1 + 9.8. FSD: 65.6% of premenopausal and 86.2% of postmenopausal women.

654 a “tighter” vagina, improved libido and orgasms, resolution of dyspareunia, and heightened partner gratification. Panman et al. (122) compared pessary treatment to PFMT and found significantly better PISQ-12 scores in the pessary group. Two RCTs published in 2016 (123, 124) assessed the efficacy of PFMT in POP patients and controls and found no improvement in SF scores in either group.

Pessaries

In the past, expert opinion regarded SA as a relative contraindication to pessary treatment (125). Recent studies have found pessaries acceptable for sexually active women, with a better impact on SF than PFMT (122). Brincat et al. (126) demonstrated that sexually active women are more likely to continue with long-term pessary management. Some studies (127, 128) demonstrated improved desire, lubrication, sexual satisfaction, and frequency of SA in pessary users. Meriwether et al. (129) found pessary satisfaction is associated with SF and body image improvements. Abdool et al. (130) reported similar improvement in SF and QoL following pessary treatment or POP surgery, while Lowenstein et al. (115) observed greater body image and SF improvement following surgery. In a review article, Rantell (131) summarizes common sexual concerns of pessary users. Women should receive instructions on which pessaries should be removed before intercourse and which, as the ring pessary, do not cause vaginal obstruction and can therefore be left in place. Clinicians can reassure women that if the pessary is correctly fitting, it should not cause harm or discomfort either to the patient or to partners, who mostly report that they are unable to feel the pessary. Intercourse may displace the pessary slightly, but there is no evidence that it will cause any harm. If SA is too uncomfortable with the pessary in situ, selfmanagement can be introduced.

Reconstructive POP surgery

When asked to prioritize the important surgery outcomes, POP patients ranked improvement in SF immediately after resolution of bulge symptoms and improvement in physical function (132). Studies addressing the impact of POP surgery on SF yield conflicting results: some report no impact (133, 134), while others demonstrate either improvement (135–140) or deterioration (140–142). A meta-analysis of 67 prospective studies (143) carried out by The Society of Gynecologic Surgeons (SGS) Systematic Review Group concluded that SA and SF improve or at least stay similar after POP surgery. The prevalence of dyspareunia decreased after all surgery types, and no surgical category showed postoperative decrease in SF (143). Organic causes for SF impairment following POP surgery may be anatomical, physiological, vascular, neural, and hormonal. Besides, psychosocial issues such as life stressors, anxiety, and depression may have an impact. Altered perception of genital health after surgery, both by the woman and her partner, and fear of damage to internal organs can also contribute to a negative impact on SF. Several studies have assessed vaginal sensitivity and arousal following POP surgery. Lakeman et al. (144) identified decreased vaginal sensitivity following vaginal POP surgery and abdominal POP surgery with anti-incontinence procedures. Nevertheless, they observed no influence on sexual well-being. The same authors prospectively evaluated vaginal sensitivity and blood flow during arousal following native tissue repair (NTR) (145) and following vaginal mesh surgery (146), measuring vaginal pulse amplitude and sensation with a special probe. Vaginal wall sensitivity decreased after NTR and increased after mesh surgery; vaginal

Textbook of Female Urology and Urogynecology vasocongestion during arousal was impaired following NTR and unchanged after mesh surgery. SF scores were not significantly affected. Lowenstein et al. (147) assessed vaginal sensation following robotic-assisted laparoscopic sacrocolpopexy (RALSCP) using a thermal and vibration Genito-Sensory Analyzer: vaginal sensitivity to temperature at the clitoris and vaginal walls was significantly higher after surgery, while vibratory sensory thresholds did not change. Table 61.3 summarizes the evidence from recent systematic reviews on the impact of POP surgery on SF. Anterior vaginal wall NTR, biologic grafting, or mesh augmentation do not appear to impact adversely on SF or cause dyspareunia (148, 149). As for posterior vaginal repair, a prospective comparative study based on data from the Swedish National Register for Gynaecological Surgery reported that 33% of women following levator ani plication had de-novo dyspareunia (150). This confirmed the findings of older studies (151, 152). Therefore, levator ani plication should be avoided in sexually active women. As for apical support procedures, abdominal/laparoscopic/robotic SCP may be the preferred procedure in sexually active women, as it has lower postoperative dyspareunia rates than vaginal procedures (153). Kuhn et al. (154) demonstrated that desire, arousal, lubrication, satisfaction, and pain improved significantly following SCP, but orgasm remained unchanged. Outcomes for SCP, high uterosacral ligament suspension, and sacrospinous ligament suspension (SSLS) are detailed in Table 61.3. A study comparing SSLS to iliococcygeal fixation (155) observed no difference in postoperative SA (58% vs. 55%) or dyspareunia (14% vs. 10%). The effect of POP surgery on SF of male partners has been assessed. Culligan et al. (156) found improvement in male SF scores after SCP. Two additional studies (140, 157) observed no change or mild improvement in SF of male partners following POP surgery.

Hysterectomy and Manchester-Fothergill procedure

Hysterectomy is often performed as part of POP surgery. Theoretically, hysterectomy poses a risk to the pelvic nerve plexus and autonomic nerve endings of the cervicovaginal fascia, potentially impacting on orgasm or sensation, and may also cause vaginal shortening and dyspareunia. Some studies have noted improved SF following hysterectomy: Rhodes et al. (158) observed improved frequency of sexual relations, less dyspareunia, and improved orgasm, vaginal dryness, and sexual desire. El-Toukhy et al. (159) reported reduction in deep dyspareunia after total abdominal, laparoscopic, or vaginal hysterectomy (TAH, TLH, or TVH). Other authors have reported worsened SF: Ercan et al. (160) found shorter vaginal length and worse PISQ-12 scores among hysterectomy patients as compared to controls; Abdelmonem (161) found shorter vaginal length and higher rate of dyspareunia following TVH (20% vs. 5%, p100 ml), UI, FI, and history of premenopausal UTI. The most recent conjecture is the urobiome, which is known to have different compositions in healthy and unhealthy bladders and undergoes changes as women age (245). Simple measures for UTI prevention include direction of wiping from front to back, pre- and postcoital voiding, and abundant water intake (246, 247). In postmenopausal women, vaginal estrogen improves the microbiome of the urogenital epithelium trough improved vaginal colonization by lactobacilli (245, 246, 248), reducing recurrent UTI. Local estrogen seems protective of recurrent UTI also in young women on oral contraceptives (249). Several studies have assessed antibiotic regimens and additional treatments. A Cochrane review (250) found that prolonged antibiotic prophylaxis reduced the rate of UTI and that postcoital ciprofloxacin is as good as prolonged treatment; in the UK, as ciprofloxacin has been shown to cause arthropathy in animal studies, trimethoprim would be used instead. A systematic review (251) concluded that long-term antibiotics reduce the risk of UTI recurrence by 24% in postmenopausal women. Alternative treatments (252) include cranberries, lactobacillus, vitamin C, methenamine salts, D-mannose (246, 252, 253), and new preparations such as hyaluronic acid intravesical injections, immunostimulants, vaccines, and inoculation with less pathogenic bacteria (252). Nightingale et al. (254) demonstrated a beneficial effect of hyaluronic acid on SF of women with Rec UTI up to a year after treatment.

Obstetric trauma and anal incontinence Healthy postpartum SF includes the resumption of SA after birth, sexual desire, pain-free sexual intercourse, and orgasm (255). Postpartum SA is influenced by a variety of factors, including exhaustion, stress, hormonal changes, the partner’s relationship, and lack of privacy. Furthermore, breastfeeding, mode of delivery, and perineal trauma are known to have a negative impact (255– 257). Postpartum FSD rates are as high as 83% in the first 3 months after delivery (255–257) and slightly decline to 64% 6 months postpartum (256). In a prospective observational case-control study conducted by Angles-Acedo et al., 73% of women after obstetric anal sphincter injury (OASI) resumed coital function 6 months

Textbook of Female Urology and Urogynecology

658 after childbirth (258). Pauls et al. found the main predictor for FSD in the postpartum period was worse urinary symptoms (259). Mode of delivery, especially operative vaginal delivery (OVD), and high-degree perineal trauma are major risk factors for dyspareunia (255–258, 260), impaired body image, and reduced sexual desire (258). The impact of high-degree perineal trauma on SA has been vastly investigated (257, 258, 261). However, also lowdegree perineal tears may have an impact (261, 262). If anatomy is not restored after a second-degree tear, it may lead to loss of DeLancey’s level III support and impair sexuality due to VL or vaginal flatus (263, 264). An RCT (262) in women with poorly healed second-degree tears found perineorrhaphy more effective than PFMT on all aspects of SF, including dyspareunia. Another study on primiparous women (261) found a perineal body length < 2 cm and pre-pregnancy dyspareunia are risk factors for postpartum dyspareunia. Clinical studies present conflicting evidence on the effect of episiotomy, and whether the latter is a risk factor for postpartum FSD is currently unclear (255, 256). Women following OASI experience worse postpartum SF and decreased sexual desire (255–258, 260). Timing of resumption of SA is affected by the presence of anal incontinence (AI) (258, 265, 266) and dyspareunia (255–258, 260). Angles-Acedo et al. (258) assessed women following different modes of delivery and OASI. They found that after a spontaneous delivery (SD), patients without OASI experienced earlier coital resumption and higher PISQ-12 scores than those with OASI, and PISQ-12 scores were better following SD than OVD, independently of the history of OASI. Breastfeeding, higher Wexner score, and OVD negatively influenced SF (258). AI is defined as involuntary loss of flatus, liquids, or solid stool, and its prevalence ranges 7–15%, according to the American College of Obstetricians and Gynecologists (267). Leader-Cramer et al. (257) investigated the influence of AI on intercourse resumption after OASI. Delayed resumption of intercourse, defined as no SA 12 weeks after delivery, was observed in 60% of patients. They concluded that postpartum follow-up visits should be extended beyond 6 weeks in women with obstetric tears to allow early counseling and intervention for both AI and FSD. Women with fecal incontinence (FI) present with a high rate of dyspareunia, fear, and avoidance of SA (265). In a group of women with FI and defecation disorders, Pellino et al. (266) observed that the strongest predictors of worse SF were prior anorectal surgery, partner ejaculation problems, reduced sexual arousal, and orgasm perception. FI of solid stool and depression related to FI were correlated with poorer SF, but did not prevent women from engaging in SA, demonstrating that it is an important aspect of their lives (268). Therapeutic options for FI include conservative measures including diet, medications, anorectal rehabilitation, anal plugs, and tibial nerve stimulation. Invasive therapies include SNM, bulking agent injection, and surgical treatment, usually external anal sphincter repair. In a review conducted by Benezech et al. (269), the efficacy of SNM for FI is about 60%. A meta-analysis conducted by Khunda et al. in 2019 (270) concluded that SNM in women with PFD, especially bladder dysfunction, seems to have a positive effect on SF. Correction of FI, irrespective of treatment modality, was associated with improved SF (271, 272). However, some studies actually suggest an equivocal impact on SF following surgical anal sphincter repair: patients after overlapping versus end-to-end sphincteroplasty reported pain during intercourse in 24% versus 4% of subjects (p = 0.04). (273). Trowbridge et al. (274) showed that SF scores were not correlated with continence scores.

Conclusion In spite of the common presentation of FSD in association with PFD, routine assessment by clinicians remains low. From a clinical point of view, the assessment of patients with urogynecology problems requires direct inquiry into SF. In order to avoid disappointment due to unmet SF goals, sexual needs and expectations should be openly discussed with PFD patients before treatment. For research purposes, the utilization of standardized tools assessing both impact and bother of PFD is of utmost importance. Currently available evidence of pelvic floor problems and their impact on SF is conflicting: to fill this gap, greater and more robust research into the effect of different urogynecologic conditions and their treatment on SF is required. The aim of urogynecologic societies and pelvic floor medicine training programs should be to increase clinicians’ confidence in approaching sexual issues, as FSD may be an important part of individualized goal setting when seeking the treatment for PFD. Furthermore, the use of validated, condition-specific SF questionnaires should be encouraged, in order to improve research quality and allow better evidence-based counseling.

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664 253. Montorsi F, Gandaglia G, Salonia A, Briganti A, Mirone V. Effectiveness of a combination of cranberries, Lactobacillus rhamnosus, and vitamin C for the management of recurrent urinary tract infections in women: results of a pilot study. Eur Urol. 2016 Dec;70(6):912–5. 254. Nightingale G, Shehab Q, Kandiah C, Rush L, Rowe-Jones C, Phillips CH. The effect of intravesical instillations with Hyaluronic Acid on sexual dysfunction in women with recurrent urinary tract infections (RUTI). Eur J Obstet Gynecol Reprod Biol. 2018 Feb;221:105–8. 255. Gutzeit O, Levy G, Lowenstein L. Postpartum female sexual function: risk factors for postpartum sexual dysfunction. Sex Med. 2020 Mar;8(1):8–13. 256. Leeman LM, Rogers RG. Sex after childbirth: postpartum sexual function. Obstet Gynecol. 2012 Mar;119(3):647–55. 257. Leader-Cramer A, Kenton K, Davé B, Gossett DR, Mueller M, LewickyGaupp C. Factors associated with timing of return to intercourse after obstetric anal sphincter injuries. J Sex Med. 2016 Oct;13(10):1523–9. 258. Anglès-Acedo S, Ros-Cerro C, Escura-Sancho S, Elías-Santo-Domingo N, Palau-Pascual MJ, Espuña-Pons M. Coital resumption after delivery among OASIS patients: differences between instrumental and spontaneous delivery. BMC Womens Health. 2019 Dec 6;19(1):154. 259. Pauls RN, Occhino JA, Dryfhout VL. Effects of pregnancy on female sexual function and body image: a prospective study. J Sex Med. 2008 Aug;5(8):1915–22. 260. O’Malley D, Higgins A, Begley C, Daly D, Smith V. Prevalence of and risk factors associated with sexual health issues in primiparous women at 6 and 12 months postpartum; a longitudinal prospective cohort study (the MAMMI study). BMC Pregnancy Childbirth. 2018 May 31;18(1):196. 261. Gommesen D, Nøhr E, Qvist N, Rasch V. Obstetric perineal tears, sexual function and dyspareunia among primiparous women 12 months postpartum: a prospective cohort study. BMJ Open. 2019 Dec 16;9(12):e032368. 262. Bergman I, Westergren Söderberg M, Ek M. Perineorrhaphy compared with pelvic floor muscle therapy in women with late consequences of a poorly healed second-degree perineal tear: a randomized controlled trial. Obstet Gynecol. 2020 Feb;135(2):341–51. 263. DeLancey JO. Anatomic aspects of vaginal eversion after hysterectomy. Am J Obstet Gynecol. 1992 Jun;166(6 Pt 1):1717–24; discussion 1724–8.

Textbook of Female Urology and Urogynecology 264. Ostrzenski A. An acquired sensation of wide/smooth vagina: a new classification. Eur J Obstet Gynecol Reprod Biol. 2011 Sep;158(1):97–100. 265. Cichowski SB, Komesu YM, Dunivan GC, Rogers RG. The association between fecal incontinence and sexual activity and function in women attending a tertiary referral center. Int Urogynecol J. 2013 Sep;24(9):1489–94. 266. Pellino G, Ramage L, Simillis C, Warren O, Kontovounisios C, Tan E, et al. Evaluation of sexual dysfunction in female patients presenting with faecal incontinence or defecation disorder. Int J Colorectal Dis. 2017 May;32(5):667–74. 267. ACOG Practice Bulletin No. 210 Summary: Fecal Incontinence. Obstet Gynecol. 2019 Apr;133(4):837–9. 268. Imhoff LR, Brown JS, Creasman JM, Subak LL, Van Den Eeden SK, Thom DH, et al. Fecal incontinence decreases sexual quality of life, but does not prevent sexual activity in women. Dis Colon Rectum. 2012 Oct;55(10):1059–65. 269. Benezech A, Bouvier M, Vitton V. Faecal incontinence: Current knowledges and perspectives. World J Gastrointest Pathophysiol. 2016 Feb 15;7(1):59–71. 270. Khunda A, McCormick C, Ballard P. Sacral neuromodulation and sexual function: a systematic review and meta-analysis of the literature. Int Urogynecol J. 2019 Mar;30(3):339–52. 271. Signorello LB, Harlow BL, Chekos AK, Repke JT. Postpartum sexual functioning and its relationship to perineal trauma: a retrospective cohort study of primiparous women. Am J Obstet Gynecol. 2001 Apr;184(5):881–8; discussion 888–90. 272. Thornton MJ, Kennedy ML, Lubowski DZ, King DW. Long-term followup of dynamic graciloplasty for faecal incontinence. Colorectal Dis. 2004 Nov;6(6):470–6. 273. Pauls RN, Silva WA, Rooney CM, Siddighi S, Kleeman SD, Dryfhout V, et al. Sexual function following anal sphincteroplasty for fecal incontinence. Am J Obstet Gynecol. 2007 Dec;197(6):618.e1–618.e6. 274. Trowbridge ER, Morgan D, Trowbridge MJ, Delancey JOL, Fenner DE. Sexual function, quality of life, and severity of anal incontinence after anal sphincteroplasty. Am J Obstet Gynecol. 2006 Dec;195(6):1753–7.

62

MENOPAUSE Elizabeth Stephenson and Timothy C. Hillard

Introduction The menopause is a biological event that occurs in all women. It has the potential to impact on a woman’s quality of life and her long-term health, so some understanding of its consequences and management is essential for all clinicians dealing with women of post-reproductive age. The average age of the menopause worldwide is approximately 52 years, so with women living well into their 80s, they can now expect to live over a third of their life in the postmenopause, a situation which is unique among all species. Consequently, over the last 50 years, there has been an increasing interest in the effects of the menopause on quality of life, its long-term health risks, and its potential treatments. Women are now working longer past middle age and wish to be able to continue to function at the same level with control of their symptoms and maintenance of the quality of life. In recent years, the internet and the burgeoning use of social media have enabled easier access to information about symptoms and their treatment and heightened focus on the effects of the peri- and postmenopause. The menopause is no longer considered a taboo subject in many cultures with more women now having access to a wide range of information to make choices around treatment for their symptoms. It is our role as health professionals to ensure that the information we give is accurate, evidence based, and up to date. This chapter gives an overview of our current understanding of the menopause, how it may affect women, and the various management strategies available.

Definitions The term “menopause” means the final menstrual period (from the Greek menos, month; pausos, ending). It occurs as a result of loss of ovarian follicular activity leading to a fall in estradiol (E2) levels below the level needed for endometrial stimulation. Strictly speaking, it can only be said to have occurred after 12 consecutive months of amenorrhea. While the menopause can sometimes be a sudden event, for most women, there is a gradual change in menstrual pattern in the years preceding the menopause as ovarian activity fluctuates, which may be accompanied by troublesome symptoms; this is often called the “perimenopause.” The menopause, or final menstrual period, represents a watershed in the reproductive life of a woman as represented in the staging system originally described by the American Society for Reproductive Medicine and updated at the Stages of Reproductive Aging Workshop +10 (Fig. 62.1) [1]. The term “climacteric” is often used synonymously with perimenopause but means the phase of transition from the reproductive to the nonreproductive state, the menopause being a specific event within that phase. It is recommended that the term now be abandoned in clinical practice to avoid confusion [2]. A surgical menopause occurs when functioning ovaries are removed such as at hysterectomy for malignancy or severe

DOI: 10.1201/9781003144236-68

endometriosis or prophylactically for ovarian cancer risk. A menopause may also be iatrogenically induced by other treatments such as radio- or chemotherapy for malignancy or temporarily during the treatment with gonadotropin-releasing hormone (GnRH) analogs for a variety of conditions. An “early” menopause occurs if the menopause happens between the ages of 40 and 45. Premature ovarian insufficiency (POI) occurs before the age of 40. This may occur naturally, be induced following surgery or other treatments, or be for other reasons (see Table 62.1). Women who experience POI are at an increased risk of a number of complications later in life and need additional support.

Etiology The ovaries produce three principal steroid hormones, E2, progesterone, and testosterone, although the latter plays no part in menstrual cycle control. Ovarian function and the normal menstrual cycle are controlled by the gonadotropins, folliclestimulating hormone (FSH), and luteinizing hormone (LH), which are released from the anterior pituitary gland. Their release is controlled by the release of GnRH from the hypothalamus, which in turn is governed by the negative feedback from circulating levels of E2, progesterone, and inhibin (a peptide hormone produced by the ovary). A detailed description of reproductive physiology can be found elsewhere [3]. In summary, each ovary contains several million germ cell units (oocytes), which achieve maximal levels in utero. There is a steady decline in these units over the prepubertal and reproductive years, but the maturation of these follicular units during this time is one of the key components of ovulation, corpus luteum formation, and ovarian steroidogenesis. It is estimated that up to 1000 follicles fail for every 1 that matures to ovulation (Fig. 62.2). As the ovary ages, the remaining follicles, which are probably the least sensitive to gonadotropins, are increasingly less likely to mature, and so, ovulation declines, and ovarian function gradually fails. Eventually, the level of E2 production is no longer sufficient to stimulate endometrial proliferation and menopause ensues. Further decline in the E2 levels over the subsequent years has effects on all estrogen-responsive tissues (which are widespread throughout the body—see Table 62.2). As a result, the effects of ovarian failure are often noted before the last period, and the effects can go on for many years. Menopause may only be a single event, but it represents a significant change in a woman’s hormonal milieu, which has implications for her future health and quality of life—hence the importance of post-reproductive health for women. The mean age of menopause in the Western world is around 51–52 years and has been so since Greek times [4]. There are significant variations around the world with some African and Asian communities reportedly having younger menopause [5]. Certain genetic and environmental factors may influence the age

665

666

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FIGURE 62.1  The Stages of Reproductive Aging Workshop +10 staging system for reproductive aging in women. (From Harlow SD et al., Climacteric 2012;15:105. With permission.) of menopause such as growth restriction in utero, low weight gain in infancy, poor nutrition in childhood, and family history [6]. Smoking may reduce the age of menopause by up to 3 years, and women with Down syndrome are also more likely to have an early menopause. Premature ovarian insufficiency POI occurs in about 5% of women under 45, 1% of women under 40, and 0.1% under 30. It is one of the commoner causes of primary and secondary amenorrhea and should always be considered in the diagnosis. The implications of this endocrine failure can be very significant particularly at a young age. The cause of spontaneous premature ovarian failure is usually unknown, but there are a number of well-established causes that should be excluded (Table 62.1). Either there may be something TABLE 62.1: Causes of Premature Ovarian Insufficiency (POI) Primary Chromosome anomalies (e.g., Turner’s syndrome and fragile X) Autoimmune disease (e.g., hypothyroidism, Addison’s disease, and myasthenia gravis) Enzyme deficiencies (e.g., galactosemia, 17-a-hydroxylase) FSH receptor gene polymorphism Secondary Surgical menopause after bilateral oophorectomy Chemotherapy or radiotherapy Infections (e.g., tuberculosis, mumps, malaria, varicella, and HIV)

wrong with the ovaries themselves (primary ovarian failure), e.g., certain chromosomal abnormalities or autoimmune disorders, or something happens to the ovary, e.g., oophorectomy, radiotherapy, or chemotherapy damage or infection. The European Society of TABLE 62.2: Symptoms and Effects of the Menopause Systemic Symptoms Vasomotor symptoms (e.g., hot flushes, night sweats) Psychological symptoms (e.g., labile mood, anxiety, tearfulness) Loss of concentration, poor memory Joint aches and pains Dry and itchy skin Hair changes Decreased sexual desire Urogenital Effects Vaginal dryness and soreness Dyspareunia Sensory urgency Recurrent urinary tract infections Urogenital prolapse Longer Term Health Effects Osteoporosis Cardiovascular disease Dementia

Menopause

667 Relative biological levels of estrogen Follicle units 1 × 107 Ovulation 1×

106

1 × 105 Climacteric

Puberty 1 × 104

1 × 103

Mucus and cornification

1 × 102

2° sex vagina urethra breasts Birth

10

20

30

40 Years

50

60

70

80

FIGURE 62.2  Correlation of follicle maturation, follicle availability, and estrogen production. (From Speroff L et al., Clinical Gynecologic Endocrinology and Infertility, Williams and Wilkins, Baltimore, MD, 1990, pp. 121–164. With permission.)

Human Reproduction and Embryology has developed clear guidance on the diagnosis and investigation of POI [7].

Investigations When to investigate

Usually, the diagnosis of menopause is straightforward and does not require specific investigation. For example, a woman in her late 40s with oligomenorrhea and classical menopausal symptoms is almost certainly perimenopausal, and no blood tests are needed [8]. Equally, a woman in her mid-50s with at least 12 months of amenorrhea has gone through the menopause, and no specific tests are required to confirm that. However, in other clinical situations, it can be helpful to confirm the diagnosis or, perhaps more commonly, to refute the diagnosis, for example, in a woman in her mid-40s with vague symptoms who thinks she is going through the menopause. Here, normal gonadotropin levels (FSH and LH) may help to reassure that this is not the cause, although it is important to remember that FSH/LH levels can fluctuate in the perimenopause. It is mandatory, however, to investigate women suspected of undergoing a premature menopause. The implications of the diagnosis have major long-term consequences in terms of both long-term treatment and also potential fertility. Younger women (under 40) require prompt, detailed assessment and specialist assessment [7].

What investigations

FSH measurements are the most useful for confirming the diagnosis especially where POI is suspected. A level of >30 IU/L is considered a diagnostic of menopause. However, there is a significant daily variation of FSH levels throughout the

cycle, and the results should be interpreted with caution and repeated if necessary. The tests are best done on days 3–5 of the cycle when FSH levels are usually at their lowest. To confirm that a woman with amenorrhea or who has been hysterectomized is menopausal, 2 measurements at least 4 to 6 weeks apart are recommended. FSH levels are of no use in predicting when menopause will occur or in assessing fertility status. Equally monitoring FSH levels in treatment is of little value. There is no value in using E2, progesterone, testosterone, or LH levels in the diagnosis of menopause. E2 levels may be useful in monitoring treatment in certain situations. Thyroid function (T4 and TSH) should be checked if there are any clinical suspicions as the symptoms of hypothyroidism can be confused with menopause or may explain poor response to estrogens. In rare, resistant cases of intractable hot flushes, 24 hour urinary collections of metanephrines vanillylmandelic acid, 5-hydroxyindoleacetic acid, and methylhistamine may be done to exclude rare causes such as pheochromocytoma, carcinoid syndrome, and mastocytosis, respectively.

Further assessment

The menopause presents an opportunity to screen for significant disease in later years and introduce appropriate preventative measures. There is a wide range of investigations that can be performed: • • • •

Breast screening and mammography Endometrial assessment of unscheduled bleeding Cardiovascular disease (CVD) risk assessment Skeletal assessment including bone density estimation and Fracture Risk Assessment (FRAX)

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668 While the majority of these are unlikely to be instigated by a urogynecologist, some understanding is helpful. A more detailed description can be found elsewhere [9].

Effects of the menopause The menopause can have significant effects throughout the body, which are summarized in Table 62.2.

Menopausal symptoms

Vasomotor symptoms, which typically manifest as hot flushes or night sweats, are the commonest symptoms of the menopause. Their exact cause is unknown, but among the many theories, it is hypothesized that a fall in circulating estrogen levels disrupts the control of the body’s thermostat, located in the hypothalamus, leading to cutaneous vasodilatation and heat loss [10]. Classically, the hot flush only affects the upper trunk and head and neck. Recent renewed interest in the cause of the hot flush has implicated a potential role for serotonin and its receptors in the central nervous system [11]. Certain triggers can be identified such as stress, spicy foods, alcohol, caffeine, and hot drinks although these are often very individual. Typically, hot flushes start to occur a year or 2 before the menopause, peaking in frequency and intensity in the first year after menopause and on average lasting for up to 7 years, but they can continue indefinitely. Not only can hot flushes have a major impact on the quality of life but also they can have potential implications for more life-threatening health problems such as CVD. About 70% of women in the west experience some form of vasomotor symptoms, but their intensity varies enormously. For some women, they are a minor nuisance, but for others, they can be very disabling and can have a major impact on their quality of life. Up to 25% of women experience severe symptoms that have a negative impact on their lives [11]. Flushes occurring at night can lead to night sweats, which may disrupt sleep and lead to tiredness, which in turn can affect mood, concentration, and libido.

Psychological symptoms

Symptoms such as irritability, depressed mood, anxiety, loss of memory and concentration, overwhelming tiredness, and mood swings are common around the menopause; there is a peak prevalence of women seeking help for this type of problem at this time, and menopausal hormone therapy (MHT) (this term is now used in preference to hormone replacement therapy) can be helpful [12, 13]. However, whether these problems are actually caused by falling estrogen levels per se or a secondary effect of other menopausal symptoms or due to other coexistent factors is not clear. Several longitudinal studies have not demonstrated any clear association between depressed mood and the menopause transition [14, 15]. Women who report psychological symptoms at the menopause are more likely to have had previous psychological problems, poor health, and premenstrual problems and have current life stresses such as dependent relatives, relationship problems, and negative attitudes to aging and the menopause [16]. The menopause occurs at a time of life when there can be many other stressful events going on, and in many societies, the woman is often the lynchpin that keeps many families together. The additional physical and emotional changes that occur at the menopause can put this balance under pressure. Whatever the underlying cause, many women may need additional support during this time and some may benefit from specific treatment for their symptoms. National Institute of Clinical Excellence (NICE)

supports the use of cognitive behavioral therapies (CBTs) and MHT as first-line treatments to help alleviate low mood associated with the menopause. There is no evidence that antidepressant medications ease low mood in this group of women and in fact can exacerbate other symptoms of the menopause including low libido [8].

Genitourinary problems

During the 4th–7th weeks of fetal development, the urogenital sinus separates from the cloaca and develops into the bladder and proximal urethra in the upper part and the distal urethra and the vestibule of the vagina in the lower part. This shared embryological origin explains why both the lower genital tract and the lower two-thirds of the urinary tract are rich in estrogen and progesterone receptors and why the loss of estrogen at the menopause can lead to the symptoms and signs of urogenital atrophy (UGA). Symptomatic UGA is common in postmenopausal women and increases with age. It affects up to 50% of postmenopausal women and up to 25% of women taking systemic estrogen [17] and is under-recognized, underdiagnosed, and thus undertreated [18]. Vulvovaginal atrophy (VVA) can have a significant impact on the quality of life and sexual function. Furthermore, for postmenopausal women with depression or urinary incontinence, vaginal symptoms have a greater impact on multiple domains of functioning and quality of life [19]. Vaginal atrophy results in the loss of the normal architecture within the vaginal epithelium (Fig. 62.3), reducing its secretions and elasticity and making it more prone to trauma, dryness, spontaneous bleeding, and infection. Clinically, this manifests as vaginal dryness, itching, dyspareunia, vaginal pain, discharge, and bleeding. Traditionally, this is referred to as VVA or UGA. However, the term genitourinary syndrome of menopause is now also used to indicate that both vaginal and urinary symptoms can occur in this condition [20]. An increased incidence of STDs is now being reported in postmenopausal women [21]. In part, this may be related to the increasing numbers of postmenopausal women restarting sexual activity but also because a hypoestrogenic vaginal epithelium is more susceptible to acquiring infection [22]. A midlife peak of urinary symptoms around the menopause has also been reported by numerous epidemiological studies [23, 24] (Fig. 62.4). Women with depressed mood scores are more likely to report symptoms of urinary incontinence [25]. Although the loss of estrogen is not the principal cause of most urinary symptoms, there is no doubt that atrophy of the distal urinary tract and, in particular, the urethra and trigon can lead to troublesome symptoms or exacerbate those already present. Typically, these women describe urinary frequency and dysuria in the absence of proven infection, sometimes referred to as the “urethral syndrome.” Thinning of the urethral mucosa and trigone results in a more sensitive and trauma-prone bladder, which in turn leads to sensory urgency and recurrent urinary tract infections, symptoms that respond well to local estrogen administration [26]. Loss of estrogen also plays a role in more widespread pelvic floor dysfunction, leading to weakening of the supporting tissues and ligaments, which may already be damaged by childbirth or other traumas, thus contributing to the increased incidence of prolapse and stress urinary incontinence seen after menopause [27]. Thinning of the urethral mucosa due to atrophy probably contributes to incomplete closure of the urethra, leading to a reduction in urethral closure pressure, which may be a factor in the development of stress incontinence [28].

Menopause

669

FIGURE 62.3  Vaginal epithelium in (a) premenopausal woman (left) and (b) postmenopausal woman (right) showing atrophic changes. (From Whitehead MI et al., Atlas of the Menopause, Parthenon Publishing, Lancaster, 1993. With permission.)

Sexual dysfunction

Percentage of women with stress incontinence

Regardless of menopausal status, sexual interest remains important to many women. The term female sexual dysfunction is now in widespread use based on a classification system introduced by the International Consensus Development Conference on Female Sexual Dysfunction [29]. Many women complain of loss of sexual desire or libido around the menopause which can be associated with significant personal and relationship distress. Hormonal changes and in particular loss of estrogen may have a direct effect on sexual desire and function, but the underlying reasons behind sexual dysfunction are often complex and multifactorial and are explored elsewhere [30]. For many women, sexual desire naturally decreases with age and the menopause may coincide with other stressful major life events. In addition, menopausal symptoms and vaginal atrophy may lead to tiredness and discomfort; there may be reduced response to sexual stimuli

and more difficulty in reaching orgasm. Male partners may also have reduced interest and have difficulty getting or maintaining an erection. This is undoubtedly a complex area but one that does require some understanding particularly in women presenting with other genital tract problems for whom maintaining sexual function is important. Correction of physical symptoms, often with systemic or vaginal estrogens, may be sufficient in many cases to overcome the problem, but in other women, the causes are more complex and may benefit from psychosexual input. In Western society, the menopause is often viewed as a negative event and some women suffer from low self-esteem, which undoubtedly does not help, but in some cultures, the menopause can be associated with an increase in libido as the shackles of monthly bleeding and risk of pregnancy are finally cast off. The role of testosterone and other treatments are discussed later.

70 60 50 40 30 20 10 0 48

49

50

51

52

53

54

Age pre-pre

peri-peri

post-post

pre-peri

FIGURE 62.4  Percentage of women in selected menopausal transition categories with stress incontinence by age (n = 843). (From Mishra GD et al., Br J Urol Int, 106(8), 1170, 2010. With permission.)

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Long-term effects Estrogen receptors are widespread throughout the body, and the fall in circulating E2 levels leads to a number of changes in a variety of organs and systems that can have notable effects on the quality of life and a potentially major impact on long-term morbidity and mortality (Table 62.2). These conditions often develop without obvious clinical manifestation in the early postmenopause but pose a significant economic burden for the future, particularly with an increasingly aging population. For women who undergo a premature menopause, the prolonged time they spend without estrogen increases the risk of these conditions developing at a younger age.

Osteoporosis

Osteoporosis is defined as “a skeletal disorder characterised by compromised bone strength predisposing to an increased risk of fracture” [31]. Bone strength is principally a reflection of bone quality and bone density (Fig. 62.5). The latter is clinically most relevant as it can be readily measured, and a woman’s osteoporotic risk is assessed using standard WHO criteria (Table 62.3). Osteoporosis is a major health problem for the Western world that will only worsen as the population ages. The commonest sites of osteoporotic fracture are the neck of femur, wrist, and vertebrae, but any long bone is susceptible. Osteoporosis is far more prevalent in women than men, and it is estimated that as many as 50% of women will suffer an osteoporotic fracture in their lifetime [32]. Bone density peaks in the mid-20s as a result of genetic and environmental influences and starts to decline in the mid-40s with an accelerated phase of around 6–10 years after menopause. Thereafter, there is a steady decline with advancing age. The accelerated postmenopausal loss is largely due to the loss of estrogen, which has antiresorptive actions. This results in an

(a)

TABLE 62.3: Definitions of Osteoporosis (World Health Organization) Description

Definition

Normal

BMD value between −1 SD and +1 SD of young adult mean (T score −1.0 to +1.0) BMD value between −1 SD and −2.5 SD of young adult mean (T score −1.0 to −2.5) BMD value equal or below −2.5 SD of young adult mean (T score −2.5 or below) BMD value equal or below −2.5 SD of young adult mean (T score −2.5 or below) plus one or more fragility fracture

Osteopenia Osteoporosis Established osteoporosis

accelerated phase of bone resorption and loss of trabecular bone. The rapid fall in bone density immediately after the menopause has triggered a wide range of strategies to prevent osteoporosis over the last 40 years [33]. Estrogen replacement has been proven to both reduce bone loss [34] and reduce the subsequent rate of hip fracture in low-risk populations [35] and is thus an effective preventative treatment in appropriate individuals [34]. Existing prevention strategies rely on identifying those individuals at high risk of subsequent fracture rather than treating large sections of the population. Current models, such as the FRAX model [36], screen postmenopausal women for risk factors including age at menopause (premature menopause being particularly high risk). Those deemed as increased risk undergo dual-energy X-ray absorptiometry bone scanning, and those with low bone density are offered preventative treatment. There is much debate about when to start preventative treatment as long-term treatments have potential adverse effects and are costly. NICE guidance specifically recommends earlier risk assessment in women with additional risk factors for osteoporosis, e.g., POI [8]. For high-risk

(b)

FIGURE 62.5  Electron micrograph of trabecular bone showing (a) normal structure (left) and (b) osteoporotic bone (right). (From Whitehead MI et al., Atlas of the Menopause, Parthenon Publishing, Lancaster, 1993. With permission.)

Menopause women below the age of 60 with no other contraindications to taking MHT, MHT should be considered as a first-line treatment and prevention strategy for osteoporosis [8, 37]. Prevention of osteoporosis remains a lifelong strategy even if, for some or most of that time, no specific treatment is used. A detailed description of all the treatments and their potential role can be found elsewhere [33, 34, 38].

671 later [55, 57]. If estrogens do have any beneficial effect on cognitive function and dementia, they probably need to be started around the time of menopause, but there is insufficient evidence at the present time to suggest this is a real benefit of MHT, and thus, MHT should not be commenced for the sole purpose of improving cognitive function [34, 49].

Management

Cardiovascular disease (CVD)

While CVD is the single commonest cause of death in women in the United Kingdom, it is relatively uncommon before the menopause, and menopausal status is considered an independent risk factor [39]. After the menopause, the risk increases considerably, and there is a large body of evidence suggesting that estrogen has a protective influence against CHD [34]. Early oophorectomy without additional estrogen is associated with a two- to fourfold increased risk of CVD compared to premenopausal women of similar age [40], and large-scale population studies over the last 30 years have suggested that taking estrogens around the time of the menopause leads to a reduction in risk [34, 41–43]. Estrogens reverse many of the adverse changes in cholesterol and other postmenopausal CVD risk factors [44] and also appear to reduce atherogenesis in animal studies [45]. Although the initial results of the large Women’s Health Initiative (WHI) randomized trial did not show any convincing evidence that taking estrogen after the menopause has any CVD benefits, subsequent analyses confirmed that for women under 60, there are no harmful effects; indeed, there was a suggestion of a potential beneficial effect [46]. A 10-year randomized trial of women receiving MHT that started early after menopause observed a significant reduction in mortality, heart failure, and stroke compared to the untreated group [47]. These results are more consistent with the previous and subsequent epidemiological data that estrogen replacement started around the time of menopause may have a beneficial effect on future CVD risk [34, 43, 48, 49], the so-called “window of opportunity” [50].

The menopause is a natural event, and for many women, there is no need to “manage” it at all, although awareness of the longterm implications such as osteoporosis and CVD should be part of good preventative medicine. However, for other women, the menopause can be a difficult time, and there are a variety of treatment options available. While MHT (or HRT as it is still commonly known) is an extremely effective option, it is only one of a number of possible approaches. For most women, menopausal symptoms are relatively short-lived and will settle within a few years, but for some, they will go on much longer, and longer term treatment may be needed. The menopause is a hormonal milestone and provides an opportunity to establish firm strategies for the prevention of the long-term disorders outlined earlier.

Cognitive function

Diet

Forgetfulness, poor concentration, memory loss, and other similar cognitive symptoms are common during midlife, and many women experience some transient cognitive impairment during the menopause [51]. While a progressive decline in cognitive function inevitably occurs with age, once this interferes substantially with social or occupational functioning, it becomes dementia. The incidence of dementia, of which Alzheimer’s disease is the commonest form, is increasing and doubles every 5 years after the age of 65, posing an increasing burden on society as a whole [52]. Alzheimer’s disease is more common in women than men, and estrogen receptors are widespread in the central and peripheral nervous systems facilitating autonomic regulation and cognitive function. However, the evidence for a role of estrogen and menopause in the pathophysiology of cognitive decline and dementia is conflicting and may depend on age and timing of intervention. A number of midlife studies have found that up to 62% of women reported memory changes during the menopause [51]. Natural menopause does not seem to be associated with objective loss of memory [53], but early surgical menopause is associated with an increased risk of dementia in later life as well as other neurological problems [54]. The WHI study and several other longitudinal studies did not show significant improvement in memory or cognitive function in women who took MHT [55–57] with an increase in the risk of dementia in women who commenced MHT

Lifestyle

Dealing with the effects of the menopause should incorporate a holistic approach. It is an ideal opportunity for the health professional to promote a healthy lifestyle to a cohort of women whose physical and mental health has been brought into focus by their changing hormonal status. For many women, the menopause can be a time of uncertainty and may be the first time they’ve sought professional help for themselves for many years. Modifiable risk factors for CVD, cancer, and osteoporosis should be highlighted, e.g., smoking, BMI, alcohol intake, diet, and exercise. Participation in cancer screening programs should be encouraged. Body weight increases on average 1 kg/year around menopause, although this does not seem to be a direct effect of the menopause itself [58]. In addition, there are metabolic changes and changes in body fat distribution with body fat shifting from the hips and thighs (gynecoid) to a more android distribution (abdomen) [59]. Thus, it is particularly important that women going through menopause eat sensibly and try and avoid excessive weight gain. A recommended diet should be rich in fruit and vegetables, whole grain and high-fiber foods, oily fish twice a week, saturated fat intake less than 10%, cholesterol less than 300 mg/day, alcohol intake no more than 1 unit/day, and sodium to 1 tsp/day [60]. For women with obesity problems, entering the menopause specialist dietary advice may be helpful. MHT is not per se associated with an increase in weight gain [58], although in some women, it can increase fluid retention and over time may lead to a reversal of the body fat changes seen at menopause. Calcium and vitamin D are particularly important for bone health around the menopause. The US National Institutes of Health recommends 1200 mg of calcium daily for postmenopausal women; 15–20 µg/day of vitamin D is thought to maintain adequate serum concentrations of 25-hydroxyvitamin D [61]. A balanced diet including at least five portions of fruit and vegetables should be sufficient to maintain adequate intakes of all vitamins and minerals.

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672 Exercise

Regular physical activity has positive effects on a variety of conditions, and physical activity can be effectively used to reduce vasomotor symptoms [62] possibly by an effect on endorphins. Regular exercise, even of relatively low intensity, can be beneficial to cardiovascular health [63]. Exercise also has a key role to play in the maintenance of bone health; not only does regular weight-bearing exercise help to conserve bone density in the hip and spine but also it does help to maintain muscle strength, joint flexibility, and overall balance, all factors that will reduce the risk of falls and subsequent fracture [64].

Alternative and complementary therapies

A wide variety of non-hormonal prescription drugs, complementary and alternative medicines, are used to improve menopausal symptoms [65–67]. Some of the licensed preparations such as clonidine, venlafaxine, and gabapentin have short-term randomized trials demonstrating their efficacy [8], but robust evidence for the efficacy and safety of most of the complementary and alternative products or methods is notably lacking [8, 67]. Despite this, the use of such treatments is widespread, and as health professionals, we must be able to give appropriate advice. These products are currently unregulated in many countries, and while the majority are likely to be harmless, a number of serious and potentially fatal interactions have been reported between herbal supplements and standard medications [68]. By contrast, the use of phytoestrogens, plant substances with similar activity to estrogen, and black cohosh appears to have some beneficial effects on menopausal symptoms [8]. A meta-analysis of 17 RCTs of soy and red clover isoflavones demonstrated a modest reduction in hot flushes particularly in those with frequent flushes [69]. The effects on other parameters such as bone loss are less clear. CBT can also be effective in alleviating low mood or anxiety that arises as a result of the menopause and is recommended as a first-line treatment rather than antidepressants [8].

Oxybutynin

Oxybutynin is a treatment for urge urinary incontinence that will be very familiar to readers of this book. Two randomized trials in menopausal women have shown superiority of oxybutynin administered at doses between 2.5 and 15 mg for vasomotor symptoms when compared to placebo [70, 71]. Not surprisingly perhaps, adverse events were common in the oxybutynin group, with over 50% reporting dry mouth and discontinuation rates

of 6.8% in the treatment group [70] although at lower doses (5–10 mg daily), discontinuation rates were better [71]. The beneficial effect of oxybutynin on vasomotor symptoms is similar to that seen with Selective Serotonin Uptake Inhibitors (SSRIs) and gabapentin [71], and it has the potential to be an alternative for these women who can’t take estrogens.

Neurokinin inhibitors

The neurokinin pathway has been identified as a key controller of the hypothalamic thermoregulatory zone and a possible mechanism for vasomotor symptoms [72]. Recent research has demonstrated that neurokinin 3 receptor antagonists are highly effective in relieving vasomotor symptoms and are well tolerated [73]. Phase 3 clinical trials are underway, but this class of drug has the potential to be a practice-changing non-hormonal option for vasomotor symptoms [74].

Treatments for urogenital atrophy

The distressing symptoms of UGA described previously can either present alone or as a wider part of menopausal symptoms. Typically in urogynecology, we see them presenting in women with vaginal prolapse the symptoms of “cystitis” without the evidence of infection or recurrent Urinary Tract Infections (UTIs). There are a number of different treatment options available (Table 62.4).

Lubricants and moisturizers

A wide range of vaginal lubricants and moisturizers are available which can be used either on their own or in conjunction with other vaginal treatments including estrogens. Lubricants may be water, oil, or silicone based and are primarily used for the short-term relief of vaginal dryness with sexual activity. Moisturizers increase the fluid content of the epithelium and can hold up to 60 times their weight in water. They replace normal vaginal secretions, thus relieving vaginal dryness and restoring the pH to normal (45 g/day E-only MHT Combined MHT

RR

Excess Cases Per 1000 Women over 5 Years

1.17 1.46 1.32 1.46 0.76–1.16 1.26–1.56

+4 +10 +8 +11 −6 to +3 + 8 to + 10

Source:

Adapted from Marsden J, Pedder H. Post Reprod Health 2020;26:126–135 [115]. Note: BMI in kg/m2; Alcohol 1 unit = 8g. Abbreviation:  BMI – body mass index; E – estrogen; MHT – menopausal hormonal therapy; RR: relative risk.

continuous combined (no-bleed) regimen. Any abnormal bleeding on MHT should be investigated, although the likelihood of underlying malignancy is much lower than with postmenopausal bleeding (1% vs. 6%) [116].

Ovarian cancer

Most of the limited data relate to estrogen alone and suggest a small increase in risk in serous and endometrioid tumors with very long-term (>10 years) treatment [117, 118]. This increase does not seem apparent with combined therapy [119, 120]. Overall, any potential risk is small and should be taken in context with the overall potential benefits of MHT. There is currently insufficient evidence to recommend any alterations in MHT prescribing practice [49].

Venous thromboembolism

MHT increases the risk of VTE twofold, with the highest risk occurring in the first year of use [121]. The background risk of VTE in women over 50 years not taking MHT is small (1.7/1000) [122], so the overall impact of this increase is low. However, the background risk is significantly increased in those women who smoke, are obese, have an underlying thrombophilia such as factor V Leiden, or have previously suffered a VTE [121]. Transdermal MHT has less impact on hemostatic mechanisms and is associated with little or no increased risk of VTE [70, 92, 93, 121, 123] and should be the treatment of choice in this group. The type of estrogen and progestogen may also influence VTE risk [93, 123].

Cardiovascular disease

Large-scale epidemiological studies have consistently shown that estrogens appear to have a protective effect on CVD [41], whereas some randomized trials have suggested a possible adverse effect [124]. Subsequent detailed analysis of these and other data suggests that the timing of the introduction of estrogen may be critical [48, 50, 125, 126]. For women starting MHT shortly after menopause, there does appear to be a protective effect on CVD, and this particularly appears to be the case for women undergoing premature menopause. However, in women many years past the menopause, starting MHT may have a detrimental effect, i.e., early benefit and late harm. There is no indication of the use of MHT purely for CVD protection [34].

Stroke

Small increases in the risk of stroke with both estrogen-only and combined estrogen and progestogen were reported in the original

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676 WHI study [124]. There was a significant age effect, with a relatively high risk in older women and no reported increase in the 50–59 age-group [46]. In general, the data suggest a trend toward a small increase incidence of stroke with MHT which increases with age [126, 127]. Transdermal and ultralow-dose oral therapy appear to have a lower risk with a neutral effect in women under 60 or within 10 years of menopause [8, 90, 127–129]. MHT should not generally be initiated in women over the age of 60 or those who have strong risk factors for stroke or CVD risk without carefully weighing up the potential risks against any potential benefits.

Practical considerations for prescribing MHT

MHT is only one option for dealing with menopausal symptoms, and other options should be considered [8, 9, 34, 65]. MHT is a clinically effective and cost-effective strategy for women with menopausal symptoms [8, 130], and for the majority of healthy, symptomatic menopausal women, the potential benefits will outweigh any small risks [8, 34, 49, 102]. However, like all treatments, the risks and benefits should be weighed individually with the patient before starting treatment. Selecting MHT regimen is a matter for the individual prescriber. If there are specific circumstances, then a particular type or route of administration may be most appropriate [9]. Follow-up should be arranged after 6–8 weeks to check the treatment’s effectiveness and side effects. It is common for women to have some problems in the first few months, and if these do not settle down, a change of preparation may be advisable. Treatment should be started at the lowest appropriate dose and can be increased if there is no symptomatic improvement after a few months. The duration of MHT use depends on the individual circumstances and indication for taking it. The “average” menopausal woman in her early 50s will probably only need it for 1–2 years, but there is no reason why she shouldn’t take it for longer if indicated. There are no particular time constraints on how long treatment should be continued [8]. Individual risks for VTE, stroke, and breast cancer should be balanced against the symptomatic benefits, improvement of the quality of life, and impact on osteoporosis and CVD. This balance may change with time and should be regularly reappraised. For the majority of women, the overall increase in any risk will be very small, and there are some women who opt to continue taking MHT for its benefits well into their 60s. For women with POI, the risk/benefit balance is strongly in favor of them taking MHT at least up until the age of 50 as a true physiological replacement [7, 8, 34, 49, 102]. Stopping MHT should be done gradually, reducing the dose to avoid rebound symptoms. At the same time, positive lifestyle factors should be emphasized, such as diet and regular exercise. Vaginal estrogens can be added in if troublesome genitourinary symptoms persist. As they are not absorbed systemically to any great extent, they can be continued after MHT has been stopped without significant risk [8, 17, 34, 49]. Reduced sexual desire is a common complaint around the menopause, which can lead to distress and have a negative impact on psychological well-being and relationships [30]. This is a complex area, and there are often multiple factors that play a part [131]. Menopausal symptoms and UGA should be treated with systemic or local estrogens, and psychosexual counseling should be considered if appropriate. Testosterone supplementation appears to be effective in postmenopausal women when given orally or transdermally as a patch or gel in women with low sexual desire [101, 132]. This is seen in both surgical and naturally occurring

menopause with or without concomitant estrogen treatment [101]. Subdermal testosterone implants, which have been used for many years in some countries, are no longer readily available. However, a transdermal testosterone cream, which is now available in Australia, may be a suitable alternative [133]. Tibolone, which is a synthetic steroid with estrogenic, progestogenic, and androgenic activity, has a licensed indication for women with loss of libido [134]. Further guidance on testosterone prescribing can be found elsewhere [135].

Contraception

Contraception should be continued until 2 years after the last period in women under 50 and 1 year in women over 50. A full review of contraceptive choices for perimenopausal women can be found elsewhere [9, 136].

Summary The menopause is a time of significant physiological change signifying the end of the reproductive phase of life. While this can be a positive development for many women, for others, the menopause can be a difficult time with distressing symptoms that impact on these women’s quality of life, employment, and relationships. The potential impact on long-term health should also be considered, and the menopause provides a good opportunity to improve lifestyle risk factors and put long-term prevention strategies in place. Women with POI have particular needs and will often benefit from specialist support. A wide range of potential treatments is available for helping women through the menopause and beyond. MHT is only one option but is effective and has a large body of evidence supporting its use. For the vast majority of healthy symptomatic menopausal women, the benefit/risk balance is in favor of using MHT for a limited period. Vaginal preparations are equally effective for women experiencing symptoms of UGA. No two women’s experience of the menopause is exactly the same, and any advice or treatment should therefore be tailored to the needs of the individual woman.

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SPORTS AND FITNESS ACTIVITIES Kari Bø Urinary incontinence is often regarded as a problem affecting older, postmenopausal, multiparous women [1]. However, several epidemiological studies have demonstrated that the symptom of stress urinary incontinence (SUI) is also common in populations of nulliparous young females [1–10]. Prevalence data vary between 12% and 80% and may be explained by differences in definitions, study design, and populations. Typically, for prevalence studies, the percentage tends to drop when the former International Continence Society (ICS) definition of symptoms being socially and hygienically problematic is used [6, 11]. The most common type of urinary incontinence in women is SUI [12], defined as involuntary leakage on physical exertion, sneezing, or coughing [13]. Cross-sectional studies in the general female population reporting that physically active women have less incontinence compared to their sedentary counterparts are difficult to interpret as this association may be because women with incontinence have stopped exercising due to the condition [12, 14–20]. Hence, the unanswered question is: Does physical activity cause continence, or are women able/willing to participate in physical activities because they are continent?

Assessment of incontinence during physical activity Usually, the diagnosis of urodynamic SUI is made during assessment in a half-sitting, lithotomy position. The validity of this evaluation can be questioned as most women only leak in a standing position. Some pad tests involve physical activities such as stair climbing and jumping [21]. Henalla et al. [22] and Hagen et al. [23] designed tests based on physical activities. The latter test involved running, jumping jacks, standing up and lying down, and abdominal curls. These were found to be nine times as provocative as the ICS test involving physical activity. The authors concluded that assessment of the degree of SUI has to be physically provocative to detect SUI. Nygaard et al. reported that 7% of women admitted to urine loss only during sports and that 40% and 17% first noted urinary incontinence during sports while in high school or junior high school, respectively [1]. Methodological problems in study design have meant that there is a lack of studies describing bladder and urethral function during physical activity. James [24] argued that assessment of SUI should be performed in standing and working positions and during physical activity. He used ambulatory bladder pressure measurements to demonstrate peaks of bladder pressure rise during running and jumping, which occurred when the feet touched the ground. Although pressure rise was higher during coughing, some women were only leaking during exercise. Kulseng-Hanssen and Klevmark [25] improved the methodology by placing bladder and urethral transducer catheters in a silicon cuff and sutured it to the external urethral opening to keep it stable during activity. In 16 of the patients, 115 leakage episodes were seen in 45 minutes. In 92 of these episodes, 680

the maximum urethral pressure decrease was larger than the detrusor pressure increase. However, some patients complained of urinary leakage during strenuous exercise (running and jumping for longer periods of time), although leakage was undetected even in this test. Similar results were seen in the study of Bø et al. [26], where the test did not detect leakage in four subjects with a convincing history of urinary leakage. As SUI may occur due to fatigue of the striated urethral wall and pelvic floor muscles (PFMs), some women may need even more vigorous and continuous activities to provoke the leakage they experience outside the laboratory. Comparing changes in foot arch flexibility in 47 continent and incontinent varsity athletes, Nygaard et al. [27] demonstrated a significantly decreased foot flexibility in incontinent women. They suggested that the way in which impact forces are absorbed may be one etiological factor for stress incontinence and that more research is required to understand how impact forces are transmitted to the pelvic floor. The high prevalence of urine loss in gymnasts may be explained by the extremely high impact during landing and takeoff and the transmission of this pressure to the pelvic floor. However, despite this high impact, many gymnasts do not leak, and this group is therefore interesting and important to study.

Prevalence of urinary incontinence among participants in sports and fitness activities SUI implies that urine loss occurs during an increase in intraabdominal pressure. Therefore, one may expect that women with this condition are likely to experience urine loss during participation in most forms of physical activity. Sedentary women are less exposed to physical exertions and this may avoid urinary leakage, despite the underlying condition potentially being present. Studies have demonstrated that SUI is common among physical education/sports students, women who exercise for fitness, and female elite athletes [28]. Bø et al. [7] demonstrated (in a study with an 84% response rate) that 26% of young physical education/sports students reported having urinary leakage during different forms of physical activity. This study also showed a difference between a group exercising three times a week in addition to daytime physical activities at the university and a group of sedentary nutrition students. The respective prevalences were 31% and 10% (p = 0.02). A subsequent study of first-year female students (n = 37) with a mean age of 20.2 years demonstrated a prevalence of 38% of SUI symptoms. Eight of 13 women (61.5%) considered the leakage a social or hygienic problem [26], giving a prevalence using the former ICS definition of 21.6% for this population of physically fit, young, exercising nulliparous women. In this latter study, the ambulatory urodynamic test was used to verify urodynamic SUI. Seven women with symptoms were evaluated by urodynamics, and in six of seven, urethral sphincter incompetence was

DOI: 10.1201/9781003144236-69

Sports and Fitness Activities confirmed. Mean leakage measured by pad test with standardized bladder volume was 12 g (range 0–46 g). Nygaard et al. [9] studied incontinence and exercise in a group of 326 women presenting to private gynecology offices (response rate 50%). Eighty-nine percent were exercising at least once per week, with an average of three times per week for 30–60 minutes per session. Forty-seven percent reported some degree of urinary incontinence. Fozzatti et al. [29] found that 24.6% of nulliparous women attending gyms compared to 14.3% in a group not attending gyms or doing high-impact activities (except running) reported UI, p = 0.006. This supports the results from a study on group fitness instructors, showing a prevalence of 26%, with the same prevalence in those teaching yoga and Pilates [30]. There is an increasing number of studies on female elite athletes and UI [2, 3, 28]. In a systematic review, Bø [28] found a variation in prevalence between sports from 0% in golfers [1] up to 80% in high-impact sports [31]. Nygaard et al. [1] surveyed all 156 women participating in varsity athletics at a large state university. The response rate was 92%. The mean age was 19.9 ± 3.3 years and they were all nulliparous. The women were asked whether they had ever experienced urinary leakage during participation in sports, during coughing, during sneezing, during heavy lifting, when walking to the bathroom, during sleeping, and upon hearing the sound of running water. They rated the frequency of leakage on a five-point scale. Twenty-eight percent reported urine loss while participating in their sports. There was a tendency in two-thirds of these women to be incontinent frequently rather than rarely. The proportion in different sports was as follows: gymnastics, 67%; basketball, 66%; tennis, 50%; field hockey, 42%; track, 29%; swimming, 10%; volleyball, 9%; softball, 6%; and golf, 0%. Sixteen percent were incontinent during practice sessions and 14% during competition [1]. Forty-two percent reported urine loss during at least one of the activities of daily life and 18% more often than rarely. Twentyone percent reported urine loss only during daily life and not during sports, and 7% noted incontinence only during sports. Bø and Sundgot-Borgen [32] compared the prevalence of symptoms of urinary incontinence in Norwegian elite athletes and age-matched controls and found a prevalence of 41% and 39% of SUI and 16% and 19% of urge incontinence in athletes and controls, respectively. In order to find out whether high-impact activity contributes to later urinary incontinence, Nygaard [33] compared former female Olympians who had competed in swimming (low impact) and gymnastics or track and field (high impact). One hundred and four women participated (response rate of 51%). When doing their sport as Olympians, high-impact athletes have a higher prevalence (36%) compared to low-impact athletes (4.5%). However, when studied more than 20 years after cessation of the sport, there was no significant difference in the prevalence of incontinence between the groups. It was concluded that participation in regular, strenuous, highimpact activity when younger did not predispose to significant urinary leakage later in life. Bø and Sundgot-Borgen [34] studied former female elite athletes 15 years later and found that they were not more likely to experience urinary incontinence later in life than controls. Former athletes from high-impact sports (running and jumping) were not more likely to report urinary incontinence. Having experienced urinary incontinence during sports was, however, strongly associated with later incontinence.

681

Consequences of SUI during physical activity Urinary incontinence may lead to withdrawal from social activities and reduction of well-being [35]. Norton et al. [36] reported that urinary leakage frequently interfered with daily life in more than 50% of their study group. Additionally, Fall et al. [37] reported that 42% of the women with incontinence had problems during sports and physical activities. Bø et al. [38] showed that two-thirds of sedentary women with urodynamic SUI reported urinary leakage to be the cause of inactivity. Twenty-seven out of 52 women had tried to participate in specific sports and fitness activities but had withdrawn from one or more activities because of leakage. Nineteen of the 27 women had withdrawn from aerobic and dance activities, despite these being among the most popular fitness activities for women. They all reported that the major leakage occurred during high-impact activities during the aerobics session, especially when performing “jumping jacks” (jumping with legs in subsequent abduction and adduction), which is one of the most commonly used high-impact exercises in aerobic dance and general fitness programs. This corresponds with the results of Nygaard et al. [9], where women most frequently reported leakage with running and highimpact aerobics. Thirty percent of the exercisers noted incontinence during at least one type of exercise. Twenty percent of these women stopped doing the activity solely because of incontinence, 18% changed the way they performed an exercise, and 55% wore a pad during exercise. Frequency, time spent per session, and duration of a particular exercise had no significant impact on the prevalence [9]. Brown and Miller [10] concluded that urinary incontinence was an important barrier to women’s participation in physical activities. Regular physical activity is an important factor for women’s health at all ages. Moderate physical activity can be one important factor in the prevention of coronary heart disease, high blood pressure, osteoporosis, musculoskeletal diseases, obesity, breast and colon cancer, anxiety, and depression [39]. If one consequence of incontinence is withdrawal from physical activity, the impact on women’s health is potentially huge.

Can physical activity cause urinary incontinence? Several risk factors have been suggested for the development of female urinary incontinence; hereditary weak connective tissue, weak or nonfunctional PFMs, hormonal factors, dyssynergia between detrusor and urethral smooth and striated muscle activity, pregnancy, vaginal delivery, heavy physical exertion, inactivity, obesity, cigarette smoking, menopause, and old age are suggested risk factors [12, 40]. To date, there is little evidence supporting a strong causal effect for many of these factors. The reality is that urinary incontinence has a multifactorial etiology in women including failure of one or more factors to compensate for another weak factor. The speed and strength of the PFM contraction may be one such important factor [41, 42].

Pelvic floor and female athletes Optimal PFM function implies a localization of the pelvic floor in an adequate anatomical position, with sufficient cross-sectional area to give structural support for the vagina, bladder, and the urethra in order to prevent descent during the increase in the

682 abdominal pressure [43]. The muscles have to be in a neurological state of “readiness for action” allowing an appropriate quick and strong response or be a part of a feed-forward loop, contracting automatically simultaneously or before the intra-abdominal pressure increase. However, such co-contractions may be too slow or weak to prevent leakage and most likely the most important factor is the firmness of the pelvic floor creating sufficient support to reduce the downward movement and opening of the levator hiatus. Typically, there are two hypotheses about female athletes and PFM strength, and the hypotheses are going in opposite directions [28]. The first hypothesis is that general physical activity may lead to the reflexive strengthening of the pelvic floor, thus making the PFMs in female athletes stronger. To date, no research has verified this hypothesis. The fact that so many female athletes report SUI [28] actually contradicts this view. The second hypothesis is that heavy exercise, e.g., marathon running with repetitive bouncing toward the pelvic floor or weight lifting, may overload the pelvic floor and weaken the muscles over time. Nichols and Randall [44] proposed that women exposed to chronic straining may have an increased prevalence of genital prolapse because of connective tissue damage due to persistent intra-abdominal pressure increase. Nichols and Milley [45] suggested that the cardinal and uterosacral ligaments, PFMs, and the connective tissue of the perineum may be damaged chronically because of repeatedly increased abdominal pressure due to, e.g., manual work and chronic cough. According to this theory, strenuous exercise raising the intra-abdominal pressure may contribute to the development of SUI in women with a predisposition to incontinence. Davis and Goodman [46] studied 512 of 2651 female soldiers who entered the airborne infantry and found that nine developed urinary incontinence during the training period. Urodynamic investigation demonstrated “detrusor instability” in three and urodynamic SUI in six of the women. All six with SUI demonstrated a definite cystourethrocele, a hypermobile vesical neck with loss of the posterior urethrovesical angle, and visible urine loss with Valsalva after the training period. Four of the women reported feeling a tearing pain in their lower quadrant on impact during a parachute jump, and one subject related a similar event during heavy lifting and doing sit-ups. From the data available today, it is not possible to conclude whether moderate- to highimpact activities can cause connective tissue or PFM damage. It is likely that there is a self-selection of continent women who undertake high-impact sports and fitness activities. Another contributing factor for SUI in female elite athletes may be hypothalamic amenorrhea due to either intensive exercise, eating disorders, or a combination of both with resultant low estrogen levels [1]. However, the association between low estrogen levels and the prevalence of SUI is not clear [47]. Most women in the studies of Bø et al. and Nygaard et al. reporting and demonstrating SUI had regular menstrual cycles [1, 26]. However, in the study by Bø and Sundgot-Borgen [32], a higher prevalence of SUI was found in those with eating disorders. Eating disorders may be associated with low estrogen levels. Nygaard et al. [1] proposed that, e.g., gymnasts may have selected their sport because of hypermobility and that changes in collagen concentration may be one factor in the higher prevalence of incontinence in gymnasts. However, although some studies have shown a reduction in collagen tissue in women with incontinence compared to continent women [48], the link between collagen, hypermobility, and SUI is not clear. There are no studies

Textbook of Female Urology and Urogynecology comparing the collagen structure in gymnasts and athletes with or without SUI with that of matched controls. Today’s gymnasts can be characterized as being strong rather than hypermobile, yet the prevalence of UI is still high [2, 3]. There are few studies measuring PFM strength in exercisers compared to sedentary controls. Bø et al. [26] did not find any significant difference between incontinent female sports students and a comparable continent group. However, the sample was small, and other studies have demonstrated significantly stronger PFMs in continent than incontinent women [41, 49, 50]. Borin et al. [51] compared PFM strength in 10 handball, 10 volleyball, and 10 basketball players and a nonexercising control group and found weaker muscles in the volleyball and basketball players compared with controls. They also found that lower strength correlates with increased symptoms of urinary incontinence. There is an urgent need for further studies on this topic.

Protection during exercise to prevent leakage Because of the health benefits of regular moderate exercise, it is important to emphasize that women should be encouraged to continue exercising despite their urinary leakage. However, they can be advised about choosing low-impact activities, e.g., walking, Nordic walking, dancing, low-impact aerobics, step training, bicycling, swimming, and cross-country skiing. If an incontinent woman wants to participate in high-impact aerobics, she may use low-impact alternatives, meaning walking while the others are running, doing “step touch” while others are doing jumping jacks, etc. In addition, if she leaks or feels downward pressure during sit-ups, she should be advised to make an attempt to contract the PFMs before doing abdominal curls/ sit-ups. It is important to notice that several studies have found that coughing and Valsalva (as in defecation) increase intraabdominal pressure to a significantly higher degree than different daily movements and exercises [52, 53]. Many exercises including abdominal exercise did not increase the intra-abdominal pressure more than rising up from a chair [53]. Hence, the fear that common exercises may hurt the pelvic floor may be exaggerated. During exercise, the woman should be encouraged to use specially designed protection. Fortunately, some of the best protecting pads are manufactured in small sizes, making active women more comfortable when wearing them while exercising. In addition, women may use urethral or vaginal devices to prevent leakage during physical activity [54, 55]. In a study by Glavind [56], six women with stress incontinence demonstrated total dryness when using a vaginal device during 30 minutes of aerobic exercise.

Treatment Generally, the least invasive treatment should be tried first [57], with pelvic floor muscle training (PFMT) being the method recommended as first-line treatment [57]. Female elite athletes are mostly young and nulliparous, and surgery is therefore not recommended. Several randomized controlled trials have demonstrated a positive effect of PFMT on SUI in the general population, but only few of them have measured the effect during physical activity [57]. Bø et al. [38] demonstrated that after specific strength training of the PFMs, 17 of 23 women had improved during jumping and running and 15 during lifting. In addition, significant improvement was obtained while dancing, while hiking, during general group

Sports and Fitness Activities exercise, and in an overall score on the ability to participate in different activities [38]. Measured with a pad test with standardized bladder volume comprising running, jumping jacks, and situps, there was a significant reduction in urine loss from a mean of 27 g (95% CI, 8.8–45.1; range 0–168) to 7.1 g (95% CI, 0.8–13.4; range 0–58.3), p < 0.01 [58]. Two small case series on elite athletes and sports students have been published [59, 60]. Rivalta et al. [59] reported total relief of reported symptoms and no leakage on pad testing after 3 months of a combination of electrical stimulation, PFMT with biofeedback, and vaginal cones. Da Roza et al. [60] reported that seven nulliparous sports students significantly improved PFM strength and reduced International Consultation on Incontinence Questionnaire (ICIQ) score and frequency and amount of leakage after 8 weeks of training. Only one RCT was found evaluating the effect of PFMT on SUI in elite athletes. In a study of 32 volleyball players, PFMT improved UI in more women than in the control group given written information only [61]. However, athletes have a low level of knowledge of the pelvic floor and how to train the PFM [62–64] and therefore need the same thorough instructions, proper assessment of ability to contract the PFM, and follow-up as the general population. On the other side, elite athletes and women engaging in fitness activities are used to conducting regular training and are motivated to exercise. One would therefore expect that the effect of supervised PFMT would be equally effective or even more effective in these specific groups of women. However, their pelvic floor needs to be able to counteract much larger impacts than what usually occurs during daily activities. In a study on ground reaction forces during landing from different heights, assessed in gymnasts, the peak vertical-force magnitudes ranged from 27.1 at 30-cm height to 56.0 N/kg at 90 cm [65]. To date, it is not possible to conclude whether general physical activity or strenuous exercise is good or bad for the pelvic floor. Most likely there is an individual threshold for what the pelvic floor can counteract [66]. Supervised PFMT has proved to be effective in the general female population; it is a functional and physiological noninvasive treatment with no known side effects that can be very costeffective compared to other treatment modalities [57]. In addition, the woman/girl herself is given the opportunity to take control of her health. She learns body awareness, and if successful, the training may enhance self-esteem and coping strategies. There is, however, a need for randomized controlled trials to discuss whether PFMT can reduce urinary leakage in subgroups of exercising women.

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References





Conclusions



SUI is prevalent in exercising women at all levels. This may well be because the activity “unmasks” a predisposition to leak and currently it is not possible to be certain whether strenuous physical activity may cause SUI or pelvic organ prolapse. Current understanding certainly suggests that more vigorous exercise is associated with higher rates of leakage and that women with problems restrict their physical activities. More research is needed to understand how the impact of different exercises may affect pelvic organs, connective tissue, and PFMs. The effect of PFMT on elite athletes and women participating in vigorous fitness activities has only yet been evaluated in one randomized controlled trial. However, based on the present knowledge of the effect of PFMT and no report of side effects, it should be suggested as the first choice of treatment.





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64

ANAL INCONTINENCE* Alison Hainsworth and Andrew Williams

Introduction Anal incontinence is the involuntary loss of flatus or feces per rectum (1). Anal incontinence is common and although the true prevalence is unknown (2) studies estimate it to be between 11% and 15% in the general adult population (3). Despite being personally and socially incapacitating only a half of sufferers will volunteer their symptoms spontaneously if not directly asked (4). The prevalence of anal incontinence is expected to increase in the future due to an aging population, more assertive patient cohorts, and the drive to break down barriers that prevent patients from reporting their symptoms (5, 6). Anal incontinence affects men and women of all ages but at the age of 45 it is eight times more common in women, implicating obstetric factors in the etiology. A study from Birmingham found that 4% of women develop fecal incontinence following childbirth (7).

Pathogenesis Multiple factors contribute to continence; stool consistency and delivery to the rectum, rectal sensitivity, capacity, compliance and storage, the integrity and function of the anal sphincter mechanism, and anal canal sensation (8, 9). The anal sphincter complex comprises two muscles: • An inner circular smooth muscle which maintains the constant resting tone and prevents passive incontinence (the internal sphincter) (10). • An outer striated muscle under voluntary control that can be contracted to defer defecation when appropriate (the external sphincter) (11). Experts agree that there are often multiple overlapping pathologies that contribute to anal incontinence (12, 13) (Table 64.1). However, the focus of this chapter is obstetric injury, which is the most important cause of anal incontinence in women. Obstetric trauma includes mechanical trauma (obstetric anal sphincter injury (OASI)) and neurogenic trauma (damage to the nerves supplying the pelvic floor or anal sphincter). Structural damage is more important than neurological factors (14). The principles of management are broadly similar regardless of etiology.

Obstetric anal sphincter injury (OASI)

OASIs are classified according to Sultan et al. (Table 64.2) (15). Sphincter injuries are more common in primiparous women; new sphincter injuries are less common with subsequent deliveries (16). Other risk factors for sphincter injury include large babies, forceps delivery, a prolonged second stage of labor, an *

We would like to acknowledge Tony Mak and Simon Radley for their previous chapter on anal incontinence.

DOI: 10.1201/9781003144236-70

occipitoposterior presentation, and high BMI (17). Some authors postulate that an episiotomy does not necessarily prevent sphincter injury (14, 17). Incidence has increased due to increased vigilance and the advent of endoanal ultrasound (15); as our understanding of the anal sphincter has improved so has the rate of recognized OASI (1.8–5.9% for first vaginal deliveries) (18). When perineal examination immediately following delivery is undertaken by a trained clinician, the incidence of detected sphincter injury is significantly increased (19). Some sphincter defects may be truly occult, occurring with minimal or no perineal injury, where the mechanism is likely to be tissue shearing during delivery. However, there is a notable variation in the incidence of recognized thirddegree tears between centers publishing their data (20) and the incidence of incontinence postpartum in women thought to have had a second-degree tear (not involving the sphincter complex). (21); these observations suggest that a proportion of anal sphincter injuries remain undetected following delivery. Even when a sphincter injury is recognized and repaired at the time of delivery, up to 85% of women still have an identifiable sphincter defect on postpartum scanning and 50% of women have some anal incontinence (17). Up to 35% of primiparas have been reported to have sphincter injury; however, some remain asymptomatic (22). It is not fully understood why some women with anal sphincter injury only develop incontinence later in life but it is likely that multifactorial factors including sphincter damage, progressive neuropathy, muscle atrophy, hormonal changes (23), and alteration in bowel function are to blame (24).

Neurological damage

Neurological damage includes pudendal neuropathy and denervation of the striated pelvic floor muscle, particularly the external anal sphincter and puborectalis (25). Pudendal nerve damage is associated with multiparity, forceps delivery, prolonged second stage of labor, third-degree tears, and increased birth weight (25). Prolonged pudendal nerve motor terminal latencies (PNMTL) are a marker of nerve injury and have been demonstrated in a third of primigravidae following vaginal delivery (26). Up to 60% may return to normal within 2 months of delivery but up to a third remain prolonged at 6 months though the presence of a prolonged PNMTL is not necessarily associated with incontinence. After emergency cesarean section late in labor, pudendal nerve latencies may be increased, indicating neurological to the pelvic floor or sphincter (16). Pudendal nerve damage and increased external sphincter fiber density (indicating a damaged nerve supply) are seen more frequently in multiparae, suggesting that nerve damage may be cumulative with subsequent deliveries (16). Neurogenic incontinence is likely to be a progressive process, rather than an acute event at the time of delivery, and therefore may be exacerbated by subsequent deliveries or prolonged straining. 685

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686 TABLE 64.1: Etiology of Anal Incontinence Action

Mechanism for Anal Incontinence

Risk Factors

Delivery to the rectum

Rapid transit

Inflammation (Inflammatory bowel disease, ischemic colitis, microscopic colitis) Infection Irritable bowel syndrome Malignancy Post cholecystectomy diarrhea Polypharmacy Tube feeds Sports such as running Nursing home residents Behavioral, lifestyle factors Medication Inflammatory bowel disease Radiation proctitis Rectal tumor Rectal surgery Obstetric Trauma Surgical Trauma (lateral sphincterotomy or anal stretch, anorectal surgery for hemorrhoids or anal fistula) Accidental Trauma Obstetric trauma causing denervation so that anorectal angle is not maintained Pelvic floor dyssynergia leading to incomplete evacuation and subsequent soiling Obstetric Trauma Surgical Trauma Mucosal or full-thickness rectal prolapse Obstetric trauma Idiopathic Peripheral neuropathy Obstetric trauma Idiopathic Peripheral neuropathy Central nervous system injury (spina bifda, spinal cord injury, stroke) Obstetric trauma

Constipation with fecal impaction

Rectal storage

Rectal compliance and capacity

Anal sphincter mechanism

Sphincter muscle injury

Puborectalis dysfunction

Nerve supply

Injury to anal mucosal folds which maintain tight seal Prevention of closure of the anal canal Pudendal nerve injury

Loss of sensation to the anorectum

Physical Mobility

Source:

Nerve supply to external anal sphincter and puborectalis Inability to reach toilet in time

Immobility Dependence on others for activities of daily living Nursing home residents

From data in Ref. (27).

Patient assessment

TABLE 64.2: Classification of OASIs Obstetric Anal Sphincter Injury

Description

First degree:

laceration of the vaginal epithelium or perineal skin only involvement of the perineal muscles but not the anal sphincter disruption of the anal sphincter muscles which are subdivided into; 3a 50% thickness of the external anal sphincter is torn 3c internal anal sphincter also torn third-degree tear with disruption of the anal epithelium

Second degree: Third degree:

Fourth degree: Note:

See further refs (15) and (17).

Patients may be assessed by subjective means (symptom assessment) and objective means (assessment of the anorectal structure and function). Symptoms are assessed with history, stool diaries, and patient questionnaires. Anorectal structure and function are assessed with examination and investigations, which include anorectal physiology, porridge continence tests, pudendal nerve terminal motor latency (PNTML), endoanal ultrasound, and endoanal MRI (28, 29).

History

Symptoms alone cannot be relied upon to determine treatment as the pathophysiology is often multifactorial but careful questioning may give a clue as to the etiological factors (30). Anal incontinence may be precipitated by a change in bowel habit with increased frequency and loose stool, which suggests underlying colorectal disease. The urgency of defecation, or incontinence

Anal Incontinence

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TABLE 64.3: Examples of Questionnaires for Anal Incontinence Questionnaire

Information

Quality of Life?

St Marks’s Incontinence Score

Severity, frequency, urgency, use of pads and antidiarrhoeal medication Severity, frequency, use of pads Bowel symptoms and bother caused Bowel and urinary symptoms

No

Wexner Score ICIQ-BS BBUSQ-22

No Yes No

associated with vigorous activity or coughing, may indicate damage to the voluntary striated external anal sphincter or its nerve supply. Passive incontinence occurring between episodes of defecation with no call to stool, indicates poor anal canal resting tone and suggests damage or degeneration of the internal sphincter muscle. Inability to discriminate solid stool from flatus suggests damage to anorectal sensory pathways. Seepage or perineal soiling may be seen in situations where there is a distortion of the anal canal by scarring or in the presence of a fistula. A careful medical history should be taken with specific attention to colonic function, previous anorectal surgery, and any potential causes of anal incontinence. An obstetric history should include details of birth weight, mode of delivery, length of labor, instrumental delivery, and details of perineal trauma. Patient questionnaires aim to quantify symptom severity, the bother inflicted upon the patient and effects on quality of life. They can be used to assess response to treatment in both research and clinical settings. Examples include the St. Marks’s score (31), the Wexner score (the Cleveland Clinic Incontinence score) (32), the ICIQ-BS (33, 34), and the Birmingham Bowel and Urinary Symptoms questionnaire (BBUSQ-22) (35) (Table 64.3). The Pelvic Floor Consortium, endorsed by the International Continence Society, recommends a combination of both the St Marks’s Incontinence score and the Wexner (The Cleveland Clinic Incontinence) score to assess the severity and impact of fecal incontinence (36). Other tools include patient interviews for qualitative assessment of patient perception and acceptability of treatments (37), bowel function diaries, and visual analog scores for quantitative assessment of severity (38).

Examination

Physical examination should include general and abdominal examination as well as an anorectal examination (1). Anorectal examination encompasses inspection of the perineum, noting scarring from previous surgery or obstetric trauma. Voluntary contraction of the external sphincter can be seen and defects in the sphincter may be observed. Gaping of the anus at rest or on gentle perineal traction suggests a low resting tone and impaired internal anal sphincter function. Descent of the perineum at rest with accentuation on straining suggests pelvic floor weakness, pudendal neuropathy, or both. Straining may also reveal an unsuspected rectal prolapse. The perineal sensation can be tested by light touch and pinprick. The digital examination will allow crude assessment of resting anal tone and voluntary squeeze pressure, and any sphincter defects may be palpable. Fissures, fistulae, prolapse, and hemorrhoids can also be assessed (1).

Investigation

Special investigations can provide useful information in the management of women with incontinence (Table 64.4). Presentation with new anal incontinence may be precipitated by a change in frequency or consistency of stool. Colonoscopy or CT colonography should be carried out to exclude pathologies such as malignancy or colitis. Anorectal physiology includes anal manometry and measurement of rectal sensation and compliance. Anal manometry allows measurement of functional anal canal length and resting and squeeze pressures. These provide objective evidence of internal and external anal sphincter function, respectively (39). Rectal sensation and compliance are usually measured by balloon distension to determine rectal hypo- or hypersensitivity and reduced or normal compliance. Anal canal sensation can be tested using a stimulating electrode and may be transiently impaired by vaginal delivery. Measurement of PNMTL assesses pudendal nerve function by stimulating the pudendal nerve on each side and measuring the evoked response in the external anal sphincter (26). Normal latencies do not necessarily exclude pudendal nerve damage since it may require 75% of the nerve to be disrupted to prolong the latency. Most centers have now moved away from routinely testing PNMTL due to a lack of reproducibility and tenuous clinical utility. Endoanal ultrasonography (EAUS) has revolutionized the understanding of anal canal anatomy (Fig. 64.1) (40, 41). Both the internal and external anal sphincters can be visualized and EAUS is the investigation of choice for the detection of defects in these sphincters (42). The detection of sphincter defects enables TABLE 64.4: Investigations for Anal Incontinence Investigation Imaging/structural Colonoscopy/CT colonography

Endoanal ultrasound (EAUS)

Magnetic resonance imaging (MRI)

Functional Anorectal Physiology • Manometry

• Rectal sensation and compliance Porridge continence tests Pudendal nerve motor terminal latency (PNMTL)

Information Colorectal pathology precipitating or contributing to incontinence Integrity of internal and external anal sphincter Thickness of internal anal sphincter Fistulae Integrity of internal and external anal sphincter Fistulae

Maximal resting anal canal pressure Maximal voluntary and involuntary squeeze pressures Endurance squeeze pressure Functional anal canal length Rectoanal inhibitory reflex First and urge sensation, maximal tolerated volume Assessment of continence Damage to pudendal nerves

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  FIGURE 64.1  (a) Normal endoanal ultrasound immediately postpartum. (b) Defects in internal and external anal sphincters. clinicians to select women to undergo surgical sphincter repair, and the accuracy of EAUS for detecting sphincter disruption has been validated by correlation with operative findings (43). Abnormal thinning of the internal sphincter can be measured accurately using EAUS; this may be indicative of idiopathic degeneration, whereas thickening of the muscle may be associated with prolapse syndromes. Magnetic resonance imaging (MRI) using an endoanal coil (mainly a research tool) provides excellent multiplanar views of the sphincter complex and can demonstrate defects in both the internal and external anal sphincters. Research has shown that external anal sphincter atrophy may only be visualized on MRI, not EUAS, although the quality of EUAS has improved since this research (44). Expertise in MRI of the sphincters is not widely available and most clinicians continue to rely on EAUS. Where both imaging facilities are available, one or both may be used for diagnosis since they are complementary. Interest in functional MRI in the wider context is increasing; however, the lack of standardization of nomenclature has limited current understanding.

Management Early recognition of obstetric injuries

Evidence of sphincter injury should be sought by careful bimanual examination in all women who have a perineal tear or who have had an instrumental delivery. This should be carried out by someone trained in the recognition of sphincter injury. In the United Kingdom, there are several courses specifically for training obstetricians in the identification and management of obstetric sphincter injuries. An adjunct to bimanual examination is the use of EAUS in the delivery suite immediately after postpartum. This is acceptable to women and can be used to diagnose sphincter injury and to assess the integrity of any repair (45). Once recognized, repair of a sphincter injury should be carried out by someone adequately trained to do so, in an operating theatre under regional or general anesthetic. Training in the repair of sphincter injury should be a part of the obstetric training program as the adequacy of sphincter repair is related to the experience of the operator (46). At postnatal follow-up visits, women should be asked directly about anal incontinence as they are about other postpartum symptoms. Increased general awareness of the risk of postobstetric sphincter injury among midwifery and obstetric staff will also aid in the early diagnosis and treatment

of anal incontinence. Early follow-up in a multidisciplinary clinic for women who have sustained obstetric trauma further increases the recognition of residual sphincter injury and enables effective early intervention where necessary (47).

Future mode of delivery

This is subject to debate and is ultimately down to patient choice (46). If a previous delivery has been complicated by OASI then the aim for future deliveries is to reduce the risk of recurrent anal sphincter injury and long-term anal incontinence. After assessment in the multidisciplinary perineal tear clinic, all women who are symptomatic or have abnormal EAUS and/or manometry should be counseled regarding the option of elective caesarean section (46). A population-based questionnaire of women whose first delivery was complicated by OASI did not show any difference in long-term anal incontinence between those who had undergone a further vaginal delivery (1472 women) or caesarean section (502 women); subsequent caesarean is not necessarily protective. However, patients who had undergone a second vaginal delivery were at risk of worsening pre-existing anal incontinence (48).

Conservative therapy

For most women, symptoms are relatively minor and should be managed conservatively, interventional procedures being reserved for those women with severe symptoms or in whom conservative measures fail.

Lifestyle

Dietary modification or a bulking agent such as ispaghula husk may improve symptoms. A daily routine for defecation may also help. The use of barrier creams such as zinc oxide ointment to prevent excoriation of perianal skin as a result of stool leakage is encouraged. High-fiber and a low-fat diet may prevent loose stools, a recognized risk factor of fecal incontinence (49). A crosssectional study of over 64,000 elderly women identified high BMI, lack of physical activity, and cigarette smoking as modifiable risk factors (50).

Drugs

Antidiarrheal agents such as codeine phosphate, loperamide, or diphenoxylate plus atropine reduce colonic motility and thus increase fluid absorption, producing more manageable formed stools. However, their side effects may include nausea,

Anal Incontinence constipation, and abdominal cramping. Enemas or rectal washouts may help some women. The enema induces a bowel action and keeps the rectum empty between bowel movements. Amitriptyline at a low dose may be of benefit for some women with anal incontinence. It is particularly useful for those with urgency and increased rectal sensitivity by slowing transit time and decreasing the amplitude and frequency of rectal motor complexes (51). In a Cochrane review on drug treatment for fecal incontinence in adults, the authors concluded that most of the drugs currently used are for the treatment of diarrhea rather than fecal incontinence, which may be due to the heterogeneous nature of the population within the review (52).

Biofeedback

Biofeedback therapy can be helpful for some women who are refractory to lifestyle and drug therapy. It is a behavioral technique using physical retraining of the anal sphincter and pelvic floor muscles with or without the aid of equipment, which provides auditory or visual feedback to alter physiological events (53). The technique uses electromyography, where a sensing device monitoring external sphincter contraction is connected to a transducer producing an audio or visual response for women. The audiovisual record of sphincter activity assists women in recognizing strength and length of contraction. Using a balloon to distend the rectum, women are encouraged to improve sphincter contraction in response to decreasing rectal distension, so that over a period of time their response becomes automatic. These techniques are most useful for women who are well motivated, have some rectal sensation, and are able to contract the external sphincter voluntarily. Interestingly, results of the investigative workup for fecal incontinence such as anorectal manometry, defecating proctogram, EAUS, MRI, and PNMTL do not predict the responders to biofeedback (54). In a series of 100 patients treated with biofeedback, 43 regarded themselves as cured and 24 symptomatically improved (55), 27 of the 46 patients in this series with structural sphincter damage also reported cure or improvement. Biofeedback is initially labor-intensive, requiring a dedicated therapist, but can be carried out at home after training. It has the advantage of being painless, safe, and complementary to other interventions. Biofeedback training has been shown to improve the functional outcomes for women with persistent symptoms following sphincter repair (56). However, some studies have suggested that it is the therapist rather than the technique that is important for the outcome (57). A systematic review of 731 patients in 8 studies found that biofeedback is recommended for the short and long-term treatment of fecal incontinence but that protocols, outcome measures, and training of providers varied across trials (58). Standards of biofeedback treatment are still lacking and an updated Cochrane review of 1525 subjects in 21 studies showed that while some elements of biofeedback may improve fecal incontinence following obstetric anal sphincter injury, larger well-designed trials are needed to enable definite conclusions (59).

Anal plug

Containment may be improved by the use of a disposable anal plug or tampon to enhance continence. The device expands after insertion and is removed to allow evacuation. The use of the anal tampon has been shown to improve continence scores and quality of life but only about half of patients found it comfortable to

689 use regularly (60). It has a role for those with severe symptoms who are awaiting (or are unsuitable for) surgery.

Surgery For some women, conservative therapies will fail and surgical options need to be considered. Two categories of patients may be identified: • Group 1: Women with evidence of a sphincter defect, especially with a deficient perineum • Group 2: Women whose sphincters are intact but weakened, secondary to denervation or muscle atrophy In the first group, direct repair of the sphincter defect should be considered; in the second group, decision-making is more difficult, the surgical options are more varied, and the outcome is less predictable.

Sphincter repair

Sphincter repair is the operation of choice where there is a single defect of the external anal sphincter, either alone or in combination with a defect of the internal anal sphincter. Two different surgical techniques have been used: direct apposition and overlapping repair. In the context where the cause of sphincter defect is due to previous obstetric trauma, then almost all are located anteriorly and a third of them will develop symptoms of anal incontinence over time (61). Sphincter repair by mobilization of the sphincter muscle, scar excision, and direct apposition resulted in a failure rate of around 40% (62), these poor results were attributed to the cutting out of sutures or retraction of the muscle ends. Parks and McPartlin subsequently modified this technique by identifying and repairing the torn internal anal sphincter separately and employing an overlapping repair of the muscle (63). There are six randomized control trials that compare the two techniques; at 36 months there appears to be no difference between them (64–69). However, a Cochrane review concluded that more evidence is needed to establish the optimum technique for repair (70). Most are in favor of immediate rather than delayed repair for third- or fourth-degree tears following delivery. Although both have demonstrated good results, immediate repair is more socially acceptable for the patient and delayed repairs should probably only be considered where expertise is lacking at the time of injury (64). The Royal College of Obstetricians and Gynaecologists in the UK recommend all immediate repairs be performed in an operating theatre with adequate light and exposure rather than in the delivery suite (46). Cooperation between obstetric and colorectal surgical colleagues (71) and a training program for obstetric trainees improves outcomes (72). ‘Sphincteroplasty’ is used to describe the secondary or delayed reconstruction of the anal sphincter muscles, usually a minimum of three months after the initial injury (73). Surgery is appropriate if there is more than one quadrant anal sphincter defect (74) and repair of concomitant cloacal defect or vaginal fistula and anterior levatorplasty can be performed (75). A defunctioning stoma following sphincter repair confers no benefit in terms of functional outcome and is associated with higher morbidity and longer hospital stay related to the stoma closure; it is only necessary where there is significant perineal sepsis (76). There is a benefit in using a laxative rather than a constipating regime (77) and prophylactic broad-spectrum antibiotics are

690 used to prevent infection, which may be linked to the breakdown of the repair. There are reports of continence to solid and liquid stool in 47% to 79% of patients undergoing overlapping sphincter repair (78–80). The outcome data should, however, be interpreted with caution as many series are small, with patients recruited over several years, often involving several operating surgeons and followup tends to be short. The groups of patients reported are often heterogeneous in terms of age, sex, and indication for repair. The frequent absence of standardized scoring systems or physiological measurements to evaluate continence pre- and postoperatively does not allow series to be readily compared. The outcome where there has also been damage to the internal sphincter is less certain. The importance of repairing the internal anal sphincter (when damaged), as well as the external sphincter, has been highlighted during the immediate repair of third-degree tears (81). The internal anal sphincter may be difficult to identify separately and therefore often repaired en-block with the anal canal mucosa in a 4th-degree tear. However, given that a persistent internal anal sphincter defect is associated with worse outcomes following repair of a 3rd- or 4th-degree repair (82, 83) separate repair of the internal anal sphincter is now recommended, if it can be identified (46, 70). Such attention should probably also be applied to repairing a deficient internal anal sphincter during the secondary repair. It is accepted, however, that internal sphincter defects may be more difficult to identify surgically and repair adequately, and soiling—together with incontinence to flatus—will remain a problem for some women.

Pre-operative factors predicting outcome from anal sphincter repair

There are no established pre-operative physiological parameters that can reliably predict outcomes (84, 85) but a number of other factors are predictive of outcomes.

Age and body habitus

Some authors have reported an adverse influence of increasing age, menopause, and obesity on outcomes (74, 86). Although older age is not a contraindication to surgery, it should certainly be considered in preoperative counseling.

External sphincter atrophy

The detection by MRI scanning of atrophy of the external anal sphincter, which is characterized by thinning and fatty replacement, has been shown to adversely affect outcomes following sphincter repair (44).

Failure of sphincter repair

A persistent defect on endoanal ultrasound is associated with early failure (87). Up to 10% of repairs may break down, resulting in persistent defects and poor functional results. Where such defects are identified, repeated sphincter repair may be successful (88) but since the operation may be technically more difficult and tissue quality poor, the outcome is less certain. Where failure has resulted from significant perineal sepsis, a temporary defunctioning colostomy may be required. Patients with an unsatisfactory outcome may be considered for adjunctive sacral neuromodulation (89).

Long-term outcomes after sphincter repair

Results appear to deteriorate with time (73, 90). In a 5-year followup study of incontinent women who had an overlapping repair for obstetric trauma, only 4 out of 38 were totally continent of solid and liquid stool and none was fully continent of stool and flatus

Textbook of Female Urology and Urogynecology (90). Whether the deterioration was due to progressive denervation of mobilized muscle or failure to repair internal sphincter defects adequately is uncertain. Long-term outcomes following a delayed repair are also suboptimal; 66% report excellent or good results in the short term but this decreases to 30–80% at 80 months and 6% at 120 months (73, 91). According to The International Consultation on Incontinence (ICI) and the Royal College of Obstetricians and Gynaecologists, sphincter repair remains the standard first approach for isolated defects, particularly in women presenting soon after obstetric injury (46, 73, 81). These women should be made aware that initial good results may not be permanent and that deterioration in continence may occur.

Postanal repair and total pelvic floor repair

Initially described by Sir Alan Parks in 1975, the postanal repair (PAR) aims to increase the length of the anal canal, restore the anorectal angle, and recreate the flap valve mechanism, previously thought to be essential to maintain continence (73). Observational studies have found that long-term results are poor, with only a third of women maintaining continence at 5-year follow-up. Total pelvic floor repair (TPFR) combines PAR with anterior sphincter plication and anterior levatoroplasty. Long-term follow-up indicates that TPFR rarely renders women fully continent, but around half have substantially improved continence and lifestyle (92). The poor long-term success rates reflect progressive neuropathy or atrophy of the muscles. These operations can have modest success in carefully selected patients but are largely obsolete due to the introduction of newer treatments (73).

Alternative surgical techniques

For women with symptomatic anal incontinence but an intact sphincter confirmed by imaging, other surgical options can be considered.

Sacral nerve modulation (SNM) or Sacral nerve stimulation (SNS)

SNM is a novel approach for women with incontinence and weak but intact internal and external sphincters which modulate the neurological control of the anorectum (Fig. 64.2). It was initially used in patients with detrusor instability and urinary retention in the 1980s (93). The observation of a simultaneous improvement in bowel symptoms in some patients led to its use by Matzel et al. in patients with anal incontinence in 1994 (94). SNM involves chronic low-frequency electrostimulation of one of the sacral spinal nerves (S2, S3, or S4). The mechanism of action remains uncertain but is most likely multifactorial and determined by the underlying condition; effects appear to be somatomotor, somatosensory, autonomic (95), mediated by somaovisceral reflexes (96), and mucosal neurochemistry (97). However, the effect of SNM on the anal sphincter is inconsistent; some authors reported an increased anal resting tone and maximum anal squeeze pressure while others reported the contrary (98–100). Clinical studies demonstrate improvement in continence in patients with external sphincter defects, suggesting the sphincter mechanism is not solely responsible for maintaining continence (101). The effects of SNM on rectal sensitivity and compliance are also unclear and conflicting (98, 99, 102). Possible reasons include small sample size and the heterogeneous etiology of anal incontinence within sample groups. Anorectal physiological studies do not appear to be a useful predictor of outcome for SNM.

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Pudendal nerve Inferior rectal nerve Posterior femoral cutaneous nerve

Dorsal nerve of clitoris or penis Posterior labial nerve Sciatic nerve Perineal nerve

FIGURE 64.2  Relationship between the position of sacral nerve stimulation device and relevant anatomy. (Courtesy of Medtronic, Inc., Minneapolis, MN Copyright 2010.) SNM is a minimally invasive, relatively safe procedure (103) with low morbidity (5–26%) (91). Morbidities include pain at implant site, seroma, excessive tingling in the vaginal region, and superficial wound infection but it does not involve any risk of direct sphincter injury (91). There are no predictors of SNM outcome and so it must be performed in two stages; patients first use a temporary electrode (percutaneous nerve evaluation (PNE)) to ensure adequate clinical response over a 1–4 week test period prior to surgical implantation of the permanent device. Following the initial trial, 60–88% of patients proceed to permanent implantation (104, 105). A meta-analysis published in 2011 of 665 patients who underwent SNM versus conservative treatment on patients with fecal incontinence found that the SNM group had reduced incontinence episodes, increased ability to defer defecation, and improved quality of life scores. A randomized controlled study by Tjandra et al. has demonstrated SNM to be more effective than optimal medical therapy, with the SNM group reporting significantly fewer incontinent episodes per week (from 9.5 to 3.1) and incontinent days per week (3.3 to 1) compared to controls (from 9.2 to 9.4 and from 3.3 to 3.1, respectively) (105). Within the same institute and population sample, Chan et al. also demonstrated that SNM improved continence in patients with external anal sphincter defects of up to 120° of circumference (101). Data on the long-term studies of SNM, with a mean followup of 51 to 74 months, have found a sustained improvement in fecal incontinence score and quality of life score (106–108). In the national registry of the Italian group of sacral nerve stimulation, Altomare et al. (108) reported a follow-up of 52 patients over a mean period of 74 months (range, 60–122). Out of 52 patients, 15 (28.8%) continued to suffer from complications, 18% achieved 100% continence, and 74% achieved at

least 50% continence. Matzel et al. (109) reported the followup of nine patients with a minimum of 7 years and a mean period of 9.8 years (range 7–14). Accidental loss of bowel content reduced from 40% to 0%, a median number of incontinence episodes/week from 9 to 0.4, and 44.4% of patients remained fully continent. A summary of the published data on long-term outcomes up to 2015 included 12 studies, ten European centers and a median follow up of 85 months (44–118) in 228 patients (110). SNM remained an effective treatment for fecal incontinence in approximately half the patients starting therapy. The longest-term published results are by Leo et al. who recently reported from St Mark’s Hospital with a median follow-up of 9 years (the longest follow up 23 years for one individual) (111). SNM was shown to be an effective treatment in the long term with an improvement in the St Mark’s Score in 60% of patients. The same group previously showed no loss of efficacy in three patients after a 10-year follow-up (112). There is increasing evidence that SNM may also be beneficial in patients with sphincter defects, either before or after attempted repair, although follow-up is still limited (73). A systematic review identified 10 studies (only 1 prospective) from 1995 to 2011 and included a total of 119 patients (113). Follow-up ranged from 4.5 to 48 months; the average number of incontinence episodes per week decreased from 12.1 to 2.3, the ability to defer defecation increased significantly and quality of life significantly improved. The International Consultation on Continence recommends SNM as a first-line surgical intervention in patients with severe incontinence refractory to conservative treatments (73).

Posterior tibial nerve stimulation

Posterior tibial nerve stimulation (PTNS) (Fig. 64.3) requires the application of electrical stimulation either percutaneously

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Textbook of Female Urology and Urogynecology does not allow stimulated transposition. The ICI recommends that unstimulated graciloplasty should not be routinely offered and is now rarely performed due to the advent of newer treatments (73).

Stimulated muscle transposition

FIGURE 64.3  Positioning of posterior tibial nerve stimulation device. (By courtesy of Uroplasty, Inc., Minnetonka, MN, all rights reserved.)

or transcutaneously, unilaterally over the posterior tibial nerve (located above and behind the medial malleolus). Currently, there are various protocols for the treatment with PTNS (e.g., one protocol involves 30 minutes per session, once a week for 12 weeks) (114). The CONFIDeNT study was a rigorous randomized control trial which compared PTNS with a sham electrical stimulation and failed to support the efficacy of PTNS. However, the secondary outcomes made it unclear as to whether PTNS may be useful for urge fecal incontinence and further studies are required to investigate this (115). At present, NICE raised no major safety concerns on the use of PTNS and concluded that there is evidence of efficacy in the short term in a limited number of patients. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research (116).

Neosphincters Non-stimulated muscle transposition

It is possible to augment the anal sphincter with another striated muscle. The muscles most commonly used are gracilis or gluteus but others such as obturator internus have also been employed (117). Graciloplasty involves mobilization of the muscle from the inner thigh, which is wrapped around the anal canal and fixed to the contralateral ischial tuberosity. Continence is reliant upon the muscle wrap being tight enough to keep the anal canal closed, as a coordinated voluntary contraction of the muscle itself is difficult. Gluteus transposition is a technically more demanding procedure but has the advantage that the muscles are easier to contract since the glutei are natural synergists of the anal sphincter. Results of unstimulated muscle transposition vary widely and it is now a rarely used technique. Bilateral graciloplasty may be useful where a lack of local technical expertise or financial resources

The observation that by chronic stimulation muscle fibers could be converted from type II fast-twitch to fatigue-resistant slowtwitch fibers led to the development of the stimulated graciloplasty, first reported in 1988 (117). The mobilization of the gracilis muscle and wrap are similar to that for unstimulated graciloplasty but involve identification of the nerve to gracilis and implantation of a stimulating electrode around the nerve trunk or its branches. The stimulator is placed in a subcutaneous pocket in the abdominal wall and the electrode wires tunneled to it. Contraindications include previous perianal sepsis or Crohn’s disease. In addition, the stimulator may interfere with pacemakers and implanted defibrillators. In a study of 52 patients undergoing stimulated graciloplasty, 73% were continent after a median follow-up of 2 years and success was associated with improved quality of life (118). Others have reported far less favorable results. Septic complications, hardware problems, and physiological imbalance have led to the high failure rates (117). Case selection is important; patients need to be well motivated and require careful preoperative assessment and counseling. The procedure has a recognized failure rate and may be associated with significant morbidity and scarring. In addition, patients may require significant input in terms of support for fine-tuning the stimulator. The ICI recommend that stimulated graciloplasty be offered to selected patients who have failed other treatment modalities, in particular where there is loss of the anal sphincter. Otherwise, this has been largely superseded by SNM (73).

Modified sphincteroplasty

Zutshi et al. have used a biologic porcine collagen mesh for the reinforcement of sphincteroplasty. Preliminary results from 10 cases show a marked reduction in continence rates and no complications (follow-up 6–24 months) but larger studies are required (119).

Artificial bowel sphincter

This innovative procedure for anal sphincter replacement was developed in the 1990s and is in effect a sophisticated modification of a Thiersch wire implantation. It comprises a cuff that is implanted around the anus and a pressure-regulating balloon that is placed behind the rectus muscles and connected to a pump placed in the subcutaneous tissues of the labia. Cuff opening is controlled by squeezing the labial pump that then empties the cuff to enable evacuation; the cuff then slowly refills from the pressure-regulating balloon over a number of minutes to close the anal canal. Contraindications include active sepsis, previous radiation, Crohn’s disease, and poor-quality perineal tissue (120). A systematic review showed that the need for surgical revision increases and continence decreases with time (121). Evacuation difficulty was common though only severe in 8% of patients. Patients should be assessed for evacuatory difficulties preoperatively and follow-up may include the need for enemas or laxatives. The device is not currently commercially available. This is going to cause problems for those patients who have experienced

Anal Incontinence good outcomes with this product when their device requires replacement (73).

Magnetic sphincter

A magnetic bead band has been initially used for the treatment of gastro-esophageal reflux disease (LINUX device, Torax® Medical) and this has also been applied for fecal incontinence (FENIX) aiming to enhance the anal sphincter pressure by its weak magnetic force. During defecation, the increased intraabdominal pressure allows the magnetic beads to separate, followed by reunion of beads to reestablish continence once stool is passed. The insertion of the titanium magnetic beads requires the patient to undergo a general anesthetic. Under aseptic technique, an incision is made in the perineal body and a tunnel is created along the circumference of the anal canal. The implant is then positioned after an estimation with a sizing tool and secured by tying sutures together. Preliminary studies showed that the implantation is simple and outcomes for fecal incontinence and quality of life were promising (122, 123). Three centers successfully implanted 14 devices with a reduction in the average number of incontinence episodes (7.2 to 0.7), a reduction in the Wexner continence score (17.2 to 7.8) and improvement in all four domains of The Faecal Incontinence Quality of Life Scoring System (122). In one comparative case-matched study, the magnetic anal sphincter was found to be as effective as the artificial sphincter in terms of improvement of incontinence and quality of life (124). However, one case series reported suboptimal results with no patients reporting a clinical response (defined as >50% reduction in the Wexner score) and a morbidity rate of 57% (125). Other case series found that some patients with an implanted magnetic anal sphincter can produce a sustainable result of up to 36 months (126). Complications from magnetic bead sphincter include infection, bleeding, perianal swelling, separation at the suture connection, and pain (124, 125, 127). Early complications include the need for device explanation due to either complications or device failure (128). Long-term outcomes from a multicenter study showed that magnetic anal sphincter augmentation provides excellent outcomes in patients who retain the device but that protocols are required to reduce early complications (128). Indeed, the SaFaRI trial which was a randomized control trial designed to compare the FENIX magnetic sphincter augmentation device with SNM in adults with fecal incontinence, ended prematurely (129). Numbers for analysis were low but of the 45 patients who underwent FENIX, 73.3% experienced at least one complication and 30% had to have their device explanted. Therefore, although early results were promising there are now concerns that morbidity and explant rates are prohibitively high and the future of the magnetic sphincter is uncertain. As a result, the device has been withdrawn from the market with the parent company focusing on the LINUX device for GORD.

Radiofrequency energy treatment

Endoscopic radiofrequency therapy (a.k.a. SECCA® procedure) aims to induce fibrosis in the anal sphincter and tighten its muscle fibers. It can be performed under general anesthetic or sedation with local anesthetic. Needle electrodes deliver heat-generated radiofrequency energy at several sites of the anal sphincter with temperature monitoring to avoid excessive heat (130). This may transiently improve continence in patients with nil to moderate symptoms but long-term results

693 are disappointing (131, 132). Reported complications include secondary hemorrhage, constipation, anal pain, and mucus discharge (133, 134).

Injectable bulking agents

The use of injectable bulking agents was first described by urologists for urinary incontinence. The technique of mechanical bulking of the anal sphincter has been used for fecal incontinence since 1993 (135). The ideal agent for injection should be biocompatible, non-allergenic, non-immunogenic, non-carcinogenic, and easy to inject and not migrate within tissues (73). There are various injectable bulking agents: Coaptite (calcium hydroxylapatite ceramic microspheres), Contigen (collagen implant), Durasphere (pyrolytic carbon-coated beads), EVOH (Ethylene Vinyl Alcohol), polyacrylamide gel (Bulkamid), and PTQ (textured silicone particles). Injections are usually into the submucosal region or at the site of the sphincter defect. More recently there has been interest in the injection of solid injectables which expand after their insertion through a custom-made introducer (Hi-HexpanTM (GatekeeperTM (136), SphinKeeperTM). The morbidities described (generally low) range from pruritus ani, persistent anal discomfort to perianal sepsis (137). A Cochrane review published in 2013 found all studies on injectable bulking agents for passive fecal incontinence to be of poor quality with no reported patient-reported outcomes or long-term results (138). Most trials did show short-term benefits. The ICI concludes that injectable biomaterials may be most useful for passive fecal incontinence (73) although one recent study has shown that GatekeeperTM leads to morphological changes in the external anal sphincter which also improves squeeze function (139). The exact role of injectables and the optimum bulking agent and technique for application are still to be determined (73).

Stem cell therapy and other tissue regeneration techniques

Experts propose that the most ideal solution to replace the function of the anal sphincter would be the biocompatible regeneration of tissue and restoration of its function (73). For example, one group has used autologous myoblasts from pectoralis muscle biopsies for injection into anal sphincter defects (140). Some are also currently exploring the use of allogeneic stem cells. These approaches remain experimental and should only be offered as part of a well-designed clinical trial (73).

Stomas

The American College of Gastroenterology clinical guideline for the management of benign anorectal disorders published in 2014 stated that colostomy should be the last resort to improve the quality of life for patients with severe intractable fecal incontinence (141). However, an end sigmoid colostomy is reasonable for patients who have failed or are not suitable for alternative treatment options, and are willing to accept the associated change in body image; in these individuals a stoma should not be seen as a treatment failure and may allow many women to return to a nearnormal lifestyle (73). Colostomy irrigation is possible and may further improve their quality of life. Unfortunately, for a few women with a colostomy, diversion colitis and persistent incontinence of mucus from the defunctioned rectum remains a problem and a proctectomy may be required (in one study, 25 out of 35 women with an end colostomy experienced persistent anal leakage and 12 of these patients required protectomy) (142).

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Summary Careful assessment and investigation of anal incontinence can usually determine the underlying cause. Most women can be managed conservatively by a combination of dietary modification, medication, and biofeedback. Where conservative treatment fails, surgery may be considered. Women with identifiable sphincter defects may benefit from overlapping sphincter repair that offers good short-term functional results. Women should be counseled that longer-term results are less certain. When sphincter repair fails or where the sphincter itself is intact but weak, SNM should be considered. Postanal repair, total pelvic floor repair, and unstimulated muscle transposition are largely obsolete. Other options include stimulated muscle transposition, SECCA® procedure, and injectables. Future developments may include stem cell therapy and other tissue regeneration techniques. For a few women who have failed all treatment modalities, diversion stomas may be recommended.

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92. Körsgen S, Deen KI, Keighley MR. Long-term results of total pelvic floor repair for postobstetric fecal incontinence. Dis Colon Rectum. 1997 July;40(7):835–9. 93. Oerlemans DJAJ, Kerrebroeck PEV van. Sacral nerve stimulation for neuromodulation of the lower urinary tract. Neurourol Urodyn. 2008;27(1):28–33. 94. Matzel KE, Stadelmaier U, Hohenfellner M, Gall FP. Electrical stimulation of sacral spinal nerves for treatment of faecal incontinence. Lancet Lond Engl. 1995 October 28;346(8983):1124–7. 95. Rosen HR, Urbarz C, Holzer B, Novi G, Schiessel R. Sacral nerve stimulation as a treatment for fecal incontinence. Gastroenterology. 2001 September;121(3):536–41. 96. Gourcerol G, Vitton V, Leroi AM, Michot F, Abysique A, Bouvier M. How sacral nerve stimulation works in patients with faecal incontinence. Colorectal Dis Off J Assoc Coloproctology G B Irel. 2011 August;13(8) :e203–211. 97. Normalization of substance P levels in rectal mucosa of patients with faecal incontinence treated successfully by sacral nerve stimulation | British Journal of Surgery | Oxford Academic [Internet]. [cited 2021 March 27]. Available from: https://academic.oup.com/bjs/ article/95/4/477/6156135 98. Roman S, Tatagiba T, Damon H, Barth X, Mion F. Sacral nerve stimulation and rectal function: results of a prospective study in faecal incontinence. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2008 October;20(10):1127–31. 99. Ganio E, Ratto C, Masin A, Luc AR, Doglietto GB, Dodi G, et al. Neuromodulation for fecal incontinence: outcome in 16 patients with definitive implant. The initial Italian Sacral Neurostimulation Group (GINS) experience. Dis Colon Rectum. 2001 July;44(7):965–70. 100. Koch SMP, van Gemert WG, Baeten CGMI. Determination of therapeutic threshold in sacral nerve modulation for faecal incontinence. Br J Surg. 2005 January;92(1):83–7. 101. Chan MKY, Tjandra JJ. Sacral nerve stimulation for fecal incontinence: external anal sphincter defect vs. intact anal sphincter. Dis Colon Rectum. 2008 July;51(7):1015–24; discussion 1024–1025. 102. Vaizey CJ, Kamm MA, Turner IC, Nicholls RJ, Woloszko J. Effects of short term sacral nerve stimulation on anal and rectal function in patients with anal incontinence. Gut. 1999 March;44(3):407–12. 103. Wexner SD, Coller JA, Devroede G, Hull T, McCallum R, Chan M, et al. Sacral nerve stimulation for fecal incontinence: results of a 120-patient prospective multicenter study. Ann Surg. 2010 March;251(3):441–9. 104. Koch SM, Melenhorst J, Uludağ O, Deutekom M, Stoker J, van Gemert WG, et al. Sacral nerve modulation and other treatments in patients with faecal incontinence after unsuccessful pelvic floor rehabilitation: a prospective study. Colorectal Dis Off J Assoc Coloproctology G B Irel. 2010 April;12(4):334–41. 105. Tjandra JJ, Chan MKY, Yeh CH, Murray-Green C. Sacral nerve stimulation is more effective than optimal medical therapy for severe fecal incontinence: a randomized, controlled study. Dis Colon Rectum. 2008 May;51(5):494–502. 106. Lim JT, Hastie IAG, Hiscock RJ, Shedda SM. Sacral nerve stimulation for fecal incontinence: long-term outcomes. Dis Colon Rectum. 2011 August;54(8):969–74. 107. Hull T, Giese C, Wexner SD, Mellgren A, Devroede G, Madoff RD, et al. Long-term durability of sacral nerve stimulation therapy for chronic fecal incontinence. Dis Colon Rectum. 2013 February;56(2):234–45. 108. Altomare DF, Ratto C, Ganio E, Lolli P, Masin A, Villani RD. Long-term outcome of sacral nerve stimulation for fecal incontinence. Dis Colon Rectum. 2009 January;52(1):11–7. 109. Matzel KE, Lux P, Heuer S, Besendörfer M, Zhang W. Sacral nerve stimulation for faecal incontinence: long-term outcome. Colorectal Dis Off J Assoc Coloproctology G B Irel. 2009 July;11(6):636–41. 110. Altomare DF, Giuratrabocchetta S, Knowles CH, Muñoz Duyos A, RobertYap J, Matzel KE, et al. Long-term outcomes of sacral nerve stimulation for faecal incontinence. Br J Surg. 2015 March;102(4):407–15. 111. Leo CA, Thomas GP, Bradshaw E, Karki S, Hodgkinson JD, Murphy J, et al. Long-term outcome of sacral nerve stimulation for faecal incontinence. Colorectal Dis. 2020;22(12):2191–8. 112. Hollingshead JRF, Dudding TC, Vaizey CJ. Sacral nerve stimulation for faecal incontinence: results from a single centre over a 10-year period. Colorectal Dis Off J Assoc Coloproctology G B Irel. 2011 September;13(9):1030–4. 113. Ratto C, Litta F, Parello A, Donisi L, De Simone V, Zaccone G. Sacral nerve stimulation in faecal incontinence associated with an anal sphincter lesion: a systematic review. Colorectal Dis Off J Assoc Coloproctology G B Irel. 2012 June;14(6):e297–304.

Textbook of Female Urology and Urogynecology 114. Findlay JM, Yeung JMC, Robinson R, Greaves H, Maxwell-Armstrong C. Peripheral neuromodulation via posterior tibial nerve stimulation – a potential treatment for faecal incontinence? Ann R Coll Surg Engl. 2010 July;92(5):385–90. 115. Knowles CH, Horrocks EJ, Bremner SA, Stevens N, Norton C, O’Connell PR, et al. Percutaneous tibial nerve stimulation versus sham electrical stimulation for the treatment of faecal incontinence in adults (CONFIDeNT): a double-blind, multicentre, pragmatic, parallel-group, randomised controlled trial. Lancet Lond Engl. 2015 October 24;386(10004):1640–8. 116. Percutaneous tibial nerve stimulation for faecal incontinence. Interventional procedures guidance (IPG395). NICE; 2011. 117. Niriella DA, Deen KI. Neosphincters in the management of faecal incontinence. Br J Surg. 2000 December;87(12):1617–28. 118. Baeten CG, Geerdes BP, Adang EM, Heineman E, Konsten J, Engel GL, et al. Anal dynamic graciloplasty in the treatment of intractable fecal incontinence. N Engl J Med. 1995 June 15;332(24):1600–5. 119. Zutshi M, Hull T, Gurland B. Anal encirclement with sphincter repair (AESR procedure) using a biological graft for anal sphincter damage involving the entire circumference. Colorectal Dis Off J Assoc Coloproctology G B Irel. 2012 May;14(5):592–5. 120. Gregorcyk SG. The current status of the Acticon® Neosphincter. Clin Colon Rectal Surg. 2005 February;18(1):32–7. 121. Hong KD, Dasilva G, Kalaskar SN, Chong Y, Wexner SD. Long-term outcomes of artificial bowel sphincter for fecal incontinence: a systematic review and meta-analysis. J Am Coll Surg. 2013 October;217(4):718–25. 122. Lehur P-A, Zerbib F, Neunlist M, Glemain P, Bruley des Varannes S. Comparison of quality of life and anorectal function after artificial sphincter implantation. Dis Colon Rectum. 2002 April;45(4):508–13. 123. Pakravan F, Helmes C. Magnetic anal sphincter augmentation in patients with severe fecal incontinence. Dis Colon Rectum. 2015 January;58(1):109–14. 124. Wong MTC, Meurette G, Stangherlin P, Lehur P-A. The magnetic anal sphincter versus the artificial bowel sphincter: a comparison of 2 treatments for fecal incontinence. Dis Colon Rectum. 2011 July;54(7):773–9. 125. Bridoux V, Gourcerol G, Leroi A-M, Ducrotte P, Michot F, Tuech J-J. Response to Barussaud et al.: the magnetic anal sphincter in faecal incontinence, is initial success sustained over time? Colorectal Dis Off J Assoc Coloproctology G B Irel. 2014 February;16(2):145–6. 126. Barussaud M-L, Mantoo S, Wyart V, Meurette G, Lehur P-A. The magnetic anal sphincter in faecal incontinence: is initial success sustained over time? Colorectal Dis Off J Assoc Coloproctology G B Irel. 2013 December;15(12):1499–503. 127. Lehur P-A, McNevin S, Buntzen S, Mellgren AF, Laurberg S, Madoff RD. Magnetic anal sphincter augmentation for the treatment of fecal incontinence: a preliminary report from a feasibility study. Dis Colon Rectum. 2010 December;53(12):1604–10. 128. Sugrue J, Lehur P-A, Madoff RD, McNevin S, Buntzen S, Laurberg S, et al. Long-term experience of magnetic anal sphincter augmentation in patients with fecal incontinence. Dis Colon Rectum. 2017 January;60(1):87–95. 129. Williams AE, Croft J, Napp V, Corrigan N, Brown JM, Hulme C, et al. SaFaRI: sacral nerve stimulation versus the FENIX magnetic sphincter augmentation for adult faecal incontinence: a randomised investigation. Int J Colorectal Dis. 2016 February;31(2):465–72. 130. Parisien CJ, Corman ML. The Secca® procedure for the treatment of fecal incontinence: definitive therapy or short-term solution. Clin Colon Rectal Surg. 2005 February;18(1):42–5. 131. Lam TJ, Visscher AP, Meurs-Szojda MM, Felt-Bersma RJF. Clinical response and sustainability of treatment with temperature-controlled radiofrequency energy (Secca) in patients with faecal incontinence: 3 years follow-up. Int J Colorectal Dis. 2014 June;29(6):755–61. 132. Abbas MA, Tam MS, Chun LJ. Radiofrequency treatment for fecal incontinence: is it effective long-term? Dis Colon Rectum. 2012 May;55(5):605–10. 133. Ruiz D, Pinto RA, Hull TL, Efron JE, Wexner SD. Does the radiofrequency procedure for fecal incontinence improve quality of life and incontinence at 1-year follow-up? Dis Colon Rectum. 2010 July;53(7):1041–6. 134. Kim D-W, Yoon H-M, Park J-S, Kim YH, Kang S-B. Radiofrequency energy delivery to the anal canal: is it a promising new approach to the treatment of fecal incontinence? Am J Surg. 2009 January;197(1):14–8. 135. Shafik A. Polytetrafluoroethylene injection for the treatment of partial fecal incontinence. Int Surg. 1993 June;78(2):159–61. 136. Ratto C, Buntzen S, Aigner F, Altomare DF, Heydari A, Donisi L, et al. Multicentre observational study of the GatekeeperTM for faecal incontinence. Br J Surg. 2016 February;103(3):290–9.

Anal Incontinence 137. Luo C, Samaranayake CB, Plank LD, Bissett IP. Systematic review on the efficacy and safety of injectable bulking agents for passive faecal incontinence. Colorectal Dis Off J Assoc Coloproctology G B Irel. 2010 April;12(4):296–303. 138. Maeda Y, Laurberg S, Norton C. Perianal injectable bulking agents as treatment for faecal incontinence in adults. Cochrane Database Syst Rev. 2013 February 28;(2):CD007959. 139. Grossi U, De Simone V, Parello A, Litta F, Donisi L, Di Tanna GL, et al. Gatekeeper improves voluntary contractility in patients with fecal incontinence. Surg Innov. 2019 June 1;26(3):321–7.

697 140. Frudinger A, Kölle D, Schwaiger W, Pfeifer J, Paede J, Halligan S. Musclederived cell injection to treat anal incontinence due to obstetric trauma: pilot study with 1 year follow-up. Gut. 2010 January;59(1):55–61. 141. Wald A, Bharucha AE, Cosman BC, Whitehead WE. ACG clinical guideline: management of benign anorectal disorders. Am J Gastroenterol. 2014 August;109(8):1141–57; (Quiz) 1058. 142. Catena F, Wilkinson K, Phillips RKS. Untreatable faecal incontinence: colostomy or colostomy and proctectomy? Colorectal Dis Off J Assoc Coloproctology G B Irel. 2002 January;4(1):48–50.

65

CONSTIPATION* Yvette Perston, Anil Bagul, Sarah Addison, and Simon Radley

Introduction “Constipation” is usually understood to imply infrequent bowel evacuations or difficult passage of feces persisting for a few weeks. It is one of the commonest medical complaints affecting patients of all ages, with an estimated UK prevalence varying from 8.2% to 52% [1]. Its incidence increases with age and is higher in those of lower socioeconomic class and with lower educational status [2]. The causes of constipation are multifactorial. These include dietary factors, toileting habits, medications, underlying medical conditions, psychological problems, organic diseases of the gastrointestinal tract (Table 65.1), and failures of the defecatory process [3]. Accurate history, clinical examination, and investigations are essential in identifying a cause for each patient’s symptoms.

Physiology of normal defecation Effective defecation requires coordinated efforts of colonic motility, intact rectal sensation, and pelvic floor relaxation. The primary function of the colon is the absorption of water from the small bowel effluent, leaving 100–150 mL of water in feces. A secondary function is to enable bacteria to ferment undigested fiber; the rectum stores feces until defecation takes place. Normal colonic transit varies from 24 to 96 hours and is generally longer in females and can be affected by the menstrual cycle [4]. The colon, rectum, and internal anal sphincter (continuation of the smooth muscle) are extrinsically innervated by the autonomic nervous system. The sympathetic innervation via the coeliac, superior, and inferior mesenteric plexus and hypogastric nerves (T11–L2) inhibits peristalsis and is sensitive to distension. The parasympathetic innervation by preganglionic vagal fibers and S2–4 splanchnic nerves increases peristalsis, contracts the rectum, and relaxes the internal anal sphincter to assist defecation. The intrinsic enteric nervous system (submucosal and myenteric plexuses) influences contractions and tone while the cells of Cajal are pacemakers. Local hormones also play a role.

Classification of constipation The Rome consensus group published the Rome IV criteria defining functional gastrointestinal disorders (Table 65.2). In order to be considered of medical significance, symptoms must be present for at least 3 months with onset of symptoms 6 months before diagnosis [5].

*

The current authors would like to acknowledge the contribution made to the original chapter by Kaori Futaba and Tony Mak.

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Subtypes of constipation

The Rome IV criteria categorize disorders of chronic constipation into four subtypes: a. b. c. d.

Functional constipation Irritable bowel syndrome with constipation Opioid-induced constipation Functional defecation disorders, including inadequate defecatory propulsion and dyssynergic defecation

These subtypes of constipation can coexist.

History “Constipation” implies different things to different people. An accurate history from the patient is important and should include size, consistency, frequency of defecation, and duration of symptoms. In a UK-based population study, 99% of healthy individuals (n = 1455) had between three bowel motions per day to three times per week [6]. The Bristol stool chart is helpful in describing consistency [7]. The presence of mucus or blood in or on stool and history of abdominal or perianal pain should be ascertained as well as any difficulty in evacuation, need for perineal pressure, or digitation vaginally or rectally. Patients with slow transit constipation may complain of infrequent bowel movements and lack of urge to defecate despite laxatives. IBS patients may present with chronic relapsing abdominal symptoms including abdominal pain and bloating associated with disturbed bowel habit [8]. If the patient has any of the red flag symptoms or signs (Box 65.1), they should be referred to a colorectal surgeon for further assessment to exclude colorectal cancer as per NICE guidance before proceeding to any further treatment [9]. Patients may have additional symptoms of urinary dysfunction or symptoms of uterine or vaginal prolapse, implying more global pelvic floor abnormality and dysfunction. It is important to ascertain if a patient has had a hysterectomy. Patients often date back the onset or exacerbation of symptoms to that time [10]. A thorough obstetric history may reveal a history of obstetric trauma; high vaginal parity; prolonged labor (which may be associated with uterine prolapse); enteroceles; rectocele; and descending perineal syndrome. These conditions may present as symptoms of obstructive defecation such as prolonged defecation with a sensation of anorectal obstruction and rectal fullness with tenesmus; as such, these are also important screening parts of a urogynecological or urological history. Women sometimes use vaginal and/ or anal digitation, or perineal pressure to aid evacuation. Initial treatment is based on lifestyle advice, and therefore, it is also mandatory to ascertain information on diet, fluid intake, exercise habits, and medical, surgical, and drug histories, as drug side effects may precipitate symptoms. Pelvic floor dysfunction is often associated with depression and anxiety, so questioning about additional contributing factors such

DOI: 10.1201/9781003144236-71

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TABLE 65.1: Causes of Secondary Constipation 1. General • Poor diet ± lack of exercise • Poor fluid intake/dehydration • Old age • Postoperative pain • Hospital environment (lack of privacy/use of bed pan) 2. Medication (BNF) Drug Group • Opiate • Antimuscarinic

• • • • • • • •

Tricyclic antidepressant Antipsychotics Parasympathomimetic alkaloid Vinca alkaloids Calcium channel blocker Diuretics Antacids Supplements

• Nicotine replacement 3. Metabolic/endocrine conditions • Amyloid • Glucagonoma • Hypercalcemia (hyperparathyroidism, milk-alkali syndrome) • Hypothyroidism • Hypokalemia • Panhypopituitary syndrome • Pheochromocytoma • Pregnancy • Porphyria • Arsenic/mercury/lead/phosphorus poisoning • Uremia 4. Bowel disorders • Obstruction: colorectal cancer, Crohn’s stricture, diverticular disease, volvulus • Pelvic mass (e.g., fetus, fibroid) • Fecal impaction • Megacolon/rectum 5. Neuromuscular conditions • Central disorder: tumors, trauma, cerovascular • Peripheral disorder: von Recklinghausen’s disease, multiple endocrine neoplasia • Spinal or pelvic nerve injury (e.g., obstetric trauma, surgery) • Aganglionosis (Hirschsprung’s and Chagas’ diseases) • Systemic sclerosis • Multiple sclerosis • Parkinson’s disease • Diabetic neuropathy • Pan gut dysmotility 6. Psychogenic • Anxiety/depression • Obsessional personality • Sexual/physical abuse • Immobility • Anorexia nervosa, bulimia, eating disorder Source:

Condition Pain control Overactive bladder Parkinson’s disease Asthma Depression Schizophrenia Xerostomia/Sjögren’s Leukemia/lymphoma Arrhythmias/hypertension Heart failure Indigestion Iron deficiency anemia Osteoporosis Aid smoke cessation

Keighley MR and Williams NS eds., Surgery of the Anus, Rectum and Colon, Saunders Ltd., 2007, with permission.

Examples Codeine, morphine, fentanyl Oxybutynin, solifenacin Procyclidine, benzhexol Ipratropium Amitriptyline, dothiepin Chlorpromazine, clozapine Pilocarpine Vincristine, vinblastine Verapamil Furosemide Calcium/aluminum + antacids Ferrous sulfate Ergocalciferol Nicotine lozenges

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Irritable Bowel Syndrome (ISC-C)

Must include at least two of the following:

1.Characterized by abdominal pain at least 1 day per week, where the pain is associated with at least two of the following:

• • • • •

Straininga Lumpy or hard stoola Sensation of incomplete evacuationa Sensation of anorectal blockagea Manual maneuvers to facilitate defecation a (digital evacuation, support of the pelvic floor) • 40 years old). • Persistent rectal bleeding for 6 weeks without anal symptoms (>60 years old) • Change in bowel habit to looser stools or increased frequency for 6 weeks (>60 years old) • Palpable right iliac fossa mass • Palpable rectal mass (intraluminal) • Unexplained iron deficiency anemia (Hb < 11 g/dL for men and Hb < 10 g/dL in nonmenstruating women) as psychiatric illness and any history of sexual abuse may yield important information that may modify treatment regimens [11]. Patients with constipation may also report an increased incidence of sexual and physical abuse and poorer health status than the general population [12]. In a study of 118 constipated patients, 32% reported physical abuse and 22% sexual abuse [13]. It is important that the issue of abuse is explored with appropriate backup from a safeguarding team where required. Patients often report that their bowel problems have adversely affected their family life, their relationships, work, and social life [14]. In a cross-sectional survey, Sun et al. [14] found that individuals with chronic constipation compared with matched controls were more likely to take sick leave and report general health impairment affecting work performance.

Clinical examination Abdominal examination may be unremarkable in most patients but it is important to rule out any intra-abdominal masses.

Rectal examination is mandatory looking for skin tags, anal fissures, external hemorrhoids, and excoriation if present. Gaping of the anal opening may suggest an underlying neurological problem or a full-thickness rectal prolapse. It is important to check for altered sensation around the perianal skin and perineum. A lack of reflex contraction of the external anal sphincter to perianal stimulation may indicate impaired pelvic innervation. Patients may demonstrate a full-thickness rectal prolapse, a bulge into the vaginal introitus indicating a rectocele, or bulging of the perineum below the ischial tuberosities indicating perineal descent. Digital rectal examination is performed systematically to assess resting anal tone and squeeze pressure by asking the patient to clench their anus on the examining finger. The finger is swept clockwise and anticlockwise to examine the entire circumference of the anal canal feeling for masses, ulceration, and tenderness. The puborectalis muscle is examined by hooking the finger posteriorly over the coccyx. The puborectalis should be relaxed when the patient is asked to strain. In patients with anismus or dyssynergia, the puborectalis muscle often fails to relax or may be felt to contract when they strain. The sensitivity and specificity of diagnosing dyssynergia on rectal examination are 75% and 87%, respectively, when two or more of the following are identified on rectal examination: impaired perineal descent, paradoxical anal contraction, or impaired push effort [15]. Rigid sigmoidoscopy or proctoscopy examination in the clinic can be a useful adjunct in assessing any mucosal abnormality in the anus and rectum as well as assessing rectoanal intussusception (mucosal folds may be visible when straining). If there is a history of vaginal prolapse or obstructed defecation, vaginal/pelvic examination should also be performed.

Investigations A systematic review looking at the clinical utility of diagnostic tests for constipation showed no clear evidence to support performing routine blood tests, radiography, and endoscopy in

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patients with constipation without “red flag” symptoms [16, 17]. So screening for metabolic causes of constipation with full blood count and biochemistry including calcium and thyroid function tests should be reserved for new patients presenting with constipation where there is a high index of suspicion or relevant medical history. A meta-analysis of prospective cross-sectional surveys and cohort studies demonstrated no increase in the prevalence of colorectal cancer in patients with constipation [18]. Patients with red flag symptoms or concerns about an intraluminal cause for their symptoms should have endoscopic (flexible sigmoidoscopy/colonoscopy) or radiological examination (CT colonography/contrast study). Additional investigations are reserved for patients who fail simple medical therapy. A modified algorithm for the management of constipation by the American Gastroenterological Association is shown in Figure 65.1 [19]. The following tests are useful in distinguishing between normal, slow-transit constipation, and obstructed defection

syndrome (ODS). The pros and cons of each investigation are summarized in Table 65.3 [16].

Diagnostic studies to evaluate anorectal function Balloon expulsion test

This is a simple bedside test performed to assess the patient’s ability to expel an artificial stool. A balloon is placed in a patient’s rectum and filled with water. The patient is then asked to expel the balloon. Normal expulsion time is within a minute. Although a failure to expel a 50 mL balloon suggests dyssynergia, a normal test does not exclude the diagnosis [17].

Anorectal manometry

This provides comprehensive information regarding rectal sensation, rectoanal inhibitory reflexes (RAIRs), and anal sphincter function. Anorectal manometry is a useful test for diagnosing

History and examination

Consider baseline tests to exclude colonic pathology and secondary cause of constipation

Trial of diet and life style modification +/– laxatives

Consider balloon expulsion test/ transperineal US scan/ anorectal manometry

Normal

Inconclusive

Abnormal

Colonoic transit study

Defaecating proctogram MR proctogram

Defaecatory disorder (DD)

Nomal

Abnormal

Normal transit constipation

Slow transit constipation (STC)

Normal

Abnormal

Colonic transit study

Normal– simple DD

Abnormal– mixed DD and STC

FIGURE 65.1  Investigation algorithm for chronic constipation. (Based on American Gastroenterological Association et al., Gastroenterology, 144(1), 211, 2013; modified.)

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TABLE 65.3: Evidence-Based Summary of the Clinical Utility of Diagnostic Tests for Chronic Constipation Test

Pros

Cons

Evidence

Recommendation

Abdominal X-ray

Simple, widely available to identify excessive fecal loading Identify megacolon/rectum, stenosis, diverticulosis, intraluminal abnormality Evaluate colonic transit, inexpensive Evaluate slow/normal/rapid transit

Lack of standardization

Poor

C

Radiation exposure

Poor

C

Inconsistent methodology Expensive, time-consuming

Good Good

B2 B2

Variable availability

Excellent

A1

Radiation exposure, interobserver bias, inconsistent, embarrassment Lack of standardization expensive, variable availability Interobserver bias, variable availability Embarrassment

Fair

B3

Fair

B3

Poor

C

Good

B2

Invasive, variable availability

Good

B2

Lack of standardization

Good

B2

Barium enema

Shapes transit study Colonic transit with scintigraphy Wireless Motility Capsule Defecating proctogram

MR proctogram

Anorectal ultrasound scan Anorectal manometry

Colonic manometry Balloon expulsion test

Evaluation of upper and lower GI transit, no radiation Identify dyssynergia, rectocele, prolapse, excessive decent, Hirschsprung’s disease Evaluates pelvic floor anatomy, sphincter morphology, and dynamic motion Visualization of anal sphincters Identify dyssynergic defecation, rectal hyposensitivity/hypersensitivity, impaired compliance Identify colonic myopathy, neuropathy Bedside assessment of dyssynergic defecation

Source: Rao SS and Meduri K, Best Pract Res Clin Gastroenterol, 25(1), 127, 2011, with permission. Notes: Grade A1: excellent; Grade B2: Good; Grade B3: Fair; Grade C: Poor. Evidence in favor of the test with some evidence on specificity, sensitivity, accuracy, and positive predictive values.

dyssynergy (Fig. 65.2) and altered rectal sensation and helps identify patients who may be suitable for biofeedback therapy [16]. A catheter-mounted balloon is inflated incrementally to 1. First constant sensation 2. Desire to defecate volume 3. Maximum tolerated volume These three simple sensory thresholds cannot distinguish the factors influencing sensation including compliance and neural pathways [20]. Decreased sensation of distension is seen in obstructed defecation, but the evidence that this is due to parasympathetic nerve damage is debatable [21, 22]. Damage to these nerves may be a factor in constipation following hysterectomy [23]. By using isobaric distension of a balloon, rectal compliance can be calculated as the steepest gradient of the curve plotting volume instilled divided by rectal pressure. Where compliance is high, greater volume needs to be instilled to achieve a given rise in pressure. This is the case in megarectum or in obstructive defecation. Decreased compliance (reduced laxity, increased hypersensitivity) is often found in inflammatory bowel disease or after pelvic radiotherapy. RAIR is the reflex relaxation of the internal sphincter that occurs when a balloon is inflated in the rectum and is absent in Hirschsprungs disease. Factors such as body position and consistency of stool play a role in one’s ability to expel stool. Up to 20%

of asymptomatic healthy adults do not produce normal relaxation during attempted defecation [24]; hence, a finding of dyssynergia on anorectal manometry alone is not diagnostic.

Defecating proctography

Defecating proctography dynamically images the rectum and pelvic floor during attempted defecation. Contrast is inserted into the rectum, vagina, and small bowel to delineate each structure. The patient is asked to defecate on a commode under fluoroscopy to assess the process and effectiveness of defecation. Functional obstruction due to paradoxical contraction of puborectalis muscle can be estimated by measuring the anorectal angle during defecation. Other causes of obstructive defecation such as rectocele, rectoanal intussusception, rectal prolapse, enterocele, sigmoidocele, vault prolapse, and excessive perineal descent can be identified. Small rectoceles may be physiological (Fig. 65.3). MR proctography has the advantages of avoiding radiation and producing better anatomical and functional images of the pelvic floor anatomy, especially in patients who have had previous surgery [25, 26] (Fig. 65.4). A study comparing the results of defecating proctography and MR proctography in patients presenting with obstructive defecation symptoms found MR underreported pelvic floor abnormalities especially when there has been poor rectal evacuation [27]. This may be due to the fact that MR proctograms are often performed in a supine position with the patient defecating lubricating gel and patients find it difficult to evacuate in this nonphysiological position [27].

Constipation

703 Insertion of 60 mL of air into rectal balloon

Anal canal resting pressure

Removal of air

Decreased pressure in anal canal as internal anal sphincter relaxes

Anal canal pressure returns to normal resting pressure

(a) Insertion of 60 mL of air into rectal balloon

Anal canal resting pressure

Removal of air

Anal canal pressure Increased as internal and sphincter contracts instead of relaxing Returns to resting pressure

(b)

FIGURE 65.2 Anal manometry showing an example of a patient with normal rectoanal inhibitory reflexes (a) and anismus (b). (Courtesy of Mrs. Joanne Hayes, Clinical Physiologist, UHB, Birmingham, U.K.)

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704

Small bowel

Vagina

Vagina Small bowel Rectocele Rectum

Rectum

Anus (a)

(b)

FIGURE 65.3  Defecating proctogram demonstrating large rectocele (a) and enterocele (b). (Courtesy of Dr. Peter Guest, Consultant Radiologist, UHB, Birmingham, U.K.) An MR-based classification for ODS has been described by Piloni et al. based on combinations of abnormalities found (Table 65.4) [28].

Ultrasound scan

Transperineal or translabial ultrasound scans allow multi-planar real-time imaging of the pelvis, providing important information

on the dynamic functional anatomy of the pelvic floor. It is reported to have excellent tissue discrimination, allowing visualization of modern mesh implants that are difficult to see in other modalities [29]. Transperineal ultrasound scanning may complement the aforementioned defecography by providing more information on rectal compliance and movement [30].

Diagnostic studies to evaluate intestinal transit

Since patient’s recall of their bowel habit is often inaccurate, it is helpful to have an objective measure of transit. In the general population, the colonic transit time is normally less than 72 hours [31]. Various modalities are now available to determine gastrointestinal transit time [32].

Bladder

Transit study using radiopaque markers

Enterocele

Rectum

Differences in performing this test exist between different institutions. One validated method is the ingestion of 10 radio-opaque markers per day for 6 consecutive days followed by a plain AXR on day 7. The number of remaining markers is counted and the colonic transit time can be calculated by dividing the number of retained markers by the daily dose [33]. Alternatively, different shaped radiopaque markers are ingested at 0, 24, and 48 hours and an abdominal X-ray is taken at 120 hours [34, 35] (Fig. 65.5). Normal colonic transit is defined as >20% markers at 12 hours and 2 cm or trapping 2nd-/3rd-/4th-degree intussusception Rectal floor descent > 5 cm below PCL Focal LA defect < 1 cm Multiple pelvic organ prolapse Multifocal LA defects > 1 cm Detachment of endopelvic fascia Anastomotic stricture/deformity Reduced rectal capacity Rectal pockets, sinus tract, granuloma Persistent rectocele, intussusception Difficult emptying/contrast retention Distortion of vaginal shape Pudendal nerve neuropathy

5

Source:

Surgical (colorectal)

Surgical (urogynecology) Multidisciplinary approach

Piloni V et al., Tech Coloproctol, 17(5), 501, 2013, with permission.

scintigraphy is used to measure regional colonic transit by swallowing a pH-sensitive capsule containing 111In absorbed on activated charcoal that is released in the terminal ileum. This will clarify if the patient has diffused or localized dysmotility [40]. Scintigraphy can be useful when considering surgical treatment.

WMC

A SmartPill wireless motility capsule (WMC) is ingested with pH, temperature, and pressure sensors allowing a noninvasive

method of measuring gastric emptying and small bowel and colonic transit [41]. WMC may reduce the need for further invasive motility tests [42, 43].

Colonic manometry

Colonic manometry catheters are placed using a colonoscope or via a guidewire. A 24-hour recording allows complete assessment of overall motor activity in the colon at rest, during sleep, while walking, and after meals and medication, which may be helpful in diagnosing underlying myopathy or neuropathy, especially in children [44].

Treatment The majority of patients presenting to their GP will respond well to simple conservative measures such as dietary and lifestyle advice and laxatives. Patients with persistent symptoms who are referred to the tertiary referral centers will benefit from investigation to identify those with slow transit constipation, obstructive defecation, or normal transit/IBS-C and to guide treatment.

Conservative management Dietary and lifestyle advice

R

FIGURE 65.5  Shapes study of a patient with slow transit constipation taken at 120 hours. (Courtesy of Dr. Peter Guest, Consultant Radiologist, UHB, Birmingham, U.K.)

In contrast to the traditional advice to increase fiber intake (fruit, vegetables, or wheat bran), Tack et al. [45] suggested that patients with slow transit constipation (STC) are unlikely to respond to increased dietary fiber. In addition, Muller-Lissner et al. [46] highlighted that an increase in fiber intake may actually worsen the symptoms of chronic constipation by increasing fermentation in the gut causing bloating. The latest NICE guidelines recommend that patients with IBS-C reduce their intake of insoluble fiber (i.e., wheat bran) and increase the proportion of soluble fiber, i.e., oats [47]. There is minimal evidence to suggest that increasing fluid intake will increase transit times unless an individual is dehydrated, but fluid intake of 1.5 L/day is usually advised. One controlled trial has shown that higher fluid intake in the presence of a high-fiber diet can improve symptoms of chronic constipation [48]. Exercise is recommended for chronic constipation, with a systematic review and meta-analysis of nine randomized controlled trials (n = 680) supporting its benefit and feasibility [50].

Textbook of Female Urology and Urogynecology

706 In addition, position when defecating is important and, in many societies, squatting is the normal posture used. The sitting position with a 90° posture is a relatively recent innovation used in Western toilets. This sitting position causes a narrow anorectal angle that increases the straining needed to empty the rectum. A study designed to compare the straining forces applied when sitting or squatting looked at normal volunteers defecating in three positions: sitting on a standard-sized toilet seat (41–42 cm high), sitting on a lower toilet seat (31–32 cm high), and squatting [51]. Both the net time needed for the sensation of satisfactory bowel emptying and the degree of straining were significantly less in the squatting position compared with both sitting positions (p < 0.0001). Thus, patients are advised to adopt a position where the knees are above the hips with feet flat on the floor. There are now several devices available to enable a squatting position to be adopted on a pedestal toilet.

Laxatives

A variety of laxatives are now available for treating constipation; all are more effective than placebo [52]. The mechanism of each type of laxative will help to determine the most appropriate type of laxative for the patient’s symptoms (Table 65.5) [33].

Bulk laxatives/fiber

Undigestible fiber is an important part of our diet to provide stool bulk. Bulk-forming laxatives attract water, forming larger and softer stool, which in turn causes colonic distension, stimulating peristalsis and effective propulsion of stool along the colon to rectum. It is useful to those patients passing small hard stools. It may cause symptoms of bloating but is usually well tolerated. A systematic review has reported that bulking agents induce an average increase of 1.4 bowel movements per week [53].

Osmotic laxatives

Osmotic laxatives increase the amount of water in the colon. Lactulose (semisynthetic disaccharide, poorly absorbed sugar), macrogols (inert polymers of ethylene glycol), or magnesium salts retain fluid in the colonic lumen causing osmotic diarrhea. Absorption of magnesium is limited but caution must be exercised in patients with impaired renal function [54]. Lactulose is less effective than macrogols [55] and its use may be limited due to flatulence and bloating caused by bacterial fermentation. Phosphate enemas are also an osmotic laxative.

Stool softeners

Stool softeners can be administered orally (liquid paraffin and docusate sodium) or rectally (glycerol) to soften and lubricate the stool.

Stimulant laxatives

Diphenylmethane derivatives such as bisacodyl, sodium picosulfate and anthraquinone derivatives such as senna are stimulant laxatives, which act on the enteric nervous system to increase intestinal motility but may cause abdominal cramps as a consequence. This can be managed by titrating the dose. Long-term use of anthraquinone-derived stimulants can generate brown discoloration of mucosa known as pseudomelanosis coli. Docusate sodium and glycerol are both stimulants and softening agents. Parasympathomimetics such as neostigmine enhance parasympathetic activity in the gut and increase intestinal activity. It is rarely used for constipation. Neostigmine can be used in selected cases for the treatment of pseudoobstruction that has failed to settle with conservative management [56].

5-HT4 receptor agonists

Prucalopride is a selective serotonin (5-HT4) receptor agonist with prokinetic activity. NICE has recommended the use of prucalopride in women with chronic constipation who have failed to improve with at least two laxatives from different classes at the highest recommended dose for at least 6 months [57]. Efficacy of the treatment should be reviewed after a 4-week trial of the medication. In elderly patients, a reduced dose of 1 mg/day is recommended. The pivotal randomized double-blinded placebocontrolled trials carried out with a total of 1999 adults with chronic constipation (PRU-INT-6, PRU-USA-11, PRU-USA-13) showed that the proportion of subjects treated with prucalopride 2 mg/day who had three or more spontaneous complete bowel movements per week during weeks 1–4 ranged from 23.7% to 32.1%, compared with 9.8% to 11.5% for placebo (all p ≤ 0.001) and during weeks 1–12 ranged from 19.5% to 28.9%, compared with 9.6% to 13.0% for placebo (all p ≤ 0.001) [58–60]. Headache, nausea, and diarrhea were more common side effects with prucalopride compared to placebo [52]. A smaller study comparing the efficacy of prucalopride on patients with different subtypes of constipation showed that all categories of constipation may respond to prucalopride [61].

Treatment of irritable bowel syndrome with constipation

It is important to identify symptoms that are affecting the individual patient and tailor the treatment accordingly [8, 47].

TABLE 65.5: Summary of Laxatives Laxative Type

Examples of Laxatives

Mechanism of Action

Side Effects

Bulk forming Osmotic

Ispaghula husk, methylcellulose Lactulose, macrogols, magnesium salts

Increase fecal mass Increase water in colon

Stool softeners

Liquid paraffin, docusate sodium

Stimulant 5-HT4 agonists

Bisacodyl, sodium picosulfate, senna Prucalopride

Colonic secretagogues

Linaclotide

Luminal water binding, increases stool bulk Increase intestinal motility stimulates colonic and intestinal peristalsis Promoted fluid secretion into GI lumen

Bloating Flatulence, bloating Dehydration Electrolyte abnormality Abdominal pain and cramps

Source:

Tack J et al., Neurogastroenterol Motil, 23(8), 697, 2011, with permission.

Abdominal pain and cramps Nausea, vomiting, abdominal pain, dyspepsia, flatulence, headache Diarrhea

Constipation

707

To treat their constipation, bulk-forming laxative, such as soluble fiber (ispaghula husk or oats), or osmotic laxatives (macrogol) are recommended. Antispasmodics or low-dose tricyclic antidepressants may ease abdominal pain associated with IBS. Linaclotide is currently licensed for the treatment of moderate to severe IBS associated with constipation and is NICE approved [62]. It is a first-in-class, oral guanylate cyclase-C receptor agonist of enterocytes. It induces intestinal chloride and fluid secretion through cyclic GMP production [63]. Three RCTs comparing linaclotide with placebo containing 1582 patients showed that 290 μg once daily significantly improved abdominal pain, bloating, and constipation associated with IBS-C [64–66]. The most frequently reported side effect was diarrhea [67, 68].

Biofeedback has been shown to be more effective than laxatives [85], relaxation training [83], and placebo [84]. A systematic review of seven trials, with a total of 413 participants, concluded that biofeedback conferred a sixfold increase in the odds of treatment success [80]. There is some evidence that evacuating regularly may also stimulate gut transit and so improve symptoms [87]. Whereas short-term results may vary from 60% to 90% improvement [88], long-term studies report sustained improvement in around 50% of patients [89]. As the treatment involves dedicated sessions with a single clinician, the development of that therapeutic relationship may also contribute to improvements in quality of life.

Opioid-induced constipation (OIC)

Psychological therapy

Opioids are a class of potent analgesics, and their use has increased markedly in recent years [69]. The GI tract is abundant in opioid receptors and their agonism leads to reduced intestinal secretion and motility giving rise to OIC. OIC occurs in up to 80% of patients receiving opioids for cancer and up to 57% of patients receiving opioids for non-cancer pain [70]. Opioids also affect sphincter function causing increased contraction of the internal anal sphincter which, in turn, results in straining, hemorrhoids and/or a sense of incomplete evacuation [71]. Peripherally acting μ-opioid receptor antagonists (PAMORAs) constitute a class of drugs which reverse opioid-induced constipation (OIC) with similar opioid analgesic effects. A recent European expert consensus statement on OIC advises PAMORAs to be prescribed if standard laxatives have failed, which is the case in up to 50% of patients [72]. Naloxegol and Naldemedine are the two orally available PAMORAs available in the UK both of which have been shown to be superior to placebo in increasing bowel movements over baseline [73, 74] and are NICE approved [75, 76].

Biofeedback

Biofeedback is based on behavior modification and operant conditioning [77] and is used to manage patients with dyssynergic defecation. It teaches patients how to control a physiological function that is not usually under conscious control by using an instrument that provides visual and/or auditory feedback of an action. Three main methods of monitoring defecation and providing biofeedback to patients are EMG biofeedback, manometric biofeedback, and balloon sensory training [78]. None have been shown to be consistently more effective than any other method [79] but EMG biofeedback is the method most widely used [80]. Gut-directed biofeedback involves patients being taught to defecate successfully using bracing of the abdominal wall muscles and effective relaxation of the pelvic floor muscles [81]. This may be enhanced by the use of a water-filled rectal balloon, which patients attempt to expel. Patients are enabled to recognize the sensations associated with relaxation of the pelvic floor and anus together with the correct use of abdominal muscles to create an effective pushing force and thus learn to defecate effectively. Patients may also be given basic instruction on gut anatomy and function to enhance their understanding, as well as behavioral advice about frequency and length of toilet visits, posture on the toilet, and dietary habits [87]. Numerous nonrandomized studies of biofeedback for idiopathic constipation have published positive results, suggesting that biofeedback is an effective intervention for constipation due to both slow gut transit [78] and evacuation disorders [83–86].

Psychological therapies can improve symptoms without interacting with pharmacological treatments [90]. Additionally, they can improve patient’s ability to cope with the symptoms thus improving quality of life. Discussion of symptoms with a supportive health-care professional who listens and responds appropriately can reduce feelings of isolation and shame. Some patients need more formalized psychological interventions, including counseling and cognitive behavioral therapy.

Rectal irrigation

Rectal irrigation was originally used in clinical practice for children with spina bifida [97]. Indications were extended to adults with neurogenic bowel dysfunction after conservative management had failed [92]. It is now used in a wider variety of conditions such as rectocele, obstructed defecation, and other functional bowel problems [93]. It is taught to patients as a self-management method. Several products are available on the market; hence, the product can be chosen to suit individual patient’s needs. They are designed to be used while sitting on the toilet to avoid accidents when transferring. Mini systems allow irrigation with up to 90 mL of water (Aquaflush Compact, Mini Qufora) and are used to aid initiation and completion of defecation, being helpful in patients with symptoms of ODS and incomplete evacuation [94, 95]. The larger systems allow irrigation with a cone or balloon catheter, enabling instillation of larger quantities of water, used in patients with slow transit constipation or neurological abnormalities (Aquaflush Quick, Qufora, Peristeen, Navina). In long-term follow-up of 169 patients over 56 months, rectal irrigation was found to be effective in 44% of patients with fecal incontinence and 62% of patients with defecatory disorders [21]. Collins and Norton retrospectively assessed 50 consecutive patients using the mini system and found that 62% improved or their symptoms completely resolved [96]. Absolute contraindications include stenosis, colorectal cancers, acute diverticulitis, and active inflammatory bowel disease. Most complications reported are minor and include abdominal cramps, minor anal bleeding, and leakage of irrigant after completion [93]. Introduction of a medical device and administration of water carry a risk of bowel perforation. In a consensus review of best practice, the perforation risk was estimated at 1 per 50,000 and was thought to be noncumulative [97]. For this reason, it is important that irrigation is taught by qualified experienced clinicians. Faaborg et al. have studied the long-term effects of using rectal irrigation in patients with functional bowel disorders and found that there was no long-term deterioration in anal sphincter function or rectal compliance [98].

Textbook of Female Urology and Urogynecology

708 Neuromodulation Percutaneous tibial nerve stimulation (PTNS)

PTNS delivers electrical stimulation through an acupuncture needle placed medially above the ankle. It is postulated that stimulation of the tibial nerve in turn stimulates the sacral nerves thus neuromodulating bowel motility and/or sphincter function. The treatment is outpatient based and consists of 12 weekly 30-minute sessions. Two observational studies have yielded conflicting results in patients with constipation and to date no randomized controlled trials have been performed [99, 100].

Sacral nerve stimulation (SNS)

Initially SNS was of interest as a first-line surgical intervention for constipation after an incidental finding of increased bowel frequency and improvement in constipation of those who underwent permanent SNS for bladder dysfunction or fecal incontinence [101, 102]. However, two recent double-blind sham-controlled randomized trials have shown no benefit, with no improvement in frequency of bowel actions [103, 104]. In addition it is an expensive invasive procedure with morbidity rates of up to 34% [105].

Complementary medicine

Many patients resort to alternative medicine in desperation to find a solution to their symptoms. A recent systematic review found that acupuncture was safe and led to an increase in stool frequency and an improvement in symptoms [106]. There are no other robust studies available on the role of complementary therapies. Patients should be advised to exercise caution when considering other interventions.

Surgical management Surgery has a role in the management of carefully selected patients with chronic constipation who fail to improve with current conservative management [107].

Antegrade continence enema

Antegrade continence enema (ACE) is considered as an alternative to a colostomy in selected patients with constipation or fecal incontinence. ACE surgery requires a continent connection to be created between the abdominal wall and caecum. Malone et al. [108] described the formation of acolonic conduit using the reversed appendix or tubularized ileal or cecal conduits if the appendix is unavailable. Patients are taught to intubate the ACE with a catheter and perform antegrade washouts with tap water. In general, success rates have been lower in adults than in children [107], but a Danish group has reported a favorable outcome in 69 adults who underwent ACE procedure with mean follow-up of 75 months [109]. Furthermore two recent systematic reviews of observational studies have found ACE to be an effective long-term treatment option and recommended that it should be offered to motivated patients before performing a definitive stoma [110, 111]. Long-term complications include stoma stenosis, leakage, or failure to effectively treat the original symptoms requiring revision, reversal, or conversion to a stoma [111]. It is worth considering combining the ACE procedure with a colostomy in disabled patients and patients with persistent left colonic inertia despite retrograde irrigation [112].

interventions [107]. In patients with slow transit constipation who have failed maximal conservative management, defunctioning ileostomy may be formed as a guide to colectomy [49]. Colectomy can be avoided in patients who have unsatisfactory ileostomy function or persistent abdominal symptoms such as pain or bloating.

Colectomy

Colectomy should only be considered as a treatment option for patients with diffuse slow colonic transit but normal gastric and small bowel transit [107, 113]. Once a decision to resect has been made, then the next consideration is how much to resect. Two studies have reported good results by performing segmental resections or subtotal colectomies based on segmental transit time measurements [40, 114]. However, limited subtotal colectomy with cecorectal or ileosigmoid anastomosis is generally reported as having an inferior functional outcome to ileorectal anastomosis [106]. The long-term results of surgery for slow transit constipation may be poor, a recent retrospective cohort study on 2000 patients reports complications rates of 25% and greater long-term health utilization due to ongoing issues [115]. However, a good outcome can be predicted in patients with slow transit constipation without impaired evacuation and overt psychological or psychiatric disease [116].

Surgical treatment options for obstructive defecation (ODS)

Surgical repair of anatomical deformities identified in patients with ODS should only be carried on those who have exhausted all conservative treatments. The aim of surgery is to correct anatomy with a relief of associated symptoms [117], although correction of anatomical abnormalities alone does not always lead to restoration of normal function [118]. To decide on the best treatment options, understanding the pelvic floor anatomy and the Delancey level of pelvic organ support (Table 65.6) will help [119].

Rectocele

Surgical repair of rectoceles in patients presenting to the colorectal surgeon is usually recommended when they are 2 cm or more in depth with the need for patient to digitate to defecate and with evidence of significant trapping on defecating proctogram or MRI proctogram [120]. Surgery is performed via transvaginal, transperineal, transanal, or abdominal approaches. Transvaginal posterior colporrhaphy was found to have the lowest rate of recurrence of rectocele/enterocele in a Cochrane Review of all TABLE 65.6: Delancey Level of Pelvic Organ Support Level 1

Level 2

Level 3

Defunctioning stoma

A stoma may be formed as definitive procedure, as a guide to further treatment, or as salvage from failed alternative

Source:

Support

Defect

Superior suspension of the vagina to the cardinal– uterosacral complex Lateral attachment of the upper two-thirds of the vagina Rectovaginal septum supporting posterior vaginal wall Distal fusion of vagina into the urogenital diaphragm and perineal body

Enterocele/sigmoidocele

Rectocele Rectal intussusception Supra-anal rectocele

DeLancey JO, Am J Obstet Gynecol, 166(6 Pt 1), 1717, discussion 24–28, 1992, with permission.

Constipation rectocele repairs [121]. Dyspareunia has been reported in up to 25% of women following posterior colporrhaphy. A systematic review of the use of biological materials in urogynecological surgery has shown that there was no additional benefit to the use of biological material in rectocele repair [122]. A systematic review of recto-vaginal reinforcement procedures concluded that 78% of patients reported a satisfactory result but that there was insufficient evidence to support one procedure over another [123].

Enterocele/Sigmoidocele

Enterocele or sigmoidocele occurs as a result of herniation of small bowel (enterocele) or sigmoid colon (sigmoidocele) through the uterosacral ligament at the vaginal apex into the pouch of Douglas, leading to separation of the rectovaginal septum. This can impede defecation leading to pelvic discomfort and perineal pressure with straining [124]. There are some physiological enteroceles, but if an enterocele or sigmoidocele impairs rectal emptying on defecating proctogram, then it is likely to be contributing to the patient’s symptoms of ODS. Enteroceles can be repaired transabdominally laparoscopically (ventral mesh rectopexy, posterior rectopexy and sacrocolpopexy) or vaginally in conjunction with pelvic floor repair (Table 65.6).

Internal intussusception/rectal prolapse

To surgically correct this the rectum is mobilized and returned to its correct anatomical position within the pelvis and many techniques have been described to achieve this [117]. In suture rectopexy, the rectum is fully mobilized and sutured to the presacral fascia. In patients with a redundant loop of sigmoid with preoperative symptoms of constipation, sigmoid resection may be considered. Laparoscopic resection rectopexy (Frykman-Goldberg procedure) has been shown to be safe with good long-term outcomes [125, 126]. The use of mesh has been introduced on the assumption that a foreign body will produce stronger adhesions and fibrosis than dissection and suture alone.† Various techniques have been described, including anterior sling rectopexy (Ripstein procedure), posterior mesh rectopexy (Well’s posterior rectopexy), and use of fascia lata to fix the sacral promontory (Orr-Loygue procedure) with further modifications using different types of mesh. A systematic review on ventral rectopexy for rectal prolapse and intussusception showed that there appears to be a reduction in postoperative constipation if posterior rectal mobilization is not performed with division of lateral ligaments [127]. Current literature has shown modern nerve-sparing laparoscopic ventral mesh rectopexy* resulted in over 50% improvement in the short and medium term [128, 129]. Robotic-assisted rectopexy has the advantages of 3D vision, a better view to identify and spare parasympathetic innervation to the rectum, and having flexible tips of instruments for suturing over laparoscopic approach. Recent literature supports the safety and feasibility of robotic-assisted rectopexy [130]. There is limited evidence of the best mesh to be used. An expert panel (grade C evidence) has recommended the use of biological mesh in young women of reproductive age, diabetics, smokers, patients with history of pelvic radiation or IBD, or intraoperative breach of rectum or vagina [129]. Perineal procedures are considered in patients with full-thickness rectal prolapse who may not be fit for an abdominal procedure and may carry a higher recurrence rate [131]. Delorme’s procedure involves transanal mucosal stripping with plication †

Mesh needs to be used with caution and following The Pelvic Floor Society’s guidance: https://thepelvicfloorsociety.co.uk

709 of the muscular wall of the rectum. The Altemeier procedure is transperineal resection of the recto-sigmoid, which can be offered to frail patients with symptomatic large prolapse.

Conclusion The management of constipation can be challenging. The majority of the patients can be managed conservatively with a multidisciplinary approach to complex patients. Patients with idiopathic constipation can be managed conservatively without recourse to major surgical interventions. Surgery carries risks of serious morbidity and patient selection for surgical intervention must be carried out with caution. For a few, surgery can offer effective treatment with improvement in function and quality of life.

References







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20. Gladman MA, Scott SM, Chan CL, Williams NS, Lunniss PJ. Rectal hyposensitivity: prevalence and clinical impact in patients with intractable constipation and fecal incontinence. Dis Colon Rectum 2003;46(2):238–246. 21. Gosselink MP, Darby M, Zimmerman DD et al. Long-term follow-up of retrograde colonic irrigation for defaecation disturbances. Colorectal Dis 2005;7(1):65–69. 22. Gladman MA, Dvorkin LS, Lunniss PJ, Williams NS, Scott SM. Rectal hyposensitivity: a disorder of the rectal wall or the afferent pathway? An assessment using the barostat. Am J Gastroenterol 2005;100(1):106–114. 23. Varma MG, Hart SL, Brown JS, Creasman JM, Van Den Eeden SK, Thorn DH. Obstructive defecation in middle-aged women. Dig Dis Sci 2008;53(10):2702–2709. 24. Evans RC, Kamm MA, Hinton JM, Lennard-Jones JE. The normal range and a simple diagram for recording whole gut transit time. Int J Colorectal Dis 1992;7(1):15–17. 25. Savoye-Collet C, Koning E, Dacher JN. Radiologic evaluation of pelvic floor disorders. Gastroenterol Clin North Am 2008;37(3):553–567, viii. 26. Foti PV, Farina R, Riva G et al. Pelvic floor imaging: comparison between magnetic resonance imaging and conventional defecography in studying outlet obstruction syndrome. Radiol Med 2013;118(1):23–39. 27. Pilkington SA, Nugent KP, Brenner J et al. Barium proctography vs. magnetic resonance proctography for pelvic floor disorders: a comparative study. Colorectal Dis 2012;14(10):1224–1230. 28. Piloni V, Tosi P, Vernelli M. MR-defecography in obstructed defecation syndrome (ODS): technique, diagnostic criteria and grading. Tech Coloproctol 2013;17(5):501–510. 29. Dietz HP. Pelvic floor ultrasound in prolapse: what’s in it for the surgeon? Int Urogynecol J 2011;22(10):1221–1232. 30. Dietz HP, Cartmill J. Imaging in patients with obstructed defecation. Tech Coloproctol 2013;17(5):473–474. 31. Lembo A, Camilleri M. Chronic constipation. N Engl J Med 2003;349(14):1360–1368. 32. Rao SS, Camilleri M, Hasler WL et al. Evaluation of gastrointestinal transit in clinical practice: position paper of the American and European Neurogastroenterology and Motility Societies. Neurogastroenterol Motil 2011;23(1):8–23. 33. Tack J, Muller-Lissner S, Stanghellini V et al Diagnosis and treatment of chronic constipation – a European perspective. Neurogastroenterol Motil 2011;23:697–710. 34. Chaussade S, Khyari A, Roche H et al. Determination of total and segmental colonic transit time in constipated patients. Results in 91 patients with a new simplified method. Dig Dis Sci 1989;34(8):1168–1172. 35. Metcalf AM, Phillips SF, Zinsmeister AR, MacCarty RL, Beart RW, Wolff BG. Simplified assessment of segmental colonic transit. Gastroenterology 1987;92(1):40–47. 36. Hinton JM, Lennard-Jones JE, Young AC. A new method for studying gut transit times using radioopaque markers. Gut 1969;10(10):842–847. 37. Rao SS, Welcher KD, Leistikow JS. Obstructive defecation: a failure of rectoanal coordination. Am J Gastroenterol 1998;93(7):1042–1050. 38. Mariani G, Pauwels EK, AlSharif A et al. Radionuclide evaluation of the lower gastrointestinal tract. J Nucl Med 2008;49(5):776–787. 39. Graff J, Brinch K, Madsen JL. Simplified scintigraphic methods for measuring gastrointestinal transit times. Clin Physiol 2000;20(4):262–266. 40. Lundin E, Karlbom U, Westlin JE et al. Scintigraphic assessment of slow transit constipation with special reference to right- or left-sided colonic delay. Colorectal Dis 2004;6(6):499–505. 41. Saad RJ, Hasler WL. A technical review and clinical assessment of the wireless motility capsule. Gastroenterol Hepatol 2011;7(12):795–804. 42. Tran K, Brun R, Kuo B. Evaluation of regional and whole gut motility using the wireless motility capsule: Relevance in clinical practice. Therap Adv Gastroenterol 2012;5(4):249–260. 43. Lee YY, Erdogan A, Rao SS. How to assess regional and whole gut transit time with wireless motility capsule. J Neurogastroenterol Motil 2014;20(2):265–270. 44. Rao SS, Singh S. Clinical utility of colonic and anorectal manometry in chronic constipation. J Clin Gastroenterol 2010;44(9):597–609. 45. Tack J, Muller-Lissner S. Treatment of chronic constipation: current pharmacologic approaches and future directions. Clin Gastroenterol Hepatol 2009;7(5):502–508; quiz 496. 46. Muller-Lissner SA, Kamm MA, Scarpignato C, Wald A. Myths and misconceptions about chronic constipation. Am J Gastroenterol 2005;100(1):232–242. 47. NICE. Irritable Bowel Syndrome in Primary Care. 2017. https://www.nice. org.uk/guidance/cg61.



48. Anti M, Pignataro G, Armuzzi A et al. Water supplementation enhances the effect of high-fiber diet on stool frequency and laxative consumption in adult patients with functional constipation. Hepatogastroenterology 1998;45(21):727–732. 49. Wong SW, Lubowski DZ. Slow-transit constipation: evaluation and treatment. ANZ J Surg 2007;77(5):320–328. 50. Gao R, Tao Y, Zhou C et al. Exercise therapy in patients with constipation: a systematic review and meta-analysis of randomized controlled trials. Scand J Gastroenterol 2019;54(2):169–177. 51. Sikirov D. Comparison of straining during defecation in three positions: results and implications for human health. Dig Dis Sci 2003;48(7):1201–1205. 52. Ford AC, Suares NC. Effect of laxatives and pharmacological therapies in chronic idiopathic constipation: systematic review and meta-analysis. Gut 2011;60(2):209–218. 53. Ramkumar D, Rao SS. Efficacy and safety of traditional medical therapies for chronic constipation: systematic review. Am J Gastroenterol 2005;100(4):936–971. 54. Golzarian J, Scott HW Jr, Richards WO. Hypermagnesemia-induced paralytic ileus. Dig Dis Sci 1994;39(5):1138–1142. 55. Lee-Robichaud H, Thomas K, Morgan J, Nelson RL. Lactulose versus polyethylene glycol for chronic constipation. Cochrane Database Syst Rev 2010;6(7):CD007570. 56. Loftus CG, Harewood GC, Baron TH. Assessment of predictors of response to neostigmine for acute colonic pseudo-obstruction. Am J Gastroenterol 2002;97(12):3118–3122. 57. NICE. Prucalopride for the treatment of chronic constipation in women. In Excellence NIfHaC, ed. NICE Technology Appraisal Guidance 211. 2010. https://www.nice.org.uk/guidance/ta211. 58. Camilleri M, Kerstens R, Rykx A, Vandeplassche L. A placebo-controlled trial of prucalopride for severe chronic constipation. N Engl J Med 2008;358(22):2344–2354. 59. Quigley EM, Vandeplassche L, Kerstens R, Ausma J. Clinical trial: the efficacy, impact on quality of life, and safety and tolerability of prucalopride in severe chronic constipation—a 12-week, randomized, double-blind, placebo-controlled study. Aliment Pharmacol Ther 2009;29(3):315–328. 60. Tack J, van Outryve M, Beyens G, Kerstens R, Vandeplassche L. Prucalopride (Resolor) in the treatment of severe chronic constipation in patients dissatisfied with laxatives. Gut 2009;58(3):357–365. 61. Jadav AM, McMullin CM, Smith J, Chapple K, Brown SR. The association between prucalopride efficacy and constipation type. Tech Coloproctol 2013;17(5):555–559. 62. NICE Irritable bowel syndrome with constipation in adults: Linaclotide 2013 ESNM16 https://www.nice.org.uk/advice/esnm16 63. Bharucha AE, Waldman SA. Taking a lesson from microbial diarrheagenesis in the management of chronic constipation. Gastroenterology 2010;138(3):813–817. 64. Quigley EM, Tack J, Chey WD et al. Randomised clinical trials: Linaclotide phase 3 studies in IBS-C—a prespecified further analysis based on European Medicines Agency-specified endpoints. Aliment Pharmacol Ther 2013;37(1):49–61. 65. Rao S, Lembo AJ, Shiff SJ et al. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation. Am J Gastroenterol 2012;107(11):1714–1724; quiz 25. 66. Chey WD, Lembo AJ, Lavins BJ et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, doubleblind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol 2012;107(11):1702–1712. 67. Layer P, Stanghellini V. Review article: Linaclotide for the management of irritable bowel syndrome with constipation. Aliment Pharmacol Ther 2014;39(4):371–384. 68. Atluri DK, Chandar AK, Bharucha AE, Falck-Ytter Y. Effect of linaclotide in irritable bowel syndrome with constipation (IBS-C): a systematic review and meta-analysis. Neurogastroenterol Motil 2014;26(4):499–509. 69. Vadivelu, N, Kai, AM, Kodumudi, V The opioid crisis: a comprehensive overview. Curr Pain Headache Rep 2018;22:16. 70. Ducrotté P, Milce J, Soufflet C, Fabry C. Prevalence and clinical features of opioid-induced constipation in the general population: a French study of 15,000 individuals. United Eur Gastroenterol J 2016;5(4):588–600. 71. Tuteja AK, Biskupiak J, Stoddard GJ. Opioid-induced bowel disorders and narcotic bowel syndrome in patients with chronic non-cancer pain. Neurogastroenterol Motil 2010;22:424–e96. 72. Farmer AD, Drewes AM, Chiarioni G et al. Pathophysiology and management of opioid-induced constipation: European expert consensus statement. United Eur Gastroenterol J 2019;7(1):7–20

Constipation 73. Chey WD, Webster L, Sostek M. Naloxegol for opioid-induced constipation in patients with noncancer pain. N Engl J Med 2014;370: 2387–2396. 74. Hale M, Wild J, Reddy J. Naldemedine versus placebo for opioid-induced constipation (COMPOSE-1 and COMPOSE-2): two multicentre, phase 3, double-blind, randomised, parallel-group trials. Lancet Gastroenterol Hepatol 2017;2:555–564. 75. NICE. Naloxegol for treating opioid-induced constipation 2015 NICE technology appraisal guidance TA345 http://www.nice.org.uk/guidance/ ta345 76. NICE. Naldemedine for treating opioid-induced constipation 2020 NICE technology appraisal guidance TA651 http://www.nice.org.uk/guidance/ ta651 77. Engel BT, Nikoomanesh P, Schuster MM. Operant conditioning of rectosphincteric responses in the treatment of fecal incontinence. N Engl J Med 1974;290(12):646–649. 78. Bassotti G, Chistolini F, Sietchiping-Nzepa F, de Roberto G, Morelli A, Chiarioni G. Biofeedback for pelvic floor dysfunction in constipation. Br Med J 2004;328(7436):393–396. 79. Woodward S, Norton C, Chiarelli P. Biofeedback for treatment of chronic idiopathic constipation in adults. Cochrane Database Syst Rev 2014; 3(3):CD008486. 80. Koh CE, Young CJ, Young JM, Solomon MJ. Systematic review of randomized controlled trials of the effectiveness of biofeedback for pelvic floor dysfunction. Br J Surg 2008;95(9):1079–1087. 81. Lindsey I, Nugent K, Dixon AR, eds. Pelvic Floor Disorders for the Colorectal Surgeon. Oxford, U.K.: Oxford University Press, 2011. 82. Norton C, Chelvanayagam S, eds. Bowel Continence Nursing. Beaconsfield, U.K.: Beaconsfield Publisher Ltd, 2004. 83. Rao SS, Seaton K, Miller M et al. Randomized controlled trial of biofeedback, sham feedback, and standard therapy for dyssynergic defecation. Clin Gastroenterol Hepatol 2007;5(3):331–338. 84. Heymen S, Scarlett Y, Jones K, Ringel Y, Drossman D, Whitehead WE. Randomized, controlled trial shows biofeedback to be superior to alternative treatments for patients with pelvic floor dyssynergia-type constipation. Dis Colon Rectum 2007;50(4):428–441. 85. Chiarioni G, Whitehead WE, Pezza V et al. Biofeedback is superior to laxatives for normal transit constipation due to pelvic floor dyssynergia. Gastroenterology 2006;130(3):657–664. 86. Simon MA, Bueno AM. Behavioural treatment of the dyssynergic defecation in chronically constipated elderly patients: a randomized controlled trial. Appl Psychophysiol Biofeedback 2009;34(4):273–277. 87. Emmanuel AV, Kamm MA Response to a behavioral treatment, biofeedback, in constipated patients is associated with improved gut transit and autonomic innervation. Gut.2001;49(2):214–219. 88. Gilliland R, Heymen S, Altomare DF, Park UC, Vickers D, Wexner SD. Outcome and predictors of success of biofeedback for constipation. Br J Surg 1997;84(8):1123–1126. 89. Wang J, Luo MH, Qi QH, Dong ZL. Prospective study of biofeedback retraining in patients with chronic idiopathic functional constipation. World J Gastroenterol 2003;9(9):2109–2113. 90. Palsson OS, Whitehead WE. Psychological treatments in functional gastrointestinal disorders: a primer for the gastroenterologist. Clin Gastroenterol Hepatol 2013;11(3):208–216; quiz e22–e23. 91. Shandling B, Gilmour RF. The enema continence catheter in spina bifida: successful bowel management. J Pediatr Surg 1987;22(3):271–273. 92. Briel JW, Schouten WR, Vlot EA, Smits S, van Kessel I. Clinical value of colonic irrigation in patients with continence disturbances. Dis Colon Rectum 1997;40(7):802–805. 93. Christensen P, Krogh K. Transanal irrigation for disordered defecation: a systematic review. Scand J Gastroenterol 2010;45(5):517–527. 94. Gardiner A, Marshall J, Duthie G. Rectal irrigation for relief of functional bowel disorders. Nurs Stand 2004;19(9):39–42. 95. Crawshaw AP, Pigott L, Potter MA, Bartolo DC. A retrospective evaluation of rectal irrigation in the treatment of disorders of faecal continence. Colorectal Dis 2004;6(3):185–190. 96. Collins B, Norton C. Managing passive incontinence and incomplete evacuation. Br J Nurs 2013;22(10):575–579. 97. Emmanuel AV, Krogh K, Bazzocchi G et al. Consensus review of best practice of transanal irrigation in adults. Spinal Cord 2013;51(10): 732–738. 98. Faaborg PM, Christensen P, Buntzen S, Laurberg S, Krogh K. Anorectal function after long-term transanal colonic irrigation. Colorectal Dis 2010;12(10 online):e314–e319.

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99. Kumar L, Liwanag J, Athanasakos E et al. Effectiveness of percutaneous tibial nerve stimulation in managing refractory constipation. Colorectal Disease 2017;19(1):45–49. 100. Collins B, Norton C, Maeda Y. Percutaneous tibial nerve stimulation for slow transit constipation: a pilot study. Colorectal Dis 2012;14(4):e165– e170. 101. Hassouna MM, Siegel SW, Nyeholt AA et al. Sacral neuromodulation in the treatment of urgency-frequency symptoms: a multicenter study on efficacy and safety. J Urol 2000;163(6):1849–1854. 102. van Wunnik BP, Baeten CG, Southwell BR. Neuromodulation for constipation: sacral and transcutaneous stimulation. Best Pract Res Clin Gastroenterol 2011;25(1):181–191. 103. Dinning P, Hunt L, Patton V et al Treatment efficacy of sacral nerve stimulation in slow transit constipation: a two-phase, double-blind randomized controlled crossover study. Am J Gastroenterol 2015; 110(5):733–740 104. Zerbib F, Sproudhis L, Lehur PA et al. Randomised clinical trial of sacral nerve stimulation for refractory constipation. Br J Surg 2017;104(3):205–213. 105. Pilkington SA, Emmett C, Knowles CH et al. Surgery for constipation, systematic review and practice recommendation: results V: sacral nerve stimulation. Colorectal Dis 2017;19(Suppl 3):92–100. 106. Wang L, Mingmin X, Zheng Q et al. The effectiveness of Acupuncture in management of functional constipation: A systematic review and metaanalysis. Evid-BasedComplement Altern Med 2020;2020:6137450. 107. Knowles CH, Dinning PG, Pescatori M, Rintala R, Rosen H. Surgical management of constipation. Neurogastroenterol Motil 2009;21(Suppl 2):62–71. 108. Malone PS, Ransley PG, Kiely EM. Preliminary report: the antegrade continence enema. Lancet 1990;336(8725):1217–1218. 109. Worsoe J, Christensen P, Krogh K, Buntzen S, Laurberg S. Long-term results of antegrade colonic enema in adult patients: assessment of functional results. Dis Colon Rectum 2008;51(10):1523–1528. 110. Patel A, Saratzis A, Arasaragnam R, Harmston C. Use of antegrade continent enema for the treatment of fecal incontinence and functional constipation in adults. a systematic review. Dis Colon Rectum. 2015; 58(10): 999–1013 111. Chan DSY and Delicata RJ. Meta-analysis of antegrade continence enema in adults with faecal incontinence and constipation. Br J Surg 2016;103(4):322–327. 112. Kotanagi H, Koyama K, Sato Y, Takahashi K. Appendicostomy irrigation for facilitating colonic evacuation in colostomy patients. Preliminary report. Dis Colon Rectum 1998;41(8):1050–1052; discussion 2–3. 113. Knowles CH, Grossi U, Horrocks, EJ et al. Surgery for constipation: systematic review and practice recommendations. Graded practice and future research recommendations. Colorectal Dis 2017;19(53):101–113. 114. You YT, Wang JY, Changchien CR et al. Segmental colectomy in the management of colonic inertia. Am Surg 1998;64(8):775–777. 115. Dudekula A, Huftless S, Bielefeldt K. Colectomy for constipation: time trends and impact based on the US Nationwide Inpatient Sample, 1998–2011. Aliment Pharmacol Ther 2015;42:1281–1293. 116. Hasegawa H, Radley S, Fatah C, Keighley MRB. Long-term results of colorectal resection for slow transit constipation. Colorectal Dis 1999;1(3):141–145. 117. Van Geluwe B, Wolthuis A, D’Hoore A. Laparoscopy for pelvic floor disorders. Best Pract Res Clin Gastroenterol 2014;28(1):69–80. 118. Gaspari AL, Sileri P, eds. Pelvic Floor Disorders: Surgical Approach. Cham (ZG), Switzerland: Springer, 2014. 119. DeLancey JO. Anatomic aspects of vaginal eversion after hysterectomy. Am J Obstet Gynecol 1992;166(6 Pt 1):1717–1724; discussion 24–28. 120. Hall GM, Shanmugan S, Nobel T et al. Symptomatic rectocele: what are the indications for repair? Am J Surg 2014;207(3):375–379; discussion 8–9. 121. Maher C, Feiner B, Baessler K, Schmid C. Surgical management of pelvic organ prolapse in women. Cochrane Database Syst Rev 2013; 22(4):CD004014. 122. Yurteri-Kaplan LA, Gutman RE. The use of biological materials in urogynecologic reconstruction: a systematic review. Plast Reconstr Surg 2012; 130(5 Suppl 2):242S–253S. 123. Grossi U, Horrocks EJ, Mason J et al. Surgery for constipation: systematic review and practice recommendations. Results IV: recto-vaginal reinforcement procedures. Colorectal Dis 2017;19(suppl 3):73–91. 124. Maro DJ, Wexner SD, eds. Disorders of the Anorectum and Pelvic Floor. Amsterdam, the Netherlands: Elsevier, 2014. 125. Cadeddu F, Sileri P, Grande M, De Luca E, Franceschilli L, Milito G. Focus on abdominal rectopexy for full-thickness rectal prolapse: meta-analysis of literature. Tech Coloproctol 2012;16(1):37–53.

712 126. Laubert T, Kleemann M, Roblick UJ et al. Obstructive defecation syndrome: 19 years of experience with laparoscopic resection rectopexy. Tech Coloproctol 2013;17(3):307–314. 127. Samaranayake CB, Luo C, Plank AW, Merrie AE, Plank LD, Bissett IP. Systematic review on ventral rectopexy for rectal prolapse and intussusception. Colorectal Dis 2010;12(6):504–512. 128. Boons P, Collinson R, Cunningham C, Lindsey I. Laparoscopic ventral rectopexy for external rectal prolapse improves constipation and avoids de novo constipation. Colorectal Dis 2010;12(6):526–532.

Textbook of Female Urology and Urogynecology 129. Mercer-Jones MA, D’Hoore A, Dixon AR et al. Consensus on ventral rectopexy: report of a panel of experts. Colorectal Dis 2014;16(2):82–88. 130. Mantoo S, Podevin J, Regenet N, Rigaud J, Lehur PA, Meurette G. Is roboticassisted ventral mesh rectopexy superior to laparoscopic ventral mesh rectopexy in the management of obstructed defaecation? Colorectal Dis 2013;15(8):e469–e475. 131. Senapati A, Gray RG, Middleton LJ et al. PROSPER: a randomized comparison of surgical treatments for rectal prolapse. Colorectal Dis 2013;15(7):858–868.

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FEMALE SEXUAL DYSFUNCTION Maria Uloko and Irwin Goldstein The objective of this chapter is to provide pertinent evidencebased clinical information to help practitioners diagnose and treat specific biological-based sexual health pathophysiologies in persons assigned female at birth. With the evolving language regarding gender identity and sexual orientation, the authors feel it is important to first define gender and sex. Gender refers to the attitudes, feelings, and behaviors that a given culture associates with a person’s biological sex. Sex is defined as either of the two main categories (male and female) into which humans and most other living things are divided on the basis of their reproductive functions.1 The authors of this chapter will use the terminology “Female Sexual Dysfunction” as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V)2 to describe anyone assigned female at birth or anyone with female internal or external genitalia. Female sexual dysfunction (FSD) is recognized as a common medical problem across all age groups. The National Health and Social Life Survey found that sexual dysfunction is more prevalent in patients assigned female at birth (43%) than in patients assigned male at birth (31%). 3 In a study by Shifren et al., it was estimated that 40% of U.S persons assigned female at birth who experienced sexual dysfunction and sexually related personal distress suffered from concurrent depression.4 Despite the high prevalence of FSD, those that are assigned female at birth have difficulty obtaining diagnostic and treatment care due to various reasons. At the time of this publication, there are still limited FDA-approved therapeutic agents for patients assigned female at birth compared to the more than 25 FDA-approved drugs for the sexual health of persons assigned male at birth.4 The first step to improving this paucity of treatment options is an accurate diagnosis. We believe that it is of utmost importance to address FSD systematically. We will present a step-by-step guide to the presentation, diagnosis, and treatment of many FSD disorders in an organized and complete fashion. A basic understanding of what sexual dysfunction means is key for any clinician seeing FSD in their office. Previously, the DSM-IV1 defined sexual dysfunction as a heterogeneous group of disorders that are characterized by a clinically significant disruption in a person’s ability to respond sexually or to experience sexual pleasure. It classified six disorders including Female Hypoactive Desire Disorder, Female Arousal Disorder, Female Orgasmic Disorder, Dyspareunia, and Vaginismus. In the revised and most recent DSM-V, there is now a required minimum duration of approximately 6 months and causing significant distress before obtaining the diagnosis of FSD. Other important changes include the merging of Female Hypoactive Sexual Disorder (HSDD) and Female Arousal Disorder (FAD) into Female Sexual Interest/Arousal Disorder (FIASD). As well as the merging of Dyspareunia and Vaginismus into Genitopelvic Pain/Penetration Disorder.1 FIASD is a controversial terminology among experts in sexual medicine as it decreases diagnostic accuracy and no current studies are looking at FIASD as a primary outcome in FSD research. Due to this, the International Consultation on Sexual

DOI: 10.1201/9781003144236-72

Medicine (ICSM) and The International Society for the Study of Women’s Sexual Health (ISSWSH) support that HSDD should be maintained as an entity separate from FSAD instead of grouped together as FIASD. To provide the best care to anyone struggling with FSD, clinicians must understand that sexual problems are commonly associated with significant personal distress including a diminution of self-worth and self-esteem, a reduction in life satisfaction, and a decline in the quality of the relationship with their partner. 5 Thus, to provide the best overall care for anyone with FSD, it is important for clinicians to be familiar with the basic aspects of appropriate sexual health delivery for persons assigned female at birth. Sexual health refers to a state of physical, emotional, mental, and social well-being related to sexuality.6 Anyone assigned female at birth has the right to a positive and respectful sexual relationship and to have pleasurable and safe sexual experiences, free of coercion, discrimination, and violence. They also have the right to sexual equity and freedom from all forms of discrimination and violence. For sexual health to be achieved and maintained, the sexual rights of all must be respected, protected, and fulfilled.7

Village health care Even though urology and urogynecology practitioners have a unique position to understand the anatomy and physiology of the peripheral genitalia and pelvic floor constituents, sexual medicine issues are usually highly complex and are, in general, secondary to interrelated psychological, physiological, and relationship issues molded with distinct couple dynamics. Historically, management of FSD usually involved evaluation by a single provider with expertise in a specific discipline (i.e., medicine, psychotherapy, or physical therapy). Based on the outcome/initial diagnosis, the patient may be referred to a provider(s) in a different discipline(s). There are limitations to this traditional model: sexual health is more than just the absence of symptoms. The expertise of the provider is often constrained by training and exposure as well as access to care by providers in different disciplines. There may be pelvic floor, psychological, or biological issues not addressed by this traditional model. For optimal diagnosis and treatment of FSD, it is necessary to take a biopsychosocial approach. In most cases, people assigned females at birth with sexual health concerns should consider undergoing concomitant psychological and physical therapy assessment and management by an appropriately trained specialist.7 At our institution, we have introduced a novel healthcare technique that is able to assess these complicated issues in one patient visit; we call it the village health-care technique where multiple providers from various backgrounds are able to take care of a single patient with complex disorders. We recognize that no one medical professional can take care of all sexual problems by themselves. This technique employs multiple healthcare specialists who treat sexual dysfunction with expertise and 713

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Blo musculoskeletal psychosocial Physiological

Musculoskeletal

Neurological problems Cardiovascular disease Cancer Urogenital disorders Medications Fatigue Hormonal loss or abnormality

High-tone pelvic floor dysfunction Low back pain Postabdominal or pelvic surgery Orthopedic conditions Urinary incontinence Pelvic organ prolapse Low-tone pelvic floor dysfunction

Sexual dysfunction

Sociocultural Influences

Interpersonal relationships

Inadequate education Conflict with religious, personal, or family values

Partner performance and technique

Societal taboos

Lack of partner Relationship quality and conflict Lack of privacy

Psychological Depression/anxiety Prior sexual or physical abuse Stress Alcohol/substance abuse

FIGURE 66.1  Stepwise, multidisciplinary approach to addressing female sexual dysfunction. training unique to their specialty. In our office, a typical patient will be evaluated by a registered pelvic floor physical therapist, a sex therapist/sexuality educator, and a sexual medicine physician. This multidisciplinary methodology (Fig. 66.1) has allowed us to have great success in the diagnosis and treatment of difficult presentations of FSD. If it is possible to recreate this office scenario in other offices, we feel that it has the highest yield for the proper diagnosis and treatment for FSD patients

Sexual health-care provider assessment clinical history

There is limited consensus on management paradigms for the diagnosis of people assigned females at birth with sexual health complaints. As it concerns biological-based sexual dysfunction, the most relevant aspect of the diagnosis is the history and physical examination. Clinical history taking centers on three components: sexual, medical, and psychosocial aspects. The sexual history should begin with the patient describing the sexual problem. The following questions may be utilized to help obtain maximal descriptive information. 1. Do you ever experience problems with sexual interest, sexual arousal, and/or sexual orgasm? 2. Sexual problems are common in people assigned females at birth who have urinary complaints. Do you have any urinary issues that bother you like frequency, urgency, or stress incontinence? 3. What is your current sexual function in terms of interest, arousal, and orgasm compared to when you were at your peak sexual function?

4. How long have you had the sexual problem? Timing? Frequency during the day, month, or year? 5. Does the sexual problem occur only during partner-related sexual activity or during manual manipulation? 6. In which situations is the sexual problem minimized? Maximized? 7. Is the sexual problem associated with any degree of discomfort, tenderness, soreness, or pain? If so, can you localize the site of pain in a schematic diagram of biologic female genitalia? 8. What tests/evaluations have you already had in regard to your sexual health concern? The medical history should include focused questions on any accompanying medical/surgical illnesses and/or the use of medications.8 Urogynecologic history taking such as incontinence9–12 , frequent urinary tract infections, interstitial cystitis,13 pelvic surgeries, childbirth,14,15 abortions, episiotomy, sexually transmitted diseases,16 pelvic inflammatory disorder, endometriosis, fibroids,17 hysterectomy with or without oophorectomy, and menopausal status18 should all be obtained. Topics of importance in the medical history should include a cursory history of the use of various birth controls the patient has taken and the timing of the sexual dysfunction in relation to starting and stopping them and neurological diseases like a spinal cord injury or trauma to the pudendal nerve and its branches. Chronic diseases like diabetes, anemia, hyperlipidemia, coronary artery disease should also be addressed including medications taken for these chronic illnesses. A history of holistic and integrative medications and vitamin supplementation is warranted to better understand the extent to which the severity of the illness

Female Sexual Dysfunction has driven the patient to such ailments. Over-the-counter and illicit drug use like cocaine, marijuana, and ecstasy should be addressed in the history. The health-care provider should briefly screen all patients for obvious psychopathology that would impact the treatment algorithm for FSD. The health-care provider should investigate if the psychiatric symptoms are currently present or have been treated previously. These symptoms may be interrelated with the sexual disorder. This will help guide the clinician in defining goals and boundaries for the patient. Psychological factors19 that can easily interplay with FSD include previous sexual trauma and abuse,20 depression,21 psychoses, anxiety, distraction, sexual neurosis, sexual inhibitions, and/or interpersonal relationship issues. There is a statistically significant increase in depression in those with FSD. If the patient is depressed, then the severity of the depression should be clarified and documented accordingly. Furthermore, all patients who experience major depression should be questioned about suicide risk.21 Thus, a close working relationship between the FSD clinician and sex therapist is typically warranted in cases of major/severe depressive symptoms. Since the endocrine system, including the sex steroids, plays a pivotal role in genital function, a complete evaluation of the endocrine function is warranted. We check nine lab values for all who present to our institute with FSD: estradiol, 22,23 progesterone, testosterone24–26 and calculated free testosterone, prolactin, sex hormone-binding globulin (SHBG), thyroidstimulating hormone (TSH), 27 luteinizing hormone, folliclestimulating hormone (FSH), and dihydrotestosterone (DHT). Along with the hormone evaluation, the medical history should routinely probe and evaluate for estrogen deficiency 23,28 such as vaginal dryness, vaginal bleeding with minimal vaginal manipulation, hot flashes and night sweats, and other symptoms of menopause. Symptoms of androgen insufficiency (i.e., menopause or a girl taking birth control pills) would include fatigue, lack of energy, diminished skeletal muscle mass and strength, depressed mood, lethargy, insomnia, hypersomnia, and lack of interest in sexual activity. 28–30 It is relevant to inquire about the sexual health of the patient’s partner. For those in a relationship with persons assigned male at birth, sexual dysfunction such as erectile dysfunction, early ejaculation, or an anatomical concern such as Peyronie’s disease may exist and need to be addressed by an urologist. Finally, an important caveat to history taking in persons with sexual health concerns is that history taking may be viewed in some as actually the beginning of their treatment as they are often empowered following a detailed discussion about their sexual health concerns. They have initiated the first step in overcoming past failures to take action in this area.

Validated questionnaires

Validated, reliable, standardized self-rated questionnaires23,28,29,31 are useful to assist in the identification of the presence or absence of the various domains of a patient’s sexual dysfunction, such as sexual desire, sexual arousal, orgasm, and/or sexual pain. The most common of such questionnaires is the female sexual function index. 30,32 This self-reported patient screening tool is used to score symptoms against normative values for populations of patients with and without sexual dysfunction. As in all areas of clinical medicine, the use of screening tools for clinical diagnosis has recognized limitations. The determination of particular psychological contributors or confounds, contextual conditions, and other features and characteristics that affect an individual person

715 require a more traditional assessment through structured history and physical examination.

Physical examination

The physical examination for a person with FSD should be tailored to the sexual medicine complaint obtained on history taking. For example, if during history taking genital itching is a major sexual health problem, a careful assessment would follow for the presence/absence of a genital dermatitis condition.33 If a person with FSD is under the age of 50 and has sexual pain, a careful physical examination should evaluate for the presence of hormonally mediated vestibulodynia vs. neuroproliferative vestibulodynia. 34,35 Similar complaints of sexual pain in a person with FSD over 50 years of age should assess for the presence of vaginal atrophy with dryness, loss of rugae, mucosal thinning, pale hue, and lack of shiny vaginal secretions; all are indications of menopausal hormonal status.23,31 The physical examination should be performed ideally without menses and without intercourse or douching for 24 hours before the exam. If dysfunction occurs at a specific time, such as midcycle dyspareunia, the physical examination should be scheduled at the time of the sexual problem. The genital-focused examination should be considered routine in the diagnosis of persons with FSD, but its personal character demands that a rational explanation exists for its inclusion in the diagnostic process. A focused peripheral genital examination is recommended in persons with FSD for complaints of dyspareunia, geni-topelvic pain/penetration disorder, genital arousal disorder, and combined arousal disorder, orgasmic disorder, pelvic trauma history, and any dermatologic disease affecting genital health such as herpes or lichen sclerosis. The examiner may also assess for anal and vaginal tone, voluntary tightening of anus, and bulbocavernosus reflexes in persons with suspected neurological disorders. 36 Patient consent to examination is particularly important. It is vital that the patient is aware of the purpose of the exam and understands that they have the final authority to terminate the physical examination, to ask questions, to have control over who is in attendance, and to understand the extent of the assessment. Inclusion of the sexual partner, with permission of the patient, is advantageous and provides needed patient support. Allowing the patient to observe any pathology via digital photography is often therapeutic, allowing, for the first time in many cases, an illustration and connection of a detected physical abnormality with the sexual health problem. If a genital sexual pain history exists, the patient should point with their finger to the location/s of the discomfort during the physical examination.29 Independent of the gender of the examining health-care clinician, it is strongly recommended that a female identifying chaperone be present with the health-care clinician during the entirety of the examination. If a chaperone is declined then this should be documented contemporaneously, preferably with witnessing. The patient should wear a sheet to cover their lower torso. The patient should be placed in the lithotomy position and the examining health-care clinician should use vulvoscopy (Fig. 66.2) with magnified vision and a focused light source.29 In addition, warming the room creates a more relaxed environment in which the patient will feel more comfortable.

Pelvic floor assessment in sexual function overview

Normal function of the pelvic floor musculature is essential in maintaining appropriate sexual function. Both “low-tone pelvic floor dysfunction” and “high-tone pelvic floor muscle

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Textbook of Female Urology and Urogynecology pelvic organ prolapse with or without urinary or fecal incontinence. Risk factors include age, heredity, trauma, menopausal status, and chronic medical conditions such as chronic obstructive pulmonary disease, obesity, and constipation. Stress incontinence that occurs with increased intra-abdominal pressure and maneuvers such as sneezing, coughing, and straining is related to abnormalities in urethral closure pressure and poor pelvic muscle support. Sexuality will often be adversely affected by a hypoactive pelvic floor since severe incontinence and prolapse symptoms are a source of anxiety and interfere with the overall sexual satisfaction experience. These patients often express concern about feeling undesirable and fearing embarrassment.8,9,39,40

Hypersensitive pelvic floor

FIGURE 66.2  Vulvoscopy. The examining health-care clinician should use vulvoscopy with magnified vision and a focused light source. The patient should be placed in the lithotomy position and wear a sheet to cover her lower torso. dysfunction” can be closely associated with female sexual disorder. Hypotonus of the pelvic floor muscles, secondary to childbirth, trauma, and/or aging, is related to urinary incontinence during orgasm, vaginal laxity, and/or thrusting dyspareunia secondary to pelvic organ prolapse. Hypertonus of the pelvic floor secondary to childbirth, postural stressors, microtrauma, infection, adhesions, and surgical trauma can contribute to symptoms of urinary retention, reduced force of stream, dysuria, urgency, penetrative dyspareunia, and/or vaginismus. The assessment of pelvic floor tone is determined by the person’s ability to isolate, contract, and relax the pelvic floor muscles. The pelvic examination should begin with a digital exam, which is performed by exerting light pressure on the lateral walls of the vagina to assess whether the patient can squeeze on the examining finger and elevate the pelvic floor without simultaneously contracting the abdominal, gluteal, or adductor muscle groups. If the patient is not able to produce sufficient muscle strength to compress the finger or is not able to sustain that pressure for several seconds, they may be exhibiting a low-tone pelvic floor dysfunction pattern. Conversely, if the patient experiences muscle tenderness or pain when pressure is applied to the lateral vaginal wall or during an attempted squeeze against resistance, she may be exhibiting a high-tone pelvic floor dysfunction pattern. A perineometer or an electromyography probe, designed to measure muscle activity, can verify these physical examination findings.37–40

Hypoactive pelvic floor

Weakness and laxity of the pelvic floor muscles represent a spectrum of symptoms and conditions that include patients with

Hypertonus of the pelvic floor musculature accounts for some of the concerns of patients who present for evaluation of FSD. Hypersensitivity disorders involving the genitourinary tract represent a spectrum of symptoms and conditions that include chronic bacterial cystitis, urinary urgency and frequency, urethral syndrome, interstitial cystitis, vulvar pain, and perineal and pelvic pain. Sexuality is adversely affected for the majority of patients with hypersensitivity disorders of the bladder, bowel, and vulva and high-tone pelvic floor dysfunction. Patients who can tolerate coitus often suffer a flare of their symptoms for days as a result of sexual activity, which then becomes a negative reinforcement for future sexual activity.8,9,39,40. One emerging technique is the use of BOTOX which may help up to 70% of these women (https://pubmed.ncbi.nlm.nih.gov/32696187/).

External examination

The first part of the examination involves inspection of the vulva and labia majora. Two gloved fingers are placed on either side of the clitoral shaft, and using an upward force in the cephalic direction, the prepuce is retracted to gain full exposure of the glans clitoris, corona, and right and left frenulum emanating at 5:00 and 7:00 from the posterior portion of the glans clitoris (Fig. 66.3a and b). The labia minora are inspected for labial resorption and for their ability to meet at the midline posterior fourchette (Fig. 66.4a and b). The maximal labial width is recorded to compare pre- and posthormone supplementation. Inspection of the urethral meatus is performed (Fig. 66.5a) and any erythema, stenosis, or meatal prolapse (Fig. 66.5b) is noted. Using gauze to maximally retract the labia minora, the labial-hymenal junction (Hart’s Line) is identified. The Q-tip cotton swab is placed at multiple locations on the vestibule, which is defined as the tissue medial to Hart’s line (Fig. 66.6). A Q-tip cotton swab test is performed, gently applying pressure on the minor vestibular glands (Fig. 66.7a), documenting the quality (0–10 pain scale works well here) of the discomfort or pain or erythema (Fig. 66.7b) in a clockwise fashion.

Internal examination

For the speculum examination, a warm, lubricated speculum is used. The periurethral tissue or G-spot region is inspected (Fig. 66.8) by lateralizing the arms of the speculum instead of the more common anterior–posterior approach. The vaginal wall is examined for the presence of vaginal rugae (Fig. 66.9a and b), inflammation, discharge, color and thickness of the vaginal walls, and any vaginal lesions. A vaginal smear and wet mount are obtained. Vaginal pH is recorded. Single-digit palpation is achieved by gently placing a finger into the vaginal opening and depressing the bulbocavernosus muscle. Two fingers are placed

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  FIGURE 66.3  (a) The prepuce is retracted to gain full exposure of the glans clitoris, corona, and right and left frenulum emanating at 5:00 and 7:00 from the posterior portion of the glans clitoris. The normal size is estimated to be about the diameter of a Q-tip. (b) Vulvoscopic view of moderate clitoral phimosis.

  FIGURE 66.4  (a) The labia minora are inspected for labial resorption and for their ability to meet in the midline posterior fourchette. (b) Vulvoscopic view of labial resorption.

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  FIGURE 66.5  (a) Inspection of the urethral meatus is performed. (b) Mild urethral prolapse in a woman with genitourinary syndrome of menopause.

FIGURE 66.6  Hart’s line (here, outlined in blue ink at the beginning of a vestibulectomy). against the lateral walls of the levator and underlying obturator muscles, which are assessed for tenderness. A rectovaginal and bimanual examination can be performed if indicated.29,41

Neurourological testing

Neurourological examination consists of sensory and reflex testing.41 The sensory neurological exam evaluates the integrity of the three branches of the pudendal nerve including the dorsal nerve of the clitoris (sensation from the glans clitoris and

clitoral shaft), the perineal nerve (sensation from the perineum and labia), and the inferior rectal nerve (sensation from the perianal skin). Testing is performed by assessing light touch (cotton ball or Q-tip) (Fig. 66.10a) and pinprick (sterile needle) (Fig. 66.10b). Testing sites include the right and left sides of the clitoral area, labia majora, labia minora, and perianal areas. The motor portion of the pudendal nerve is derived from the pelvic floor muscles. Sacral reflexes include the bulbocavernosus reflex and the anal wink reflex, and both sensory and motor arms of these reflexes are branches of the pudendal nerve. The afferent arm of the bulbocavernosus reflex is the dorsal nerve of the clitoris, and the efferent arm is the perineal nerve. The index and middle fingers are placed along the posterolateral aspect of either the right or left vaginal wall overlying the bulb of the clitoris, surrounded by the bulbocavernosus muscle. A gentle pinch of the glans clitoris with the opposite hand will elicit contraction of the bulbocavernosus muscle (Fig. 66.11). The examination is repeated with the examining fingers facing the opposite vaginal wall. The afferent and efferent arms of the anal wink reflex both arise from the inferior rectal nerve. The anal wink reflex is performed using the wooden shaft end of the Q-tip and is assessed by touching the perianal skin, about 1 cm from the anus at the 3 o’clock and the 9 o’clock positions. Visible contraction of the anal sphincter will be noted after touching the skin.41 Neurophysiological tests are not yet consensed so the history and physical examination remain the best methodology to screen for neurological causes for FSD. Objective sensory nerve testing may be performed with a biothesiometer (Fig. 66.12a). This quantitative sensory test measures vibratory perception thresholds (expressed in volts) and values are obtained in a nongenital reference site (pulp index finger) as well as in multiple genital sites such as the glans clitoris (dorsal nerve of the clitoris) and the right and left labia minora (the perineal nerve). Other quantitative sensory testing involves the determination of hot and cold perception threshold values in these test sites (Fig. 66.12b).29 The health-care clinician may also perform a complete physical exam, such as examining for a thyroid goiter, to rule out other comorbid conditions that might be causing sexual dysfunction. A general physical exam is highly recommended in patients with

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  FIGURE 66.7  (a) A Q-tip cotton swab test is performed, gently applying pressure to the minor vestibular glands. This woman has no pain and no erythema overlying the minor vestibular glands. (b) This woman had pain, discomfort, and erythema overlying minor vestibular glands.

 

FIGURE 66.8  With the speculum turned horizontal, the periurethral tissue and G-spot region are inspected. chronic illnesses and as part of good medical care, including a detailed breast exam and evaluation of blood pressure and heart rate.

Laboratory testing

There are evidence-based, placebo-controlled, doubleblind data supporting the efficacy of exogenous sex steroid hormone treatment in patients assigned female at the birth with sexual health concerns.28–30,42,43 The human vagina consists of three layers of tissue: the epithelium (composed of squamous cells), the lamina propria, and the muscularis (inner circular and outer longitudinal smooth muscle).23,31 The epithelium undergoes mild changes during the menstrual cycle. The lamina propria is replete with

FIGURE 66.9  (a) The vaginal wall is examined for the presence of vaginal rugae. (b) Absent vaginal rugae in a woman with genitourinary syndrome of menopause.

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  FIGURE 66.10  (a) Neurological testing is performed by assessing light touch (cotton ball or Q-tip). (b) Neurological testing is performed by assessing the pain response to pinprick (sterile needle). tiny blood vessels that become engorged with blood during sexual arousal, leading to lubrication. The smooth muscle of the muscularis enables the vagina to dilate and lengthen during penile penetration. Relaxation of that muscle leads to arousal. These three layers of tissue may function in an interrelated way. It is hypothesized that the blood vessels in the lamina propria that allow for lubrication are dependent on growth factors and that the growth factors are derived from the muscularis. Postmenopausal atrophy

FIGURE 66.11  The afferent arm of the bulbocavernosus reflex is the dorsal nerve of the clitoris, and the efferent arm is the perineal nerve. The index and middle fingers are placed along the posterolateral aspect of either the right or left vaginal wall overlying the bulb of the clitoris, surrounded by the bulbocavernosus muscle. A gentle pinch of the glans clitoris with the opposite hand will elicit contraction of the bulbocavernosus muscle.

of vaginal tissues may be due to decreased synthesis of these growth factors resulting in a diminished number of critical blood vessels in the lamina propria.23,31 Increased vaginal blood flow is an indicator of sexual arousal.44 Genital swelling and lubrication are responses to increased clitoral and vaginal perfusion; increased length and diameter of the vaginal canal and clitoral corpora cavernosa; engorgement of the vagina wall, clitoris, and labia major and minora; and transudation of lubricating fluid from the vaginal epithelium. The muscularis, the muscle that enables the vagina to lengthen and widen during sexual arousal, also atrophies without estrogen. In postmenopausal patients who do not take hormone therapy, the vaginal epithelium, lamina propria blood vessels, and muscularis all decrease. Like the epithelium, the muscularis responds to estradiol by increasing in thickness.45 In animal studies,45 blood flow to the vagina was greatly reduced in the oophorectomized rats compared with the intact rats. Contrary to what one might expect, subphysiological doses of estradiol increased vaginal blood flow in oophorectomized rats more than either physiological or supraphysiologic doses. Ovariectomy-deprived estradiol values caused the vaginal epithelium to thin down to a single layer. Subphysiologic doses of estradiol increased the thickness of the vaginal epithelium the most because the oophorectomized rats had more estrogen-alpha receptors in the epithelium than the intact animals. A small amount of estradiol delivered to tissue with many estrogen-alpha receptors produced a huge response. Thus, estradiol regulates estrogen receptors through a negative feedback system. Despite these studies, there still remains no consensus on recommended routine laboratory tests for the evaluation of patients with desire, arousal, and orgasm sexual health concerns. There is still a lack of clinical consensus as to the value, specificity, and sensitivity of individual hormone blood tests. It is important to discuss with the patient the strategy of serial blood test surveillance testing to address safety concerns during such treatment. Blood testing should be dictated by clinical suspicion, especially from the results of the history and physical examination. If

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  FIGURE 66.12  (a) A biothesiometer measures vibratory perception thresholds (expressed in volts) on a genital reference site (index finger) as well as in multiple genital sites such as the glans clitoris (dorsal nerve of the clitoris) and the right and left labia minora (the perineal nerve). (b) Quantitative sensory testing involves the determination of hot and cold perception threshold values in the same test sites as the biothesiometer. appropriate, the healthcare clinician may assess multiple androgen and estrogen values29 such as (nine hormone values) total testosterone, free testosterone, SHBG, DHT, estradiol, and progesterone. A pituitary function may be measured by obtaining luteinizing hormone (LH), FSH, and prolactin. TSH should be measured to exclude subclinical thyroid disease.29 Androgens, including testosterone, are necessary for reproductive function and hormonal balance in patients and also represent important precursors for the biosynthesis of estrogens. Historically, androgens were identified predominantly with male sexual function, contributing to a lack of recognition of the effects of androgens in persons assigned female at birth. We know that androgens have multiple biochemical effects in the body including, but not limited to sexual desire, bone density, muscle mass and strength, mood, energy, and psychological well-being. The normal ranges of testosterone concentration values in people assigned females at birth of different age groups without sexual dysfunction are not well defined. Testosterone levels reach a peak during the early follicular phase, with small but less significant variation across the rest of the cycle. Testosterone assays are not uniformly sensitive or reliable enough to accurately measure testosterone at the low serum concentrations typically found in people assigned females at birth. Free testosterone is clinically more important than total testosterone in sexual function because the vast majority of testosterone is bound to SHBG and only a small amount of total testosterone is biologically available. The measurement of SHBG is relatively simple to perform with good reproducibility. Equilibrium dialysis is a highly sensitive assay for free testosterone; however, this method is not feasible for clinical practice. Measurement of free testosterone by analogue assays is unreliable. Free androgen may also be calculated using the free androgen index, defined as total testosterone (nmol/L) divided by SHBG (nmol/L). Calculated free testosterone may be determined and takes into account total testosterone, SHBG, and albumin. A calculator for the free testosterone is available online at http:// www.issam.ch/freetesto.htm.

There are multiple concerns with the determination of serum hormone levels, especially testosterone.28–30 Sex steroid hormone actions are quite complex and involve critical enzymes and critical hormone receptors that determine tissue exposure, tissue sensitivity, and tissue responsiveness. For example, in individuals, there are variations in the amount and activity of critical enzymes such as the 5-alpha-reductase enzyme, which is important in converting free testosterone into DHT. In our office, we have located a small subset of patients assigned female at birth who do not respond to typical doses of testosterone (1/10 the dose for those that identify as male), and we hypothesize that they have a deficiency in the 5-alpha-reductase enzyme.10 We performed an IRB-approved retrospective chart review of 17 people assigned females at birth examined between 2007 and 2013 who presented with persistent sexual side effects despite being treated with testosterone replacement therapy (TRT). Data collected included DHT, testosterone, SHBG, and calculated free testosterone values. The duration of use and duration of persistent side effects were recorded. Data from psychometrically validated questionnaires were assessed for parametric data analysis. Treatment regimens used in this study to achieve free testosterone of 0.8 ng/dL were testosterone pellets labeled Testopel. The mean age of all 17 patients in this study was 57 years old. The mean pretreated testosterone values were 18.55 ng/dL; mean free testosterone values, 0.19 ng/dL; and mean DHT values, 10 ng/mL. After initial treatments with one testosterone pellet, the mean treated testosterone values increased to 141.89 ng/dL, mean free testosterone values to 1.40 ng/dL, and mean DHT values to 13.21 ng/mL. Since these patients continued to have persistent sexual side effects, we increased treatment in the 17 patients to two pellets. The mean testosterone values increased to 174.50 ng/dL, mean free testosterone values to 1.61 ng/dL, and mean DHT values to 23.63 ng/mL with subsequent improvement in symptoms. No major adverse side effects were encountered in this study; however, two patients did experience mild acne and hair growth, which were both treated with local skin care. The mechanistic

722 hypotheses to describe this phenomenon include persistent endocrine and epigenetic gene expression alterations of the 5-alphareductase enzyme. To improve symptoms in these patients, we have found that increasing the serum-free testosterone levels above 0.8 ng/dL slowly drives DHT levels to the upper tertile of the normal range. Patients should be informed of possible persistent side effects of TRT and the need to drive testosterone values higher to see improvements in sexual side effects. In addition, individuals have variations in individual sex steroid hormone receptor sequencing. Thus, independent of the values of sex steroid hormones, the unique individual variations in critical enzymes and sex steroid hormone receptors result in individual differences in tissue exposure, tissue sensitivity, and tissue responsiveness. More research is needed in the blood testing of sex steroid hormones in patients with FSD.

Typical FSD patient assessment and treatment algorithms Phase 1 (Local Tissue Hormone Supplementation)

It is important to emphasize that no single type of hormonal intervention or regimen will be effective in all patients with desire, arousal, and orgasm sexual health concerns.29 The hormonal abnormalities that are identified will determine which of the following biological treatment options patients are offered in Phase 1. Based on the history and physical examination, local estrogen treatment may be achieved with vestibular estradiol alone, intravaginal estradiol alone, or a combination of both. Local estrogen and testosterone, in the form of estradiol 0.03% + testosterone 0.1% in a hypoallergenic base, improve vaginal perfusion, lubrication, tissue tone, and elasticity and restore the normal vaginal pH and vaginal health. 23,31,41,43,46–48 Vaginal estradiol relieves dyspareunia, atrophic vaginitis, and vaginismus. Some systemic estradiol absorption occurs with all local vaginal estrogens, and regular estradiol blood testing may be necessary for some patients. Daily application of a film of vestibular estrogen is recommended as well, because it promotes the health of the frenulum (the most sensitive part of the external genitalia), labia minora, urethral meatus, hymenal tissue, and vestibular glands. 23,31,49–51 Patients with Female Sexual Disorder who are placed on Phase 1 treatment (local estrogen/testosterone to the vestibule and into the vagina) need to undergo surveillance blood tests after 3 months of therapy to monitor the patient’s levels of estradiol, progesterone, DHEA, testosterone, androstenedione, DHT, FSH, LH, prolactin, and TSH as indicated. Those with desire, arousal, and orgasm sexual health concerns whose symptoms of distress are not resolved satisfactorily with Phase 1 treatments may consider progressing to Phase 2 treatments.

Phase 2 (Bioidentical Systemic Hormone Supplementation)

In Phase 2, patients receive systemic estrogen and/or systemic testosterone (no FDA-approved testosterone replacement exists for patients with FSD). Several clinical trials have shown that the distressing symptoms of vaginal atrophy associated with low-estrogen states are ameliorated after systemic estrogen therapy.29,49,52 Low doses of systemic bioidentical non-synthetic 17-beta-estradiol reduced vaginal atrophy compared with placebo in healthy menopausal patients.29,49,52 Systemic estrogen therapy can also successfully improve hot flushes, night sweats,

Textbook of Female Urology and Urogynecology and sleep disturbances that negatively affect body image, mood, and sexual desire. All efforts are made to keep serum estradiol levels between 30 and 50 ng/dL. The concept of maintaining estradiol values at low levels is to reduce the side effect risk while achieving a minimum efficacious dose.29 Risks of systemic estrogen use should be discussed at length with the patient; they include breast cancer, heart attack, and stroke. In those with an intact uterus, systemic estrogen should always be opposed by a progestogen. All efforts are made to use bioidentical nonsynthetic progesterone and keep values in the range of 1 ng/dL.29 Systemic androgens (systemic DHEA and/or systemic testosterone) have been shown to improve mood, energy, stimulation, sensation, arousal, and orgasm in patients with FSD. Limited clinical trials have examined the effects of systemic DHEA therapy on sexual function in patients with FSD. 53–55 Baulieu and colleagues 49 administered systemic DHEA (50 mg) or placebo to 140 patients assigned female at birth between the ages of 60 and 79 years for 12 months. Systemic DHEA treatment produced approximately a doubling of serum total testosterone concentration and also significantly increased skin hydration and bone density. Libido was increased after 6 months of treatment; sexual activity and sexual satisfaction were both increased after 12 months.49 One benefit of administering systemic DHEA and systemic testosterone is that these hormones will endogenously aromatize to estradiol, thus relieving hot flashes and night sweats without the administration of systemic estrogen. 29 Systemic testosterone has been used to treat patients with FSD since the 1940s. 52 It has again (no FDA-approved testosterone replacement exists for patients assigned female at birth) gained increased interest and use amongst clinicians treating FSD in their practice. The simple reason is that systemic testosterone supplementation can help alleviate a whole host of symptoms from dyspareunia in hormonally mediated vestibulodynia to low mood, desire, and libido. Systemic testosterone can be administered via transdermal application or intramuscular injection or with a pellet inserted into the adipose tissue of the buttocks. Transdermal patches or gels or subcutaneous pellets are being studied for their safety and efficacy in reducing sexual symptoms associated with testosterone insufficiency. 28–30 Transdermal testosterone patches have been compared with placebo in estrogenized patients who had undergone oophorectomy and hysterectomy. One study 56 showed that the 300 μg testosterone patch was significantly more effective than the 150 μg patch or placebo in improving the frequency of sexual activity, pleasure, and fantasy during a 12-week period. The dose for any systemic testosterone given to patients with FSD is at one-tenth the dose administered to those that identify as male. When checking laboratory values, it is important to keep these patients in a range of free testosterone between 6 and 8 ng/dL. In addition, we check a DHT value, which we aim to keep in the upper tertile range, since on occasion even with a free testosterone between 6 and 8 ng/dL they may still be symptomatic. In that scenario, we hypothesize that there is a downstream abnormality or deficiency in the 5-alpha-reductase enzyme, and thus, the testosterone value will have to be increased to offset the lower DHT. Finally, if side effects like male pattern balding or facial hair or acne become a problem, a low dose 5-alpha-reductase inhibitor (finasteride 1 mg) once to twice a month can be administered.

Female Sexual Dysfunction Phase 3 (Nonhormonal Medication)

In phase 3, attention is given to the role of FDA-approved nonhormonal medications in facilitating desire and orgasm sexual responses.49–51 Sexual motivation is encouraged, sustained, and ended by a number of central nervous system neurotransmitter and receptor changes induced, in part, by the action of sex steroids, androgens, estrogens, progestins, and the central neurotransmitter dopamine.57 The activation of dopamine receptors may be a key intermediary in the stimulation of incentive sexual motivation and sexual reward. These neurotransmitters and receptor changes in turn activate central sexual arousal and desire. Contemporary animal research reveals that dopamine neurotransmitter systems may play a critical intermediary role in the central regulation of sexual arousal and excitation, mood, and incentive-related sexual behavior, in particular, in the motivational responses to conditioned external stimuli. In summary, the complex central neurochemical actions of neurotransmitters stimulate sensory awareness, central sexual arousal, mood, and reward, which relates to relevant individuals’ sexual experiences involving a partner, a place, and an action.57 Bupropion, which is a noradrenaline and dopamine reuptake inhibitor with nicotinic antagonist properties originally marketed as an antidepressant, may have a beneficial effect on those with FSD characterized by hypoactive sexual desire disorder.29,50,51 In a placebo-controlled trial, 58 bupropion produced an increase in desire and frequency of sexual activity compared with placebo. Traditional dosing starts at 150 mg twice a day; we have found that a low dose of 75 mg twice a day achieves an optimal improvement in sexual dysfunction symptoms. Two newer FDA-approved medications for the treatment of decreased libido/arousal are flibanserin and brimolanitide. Flibanserins (Addyi™) has two principal pharmacological actions: it acts as a full agonist at postsynaptic 5HT1A receptors and an antagonist at postsynaptic 5HT2A receptors.59,60 Exclusive binding at these receptors differentiates flibanserin from buspirone and bupropion. Once bound at the receptors in the prefrontal cortex, flibanserin causes the downstream release of dopamine and norepinephrine and reduction of serotonin.59,61,62 Flibanserins is taken daily as a treatment and we recommend it at night due to its side effect of drowsiness. Bremelanotide (Vyleesi ™) is a melanocortin receptor (MCR) agonist that non-selectively activates several receptor subtypes with the following order of potency: MC1R, MC4R, MC3R, MC5R, MC2R. At therapeutic dose levels, binding to MC1R and MC4R is most relevant. Neurons expressing MC4R are present in many areas of the central nervous system (CNS). Investigations into the role of the melanocortin system on sexual response has focused on the melanocortin 3 (MC3R) and melanocortin 4 (MC4R) receptors in the CNS. There is abundant expression of both MC3R and MC4R in the brain and in peripheral genital sensory outputs.63 However, MC4R has been shown to modulate the erectile function and sexual behavior, whereas MC3R has not been shown to have a pro-erectile effect.64 MC4R is expressed in the rat and human penis, as well as in rat spinal cord, hypothalamus, brainstem, and pelvic ganglion, but not in rat corpus cavernosal smooth muscle cells. In mice, administration of an MC4R agonist increased copulation, whereas knockout mice lacking the gene encoding for the receptor showed decreased copulatory behavior. Other dopamine agonists used are cabergoline administered at 0.5 mg up to three times per week, and ropinirole at 0.25 mg administered daily.45,49 Oxytocin lozenges, linked to improved arousal

723 and desire, are administered at 250IU sublingual 30 minutes to 1 hour before sexual activity. Research with oxytocin has shown marked improvement in a number of components of sexual function, including libido, erection, and orgasm.45 Amphetamines like Adderall and other drugs used to treat attention deficit disorder have been increasingly useful in helping patients to concentrate and thus improving orgasmic response and intensity.57

Vasodilators

Basic science studies58,65 investigating the physiology of sexual function utilizing female animal models support the role of nitric oxide cyclic guanosine monophosphate phosphodiesterase type 5 pathways in the peripheral arousal physiology of the clitoral corpus cavernosum, corpus spongiosum, vaginal epithelium, and vaginal lamina propria. There have been several clinical studies66–68 on selective phosphodiesterase inhibitors (PDE5i) over the last few years, conducted with either premenopausal or postmenopausal patients with arousal sexual health concerns as well as healthy patients without FSD. Many studies did not take into account the hormonal milieu of the subjects in the inclusion and exclusion criteria. An important point in treating patients with arousal sexual health concerns is that an adequate sex steroid (androgen and estrogen) hormonal milieu is critical for benefits from selective phosphodiesterase inhibitor treatment. One study, a double-blind, crossover, placebo-controlled safety and efficacy study by Nurnberg et al.68 with selective PDE5i, was performed in premenopausal patients with normal ovulatory cycles and normal levels of steroid hormones who were affected by female sexual arousal disorder without hypoactive sexual desire disorder. Subjects were observed to benefit from treatment with the active selective PDE5i, showing improvement in sexual arousal, orgasm, frequency, and enjoyment of sexual intercourse versus placebo. Nurnberg found that sildenafil significantly improved sexual function, especially orgasm in patients whose free testosterone values were in the normal range and also in patients who developed sexual health problems following use of selective serotonin reuptake inhibitors.68

Sexual pain management

Biological pathophysiologies resulting in FSD associated with sexual pain may occur in the clitoris, urethra, bladder, vulva, vestibule, vagina, and pelvic floor muscles.

Clitoris, prepuce, and frenula

In patients with focused clitoral pain, clitoral itching, or clitoral burning, careful inspection of the glans clitoris should be performed.69 Failure to visualize the whole glans clitoris with the corona is consistent with some degree (mild, moderate, or severe) of preputial phimosis, based on the elasticity of the prepuce and its ability to retract on examination. Since phimosis may create a closed compartment, phimosis is often the underlying pathology in clitoral glans balanitis associated with recurrent fungal infections. Initial treatment may be conservative with topical estrogen and/or testosterone creams to see if the prepuce can be made more elastic and retractile. Topical antifungal agents such as nystatin or oral antifungal agents such as fluconazole may be considered. Infections can also be related to the herpes virus, with appropriate treatment administered such as acyclovir. If conservative treatment fails due to the phimotic prepuce, surgical management by lysis of adhesions or dorsal slit pending on the severity of phimosis should be considered.70

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Gentle retraction of the labia minora should provide a full view of the urethral meatus. Prolapse of the urethral mucosa out of the urethral lumen is highly associated with estrogen deficiency states such as following bilateral oophorectomy, oral contraceptive use, natural menopause, or following chemotherapy for malignancy. Clinical symptoms include urgency, frequency, and discomfort during urination as well as spotting of blood, which may be observed on the toilet paper after wiping following voiding. The abnormal voiding history is often accompanied by a unique sexual history. Patients with urethral prolapse often have the ability to have full sexual pleasure and satisfaction during self-stimulation of the clitoris; however, during sexual activity with the partner or with a mechanical device, they experience pain and/or urgency to urinate and/ or inability to have orgasm secondary to distracting pain. Conservative treatment options include topical or systemic estrogens, although the risks and benefits of estrogen treatment need to be fully discussed.

Vulva/vestibule

Genital sexual pain in the vulva/vestibule may be related to varied specific disorders. 35,71,72 The treatment of any genital sexual pain disorder involves the multidisciplinary team approach, and this is especially true for the disabling condition of vestibulodynia. Patient management includes education and support, especially regarding avoidance of contacts and practice of healthy vulval hygiene, pelvic floor physical therapy treatment, management of concomitant depression, and management of any associated neurological, dermatological, gynecological, orthopedic, or urological conditions.

Hormonally mediated vestibulodynia Hormonally mediated vestibulodynia symptoms are similar to those of neuroproliferative but seen more commonly in younger patients who have been exposed to birth control pills or menopausal patients. Symptoms include vaginal dryness, dyspareunia, itching, and burning upon palpation of the vestibule. On physical exam, the vulva may appear atrophic and resorbed, the clitoris can be shrunken, and the telltale sign of hormonally mediated vestibulodynia is an inflamed and painful vestibule and periurethral glands. These are provoked with a Q-tip and are graded on a 0–10 pain scale. The hormonally depleted vagina typically has lost the rugae, has a pale complexion, has a lack of lubricating substance, and will bleed with minimal contact. On wet mount, the microscopic examination reveals parabasal cells and increased white blood cells. The vaginal pH is typically elevated to 6.0–7.0 (normal 4–4.5). Conservative treatment begins with local topical and intravaginal estrogens. Important, however, is to address the testosterone receptors within the vestibule as this tissue is derived from the endoderm compared with the estrogen-rich ectoderm of the vulva and the vagina-derived mesoderm. We routinely will have these patients apply a compounded 0.01% testosterone + 0.3% estrogen cream to the vestibule and into the vagina.

Neuroproliferative vestibulodynia Neuroproliferative vestibulodynia is a disorder seen more commonly in younger patients who have either been living with vestibular pain since they can remember (congenital) or developed

symptoms over time, consistent with neuroproliferative vestibulodynia. Typically, these patients have failed conservative management first: physical therapy, hormone replacement (if necessary), medical management like tricyclic antidepressants or gabapentin, topical xylocaine/lidocaine, and positive VAT. When the VAT is positive, the patient is offered a complete vestibulectomy (Fig. 66.13a and b), which is a surgical procedure in which the entire vestibule and associated glands are surgically excised.

Physical therapy treatment

Although treatment regimens for high and low pelvic floor tone with resultant sexual dysfunction need a separate chapter, we will go over a few important tools that physical therapists use to treat the aforementioned disorders. Burning, stinging, irritating, raw, tearing, and searing pains are the most common complaints reported during and after vaginal penetration. If these symptoms are felt at the vaginal introitus and superficial structures such as the vulva, perineal body, posterior fourchette, and episiotomy site, then most likely the superficial muscle layers of the pelvic floor are implicated. If deeper vaginal pain occurs, restriction of the vaginal canal, levator ani and obturator internus muscle trigger points, or sacroiliac, symphysis pubis, hip, or lumbosacral joint dysfunction may be implicated. 39 Disorders of the pelvic floor that results in bladder/urethra dysfunction and/or sexual dysfunction are common. Conservative therapies for hypersensitivity disorders of the pelvic floor are aimed at muscle reeducation. An individualized pelvic floor rehabilitation program aimed at facilitating sexual comfort and pleasure for patients can be designed. Massage of the pelvic floor can be performed to elongate shortened muscles and decrease hightone spasms in such patients. Conservative therapies for low-tone pelvic floor dysfunction are also aimed at muscle reeducation. Pelvic floor muscle strengthening exercises, augmented with biofeedback and/or electrical stimulation to the pelvic floor, can be initiated. 37,39,40 Once the musculoskeletal diagnosis for vaginismus and dyspareunia has been established, treatment should include the following steps: 1. Correct any joint malalignment to promote pain-free joint mobility. 2. Teach the patient self-correction joint techniques. 3. Inform about positions for sexual intimacy. 4. Eliminate tender trigger points in all of the muscles. 5. Eliminate or reduce scar adhesions and tissue restrictions. 6. Teach pelvic floor muscle awareness with a biofeedback device. 7. Reeducate the pelvic floor muscles to be relaxed upon penetration. 8. Stretch the muscles surrounding the vagina by combining down training with dilators. 9. Correct muscle imbalances by down training (relaxation) and up training (strengthening). 10. Correct muscle imbalances by teaching correct muscle timing and recruitment. 11. Educate about lubricants.

Dermatological conditions lichen sclerosis

Lichen sclerosis73 (Fig. 66.14) is a chronic genital dermatitis condition that is associated with varying intensity of symptoms including vulval itching and/or burning and various degrees of vulval scarring leading to narrowing of the introitus and with

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  FIGURE 66.13  (a) Complete vestibulectomy with vaginal advancement flap includes excision of the vestibular mucosa adjacent to the urethral meatus/Skene’s glands region anteriorly. (b) Picture from the end of a vestibulectomy. All vestibular mucosal tissue has been removed, laterally and posteriorly, with reconstruction including the posterior vaginal flap advancement. subsequent dyspareunia. The typical presentation of burning and itching symptoms can be so intense as to severely interfere with sexual activity, day-to-day activities, and even sleep. If the scarring of lichen sclerosis involves the perianal area, the patient may also complain of perianal fissuring and painful defecation. The diagnosis of lichen sclerosis is suspected by physical examination showing a white color genital, vulval, and vestibular tissue

with paleness, loss of pigmentation, and characteristic “cigarette paper” wrinkling. Classically, the genital tissue changes do not involve the inside of the vagina, and if they involve the perianal area, there is a traditional “figure of eight” extension. The lichen sclerosis condition commonly involves the vestibule with associated labia minora atrophy and the vaginal introitus with loss of elasticity and narrowing.73 Diagnosis is confirmed with a biopsy of the affected areas. Once a diagnosis is made, treatment with clobetasol 0.05% topical cream is applied to all affected areas daily for 12 weeks and then decreased to 3 times a week. For more severe disease, 10% hydrocortisone acetate is compounded in a vaginal cream, and 3–5 g (300–500 mg) is inserted nightly for 2 weeks and then decreased to Monday, Wednesday, and Friday. There are no safety data on these products and local atrophy may occur. Yeast infections must be suppressed using fluconazole 150 mg weekly. Adrenal axis suppression can occur with prolonged use.73 Failure to respond may require more specialist gynecological, dermatological, or plastics support. There is emerging and exciting data around the use of Laser as an alternative to steroids (https://www. sciencedirect.com/science/article/pii/S2352647519300486) and further studies are now being undertaken with CO2 laser (https:// clinicaltrials.gov/ct2/show/NCT03665584)

Lichen planus FIGURE 66.14  Lichen sclerosis is diagnosed by physical examination. The typical presentation is genital, vulval, and vestibular tissue with paleness, loss of pigmentation, and characteristic “cigarette paper” wrinkling. Classically, the genital tissue changes do not involve the inside of the vagina. Lichen sclerosis commonly involves the vestibule with associated labia minora atrophy and the vaginal introitus with loss of elasticity and narrowing.

Lichen planus is another chronic genital dermatitis condition, which is likely to have a pathophysiology related to varied altered immunological disorders, and as a result, the presenting symptoms may vary widely. Lichen planus may occur secondary to drugs, such as antihypertensives, diuretics, oral hypoglycemics, and nonsteroidal anti-inflammatory agents. One presentation is primarily associated with itching and does not result in scarring. Another is erosive and destructive. Overall, patient

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inflammatory vaginitis of noninfectious etiology, with secondary bacterial microbiota disruption.74 DIV is characterized by pain (dyspareunia, vaginal/introital pain, burning) with diffuse exudative vaginitis and epithelial cell exfoliation, resulting in profuse vaginal discharge (usually yellow but may be gray or green). In a large series of 98 patients diagnosed with DIV (mean age 49.6 years), 70–90% had purulent vaginal discharge, dyspareunia, and vaginal inflammation.75 Treatment is aimed at alleviating the chronic discharge with various compounded mixtures of antibiotics, steroids, and hormones applied topically to the inside of the vagina as a suppository. Currently, we use a compounded vaginal suppository of 10% hydrocortisone + 2% clindamycin + 0.02% estradiol. Anytime a treatment regimen involves a strong steroid like hydrocortisone or clobetasol, antifungal should be used since resultant yeast infections can be common.

complaints may include severe vulval itching, pain, burning, and irritation similar to lichen sclerosis. Dyspareunia occurs secondary to vaginal introital scarring. Some types of lichen planus, unlike lichen sclerosis, may involve the vaginal mucosa. If there is vaginal involvement, a purulent malodorous discharge may be noted. Findings on physical examination of patients with lichen planus vary widely. The pruritic type of lichen planus is associated with a purple color and multiple papules and plaques on the vulva and vestibule. The erosive type is associated with vestibular ulcers, scarring, clitoris and labia minora atrophy, and occasionally destruction of the vagina has been reported.43 Similar to lichen sclerosus, biopsy proven disease with lichen planus is treated similarly with a topical steroid, clobetasol 0.05%. Daily treatment may be needed for 8–12 weeks to gain adequate control. Education is very important here. The patient needs to know exactly where to apply the ointment and how much. A diagram is very useful and a clinical photograph of the female patient’s affected area is even better. For long-term use consider intermittent application, such as treatment on Monday, Wednesday, and Friday, or switch to a low potency steroid. If there is concern about recurrent yeast infections prescribe oral fluconazole 150 mg weekly for suppression.

Surgery Surgical treatment for neuroproliferative vestibulodynia

Surgical intervention for the management of patients with neuroproliferative vestibulodynia is offered to those who have failed initial conservative medical, psychological, and/or physical therapy-focused treatment. Surgery is based on the hypothesis that the pathophysiology of neuroproliferative vestibulodynia is associated with inflamed, irritated, and hypersensitive vestibular glandular tissue and related increased nerve density in the vestibular mucosa. Surgical success is therefore based on excision of this abnormal glandular and nerve tissue in the vestibule. In patients with neuroproliferative vestibulodynia, the procedure entitled complete vestibulectomy with vaginal advancement flap includes excision of the vestibular mucosa adjacent to the urethral meatus/Skene’s glands region anteriorly, excision of vestibular mucosa laterally, and posteriorly to the hymen with reconstruction including the posterior vaginal flap advancement

Desquamative inflammatory vaginitis

Patients who present because of a qualitative or quantitative alteration in vaginal discharge should be evaluated by clinical examination and appropriate laboratory tests, such as pH and microscopy. Bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis vaginitis are the most common causes of vaginal discharge in premenopausal patients. When these conditions have been excluded, other causes of vaginal discharge must be considered in the differential diagnosis of patients with vaginal complaints. Desquamative inflammatory vaginitis (DIV) (Fig. 66.15a and b) is a chronic clinical syndrome of unknown etiology. Most investigators believe that it is primarily an

  FIGURE 66.15  (a) and (b) Desquamative inflammatory vaginitis. Copious yellow discharge, usually described by patients as “dries like glue” and “sticks to underwear.” Under microscopy, we see leukorrhea and parabasal cells.

Female Sexual Dysfunction (Fig. 66.13a and b). This procedure is usually performed under general or regional anesthesia. Complications include bleeding, infection, increased pain, hematoma, wound dehiscence, vaginal stenosis, scar tissue formation, and Bartholin duct cyst formation. During vestibulectomy, the vaginal advancement may cover the ostia of the Bartholin glands; however, the risk of postoperative Bartholin gland cyst formation is only 1%. As always with surgery, the risk of these complications can be reduced with appropriate surgical techniques. Various closure techniques have been described to minimize the risks of postoperative complications. Specifically, the vaginal advancement flap should be anchored by multiple interrupted horizontal mattress sutures of 3–0 Vicryl placed in an anterior-posterior direction. The remaining mucosal flap is then approximated to the perineum with interrupted stitches of 4–0 Vicryl. Intraoperative bupivacaine extended-release liposome is applied conservatively to the dissected tissue to aid in 72 hours of postoperative recovery. Postoperative care includes oral opioid pain medications for the first few weeks, including warm baths nightly. At 6 weeks postoperative follow-up, we will (1) perform vulvoscopy and a vaginal ultrasound to determine the presence or absence of Batholin’s cysts if there is clinical suspicion and (2) perform a Q-tip test to see if any recurrent glands are causing pain. Ultrasound allows visualization of Bartholin cyst formation. We have found that cysts >10 mm, when painful, are easily drained via intraoperative marsupialization.

Conclusions In a comprehensive textbook on urology and urogynecology, it is important and appropriate to have a detailed chapter on the biologically focused management of Female Sexual Dysfunction. In the twenty-first century, increasing numbers of health-care clinicians will need to be able to manage patients assigned female at birth with sexual health concerns since more and more will expect and demand such management. In addition, those healthcare clinicians who want to maximize overall health-care delivery will increasingly engage in the management of patients assigned female at birth sexual health concerns, in addition to the traditional focus on continence and urological conditions. The need to address these issues is such that in future it will be increasingly more difficult for urologists and urogynecologists to not provide at least first-line sexual health care to these patients. The basic premise of biologically focused management of FSD is that the normal physiological processes regulating sexual activity can be altered by biological pathology. Increased intensive basic science investigation is required to determine how each specific medical condition modulates sexual health. From the perspective of biologically focused clinicians, identification of the underlying pathophysiology of the sexual dysfunction is essential. If the biological basis of the sexual health concern can be diagnosed by history and physical examination and laboratory testing, then management outcome may be successfully directed to the source pathophysiology. Of the many challenges facing health-care professionals today, the first is to improve the ability to accurately diagnose patients assigned female at birth with sexual health concerns, and the second is to ensure that they receive the best evidence-based available management options. The biologically focused clinician needs to have access to new developments in evidence-based, state-of-the-art data concerning biologically focused management strategies for the sexual health of patients assigned female at birth. As previously stated,

727 membership in specialized societies such as the International Society for the Study of Women’s Sexual Health (ISSWSH) will help the interested clinician achieve this goal.

ISSWSH Clinicians who are particularly interested in sexual health of patients assigned female at birth or want to improve their clinical management skills may wish to become members of the ISSWSH, an international, multidisciplinary, academic, clinical, and scientific organization. The purposes of the ISSWSH are to provide opportunities for communication among scholars, researchers, and practitioners about the sexual health of patients assigned female at birth; to support the highest standards of ethics and professionalism in research, education, and clinical practice relative to the sexual health of patients assigned female at birth; and to provide the public with accurate information about the sexual health of patients assigned female at birth. Interested health-care professionals should visit the organization’s website: http://www. isswsh.org.

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The Journal of Sexual Medicine. 2007;4. doi:10.1111/j.1743-6109.2007.00450.x 25. Panzer C, Guay A. Testosterone replacement therapy in naturally and surgically menopausal women (CME). Journal of Sexual Medicine. 2009;6(1). doi:10.1111/j.1743-6109.2008.01128.x 26. Kingsberg SA, Simon JA, Goldstein I. The current outlook for testosterone in the management of hypoactive sexual desire disorder in postmenopausal women. Journal of Sexual Medicine. 2008;5(Suppl. 4). doi:10.1111/j.1743-6109.2008.00961.x 27. Veronelli A, Mauri C, Zecchini B, et al. Sexual dysfunction is frequent in premenopausal women with diabetes, obesity, and hypothyroidism, and correlates with markers of increased cardiovascular risk. A preliminary report. Journal of Sexual Medicine. 2009;6(6). doi:10.1111/j.1743-6109.2009.01242.x 28. Derogatis L, Clayton A, Lewis-D’agostino D, Wunderlich G, Fu Y. Validation of the female sexual distress scale-revised for assessing distress in women with hypoactive sexual desire disorder. Journal of Sexual Medicine. 2008;5(2). doi:10.1111/j.1743-6109.2007.00672.x 29. Davison SL, Bell RJ, la China M, Holden SL, Davis SR. Assessing sexual function in well women: validity and reliability of the Monash women’s health program female sexual satisfaction questionnaire. Journal of Sexual Medicine. 2008;5(11). doi:10.1111/j.1743-6109.2008.00967.x 30. Ferguson GG, Nelson CJ, Brandes SB, Shindel AW. The sexual lives of residents and fellows in graduate medical education programs: a single institution survey. Journal of Sexual Medicine. 2008;5(12). doi:10.1111/j.1743-6109.2008.01002.x 31. Derogatis LR, Allgood A, Rosen RC, Leiblum S, Zipfel L, Guo CY. Development and evaluation of the women’s sexual interest diagnostic interview (WSID): a structured interview to diagnose hypoactive sexual desire disorder (HSDD) in standardized patients. Journal of Sexual Medicine. 2008;5(12). doi:10.1111/j.1743-6109.2008.01008.x 32. Aslan E, Beji NK, Gungor I, Kadioglu A, Dikencik BK. Prevalence and risk factors for low sexual function in women: a study of 1,009 women in an outpatient clinic of a University Hospital in Istanbul. Journal of Sexual Medicine. 2008;5(9). doi:10.1111/j.1743-6109.2008.00873.x 33. Burrows LJ, Shaw HA, Goldstein AT. The vulvar dermatoses. Journal of Sexual Medicine. 2008;5(2). doi:10.1111/j.1743-6109.2007.00703.x 34. Landry T, Bergeron S. How young does vulvo-vaginal pain begin? Prevalence and characteristics of dyspareunia in adolescents. Journal of Sexual Medicine. 2009;6(4). doi:10.1111/j.1743-6109.2008.01166.x 35. Goldstein AT, Burrows L. Continuing medical education: vulvodynia (CME). The Journal of Sexual Medicine. 2008;5(1). doi:10.1111/j.17436109.2007.00679.x 36. Yang CC. The neurourological examination in women. Journal of Sexual Medicine. 2008;5(11). doi:10.1111/j.1743-6109.2008.01022.x 37. Rivalta M, Sighinolfi MC, de Stefani S, et al. Biofeedback, electrical stimulation, pelvic floor muscle exercises, and vaginal cones: a combined rehabilitative approach for sexual dysfunction associated with urinary incontinence. Journal of Sexual Medicine. 2009;6(6). doi:10.1111/j.1743-6109.2009.01238.x

























38. Voorham-van Der Zalm PJ, Lycklama à Nijeholt GAB, Elzevier HW, Putter H, Pelger RCM. “Diagnostic investigation of the pelvic floor”: a helpful tool in the approach in patients with complaints of micturition, defecation, and/or sexual dysfunction. Journal of Sexual Medicine. 2008;5(4). doi:10.1111/j.1743-6109.2007.00725.x 39. Beck JJH, Elzevier HW, Pelger RCM, Putter H, Voorham-van Der Zalm PJ. Multiple pelvic floor complaints are correlated with sexual abuse history. Journal of Sexual Medicine. 2009;6(1). doi:10.1111/j.1743-6109.2008.01045.x 40. Rosenbaum TY, Owens A. The role of pelvic floor physical therapy in the treatment of pelvic and genital pain-related sexual dysfunction. Journal of Sexual Medicine. 2008;5(3). doi:10.1111/j.1743-6109.2007.00761.x 41. Buckler H, Al-Azzawi F. The effect of a novel vaginal ring delivering oestradiol acetate on climacteric symptoms in postmenopausal women. BJOG: An International Journal of Obstetrics and Gynaecology. 2003;110(8). doi:10.1111/j.1471-0528.2003.02408.x 42. Alatas E, Yagci B, Oztekin O, Sabir N. Effect of hormone replacement therapy on clitoral artery blood flow in healthy postmenopausal women. Journal of Sexual Medicine. 2008;5(10). doi:10.1111/j.1743-6109.2008.00887.x 43. Nijland EA, Schultz WCMW, Nathorst-Boös J, et al. Tibolone and transdermal E2/NETA for the treatment of female sexual dysfunction in naturally menopausal women: results of a randomized active-controlled trial. Journal of Sexual Medicine. 2008;5(3). doi:10.1111/j.1743-6109.2007.00726.x 44. Giraldi A, Marson L, Nappi R, et al. Physiology of female sexual function: animal models. Journal of Sexual Medicine. 2004;1(3). doi:10.1111/j.1743-6109.04037.x 45. MacDonald K, Feifel D. Dramatic improvement in sexual dunction induced by intranasal oxytocin. Journal of Sexual Medicine. 2012;9(5). doi:10.1111/j.1743-6109.2012.02703.x 46. Çayan F, Dilek U, Pata Ö, Dilek S. Comparison of the effects of hormone therapy regimens, oral and vaginal estradiol, estradiol + drospirenone and tibolone, on sexual function in healthy postmenopausal women. Journal of Sexual Medicine. 2008;5(1). doi:10.1111/j.1743-6109.2007.00635.x 47. Barentsen R, van de Weijer PHM, Schram JHN. Continuous low dose estradiol released from a vaginal ring versus estriol vaginal cream for urogenital atrophy. European Journal of Obstetrics and Gynecology and Reproductive Biology. 1997;71(1). doi:10.1016/S0301-2115(96)02612-7 48. Rioux JE, Devlin CM, Gelfand MM, Steinberg WM, Hepburn DS. 17β-Estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis. Menopause. 2000;7(3). doi:10.1097/00042192-200007030-00005 49. Pfaus JG. Pathways of sexual desire. Journal of Sexual Medicine. 2009;6(6). doi:10.1111/j.1743-6109.2009.01309.x 50. Clayton AH, Warnock JK, Kornstein SG, Pinkerton R, Sheldon-Keller A, McGarvey EL. A placebo-controlled trial of bupropion SR as an antidote for selective serotonin reuptake inhibitor-induced sexual dysfunction. Journal of Clinical Psychiatry. 2004;65(1). doi:10.4088/JCP.v65n0110 51. Segraves RT, Clayton A, Croft H, Wolf A, Warnock J. Bupropion sustained release for the treatment of hypoactive sexual desire disorder in premenopausal women. Journal of Clinical Psychopharmacology. 2004;24(3). doi:10.1097/01.jcp.0000125686.20338.c1 52. Loeser AA. Subcutaneous implantation of female and male hormone in tablet form in women. BMJ. 1940;1(4133). doi:10.1136/bmj.1.4133.479 53. Baulieu EE, Thomas G, Legrain S, et al. Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHE age study to a sociobiomedical issue. Proceedings of the National Academy of Sciences of the United States of America. 2000;97(8). doi:10.1073/pnas.97.8.4279 54. Baulieu EE. Dehydroepiandrosterone (DHEA): a fountain of youth? Journal of Clinical Endocrinology and Metabolism. 1996;81(9). doi:10.1210/ jcem.81.9.8784058 55. Arlt W, Callies F, van Vlijmen JC, et al. Dehydroepiandrosterone replacement in women with adrenal insufficiency. New England Journal of Medicine. 1999;341(14). doi:10.1056/nejm199909303411401 56. Shifren JL, Braunstein GD, Simon JA, et al. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. Obstetric and Gynecologic Survey. 2001;56(2). doi:10.1097/00006254-200102000-00021 57. Winland C, Haycox C, Bolton JL, et al. Methamphetamine enhances sexual behavior in female rats. Pharmacology Biochemistry and Behavior. 2011;98(4). doi:10.1016/j.pbb.2011.03.001 58. Park K, Moreland RB, Goldstein I, Atala A, Traish A. Sildenafil inhibits phosphodiesterase type 5 in human clitoral corpus cavernosum smooth muscle. Biochemical and Biophysical Research Communications. 1998;249(3). doi:10.1006/bbrc.1998.9206 59. Stahl SM. Mechanism of action of flibanserin, a multifunctional serotonin agonist and antagonist (MSAA), in hypoactive sexual desire disorder. CNS Spectrums. 2015;20(1). doi:10.1017/S1092852914000832

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60. Stahl SM, Sommer B, Allers KA. Multifunctional pharmacology of flibanserin: possible mechanism of therapeutic action in hypoactive sexual desire disorder. Journal of Sexual Medicine. 2011;8(1). doi:10.1111/j.17436109.2010.02032.x 61. Woodard TL, Nowak NT, Balon R, Tancer M, Diamond MP. Brain activation patterns in women with acquired hypoactive sexual desire disorder and women with normal sexual function: a cross-sectional pilot study. Fertility and Sterility. 2013;100(4). doi:10.1016/j.fertnstert.2013.05.041 62. Benabdallah G, Alj L, Benkirane R, et al. Who guideline: Reporting and learning systems for medication errors: The role of pharmacovigilance centres. Drug Safety. Published online 2015. 63. Giuliano F. Control of penile erection by the melanocortinergic system: experimental evidences and therapeutic perspectives. Journal of Andrology. 2004;25(5). doi:10.1002/j.1939-4640.2004.tb02842.x 64. van der Ploeg LHT, Martin WJ, Howard AD, et al. A role for the melanocortin 4 receptor in sexual function. Proceedings of the National Academy of Sciences of the United States of America. 2002;99(17). doi:10.1073/ pnas.172378699 65. Burnett AL, Calvin DC, Silver RI, Peppas DS, Docimo SG. Immunohistochemical description of nitric oxide synthase isoforms in human clitoris. Journal of Urology. 1997;158(1). doi:10.1097/00005392199707000-00020 66. Caruso S, Intelisano G, Lupo L, Agnello C. Premenopausal women affected by sexual arousal disorder treated with sildenafil: a double-blind, cross-over, placebo-controlled study. British Journal of Obstetrics and Gynaecology. 2001;108(6). doi:10.1016/S0306-5456(00)00143-1 67. Caruso S, Intelisano G, Farina M, di Mari L, Agnello C. The function of sildenafil on female sexual pathways: a double-blind, crossover, placebo-controlled study. European Journal of Obstetrics and

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MULTIDISCIPLINARY CLINICS Urogynaecology, Colorectal, and Urology Hayser Medina Lucena, Ivilina Pandeva, and Ashish Pradhan

Introduction In 1995, the Calman–Hine report outlined steps to reduce inequalities in cancer care and improve survival rates in the United Kingdom (1). A major recommendation of the report was for clinicians to practice a multidisciplinary team (MDT) approach where a range of specialists from relevant departments would work together to collaborate, share information and thereby improve patient outcomes (1). This was cemented in 2001 when the national cancer peer review programme was introduced. Although there is evidence that MDTs have a significant positive impact on cancer care in the UK (2, 3), there have been some studies that state they make no difference to the clinical outcomes (4, 5). Since the introduction of MDT for cancer care, there have been a range of specialties that have adopted the same approach to address complex conditions. There is evidence that in benign cases such as inflammatory bowel disease and lung disease, an MDT in a formal environment can improve patient outcomes (6, 7). Morar et al. stated that a successful MDT depends on adequate attendance, proactive involvement, a need to define core members and appropriate and functional information and technology facilities (7). In 2013 in the United Kingdom, the National Institute for Health and Care Excellence (NICE) advised on the use of MDT meetings in urogynaecology, which led to this being adopted as a standard practice (8). The guideline for the management of urinary incontinence in women recommended the use of local MDT meetings to review cases where invasive procedures were offered for primary stress urinary incontinence and overactive bladder (8). In 2019, these guidelines were updated and the recommendations were extended to include a review of women with primary stress urinary incontinence, overactive bladder and primary prolapse in local MDT meetings. Additionally, the guidelines recommended regional MDT meetings to address the management of complex pelvic floor dysfunction (PFD) and mesh-related complications (9). In the context of urogynaecology, a MDT meeting has the potential of arriving at a better outcome for patients as a result of increased reflection and clinical discussion. A greater number of expert perspectives during the decision-making process can help with advising patients on a broader range of treatment options than might be available under one specialty. Such a positive working environment also provides a valuable learning experience for all concerned (10). Some could argue that MDT meetings consisting of only urogynaecologists, physiotherapists and urogynaecology nurse specialists, do not cover all the expertise that is required in more complex cases of PFD where the input of all three domains (urogynaecology, colorectal and urology) is needed, and therefore lead to a less than optimal outcome, but this can be resolved by inviting more specialists to take part (11). 730

This chapter will cover the role of the joint pelvic floor multidisciplinary service (meetings and clinics) in the management of complex PFD, the specific conditions that are discussed and the appropriate expertise and advice given by the main specialist services: Urogynaecology, Urology and Colorectal.

Pelvic floor dysfunction PFD is a broad term used to describe the combination of a variety of symptoms including urgency and stress urinary incontinence, pelvic organ prolapse, sensory abnormalities of the lower urinary tract, faecal incontinence and voiding and defecatory dysfunction (12). PFD affects a significant number of women and the incidence increases with age. It has been reported that around 24% of women over the age of 20 experience at least one pelvic floor disorder, 16% urinary incontinence, 9% faecal incontinence and 3% pelvic organ prolapse (13). A more recent study showed the lifetime risk for stress urinary incontinence or pelvic organ prolapse surgery by the age of 80 is 20% (14). Parity, obesity and ageing have a significant association with PFD (15). With improvements in healthcare, the population of many countries is older due to increased longevity (16). Hence, we are seeing an increase in the incidence of PFD and consequently an increase in healthcare costs associated with PFD (17). This again emphasises the importance of management of these women’s complex conditions by an MDT, providing a holistic approach to care thus ensuring the most appropriate and effective treatment is offered.

Joint pelvic floor clinic/MDT The multidisciplinary joint pelvic floor team includes: • A subspecialist in urogynaecology who offers prolapse and incontinence surgery, conservative therapies, as well as simultaneous treatment of any coexistent gynaecological problems, i.e. menorrhagia, dyspareunia, etc. • A urologist with specialist expertise in female and reconstructive urology. They are trained to perform urinary diversions, augmentation cystoplasty, urethroplasty, treatment of stones, sacral neuromodulation and fistula repairs, etc. • A colorectal surgeon with a special interest in functional bowel disorder and pelvic floor reconstruction who offers sacral neuromodulation, surgical options for rectal prolapse (e.g. Delorme’s procedures, laparoscopic/open rectopexy) or conservative management of bowel dysfunction and biofeedback. • A urogynaecology and/or urology continence nurse who provides support and conservative management according

DOI: 10.1201/9781003144236-73

Multidisciplinary Clinics to their area of expertise i.e. pessary management, bladder instillations etc. • A women’s health physiotherapist with a special interest in pelvic floor dysfunction who offer support in teaching patients pelvic floor exercises, bladder training and relaxation techniques for the pelvic floor muscle complex. • A pain specialist with an interest in the management of chronic pelvic pain. • A radiologist with a special interest in pelvic floor imaging. It may also include: • A nurse specialist trained in biofeedback and trans-anal irrigation • A clinical psychologist • A member of the care of the elderly team • An occupational therapist • A plastic surgeon with expertise in operating in the obturator region As per the updated NICE recommendations, the above list of experts corresponds to the members and collaborative services suggested for a regional PFD MDT (9). The recommendations extend to the availability of ready access or a dedicated referral pathway to Psychosexual Counselling and Neurology services (9). The concept of a MDT is gaining increasing popularity in the management of pelvic floor disorders. A survey of members of the Pelvic Floor Society found that 84% of tertiary and 75% of regional units held or attended some form of regular MDT meeting (18). Currently, there are no clear guidelines on the frequency and length of MDT meetings. A joint MDT meeting conducted at least twice monthly for approximately one hour and a joint pelvic floor clinic once a month is advisable. The current NICE guideline recommends that the local MDTs review the proposed treatment for all women offered invasive treatment for primary urinary incontinence or primary prolapse (9). Hence a bi-monthly MDT may not be adequate to be able to discuss all the cases and the frequency of these meetings will depend upon the volume and complexity of cases to discuss. Although not all centres in the United Kingdom have the infrastructure or personnel for an extended pelvic floor MDT, it is clear that these services and members are a requirement in the setup of mesh removal centres (9).

Aims of the joint pelvic floor clinic NICE recommends a regional MDT approach to be set up in every NHS service to discuss complex PFD and mesh-related problems (Table 67.1) (9). The aim of the joint pelvic floor clinic is: • Discuss the role of further diagnostic tests and/or treatment. • Allow holistic evaluation and approach for comprehensive care. • Facilitate follow-up and monitoring. • Aid reassurance to patient. • Inform and educate team members, which leads to a more positive working environment and richer work experience. • Encourage research and establish collaborations on clinical improvement projects. • Optimise and streamline patient’s journey.

731 • Feedback to health-care professionals when appropriate to improve overall management of patients. • Provide a setting for training and education for trainees in all relevant disciplines. TABLE 67.1: Cases to Review in Regional MDT as per NICE Guidelines Cases to Review in Regional MDT as per NICE Guidelines Recurrent incontinence Recurrent same-site prolapse Coexisting bowel disorders requiring additional colorectal input Discuss option of mesh for prolapse or urinary incontinence Mesh complications or unexplained symptoms after mesh surgery for urinary incontinence or prolapse Opting for surgery when family is not complete Favoured treatment option is not available in the referring hospital

Recurrent urinary incontinence Lower urinary tract dysfunction tends to be the predominant complaint discussed in the joint pelvic floor MDT meetings (11). According to Pandeva et al., the majority of the cases discussed are stress urinary incontinence (35%), mixed urinary incontinence (32%) and urge urinary incontinence (22%). MDT input led to a change in the initial management plan in 20% of the cases. The changes were in patients with complex urinary incontinence (e.g. failed primary treatment, those requiring secondary surgery or coexisting symptoms involving multiple pelvic compartments) (11). In line with the NICE guidelines, a joint pelvic floor MDT (regional MDT) review should be conducted for patients who have recurrent urinary incontinence and require surgical treatment (9). The complexity of these cases requires surgical expertise and careful counselling on the pros and cons of management options and necessitates the involvement of allied specialties. This allows access to specialist investigations such as video urodynamics or ambulatory urodynamics studies, advanced pelvic floor imaging or more invasive/complex surgery such as urinary diversion, augmentation cystoplasty or artificial urinary sphincters. Percutaneous nerve stimulation can be offered as an alternative treatment in patients with refractory overactive bladder (OAB) where intradetrusor injections with onabotulinum toxin A (Botox®) have not been effective or they are not prepared to accept the risks of needing intermittent self-catheterisation associated with Botox® (9). These patients are discussed in the joint pelvic floor MDT forum and subsequently seen in the joint clinic to guarantee a holistic approach to their care. Sacral nerve stimulation appears to be effective but it is also known to result in a discreetly high rate of complications, need for surgical revision and higher cost of the neurostimulator machine (19–21). Integrated care by the MDT provides a wide area of expertise and advice which is required in the short and long term, with the aim of reducing complications and optimising care. A cross-functional approach in clinics will also guarantee appropriate management at the time of surgery, especially when dual expertise is required. Some examples include resection of migration/extrusion of bulking agent (Fig. 67.1), partial or complete excision of the eroded mesh into the bladder/urethra, urethral diverticulectomy and vesicovaginal fistula repair.

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FIGURE 67.1  Cystoscopic image of extrusion of para-urethral bulking agent (Zuidex) into urethral lumen.

Complex pelvic floor disorders associated with bowel dysfunction Bowel dysfunction commonly coexists in patients with urinary incontinence or pelvic organ prolapse (13). Studies show that 1 in 5 women experience concomitant anal incontinence, alongside urine leakage or uterovaginal prolapse (22). There are advantages to managing patients presenting with pelvic organ prolapse and concomitant obstructive defaecation and/or bowel dysfunction in a multidisciplinary setting. Pandeva et al. reported change in the primary care team in 16% of cases, following pelvic floor MDT discussion, ensuring management by the most appropriate team and optimal outcome (11). Faecal incontinence was reported to be the predominant symptom in around 10% of the cases discussed in the joint pelvic floor MDT (11). These cases tend to reflect patients who have exhausted conservative treatment and/or biofeedback and are therefore suitable for the consideration of other specialist treatment options. Sacral nerve stimulation (SNS) as a treatment option for faecal incontinence has shown to be beneficial in patients resistant to conservative treatment in the medium and long term (23, 24). Better results are seen where patients have an intact anal complex sphincter (23). SNS is expensive and this needs to be considered when recommending this treatment (19). A joint pelvic floor MDT approach is also valuable and effective for complex cases such as women presenting with multi-compartmental prolapse i.e. rectal prolapse, alongside apical vaginal wall prolapse. These cases provide an excellent opportunity for multidisciplinary surgical approach in a single setting as a combined procedure, leading to optimising care and minimising the need for multiple anaesthetics and separate procedures. The broader scope of experience offered by multiple clinicians who care for patients with complex pelvic floor disorders, especially colorectal surgeons, urogynaecologists and bowel function nurses, helps to provide a consensus opinion on the management of these challenging cases.

extrusion, infection, chronic pain and sexual dysfunction as well as ongoing disability following removal (26, 27). The presentation interval of mesh-related complications can vary greatly with studies showing 10% presentation around the time of surgery and 30% being symptomatic at four weeks or presenting many years after insertion (28). The number of mesh-related complication cases discussed in MDT meetings corresponded to less than 5% of the overall caseload (11, 29); however, this number is expected to increase when the management of mesh-related complications is centralised in mesh referral centres as per recommendations of the Independent Medicines and Medical Devices Safety review (IMMDS) in UK (30). The International Urogynaecological Association (IUGA) and the International Continence Society (ICS) published a classification system of mesh complications in 2011; the list illustrates the different compartments that could get affected (31). The urinary tract complications can vary between perforation, fistula, calculus; the bowel complications include erosion, stricture or fistula formation; vaginal complications encompass vaginal mesh exposure or extrusion and skin and/or musculoskeletal complications: discharge, chronic pain, presence of a lump or sinus tract formation (Fig. 67.2) (31). ICS/IUGA have not published any specific recommendations about the role of MDT in managing women with mesh-related complications. Due to the complexity of symptoms with multiple compartment involvement, some women would require multiple procedures (24). Choosing the appropriate investigations and optimisation of treatment at the initial diagnosis of any meshrelated complication is extremely important and can be better achieved by a multi-professional approach. For those women who have complete or partial mesh excision, a proportion of them will experience further complications such as recurrence of stress urinary incontinence or pelvic organ prolapse or both and/or persistence of pain. These cases have access to enhanced services and

Mesh-related complications Synthetic implants (Mesh) have been widely used to treat urinary incontinence and uterovaginal prolapse over the last several years (25). As a result, there has been a rise in the number of patients developing mesh-related symptoms and complications, including

FIGURE 67.2  MRI image of thigh abscess secondary to transobturator route tape procedure.

Multidisciplinary Clinics potentially better care when managed by joint clinical care due to the multifactorial aetiology (9). In line with the most updated recommendations from NICE (9) and the recent Independent Medicines and Medical Devices Safety (IMMDS) review on the use of surgical mesh for pelvic surgery (30), the adoption of a joint pelvic floor MDT provides an excellent forum for discussion and management of cases of meshrelated complications. The most updated NICE guideline on the management of pelvic organ prolapse and urinary incontinence, recommends the development of an individualised investigation plan for each woman with suspected or confirmed mesh-associated complications and discussion with members of the regional/joint MDT in order to make decisions on possible investigations and further management (9). This will not only help provide a standardised practice for the management of these patients but will also centralise care and increase the volume of those cases discussed in the pelvic floor MDT. A key component of the joint MDT is using defined criteria for referral to minimise delay in management due to large numbers of inappropriate referrals, which should be managed by the local MDT. The IMMDS review report specifically advises on networks of specialist centres to be set up to provide comprehensive treatment, care and advice for those affected by mesh (30) as well as a central patient-identifiable database containing key details of the implantation of all devices at the time of the operation. This can then be linked to specifically created registers to research and audit the outcomes both in terms of the device safety and patientreported outcomes measures (PROMS) (11). This could only be achieved by having regional mesh centres and patients discussed in the joint pelvic floor MDTs (Fig. 67.3 (32)). In agreement with other studies, a multidisciplinary approach will help to identify and prioritise gaps in evidence concerning specific mesh complications and their treatment, which could then be addressed with further robust research (33). As a result, the MDT approach is likely to ultimately optimise the outcomes of treatments for these complications. The Pelvic floor disorders network in the USA is a good example of how an MDT approach can be a good platform to collaborate and advance research in this area.

Recurrent urinary tract infection (rUTI) and bladder pain syndrome (BPS) Out of the total number of patients seen in the joint clinic, a small percentage of patients (5%) had recurrent urinary tract infections (rUTI) and bladder pain syndrome (BPS) and were seen and discussed in the joint pelvic floor MDT clinics (11). The management of these conditions can present a challenge because patients are likely to comprise a number of clinical phenotypes known to react differently to the numerous treatments available (34); further emphasising the need for combined experience enabled by a multidisciplinary approach. Usually, patients with rUTI or BPS are discussed in the joint pelvic floor MDT when initial treatment has failed to improve their symptoms and further input from other specialties is required. Although no definitive treatment is currently available for rUTIs or BPS, there are several intravesical or oral preparations available on the market to manage these conditions (34) (see chapters on rUTI and BPS). However, none of these provide level

733 Primary Care

Secondary Care

Tertiary Care

Specialised Mesh Removal Service MDT

Management Plan

Complex vaginal mesh removal surgery Designated Specialised Complex Mesh Removal Service

Non complex vaginal mesh removal surgery

Non-surgical management

Designated Specialised Complex Urogynaecology Conditions Service

FIGURE 67.3  NHS England mesh referral pathway flow diagram. (With permission from ref (32).)

A evidence or have confidently proved to be highly effective in the long term (34–37). This confirms that with no clear evidence or national/international guidelines on which bladder instillation is best for each condition, a multi-professional approach offers optimisation of care and where the full range of therapeutic options could be considered (11).

Conclusions The close anatomy and functional relationship between the lower urinary tract, lower genital tract and anorectum results in symptoms of multiple compartments (38) and as such, an integrated approach across specialties could lead to improved patient care (10, 11, 29, 38). Joint multidisciplinary meetings and clinics have proved to refine the management of patients with complex PFD disorders (10, 11, 29). Studies have shown no significant detrimental impact on waiting times for diagnostics or treatment (10) and the feasibility of joint MDT meetings in the NHS settings. Although there is no evidence of cost-effectiveness of pelvic floor MDT, the role of an MDT in cancer centres suggests that it can be costly and time-consuming (39). Many may argue that MDT meetings take the specialists away from direct patient care and may lead to delays in care (39), however with the clear benefit of the management of complex pelvic floor conditions, a refinement of the criteria for referral to joint pelvic floor MDT may

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734 address some of these issues (9, 11). This, combined with a continuous process of audit and governance, offers efficiency and justifies the effectiveness of MDTs. Wales et al. highlight this as an area to expand for research (29). However, this will require buy-in from clinicians who may not be convinced of the benefits of the MDT and may feel they are giving up control over the decisionmaking process for their patients. Hence future research in this area is required and should also address the impact of pelvic floor MDT on patient satisfaction and quality of life (5). Given the UK guideline recommendations, there is a clear role for an MDT in the management of complex pelvic floor disorders cases. MDT should ensure optimal care to patients where the full range of therapeutic options are considered, improves collaboration between specialties, and provides an excellent learning and teaching opportunity (11).

References











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INDEX Note: Locators in italics represent figures and bold indicate tables in the text.

A AAGL, see American Association of Gynecologic Laparoscopists Abdominal examination, 262 Abdominal leak point pressure (ALPP), 294, 302–303, 737, 837 Abdominal mesh sacrocolpopexy, 1124 Abdominal muscle recruitment, 425 Abdominal pressure, 291 Abdominal sacrocolpopexy (ASC), 935, 971, 1077 Abdominal sacrohysteropexy (ASH), 939 Abdominal straining/Crede manoeuvre, 560 Abdominal suture sacrohysteropexy, 1089 Abdominal wall muscles, 1050 Abdominoplasty, 1259–1260 Abnormal urinary frequency, 258 Abobotulinumtoxin A, 228 ABOG, see American Board of Obstetrics and Gynecology AC, see Anterior colporrhaphy Accessory and Cavitated Uterine Mass (ACUM), 1222 ACE, see Antegrade continence enema Acellular tissue matrices, 197 Acetylcholine (ACh), 207, 248–249, 459–460 ACG, see Anterior cingulate gyrus ACRM, see Anesthesia crisis resource management Activity of daily living (ADL), PRO, 81 ACUM, see Accessory and Cavitated Uterine Mass α-adrenoceptors (ARs), 221 ADH, see Antidiuretic hormone Adipose-derived stem cells (ASCs), 199 Adjustable continence therapy (ACT), balloons, complications of, 864–865 α-adrenergic antagonists, 478–479 β-adrenergic antagonists, 475 α-adrenergic blockers, 478 β-adrenergic receptors, 207–208 α1-adrenergic receptors, 208 α-adrenoceptors, 223 β3-adrenoceptors (ARs), 219 Adult stem cells, 198–199 Afferent pathways, micturition, 208–209 Air-charge catheters, 299 ALARA principles, 307 Alcohol consumption, 262 Aldosterone, 248 Aldridge sling, 766 Allantois, 179–180 Allodynia, 577 Allografts, 769–770 Alpha-adrenergic agonists, 474–475 Alpha-blocker, 560 ALPP, see Abdominal leak point pressure Altis SIS system, 817 Ambulatory urodynamics, 313–322 additional event marker information, 315 analysis, 316–317 clinical application, 318–322

clinical report, 317 comments, 317–318 patient preparation, 317–318 procedure, 318 vs. conventional UDS, 318–319 diary, 314 equipment, 313–315 future technological advances, 315 and incontinence, 319–320 indications, 313 invasive OAB treatment, effect evaluation of, 320 for investigation of LUTS, 313 onabotulinumtoxinA, 320 patient bother, 318 pharmacologic treatment monitoring, 320 sacral neuromodulation, 320 signal quality, 315–316 signals, 315 and spinal cord injury patients, 321 standardization of, 315–317 and storage dysfunction, 318 symptoms and conventional UDS, poor correlation between, 318 terminology, 315 and voiding dysfunction, 321–322 American Association of Gynecologic Laparoscopists (AAGL), 1058 American Board of Obstetrics and Gynecology (ABOG), 1058 American Medical System-800, 837–838 American Society for Reproductive Medicine (ASRM), 665, 1219 American Urogynecologic Society (AUGS), 991 American Urological Association, 594 Aminoglycosides, 620 Amitriptyline/nortriptyline, 591 Amnion-derived stem cells, 198 Amnion stem cells (ASCs), 198 Amoxicillin, 619 AMP, see Antimicrobial, cationic peptides Amyloid neuropathy, 557 Anaemia, 744 Analgesia, postoperative care, 750–751 Anal incontinence conservative therapy, 688–689 anal plug, 689 biofeedback therapy, 689 drugs, 688–689 lifestyle, 688 early recognition of obstetric injuries, 688 etiology of, 686 future mode of delivery, 688 management, 688–689 outcome from anal sphincter repair, 690 age and body habitus, 690 external sphincter atrophy, 690 pathogenesis, 685 neurological damage, 685 obstetric anal sphincter injury, 685 patient assessment examination, 687

history, 686–687 investigations, 687–688 prevalence of, 685 surgery, 689–693 failure of sphincter repair, 690 long-term outcomes after sphincter repair, 690 neosphincters, 692–693 postanal repair and total pelvic floor repair, 690 posterior tibial nerve stimulation, 691–692 sacral nerve modulation, 690–691 sacral nerve stimulation, 690–691 sphincter repair, 689–690 Anal manometry, 703 rectocele, 914 Anal sampling, 1038 Anal sphincter, 645, 646, 1038 internal and external trauma, 646 Anal triangle, 1000–1001 Anatomy anterior vaginal wall prolapse (cystocele), 889–890 apical uterovaginal prolapse, 926–927 bladder, 164, 207–208 dorsal genital nerve (DGN) stimulation, 514 enteroceles, 902 female urethral stricture disease, 1201 functional terms, 168 laparoscopic pelvis, 1049–1053 lower urinary tract, 164–168 LUT, 164–168 ODS, 1038–1039 pelvic floor, 168–177 of perineum, 1000 pouch of Douglas, 902–903 pudendal nerve stimulation, 513 rectocele, 912 sacral promontory, 1077–1079 trans-obturator tape (TOT) sling, 807–808 trigone, 164 urethra, 164–167 urethral diverticulum, 1189–1190 urethral stricture, 1201 Androgens, sexual differentiation, 181 Anesthesia, 47–48 Anesthesia crisis resource management (ACRM), 60 Animal studies, 212–213 Anismus, see Dyssynergia Anorectal malformations (ARM), 181 Anorectal manometry, 701–702 Anorectum, 1038 Antegrade continence enema (ACE), 708, 1033 Anterior abdominal wall, 1049, 1051 Anterior cingulate gyrus (ACG), 212 Anterior colporraphy, 43 Anterior colporrhaphy (AC), 758–759 Anterior compartment assessment, ultrasonography in, 354–355 Anterior vaginal wall prolapse (cystocele), 889

I-1

Index

I-2 anatomy, 889–890 anti-incontinence operations and, 893 defects, 890 3D ultrasound, 891 etiology of, 889 evaluation diagnostic tests, 891 history, 890–891 physical examination, 891 midline defects, 889–890, 892, 894 pathology, 889–890 reduction, urodynamic testing, 891 with STI, 890 surgical repair techniques anterior colporrhaphy, 891–893 anterior prolapse repair with grafts, 893–895 complications, 899–900 cystoscopy, 897 results, 897–899 vaginal paravaginal defect repair, 895–897 symptoms and signs, 890 terminology, 889 transverse defects, 889 Anterior vaginal wall suspension (AVWS), 765 Antibiotic prophylaxis, 375, 622 Anticoagulants, 746–747 Antidepressants, 469–470, 475–477 Antidiuretic hormone (ADH), 248, 481 Antidiuretic vasopressin (AVP), 248 Antifibrosis strategies, 247 Antihistamines, 591 Antimicrobial, cationic peptides (AMP), 250 Antimicrobial factors, 612 Antimuscarinic agents, 544–545, 559 Antimuscarinics (anticholinergics), 223, 459–460, 464–473 Anxiety, 284 Apamin, 227 Apical uterovaginal prolapse, 925 anatomy of supports, 926–927 background, 925–926 extraperitoneal uterosacral-cardinal ligament complex vault suspension, 930–932 iliococcygeus vault suspension for PHVP, 931–932 sacrospinous fixation for PHVP, 931 HUSLS for, 929 intraperitoneal uterosacral-cardinal ligament complex vault suspension, 929–930 Le Fort partial colpocleisis for, 932 obliterative procedures for, 932 post-hysterectomy vault prolapse iliococcygeus vault suspension for, 931–932 sacrospinous fixation for, 931 vaginal repair of, 929 surgical options, 926–927 total colpocleisis for, 932 uterine preservation surgeries, 927–928 Manchester repair, 927 sacrospinous hysteropexy, 927 vaginal hysteropexy with mesh, 927–928

vaginal hysterectomy for, 928–929 McCall cudolplasty at hysterectomy, 928–929 sacrospinous fixation at hysterectomy, 929 vaginal repair procedures of, 927–932 Aprepitant, 221 AQoL, see Assessment of quality of life Aquaporin (Aqp2), 248 β3-AR agonists, 224 α 2-AR antagonists, 475 Arcus tendineus fascia pelvis (ATFP), 758, 889 Arcus tendineus levator ani (ATLA), 172, 175–176 ARM, see Anorectal malformations Artificial bowel sphincter, 692–693, 1029 Artificial urinary sphincter (AUS), 837–845 implantation of complications, 843–844 endoscopic, 843 ideal candidates for, 838 results, 844–845 success rates for, 844–845 transabdominal, 841–843 transvaginal, 838–841 intraoperative complications, 863–864 parts of, 837 postoperative complications, 864 preinsertion assessment, 837–838 ASC, see Abdominal sacrocolpopexy; Adipose-derived stem cells; Amnion stem cells ASH, see Abdominal sacrohysteropexy Assessment of quality of life (AQoL), 154 Asymptomatic bacteriuria (ABU), 610 ATFP, see Arcus tendineus fascia pelvis ATLA, see Arcus tendineus levator ani ATP, 227, 248–249 Atropine, 460 Attitudes, public (to incontinence), 11, 13–14 Augmentation cystoplasty, 561 Augmented reality trainers, 1055 AUGS, see American Urogynecologic Society AUS, see Artificial urinary sphincter Australian Pelvic Floor Questionnaire (APFQ), 95, 147–148 Autoimmune disorders, 585–586 Autologous fascial lata sacrocolpopexy, 1128–1129 Autologous grafts, 965 Autologous myoblast injection, 1033 Autologous PRP (APRP), 527 Autonomic nervous system (ANS), 577 Autonomic system testing, 337–338 sympathetic skin response, 338 Auxillary/absent ureteral orifices, 382 Average flow rate (Qave), urine flow, 281 AVP, see Antidiuretic vasopressin AVWS, see Anterior vaginal wall suspension Axonics r-SNM System™, 518 Aδ-fiber, 208

B Bacillus Calmette-Guerin (BCG), 592 Baclofen, 472, 480–481 Bacterial cystitis in urogynaecology antimicrobial therapy, 618–619

duration of, 620 individual antibiotics, 619–620 background, 609 bacteriuria, 609–610 causative organisms and antibiotic resistance, 615–616 emerging antibiotic resistance, 616 hospital- vs. community-acquired infections, 616 clinical classification of cystitis, 611 complicated UTI, 611–612 definitions, 611 host defences, 612–613 antimicrobial factors, 612 epithelial factors, 612–613 immunologic factors, 613 Toll-like receptors, 613 investigations, 616–618 microbiologic investigations, 616 microscopy and culture, 616–617 pathogenesis, 612 prevalence, 612 prevention of, 620–622 antibiotic prophylaxis, 622 cranberries, 621 D-mannose oral therapy, 621–622 immunoprophylaxis, 622 Methenamine hippurate (Hiprex), 620–621 oestrogen therapy in postmenopausal women, 620 probiotics, 622 prophylaxis, 620 recurrent bacterial cystitis, 610–611 risk factors for UTI, 613–615 age, 613–615 behavioural factors, 615 instrumentation of the urinary tract, 615 obesity, 615 voiding dysfunction, 615 role of bacterial pathogen, 613 adherence, 613 uropathogens: structure and function, 613 treatment, 618 woman with refractory DO, 622–623 bacterial cystitis and OAB, 622–623 Bacteriophages (phages) viruses, 250 Bacteriuria, 609–610 asymptomatic, 610 pyuria, 610 sterile urine, 610 B3 adrenergic agonists, 559 Balloon expulsion test, 701 Bartholin’s glands, 1228 Basal ganglia, 214 Basic fibroblast growth factor (bFGF), 201, 251 BBUSQ, see Birmingham bowel and urinary symptoms questionnaire BC, see Bethanechol chloride B cells, 199 BCR, see Bulbocavernosus reflex BDD, see Body dysmorphic disorder Behavioral therapies, 410–416 behavioral training, 410–412 for bladder/voiding diary, 414–415 candidate for, 416

Index continence nurse specialist, 406 for decreasing voiding frequency, 413 bladder training, 413 delayed voiding, 413 for lifestyle changes, 415–416 bladder irritants, avoiding, 415 bowel management, 416 caffeine reduction, 415 fluid management, 415 weight loss, 415 models of delivery, 416 patient participation/adherence, encouraging, 416 pelvic floor muscle training, 410–412 common problem encountered in, 411 exercises, 411 to prevent stress incontinence, 411–412 teaching for, 410–411 for stress urinary incontinence, 410–412 for timed voiding, 413–414 for urge incontinence, 412–413 urge suppression strategies, 412–413 Benefit, Satisfaction, and Willingness to Continue (BSW) measure, 81, 104 Benign prostatic hyperplasia (BPH), 479 Benzodiazepines, 261, 480 BESIDE study, 225–226 β-adrenoceptors (β-ARs), 223–224, 468 Bethanechol chloride (BC), 477 BFB, see Biofeedback Bicornuate uterus, 1222 Biofeedback (BFB), 411, 420, 427–430 as active re-education, 430 conditions, 428 EMG, 427–428 limitations of, 430 pelvic floor rehabilitation using, 427–428 recruitment, 428–429 relaxation, 430 training/control, 429–430 Biofeedback therapy, 573 anal incontinence, 689 constipation, 707 Biological grafts, 965 basic science of, 968–969 clinical use in anterior compartment defects, 969–970 in apical prolapse, 971 in posterior compartment defects, 970–971 for native tissue repair, 965 for pelvic organ prolapse, 965 in plastic surgery, 967 for reconstructive pelvic surgery, 966 types, 965–968 in urogynecological reconstruction, 965–968 Biomaterials for urinary tract, 249–251 Bio-tribology, 250 Birmingham bowel and urinary symptoms questionnaire (BBUSQ), 122 BISF-W, see Brief index of sexual functioning for women BK channels, 227 Bladder anatomy, 164, 207–208 biopsy, 376

I-3 cancers, 382 capacity, increasing, 473–477 circle of life, 208 compliance, 294 compliance, low bladder control, selfassessment questionnaire, 99–101 contractility, decreasing, 459–473 descent with pelvic floor laxity, 737 diary, 414–415, 543, 568 questionnaires, 557 diverticulectomy, 385 embryological development, 179, 186 emptying catheterization for, 441 drugs for improve, 262, 477–481 facilitation of, 477–481 exstrophy, 1227 filling FSF, 293 physiology, 207–208 hypersensitivity, 293 incomplete emptying, 259–260 irritants, avoiding, 415 normal position, 737 outlet classification of dysfunction, 238–242 mixed–combined disorders, 244 overactive, 238, 243 resistance, 283 sensory disorders, 244 underactive, 242–244 pain, 260, 378–381 pharmacological intervention, 219–229 α-adrenoceptors, 221 antimuscarinics (anticholinergics), 223 botulinum toxin, 228–229, 470–473, 481 calcium channels, 226–227, 467 CNS targets, 219–221 dopamine/dopamine receptors, 222 GABA, 220–221, 480 gabapentin, 221–222 mirabegron, 224–225 muscarinic receptors, 222–223 myocytes, 227 NK1-receptor antagonists, 221–222 noradrenaline, 221 opioid receptors, 220 peripheral targets for, 222–223 potassium channels, 227 sensory nerves and vanilloid receptors, 228 serotonin (5-HT) mechanisms, 220 urothelium, 227 vibegron (MK-4618), 225–226 α-adrenoceptors, 223 β-adrenoceptors, 223–224, 468 β3-AR agonists, 224 physiology, 207–208 pressure measurement, 291 sensation, 293 smooth muscle cells, 199 tissue engineering, 200–201 trabeculations, 378–379 training, 413 tumours, management of, 383 wall pathology, 378–380 Bladder Assessment Tool (BAT), 266

Bladder emptying catheterization for, 441 completeness, 891 drugs for improve, 262, 477–481 emptying phase, 219 vesico-bulbo-vesical micturition reflex, 219 vesico-spinal-vesical micturition reflex, 219 facilitation of, 477–481 incomplete, 259–260 nervous mechanisms for, 218–219 physiology, 207 storage phase, 219 Bladder neck mobility postpartum, 26 quantification of, 343–350 ultrasonography of, 353–354 position, postpartum changes, 26 Bladder outflow obstruction (BOO), 847 after anti-incontinence surgery diagnostic evaluation, 848–850 endoscopy/imaging, 849 etiology, 847–848 history and physical examination of patient, 849 identifying risks, 848 incidence, 847–848 management, 850–857 urodynamics, 849–850 Bladder outlet obstruction (BOO), 221, 566 Bladder pain syndrome/interstitial cystitis (BPS/IC), 733 aetiology, 585–586 autoimmune disorders, 585–586 dysfunctional bladder epithelium and potassium cycling, 586 infection, 585 mast cells, 586 vascular abnormalities and hypoxia, 586 clinical features, 586 conservative, 590–591 behavioural modification, 590 dietary manipulation, 590 Hunner’s lesions, 591 stress management, 591 emerging treatments, 593 cannabinoids, 593 enhanced intravesical drug delivery systems, 593 extracorporeal shockwave therapy, 593 monoclonal antibodies, 593 phosphodiesterase-5 inhibitors, 593 in females, prevalence of, 586 incidence, 585 intravesical treatments, 591–592 Bacillus Calmette-Guerin, 592 Botulinum toxin A, 592 chondroitin sulphate, 592 dimethyl sulfoxide, 592 heparin, 592 hyaluronic acid, 592 investigation and assessment, 586–590 cystoscopy, 590 pelvic examination, 586

Index

I-4 questionnaires and symptom scales, 587–588 urine studies, 586–587 urodynamics, 589 voiding diary, 589 management, 590 neuromodulation, 592 O’Leary-Sant questionnaire, 587 oral therapy, 591 amitriptyline/nortriptyline, 591 antihistamines, 591 cyclosporin A, 591 gabapentin/pregabalin, 591 Pentosan polysulfate sodium, 591 pelvic pain and urgency/frequency scale, 588 surgery, 592–593 Bladder reconstruction, 1210–1217 augmentation cystoplasty, 1211–1212 autoaugmentation, 1213 bladder outlet considerations, 1213 bladder preserving reconstruction, 1210–1211 common conditions for, 1210 continent catheterizable channels, 1212–1213 Mitrofanoff appendicovesicostomy, 1212–1213 Yang-Monti transverse ileal tube, 1213 etiology, 1210 perioperative considerations for, 1210 postoperative complications, 1211 postoperative considerations for, 1210 preoperative bowel preparation for, 1210 Bladder self-assessment questionnaire (B-SAQ), 99–101 Bladder submucosa (BSM), 197 Blue light cystoscopy, 375 BMSCs, see Bone marrow stem cells Body dysmorphic disorder (BDD), 1249 Body mass index (BMI), 569 Body-worn systems, 448 Bone anchoring, 763–765 Bone marrow stem cells (BMSCs), 199, 204 Bone Morphogenic Protein type 4 (BMP-4), 181 Bonney, Victor, 1088 BoNT, see Botulinum toxin BOO, see Bladder outlet obstruction Boston Area Community Health populationbased random epidemiological survey, 12 Botox, 573–574 Botulinum toxin-A (BnTx-A), 228–229, 248, 473, 481, 490–497, 546, 592 Botulinum toxin-B (BnTx-B), 490 Botulinum toxin (BoNT), 228–229, 470–473, 481, 490–497, 520–521 adverse effects, 228–229, 496 maximum dosing, 496 neutralizing antibodies, 497 urinary retention, 496–497 UTI, 497 biology, 490–491 for detrusor sphincter dyssynergia, 490 history, 490–491 in idiopathic overactive bladder, 493–495 cost-effectiveness of, 495

dosing recommendations, 494 epidemiology, 494 FDA regulatory trials in, 494 financial implications, 494 persistence and long-term use, 495 injection techniques, 495–496 depth, 495 location, 495 number, 495–496 mechanism of action, 490–491 in neurogenic detrusor overactivity, 491–493 associated sequelae, 491 dosing recommendations, 492–493 FDA regulatory trials, 492 multiple sclerosis populations, 491–492 non-incontinence-related outcomes, 493 persistence and long-term use of, 493 spinal cord injury, 491–492 for patients with urinary incontinence, 490–497 products, 490–491 serotypes, 490 Bowel function, questionnaires to assess, 119–127 constipation/bowel evacuation difficulties, symptoms/QoL in patients with, 124–127 Chinese Constipation Questionnaire, 124 constipation severity instrument, 124, 126 gastrointestinal quality of life (QoL), 127 KESS Score, 124 medical outcome profile, 127 ODS, 127 PAC-QOL, 124 PAC-SYM, 124, 127 pelvic floor consortium, 127 PROMIS constipation module, 124 Rome IV diagnostic questionnaire, 124 Wexner constipation score, 124 faecal incontinence, symptoms/QoL in patients with, 119–123 BBUSQ, 122 EQ-5D, 123 ESBQ, 123 FICA, 123 FIQoL, 122 FISI, 122 ICIQ-B, 122 Manchester health questionnaire data, 122–123 Mayo faecal incontinence survey, 123 pelvic floor consortium, 123 Pescatori incontinence score, 123 St. Mark’s incontinence score, 123 Wexner Score, 123 schemas grade A–highly recommended, 119 grade B–recommended, 119 grade C–with potential, 119 Bowel injury, 1103 direct injury, 1104 electrosurgical injury, 1104 prevention of, 1104 Bowel management, 416

Box trainers, 1055–1056 BPH, see Benign prostatic hyperplasia Brain stem circuitry, 210–212 neurons in PMC, properties of, 211 PAG, role of, 212 PMC, role of, 210–211 Brainstem lesions, 554 Breathing exercises, 426–427 Brief index of sexual functioning for women (BISF-W), 114 Bristol Female Lower Urinary Tract Symptoms Questionnaire and its short-form (BFLUTS and BFLUTS-SF), 95 B-SAQ, see Bladder self-assessment questionnaire BSM, see Bladder submucosa Buccal mucosa, 575 Bulbocavernosus reflex (BCR), 327, 337 Bulkamid, 533–534 Bulking agents, 739, 770–771, 865 in treatment of female stress UI Bulkamid, 533–534 bulking agent, selection of, 532 Coaptite, 532 complications, 535 Durasphere EXP, 532–533 efficacy, 535 imaging, 535–536 indications, 531 Macroplastique, 532 mechanism of action, 532 outcomes from major RCTs and disadvantages, 532–534 results, 532 techniques, 534–535 Urolastic, 534 Bulk laxatives/fiber, 706 Bumetanide, 482 Buprenorphine, 220 Burch colposuspension, 1061

C Caesarean section (CS), 31 anal/fecal incontinence, protection for, 32 POP, protection for, 32–33 UI, protection for, 32 Caffeine reduction, 415, 420 CAH, see Congenital adrenal hyperplasia CAIS, see Complete Androgen Insensitivity Syndrome Calcium channels, 226–227, 467 CAMP, see Cyclic adenosine monophosphate Cannabinoids, 593 Cannabis, 262 Capsaicin, 473–474 Carbapenems, 620 Carbodiimide, 967 Carbon dioxide (CO2) fractional lasers, 1262 Cardinal ligaments (CLs), 168–170 Cardiovascular disease (CVD), 671, 675 CAT, see Computer adaptive testing Catheter-acquired UTIs (CAUTI), 249–250 Catheter fouling, 249–250 Catheters/catheterization, 441–448 CISC, 441

Index complications, 446–447 CAUTI, 446 infection/hematuria/trauma, 446–447 leakage, 447 drainage bags, 447 drainage valves, 447–449 goals of, 441 history of, 441 indwelling vs. clean intermittent catheterization vs. suprapubic, 443–446 catheter tip vs. council tip, 444 patient selection, 443–444 urethral, 441–443 definition, 441 designs/materials, 441–442 size and length, 441–443 Catheter specimen of urine (CSU), 387 Cauda equina lesions, 332 Cauda equina syndrome, 556 CAUTI, see Catheter-acquired UTIs Cave of Retzius, 1061 CBA, see Cost-benefit analysis CCA, see Cost-consequence analysis CCF-FIS, see Cleveland Clinic Florida Fecal Incontinence Score CEA, see Cost-effectiveness analysis Cell-based hormone replacement therapy, 204 Cell–cell interactions, smooth muscle development, 183–184 Cell transplantation, 197, 200 Central nervous system (CNS), 541 Cephalosporins, 619 Cerebellum, 214 Cerebral/cortical disease, 550–554 cerebral palsy, 553 dementia, 553 multiple system atrophy, 553–554 Parkinson disease, 553, 554 stroke, 550–551 traumatic brain injuries, 552–553 Cerebral palsy (CP), 553 Cervical cancer, staging of, 382 Cervical cells, 201–202 Cervical/vaginal agenesis, 1223 Cervicosacropexy (CESA), 1125–1126 C-fiber axons, 208 Changes in sexual functioning questionnaire (CSFQ), 114 Checklists for surgical care, 63–64 Childbirth, 29–30 FI and, 29–30 impact on pelvic floor disorders, 643–645 anal incontinence, 645 caesarean section, 645 pelvic organ prolapse, 643–645 urinary incontinence, 643 mechanisms of pelvic floor injury, 640–643 muscle trauma, 640–642 nerve injury, 642–643 typical bilateral avulsion injury, 642 ultrasound of pelvic floor, 640 unilateral avulsion on ultrasound, MRI and tomographic ultrasound, 641 OASI and, 29 pelvic floor dysfunction and, 29

I-5 POP and, 29–30 UI and, 29–30 urinary incontinence after etiologic mechanisms, 26–27 Chinese Constipation Questionnaire, 124 Chondroitin sulphate (CS), 592 Chronic pelvic pain (CPP) anatomical considerations, 579–581 altered pain sensation, 580 central and peripheral sensitization, 580–581 pain pathways in abdomen and pelvis, 579–580 pain receptors, 580 sympathetic and parasympathetic innervation of pelvis, 579 definitions, 578 pharmacological aspects, 581–582 stress and psychosocial bases, 581 trigger points and mechanosensitivity, 582 CIC, see Clean intermittent catheterization Circadian rhythms, 249, 284 CISC, see Clean intermittent self-catheterization Cisgender, 1270 Clean intermittent catheterization (CIC), 229, 546 Clean intermittent self-catheterization (CISC), 322, 441, 444–445, 751 general guidelines for, 444 technique of, 444 Clenbuterol, 468, 475 Cleveland Clinic Florida Fecal Incontinence Score (CCF-FIS), 1025 Clinical Negligence Scheme for Trusts (CNST), 77 Clinical neurophysiology tests, 325–326 Clinical reasoning, 401 Clitoral hood reduction, 1254 Clitoris, 723 Clitoroplasty, 1241–1242, 1255–1257 Cloaca cloacal membrane, 179 division, 179–182 formation, 180 molecular control of differentiation, 181 Cloacal bladder exstrophy, 1237–1238 Cloacal malformations, 202, 1225 Clonidine, 481 Clostridium botulinum, 490 CLPP, see Cough leak point pressure CLs, see Cardinal ligaments CMA, see Cost-minimization analysis CMAP, see Compound muscle action potential CN, see Continence nurse CNS, see Central nervous system CNST, see Clinical Negligence Scheme for Trusts Coaptite, 532 Cognitive function, 671 Cognitive interviews, 83 Coital incontinence history, 258 symptoms, 258 CO2 laser therapy, 526 Colectomy, 708 Collagen, 197

Collagen denaturation/micro-remodeling, RF, 527–528 Colley Model, 400–401 Colon conduit, 1213–1214 Colonic manometry, 705 Colorectal-Anal Distress Inventory (CRADI), 145 Colpocleisis, 149 Colpocleisis for urogenital prolapse, 958 background, 958 vs. colpectomy, 959 historical aspects, 958 indications/preparation, 958–959 results/complications, 962–963 malignancies, 963 recurrence, 963 regret after colpocleisis, 963 techniques, 959–962 bladder function management, 962 bowel function management, 962 colpocleisis vs. colpectomy, 959 preferred technique, 959–961 variations in, 961–962 Colpopexy And urinary Reduction Effort (CARE), 1063 Colposuspension, 35 economic analysis, 783 vs. MMK, 780 operative technique, 777–779 outcome, 780 vs. anterior colporrhaphy, 780 vs. laparoscopic colposuspension, 782 vs. MMK, 780–781 vs. needle suspension procedures, 781 vs. paravaginal repair, 781 redo colposuspension, 780 vs. tension-free vaginal tape, 781 vs. traditional sling procedures, 781 vs. transobturator tape, 782 perioperative complications, 782 post-operative complications OAB, 782 sexual dysfunction, 783 urogenital prolapse, 782–783 voiding difficulty, 782 results, 779–780 Combined oral contraceptive (COC) pills, 744 Commodes, 453 Common cloaca, 188–189 Communication, 60–61 Complementary medicine, 708 Complete Androgen Insensitivity Syndrome (CAIS), 1224 Complex repetitive discharges (CRDs), 333, 573 Compliance, 407 Complicated UTI, 611–612 Compound muscle action potential (CMAP), 326 Compound nerve action potential, 327 Compressive spondylotic myelopathy, 555 Compressor urethrae, 164–167, 174 Computer adaptive testing (CAT), 85 Concentric needle EMG (CN EMG), 330–331 Concomitant medication, 744 Conduction across nerves, testing of, 326–327 Conduction velocity (CV), 326 Confirmatory focus groups, 83

Index

I-6 Congenital adrenal hyperplasia (CAH), 1223–1224, 1255–1256 Congenital enteroceles, 905 Congenital vaginal anomalies, 190–191 Connective tissue, urethra, 167 Conservative management, 559, 572–573 Conservative treatment of enteroceles, 906 of female urethral stricture disease, 1202–1203 iatrogenic bladder outflow obstruction, 850 of obstructed defecation symptoms, 1042–1043 of urethral diverticulum, 1194–1195 of urethral stricture, 1202–1203 Constipation anal manometry, 703 anorectal function, evaluation of, 701 anorectal manometry, 701–702 balloon expulsion test, 701 defecating proctography, 702, 704 ultrasound scans, 704 causes of secondary constipation, 699 chronic, 701, 702 classification of, 698 clinical examination, 700 colorectal cancer, red flag symptoms and signs of, 700 conservative management, 705 biofeedback, 707 dietary and lifestyle advice, 705–706 laxatives, 706 neuromodulation, 708 psychological therapies, 707 rectal irrigation, 707 history, 698, 700 intestinal transit, evaluation of, 704 colonic manometry, 705 gastrointestinal transit scintigraphy, 704–705 radiopaque markers, 704 SmartPill WMC, 705 investigations, 700–701 MR defecography, 704 obstructive defecation syndrome, MRbased classification, 705 physiology of normal defecation, 698 proctogram, 704 Rome IV Criteria, 700 severity instrument, 124, 126 slow transit, 705 subtypes of, 698 surgical management, 708 antegrade continence enema, 708 colectomy, 708 defunctioning stoma, 708 Delancey level of pelvic organ support, 708 enterocele or sigmoidocele, 709 internal intussusception/rectal prolapse, 709 options for obstructive defecation, 708 rectoceles, 708–709 treatment, 705 Continence nurse (CN), 400–408 assessment, 400–401 conservative management, 406 in coordination of care, 408

counseling skills, 406–407 decision-making, 401–406 education, role in, 407 health promotion and prevention, role in, 407 in maintaining privacy and dignity, 408 management role, 408 maximizing compliance, role in, 407 minor surgery, role in, 406 pads/catheters/anti-incontinence devices, management with, 406 pharmacological management, 406 in research/audit, 408 roles, 400–401 specialist investigation, 401 Continence Product Advisor, 454 Continence products, information sources, 13–14 Continence promotion International Continence Society, 14 national organizations, 14 survey of national organizations, 14 Continence surgery, 43 Continence Worldwide, 14 Continent catheterizable pouches, 1215 Continent urinary diversion, 1214–1216 continent catheterizable pouches, 1215 Indiana Pouch, 1215 orthotopic urinary diversions, 1216 rectal bladder diversions, 1215–1216 Contraception, 676 Cooper’s ligaments, 1062 Cord blood stem cells, 199 Cortical modulation of micturition, 212–213 animal studies, 212–213 human imaging studies, 212 Cortical somatosensory evoked potentials, 335–336 Corticotropin-releasing hormone (CRH), 211, 581 Corynebacterium, 387 Cosmetic gynecology, energy devices in, 1260–1262 carbon dioxide (CO2) fractional lasers, 1262 Er:YAG laser treatments, 1260–1261 laser, 1260–1262 radiofrequency (RF) technology, 1262 vulvovaginal atrophy, 1262–1263 vulvovaginal laxity, 1262–1263 Cost-benefit analysis (CBA), 154 Cost-consequence analysis (CCA), 154 Cost-effectiveness analysis (CEA), 154 in health care, 1118 direct costs of treatment, 1118–1119 indirect costs of treatment, 1119 perspective, 1118 laparoscopic/robotic sacrocolpopexy, 1119–1121 open vs. laparoscopic vs. robotic sacrocolpopexy, 1120–1121 open vs. robotic sacrocolpopexy, 1120 outcome, 1119–1120 robotic vs. laparoscopic sacrocolpopexy, 1120 vaginal apical suspension vs. laparoscopic vs. robotic sacrocolpopexy, 1121

Cost-minimization analysis (CMA), 154 Cost-utility analysis (CUA), 154, 156–157 Cough leak point pressure (CLPP), 302 COVID-19 considerations, 754 COVID-19 pandemic, 6–7 CRADI, see Colorectal-Anal Distress Inventory Cranberries, 621 CRDs, see Complex repetitive discharges Crew resource management (CRM), 60 CRH, see Corticotropin releasing hormone CRM, see Crew resource management Cromakalim, 467 Cross-sectional area (CA) relationship, 281 Cryogen-cooled monopolar RF (CMRF), 528 Cryopreservation of ovarian tissues, 202 CS, see Caesarean section CSFQ, see Changes in sexual functioning questionnaire CSU, see Catheter specimen of urine CUA, see Cost-utility analysis Culture of safety, 57 Cumulus–oophorus complexes (COCs), 203 Currarino syndrome, 189–190 CV, see Conduction velocity Cx43/Cx26 hemichannels, 249 Cyclic adenosine monophosphate (cAMP), 208 Cyclosporin A, 591 Cystitis, 261–262, 378–381 bacterial, 622–623 clinical classification of, 611 definitions of, 611 and OAB, 622–623 in urogynaecology, 622–623 Cystocele, 259–260 repairs, 49–50 Cystodistension, 375–376 Cystometry, 306 aims, 288 definition, 288 equipment, 291–293 filling, 288 filling medium, 291 filling rates, 291 filling urethro-cystometry, 299–300 indications, 288 measurements, 293 method, 293–295 bladder compliance, 294 bladder sensation, 293 detrusor activity, 293–294 filling phase, 293 urethral function, 294–295 voiding cystometry, 295 natural (orthograde) fill, 313 normal, 297 patient position for, 289–291 pitfalls of, 295–297 preparation for, 288–293 pressure–flow studies of voiding, 288 quality control during, 288–289 voiding, 295 Cystoscopic bladder neck injection, 383 Cystoscopy, 373–383, 570, 590 antibiotic prophylaxis in, 375 common findings auxillary/absent ureteral orifices, 382 bladder cancers, 382

Index bladder trabeculations, 378–379 cervical cancer, staging of, 382 cystitis/bladder pain syndrome, 378–381 external inspection, 376 fistulae, 382 foreign bodies and calculi, 377–378, 381–382 ureterocele, 382 urethral diverticulum, 377 urethral fistula, 377 urethral masses, 377–378 urethritis, 376–377 equipment, 373–375 blue light cystoscopy, 375 distension medium, 373–374 flexible cystoscopes, 373–374 narrow band imaging, 374–375 rigid cystoscopes, 373, 375–376 urethroscope, 373 indications, 373–374 operative bladder tumours, management of, 383 cystoscopic bladder neck injection, 383 intravesical onabotulinum toxin type A, 383 suprapubic catheter, insertion of, 382 ureteral stents/catheters, 382 urolithiasis, management of, 383 overview, 373 Cystourethrogram, 837–838

D Danish Prolapse Questionnaire, 147 Dantrolene, 481 Darifenacin, 461 DARPA, see Defense Advanced Research Projects Agency Da Vinci® surgical system, 1109–1110 Da Vinci Surgical System, 1059 DAX1, 1219 Daytime urinary frequency, 258 DB, see Decelerating burst Decelerating burst (DB), 333 Decellularization, 966–967 Decision-making errors, 64–66 Defecating proctography, 702, 704 Defecography, rectocele, 913–914 Defense Advanced Research Projects Agency (DARPA), 1109 Defunctioning stoma, 708 Dehydroepiandrosterone (DHEA), 673 Delancey level of pelvic organ support, 708 Delayed voiding, 413 Dementia, 553 De novo UUI, 35 Derogatis inventory of sexual functioning, 114 Desara One (Caldera Medical), 817 Descending perineum syndrome enterocele formation, 905 rectocele formation, 905 Desmopressin (DDAVP), 481–482, 545, 561 Desquamative inflammatory vaginitis, 726 Detrusor, 164 contractility, 283 bladder emptying, 208 loop, 164

I-7 Detrusor leak point pressure (DLPP), 301–302 Detrusor overactivity (DO), 541 drugs used in treatment of, 458 fesoterodine for, 461 flavoxate in, 464 hyoscyamine for, 460–461 prevention of, 36–37 propantheline bromide for, 462 PTNS for, 509–513 scopolamine for, 462 Detrusor-sphincter dyssinergia (DSD), 311, 329, 575 Diabetic neuropathy, 557 Diagnostic errors, 64–66 DIAPPERS, 28 Dihydropyridines, 227 Dilation, 1221 Dimethyl sulfoxide (DMSO), 592 Disorders of sex determination (DSD), 1240 Diuretics, 261, 283 DLPP, see Detrusor leak point pressure D-mannose oral therapy, 621–622 Donald, Archibald, 1088 Dong quai (Angelicae sinensis), 744 Dopamine, 222 receptors, 222 Dorsal genital nerve (DGN) stimulation, 514 anatomy, 514 results, 514 Dorsal root ganglia (DRG), 208 DotNet programming, 135 Doxazosin, 221, 261, 479 Doxepin, 469 Drainage bags, 447 valves, 447–449 DRG, see Dorsal root ganglia Dry laboratory training, 1058 DSD, see Detrusor–sphincter dyssinergia; Disorders of sex determination Duloxetine therapy, 469–470, 475–476, 528–529 Durasphere EXP, 532–533 Duration, 266 Dysfunctional bladder epithelium, 586 Dyspareunia, 921–922 pain, 260 Dyssynergia, 329, 1039

E EAS, see External anal sphincter ECM, see Extracellular matrix Ectoderm, 179 Ectopic ureter, 191–192 Elderly bowel symptoms questionnaire (ESBQ), 123 Electrical stimulation (ES), 501 for OAB, 504–505 evidence for use, 505 rationale, 504 for stress urinary incontinence, 501–504 adverse events, 503 evidence for use, 503 muscle strength, 503 parameters, 502–503 types, 503 types, 503

Electrocautery, 788 Electromyography (EMG), 326–334 biofeedback (EMG-BFB), 427–428 in cauda equina lesions, 332 CNE, 330–331 denervation, findings due to, 331–333 diagnostic usefulness of, 334 in idiopathic incontinence, 332–333 kinesiological, 327–329 in multiple system atrophy, 332 for normal vs. pathological muscle, 329–331 in obstructed voiding, 333 in primary muscle disease, 333–334 rectocele, 914 reinnervation, findings due to, 331–333 SFEMG, 329–331 in women with urinary retention, 333 Electronic diaries, 267–269 Electronic patient-reported outcome measures (ePROMs), 135 Electronic Personal Assessment Questionnaire-Pelvic Floor (ePAQ-PF), 95, 148 clinical decision-making, 141–142 clinical pathways, 142 deployment, 141 development of, 135–136 domains of, 138 internet completion, 141 multidisciplinary team working, 142 other instruments, 143 overview, 135 psychometric evaluations of, 137 reports/progress reports, 139–141 structure/content, 136–139 virtual clinics, 142–143 Electrostimulation (ES), 420 Embryology bladder, 186 division of cloaca, 179–182 early embryogenesis, 179 innervation, 186–187 Müllerian differentiation, 182 smooth muscle differentiation, 183–184 sphincters, 184 trigone and upper urinary tract, 184–186 urothelium, 182–183 EMEA, see European Agency for the Evaluation of Medicinal Products EMG, see Electromyography EMIG project, 1058 EMPOWUR, 225 Enacted stigma, 11 Endoanal ultrasonography (EAUS), 687 Endoderm, 179, 181–184 Endometrial cancer, 675 Endopelvic fascia defects, enterocele, 909 EndoWrist® instruments, 1109 Enhanced recovery after surgery (ERAS), 752–754 Enterocele or sigmoidocele, 709 Enteroceles, 902–909 clinical assessment/investigations, 905–906 congenital, 905 conservative treatment of, 906

Index

I-8 deep pouch of Douglas as predisposing factor, 902–903 definition, 902 descending perineum syndrome, 905 endopelvic “fascia,” 902, 904–905 epidemiology, 905 etiology, 902–905 iatrogenic, 905 normal anatomy, 902 pathophysiology of, 905 prevalence of, 905 prevention of, 906 pulsion, 905 rectal prolapse, 905 scope, 902 surgical treatment of, 906–909 symptoms, 905 synopsis, 909 traction, 905 vaginal axis, 902, 904 Enuresis, 1233 EoSim, 1055 EPAQ-menstrual, pain, and hormonal (ePAQMPH), 143 EPAQ-PF, see Electronic Personal Assessment Questionnaire-Pelvic Floor EPAQ-preoperative assessment (ePAQ-PO), 143 EPAQ-Vulva, 143 Ephedrine, 474 Ephrin B, 182 Epithelial factors, 612–613 Epithelial Na+ channels (ENaC), 249 EPROMs, see Electronic patient-reported outcome measures EQ-5D, 154 ERAS, see Enhanced recovery after surgery Erosion, 869 Er-YAG laser therapy, 525–526 Er:YAG laser treatments in gynecology, 1260–1261 ES, see Electrical stimulation; Electrostimulation ESBQ, see Elderly bowel symptoms questionnaire Escherichia coli, 250, 394–395 Essentials in Minimally Invasive Gynecology (EMIG) LaparoBowl System, 1055 Estrogen, 472 Estrogen receptor (ESR-1), 211 Estrogens, 476–477 European Agency for the Evaluation of Medicinal Products (EMEA), 85 European Society for Gynaecological Endoscopy (ESGE), 1219 European Society of Human Reproduction and Embryology (ESHRE), 1219 EuroQol group with five dimensions (EQ-5D), 123 EUS, see External urethral sphincter Examination, 262–264 abdominal, 262 gynaecological, 263 neurological, 264 Expanded quantitative urine culture (EQUC) protocol, 394 Exposure, 869 External anal sphincter (EAS), 172–173, 329

External collecting devices, toileting aids, 453–454 External genitalia, development of, 181 External urethral sphincter (EUS), 208–209, 251 botulinum toxin injection, 560 Extracellular matrix (ECM), 247 Extracorporeal shockwave therapy (ESWT), 593 Extrusion, 869

F Faecal incontinence and constipation assessment (FICA), 123 Faecal incontinence quality of life scale (FIQoL), 122 Faecal incontinence severity index (FISI), 122 Fast-twitch fibers, 736 Fatty tissue, 199 FCGS, see Female cosmetic genital surgery FDA, see Food and Drug Administration Fecal incontinence (FI), 1025 augmentation for, 1028–1029 injectable materials, 1028–1029 radio-frequency energy application, 1029 trans-obturator post-anal sling, 1029 CCF-FIS, 1025 childbirth and, 29–30 CS for, 32 fecal diversion for, 1033–1034 antegrade continence enema, 1033 stoma, 1033–1034 natural history of, 28 nonsurgical therapy for, 1025–1027 adjuvant perineal devices, 1026–1027 biofeedback, 1026 dietary and medical management, 1025–1026 prevalence, 28, 1025 risk calculator, 31 risk factors associated with, 1025 sphincter repair for, 1027–1028 overlapping anterior sphincteroplasty, 1027–1028 postanal repair, 1028 sphincter replacement for, 1029–1031 artificial bowel sphincter, 1029 graciloplasty, 1029–1031 magnetic anal sphincter, 1031 stimulation for, 1031–1033 autologous myoblast injection, 1033 posterior tibial nerve, 1032–1033 sacroneuromodulation, 1031–1032 treatment for, 1025 Federation International of Gynecology and Obstetrics (FIGO), 2 Felt/perceived stigma, 11 Female cosmetic genital surgery (FCGS), 1249–1266 clitoral hood reduction, 1254 clitroplasty, 1255–1257 combined procedures, 1255 cosmetic gynecology, energy devices in, 1260–1262 carbon dioxide (CO2) fractional lasers, 1262

Er:YAG laser treatments, 1260–1261 laser, 1260–1262 radiofrequency (RF) technology, 1262 vulvovaginal atrophy, 1262–1263 vulvovaginal laxity, 1262–1263 fat transfer, 1255 female genital mutilitation, 1254 HiFU in, 1263–1265 hymenoplasty, 1257 labia majora reduction, 1254–1255 labiaplasty, 1250–1254 mons pubis and labia majora, augmentation of, 1255 perinoplasty, 1257 vaginal narrowing procedures, 1257–1260 abdominoplasty, 1259–1260 G-spot augmentation, 1258 hyalurinic acid (HA) injections in vulva and vagina, 1257–1258 orgasm shot/O-Shot, 1258–1259 vaginoplasty, 1257 vulvar lipoplasty, 1257–1258 Female embryology, 1227–1228 Female epispadias, 1238 Female genitalia, disorders of, 1240–1242 DSD, 1240 pull-through vaginoplasty, 1242 skin-flap vaginoplasty, 1242 vaginal replacement/interposition, 1242 46,XX DSD, 1240–1241 46,XY DSD, 1241–1242 Female genital mutilitation (FGM), 1254 Female orgasmic disorder (FOD), 102–103, 112 Female reproductive organs approaches in ovarian biology, 202–204 autologous transplantation, 202 ovarian tissues from stem cells, regenerating, 202 ovary, 202 uterine cervix, 201–202 uterus, 201 vagina, 202 Female sexual arousal disorder (FSAD), 102–103 Female sexual dysfunction (FSD), 112 definitions, 112 hormonally mediated vestibulodynia, 724 ISSWSH, 727 neuroproliferative vestibulodynia, 724–727 outcome measures clinician measures, 113 objective measures, 112 patient-reported, 113 subjective measures, 112 questionnaires to assess, 114–116 clinical practice vs. clinical trials, 116 condition-specific measures, 114–115 disease-specific questionnaires for use in women with PFD, 115–116 generic, 114 surgery, 726–727 in urogynecology, 112 village health care pelvic floor assessment, 715–716 sexual health-care provider assessment, 714–715 sexual pain management, 723–724

Index typical FSD patient assessment, 722–723 vasodilators, 723 Female sexual function, 111–112 Female sexual function index (FSFI), 112–116 Female sexuality, questionnaires assessment, 114–116 clinical practice vs. clinical trials, 116 condition-specific measures, 114–115 disease-specific questionnaires for use in women with PFD, 115–116 generic, 114 Female urethral stricture disease, 1201–1208 anatomy, 1201 conservative management of, 1202–1203 diagnosis of, 1201–1202 endoscopic management of, 1203 etiology, 1201 salvage procedures, 1207–1208 treatment of, 1202 urethroplasty, 1203–1207 distal urethrectomy with advancement meatoplasty, 1204–1205 distal urethroplasty with vaginal/ vestibular inlay flaps, 1205–1206 vaginal flap urethroplasty, 1206–1207 Feminizing genitoplasty reconstructive surgery (FGRS), 1241–1244 controversies regarding, 1242–1244 historical context, 1243 Mayer-Rokitansky syndrome, 1243–1244 timing of, 1243 vaginal agenesis, 1243–1244 Fesoterodine, 461 FGM, see Female genital mutilitation FGRS, see Feminizing genitoplasty reconstructive surgery FI, see Fecal incontinence Fibroblasts, 247 Fibrosis, 247 FICA, see Faecal incontinence and constipation assessment 15D, 154 FIGO, see Federation International of Gynecology and Obstetrics Filling cystometry, 288 Filling urethro-cystometry, 299–300 FIQoL, see Faecal Incontinence Quality of Life Scale First desire to void (FDV), 293 First sensation of bladder filling (FSF), 293 First-stage lead placement (FSLP), 518 FISI, see Faecal incontinence severity index Flap coverage, 1157–1158 Flavoxate, 464 Flexible cystoscopes, 373–374 Flow rate (Q), urine flow, 281–282 Flow time, urine flow, 281 Fluid management, 415 Fluoroquinolones, 619 Fluoroscopy cystoproctography, 367–369 Flurbiprofen, 467 FOD, see Female orgasmic disorder Follicle maturation/availability and estrogen production, 667 Follicle-stimulating hormone (FSH), 665 Food and Drug Administration (FDA), 990 Fosfomycin, 619

I-9 Four-corner vaginal patch, 765 4-D ultrasonography, 359–360 Fowler’s syndrome, 574 Frenula, 723 Frequency daytime urinary, 258 pregnancy, 26 Friction, 250 FSAD, see Female sexual arousal disorder FSD patient assessment and treatment algorithms, 722 phase 2 (bioidentical systemic hormone supplementation), 722 phase 1 (local tissue hormone supplementation), 722 phase 3 (nonhormonal medication), 723 FSFI, see Female sexual function index FSLP, see First-stage lead placement Functional urinary incontinence, 238, 240 Fundamentals of Laparoscopic Surgery (FLS™), 1055

G GABA, see γ-aminobutyric acid (GABA) GABAergic cells, 211 Gabapentin, 221–222, 472–473 Gabapentin/pregabalin, 591 GAD, see Glutamic acid decarboxylases Gadolinium, 363 γ-aminobutyric acid (GABA), 220–221, 480 Gartner’s duct cysts, embryologic basis, 182, 192 GAS, see Goal attainment scaling Gastroesophageal reflux disease (GERD), 1029 Gastrointestinal quality of life (QoL) questionnaire, 127 Gastrointestinal transit scintigraphy, 704–705 Gatekeeper™ (GK), 1028–1029 GCNIS, see Germ cell neoplasia in situ GD, see Gonadal dysgenesis GDPR, see General Data Protection Regulations GEARS, see Global Evaluative Assessment of Robotic Skills Gender identity, 1270 General Data Protection Regulations (GDPR), 143 Gene therapy/transfer, 229 Genital gender-affirming surgery (GGAS), 1271–1275 Genital hiatus (GH), 913 Genitoanorectal fistulas, 1165 Genitourinary (GU) fistula, 1152, 1165 GenitoUrinary Molecular Anatomy Project, 179 Genitourinary problems, 668 GERD, see Gastroesophageal reflux disease Germ cell layers, 179 Germ cell neoplasia in situ (GCNIS), 1224 GGAS, see Genital gender-affirming surgery GH, see Genital hiatus Giggle incontinence, 1233 Ginkgo biloba, 744 Ginseng Abuse Syndrome, 744 Gittes operation, 762 Glands, of urethra, 167

Global Evaluative Assessment of Robotic Skills (GEARS), 1058 Global Ratings of Patient Satisfaction and Perceptions of Improvement questionnaire, 104 Global Trigger Tool, 56 Glutamic acid decarboxylases (GAD), 211 Glutaraldehyde, 967 Gluteoplasty, 1029–1031 Glycosaminoglycan (GAG), 592 Goal attainment scaling (GAS), 107–108 background, 107–108 multidimensional assessment of symptoms, bother, impacts, and satisfaction, 108 OAB-BAT, 108 Golombok Rust inventory of sexual satisfaction, 114 Gonadal dysgenesis (GD), 1224 Gonadal stem cells (GSCs), 202 Gonadotrophin-releasing hormone (GnRH), 665, 744 Graciloplasty, 1029–1031 Graft materials, 8 Grande fosse pelvienne, 902–904 Gravimetric method, 280–281 GSCs, see Gonadal stem cells G-spot augmentation, 1258 Guanylate cyclase activators, 247 Guarding reflex, 422 Gynaecological developmental abnormalities, 1219–1225 classification, 1219 differences in sex development, 1223–1225 Cloacal malformation, 1225 Complete Androgen Insensitivity Syndrome, 1224 congenital adrenal hyperplasia, 1223–1224 gonadal dysgenesis, 1224 psychology, 1225 Turner syndrome, 1224–1225 embryology, 1219 Mullerian duct anomalies, 1219–1223 cervical/vaginal agenesis, 1223 classification, 1219 imperforate hymen, 1219 longitudinal vaginal septa, 1221 Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, 1222–1223 transverse vaginal septa, 1219–1221 uterine anomalies, 1221–1222 Gynaecological examination, 263 Gynaecological history, 261

H Haematuria, 261 Haemorrhage, 1124 Haemorrhagic cystitis, 378 Hammock theory, 738 Hart’s line, 716, 718 HCPs, see Health-care professionals Health, WHO definition, 111 Health and Social Care Network (HSCN), 141 Health-care professionals (HCPs), 402

Index

I-10 Health-related quality of life (HRQoL), 81, 89–95 definition, 89 PROMs, 89–90 global pelvic floor, 95 Grading of, 90–91 for LUTS, 91–94 questionnaire selection, 90 sexual function, 95 urgency-specific, 95 Health utility index (HUI), 154 Hematopoietic stem cells, 199 Heparin, 592 Herbal medication, 744–746 HESCs, see Human embryonic stem cells Hesitancy, 259, 280 Hexamethylenediamine carbamate, 967 HiFU, see High-intensity focused ultrasound High-definition signals catheters, 305 High-intensity focused ultrasound (HiFU), 1263–1265 High-Intensity Interval Training (HIIT), 425 High reliability organizations (HROs), 57 High tone non-relaxing sphincter (HTNRS), 569 High uterosacral ligament suspension (HUSLS), 929 HIIT, see High-Intensity Interval Training Hiprex on UTI, 621 History, 256 coital incontinence, 258 gynaecological, 261 insensible incontinence, 258 LUTS, 256 medication, 261–262 mixed urinary incontinence, 258 neurological, 261 neurological symptoms, 325 nocturia, 258–259 obstetric, 261 past medical, 261 past surgical, 261 postural urinary incontinence, 258 questionnaires, 256 social, 262 SUI, 258 urgency urinary incontinence, 257–258 urinary incontinence, 256–257 urinary urgency, 257–258 urogynecology/female urology behavior modification and devices, 7 COVID-19 pandemic and, 6–7 diagnosis/investigation, 6 education, 7 graft materials, 8 of IUGA, 2–4 neurophysiology, 7 stem cell research, 8 success rates, 6 surgery, field of, 7 treatment, 5 in twentieth/twenty-first centuries, 5–7 ultrasonography/magnetic resonance imaging (MRI), 7–8 urogynecology training programs, 4 uropharmacology, 7 H-line, 352 5-HMT, see 5-hydroxymethyl tolterodine Home uroflowmetry, 285 Honey, 47

Hormonally mediated vestibulodynia, 724 Hormone replacement therapy (HRT), 28–29, 744 Hospital-Acquired Conditions (HACs) Initiative, 446 HROs, see High reliability organizations HRQoL, see Health-related quality of life HRT, see Hormone replacement therapy HSCN, see Health and Social Care Network HSDD, see Hypoactive sexual desire disorder HUGO RAS platform, 1109 HUI, see Health utility index Human embryonic stem cells (hESCs), 197–198 Human imaging studies, 212 Hunner’s lesions, 591 HUSLS, see High uterosacral ligament suspension Hyalurinic acid (HA) injections, 1257–1258 Hyaluronic acid (HA), 592 Hydrometrocolpos, 1230 Hydronephrosis, ectopic ureter, 184, 192 Hydrophilic polymers, 250 5-Hydroxymethyl tolterodine (5-HMT), 461 Hymenoplasty, 1257 Hyoscyamine, 460–461 Hypersensitive pelvic floor, 716 Hypoactive pelvic floor, 716 Hypoactive sexual desire disorder (HSDD), 102–103, 115 screener, 102 Hypopressive techniques, 426 Hypothalamic-pituitary-adrenal (HPA) axis, 581 Hypothalamus, 214 Hysterectomy, and UI, 34 Hysteropexy, 1111

I IAS, see Internal anal sphincter Iatrogenic enteroceles, 905 Iatrogenic ureteral injury, 1175–1182 incidence, 1175 intraoperatively detected, 1176 management, during surgery, 1177–1178 postoperative, 1178 postoperative stent discomfort, 1178 unrecognized ureteral obstruction, 1179–1180 unrecognized ureterotomy, 1179 ureteroneocystostomy, 1181–1182 ureterovaginal fistula, treatment of, 1180–1181 preventing, 1176 risks factors associated with female pelvic surgery, 1175–1176 apical prolapse, procedures for, 1175 hysterectomy, 1175 stress incontinence, procedures for, 1175–1176 ureteral integrity, intraoperative assessment of, 1176–1177 during cystoscopy, 1176 retrograde ureterography, 1177 Iberiotoxin, 227 IC, see Interstitial cystitis ICCs, see Interstitial cells of Cajal

ICER, see Incremental cost-effectiveness ratio ICIQ, see International Consultation on Incontinence Questionnaire ICIQ-B, see International consultation on incontinence modular questionnaire bowel ICIQ bladder diary, 266–267 ICIQ-FLUTS, 132 ICIQ-VS, see International Consultation on Incontinence QuestionnaireVaginal Symptoms ICM, see Iliococcygeal muscle ICS, see International Continence Society ICS 1-hour pad test, 273–274 ICSI, see Interstitial Cystitis Symptom Index IDC/suprapubic catheter, 560 Idiopathic incontinence, 332–333 Ileal conduit, 1213–1214 Iliococcygeal muscle (ICM), 172–173 Iliopectineal ligament, 1125 Imaging; see also Magnetic resonance imaging (MRI); X-ray imaging human studies, 212 of LUTD, 343 narrow band, 374–375 of upper urinary tract, 343 of UUT, 343 intravenous urography, 343 techniques, 343 Imidafenacin, 461–462 Imipramine, 470, 476 Immunologic factors, 613 Immunoprophylaxis, 622 Imperforate hymen, 1219 Implantable pulse generator (IPG), 518 Incobotulinumtoxin A, 228 Incontinence Impact Questionnaire (IIQ), 114, 145 Incontinence Quality of Life Questionnaire (QOL), 95 Incontinence theories anatomic theories, 736–737 hammock theory, 738 integral theory, 737–738 intrinsic dysfunction theories, 737 timeline of, 738 trampoline theory, 738 Incontinent urinary diversion, 1213–1214 colon conduit, 1213–1214 ileal conduit, 1213–1214 jejunal conduit, 1214 ureterointestinal anastomosis, 1214 Incremental cost-effectiveness ratio (ICER), 154 Indevus urgency severity scale (IUSS), 95 Indiana Pouch, 1215 Indomethacin, 467–468 Induced pluripotent state (iPS) cells, 198 Indwelling urinary catheter (IUC), 445 Inferior hypogastric plexus (IHP) (pelvic plexus), 579 Infrasacral/peripheral lesions, 556–557 Cauda equina syndrome, 556 peripheral neuropathies, 557 amyloid neuropathy, 557 diabetic neuropathy, 557 post-surgery nerve injury, 556–557 viral infections, 556

Index Injectable bulking agents, 693 Innervation, 186–187 Innervation ratio, 327 Inositol triphosphate (IP3), 207 Insensible incontinence history, 258 symptoms, 258 Institute of Medicine (IOM), 56 Instrumental delivery choice of, 30 rates (UK), 30 Intercurrent illness, 744 Interlabial masses, pediatric urogynecology, 1228–1232 Bartholin’s glands, 1228 hydrometrocolpos, 1230 introital hemangiomas, 1231 prolapsed ureterocele, 1228, 1230 rhabdomyosarcoma, 1230–1231 Skene’s glands (paraurethral glands), 1228, 1230 urethral polyps, 1231–1232 urethral prolapse, 1230 Intermittency, 280 Intermittent catheterisation, 560 Intermittent stream, 280 Internal anal sphincter (IAS), 1017 Internal intussusception/rectal prolapse, 709 International consultation on incontinence modular questionnaire bowel (ICIQ-B), 122 International Consultation on Incontinence Questionnaire (ICIQ), 119, 129–133 aims and objectives, 129 development, 129 electronic adaptation of, 133 licensing, 133 lower pelvic dysfunction, modules for assessment of, 131 modular structure, 131 online library, 133 overview, 129 QoL, modules for assessment of, 132 scoring of, 132–133 sexual matters, modules for assessment of, 132 standard protocol, 129–130 translations, 133 uptake of, 133 use, 130–133 website, 133 International Consultation on Incontinence Questionnaire-Vaginal Symptoms (ICIQ-VS), 147 International Continence Society (ICS), 14, 273–274, 680, 1061 International Urogynecological Association (IUGA), 2–4, 1061 Intersex Society of North America (ISNA), 1243 InterStim Micro™, 518 Interstitial cells of Cajal (ICCs), 227 Interstitial cystitis (IC), 102 Interstitial cystitis/painful bladder syndrome (IC/PBS), 594 problems associated with sexual activity, 657 Interstitial Cystitis Symptom Index (ICSI), 102

I-11 Interviewer-administered questionnaires, 84 Intestine, embryological development, 179 Intra-abdominal pressure modulations, 283 Intradetrusor botulinum toxin injection, 559–560 Intraperitoneal uterosacral-cardinal ligament complex vault suspension, 929–930 Intravenous urography (IVU), 343 Intravesical onabotulinum toxin type A, 383 Intrinsic sphincter deficiency (ISD), 303, 737, 837 classification, 239 Introital hemangiomas, 1231 IOM, see Institute of Medicine Ion channels, 226 IPG, see Implantable pulse generator Irreparable fistula, 1171–1172 Irritable bowel syndrome, with constipation, treatment of, 706–707 IRT, see Item response theory ISD, see Intrinsic sphincter deficiency ISNA, see Intersex Society of North America ISSWSH, 727 Item response theory (IRT), 85 IUC, see Indwelling urinary catheter IUGA, see International Urogynecological Association IUSS, see Indevus urgency severity scale IVU, see Intravenous urography

J Jejunal conduit, 1214 Just culture, 57

K K+ channels, 207–208 Kelly’s plication, 736–737 Ketamine, 262 Kidneys, embryological development, 184–186 Kinesiological electromyography, 327–329 diagnostic usefulness of, 329 method, 327–328 normal/abnormal conditions, findings in, 328–329 King’s health questionnaire (KHQ), 114 Knack/counterbracing, 423–424 Knowles Eccersley Scott symptoms (KESS) Score, 124

L Labia majora reduction, 1254–1255 Labiaplasty, 1242, 1250–1254 Laboratory-generated stem cells, 198 Laparoscopic-assisted vaginal hysterectomies (LAVH), 1135 Laparoscopic colposuspension, 1061–1073 cost analysis, 1072 disadvantages, 1068 efficacy of, 1067–1068 evolution of, 1061–1062 laparoscopic transperitoneal modified Burch colposuspension, 1063–1066 non-suture colposuspension, 1067 vs. open colposuspension, 1068–1071 overview, 1061

preoperative considerations, 1062–1063 role of, 1066–1067 safety of, 1068 vs. synthetic mid-urethral sling, 1071–1072 Laparoscopic lateral suspension (LLS), 1126–1127 Laparoscopic pectopexy, 1124–1125 Laparoscopic pelvic floor surgery, 1098–1106 access complications, 1100–1101 secondary trocars, 1101 techniques for entry, 1100 trocar-associated complications, 1100–1101 trocar site/incisional hernias, 1101 anaesthetic complications, 1099–1100 bowel injury, 1103 direct injury, 1104 electrosurgical injury, 1104 prevention of, 1104 direct injury, 1104 haemorrhage controlling, 1102–1103 inferior epigastric artery perforation, management of, 1101–1102 learning curve, 1098 mesh exposure, 1105–1106 osteomyelitis/discitis, 1105 patient positioning, 1098 perioperative prevention of complications, 1098–1099 pneumoperitoneum complications, 1099–1100 simulation, 1054–1055 urinary tract injury, 1104–1105 bladder injuries, 1104 prevention of, 1105 ureteric injuries, 1104–1105 vascular injuries, 1105 sacral bleeding, 1105 Laparoscopic sacral hysteropexy (LSH), 1083 Laparoscopic sacrocolpopexy (LSC) advantage of, 1077 anatomic considerations, 1077–1078 vs. ASC, 1077 clinical assessment, 1078 comparative studies, 1084–1085 complications, 1085 concomitant anti-incontinence surgery, 1083 concomitant laparoscopic hysterectomy/ subtotal hysterectomy, 1083 contraindications, 1079 cost associated with, 1117 indications, 1078–1079 learning curve associated with, 1098, 1112 NOTES (natural orifice transluminal endoscopic surgery), 1082–1083 patient selection, 1078 prosthesis used for, 1081–1082 results, 1083–1084 sacral promontory, anatomy of, 1077–1079 vs. sacrocolpopexy, 1077 surgical technique, 1079–1082 prosthesis, types of, 1081–1082 robotic assistance, 1082 sacral promontory fixation, 1082 vaginal fixation, 1082 Laparoscopic sacrohysteropexy, 1088–1095 aims of, 1090

Index

I-12 anatomical anomalies, 1091 broad ligament, 1091, 1093 pelvic sidewall, 1091, 1093 sacral promontory, 1091, 1093 disadvantages, 1095 mesh, use of, 1090 outcomes, 1091, 1094–1095 efficacy data, 1094–1095 in older patient, 1095 in pregnancy, 1095 safety data, 1091, 1094 oxford hysteropexy, 1090–1091 day of surgery, 1090–1091 preoperative preparation, 1090 uterine preserving prolapse surgery, history of, 1088–1090 abdominal approach, 1089 laparoscopic approach, 1089–1090 vaginal approach, 1089 uterine prolapse, traditional approach for, 1088 Laparoscopic surgery advantages, 1052 laparoscopic entry adhesions, 1049 great vessels, 1049–1050 ports, insertion of, 1049–1050 presacral space, 1051–1052 retropubic space (cave of Retzius), 1052–1053 secondary ports, insertion of, 1050–1051 veress, insertion of, 1049 in urogynecology, 1048 Laparoscopic suturing (LS), 1055 LAP Mentor™, 1055 LapSim®, 1055 LapVR, 1055 Latissimus Dorsi Detrusor Myoplasty (LDDM), 322 LAVH, see Laparoscopic-assisted vaginal hysterectomies Law of Laplace, 247 Laxatives, 706 bulk laxatives/fiber, 706 5-HT4 receptor agonists, 706 opioid-induced constipation, 707 osmotic laxatives, 706 stool softeners, 706 summary of, 706 treatment of irritable bowel syndrome with constipation, 706–707 Lay buccal mucosa urethroplasty, 575 LDDM, see Latissimus Dorsi Detrusor Myoplasty Leak point pressure (LPP), 737 Le Fort colpocleisis, 49, 954 Le Fort partial colpocleisis, 932 Levator ani muscles, 172–174 Levcromakalim, 467 Lichen planus, 725–726 Lichen sclerosis, 724–725 Licorice root (Glycyrrhiza glabra), 744 Lifestyle changes, 415–416 bladder irritants, avoiding, 415 bowel management, 416 caffeine reduction, 415 fluid management, 415

physiotherapy for UI, 420 weight loss, 415 Likert scale, 127 Litigation in urogynecology, 72–74 avoidance of, 77 causes for, 74–77 communication, 74–75 consent, 74–75 governance requirements, failing to meet, 76–77 medical device problems, 76 treatment complications, 75–76 stages pre-trial, 73–74 trial, 74 LLS, see Laparoscopic lateral suspension LMWH, see Low-molecular-weight heparin Loin pain, 260 Long-duration pad tests, 275–276 detection limit, 275 versus short pad tests, 276–277 validity/reliability, 275–276 Longitudinal vaginal septa, 1221 “Loser pays” policy, 72 Lower urinary tract disease (LUTD), 623 drug treatment of, 457–482 in female patient, 238–245 imaging of, 343 Lower urinary tract (LUT) bladder, 164 dysfunction in female patient, 238–245 functional anatomy of, 164–168 functions, 457 emptying of urine, 457, 477–481 urine storage, 457–477 pelvic floor, 168–177 tissue engineering, 199–200 trigone, 164 urethra, 164–167 uropharmacology, 457 vesical neck, 167–168 x-ray imaging of, 343–350 bladder neck mobility, quantification of, 343–350 videourodynamics, 350 Lower urinary tract symptoms (LUTS), 17, 89, 541; see also Lower urinary tract disease ambulatory urodynamics for, 313 BoNT for treatment of patients with, 490–497 B-SAQ instrument, 99–101 cystometry for, 288 emerging treatments, 229–230 flow-related, 280 GAS measure, 108 global health economic consequences, 22–23 history, 256 HRQoL PROMs for, 91–94 neuroimaging for, 325 pharmacological intervention, 219–229 prevalence of, 21 progression/regression of, 21 progression/remission, natural history of, 26–27 screeners, 99–101 stigma of incontinence, 12

symptom, 256 urinalysis for, 387 urinary diary in, 266 urodynamics for, 306 Low-molecular-weight heparin (LMWH), 746–747 LPP, see Leak point pressure LS, see Laparoscopic suturing LSCC, see Lumbar Spinal Coordinating Center LSH, see Laparoscopic sacral hysteropexy Lubricants and moisturizers, 672 Lubrication, 250 Lumbar Spinal Coordinating Center (LSCC), 211 LUT, see Lower urinary tract LUTD, see Lower urinary tract disease Luteinizing hormone (LH), 665 LUTS, see Lower urinary tract symptoms Lymphoid lineages, 199

M Macroplastique, 532 Magnetic anal sphincter, 1031 Magnetic resonance defecography, 367 Magnetic resonance imaging (MRI), 7–8, 362–371 artifacts, 363 changes in urogynecological patients, 363–365 dynamic, 369–370 vs. fluoroscopy cystoproctography, 367–369 magnetic resonance defecography, 367 methodology, 362 new reference parameters on, 365–367 of normal female pelvic anatomy, 362–363 overview, 362 pelvic floor, 362–367 in postoperative evaluation, 369–370 protocols, 362–363 of rectocele, 914 3-D anatomy, 362 3-D female pelvic floor reconstruction, 370–371 of urethra, 364 of urethral diverticulum, 1193 vaginal apex sacrocolpopexy, 935–936 Magnetic sphincter, 693 Magnetic stimulation (MStim), 505–506 evidence for, 506 to treat urinary incontinence, 505–506 Mahati, 47 Malone procedure, see Antegrade continence enema (ACE) Manchester-Fothergill procedure, 954 Manchester health questionnaire data, 122–123 Manchester repair (MR), 927 Manual perineal protection (MPP), 33 Manufacturer and user facility device experience (MAUDE) database, 990 Markov model, 155–160 Marshall–Marchetti–Krantz (MMK), 737, 757 vs. colposuspension, 780 complications, 777 operative technique, 777 procedure, 777 results, 777

Index Mast cells, 586 Maximal urethral pressure (MUP), 474–475 Maximum flow rate (Qmax), urine flow, 281 Maximum urethral closure pressure (MUCP), 274, 300–301, 364, 424, 474–476 Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome, 202, 1222–1223, 1242 Mayer-Rokitansky syndrome, 1243–1244 Mayo faecal incontinence survey, 123 McCall’s culdoplasty, 51, 928–929, 1175 Mediation, 74 Medical, Epidemiological, and Social Aspects of Aging questionnaire, 102 Medical error and patient safety in surgery, 55–68 checklists for surgical care, 63–64 culture of safety, 57 decision-making and diagnostic errors, 64–66 disclosure and apology of adverse events and errors, 66–67 in female urology, 59–60 HROs, 57 human factors and demands, 57–58 methods for mitigating error, 60–61 communication, 60–61 teamwork, 60–61 overview, 56–57 practice-related issues, 58 simulation-based training of surgical teams, 61–62 sources of error in surgery, 58–59 surgical team training interventions and, 61–62 technical skills training, surgical simulators for, 62–63 trends in surgical volume and site, 55–56 in urogynecology, 59–60 Medical therapy, 573 Medication history, 261–262 Medicines and Healthcare products and Regulatory Agency (MHRA), 795 Medicolegal issues in urogynecology, 72–78 Melatonin, 561 Menopausal hormone therapy (MHT), 673 benefits of, 674 and breast cancer, 675 estrogen, 673 practical considerations, 676 progestogens, 674 risks of, 674–675 testosterone, 674 Menopausal symptoms, 668 Menopause, 28–29, 472 definitions, 665 effects of, 668 genitourinary problems, 668 menopausal symptoms, 668 psychological symptoms, 668 sexual dysfunction, 669 etiology, 665–667 follicle maturation/availability and estrogen production, 667 investigations, 667–668 long-term effects, 670–671 cardiovascular disease, 671 cognitive function, 671 osteoporosis, 670–671

I-13 management, 671–676 alternative and complementary therapies, 672 cardiovascular disease, 675 contraception, 676 dehydroepiandrosterone, 673 diet, 671 endometrial cancer, 675 exercise, 672 lifestyle, 671 lubricants and moisturizers, 672 menopausal hormone therapy, 673 neurokinin inhibitors, 672 Ospemifene, 673 ovarian cancer, 675 oxybutynin, 672 stroke, 675–676 treatments for urogenital atrophy, 672 vaginal estrogens, 673 vaginal laser therapy, 673 venous thromboembolism, 675 stress incontinence, 669 symptoms and effects of, 666 urogenital atrophy/genitourinary syndrome, 672 vaginal epithelium, 669 MEPs, see Motor evoked potentials Mesenchymal stem cells, 199 Mesenchyme, 179–184, 186 Mesh, 358–359 Mesh complications, 868–876; see also Synthetic meshes algorithm for management of, 876 calculator, 870 classification, 869–870 factors associated with mesh-related, 868–869 patient-related, 869 surgery-related, 869 intraoperative, 870–871 bladder/urethral/vaginal wall injury, 870–871 bowel injury, 871 neurovascular injury, 871 post-operative, 871–875 autoimmune/systemic complications, 874 bladder/urethral extrusion, 872 LUTS, 874 pain, 873 sexual dysfunction, 873–874 vaginal mesh exposure, 871–872 terminology for, 869 Mesh removal surgery, 874–875 IUGA/AUGS classification, 874 multidisciplinary team, role of, 875 principles of, 874–875 Mesoderm, 179, 182, 184 Mesonephros, 184 Metanephros, 184 Methenamine hippurate (Hiprex), 620–621 Methicillin-resistant Staphylococcus aureus (MRSA), 750 Metoidoplasty, 1277 MFSSQ, see Monash female sexual satisfaction questionnaire MHRA, see Medicines and Healthcare products and Regulatory Agency

Microsoft Access® “Q-Builder” software, 135–136 Microtip transducer catheters, 298–299 Micturition afferent pathways, 208–209 cortical modulation of, 212–213 animal studies, 212–213 human imaging studies, 212 parasympathetic pathways, 207 peripheral nervous system, 207 physiology, 207–215 position-dependent, 260 somatic pathways, 207 storage reflexes, organization of spinal reflex pathways, 209 supraspinal pathways, 209 subcortical modulation of, 213–214 basal ganglia, 214 cerebellum, 214 hypothalamus, 214 substantia nigra pars compacta, 214 ventral tegmental area, 214 sympathetic pathways, 207–208 voiding reflexes, organization of, 209–212 brain stem circuitry, 210–212 spinobulbospinal reflex pathways, 210 MID, see Minimal important difference Midodrine, 474 Mid-stream urine culture (MSU), 387, 390–393 Midurethral slings (MUS), 56, 740–741 obstruction complicating sling loosening/incision, 851 timing of intervention, 850 transvaginal sling incision/excision, 851–854 Mid-urethral tapes, 45 vs. colposuspension, 35 procedures, 35 MiniArc (American Medical Systems), 817 Minimal important difference (MID), 85, 90 Minimally invasive surgery, urogynecology, 1048 Minimally Invasive Surgery Training-Virtual Reality (MIST VR), 1055 Mirabegron, 224–225, 468–469, 545, 546 adverse effects, 224–225 cardiac safety of, 225 efficacy, 224 pharmacokinetics, 225 tolerability of, 224 Mitrofanoff appendicovesicostomy, 1212–1213 Mixed–combined disorders, 244 Mixed urinary incontinence history, 258 symptoms, 258 Mixed urinary leakage (MUI), 19 MMK, see Marshall–Marchetti–Krantz Modified Burch colposuspension, 1063–1066 Modified 1-hour pad tests, 274–275 Modified Oxford Scale, 263 Modified sphincteroplasty, 692 Monash female sexual satisfaction questionnaire (MFSSQ), 115 Monoclonal antibodies, 593 Morphine, 220 Moschcowitz procedure, 906–907

Index

I-14 Motor and cognitive impairment, impact of, 558 Motor evoked potentials (MEPs), 327 Motor neurons, 327 Motor unit, 327 Motor unit potentials (MUPs), 328–331 MPP, see Manual perineal protection MR, see Manchester repair MR defecography, 704 MRI, see Magnetic resonance imaging MRSA, see Methicillin-resistant Staphylococcus aureus MSA, see Multiple system atrophy Mucosa, 167 MUCP, see Maximal Urethral Pressure; Maximum urethral closure pressure MUI, see Mixed urinary leakage Müllerian ducts, differentiation, 182 Multidisciplinary team (MDT), 730 bladder pain syndrome, 733 complex pelvic floor disorders, 732 joint pelvic floor clinic, 730–731 aims of, 731 mesh-related complications, 732–733 pelvic floor dysfunction, 730 recurrent urinary incontinence, 731 recurrent urinary tract infection, 733 regional MDT, 731 Multiple sclerosis (MS), 555–556 Multiple system atrophy (MSA), 332, 553–554 MUP, see Maximal urethral pressure; Motor unit potentials Muscarinic receptors, 222–223 Muscle electrical activity, 327 Myeloid, 199 Myelomeningocele, 1234–1235 Myocytes, 227 Myofibroblasts, 247 Myogenic activity, 227

N Naloxone, 220, 478 Narrow band imaging, 374–375 NASHA/Dx injection, 1028 National continence organizations continence promotion role, 14 results of survey, 14 National Institute for Health and Care Excellence (NICE), 90, 795, 1063 Native progenitor cells, 198–199 Native tissue repair (NTR), 965 Natural killer (NK) cells, 199 N-desethyloxybutynin (DEO), 464 NDO, see Neurogenic detrusor overactivity Needle electromyography, 573 Needle suspensions, 44, 760–763 evidence, 763 Gittes operation, 762 outcomes, 762–763 Raz, 762 Stamey, 760–762 Neosphincters; see also Anal incontinence artificial bowel sphincter, 692–693 injectable bulking agents, 693 magnetic sphincter, 693 modified sphincteroplasty, 692 non-stimulated muscle transposition, 692

radiofrequency energy treatment, 693 stem cell therapy and other tissue regeneration techniques, 693 stimulated muscle transposition, 692 stomas, 693 Nerve conduction studies, rectocele, 914 Nervous pathways, testing of, 326–327 Neural control of lower urinary tract in health, 550 Neurogenic detrusor overactivity (NDO), 321, 490–493 Neuroimaging, 325 Neurokinin inhibitors, 672 Neurological disorders assessment focus on patients bladder diary – questionnaires, 557 follow-up, 558–559 history, 557 impact of motor and cognitive impairment, 558 impact of progressive disease and ageing, 558 investigations, 558 physical examination, 557 role of associated factors, 557–558 changes in LUT functions, 550 infrasacral/peripheral lesions, 556–557 Cauda equina syndrome, 556 peripheral neuropathies, 557 post-surgery nerve injury, 556–557 viral infections, 556 management, 559 conservative management, 559 management of voiding dysfunction – DSD/DU, 560 treatment of OAB/DO, 559–560 neural control of lower urinary tract in health, 550 neurogenic LUT dysfunction, 557 prevalence and clinical presentation, 550–556 brainstem lesions, 554 cerebral/cortical disease, 550–554 multiple sclerosis, 555–556 others inflammatory disorders, 556 spinal cord injury, 554–555 spinal dysraphism, 556 surgical treatment, 561 augmentation cystoplasty, 561 non-continent urinary diversion, 561 treatment of nocturia, 561 treatment of stress urinary incontinence, 561 Neurological evaluation of patient, 325–338 autonomic system testing, 337–338 clinical examination, 325 clinical neurophysiology tests, 325–326 conduction across nerves, testing of, 326–327 electromyography, 326–334 history, 261, 325 motor unit, 327 nervous pathways, testing of, 326–327 neuroimaging, 325 neurologic function, investigations of, 325 quantitative sensory testing, 325 sacral motor system, conduction studies of, 334–335

anterior sacral root (cauda equina) stimulation, 334–335 central motor pathways, assessment of, 335 sacral reflexes, 336–337 sacral sensory system, conduction studies of, 335–336 anal canal, electrical stimulation of, 336 bladder, electrical stimulation of, 336 cortical somatosensory evoked potentials, 335–336 urethra, electrical stimulation of, 336 Neurological examination, 264 Neurological history, 261 Neuromodulation, 592, 708 complementary medicine, 708 and nerve stimulation, 546–547 percutaneous tibial nerve stimulation, 708 sacral nerve stimulation, 708 Neuronal nitric oxide (nNOS) synthetase, 184 Neurophysiology, 7 Neuroproliferative vestibulodynia, 724–726 dermatological conditions lichen sclerosis, 724–725 desquamative inflammatory vaginitis, 726 lichen planus, 725–726 physical therapy treatment, 724 surgical treatment for, 726–727 NICE, see National Institute for Health and Care Excellence Nifedipine, 227, 467 Nimodipine, 467 Nitrofurantoin, 619 NK1-receptor antagonists, 221–222, 473 NMIBC, see Non-muscle invasive bladder cancer; Non-muscle invasive bladder cancers NOACs, see Novel oral anticoagulants Nocturia, 248–249 with age, 259 circadian rhythms, 249 definition, 258–259 desmopressin and melatonin, 561 future studies, implications for, 249 history, 258–259 nocturnal voids and, 259 renal circadian rhythms, 248–249 salt and water movement across urinary tract, 249 sub-types, 248 symptoms, 258–259 treatment of, 561 urothelium and sensations of bladder fullness, 249 Nocturnal enuresis, 1233 causes, 259 symptoms, 259 Nocturnal polyuria syndrome (NPS), 248–249, 259 Non-continent urinary diversion, 561 Non-muscle invasive bladder cancers (NMIBC), 374–375, 383 Nonneurogenic voiding dysfunction and urinary retention bladder diary, 568 clinical history and assessment, 568 examination, 569 investigations, 569–575

Index Botox, 573–574 conservative management, 572–573 cystoscopy and examination under anaesthetic, 570 imaging, 570 management, 572 medical therapy, 573 sacral neuromodulators, 574–575 self-catheterisation, 573 surgery, 575 ultrasound assessment, 569 urethral pressure profilometry, 571–572 urodynamics, 570–571 uroflow, 569 patient recorded outcome measures, 568–569 voiding, 567–568 Non-neuropathic voiding disorders, 329 Nonobstructive urinary retention (NOUR), 517 sacral neuromodulation for, 521–522 Non-stimulated muscle transposition, 692 Non-suture colposuspension, 1067 Noradrenaline, 221 reuptake, 220 Norfenefrine, 474 Normal cystometry, 297 Normative values, 269 NOTES (natural orifice transluminal endoscopic surgery), 1082–1083 NOUR, see Nonobstructive urinary retention Novel oral anticoagulants (NOACs), 746–747 “No win, no fee,” 72 NPS, see Nocturnal polyuria syndrome NRM, see Nucleus raphe magnus NROB1 gene, 1219 NTR, see Native tissue repair Nuclear reprogramming mechanism, 198 Nucleus raphe magnus (NRM), 209 Nucleus reticularis pontis oralis, 209

O OAB, see Overactive bladder OAB Bladder Assessment Tool (OAB-BAT), 108 OAB/DO, treatment of, 559–560 antimuscarinic agents, 559 B3 adrenergic agonists, 559 intradetrusor botulinum toxin injection, 559–560 sacral neuromodulation, 560 tibial nerve stimulation, 559 OAB-q, 85 OAB-SAT-Q, see Overactive bladder satisfaction with treatment questionnaire OAB-V8/OAB awareness tool, 102 OASIs, see Obstetric anal sphincter injuries Obesity, 29, 415, 420 Obstetric anal sphincter injuries (OASIs), 28–29, 685, 686, 1013–1021 childbirth and, 29 classification of, 1013–1014 definition, 1013 incidence of, 1013 instrumental delivery and, 30

I-15 intrapartum prevention of, 33–34 episiotomy, 33–34 MPP, 33 recommendations, 34 perineal tears, classification of, 1013–1014 prevalence of, 1015 prevention of, 33 primary repair, 1013 management of subsequent pregnancy after, 1021 outcome of, 1013–1016 principles of, 1018–1021 technique of, 1016–1021 secondary repair, 1013 Obstetric history, 261 Obstetric trauma, 202 anal incontinence, 657–658 Obstetric urogenital fistula, 1160–1172 epidemiology, 1160–1161 etiology, 1160–1161 failed repairs, 1171 immediate management, 1165 investigations of, 1164 irreparable fistula, 1171–1172 postoperative care, 1170 postoperative complications, 1170–1171 frequency and voiding disorders, 1171 ongoing incontinence, 1170–1171 ongoing sexual and reproductive complications, 1171 social and mental health issues, 1171 urinary retention, 1171 prevalence of, 1161 prognostic factors and classification, 1164 results, 1170 route of repair, 1165–1167 bladder, mobilization of, 1166 closure of bladder, 1166 closure of vagina, 1167 dye test to watertight closure, 1166 exposure of fistula, 1166 outcomes, 1166–1167 protection of ureter, 1166 pubourethral ligament, reconstruct, 1167 surgical treatment, 1165–1166 urethra to normal width and length, maintain/reconstruct, 1166–1167 surgical problems, 1167–1169 absent urethra, 1167–1169 circumferential fistulae, 1169 no vaginal tissue remaining, 1169 rectovaginal fistula, 1169 symptoms and signs, 1161 bladder stones, 1163 bones, 1163 limb contractures, 1163 malnutrition, 1163 mental health issues, 1163 muscles, 1163 nerves, 1163 rectovaginal injuries, 1162 reproductive outcomes, 1163–1164 reproductive tract, 1162–1163 social consequences, 1163 upper renal tract damage, 1163 ureteric injury, 1161–1162 urine dermatitis, 1163 vesicovaginal fistula, 1161

timing of repair, 1164–1165 Obstructed defecation symptoms (ODS), 1038 anatomy, 1038–1039 biomechanics of, 1038–1039 definition, 1038 epidemiology, 1038 etiology of, 1039–1041 dyssynergia, 1039 hyper-relaxed pelvic floor, 1040–1041 rectal support defects vs. rectocele, 1039–1040 imaging in evaluation, 1041–1042 MR defecography, 1041 pelvic floor ultrasound, 1041–1042 treatment options for, 1042–1044 conservative management, 1042–1043 surgical treatment, 1043–1044 Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome, 1221–1222 Obstructive defecation syndrome (ODS), 127, 708 Obturator foramen, 807 Occult incontinence, 261 ODS, see Obstructive defecation syndrome Oestrogen therapy, 545–546, 620 O’Leary-Sant questionnaire, 587 Onabotulinumtoxin A, 228, 320, 490, 494–497 Operation profile, 58 Opioid antagonists, 478 Opioid-induced constipation (OIC), 707 Opioid peptides, 220 μ-opioid receptor antagonist, 220 Opioid receptors, 220 δ-opioid receptors, 220 Oral therapy, 591 Orgasm shot/O-Shot, 1258–1259 Oropharyngeal membrane, 179–180 Orthotopic urinary diversions, 1216 Osmotic laxatives, 706 Ospemifene, 673 Osteoporosis, 670–671 Ottava robotic platform, 1109 Outcome measures, female sexual health research clinician, 113 objective, 112 subjective, 112 Ovarian biology, tissue engineering approaches, 202–204 Ovarian cancer, 675 Ovarian sex steroids, 202 Ovarian tissues, autologous transplantation, 202 Ovaries cryopreservation of ovarian tissues, 202 tissue engineering, 202 Overactive bladder (OAB), 21, 247–248, 623 ATP and, 248 atropine for, 460 BoNT in, 493–495 botulinum toxin A, 546 darifenacin for, 461 differential diagnosis of, 543 drugs potentially affecting continence, 543 drug targets for, 248, 458 electrical stimulation for, 504–505

Index

I-16 emerging treatments, 229–230 epidemiology and natural history, 542 fesoterodine for, 461 flavoxate in, 464 GAS measure, 108 hypothesis for genesis of, 26–27 neuromodulation and nerve stimulation, 546–547 OAB-V8/OAB awareness tool, 102 origin of, 542, 543 pathogenesis, 248 pathologies, 248 patient assessment, 542–544 bladder diary, 543 questionnaires, 543 urodynamics, 543–544 pharmacological intervention, 219–229 pharmacotherapy, 544–546 antimuscarinic agents, 544–545 combination, 545 desmopressin, 545 mirabegron, 545, 546 oestrogen, 545–546 transdermal oxybutynin formulations, 545 vibegron, 545 β3-adrenergic agonist, 545 physiology and pathophysiology, 542 prevalence, 21 progression/regression of, 21 progression/remission, 26–27 propantheline bromide for, 462 PTNS for, 509–513 sacral neuromodulation for, 517–521 selective 5-HT for, 220 SSRIs for treatment of, 220 surgery, 547 symptoms, 12, 259 therapeutic exercise for, 427 treatment, 544 and urgency, 29 urinary microbiome in, 395 β3-AR agonists for treatment of, 224 Overactive bladder outlet, 238, 243 Overactive Bladder Questionnaire (OAB-q), 102 Overactive Bladder Satisfaction (OAB-S) measure, 81 Overactive bladder satisfaction with treatment questionnaire (OAB-SAT-Q), 107 Overactive bladder treatment satisfaction questionnaire, 107 Oxford hysteropexy, 1090–1091 day of surgery, 1090–1091 preoperative preparation, 1090 OXY, see Oxybutynin Oxybutynin (OXY), 460, 464–465, 672

P PAC-SYM, see Patient assessment of constipation symptoms and quality of life Pads/pants, 448–453 for beds and chairs, 451 design factors, 448–449 economical and environmental issues, 451 ICS recommendations for, 451–452

resources, 454–455 as reusable products, 450 SAP, use of, 449–450 skin barriers vs. treatments, 453 skin care and, 451–452 skin pH and, 452 standardization for, 449 tests historical aspects, 272 indications, 272 long-duration, 275–276 reliability, 272–273 short, 273–275 standardized 1-hour pad test, 273 validity, 272–273 for undergarments, 450 PAG, see Periaqueductal gray PAHG, see Polyacrylamide hydrogel Pain bladder, 260 dyspareunia, 260 loin, 260 perineal, 260 urethral, 260 PAM, see Puboanal muscle Paper Towel Test, 277 Paracolpium, 169 Pararectal fascia, 912 Parasympathetic pathways, 207 Parasympathomimetic agents, 477 Parasympathomimetic (bethanechol), 573 Paravaginal defect repair (PVdR), 759–760 Parkinson disease (PD), 553 Parkinsonian syndromes, 554 PARSEC, 1110 Past medical history, 261 Past surgical history, 261 Patient assessment of constipation symptoms and quality of life (PAC-SYM), 124 Patient-centered care, 14 Patient education behavioral therapies, 410 continence nurse role in, 407 Patient Global Impression of Improvement (PGI), 148–149 POP questionnaires and pessary usage, 148 POP questionnaires and physiotherapy, 148–149 POP questionnaires and surgery, 149 POP questionnaires in clinical and research practice, 148 Patient Global Impression of Improvement (PGI-I) questionnaire, 1129 Patient reported outcome measures (PROMs), 89, 135 Patient-reported outcome (PRO), 80–86 classifications of, 80–82 activity of daily living, 81 cost and economic assessments, 82 discomfort, 81 productivity, 81–82 quality-adjusted life-year, 82 symptom frequency and bother, 81 treatment satisfaction, 81 clinical trials and clinical practice, selecting measures for, 86 condition-specific measures, 80 generic measures, 80

linguistic and cultural validation, 85–86 questionnaire modification, 86 regulatory oversight, 85 steps, 85 measure scores, 85 psychometric properties, 84–85 construct-related validity, 84 convergent validity, 84 criterion validity, 84 discriminant validity, 84 internal consistency reliability, 84 interrater reliability, 84 reliability, 84 responsiveness, 84–85 test–retest reliability, 84 validity, 84 questionnaire development and validation, 82–84 content validity, 83–84 intent and purpose, 82–83 items, 83 mode of administration, 84 study design considerations, 86 types of, 80 Patient-Reported Outcomes Measurement Information System (PROMIS), 81, 124 Patient satisfaction and expectations, 102, 104–107 background, 102, 104 BSW questionnaire, 104 Global Ratings of Patient Satisfaction and Perceptions of Improvement questionnaire, 104 OAB-S, 107 OAB-SAT-Q, 107 PSTB, 107 SATMED-Q, 104 TSQM, 104 Patient satisfaction with treatment benefit questionnaire (PSTB), 107 Pay-outs in NHS, 72 PBS, see Pelvic pain syndrome PCL, see Pubococcygeal line PCR, see Polymerase chain reaction Pectopexy surgical technique, 1124–1125 Pediatric urogynecology, 1227–1246 bladder exstrophy, 1237–1238 classic, 1237 cloacal, 1237–1238 female epispadias, 1238 cloacal malformations, 1238–1239 congenital anomalies, 1237 female embryology, 1227–1229 female genitalia, disorders of, 1240–1242 DSD, 1240 pull-through vaginoplasty, 1242 skin-flap vaginoplasty, 1242 vaginal replacement/interposition, 1242 46,XX DSD, 1240–1241 46,XY DSD, 1241–1242 FGRS, 1242–1244 interlabial masses, 1228–1232 Bartholin’s glands, 1228 hydrometrocolpos, 1230 introital hemangiomas, 1231 prolapsed ureterocele, 1228, 1230 rhabdomyosarcoma, 1230–1231

Index Skene’s glands (paraurethral glands), 1228, 1230 urethral polyps, 1231–1232 urethral prolapse, 1230 urinary incontinence in girls, 1232–1237 bilateral single ectopic ureters, 1237 causes of, 1232–1234 duplicated ectopic ureters, 1235–1237 etiology, 1232 mechanisms of, 1232 neurogenic, 1234–1235 urinary tract reconstruction, 1244–1245 lower, 1244–1245 Mitrofanoff principle of, 1244–1245 and pregnancy, 1246 tissues available for, 1244 transitioning congenital anomaly patients from pediatric to adult care, 1245–1246 urogenital sinus anomalies, 1238–1239 Pelvic diaphragm, 172–174 Pelvic examination, 586 Pelvic floor anatomy, 168–177 components, 168 external genital muscles, 174 levator ani muscles, 172–174 muscle and connective tissue, interaction between, 174 pelvic diaphragm, 172–174 perineal membrane, 174 urethra, position and mobility of, 174–177 viscerofascial layer, 168–172 Pelvic floor assessment in sexual function, 715–716 external examination, 716, 717, 718 hypersensitive pelvic floor, 716 hypoactive pelvic floor, 716 internal examination, 716, 718, 719 laboratory testing, 719–722 neurourological testing, 718–719, 720, 721 Pelvic floor consortium, 123, 127 Pelvic floor disorders, 7 risk calculator, 31 Pelvic Floor Distress Inventory-20 (PFD20), 135 Pelvic Floor Distress Inventory (PFDI), 81, 145 Pelvic floor dysfunction (PFD), 111, 115–116, 730 childbirth and, 29 prevalence of, 111 sexual function in, difficulties specific to, 113–114 Pelvic Floor Dysfunction Questionnaire (PFDQ), 147 Pelvic Floor Impact Questionnaire-7 (PFIQ-7), 135, 145 Pelvic floor muscle hyperalgesia (PFMH) scoring system, 264 Pelvic floor muscles (PFMs), 680 Pelvic floor muscle therapy (PFMT), 743, 1061 Pelvic floor muscle training (PFMT), 31–32, 410–412, 416 clinical situations for, 421 common problem encountered in, 411 exercises, 411 in female UI, 420–421 goals for, 420

I-17 hypopressive techniques, 426 knack/counterbracing, 423–424 muscle recruitment, awareness of, 421 prevention with, 31–32 to prevent stress incontinence, 411–412 strength training, 424–425 teaching for, 410–411 through abdominal muscle recruitment, 425 voluntary muscle contraction, 422–423 Pelvic floor overactivity, 656–657 Pelvic floor physical therapy (PFPT), 947 Pelvic floor surgery accreditation, necessity of, 1054 advanced laparoscopic skills for, 1055–1056 laparoscopic suturing, 1055 urogynecology, laparoscopic training for, 1055–1056 credentialing in, 1058–1059 laparoscopic, 1098–1106 access complications, 1100–1101 anaesthetic complications, 1099–1100 autologous fascial lata sacrocolpopexy, 1128–1129 bowel injury, 1103–1104 cervicosacropexy, 1125–1126 haemorrhage controlling, 1102–1103 inferior epigastric artery perforation, management of, 1101–1102 laparoscopic lateral suspension, 1126–1127 laparoscopic pectopexy, 1124–1125 learning curve, 1098 mesh exposure, 1105–1106 osteomyelitis/discitis, 1105 patient positioning, 1098 perioperative prevention of complications, 1098–1099 pneumoperitoneum complications, 1099–1100 simulation, 1054–1055 urinary tract injury, 1104–1105 vaginosacropexy, 1125–1126 vascular injuries, 1105 vNOTES, 1127–1128 robotic training/simulation for, 1056–1058 simulators, 1054 training, necessity of, 1054–1055 Pelvic Floor Symptom Bother Questionnaire (PFBQ), 147 Pelvic inclination correction system (PICS), 366 Pelvic organ prolapse (POP), 17, 652–656, 880 biological grafts for, 965 childbirth and, 29–30 CS for, 32–33 definition for condition of, 21–22 effect on sexual function, 652–654 pessaries, 654 physiotherapy, 652, 654 reconstructive POP surgery, 654 epidemiology, 145, 883–884 etiology of, 884–887 failed surgery, prevention of, 36 family history and, 886–887 global health economic consequences, 22–23 grading systems, 881

hormone replacement therapy and, 886 HRT for, 28–29 Hysterectomy and Manchester-Fothergill procedure, 654–656 obliterative POP surgery, 656 vaginal mesh surgery, 656 impact on short pad tests, 275 medical illnesses and, 886 menopausal status and, 886 modifiable lifestyle risk factors, 885–886 MRI for, 362 natural history of, 27–28, 887 OECD on, 925 pelvic organ support, classification of, 880–881 pelvic reconstructive surgery and, 34–35 pessaries for, 433–437 care, 435–437 effectiveness, 433–434 fitting, 435 pessary vs. surgery, 434–435 quality of life, 435 sexual function, 435 PFMT for, 32 PGI to assess, 148–149 POP-SS to assess, 148 pregnancy and, 885 prevalence of, 17, 145, 256 prior pelvic surgery and, 886 quantification system, 880–883 examination, 880–882 simplified, 883 staging, 882 questionnaires to assess, 145–149 Australian Pelvic Floor Questionnaire, 147–148 CRADI, 145 Danish Prolapse Questionnaire, 147 ePAQ-PF, 148 HRQoL, 145 ICIQ-VS, 147 IIQ, 145 PFBQ, 147 PFDI, 145–146 PFDQ, 147 PISQ, 147 POPDI, 145 P-QoL, 146 UDI, 145 race and, 886 raised BMI and, 29 rate of surgery, 22 risk calculator, 31 risk factors, 20, 22, 145 risk groups/factors, 28–29 age, 28 familial and genetic factors, 29 HRT, 28–29 obesity and, 29 overactive bladder, 29 surgery, history of, 47–53, 145 ancient history (3000 BC-AD 500), 47 early modern period (16th-18th century), 47 middle ages (5th-15th century), 47 21st century, 52–53 19th and 20th century, 47–52 symptoms, 145, 260–261

Index

I-18 synthetic mesh for repairs (see Synthetic meshes) uroflowmetry, 280 VAS to assess, 148 Pelvic organ prolapse quantification (POPQ), 21–22, 29, 52, 263, 880–883, 889, 913 examination, 880–882 simplified, 883 staging, 882 Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12), 135, 147 PROMs, 135 Pelvic organ support, 902, 905 Pelvic pain and urgency/frequency (PUF) questionnaire, 102 Pelvic pain and urgency/frequency scale, 588 Pelvic pain syndrome (PBS), 102 Pelvic parasympathetic nerves, 207 Pelvic reconstructive surgery, 34–35 Pelvic sidewall, 1091 Pelvis laparoscopic anatomy, 1049–1053 vasculature, 1049 Pentosan polysulfate sodium (PPS), 591 Percutaneous nerve evaluation (PNE), 518 Percutaneous tibial nerve stimulation (PTNS), 159, 509–513, 546–547, 708 clinical results, 510–511 history, 509 implants, 511–513 prognostic factors for, 511 technique, 509–510 working mechanism, 510 Periaqueductal gray (PAG), 207, 212, 541 Pericatheter leakage, 447 Perimenopause, 665 Perineal body, 1000–1001 Perineal pain, 260 Perineal tears, classification of, 1013 Perineum, 1000 anal triangle, 1000–1001 anatomy of, 1000 injury/trauma, 1000–1009 perineal body, 1000–1001 superficial muscles of, 1000–1001 training in diagnosis/management of, 1009–1010 urogenital triangle, 1000 Perinoplasty, 1257 Peripheral nervous system, 207 Peripheral neuromodulation, 509–514 dorsal genital nerve stimulation, 514 anatomy, 514 results, 514 methods, 509 PTNS, 509–513 clinical results, 510–511 history, 509 implants, 511–513 prognostic factors for, 511 technique, 509–510 working mechanism, 510 pudendal nerve stimulation, 513–514 anatomy, 513 results, 513–514 technique, 513 working mechanism, 513

Peritoneovaginal fistulae, 1137 Peroxisome proliferator–activated receptor (PPAR), 247 Pescatori incontinence score, 123 Pessaries, 47 adverse events related to use, 439–440 overview, 433 for pelvic organ prolapse, 433–437 care, 435–437 effectiveness, 433–434 fitting, 435 pessary vs. surgery, 434–435 quality of life, 435 sexual function, 435 for stress urinary incontinence, 437–439 effectiveness, 437–438 mechanism of action, 437 vaginal and urethral devices, other types of, 438 Petroleum, 47 PFBQ, see Pelvic Floor Symptom Bother Questionnaire PFD, see Pelvic floor dysfunction PFDI, see Pelvic Floor Distress Inventory PFDQ, see Pelvic Floor Dysfunction Questionnaire PFMT, see Pelvic floor muscle therapy; Pelvic floor muscle training PFPT, see Pelvic floor physical therapy PGA, see Polyglycolic acid PGE2, 477 PGF2α, 478 PGI, see Patient Global Impression of Improvement P-glycoprotein (P-gp), 225 PGs, 477 Phalloplasty, 1278 Pharmacology of bladder, 219–229 α-adrenoceptors, 221 antimuscarinics (anticholinergics), 223 botulinum toxin, 228–229, 470–472, 481 calcium channels, 226–227, 467 CNS targets, 219–221 dopamine/dopamine receptors, 222 GABA, 220–221, 480 gabapentin, 221–222 mirabegron, 224–225 muscarinic receptors, 222–223 myocytes, 227 NK1-receptor antagonists, 221–222 noradrenaline, 221 opioid receptors, 220 peripheral targets for, 222–223 potassium channels, 227 sensory nerves and vanilloid receptors, 228 serotonin (5-HT) mechanisms, 220 urothelium, 227 vibegron (MK-4618), 225–226 α-adrenoceptors, 223 β-adrenoceptors, 223–224, 468 β3-AR agonists, 224 Pharmacotherapy, 544–546 Phenoxybenzamine (POB), 479 Phenylpropanolamine (PPA), 474–475 Phosphodiesterase-5 inhibitors (PDE5-i), 593 Phosphodiesterase (PDE) inhibitors, 226, 470 Phosphodiesterase type-5 inhibitors, 247 Phosphorylation, 249

PHVP, see Post-hysterectomy vaginal prolapse Physiotherapy for UI, 420–430 assessment, 420 biofeedback, 427–430 exercises, 420–427 abdominal muscle recruitment, 425 breathing exercises, 426–427 hypopressive techniques, 426 knack/counterbracing, 423–424 muscle recruitment, awareness of, 421 with other therapeutic techniques, 427 for overactive bladder, 427 postural re-education, 426–427 strength training, 424–425 voluntary muscle contraction, 422–423 lifestyle interventions, 420 PICS, see Pelvic inclination correction system Pinacidil, 467 Piperacillin-Tazobactam, 620 Pipe-stem urethra, 303 PISQ, see Prolapse and incontinence sexual questionnaire PLA, see Polylactic acid Platelet-rich plasma (PRP) therapy, 527, 1146 Pluripotent stem cells, 198 PMC, see Pontine micturition center PNE, see Percutaneous nerve evaluation Polyacrylamide hydrogel (PAHG), 383 Polyglycolic acid (PGA), 197 Polylactic acid (PLA), 197 Poly(lactic-co-glycolic acid) (PLGA), 197 Polymerase chain reaction (PCR), 394 Polymers, 250 Polysynaptic inhibitors, 472 Polyzwitterionic coatings, 250 Pontine micturition center (PMC), 207, 210–211, 541 Pontine urine storage center (PUSC), 209 POP, see Pelvic organ prolapse POPDI, see POP Distress Inventory POP Distress Inventory (POPDI), 145 POPQ, see Pelvic organ prolapse quantification; Pelvic Organ Prolapse Quantification POP-SS, see POP-Symptom Score POP-Symptom Score (POP-SS), 148 Position-dependent micturition, 260, 280 Posterior compartment, ultrasonography in, 355–356 Posterior tibial nerve stimulation (PTNS), 691–692, 1032–1033 Posterior urethrovesical angle (PUV), 737 Posterior urethrovesical (PUV) angle, 344–345 Post-hysterectomy vaginal prolapse (PHVP), 927 iliococcygeus vault suspension for, 931–932 sacrospinous fixation for, 931 Post-micturition dribble, 260 Postoperative care analgesia, 750–751 bowels, 752 ERAS, 752–754 follow-up, 754 immediate, 750 indwelling catheter care, 751 infection, 752 intraoperative haemorrhage, 751

Index mobilisation, 752 postoperative haemorrhage, 752 suture and pelvic drains, removal of, 752 vaginal pack, 751 voiding problems, anticipation of, 751 Postoperative urodynamics, 280 Post-surgery nerve injury, 556–557 Postural re-education, 426–427 Postural urinary incontinence history, 258 symptoms, 258 Post void residual volume (PVR), 569 Potassium channels, 227 openers, 467 Potassium cycling, 586 Potassium sensitivity test (PST), 586 Pouch of Douglas, 902, 904 anatomy, 902–903 deep, 902, 904–905 obliteration, 906–908 rectal prolapse and, 905 and vagina, 905 PPAR, see Peroxisome proliferator–activated receptor Prazosin, 479 Pregnancy frequency, 26 and puerperium, 286 Pregnancy, effect on pelvic floor function anal sphincter, 645, 646 bowel symptoms in pregnancy, 640 and childbirth on pelvic floor (see Childbirth) internal and external sphincter trauma, 646 lower urinary tract symptoms, 639–640 frequency and nocturia, 639 urinary incontinence, 639–640 voiding difficulties, 639 muscle/ligaments, 638 urinary tract in pregnancy, 638–639 Valsalva manoeuvre, 644 Premature ovarian insufficiency (POI), 665, 666 Preoperative assessment, 280 Preoperative care alternative therapies, 743 anaesthetic pre-assessment, 748 anticoagulants, 746–747 biochemical investigations, 747 blood glucose control, 747 bowel preparation, 749 complementary/alternative medication, 744 deferral of surgery, 744 ECG, 747 haematological investigations, 747 herbal medication, 744–746 hormonal therapy, 744, 746 imaging, 747–748 infection screening, 750 information leaflets, 743–744 informed consent, 748 capacity to, 748 knowledge, 748–749 volition, 748 nurse assessment, 744 physical fitness for surgery

I-19 anaemia, 744 concomitant medication, 744 intercurrent illness, 744 smoking, 744 weight loss, 744 prophylactic antibiotics, 750 pulmonary assessment, 748 thromboprophylaxis, 749–750 urinalysis, 747 VTE, patient-related risk factors for, 750 Prepuce, 723 Pressure transmission ratio (PTR), 299 PRM, see Puborectal muscle PRO, see Patient-reported outcome Probiotics, 622 Procidentia, 47 Proctogram, 704 Program to Reduce Incontinence with Diet and Exercise (PRIDE), 415 Progressive disease and ageing, impact of, 558 Prolapse and incontinence sexual questionnaire (PISQ), 112 Prolapsed ureterocele, 1228, 1230 Prolapse QoL (P-QoL) questionnaire, 146 Prolapse surgery anterior vaginal wall prolapse, 891–900 cost, 1117 Prolapse uteri, 47 PROMIS, see Patient-Reported Outcomes Measurement Information System ProMIS™, 1055 PROMs, see Patient reported outcome measures Pronephros, 184 Propantheline bromide, 462 Prophylaxis, 620 Propiverine, 465–466 Propranolol, 475 Prostaglandins (PGs), 248, 467–468 Prosthetic materials, 893 Proteus mirabilis, 250 PRP, see Platelet-rich plasma PRV, see Pseudorabies virus Pseudoephedrine, 475 Pseudomonas aeruginosa, 250 Pseudorabies virus (PRV), 212–213 PSTB, see Patient satisfaction with treatment benefit questionnaire Psychological symptoms, 668 Psychological therapies, 707 PTNS, see Percutaneous tibial nerve stimulation PTR, see Pressure transmission ratio Puboanal muscle (PAM), 172 Pubocervical fascia, 168 Pubococcygeal line (PCL), 365 Puborectalis muscle, 1038 Puborectal muscle (PRM), 172–173 Pubovaginal muscle (PVM), 172–173, 176 Pubovaginal sling (PVS), 740, 765–768 Aldridge sling, 766 autologous fascial, 767–769 complications of surgery, 792 materials, 768–770 allografts, 769–770 synthetics, 770 xenografts, 770 operative procedure, 787–791

abdominal wound closure, 791 adjusting sling tension, 790 fascial harvest, 788–789 outcomes of autologous PVS surgery, 791–792 patient positioning and preparation, 788 postoperative care, 790–791 preoperative considerations, 787–788 sling placement and fixation, 789–790 vaginal dissection, 789–790 outcomes, 768 procedures, 765–766 for SUI, 787–793 surgical management of voiding dysfunction after surgery, 792–793 Pubovesical muscles, 164 Pudendal nerve motor terminal latencies (PNMTL), 685 Pudendal nerve stimulation, 513–514 anatomy, 513 results, 513–514 technique, 513 working mechanism, 513 Pudendal nerve terminal motor latency (PNTML) test, 334 Pudendal neuropathy, 334 Pull-through vaginoplasty, 1242 Pulsion enterocele, 905 PUSC, see Pontine urine storage center PUV, see Posterior urethrovesical angle PVdR, see Paravaginal defect repair PVM, see Pubovaginal muscle PVS, see Pubovaginal sling P2X3 receptor, 229 P2X receptors, 229 ‘Pyramid’ exercise, 424–425 Pyridium test, 275 Pyuria, 610 Pyxus HD Move, 1055

Q QALY, see Quality-adjusted life-year QoL, see Quality of life Quality-adjusted life-year (QALY), 81–82, 154, 158–160 Quality of life (QoL), 577 definition, 89 nocturia and, 248–249 stigma of incontinence, 12–14 in women with POP, 145 Quantitative sensory testing, 325 Questionnaire for assessment of faecal incontinence and constipation, 122 Questionnaires, 543

R Radiofrequency energy treatment, 693 Radiofrequency (RF) technology, 1262 Radiofrequency therapy collagen denaturation/micro-remodeling, 527–528 cryogen-cooled monopolar, 528 Radiopaque markers, 704 RAIR, see Recto-anal inhibitory reflex Raised BMI, 29

Index

I-20 Rayon, 450 Raz, Shlomo, 762 Readjustable slings, 822; see also REMEEX system; SAFYRE sling κ-receptor agonist, 220 μ-receptor antagonist, 220 Recruitment biofeedback, 428–429 Rectal bladder diversions, 1215–1216 Rectal irrigation, 707 Rectal prolapse, 905 Recto-anal inhibitory reflex (RAIR), 1038 Rectoceles, 708–709, 912–922 additional considerations continued defecatory dysfunction after rectocele repair, 922 dyspareunia, 921–922 genital hiatus, size of, 921 postoperative urinary retention, 922 anatomy, 912 clinical presentation patient symptoms, 912–913 physical examination, 913 diagnostic studies anal manometry, 914 defecography, 913–914 electromyography, 914 imaging studies, 913 magnetic resonance imaging, 914 nerve conduction studies, 914 ultrasonography, 914 etiology, 912 non-surgical management, 914 results/complications abdominal sacrocolpopexy (colpoperineopexy) with/without concurrent ventral rectopexy, 921 graft-augmented rectocele repair, 919–921 site-specific rectocele repair, 918–919 traditional posterior colporrhaphy with midline plication, 918 risk factors for, 912 surgical management, 914–918 abdominal sacrocolpopexy (colpoperineopexy) with/without concurrent ventral rectopexy, 918 graft-augmented posterior repair, 917–918 posterior colporrhaphy with midline plication, 915–916 site-specific rectocele repair, 916–917 Rectovesical septum, 912 Rectus sheath, 1049 Recurrent bacterial cystitis, 610–611 Recurrent urinary tract infection (rUTI), 733 “Referred visceral pain,” 580 Reflex micturition control, 207 Reflex voiding, 560 Regenerative medicine biomaterials, 197 tissue engineering, 197–204 Relaxation BFB, 430 Reliability, 84, 90, 270 test–retest, 84 REMEEX system, 829–835 adjustment technique, 831–835 clinical data, 834 device and surgical technique, 831 features of, 829–831

Renal circadian rhythms, 248–249 Resiniferatoxin (RTX), 474 Resources, 454–455 Responsiveness, 84–85, 90 Retropubic mid-urethral sling (MUS) surgery, 795–803 clinical outcomes, 796–797 complications, 801–802 cough test, 796 in intrinsic sphincter deficiency, 798 long-term post-operative complications, 802 autoimmune disease, 802 De novo malignancy, 802 dyspareunia, 802 erosion/exposure/extrusion/ perforation, 802 pain, 802 long-term results, 797 in mixed urinary incontinence, 799–800 in obese women, 798–799 pregnancy and delivery after, 800 recurrent urinary incontinence, 797–798 removal/cutting, 803 retropubic top to bottom retropubic approach, 796 sexual function after, 800–801 technique, 796 Retropubic suspensions, 739–740 Retropubic tape (RPT), 807–815 Retropubic urethropexy, 44, 776–783 colposuspension, 778–783 history, 776–777 MMK, 777 Reverse pyramid, 425 Re-void, need to immediately, 280 Rhabdomyosarcoma, 1230–1231 Ribosomal RNA (rRNA) genes, 394 16s ribosomal RNA (rRNA) genes, 394 Rigid cystoscopes, 373 procedure, 375–376 bladder biopsy, 376 cystodistension, 375–376 intra-/post-operative assessment, 376 Robotic-assisted laparoscopic sacrocolpopexy (RSC), 971 Robotic surgery, 1109–1113 alternative surgical robots, 1109 burch colposuspension, 1111 complications, 1111 cost associated with, 1109–1110, 1117 cost-effectiveness, 1119–1121 open vs. laparoscopic vs. robotic sacrocolpopexy, 1120–1121 open vs. robotic sacrocolpopexy, 1120 outcome, 1119–1120 robotic vs. laparoscopic sacrocolpopexy, 1120 vaginal apical suspension vs. laparoscopic vs. robotic sacrocolpopexy, 1121 credentialing in, 1059 da Vinci® system, 1109–1110 hysteropexy, 1111 learning curve associated with, 1112 patient side training for, 1057 robotic console training, 1057–1058 dry laboratory training, 1058 online modules for, 1057

VR simulators for, 1057–1058 wet laboratory training, 1058 role of, 1109–1113 sacrocolpopexy, 1110–1111 safety in, 1112–1113 surgeon ergonomics in, 1113 training in, 1111–1112 courses, 1112 dual console, 1112 live surgery and proctoring, 1112 training/simulation, 1056–1058 vesicovaginal fistula repair, 1111 Robotic training/simulation, 1056–1058 Rome IV Criteria, 700 Rostral pontine reticular formation (RPRF), 209 RPRF, see Rostral pontine reticular formation RPT, see Retropubic tape RSC, see Robotic-assisted laparoscopic sacrocolpopexy

S SAC, see Sacral promontory Sacral hysteropexy, 52 Sacral motor system, conduction studies of, 334–335 anterior sacral root (cauda equina) stimulation, 334–335 central motor pathways, assessment of, 335 Sacral nerve stimulation (SNS), 159–160, 509, 690–691, 708 Sacral neuromodulation (SNM), 517–523, 546, 560, 574–575, 690–691 adverse events, 522 ambulatory urodynamics, 320 devices, 518 follow-up visits, 522 mode of action of, 517 for NOUR, 521–522 for OAB, 517–521 optimal lead placement, key steps to, 518 preoperative evaluation, 517–518 results, 519–520 surgical technique, 518 Sacral promontory (SAC), 172–173, 1091 anatomy of, 1077–1079 fixation, 1082 Sacral reflexes, 336–337 diagnostic usefulness of, 337 on mechanical stimulation, 337 methods, 336–337 penis/clitoris, on electrical stimulation of, 337 physiological background, 336 terminology, 336 Sacral sensory system, conduction studies of, 335–336 anal canal, electrical stimulation of, 336 bladder, electrical stimulation of, 336 cortical somatosensory evoked potentials, 335–336 urethra, electrical stimulation of, 336 Sacrocolpopexy (SCP), 52, 1077–1085 abdominal mesh, 1124 challenge in, 1124 complications, 1085, 1124 cost associated with, 1117

Index definition, 1077 haemorrhage, intraoperative complication of, 1124 vs. laparoscopic sacrocolpopexy, 1077 advantage of, 1077 anatomic considerations, 1077–1078 vs. ASC, 1077 clinical assessment, 1078 comparative studies, 1084–1085 complications, 1085 concomitant anti-incontinence surgery, 1083 concomitant laparoscopic hysterectomy/subtotal hysterectomy, 1083 contraindications, 1079 indications, 1078–1079 NOTES (natural orifice transluminal endoscopic surgery), 1082–1083 patient selection, 1078 prosthesis used for, 1081–1082 results, 1083–1084 sacral promontory, anatomy of, 1077–1079 vs. sacrocolpopexy, 1077 surgical technique, 1079–1082 overview, 1077 robotic surgery, 1110–1111 Sacrohysteropexy anatomical anomalies, 1091 broad ligament, 1091, 1093 pelvic sidewall, 1091, 1093 sacral promontory, 1091, 1093 disadvantages, 1095 laparoscopic, 1088–1095 aims of, 1090 indication, 1088 outcomes, 1091, 1094–1095 mesh, use of, 1090 outcomes, 1091, 1094–1095 efficacy data, 1094–1095 in older patient, 1095 in pregnancy, 1095 safety data, 1091, 1094 oxford hysteropexy, 1090–1091 day of surgery, 1090–1091 preoperative preparation, 1090 uterine preserving prolapse surgery, history of, 1088–1090 abdominal approach, 1089 laparoscopic approach, 1089–1090 vaginal approach, 1089 uterine prolapse, traditional approach for, 1088 Sacroneuromodulation (SNM), 1031–1032 Sacrospinous fixation at hysterectomy, 929 Sacrospinous hysteropexy, 927 Safety Attitude Questionnaires (SAQs), 61 SAFYRE sling, 822–829 features, 822 readjustment technique loosening, 827 tightening, 827 retropubic placement through transvaginal/suprapubic approach, 822–823 SV technique, 822, 824 VS technique, 822–823

I-21 transobturator approach (SAFYRE T), 823–825 crossover techniques, 828–829 and urethral reconstruction, 826–827 Saline, cystometry filling medium, 291 SAQs, see Safety Attitude Questionnaires Satisfaction with medication questionnaire (SATMED-Q), 104 SATMED-Q, see Satisfaction with medication questionnaire Saturation, 83 SCENIHR, 795–796 SCNT, see Somatic cell nuclear transfer Scopolamine, 460, 462 SCP, see Sacrocolpopexy Screening tools (screeners), 99 SECCA® procedure, 1029 Secondary constipation, causes of, 699 Selective serotonin reuptake inhibitors (SSRIs), 220 Self-administered PRO questionnaires, 84 Self-Assessment Goal Achievement (SAGA) questionnaire, 108 Self-catheterisation, 573 Self-stigma, 11 Sensory nerves receptor, 228 Sensory neurogram, 327 SEPs, see Somatosensory evoked potentials Serotonin (5-HT), 220 Serotonin–norepinephrine reuptake inhibitor (SNRI), 469 Sex, 1270 Sex-determining region of Y chromosome (SRY), 1219 Sex development, 1219, 1223–1225 Cloacal malformation, 1225 Complete Androgen Insensitivity Syndrome, 1224 congenital adrenal hyperplasia, 1223–1224 gonadal dysgenesis, 1224 psychology, 1225 Turner syndrome, 1224–1225 Sexual activity, problems associated with interstitial cystitis/painful bladder syndrome, 657 obstetric trauma and anal incontinence, 657–658 pelvic floor overactivity, 656–657 POP (see Pelvic organ prolapse (POP)) Sexual Function Questionnaires, 651 urinary incontinence, 651–652 urinary tract infections, 657 vaginal laxity, 656 in women with pelvic floor dysfunction, 650–651 Sexual differentiation, external, 181 Sexual dysfunction, 102, 669 need for questionnaires, 111 questionnaires, 102–103 Sexual function assessment development of measures, 114 female, 111–112 outcome measures, female sexual health research clinician measures, 113 objective measures, 112 subjective measures, 112

PFD, 111, 113–114 PRO measures to, 111 questionnaires to, 111–116 FSD, 114–116 need for, 111 Sexual function questionnaires (SFQ), 111–116, 651 Sexual health, 111 Sexual health assessment in women with pelvic floor dysfunction, 650–651 Sexual health-care provider assessment clinical history, 714–715 physical examination, 715 validated questionnaires, 715 Sexual orientation, 1270 Sexual pain management, 723–724 clitoris, prepuce, and frenula, 723 urethral meatus, 724 vulva/vestibule, 724 SF-6D measures, 154 SFEMG, see Single-fiber EMG SFQ, see Sexual function questionnaire Short pad tests, 273–275 detection limit, 273 ICS 1-hour pad test, 273–274 versus long-duration pad tests, 276–277 modified 1-hour pad tests, 274–275 pelvic organ prolapse on, impact of, 275 pyridium test, 275 Sildenafil, 470 Silodosin, 480 SIMS, see Single-incision mini-slings Simulation, 1054 laparoscopic pelvic floor surgery, 1054–1055 robotic surgery, 1056–1058 Simulation-based training of surgical teams, 61–62 Single-fiber EMG (SFEMG), 329 Single-incision mini-slings (SIMS), 817–821 complications, 820–821 indications for, 817 outcomes, 819–820 patient selection for, 817 surgical technique cystoscopy, 819 insertion of sling, 818–819 patient positioning, 817 preoperative considerations, 817 preparation of sling, 818 vaginal closure, 819 vaginal flap dissection, 818 vaginal incision, 817–818 types of, 817 SIS, see Small intestinal submucosa SK channels, 227 Skene’s glands (paraurethral glands), 1228, 1230 Skin-flap vaginoplasty, 1242 Sleeve gastrectomy, 569 Slings, 356–358, 822; see also specific slings Slow stream, 280, 849 Slow transit, 705 Slow-twitch muscle fibers, 736 Slow urinary stream, 260 Small intestinal submucosa (SIS), 197 SmartPill wireless motility capsule (WMC), 705

Index

I-22 SMAS, see Superficial muscular aponeurotic system SMCs, see Smooth muscle cells Smoking, 262, 744 Smooth muscle, embryology, 183–184 Smooth muscle cells (SMCs), 199 sMUS, see Synthetic mid-urethral slings SNM, see Sacral neuromodulation; Sacroneuromodulation SNRI, see Serotonin–norepinephrine reuptake inhibitor SNS, see Sacral nerve stimulation Social history, 262 Solifenacin, 462–463 Solomon-Greenwell nomogram, 571 Solyx SIS system, 817 Somatic cell nuclear transfer (SCNT), 198 Somatic pathways, micturition, 207 Somatosensory evoked potentials (SEPs), 327 Sonic hedgehog (Shh), 181 SOX9 gene, 1219 Sphincter EMG, 311 Sphincters, 184 SphinKeeper™ (SK), 1029 Spinal cord injury, 554–555 compressive spondylotic myelopathy, 555 ischemic, 555 traumatic, 554–555 Spinal dysraphism, 556 Spinal reflex pathways, micturition, 209 Spinning disc method, 281 Spinobulbospinal reflex pathways, 210 Splitting, urine stream, 280 S-POP system, 880 Sports and fitness activities assessment of incontinence during physical activity, 680 consequences of SUI during physical activity, 681 pelvic floor and female athletes, 681–682 physical activity causing urinary incontinence, 681 prevalence of UI among participants, 680–681 protection during exercise to prevent leakage, 682 treatment, 682–683 Spraying (splitting) of urine stream, 280 SPT, see Suprapubic tube SSR, see Sympathetic skin response SSRIs, see Selective serotonin reuptake inhibitors St. Mark’s incontinence score, 123 Stages of Reproductive Aging Workshop +10 staging system, 666 Stamey, Tom, 760–762 Standardization of terminology and methods (ICS), lower urinary tract dysfunction, 238 Staphylococcus, 387 Staphylococcus aureus, 250 Stapled transanal rectal resection (STARR), 909 STARR, see Stapled transanal rectal resection Stem cells, 197–198 research, 8 therapy, 693 Sterilization, 966–967

Steroidogenic factor 1 (SF1), 1219 Stigma of incontinence, 10–14 association with, 10–12 and attitudes, 13–14 avoidance of, 11 basis, 10 and beliefs, 13–14 bladder and bowel control, lack of, 12–13 care-seeking, effect on, 13 cycle of, 11 definition, 10 national organizations, role of, 14 patient-centered care, 14 types, 11 UI in different ethnic groups, perceptions about, 11–12 Stimulated muscle transposition, 692 Stomas, 693, 1033–1034 Stool softeners, 706 Straining, to void, 259, 280 Strength training, 424–425 Stress incontinence, 669 Stress urinary incontinence (SUI), 19, 525 anatomic theories, 736–737 artificial urinary sphincter for, 837–845 behavioral therapies for, 410–412 classification, 737 CO2 laser therapy in, 526 complications of surgery, 860–865 ACT balloons, 864–865 AUS, 863–864 bladder erosion, 861–862 bladder injuries, 860–861 bowel perforations, 861 bulking agents, 865 colposuspension, 863 de novo urgency, 862 dyspareunia, 863 groin and thigh pain, 862–863 hemorrhage, 861 midsuburethral slings, 860 pubovaginal slings, 863 standardized classification, 865 urethral erosion/injury, 862 urethral injuries, 860–861 UTIs, 862 vaginal extrusion, 861 vaginal perforation, 861 voiding dysfunction, 862 consequences during physical activity, 681 conservative/behavioral therapy for, 157 defined, 680 definition, 736, 1061 drugs used in treatment of, 459 duloxetine therapy in, 528–529 electrical stimulation for, 501–504 Er-YAG laser therapy in, 525–526 familial and genetic factors and, 29 function/activity-based classification, 238–240 history, 258 hypothesis for genesis of, 26–27 integral theory, 737–738 intrinsic dysfunction theories, 737 mechanism, 736 mid-urethral slings in, 740–741 MRI for, 363–365 past medical history, 261

pathophysiology, 44, 787 pessaries for, 437–439 effectiveness, 437–438 mechanism of action, 437 vaginal and urethral devices, other types of, 438 PFMT in, 31 platelet-rich plasma therapy in, 527 postpartum in, 26 prevalence, 256 progression/remission, natural history of, 26–27 pubovaginal slings in, 740 PUV angle, 737 PVS for, 787–793 radiofrequency therapy in, 527–528 collagen denaturation/microremodeling, 527–528 cryogen-cooled monopolar, 528 recurrence following vault prolapse surgery, 35 retropubic MUS for, 795–803 retropubic suspensions in, 739–740 surgery for, 35, 158 colposuspension, 35 concomitant, 35 failed, prevention of, 35–36 history of, 43–45 midurethral tape procedures, 35 midurethral tapes vs. colposuspension, 35 prolapse, 35 trends, 55–56 surgical management of, 757 age, parity, estrogenization, and body mass index, 757 aim, 757 anterior colporrhaphy, 758–759 bone anchoring, 763–765 bulking agents, 770–771 four-corner vaginal patch, 765 individual choices, 757 literature, interpreting, 757–758 needle suspensions, 760–763 paravaginal defect repair, 759–760 pubovaginal sling, 765–770 randomized controlled trial in, 757–758 surgical procedures, 738 symptom, 258 tissue implants for, 250–251 TOT sling for, 807–815 transvaginal suspension in, 739–740 urethral injection therapy, 739 urethral mobility theories, 736–737 Striated urogenital sphincter, 164–166 Stricturotomy, 575 Stroke, 550–551, 675–676 Strong desire to void (SDV), 293 Structured Query Language (SQL) server, 135 Subcortical modulation of micturition, 213–214 basal ganglia, 214 cerebellum, 214 hypothalamus, 214 substantia nigra pars compacta, 214 ventral tegmental area, 214 Submucosal vasculature, 166–167 Substantia nigra pars compacta, 214 SUI, see Stress urinary incontinence

Index Superabsorbent polymer (SAP), 449–450 Superficial muscular aponeurotic system (SMAS), 1263 Suprapubic catheters, 445–446 Suprapubic tube (SPT), 445–446 Supraspinal pathways, micturition, 209 Surgical team training interventions, 61–62 Sympathetic pathways, micturition, 207–208 Sympathetic skin response (SSR), 338 Sympathomimetic drugs, 261 SYMPHONY trial, 225 Symphysis orifice (SO) distance, 348 Symptoms, 256 coital incontinence, 258 haematuria, 261 insensible incontinence, 258 LUTS, 256 mixed urinary incontinence, 258 nocturia, 258–259 nocturnal enuresis, 259 nocturnal polyuria, 259 OAB, 259 POP, 145, 260–261 postural urinary incontinence, 258 scores, 269–270 SUI, 258 urgency urinary incontinence, 257–258 urinary incontinence, 256–257 urinary urgency, 257–258 voiding, 259–260 SYNERGY study, 225 Synthetic meshes, 965 boundary conditions, 982–984 complications, 972–973, 990–998 after sacrocolpopexy, 994–995 after transvaginal mesh, 995–998 FDA warnings, 990–991 IUGS-ICS Classification System for, 991–992 management of, 993 for mid urethral sling, 993–994 modifiable risk factors for, 992–993 patient selection to avoid, 992 standardized terminology and classification for, 991–992 surgical technique/mesh selection to avoid, 992 factors influencing host response, 976–979 fiber pattern, 977–978 filament type, 977 material type, 977 mesh weight, 979 pore size, 978–979 FDA warnings on, 990–991 implanted in vagina, host response to, 974–976 overview of, 971–972 professional society guidelines for, 991 prolapse, characteristics of, 973 structural properties, 974 host response to synthetic meshes implanted in vagina, 974–976 stiffness, 974 ultimate elongation, 974 ultimate load, 974 textile properties, 973 material, 973 mesh weight, 973

I-23 pore size, 973–974 porosity, 974 vaginal mesh implants, considerations for, 979 biological environment, 979–980 mechanical environment, 980–982 Synthetic mid-urethral slings (sMUS), 158 Synthetic polymers, biomaterials, 197 Synthetics, 770

T Tachykinins, 473 Tadalafil, 470 Tamsulosin, 479–480 TCAs, see Tricyclic antidepressants T cells, 199 Teamwork, 60–61 Technical skills training, surgical simulators for, 62–63 Tension-free vaginal tape (TVT) surgery, 795–803 clinical outcomes, 796–797 complications, 801–802 cough test, 796 in intrinsic sphincter deficiency, 798 long-term post-operative complications, 802 autoimmune disease, 802 De novo malignancy, 802 dyspareunia, 802 erosion/exposure/extrusion/ perforation, 802 pain, 802 long-term results, 797 in mixed urinary incontinence, 799–800 in obese women, 798–799 pregnancy and delivery after, 800 recurrent urinary incontinence, 797–798 removal/cutting, 803 retropubic top to bottom retropubic approach, 796 sexual function after, 800–801 technique, 796 Terazosin, 479 Terbutaline, 468 Testosterone, 1276 Tetracyclines, 619 TGF-β, 229 TGF-β receptor (TGF-βR), 247 THD Gatekeeper™ Delivery System, 1028–1029 Thick transverse vaginal septum, 202 3-D bioprinting techniques, 251 3-D female pelvic floor reconstruction, 370–371 3-D ultrasonography, 359–360 Thromboprophylaxis, 749–750 Tibial nerve stimulation, 559 Timed voiding, 413–414 Time to maximum flow, urine flow, 281 Tissue engineering biomaterials in, 197 bladder, 200–201 cells for, 197–199 adipose-derived stem cells, 199 adult stem cells, 198–199 amnion-derived stem cells, 198 bone marrow stem cells, 199

cord blood stem cells, 199 hESCs, 197–198 laboratory-generated stem cells, 198 native progenitor cells, 198–199 female reproductive organs approaches in ovarian biology, 202–204 autologous transplantation, 202 ovarian tissues from stem cells, regenerating, 202 ovary, 202 uterine cervix, 201–202 uterus, 201 vagina, 202 lower urinary tract, 199–200 Tissue implants for pelvic floor support, 250–251 for SUI, 250–251 T-LESS, see Transvescial laparoendoscopic single-site surgery Toileting aids, 453–454 commodes, 453 external collecting devices, 453–454 odor control, 454 resources, 454–455 urinals for females, 453 early childhood, 10 Toll-like receptors (TLRs), 613 TOLT, see Tolterodine Tolterodine (TOLT), 461–463 TOT, see Trans-obturator tape Total colpocleisis, 932 Total genital prolapse, 48 Trabecular bone, 670 Traction enterocele, 905 Training in diagnosis/management of perineum, 1009–1010 laparoscopic, for urogynecology, 1055–1056 of pelvic floor surgery, 1054–1058 in robotic surgery, 1111–1112 Training/control biofeedback, 429 Tramadol, 220, 473 Trampoline theory, 738 Transabdominal VVF, 1152–1155 conventional laparoscopy, 1154 indications for, 1152–1153 minimally invasive transabdominal approaches, 1154–1155 outcomes, 1157–1158 robot-assisted laparoscopic repair, 1155 timing of repair, 1152 Transdermal oxybutynin formulations, 545 Transgender, 1270 Transgender and gender diverse (TGD) populations, 1270 definitions, 1270 genital gender-affirming surgery for, 1271–1275 hormonal transition, 1271 hormone management of, 1276 metoidoplasty for, 1277 pelvic health maintenance, 1278 phalloplasty, 1277–1278 societal context, 1270–1271 surgical management for, 1276–1277 surgical options for, 1271

Index

I-24 terminology, 1270 trauma-informed care, 1270–1271 vaginoplasty, 1271–1275 complication rates of, 1274–1275 health maintenance after, 1275–1276 preoperative surgical preparation and counseling, 1274 Transient receptor potential (TRP), 229 Transition, 1271 Transmitter signal pathways, 208 Trans-Obturator Post-Anal Sling (TOPAS) system, 1029 Trans-obturator tape (TOT) sling, 740–741, 807–815 anatomy, 807–808 clinical performance of, 811–815 complications for, 814 history, 807 outcomes for, 812–813 overview, 807 surgery anesthesia, 808 patient position, 808 postoperative care, 811 prosthesis/surgical instruments, 807–808 technique, 807–811 Transperineal ultrasound (TPUS) technique, 352–353 Transvaginal mesh (TVM), 965, 995–998 FDA general recommendations for, 990–991 mesh-related complications after, 995–998 dyspareunia/pelvic/vaginal pain, 997–998 mesh exposure, 996–997 visceral injury, 998 Transvaginal mesh (TVM) implantations, 52–53 Transvaginal NOTES surgery (vNOTES), 1082–1083, 1127–1128 Transvaginal sacrospinous fixation, 51 Transvaginal suspension, 739–740 Transvaginal tape (TVT), 738, 740–741, 795–803 Transverse vaginal septa (TVS), 1219–1221 Transvescial laparoendoscopic single-site surgery (T-LESS), 384 Traumatic brain injuries, 552–553 Treatment Satisfaction Questionnaire for Medication (TSQM), 81, 104 TrEndo, 1055 Tricyclic antidepressants (TCAs), 469–470 Trigone, 164 anatomy, 164 embryological development, 184–186 Trimethoprim, 619 Trocars complications, 1100–1101 secondary, 1101 site/incisional hernias, 1101 Trospium, 463–464 TRP, see Transient receptor potential True hernia, 905 “True visceral pain,” 580 TSQM, see Treatment Satisfaction Questionnaire for Medication Turner syndrome, 1224–1225

TVM, see Transvaginal mesh TVS, see Transverse vaginal septa TVT, see Transvaginal tape TVT-Secur, 817 Type 1 polypropylene mesh, 1090

U UAB, see Underactive bladder syndrome UD, see Urethral diverticulum; Urinary diary UDS, see Urodynamics UI, see Urinary incontinence U-IIQ, see Urge incontinence impact questionnaire UIQ, see Urinary incontinence questionnaire Ultrasonography, 7–8, 352–361 in anterior compartment assessment, 354–355 basic approach, 352–353 bladder neck, mobility of, 353–354 urethra, mobility of, 353–354 3D, 359–360 4D, 359–360 in implants mesh, 358–359 sling, 356–358 overview, 352 in posterior compartment, 355–356 rectocele, 914 TPUS technique, 352–353 in urogenital prolapse, 354 Ultrasound assessment, 569 Umbilical artery, 1050 Umbilical cord blood (UCB) stem cells, 199 Umbilicus, 1049–1050, 1053 Underactive bladder syndrome (UAB), 247 antifibrotic strategies, 247 ECM and, 247 risk factors for, 247 UP3, see Uroplakin III UPP, see Urethral pressure profile Upper urinary tract (UUT) embryological development, 184–186 imaging of, 343 intravenous urography, 343 techniques, 343 UPR, see Urethral Pressure Reflectometry Urachus, 179 UR-CHOICE risk calculator, 31 Ureteral reimplantation, 385 Ureteric buds abnormal development, 184 branching morphogenesis, 184 formation, 184–186 Mackie and Stephens hypothesis, 184, 186, 192 Ureterocele, 192–194, 382 Ureterofallopian fistulae, 1137 Ureterointestinal anastomosis, 1214 Ureteroneocystostomy, 1181–1182 Ureterovaginal fistulae (UVF), 1136–1137, 1176 treatment of, 1180–1181 Ureter(s) ectopic, 191–192 embryological development, 179, 182, 184 Urethra anatomy, 164–167

catheters/catheterization of, 441–443 definition, 441 designs/materials, 441–442 size and length, 441–443 connective tissue of, 167 embryological development, 179 function, 298 glands of, 167 leak point pressure measurement, 301–303 abdominal, 302–303 detrusor, 301–302 loss of paraurethral support, 737 mobility, ultrasonography of, 353–354 mobility theories, 736–737 MRI of, 364 mucosal lining of, 167 pain, 260 pipe-stem, 303 position and mobility of, 174–177 pressure correlated measurement of, 303–304 definition, 298 filling urethro-cystometry for, 299–300 high-definition signals catheters, 305 instability, 300 LPP measurement, 301–303 measurements, 298–305 MUCP, 300–301 profilometry, 300–301 PTR, 299 reflectometry, 303–304 techniques, 298–299 urethral sleeve sensor, 305 URRP, 304–305 variation, 300 smooth muscle of, 165–166 striated urogenital sphincter, 164–166 submucosal vasculature of, 166–167 testing of function, 298–305 air-charge catheters, 299 correlated measurement of urethral pressure, 303–304 high-definition signals catheters, 305 LPP measurement, 301–303 microtip transducer catheters, 298–299 purposes of, 298 urethral sleeve sensor, 305 URRP, 304–305 water perfusion technique, 298 topography of, 165 Urethral bulking agents, 44–45 Urethral crest, 375 Urethral diverticulum (UD), 377, 1189–1199 anatomy, 1189–1190 anterior vaginal wall lesions, differential diagnosis of, 1190 associated conditions, 1190 classification systems for, 1193–1194 etiology, 1189 evaluation/diagnosis, 1190–1194 cystourethroscopy, 1192 history, 1191–1192 imaging, 1192 MRI studies, 1193 periurethral lesions, differential diagnosis of, 1191 physical examination, 1191–1192 radiography, 1192–1193

Index ultrasound, 1193 urine studies, 1192 urodynamics, 1193 management, 1194–1199 complications, 1198–1199 conservative, 1194–1195 diverticular excision and repair, 1195–1196 postoperative, 1196–1198 results, 1198–1199 surgical, 1195 pathophysiology, 1189 presentation, 1189–1190 signs and symptoms of, 1190 Urethral fistula, 377 Urethral hypermobility, 737 Urethral injection therapy, 739 Urethral masses, 377–378 Urethral meatus, 724 Urethral polyps, 1231–1232 Urethral pressure profile (UPP), 333 Urethral pressure profilometry (UPP), 300–301, 571–572 Urethral Pressure Reflectometry (UPR), 303–304 Urethral prolapse, 1230 Urethral retro-resistance pressure (URRP), 304–305 Urethral sleeve sensor, 305 Urethral sling surgery, 43–44 Urethral smooth muscle, 165–166 Urethral stricture, 570, 1201–1208 anatomy, 1201 conservative management of, 1202–1203 diagnosis of, 1201–1202 endoscopic management of, 1203 etiology, 1201 salvage procedures, 1207–1208 treatment of, 1202 urethroplasty, 1203–1207 distal urethrectomy with advancement meatoplasty, 1204–1205 distal urethroplasty with vaginal/ vestibular inlay flaps, 1205–1206 vaginal flap urethroplasty, 1206–1207 Urethritis, 376–377 Urethrolysis failure of, 856 goal of, 854 results, 849 retropubic, 856 series on, 853–854 transvaginal, 855–856 Urethropelvic angle, 348 Urethroscope, 373 Urethrovaginal fistula (UVF), 1137, 1185–1188 concomitant procedures, 1188 operative technique, 1185–1186 postoperative care and considerations, 1187–1188 preoperative considerations, 1185 tissue interposition, 1186–1187 Urge incontinence, 158 behavioral therapies for, 412–413 urge suppression strategies, 412–413 Urge incontinence impact questionnaire (U-IIQ), 95 Urgency, 29, 293

I-25 Urgency, de novo, after anti-incontinence surgery, 848 Urgency urinary incontinence (UUI), 19 history, 257–258 hypothesis for genesis of, 26–27 mobility impairment and, 29 progression/remission, natural history of, 26–27 symptom, 257–258 Urge suppression strategies, 412–413 Urge urinary distress inventory (U-UDI), 95 Urinals for females, 453 Urinalysis, 387–390 analysis specimen collection, 387–388 biochemical testing, 388 bilirubin, 389 blood, dipsticks for, 388 glucose, dipsticks for, 389 ketones, dipsticks for, 389 leukocyte esterase/nitrates, dipsticks for, 388 pH of urine, 389 protein, dipsticks for, 388–389 specific gravity, 389 urobilinogen, 389 microscopy of urine, 389–390 for casts, 390 epithelial cells, 389–390 for red blood cells, 390 white cells, 389–390 physical examination, 388 preservation specimen collection, 387 specimen collection, 387 Urinary diary (UD), 266 Urinary diversion, 1213 continent, 1214–1216 continent catheterizable pouches, 1215 Indiana Pouch, 1215 orthotopic urinary diversions, 1216 rectal bladder diversions, 1215–1216 incontinent, 1213–1214 colon conduit, 1213–1214 ileal conduit, 1213–1214 jejunal conduit, 1214 ureterointestinal anastomosis, 1214 minimally invasive reconstruction, 1216–1217 Urinary incontinence in girls, 1232–1237 bilateral single ectopic ureters, 1237 causes of, 1232–1234 bladder overactivity, 1233 dysfunctional voiding, 1233 enuresis, 1233 functional urinary incontinence, 1232–1233 giggle incontinence, 1233 stress urinary incontinence, 1234 vaginal voiding, 1233–1234 voiding dysfunction, 1233 duplicated ectopic ureters, 1235–1237 bypass of sphincter mechanism, 1237 etiology, 1232 mechanisms of, 1232 neurogenic, 1234–1235 abnormal sphincter, 1235 bladder neck, 1235 myelomeningocele, 1234–1235 urethral control mechanisms, 1235

Urinary incontinence questionnaire (UIQ), 95 Urinary incontinence (UI), 17, 651–652 BoNT for treatment of patients with, 490–497 causes of, 257 childbirth and, 29–30 classification of symptoms into groups, 257 coital incontinence (CI), 651 CS for, 32 economic aspects of, 152–160 AQoL, 154 CBA, 154 CCA, 154 CEA, 154 CMA study, 154 cost of illness vs. economic analysis studies, 152–153 CUA, 154, 156–157 15D, 154 decision analysis, 155–156 EQ-5D, 154 formal economic analyses, 154 HUI, 154 PTNS, 159 QALYs, 154–156 SF-6D measures, 154 SNS, 159–160 studies of multiple antimuscarinic agents, 159 studies regarding botulinum toxin type A (Botox A) injections, 159 effect of UI treatment on sexual function, 651–653 in elderly women, 17 global health economic consequences, 22–23 history, 256–257 hysterectomy and, 34 incidence/regression of, 20 magnetic stimulation to treat, 505–506 Medical, Epidemiological, and Social Aspects of Aging questionnaire, 102 natural history of of progression and remission, 26–27 SUI, 26–27 UUI, 26–27 obesity and, 29 PFMT in, 31 physiotherapy for, 420–430 prevalence, 17–19, 256 questionnaire for symptoms, 257 risk calculator, 31 risk factors on prevalence of, 19–20 risk groups/factors, 28–29 age, 28 familial and genetic factors, 29 HRT, 28–29 obesity and, 29 overactive bladder, 29 UUI, 29 symptom, 256–257 in women vs. men, 17 Urinary leakage, 17, 19 Urinary microbiomes, 394–396, 598 application to clinical practice, 396 bacterial urinary microbiota, 394–395 in bladder cancer, 396 culture or DNA sequencing, 599

Index

I-26 in interstitial cystitis/bladder pain syndrome, 396 normal microbiome of urine and adjacent anatomical sites, 599 in OAB, 395 in recurrent urinary tract infections, 395–396 sampling of urine, 598–599 study of, 394 urinary mycobiome and virome, 601–602 and urogenital disease, 602–604 bladder cancer, 603–604 examples of bacterial phyla, 600 examples of species distribution, 601 factors involved in study, 600 interstitial cystitis, 603 LUTS/urge incontinence, 602 OAB/UUI, 602–603 urinary tract infection, 602 urolithiasis, 603 Urinary retention, 568 Urinary tract embryology, 179–187 Urinary tract fistulae, surgical management of, 43 Urinary tract infections (UTIs), 387, 541, 657, 672 indwelling catheter for, 446 recurrence of, 622 risk factors for, 613–615 age, 613–615 behavioural factors, 615 instrumentation of the urinary tract, 615 obesity, 615 voiding dysfunction, 615 signs and symptoms of, 446 urinary microbiome in, 395–396 and vaginal microbiome, 605 Urinary tract injury (UTI) bladder injuries, 1104 laparoscopic pelvic floor surgery, 1104–1105 prevention of, 1105 ureteric injuries, 1104–1105 Urinary urgency history, 257–258 symptom, 257–258 Urine culture, 390–392 methods for enhancing urine microbiology, 390–392 using chromogenic agar, 391 Urine flow continuous, 280 intermittent, 280 symptoms related to, 280 Urine retention, 259–260 Urine storage drugs that improve, 262 facilitation of, 457–477 Urine stream intermittency, 280 slow stream, 280 splitting/spraying, 280 Urine studies, 586–587 Urodynamic stress incontinence (USI), 258, 294, 776 causes of, 777 pathophysiology, 776 prevalence, 776

Urodynamic stress urinary incontinence (USUI), 1170 Urodynamics (UDS), 306, 313–322, 543–544, 570–571, 589, 837 Urodynamic tests in women, 288 Uroflow, 569 Uroflowmeters accuracy, 281 gravimetric, 281 rotating disk, 281 technical problems, 281 Uroflowmetry, 280–286 accuracy of, 281 equipment, 280–281 in female patients, 286 in healthy volunteers, 286 history, 280 home, 285 influence of urethral manipulation on, 283 measurement, 281 parameters of, 281 recommendations for measurement, 285–286 shape of flow curve, 281–282 values/curves, interpretation of, 282–285 Urogenital atrophy genitourinary syndrome, 672 treatments for, 672 Urogenital Distress Inventory, 81, 145 Urogenital fistulae, 1134–1143 etiology of, 1134–1135 evaluation/diagnosis, 1137–1143 algorithm, 1138 differential diagnosis, 1139 dye test, 1140 endoscopic evaluation, 1141 history, 1137–1139 imaging, 1141–1142 physical examination, 1140 symptoms, 1139–1140 tests, 1139 timing, 1140 urodynamics, 1142–1143 pathophysiology of, 1134–1135 risk of, 1135 types of, 1135–1137 peritoneovaginal fistulae, 1137 ureterofallopian fistulae, 1137 ureterovaginal fistulae, 1136–1137 urethrovaginal fistulae, 1137 vesicouterine fistulae, 1137 vesicovaginal fistulae, 1136 Urogenital prolapse, colpocleisis for, 958 background, 958 vs. colpectomy, 959 historical aspects, 958 indications/preparation, 958–959 results/complications, 962–963 malignancies, 963 recurrence, 963 regret after colpocleisis, 963 techniques, 959–962 bladder function management, 962 bowel function management, 962 colpocleisis vs. colpectomy, 959 preferred technique, 959–961 variations in, 961–962 Urogenital prolapse, ultrasonography in, 354

Urogenital sinus, 187–188 Urogenital triangle, 1000 Urogynecology ethical issues in, 77 female sexual dysfunction in, 112 laparoscopic surgery in, 1048 laparoscopic training for, 1055–1056 litigation in, 72–74 avoidance of, 77 causes for, 74–77 communication, 74–75 consent, 74–75 failing to meet governance requirements, 76–77 medical device problems, 76 pre-trial, 73–74 treatment complications, 75–76 trial, 74 mediation in, 74 medical indemnity in, 77 medicolegal issues in, 72–78 training programs, 4 Urolastic, 534 Uropathogens, structure and function, 613 Uropharmacology, 7 Uroplakin III (UP3), 387 Urorectal septum, 180–182 Urothelium, 182–183, 227 URRP, see Urethral retro-resistance pressure USI, see Urodynamic stress incontinence USLs, see Uterosacral ligaments USUI, see Urodynamic stress urinary incontinence Uterine anomalies, 1221–1222 Uterine cervix, tissue engineering, 201–202 Uterine preservation surgeries Manchester repair, 927 sacrospinous hysteropexy, 927 Uterine prolapse, 945–955 preserving surgery, 1088–1090 abdominal approach, 1089 laparoscopic approach, 1089–1090 vaginal approach, 1089 surgery, 947–954 hysterectomy vs. uterine preservation, 948–949 uterine-sparing procedures, 949–954 vaginal vs. abdominal, 947 traditional approach for, 1088 treatments of, 946 PFPT, 947 surgery, 947–954 vaginal pessaries, 947 uterine-sparing procedures, 949–954 anterior sacrospinous hysteropexy technique, 952 LeFort colpocleisis, 954 Manchester-Fothergill procedure, 954 mesh-augmented sacrospinous hysteropexy, 952–953 sacrospinous hysteropexy, 949–952 uterosacral hysteropexy, 953–954 uterine support, principles of, 946 Uterine support, principles of, 946 Uterosacral ligaments (USLs), 168–170 Uterosacral ligament suspension (USLS), 1175

Index Uterus embryological development, 179 tissue engineering, 201 Uterus didelphys, 1222 UTI, see Urinary tract infection U-UDI, see Urge urinary distress inventory UUI, see Urgency urinary incontinence UVF, see Ureterovaginal fistulae; Urethrovaginal fistula

V Vagina embryological development, 181–184, 187 tissue engineering, 202 Vaginal agenesis, 1243–1244 Vaginal apex, 935 complications, 940 intraoperative, 940 mesh, 942 postoperative, 940, 942 sacrocolpopexy abdominal uterosacral ligament suspension, 939 ASC, 935 complications, 940–942 efficacy outcomes, 935–938 enterocele repair, 939 MRI, 935–936 technique, 935 sacrohysteropexy ASH, 939 complications, 940–942 efficacy outcomes, 940 technique, 939–940 spina bifida/bladder exstrophy, 935 Vaginal atresia, 182, 191 Vaginal atrophy, 263 Vaginal axis, enterocele formation and, 902, 904 Vaginal Bowel Control System (VBCS), 1026–1027 Vaginal delivery, urinary incontinence risk, 26 Vaginal epithelium, 669 Vaginal estrogens, 673 Vaginal flap urethroplasty, 1206–1207 onlay urethroplasty using free graft, 1206–1207 outcomes for, 1206 Vaginal hysterectomy (VH), 47, 925, 1088 McCall cudolplasty at hysterectomy, 928–929 sacrospinous fixation at hysterectomy, 929 Vaginal hysteropexy with mesh, 927–928 Vaginal laser therapy, 673 Vaginal laxity, 656 conservative therapy, 656 surgical therapy, 656 Vaginal microbiome (VM), 604–605 bacterial vaginosis (BV), 605 and disease states, 605–606 and genital cancer, 606 urinary tract infection, 605 vulvovaginitis, 605–606 Vaginal narrowing procedures, 1257–1260 abdominoplasty, 1259–1260 G-spot augmentation, 1258

I-27 hyalurinic acid (HA) injections in vulva and vagina, 1257–1258 orgasm shot/O-Shot, 1258–1259 Vaginal repair of VVF, 1146–1151 Latzko repair, 1147 multilayer repair with/without tissue interposition, 1147–1149 operative aides, 1147 outcomes, 1151 postoperative management, 1149–1151 preoperative optimization, 1146–1147 procedures for, 1147 timing, 1146 Vaginal replacement/interposition, 1242 Vaginal vault prolapse, 925 prevalence, 925 symptoms, 925 Vaginoplasty, 1242, 1257 female cosmetic genital surgery, 1257 pull-through, 1242 skin-flap, 1242 for TGD populations, 1271–1274 complication rates, 1274–1275 health maintenance after, 1275–1276 preoperative surgical preparation and counseling, 1274 Vaginosacropexy (VASA), 1125–1126 Validation studies, 270 Validity, 90 Valsalva leak point pressure (VLPP), 274, 294, 302 Valsalva manoeuvre, 644 Vanilloid receptor, 228 Vanilloids, 473 Vardenafil, 470 Varitensor, 831 VAS, see Visual Analog Scale Vascular abnormalities and hypoxia, 586 Vasculature, pelvic, 1049 Vasodilators, 723 VBCS, see Vaginal Bowel Control System VCU, see Videocystourethrography VCUG, see Cystourethrogram; Voiding cystourethrogram VD, see Voiding difficulty Venous thromboembolism (VTE), 673, 675, 746–747 patient-related risk factors for, 750 Ventral tegmental area (VTA), 214 Verapamil, 467 Versius robotic platform, 1109 Vertebral, anorectal, cardiovascular, tracheoesophageal, renal, and limb abnormalities (VACTERL) syndrome, 1239 Vesical neck, 164, 167–168 Vesical trigone, 164 Vesico-bulbo-vesical micturition reflex, 219 Vesicoscopy, 383–385 benefits, 384 complications, 384 distension medium, 384 indications bladder diverticulectomy, 385 mesh complications, management of, 384 ureteral reimplantation, 385 vesicovaginal fistula, repair of, 384

limitations, 384 overview, 383 procedure, 384 Vesico-spinal-vesical micturition reflex, 219 Vesicouterine fistulae, 1137 flap coverage, 1157–1158 minimally invasive transabdominal approaches, 1156–1157 open repair, 1155–1156 outcomes of repair, 1157–1158 Vesicovaginal fistula, 1161 Vesicovaginal fistulae (VVFs), 1136, 1146 endoscopic fulguration of, 1146 flap coverage, 1157–1158 Latzko repair of, 1147 minimally invasive management options for, 1146 outcomes, 1157–1158 robotic surgery for repair, 1111 transabdominal, 1152–1155 conventional laparoscopy, 1154 indications for, 1152–1153 minimally invasive transabdominal approaches, 1154–1155 outcomes, 1157–1158 robot-assisted laparoscopic repair, 1155 timing of repair, 1152 vaginal repair of, 1146–1151 Latzko repair, 1147 multilayer repair with/without tissue interposition, 1147–1149 operative aides, 1147 outcomes, 1151 postoperative management, 1149–1151 preoperative optimization, 1146–1147 procedures for, 1147 timing, 1146 VH, see Vaginal hysterectomy Vibegron (MK-4618), 225–226, 469, 545 antimuscarinics, combinations with, 225–226 ion channels, 226 pharmacokinetics, 225 phosphodiesterase inhibitors, 226 Videocystourethrography (VCU), 306 Videourodynamics (VUDS), 273–274, 306–312, 350 basic principles of, 307–309 diagnoses, 310–311 bladder outlet obstruction, 310 detrusor overactivity, 309 detrusor underactivity, 310–311 dysfunctional voiding, 311 incomplete bladder emptying, 311 increased filling sensation, 309–310 occult USI on prolapse reduction, 310 quality of pelvic floor support, 310 structural abnormalities, 310, 311 USI, 309 future developments, 312 limitations of, 311 anaphylactic reaction, 311 other factors, 311 radiation exposure, 311 specific requirements for, 306–307 who should undergo, 309 Vinpocetine, 470 Viral infections, 556

Index

I-28 Virtual Clinics, 90 Virtual reality simulators (VRS), 1055 Virtual Urogynaecology Clinic (VUC), 142–143 Viscerofascial layer, 168–172 Visual Analog Scale (VAS), 148, 274 VLPP, see Valsalva leak point pressure VNUT (vesicular nucleotide transporter), 249 VOCC, see Voltage-operated calcium channels Voided volume (V), urine flow, 281 healthy volunteers, 286 uroflowmetry, 281–282, 286 Voiding, 567–568 delayed, 413 diary, 589 pressure–flow studies of, 288 symptoms, 259–260 time, 281, 286 timed, 413–414 Voiding cystourethrogram (VCUG), 344, 1192–1193 Voiding difficulty (VD), after antiincontinence surgery, 848–850 diagnostic evaluation, 848–850 endoscopy/imaging, 849 etiology, 847–848 history and physical examination of patient, 849 identifying risks, 848 incidence, 847–848 management, 850–857 urodynamics, 849–850 Voiding dysfunction (VD), 457, 567 classification, 242–244 bladder and outlet activity, 240 expanded to include pelvic floor activity, 242–244 by function/activity, 241–242 by neurological activity, 240 by symptoms, 239 by urodynamic parameters, 240

DSD/DU, management of, 560 abdominal straining/Crede manoeuvre, 560 alpha-blocker, 560 external urethral sphincter botulinum toxin injection, 560 IDC/suprapubic catheter, 560 intermittent catheterisation, 560 reflex voiding, 560 treatments of, 457 Voiding reflexes, organization of, 209–212 brain stem circuitry, 210–212 spinobulbospinal reflex pathways, 210 Voiding symptoms, 259–260 hesitancy, 259 incomplete bladder emptying, 259–260 position-dependent micturition, 260 post-micturition dribble, 260 slow urinary stream, 260 straining to void, 259 urine retention, 259–260 Voltage-operated calcium channels (VOCC), 227 VRS, see Virtual reality simulators VTA, see Ventral tegmental area VTE, see Venous thromboembolism VUC, see Virtual Urogynaecology Clinic VUDS, see Videourodynamics Vulvar lipoplasty, 1257–1258 Vulva/vestibule, 724 Vulvoscopy, 715, 716 Vulvovaginal atrophy, 1262–1263 Vulvovaginal laxity, 1262–1263 VVFs, see Vesicovaginal fistulae

W Water, cystometry filling medium, 291 Water perfusion technique, 298 Weight/body mass index, 283

Weight loss, 415 Wet laboratory training, 1058 Wexner constipation score, 124 Wexner Score, 123 WHO, see World Health Organization WNT4, 1219 Wnt/β-catenin signalling, 247 Wolffian ducts, 182–184, 192 Work Productivity and Activity Impairment (WPAI), 81–82 World Health Organization (WHO), 55 WPAI, see Work Productivity and Activity Impairment

X Xenografts, 250, 770, 967 X-ray imaging, of lower urinary tract, 343–350 46,XX DSD, 1240–1241 46,XY DSD, 1241–1242 clitoroplasty, 1241–1242 feminizing genitoplasty reconstructive surgery, 1241 labioplasty, 1242 vaginoplasty, 1242

Y Yang-Monti transverse ileal tube, 1213 Yolk sac, 179–180 Youssef’s syndrome, 1137

Z ZD0947, 467 Zeitgebers, 248 Zero pressure, 288