Gender, Health and Healthcare: Women’s and Men’s Experience of Health and Working in Healthcare Roles [1 ed.] 1409468364, 9781409468363

Citation preview

About the pagination of this eBook Due to the unique page numbering scheme of this book, the electronic pagination of the eBook does not match the pagination of the printed version. To navigate the text, please use the electronic Table of Contents that appears alongside the eBook or the Search function. For citation purposes, use the page numbers that appear in the text.

Women’s Healthcare in ADVANCED PRACTICE NURSING

Ivy M. Alexander, PhD, APRN, ANP-BC, FAANP, FAAN, is clinical professor of nursing and medicine and director of the ‌‌‌‌‌‌Adult-Gerontology Primary Care Nurse Practitioner Program at the University of Connecticut (UConn). Her clinical, scholarly, and research interests are in midlife women’s healthcare and increasing access to primary care for underserved populations. She has worked extensively with menopause and osteoporosis management and has published and presented widely regarding these subject areas, including two books, which have been translated into Spanish, Greek, and Italian. She has been principal investigator on studies evaluating women’s relationships with their primary care providers; Black women’s perceptions of menopause, midlife health risks, and self-management techniques used to manage menopause symptoms and reduce health risks; and osteoporosis risks and management. She has served as Project Director for multiple Health Resources & Services Administration–funded programs supporting education and training of primary care nurse practitioners for underserved populations. She has consulted for national and international companies to develop educational programs, conduct research, and provide focused clinician education programs. Versie Johnson-Mallard, PhD, APRN, WHNP-BC, FAANP, FAAN, Robert Wood Johnson Nurse Faculty Scholar alumna, is a National Certification Corporation board–certified women’s health nurse practitioner, faculty, and dean at Kent State University College of Nursing. Scientific discovery and funding were with the Robert Wood Johnson Foundation, Department of Health and Human Services Office on Women’s Health, National Institute of Nursing Research (NINR), and National Cancer Institute (NCI) under the National Institutes of Health (NIH). Sexual and reproductive health clinical inquiry was the impetus to advance scientific knowledge about innovative educational interventions designed to promote reproductive health and cancer prevention among young adults. Dr. Johnson-Mallard’s board service, clinical interest, research, and publications are in the areas of women’s health, sexual and reproductive health promotion, human papillomavirus (HPV)/cancer screening/prevention/vaccination, and behavior change in response to sex, race, and culturally appropriate educational interventions. Dr. Johnson-Mallard provides consultation to partners who share interest in the development of education material, clinical guidelines, and policy around reproductive health and cancer prevention. Elizabeth A. Kostas-Polston, PhD, APRN, WHNP-BC, FAANP, FAAN, is a U.S. Air Force Veteran; associate professor of nursing at the Daniel K. Inouye Graduate School of Nursing at the Uniformed Services University of the Health Sciences, Bethesda, MD; a board-certified women’s health nurse practitioner at Holy Cross Hospital, Germantown, Maryland; and a Robert Wood Johnson Foundation Nurse Faculty Scholar alumna. She received her bachelor of science in nursing from Arizona State University, a master of science in nursing with specialization in women’s health (obstetrics, gynecology, and primary care of women) from the University of Florida, and a doctor of philosophy from Loyola University Chicago. Over the last 38 years, her clinical practice, scholarly activities, and leadership have impacted women’s health—both within and outside of the U.S. Department of Defense. In her research role, Dr. Kostas-Polston’s innovative scholarship is focused on enhancing military women’s health and warfare capability through the development of innovative technologies designed to support and maintain urogenital health and operational readiness. She also works to effectively translate new knowledge to inform novel approaches to health promotion and infectious disease prevention in our nation’s female warfighters when serving in austere environments across the globe. She has received funding from the National Institutes of Health (NIH)/National Institute of Nursing Research (NINR); the Department of Defense (DoD); the Robert Wood Johnson Foundation; Sigma Theta Tau International (STTI) Nursing Honor Society; and the Faye G. Abdellah Center for Military and Federal Health Research Endowment. The primary aim of Dr. Kostas-Polston’s clinical practice is to improve the health of women across the life space and their families. Toward this end, she works with others interested in the development of health promotion and disease-prevention strategies, evidence-based clinical guidelines, and health policy. She is a Fellow and the Immediate Past-Chair of the American Academy of Nursing’s Women’s Health Expert Panel. Joyce D. Cappiello, PhD, APRN, FNP-BC, FAANP, is an associate professor emerita of nursing at the University of New Hampshire, where she taught family nurse practitioner and prelicensure nursing students. Her approach to education is through case-based and inquiry-based learning. She was a coeditor and case writer for A Day in the Office: Case Studies in Primary Care (2017), and authored numerous cases and simulations for the classroom, objective structured clinical examination (OCSE) evaluation, and statewide Area Health Education Center (AHEC) projects. Her clinical, research and scholarly interests explore how nursing education ensures that graduates can provide expert sexual and reproductive healthcare. Her research promulgated core educational competencies for sexual and reproductive healthcare and early pregnancy decision-making. During her career, she provided prenatal care at an FQHC and comprehensive reproductive healthcare to men and women at a nonprofit feminist health center. Her most recent international research includes collaboration with Australian nursing educators and Kenyan activists working to improve the reproductive health of adolescents postpandemic. Heather S. Hubbard, DNP, APRN, WHNP-BC, CNE, is a board-certified women’s health nurse practitioner; military officer; and instructor at Bradley University Department of Nursing. She has worked extensively to advance maternal health policy through leadership roles within the Defense Health Agency and as the DoD representative for the U.S. Surgeon General’s Maternal Health Working Group.

Women’s Healthcare in ADVANCED PRACTICE NURSING Third Edition Editors Ivy M. Alexander, PhD, APRN, ANP-BC, FAANP, FAAN Versie Johnson-Mallard, PhD, APRN, WHNP-BC, FAANP, FAAN Elizabeth A. Kostas-Polston, PhD, APRN, WHNP-BC, FAANP, FAAN Joyce D. Cappiello, PhD, APRN, FNP-BC, FAANP Heather S. Hubbard, DNP, APRN, WHNP-BC, CNE Editors Emeritae Catherine Ingram Fogel Nancy Fugate Woods

Copyright © 2024 Springer Publishing Company, LLC All rights reserved. Chapters 8, 16, 17, 21, 22, 24, 28, 32, 37, 38, and 39: The views expressed in these chapters are those of the author(s) and do not reflect the official policy or position of the Department of Defense or the U.S. Government. First Springer Publishing edition 978-0-8261-9001-7, 2017 No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior permission of Springer Publishing Company, LLC, or authorization through payment of the appropriate fees to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400, fax 978-646-8600, [email protected] or at www.copyright.com. Springer Publishing Company, LLC connect.springerpub.com Acquisitions Editor: Elizabeth Nieginski Content Development Editor: Lucia Gunzel Production Manager: Kris Parrish Compositor: Amnet ISBN: 978-0-8261-6721-7 ebook ISBN: 978-0-8261-6722-4 DOI: 10.1891/9780826167224 SUPPLEMENTS: A robust set of instructor resources designed to supplement this text is available. Qualifying instructors may request access by emailing [email protected]. Instructor Materials: LMS Common Course Cartridge (All Instructor Resources) ISBN: 978-0-8261-6723-1 Instructor Case Studies ISBN: 978-0-8261-6774-3 Instructor Text Bank ISBN: 978-0-8261-6776-7 Instructor PowerPoints ISBN: 978-0-8261-6775-0 Image Bank ISBN: 978-0-8261-6777-4 Mapping to AACN Essentials ISBN: 978-0-8261-6719-4 Transition Guide to the Third Edition ISBN: 978-0-8261-6724-8 23 24 25 26 / 5 4 3 2 1 The author and the publisher of this Work have made every effort to use sources believed to be reliable to provide information that is accurate and compatible with the standards generally accepted at the time of publication. Because medical science is continually advancing, our knowledge base continues to expand. Therefore, as new information becomes available, changes in procedures become necessary. We recommend that the reader always consult current research and specific institutional policies before performing any clinical procedure or delivering any medication. The author and publisher shall not be liable for any special, consequential, or exemplary damages resulting, in whole or in part, from the readers’ use of, or reliance on, the information contained in this book. The publisher has no responsibility for the persistence or accuracy of URLs for external or third-party Internet websites referred to in this publication and does not guarantee that any content on such websites is, or will remain, accurate or appropriate. Library of Congress Cataloging-in-Publication Data‌‌‌‌‌ Names: Alexander, Ivy M., editor. | Johnson-Mallard, Versie, editor. | Kostas-Polston, Elizabeth A., editor. | Cappiello, Joyce D., editor. | Hubbard, Heather S., editor. Title: Women’s healthcare in advanced practice nursing / Ivy M. Alexander, Versie Johnson-Mallard, Elizabeth A. Kostas-Polson, Joyce D. Cappiello, Heather S. Hubbard, editors. Other titles: Women’s health care in advanced practice nursing Description: Third edition. | New York, NY : Springer Publishing Company, [2024] | Preceded by Women’s health care in advanced practice nursing / Ivy M. Alexander, Versie Johnson-Mallard, Elizabeth A. Kostas-Polston, Catherine Ingram Fogel, Nancy Fugate Woods, editors. Second edition. 2017. | Includes bibliographical references and index. Identifiers: LCCN 2023027812 (print) | LCCN 2023027813 (ebook) | ISBN 9780826167217 (paperback) | ISBN 9780826167224 (ebook) Subjects: MESH: Women’s Health Services | Nursing Care | Women’s Health | Advanced Practice Nursing | Health Promotion Classification: LCC RT42 (print) | LCC RT42 (ebook) | NLM WA 309.1 | DDC 613/.04244--dc23/eng/20230717 LC record available at https://lccn.loc.gov/2023027812 LC ebook record available at https://lccn.loc.gov/2023027813 Contact [email protected] to receive discount rates on bulk purchases. Publisher’s Note: New and used products purchased from third-party sellers are not guaranteed for quality, authenticity, or access to any included digital components. Printed in the United States of America.

The editors dedicate this book to the clinicians who provide excellent, individualized care to women and people of minoritized genders.

Contents

Contributors  ix Foreword Joan L. Shaver, PhD, RN, FAAN xiii Preface xv Acknowledgments xvii Springer Publishing Resources xix

PART I  Lives and Health for Women and Minoritized Gender Persons 1 Women and Their Health  03

Sharon M. Adams, Shavondra Huggins, and Versie Johnson-Mallard

2 Women and Healthcare Workforce: Caregivers and Consumers  29

Meghan Eagen-Torkko, Diana Taylor, and Molly Altman

3 Women and Healthcare  61

Kim Curry and Versie Johnson-Mallard

4 Oppression, Racism, Income Inequity, and Women’s Health Outcomes  89 Kenya Massey, Jody Early, Cheryl L. Cooke, and Selina A. Mohammed

5 Legal Issues in Women’s Healthcare  95 Anna G. Small

6 Seeing the Whole: Feminist Theory as a Model for Patient Care  105

9 Midlife Women’s Health  167

Ivy M. Alexander, Annette Jakubisin-Konicki, Jessica L. Palozie, Amanda M. Swan, Christine Alexandra Bottone, and Rubby Koomson

10 Older Women’s Health  199 Christine Alexandra Bottone

11 Well Women’s Health  215

Eldora Lazaroff, Lynn M. Gaddis, and Versie Johnson-Mallard

12 Mental Health  227

Sandra J. Janashak Cadena

13 Nutrition for Women  247 Heather Hutchins-Wiese

14 Healthy Practices: Physical Activity  281 JiWon Choi

15 Healthy Practices: Sleep  289 Julie L. Otte and Shalini Manchanda

16 Genetics and Women’s Health  309

Sarah E. Martin and Elizabeth A. Kostas-Polston

17 Women and the Workplace  319

Kim Shaughnessy-Granger, Cynthia A. Kuehner, Lana J. Bernat, Timothy G. Whiting, and Brookes Williams

Meghan Eagen-Torkko, Selina A. Mohammed, and Cheryl L. Cooke

18 Health Considerations for Women Caregivers  339

PART II  Health Promotion and Prevention

19 Women’s Sexual Health  359

Christine DiLeone

Susan M. Seibold-Simpson and Justin M. Waryold

7 Women’s Bodies, Women’s Health  117

20 Primary Care of Lesbian, Gay, and Bisexual Individuals  375

8 Young Women’s Health  147

21 Fertility Self-Management and Shared Management  379

Ivy M. Alexander, Annette Jakubisin-Konicki, Lauren Eddy, Jenny Yung, and Carolyn Levy

Catherine Takacs Witkop, Danielle Wright, Kristi Norcross, and Kim Shaughnessy-Granger

Kathryn S. Tierney

Richard M. Prior, Heather C. Katz, and Leslie L. Balcazar de Martinez‌‌‌‌

vii

viii  contents 22 Preconception Counseling  397

Kristi Rae Norcross, Jacqlyn C. Sanchez, and Elizabeth A. Kostas-Polston

23 Prenatal Care and Anticipating Birth  417 Lisa L. Ferguson

PART III  Managing Symptoms and Health Considerations 24 Breast Health Considerations  437 Leslie L. ‌‌‌‌‌Balcazar de Martinez and Annesley W. Copeland

34 Menopause  633

Ivy M. Alexander, Annette Jakubisin-Konicki, Amanda M. Swan, Jessica L. ‌‌‌‌‌Palozie, and Jenna LoGiudice

35 Osteoporosis  653

Ivy M. Alexander, Matthew Witkovic, Kara Vignati, and Daniela LaRosa Karanda

36 Pregnancy Decision-Making and Supportive Care  665 Katherine Simmonds and Joyce D. Cappiello

37 Infertility  683

Rachel Oldani Bender and Elizabeth A. Kostas-Polston

25 Caring for the Transgender and Gender Nonbinary Patient  453

38 High-Risk Childbearing  695

26 Sexual Health Problems and Dysfunctions  465

39 Intrapartum and Postpartum Care  715

Nathan Levitt

Megan R. Mays

27 Vulvar and Vaginal Health  481 Debbie T. Devine, Susan Salazar, and Versie Johnson-Mallard

28 Perimenstrual and Pelvic Symptoms and Syndromes  503 Regina A. McClure, Jacqlyn C. Sanchez, Gretchen E. Szymanski, and Elizabeth A. Kostas-Polston

29 Urologic and Pelvic Floor Health Problems  531

Richard S. Bercik and Cherrilyn F. Richmond

30 Sexually Transmitted Infections  551

Joyce D. Cappiello and Maureen Boardman

31 Women and HIV/AIDS  579

Rasheeta Chandler and Crystal Chapman Lambert

32 Human Papillomavirus  599

Elizabeth A. Kostas-Polston, Versie Johnson-Mallard, and Naomi Jay

33 Gynecologic Cancers  613

Zahra Amirkhanzadeh Barandouzi and Lynda Lee Lapan

Heather S. Hubbard, Monica A. Lutgendorf, and Stephanie N. Shivers Alyssa Davis Larsen, Kady Frye, Rachel Cox, Rebeccah Dindinger, and Brittany Jessica Hannigan

40 Mental Health Challenges  745 Deborah Antai-Otong

41 Substance Abuse and Women  769 Elizabeth Mayerson

42 Gender-Based Violence and Women’s Health  787 Angela Frederick Amar and Necole Leland

43 Cardiovascular Disease in Women  797

Kristin A. Bott, Sandra Biolo, Maria Cutrali, Annette Jakubisin-Konicki, and Joanne Thanavaro

44 Endocrine-Related Problems  841 Traci Sharkey-Wells

45 Chronic Illness and Women  869

Tara Fernandez Bertulfo, Annette Jakubisin-Konicki, Jennifer Wright, and Versie Johnson-Mallard

46 Care of Women With Disabilities  881 Tracie Harrison and Janiece L. Taylor

Index  891

Contributors Sharon M. Adams, DNP, CNM, ARNP

Christine Alexandra Bottone, MS, DNP, APRN, NP-C

Ivy M. Alexander, PhD, APRN, ANP-BC, FAANP, FAAN

Sandra J. Janashak Cadena, PhD, APRN, FAAN

Clinical Assistant Professor, University of Florida, College of Nursing, Gainesville, Florida Clinical Professor; Director, Adult-Gerontology Primary Care Nurse Practitioner Program; University of Connecticut School of Nursing, Storrs, Connecticut

Molly Altman, PhD, CNM, MPH, FACNM

Assistant Professor; Child, Family, and Population Health Nursing; University of Washington School of Nursing, Seattle, Washington

Angela Frederick Amar, PhD, RN, FAAN

Professor and Dean, University of Nevada, Las Vegas, Las Vegas, Nevada

Deborah Antai-Otong, RN, MS, APRN, PMHCNS-BC, FAAN Psychiatric Mental Health and Behavioral Consultant, Dallas, Texas

Leslie L. Balcazar de Martinez, DNP, MSN, BSN*

Women’s Health Nurse Practitioner/Certified Nurse Midwife, U.S. Air Force

Zahra Amirkhanzadeh Barandouzi, PhD

University of Connecticut, Storrs, Connecticut; CLAIM, LLC (Clinical Associates in Medicine), Farmington, Connecticut Professor, Nursing and Medicine/Public Health, Universidad el Bosque, Bogota, Colombia, South America; Professor, Nursing, Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia, South America

Joyce D. Cappiello, PhD, FNP-BC, FAANP

Associate Professor of Nursing, Emerita, University of New Hampshire, Durham, New Hampshire

Rasheeta Chandler, PhD, RN, FNP-BC, FAANP, FAAN

Associate Professor, Emory University, Nell Hodgson Woodruff School of Nursing, Atlanta, Georgia; Adjunct Professor, Morehouse School of Medicine, Department of Community Health and Preventive Medicine, Atlanta, Georgia; Visiting Professor, Center for AIDS Prevention Studies University of California, San Francisco

JiWon Choi, PhD, RN

Postdoctoral Fellow, Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia

Associate Adjunct Professor, Department of Social and Behavioral Sciences, Institute for Health and Aging, University of California, San Francisco, California

Richard S. Bercik, MD

Cheryl L. Cooke, PhD, DNP, PMHNP-BC

Associate Professor, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine; Urogynecology and Reconstructive Pelvic Surgeon, Ob/Gyn Department, Yale Medicine; New Haven, Connecticut

Owner, CookeTherapy PLLC, Edmonds, Washington

Annesley W. Copeland, MD, FACS

Lieutenant Colonel, U.S. Army Nurse Corps, Falls Church, Virginia

Core Surgery Clerkship Director and Clinical Professor, The Department of Surgery at Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, Maryland

Tara Fernandez Bertulfo, DNP, RN, WHNP, CNE

Rachel Cox, MSN, RNC-OB, C-EFM*

Sandra Biolo, APRN, ANP BC

Kim Curry, PhD, FNP-C, FAANP

Maureen B. Boardman, MSN, FNP-C, FAANP

Maria Cutrali, APRN, ANP-BC, CHFN, CCRN, BSN

Kristin A. Bott, DNP, APRN, ACNP-BC

Debbie T. Devine, PhD, APRN, FNP

Lana J. Bernat, DNP, CNM, CPHQ*

Clinical Associate Professor, Georgia Baptist College of Nursing, Mercer University, Atlanta, Georgia Cardiology Lead Advanced Practice Provider, Western CT Medical Group, Danbury, Connecticut Clinical Assistant Professor of Community and Family Medicine, Dartmouth, Geisel School of Medicine, Hanover, New Hampshire Assistant Professor, Director, AGACNP Program, University of Connecticut School of Nursing, Storrs, Connecticut

Flight Commander, Family Birthing Center, Keesler Air Force Base, Mississippi Editor in Chief, Journal of the American Association of Nurse Practitioners, Gainesville, Florida Nuvance Health Medical Practices – Cardiology, Danbury, Connecticut

Clinical Assistant Professor, University of Florida College of Nursing, Gainesville, Florida

*The views expressed are the contributor's own and do not reflect the official policy or position of the Department of Defense or the U.S. Government.

ix

x  contributors Christine DiLeone, PhD, RN

Assistant Professor, University of Connecticut School of Nursing, Storrs, Connecticut

Rebeccah Dindinger, CNS, DNP, RNC-OB, IBCLC

Maternal Infant Clinical Nurse Specialist, Center for Nursing Science and Clinical Inquiry, Landstuhl Regional Medical Center, Landstuhl, Germany

Meghan Eagen-Torkko, PhD, CNM, ARNP, FACNM

Versie Johnson-Mallard, PhD, RN, APRN, FAANP, FAAN

Dean, Professor, and Henderson Endowed Chair, College of Nursing, Kent State University, Kent, Ohio

Daniela LaRosa Karanda, MS, APRN, FNP-BC

Nurse Practitioner, Hartford Healthcare Medical Group, Hebron, Connecticut

Heather C. Katz, DNP, MSN, WHNP-BC, RN

Associate Professor and Director of Nursing, School of Nursing and Health Studies, University of Washington Bothell, Bothell, Washington

Senior Health Management Consultant‌‌‌‌‌

Jody Early, PhD, MS, MCHES

Instructor, University of Connecticut, School of Nursing, Storrs, Connecticut

Professor, School of Nursing and Health Studies, University of Washington Bothell, Bothell, Washington

Lauren Eddy, DNP, APRN, FNP-BC

Rubby Koomson, MSN, APRN, FNP-C

Elizabeth A. Kostas-Polston, PhD, APRN, WHNP-BC, FAANP, FAAN

Clinical Assistant Professor, College of Nursing, University of Florida, Gainesville, Florida

Tenured Associate Professor, and Deputy Director, PhD in Nursing Science Program, Daniel K. Inouye Graduate School of Nursing; Uniformed Services University of the Health Sciences; Robert Wood Johnson Foundation Nurse Faculty Scholar Alumna; Women’s Health Nurse Practitioner; American Academy of Nursing Women’s Health Expert Panel, Past-Chair; Bethesda, Maryland

Kady Frye, BSN, RNC-OB, C-EFM

Cynthia A. Kuehner, DNP, FNP-BC, NEA-BC*

Lynn Gaddis, DNP, APRN, FNP-BC

Crystal Chapman Lambert, PhD, CRNP, FNP-BC, ACRN, FAAN

Adjunct Clinical Professor, Family Nurse Practitioner Program; University of Connecticut School of Nursing, Storrs, Connecticut

Lisa L. Ferguson, DNP, APRN, WHNP-BC, CNE

Clinical Nurse, Labor and Delivery, RAF Lakenheath, Brandon, Suffolk, England Assistant Professor, College of Nursing, Kent State University, Kent, Ohio

Brittany Jessica Hannigan, DNP, CNM

Chief of Midwifery Services, OB/GYN Clinic, Landstuhl Regional Medical Center, Landstuhl, Germany

Tracie Harrison, RN, PhD, FAAN, FGSA

Professor, Sun Endowed Chair in Geriatrics/Gerontology, College of Nursing, The University of Arkansas Medical Sciences, Little Rock, Arkansas

Heather S. Hubbard, DNP, APRN, WHNP-BC, CNE*

U.S. Air Force Military Officer and Instructor, Department of Nursing, Bradley University, Peoria, Illinois

Shavondra Huggins, DNP, CNS, WHNP-BC, FNP-C, APRN, CNE

Clinical Assistant Professor, University of Florida, College of Nursing, Gainesville, Florida

Heather Hutchins-Wiese, PhD, RD

Professor, Dietetics and Human Nutrition Programs; Faculty Affiliate Aging Studies Program; Eastern Michigan University, Ypsilanti, Michigan

Annette Jakubisin-Konicki, PhD, APRN, ANP-BC, FNP-BC, FAANP, FAAN Clinical Professor; Interim Associate Dean for Graduate Studies; Director, Family Nurse Practitioner Program; University of Connecticut School of Nursing, Storrs, Connecticut

Naomi Jay, RN, NP, PhD, FAAN

Women’s Health Nurse Practitioner, UCSF Anal Neoplasia Clinic, Research and Education (ANCRE) Center, San Francisco, California

Rear Admiral, U.S. Navy

Associate Professor, School of Nursing; Family, Community and Health Systems, The University of Alabama at Birmingham; Birmingham, Alabama

Lynda Lee Lapan, MSN, APRN, FNP-BC, AOCNP Nurse Practitioner, Champlain Valley Hematology Oncology, Colchester, Vermont

Alyssa Davis Larsen, CNM, DNP

Certified Nurse-Midwife, OB/GYN, RAF Lakenheath, Brandon, Suffolk, England

Eldora Lazaroff, DNP, RN, CNP-BC

Professor, College of Nursing, Kent State University, Kent, Ohio

Necole Leland, DNP, RN, PNP, CPN

Assistant Professor in Residence, University of Nevada, Las Vegas, Las Vegas, Nevada

Nathan Levitt, FNP-BC, MSN, BSN, RN, MA

Director of LGBTQ and Gender Justice Learning, Yale School of Nursing, Orange, Connecticut

Carolyn Levy, MSN, CPNP-PC, IBCLC

Doctoral Candidate, School of Nursing, University of Connecticut, Storrs, Connecticut; Pediatric Nurse Practitioner, Lactation Consultant, Children’s Medical Group, Hamden, Connecticut

Jenna LoGiudice, PhD, CNM, RN, FACNM

Associate Professor, Midwifery DNP Program Director, Egan School of Nursing and Health Studies, Fairfield University, Fairfield, Connecticut

Monica A. Lutgendorf, MD, FACOG, CAPT, MC, USN* Maternal-Fetal Medicine Physician, Chair and Associate Professor, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland

*The views expressed are the contributor's own and do not reflect the official policy or position of the Department of Defense or the U.S. Government.

contributors xi

Shalini Manchanda, MD

Professor of Clinical Medicine, Indiana University School of Medicine, Section of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indianapolis, Indiana

Sarah E. Martin, DNP, APRN, CNM, WHNP-BC*

Lt. Colonel, U.S. Air Force; Advanced Practice Registered Nurse; Certified Nurse Midwife; Women’s Health Nurse Practitioner; Oakwood, Ohio

Kenya Massey, MSW, LSW, LCSW

Doctoral Student, Department of Sociology, University of Missouri, Columbia, Missouri

Elizabeth Mayerson, DNP, RN, APRN, FNP-BC, CNE

Assistant Clinical Professor, University of Connecticut School of Nursing, University of Connecticut School of Medicine, Storrs, Connecticut

Megan R. Mays, DNP, WHNP-BC

Kim Shaughnessy-Granger, DNP, CNM, FACHE, FACNM, FAAN* Captain, Nurse Corps, U.S. Navy, Vienna, Virginia

Stephanie N. Shivers, DNP, CNM*

Officer in Charge, Obstetrics and Gynecology Clinic, Landstuhl Regional Medical Center, Landstuhl, Germany

Katherine Simmonds, PhD, MPH, RN, WHNP-BC

Clinical Professor, Roux Institute/Bouve College of Health Sciences, Northeastern University, Portland, Maine

Anna G. Small, CNM, MSN, JD, CHC

Senior Vice President and Chief Compliance Officer, Nemours Children’s Health, Jacksonville, Florida

Amanda M. Swan, MSN, WHNP-BC

Atrius Health, Boston, Massachusetts

Owner, Swan Integrative Health and Wellness LLC, Glastonbury, Connecticut

Regina A. McClure, WHNP-BC, BSN, RN

Gretchen E. Szymanski, CNM, WHNP-BC*

Women’s Health Nurse Practitioner, Fort Worth, Texas

Selina A. Mohammed, PhD, MPH, MSN, RN

Professor and Associate Dean, School of Nursing and Health Studies, University of Washington Bothell, Bothell, Washington

Kristi Rae Norcross, DNP, CNM*

U.S. Air Force Certified Nurse Midwife Retired, Landstuhl Regional Medical Center, CNSCI and Women’s Health Clinic, Landstuhl, Germany

Rachel Oldani Bender, MSN, WHNP-BC

Mercy Hospital Saint Louis, Department of OBGYN, St, Louis, Missouri

Julie L. Otte, PhD, RN, FAAN

Associate Professor, Indiana University School of Nursing, Indianapolis, Indiana

Jessica L. Palozie, DNP, APRN, ACNP-BC, CNE

Assistant Clinical Professor of Nursing, University of Connecticut, Storrs, Connecticut

Richard M. Prior, DNP, FNP-BC, FAANP

University‌‌‌‌‌ of Cincinnati College of Nursing, Cincinnati, Ohio

Cherrilyn F. Richmond, MS, WHNP(BC)

Clinical Instructor/Lecturer, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine; Women’s Health Nurse Practitioner, Urogynecology and Re-constructive Pelvic Surgery, Yale Medicine; New Haven, Connecticut

U.S. Air Force, OB/GYN Department, Landstuhl Regional Medical Center, Landstuhl, Germany

Diana Taylor, PhD, RNP, FAAN

Professor Emerita, School of Nursing, University of California, San Francisco, San Francisco, California

Janiece L. Taylor, RN, PhD, FAAN

Assistant Professor, School of Nursing, Johns Hopkins University, Baltimore, Maryland

Joanne Thanavaro, DNP, RN, AGPCNP-BC, AGACNP-BC, DCC, FAANP

Professor of Nursing, Associate Dean of Graduate Nursing Education, Director of Advanced Practice Nursing and DNP programs, Coleman/Chaifetz Entrepreneurship Fellow, Trudy Busch Valentine School of Nursing, Saint Louis University, St. Louis, Missouri

Kathryn S. Tierney, MSN. APRN, FNP-BC, FAANP

Medical Director, Middlesex Health Center for Gender Medicine and Wellness; Nurse Practitioner, Middlesex Health Multispecialty Group Endocrinology; Middletown, Connecticut

Kara Vignati, AGPCNP-BC

Advanced Practice Registered Nurse, Starling Physicians, Wethersfield, Connecticut

Susan Salazar, PhD, MSN, CNM, WHNP

Justin M. Waryold, DNP, RN, ANP-C, ACNP-BC, GS-C, CNE, FAANP

Assistant Professor, University of South Florida, College of Medicine/ Family Practice, Tampa, Florida

Assistant Professor, SUNY Upstate Medical University, College of Nursing, Syracuse, New York

Jacqlyn C. Sanchez, WHNP, DNP*

Timothy G. Whiting, MPH/CPH, MBA, BSN-RN

Major, Primary Care Flight Commander, USAF, Spangdahlem AB, Germany

Arlington, Virginia

Susan M. Seibold-Simpson, PhD, MPH, RN, FNP

Commander, Nurse Corps, U.S. Navy

Adjunct Faculty, School of Nursing, State University of New York at Delhi, Delhi, New York

Traci Sharkey-Wells, CNP, CDCES

Diabetes Management Team, Center for Thyroid Diseases and Endocrinology, Parma Heights, Ohio

Brookes Williams, MSN, FNP, AG-ACNP* Catherine Takacs Witkop, MD, PhD, MPH*

Colonel (Ret), U.S. Air Force, MD; Associate Dean for Medical Education, Professor, Preventive Medicine and Gynecologic Surgery and Obstetrics, Uniformed Services University, School of Medicine, Bethesda, Maryland

*The views expressed are the contributor's own and do not reflect the official policy or position of the Department of Defense or the U.S. Government.

xii  contributors Matthew Witkovic, DNP

Jennifer Wright, MSN, APRN

Danielle Wright, MD

Jenny Yung, MS, APRN, FNP-C

Adjunct Clinical Professor, School of Nursing, University of Connecticut, Storrs, Connecticut Assistant Professor, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland

Dartmouth Hitchcock Medical Center, Neurology, Headache Clinic, Lebanon, New Hampshire Nurse Practitioner, Community Health Center, Inc., New Britain, Connecticut

Foreword If you picked up this new third edition of Women’s Health Care in Advanced Practice Nursing to put yourself on the leading edge of contemporary, equitable, diverse, and inclusive care for women, you have done the right thing. After reading it, I am certain you will keep it nearby, especially if you are an advanced practice registered nurse (APRN) or other provider who delivers, aspires to deliver, or wants to influence superlative healthcare for women—at any age and at any stage. Building on the superb foundation of the second edition, important updates warrant perusing this one even if you prized the last edition. Throughout the text and pertinent to today’s growing sensitivity to the effects on health of personal implicit bias and system structural bias, you will see enhanced attention to the diversity of women by sex and gender variation (SGV) groups (e.g., women who identify as nonbinary, lesbian, bisexual, or transgender, or who identify as other than completely heterosexual). This is in recognition of evidence that compared to cisgender heterosexual counterparts, women in SGV groups have preexisting vulnerabilities and environmental risks, showing excess prevalence of certain chronic and mental health conditions, greater engagement with health-jeopardizing behaviors (e.g., hazardous alcohol, drug, and tobacco use), and are exposed to excess stressors and experiencing culturally incongruent and insensitive healthcare. This edition remains visionary, leading, and timely. As I noted for the second edition, the foundational editors are long-standing women’s health icons in our field of nursing (Catherine Ingram Fogel and Nancy Fugate Woods). Fogel and Woods conceived of the first version in the early 1980s, a time in women’s health when the biomedicine dominance made it narrowly defined (it was mostly about the reproductive phase), and the study of women’s health lacked popularity and certainly was not comprehensive. The editors parted from the typical biomedical approach and articulated a framework to speak directly to us in nursing, focusing on what I call health ecology (women within their environments or what some refer to as the context of their lives). Part I will immerse you in this frame. Already started but accelerated by the recent SARS COVID-19 pandemic, attention to a national disease prevention strategy grows. Part II continues to encompass well-versed current perspectives on preventive care (and health promotion care) for women across the life span. Based on knowing that women most often initiate healthcare for bothersome symptoms associated with chronic physical or emotional conditions, reproductive (pregnancy)

or sexual health–related conditions, and the consequences of violence, Part III covers the most prominent women’s health issues open to health restoration though astute APRN clinical practice. You can be assured that the editors of this book represent the “best in class” for conveying contemporary and futuristic perspectives. The foundational editors (Fogel and Woods) with their early grasp on what would come to be a widespread emphasis on women and their health added much influential discovery and practice scholarship to the field. Cognizant of coalescing ever-burgeoning knowledge to influence everexpansive clinical practice, added to the editorial team were expert APRN scholars Ivy M. Alexander, Versie JohnsonMallard, and Elizabeth A. Kostas-Polston. As an adult nurse practitioner clinician scholar, Ivy M. Alexander has focused on midlife women’s health and healthcare, especially menopause and osteoporosis. In her scholarly emphases as a women’s health nurse practitioner, Versie Johnson-Mallard, sheds new light on women’s sexual and reproductive health, including human papillomavirus (HPV)/cancer screening and prevention and behavioral change in response to culturally appropriate educational interventions. In the laboratory as well as the clinic, Elizabeth A. Kostas-Polston, a women’s health nurse practitioner, addresses health promotion and disease prevention strategies focused on sexual and reproductive health and HPV-related cancer prevention. With this third edition, two additional scholars in women’s health expand the editorial team. Joyce D. Cappiello expands the focus on education related to sexual and reproductive health and early pregnancy decision-making. Importantly, Heather S. Hubbard rounds out the team with her expertise in maternal health. You can have confidence that the whole editor/author team comprises remarkably knowledgeable “thought leaders” who are powerfully enthusiastic about women’s health and evolving access to equitable, inclusive, and culturally congruent healthcare for all women. Indicative of such is their engagement in calling attention to missing links within the national women’s health research and clinical services policy agendas. For example, the editors and several contributing authors to this book have participated, as I do, in the Women’s Health Expert Panel of the American Academy of Nursing. It is made up of peer-nominated/elected scholars from academia and healthcare practice focused on shaping superior policy for effective healthcare delivery and clinical practice. Collectively, this group has published and spoken out publicly on what is

xiii

xiv  foreword

crucial to the health of women, critiqued written exposés that were missing a nursing voice, and recently summarized policy agenda considerations stemming from SARS COVID-19 pandemic effects on women’s health. By now you have gathered that it is my honor to urge you to read this forward-looking third edition. We continue to see APRNs bringing a comprehensive approach to primary and collaborative specialty care. No group is better positioned to model the elements brought forward by this book than women’s health APRNs. So, whether you are an ardent advocate

for, thinking about becoming, on the path to becoming, or are an APRN in women’s health, this book should be your provocative and affirming handbook—an accelerant for helping ensure that you are an influential women’s health provider, scholar, leader, policy maker, and spokesperson. Joan L. Shaver, PhD, RN, FAAN Professor and Dean Emerita University of Arizona College of Nursing Tucson, Arizona

Preface We support an individual’s right to autonomy in decision-making about their health based on the personal context of their lives, including but not limited to early pregnancy decision-making and gender affirmation. We believe that individuals have the right to high value, equitable, and unbiased care. In this third edition of Women’s Healthcare in Advanced Practice Nursing, we attempt to make high value, equitable, and unbiased care more evident than in prior editions. While the number of women included in research studies is increasing, we remain limited in our ability to accurately address perspectives and needs for minoritized gender persons because of the lack of research that focuses on, includes, or even identifies transgender and nonbinary persons. Throughout the book we have attempted to use inclusive language while remaining true to research findings, which are translated into evidence-based practice. In many instances, this means we use the terms woman, women, she, her, and hers because that usage reflects the data that are available. We purposefully use they, them, theirs, patient, person, etc. whenever possible. Women’s health has been defined from a variety of perspectives. Women themselves and those who identify as transgender, nonbinary, and queer describe what it means to be healthy. Often their descriptions allude to experiencing the absence of illness or symptoms but more often to being able to perform their roles, and self-identify their gender, and having the mental wellness capacity to respond to stress and strain. This textbook originated in the 1970s as Catherine Ingram Fogel and Nancy Fugate Woods recognized the need for resources for nurses, advanced practice nurses, and nursing students who were interested in the emerging science and healthcare needs of women. The textbook was revised, updated, and renamed to remain current and address timely issues in 1995, 2008, and 2019. The current edition of Women’s Healthcare in Advanced Practice Nursing continues the women-centered focus of previous editions and has been expanded to include, as fully as possible, minoritized gender, nonbinary, transgender, and racialized persons, and confront prejudice in healthcare. Over the past decades, nursing scholars have studied women’s health through the lenses of feminist theory, nursing theory, and more recently through critical race theories, postcolonial theories, and womanist theory. In this relatively short period of history—propelled by a fusion of the U.S. feminist movement, a global pandemic, women’s health being politicalized, and the popular health movement—scholars redefined women’s health as more than women’s reproductive

health. Women’s health grew to be understood to include a holistic view of what it means to be a healthy woman. Indeed, women’s health as a discipline was transformed from gynecology to “Gyn Ecology,” an understanding of women’s health in the context of everyday life. An ecologic perspective considers the multiple environments in which women live their lives, including influences of society, culture, institutions, community, families, and mental and physical health. Taking the lead from patients, clinicians and researchers alike redefined being healthy as the processes of attaining, regaining, and retaining mental and physical health. Moreover, it became more fully appreciated that an individual’s health at one part of the life span influences health later in life. This holistic perspective placed women at the center of clinical services as well as research, focusing on their individual health in the context of their sex and their lives and their communities. Frameworks for understanding women’s health shaped by research and clinical scholarship are expanding to include transgender and nonbinary persons. Scholars challenge investigators to consider the intersectionality of a person’s identities and their health. One’s gender, a social construct, is only one component of who one is: sex (biology), race (social construct), ethnicity, social class, sexual orientation, gender identity, and disability/ableness all intersect in influencing one’s definition of health. And yet, one’s gender identity is important and must be respected for what it is for that person. Additionally, frameworks prompted by globalization reinforce the need to use many different lenses in viewing the health of each person around the world. Efforts to integrate women’s health literature across disciplines has enlarged the perspectives with which communities of nurse scholars and clinicians have come to view women and their health, and provide a solid foundation for doing the same with transgender and nonbinary persons. Over recent decades, we have also seen dramatic changes in advanced practice nursing. Advanced practice nurses now are an essential part of the healthcare workforce, providing increased access to primary and specialty care. As educational programs transition, the push for educating advanced practice nurses about unique healthcare problems, various models of care, and individualized approaches to providing evidence-based care appropriate for all patients has escalated. Part I, Lives and Health for Women and Minoritized Gender Persons,‌‌‌‌‌ views health as inextricably linked to the context in which an individual lives their life, making it impossible to understand health without appreciating the challenges

xv

xvi  preface

and opportunities they face in everyday living. Understanding lived experiences has become key to understanding their well-being and opportunities for health. In Part I, we consider health for individuals within a population, while appreciating lived experiences. This perspective is limited due to the lack of diversity in research and evidence-based data available. Considerations for vulnerable populations, working as caregivers and being healthcare providers, are explored. The emergence of clinical scholarship of women’s health, in contrast to gynecology and obstetrics, gave rise to the need to transform women’s health research as well as models of care and health policy. Refocusing to person-centric and person-sensitive models of care has been influential in shaping the delivery of services in a variety of healthcare settings. Part II, Health Promotion and Prevention, calls attention to the significance of health promotion and prevention, reflected both in one’s own self-care as well as the delivery of professional services. Viewed through the lenses introduced in Part I, health for a person is recognized as a multidimensional experience, much of which is managed by the person, with support from health professionals. What a person does to stay healthy has been studied by numerous disciplines. Those who assume the role of health agent for their families often demonstrate a high level of interest in health-related information. Many justify not attending to their own health due to their need to care for their families. They may manage their own and family members’ illnesses, and simultaneously provide illness-related care to their children, partners, and parents. Health-promotion advice may be sought from professionals to help sort out valid information and recommendations about staying healthy. In Part II, we trace experiences of health and health promotion in young, midlife, and older people as a foundation for understanding wellness and health. Given the lack of focused research, we extrapolate on this to attempt to understand needs for other minoritized gender persons. The emergence of the emphasis on wellness visits prompts us to consider: What is physical health? What is mental health? How does one attain and maintain optimal health? Health practices span nutrition, exercise/activity, and sleep, each of which demonstrably shapes our health. In an

era of personalized healthcare, we examine the influence of the “omics” sciences as foundational to understanding emerging approaches to healthcare delivery. Simultaneously, we consider contextual implications for health and healthcare related to roles in society such as family role, employment role, and, importantly, social perspective of the person and their identified gender. Sexual health, including special considerations for women, lesbians, transgender, bisexual, nonbinary, and questioning persons, and life-stage warrant special consideration for intersection with healthcare access, quality, and choice. Part III, Managing Symptoms and Health Considerations, includes multiple healthcare problems that advanced practice nurses address. In addition to underscoring the importance of listening, validating, and respecting every patient, Part III includes current information about identifying and managing healthcare needs ranging from cardiovascular and endocrine disorders, sexual and reproductive healthcare, menopause, osteoporosis, human papillomavirus, mental health problems, chronic illness, and many more. Some topics are specific to persons with ovaries and a uterus, while many others are not. All are considered from the unique presentation and perspective of the person experiencing it. Several online resources are available for each chapter. Case studies provide real-world application of the materials. Test bank review questions reflect the most salient points of content. Sources for additional information, such as websites and apps for smartphones, are provided. Additionally, PowerPoint slides are available for each chapter and may be used as instructional aids or for content review. Supplemental material is available to qualified instructors by emailing Springer Publishing Company at textbook@ springerpub.com. Ivy M. Alexander Versie Johnson-Mallard Elizabeth A. Kostas-Polston Joyce D. Cappiello Heather S. Hubbard

Acknowledgments The editors gratefully acknowledge the outstanding work of the many current and past contributing authors and emeritus editors whose excellence in research and patient care delivery has enriched this book. We acknowledge the assistance of Springer Publishing Company staff, especially Elizabeth

Nieginski, VP and Publisher, Nursing; Lucia Gunzel, Senior Content Development Editor; and Kris Parrish, Senior Production Manager; as well as Vinodhini Kumarasamy, Compositor for this edition and Project Manager at Amnet.

xvii

Springer Publishing Resources

A robust set of instructor resources designed to supplement this text is available. Qualifying instructors may request access by emailing [email protected].

INSTRUCTOR RESOURCES ● ● ● ● ● ● ●

LMS Common Cartridge—All Instructor Resources Case Studies Test Bank Questions PowerPoint Slides Image Bank Mapping to AACN Essentials: Core Competencies for Professional Nursing Education Transition Guide: Second Edition to Third Edition

Part

I

Lives and Health for Women and Minoritized Gender Persons

Chapter

1

Women and Their Health* Sharon M. Adams, Shavondra Huggins,

Women’s health can be viewed from a multiplicity of perspectives. Women, themselves, are articulate in their descriptions of what it means to be healthy. The World Health Organization’s (WHO’s) definition of health is "a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity" (1946, para.1). Melnyk and Fineout-Overholt (2019) define the evidence-based practice (EBP) approach to health and wellness as clinical decision-making that integrates the most relevant research evidence, one’s own clinical experience, and client preferences and values. Including client’s values in clinical decision-making recognizes the influence that client values and beliefs have on health and wellness outcomes of care and situates EBP within the client’s cultural context (Connor et al., 2023; Melnyk & Fineout-Overholt, 2019). Women’s health is inextricably linked to the context in which women live their lives, making it impossible to understand women’s health without an appreciation of women’s lived experiences in the family unit, community, and work. This approach is key to understanding their chances for health and well-being. The 21st century witnessed a remarkable change in our understanding of women’s health and saw extraordinary improvements in the health and well-being of women in the United States resulting from an increase in access to care, research, policy, and innovative approaches to healthcare. Our understanding of women’s health and unique challenges—informed by research that extends from genomic molecular events to behavioral, psychological, societal, and economic phenomena— continues as one of the most exciting challenges of scientific inquiry and political inquiry. Despite the progress, the health of women in the United States remains subject to wide disparities. Health disparities is a term used to describe inequalities in health, social, political, economic, and environmental resources that adversely affect communities that are socially and/or economically disadvantaged (Brabeman, 2018; Centers for Disease Control and Prevention [CDC], n.d.-a). Disparities among women are thought to result from a complex interaction among biological factors, environment, socioeconomic

and

Versie Johnson-Mallard

factors, and health behaviors. Social determinants of health are included in contributing to disparities and are considered nonbiological factors that have profound influences on health (Brown & Homan, 2023; Lowdermilk et al., 2020; WHO, 2008). It is important to note that health disparity is not just health difference, but rather a difference that is plausibly avoidable and impacts individuals from communities that are socially, politically, and/or economically disadvantaged, such as people who are lesbian, gay, bisexual, transgender, queer (LGBTQ), immigrant, poor, disabled, and/or of color (Brabeman, 2018). An understanding of women’s health issues, if it is to be truly comprehensive, must consider such factors and trends. The first section of this chapter describes selected sociodemographic characteristics of women in the United States. Some of the most notable of these characteristics at the beginning of the 21st century are the changing educational status of women and racial/ethnic populations. The second section presents selected measures of health status. These include mortality, morbidity, and healthcare access and utilization. Next, we discuss the complicated interplay between the steadily changing scientific knowledge regarding the areas of biology and environment. We conclude with an exploration of the future directions for women’s health, including global health trends.

SOCIAL CONTEXT FOR WOMEN’S HEALTH In 2021, the U.S. population of women was estimated at 167.5 million, with women outnumbering men at 3.8 million to 2.2 million at the age of 85 years and older (U.S. Census Bureau, n.d.-b). Who are these women and how healthy are they? To understand the health of women in the U.S. social context, we present the most recently available data on selected social characteristics of women, with a focus on the changing population demographics. Differences in the life circumstances of women are influenced through several pathways, many of which are not yet understood. Considering the health of

*This chapter is a revision of the chapter that appeared in the second edition of this textbook, coauthored with Nancy Fugate Woods, and we thank her for her original contribution.

3

4  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

women within their broad sociostructural environment is important in light of race/ethnicity and socioeconomic status, all of which have an impact on women’s health. Gender differences in some aspects of health status are presented when the differences are remarkable. Notably, data regarding women’s health are limited and often are not available by important demographic characteristics. Race/ethnic variation is discussed when the data sources are available. We recognize the limitations of reporting demographics such as race and ethnicity, because definitions vary over time, and data are inconsistently available for small but growing populations. Furthermore, reporting can obscure the diversity within and among subgroups of women. For example, the Asian/Pacific Islanders category includes more than 25 heterogeneous groups, and no distinction is made in terms of their immigration status. The category “Black” includes African Americans whose families have lived in the United States for generations as well as more recent immigrants such as refugees from war-torn countries such as Somalia. In addition, Hispanic origin is separated by the Census Bureau as an ethnicity not a race. In 2021, about 42 million Americans chose two or more racial categories when asked about their race (American Immigration Council, 2020; Kerns-D’Amore et al., 2023). Also, because detailed racial/ethnic information is frequently unavailable, and because socioeconomic status and cultures of ethnic and racial groups may vary dramatically with important health consequences, racial labeling may mask notable health differences and thus should be considered with caution. Finally, given the strong association between socioeconomic status as measured by family income, poverty threshold, or level of education and the health of women, differences are also noted when data permit.

Growth In 2019, single race non-Hispanic population was about 40 million. Among the U.S. Black population, both multiracial and Hispanic numbers have grown since 2000 (Pew Research Center, 2023). America is becoming a more racially diverse country. The social demographics of multiracial Americans in the United States are steadily growing as a whole. As of 2019, most multiracial Black people in the United States were members of Generation Z (Gen Z; born between 1997 and 2012) or younger, reflecting their youth (Pew Research Center, 2021). Per the U.S. Census Bureau, Gen Z makes up 20.66% of the population and they are said to be the most racially and ethnically diverse. However, millennials (born between 1981 and 1996) still make up the largest generational population at 72.19 million as of 2021 (Duffin, 2022). In 2020, the total female population was racially and ethnically diverse and was composed of White (76.3%); Black or African American (13.4%); Hispanic or Latinx (18.5%); Asian (5.9%), Pacific Islander (0.2%); and American Indian and Alaska Native (1.3%; Kerns-D’Amore et al., 2023). Population growth rates remain higher among the Hispanic population than among White non-Hispanic or Black subgroups since last noted in 2015. In fact, by the year 2060, population projections indicate that Hispanic (27.5%), Black (15.0%), American Indian (1.4%), Asian (9.1%), and two or more (6.2%) will constitute 59.2% of the total population (Vespa et al., 2020). By the year 2030, racial ethnic minority youth, age 18 years

and younger, will be 53% shifting to 59% by 2045 (U.S. Census Bureau, 2020). In 2021, the general fertility rate was 56.6 births per 1,000 women age 15 to 44, the first increase in the rate since 2014 (Hamilton et al., 2022).

Immigration The United States is largely a nation of immigrants, and the immigrant population is increasing. In 2020, there were 86 million immigrants in the United States, which made up 26% of the population (Kerns-D’Amore, 2023; U. S. Department of Homeland Security, n.d.). There are more than 23.2 million female immigrants in the United States today, outnumbering men. Since 2018, foreign women make up 51.8% of the total foreign-born population (American Immigration Council, 2020). Among the immigrant population, 23.26% were born in Mexico, 5.43% in India, 5.34% in China, 5.22% in the Philippines, 3.11% in Vietnam, 3.07% in El Salvador, 2.93% in Cuba, 2.86% in Dominican Republic, 2.64% in Korea, 1.97% in Colombia, and 44.17% from other areas of the world (American Immigration Council, 2020). The continuing influx of immigrants contributes to growing racial/ethnic diversity in the U.S. population. Regardless of the country of origin, most immigrants confront challenges such as linguistic differences and changes in financial status on arriving in the United States. The process of immigration can affect health status and behaviors adversely through disruption of social networks; new exposure to racial and class-based discrimination; differential adverse environmental exposures; and adjustment to new language, culture, and values. For example, rates of obesity, smoking, alcohol, and illicit drug use tend to increase among Mexicans who immigrate to the United States.

Linguistic Differences The United States is not known for being multilinguistic, leading to marked linguistic challenges for some, but not all, immigrant populations. For example, among foreign-born Blacks, most of whom are from island nations such as the Dominican Republic, Haiti, Jamaica, and Trinidad, English proficiency is common. In contrast, more traditional Hispanic immigrants often have limited English proficiency. Similarly, Asian/Pacific Islander women, who emigrate from more than 20 countries, may speak one of more than 1,000 different languages. When immigrant women enter healthcare organizations, their level of English proficiency combined with the healthcare provider’s potential lack of linguistic and cultural competence can lead to the underutilization of healthcare services and unintended adverse health outcomes. Linguistic differences may play a role in family dynamics and social, educational, and employment opportunities for immigrants.

Educational Attainment Educational attainment is one of the most important influences on economic well-being among women and has a profound impact on women’s health. Graduating from high school and college significantly improves women’s health and well-being by increasing economic security and providing

Chapter 1  Women and Their Health 5

the literacy skills necessary to navigate the healthcare system. Conversely, lacking a high school diploma may cause women to have lower earnings and greater difficulty in obtaining healthcare; in addition, they are more likely to engage in substance abuse and suffer from other adverse health consequences. Although the U.S. overall trends reflect a more educated population, significant differences in educational attainment persist with regard to gender and race/ethnicity. Persons with less than a high school education have death rates at least double the rates of those with education beyond high school. Nonetheless, the educational attainment of women indicates a dramatic improvement for a group that has historically been less educated, and these differences have been decreasing in recent years. Almost one third (31.7%) of immigrant women age 25 and older had a bachelor’s degree or more education in 2018, compared to 33.6% of native-born women and 32.4% of foreign-born men. Immigrant women had a higher percentage of bachelor’s degrees or higher compared to their male counterparts in five out of 10 of the top origin countries for female immigrants. Women’s progress in educational attainment has been striking over the years. The share of immigrant women with a bachelor’s degree or higher education increased from 27.5% in 2012 to 31.7% in 2018. The share of native-born women with a comparable level of education also increased from 29.4% in 2012 to 33.6% in 2018 (American Immigration Council, 2020). Women have earned more bachelor’s degrees than men since 1982, more master’s degrees than men since 1987, and more doctorate degrees than men since 2006 (Catalyst, 2022). Despite the narrowing in educational attainment between women and men, persistent differences among racial/ ethnic groups may contribute to restricted employment opportunities and decreased financial solvency for less educated women. The educational attainment of foreign-born women in 2018 varied widely according to country of origin. Among the top 10 origin countries for female immigrants, the highest percentage of immigrant women with a bachelor’s degree or more education came from India (76.3%), Philippines (51.6%), and Korea (51.1%). At the other end of the spectrum was Mexico and El Salvador (both at 7.9%), and the Dominican Republic (16.8%). Racial/ethnic disparities in education are evident (American Immigration Council, 2020).

Veteran Status In 1973, the end of the draft and transition to the All-Volunteer Force (AVF) marked a dramatic increase in women’s opportunity to serve in the military. This had a huge impact on why women account for an increasing proportion of veterans of the U.S. Armed Forces. In 2020, 1.7 million women were veterans of the Armed Forces. They accounted 9% of the total veteran population and 2% of the total adult female population, and 82% of all female veterans were of working age (18–64 years old), compared with 79.7% of nonveteran women. More than 78% of these women are under the age of 45, with 23% being Black/non-Hispanic and 12% Hispanic. Also, for this same age group, a higher percentage of veterans generally have completed some form of college education compared to nonveteran women (Arsitio & Gutierrez, 2023; Betancourt et  al., 2023; Brady & Keller, 2023). Continuous

changes in the military roles of women as well as their multiple deployments and blurring of combat and noncombat operations suggest that the needs of these women may differ greatly from those of women veterans from previous eras. Women veterans are younger than their male counterparts, with 21% younger than 35 years compared with 7% of male veterans, and women account for a much smaller proportion of veterans older than 65 years (45% for men, 16% for women; Eichler, 2022; Holliday et al., 2023). The poverty rate is higher than for male veterans; 10% of women veterans live below the poverty level versus 16% of male veterans (Cohen et al., 2022). Military sexual trauma (MST), sexual assault, and/or severe and threatening sexual harassment occurring during military service have been identified in 15% of women and 7% of men. MST, along with deployment to war zones and combat exposure, increases the risk of posttraumatic stress disorder (PTSD), depression, and substance abuse. Efforts to provide gender-sensitive care for women veterans are discussed in Chapter 3, Women and Healthcare.

Employment The proportion of women to men in the workforce has changed from previous generations. In 2019, 57.4% of all women participated in the labor force compared to 69.2% of men. From 1970 to 2019, the proportion of women in the labor force holding college degrees ages 25 to 64 quadrupled, yet the proportion of men holding college degrees barely doubled over the same time frame (U.S. Bureau of Labor Statistics, 2021). Although women hold more college degrees, their pay is still less compared to men. Women in the United States earned approximately 82 cents for every dollar earned by men; women of color earn even less. Compared to every dollar earned by White men, Asian women earned 81 cents, Native Hawaiian and other Pacific Islander women earned 63 cents, Black women earned 63 cents, Latinas earn 55 cents, and Native American women earn 60 cents (U.S. Bureau of Labor Statistics, 2021). Employment can have beneficial or negative effects on the well-being of women. The highest percentage of women in the labor workforce by age is 25 to 54 years. Estimates from the U.S. Bureau of Labor Statistics (2021) are that 76% are age 25 to 54 years, 59.6% are 55 to 64 years, and 16.4% are 65 years and older. The labor force participation rates of women have been increasing across age groups, except among young and older women. Women 16 years and older account for 51.5% of those employed in management, professional, and related occupations (U.S. Bureau of Labor Statistics, 2023). The number of women working full time or with children (or combination of both) have increased their participation in the labor force considerably. The increase in the percentages of women with children and two-parent families who are employed outside the home highlights the importance of child care issues and support systems for women faced with multiple responsibilities. The United States is one of the few industrialized countries that does not provide paid maternity leave and health benefits guaranteed by law. Although the 1993 Family and Medical Leave Act (FMLA) guarantees unpaid leave to workers in businesses with 50 or more employees, the FMLA disproportionately excludes low-wage workers who often work in smaller businesses. Prior to March 2010, women who were

6  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

eligible for FMLA may have opted not to take it due to their plan to breastfeed. However, on March 23, 2010, the Fair Law Standard Act (FLSA) was amended by the Patient Protection and Affordability Act requiring employers to allow a place and time for a breastfeeding parent to express milk from their breast as well as a place for storage (U.S. Department of Labor, n.d.). Per the 2018 FMLA Employee Survey, although men need and take leave for the same reasons as women, women seem (a) to need leave more, yet a higher percentage forgo taking leave when needed and (b) take longer leaves since maternity leave is three times longer than paternity leave on average. Compared to men, the financial loss for women taking FMLA leave is greater. This is not only due to longer leave time, but also due to being a single household, earning lower pay, or facing career penalties for taking leave (Brown et al., 2020). In 1996, the United States dramatically altered its welfare program with the passage of the Personal Responsibility and Work Opportunity Reconciliation Act (PRWORA), which ended federal administration of welfare and replaced it with block grants to the states. This cash assistance program, known as Temporary Aid to Needy Families (TANF), imposes lifetime limits on benefits, more stringent work requirements, and a host of behavioral mandates (Balbus, 2022; Cheng & Lo, 2022; Fusaro & Gerwirtz, 2022). Overall, most women report that they did not receive paid sick leave, paid vacation, or health benefits. The working conditions faced by mothers who had been on welfare previously are worse in part because of their significant lower levels of education, which increases the likelihood of their having to work in poorer conditions, including part-time positions that lack benefits (Brown, 2022; Lleras, 2008; Park & Choi, 2023). Women in the workforce were impacted by COVID-19 because women make up a huge portion of those working in areas considered essential such as healthcare and education (Laughlin & Wisniewski, 2021).

Economic Status Between 2019 and 2020, poverty rates increased for married couple families and families with a female householder. The poverty rates for married couple families increased from 4.0% in 2019 to 4.7% in 2020. For families with a female householder, the rate increased from 22.2% in 2019 to 23.4% in 2020. The poverty rate for families with a male householder was 11.4% in 2020 (not much difference from 2019; Shrider et al., 2021). Poverty is most prevalent among the Hispanic and Black ethnic groups, representing 36% living in poverty. The Black ethnic group represent 19.5%. Hispanics are close behind at 17.1%, while white non-Hispanic rates were at 8.1% in 2021 (Creamer et al., 2022; Table 1.1). In 2021, poverty rates in the United States among women under the age of 18 represent 17%, women 18 to 24 represent 21.55%, women 25 to 34 represent 14.75%, women 35 to 44 represent 12.64%, women 45 to 54 represent 10.08%, women 55 to 64 represent 11.45%, women 65 to 74 represent 10.25%, and women 75 years and over represent 13.51% (Statista, n.d.). Poverty status is related to age. Regardless of race/ethnicity, women 45 to 54, 55 to 64, and 65 to 74 years of age are less likely to experience poverty than those age 18 to 44 years. Women 75 years and over experienced an increase of poverty rate (12.54%). Clearly, poverty status does not discriminate. A person’s status can change based on gender, ethnicity,

TABLE 1.1  Persons Below Poverty Level, by Selected Ethnic Groups in the United States, 2021 RACE/ETHNICITY

POVERTY RATE (%)

White

10

Black

19.5

Asian

8.1

Hispanic or Latino

17.1

White, non-Hispanic

8.2

Source: Adapted from Statista Research Department. (2022, September 30). Poverty rate in the United States by ethnic group 2021. https://www.statista.com/statistics /200476/us-poverty-rate-by-ethnic-group

age, educational attainment, or health hazards, specifically the COVID-19 pandemic. Before the most recent recession, caused by COVID-19 pandemic, the median household income was $67,521 in 2020, a decrease of 2.9% from 2019 median of $69,560, the first statistically significant decline in household median increase since 2011 (Shrider et al., 2021).

Household Composition Dramatic changes in family formation and marriage patterns have occurred since the mid-1960s, especially with the legalization of same-sex marriages in all 50 states as of June 26, 2015. This focus represents the family diversity growing within the United States, married or not. As of 2021, there were roughly 710,000 same-sex married couple households and 500,000 households with same-sex unmarried partners cohabiting (Borelli, 2023; Scherer, 2022; Pathak & Dev, 2023). There has also been a significant increase in the percentage of people, over the age of 15, who have never been married from 23% in 1950 to 34% in 2021. Living arrangements for young adults (ages 18–24) differ greatly now compared to before as well; they represent approximately 58% of population still living within a parent home (U.S. Census Bureau, 2021).

Caregivers In addition to contributing solely or significantly to their family’s income through employment, many women are the main caregivers of children and aging parents for their families. Given that women disproportionately carry the responsibility for family caregiving, they may struggle to meet the demands of both work and family care. Caregiving for women is discussed in detail in Chapter 18, Health Considerations for Women Caregivers.

Reproductive Trends FERTILITY

The general fertility rate for the United States relates the number of births to the number of women of childbearing age. In 2021, the overall fertility rate was 56.3 per 1,000 women of childbearing age (Martin et al., 2022), which is a decrease from 68.7 per 1,000 women in 2008 (Hamilton et al., 2010) The U.S. fertility rate hit a record low in 2020, just as it did

Chapter 1  Women and Their Health 7

in 2019 and 2018. Although the COVID-19 pandemic seems to have accelerated this decline, the drop has been underway for years. The overall trend in declining birth rates, however, are largely due to women’s changing roles, employment shifts, and advances in reproductive health. After WWII, the United States saw rapid change in gender roles with the expansion of women’s education and entry into the labor force as previously discussed (McPhail et al., 2023; Toosi & Morisi, 2017). BIRTH RATES FOR TEENAGERS

The drop in U.S. birth rates for teenagers was first noted after 2007, dropping 7% annually. The teen birth rate has declined to a new low each year since. In 2020, the teen birth rate was 15.4 births for every 1,000 females age 15 to 19, down 8% from 2019 and down 73% from the 1991 peak of 61.8% (U.S. Department of Health & Human Services [DHHS], 2022). SINGLE-PARENT CHILDBEARING

After rising 13-fold from 1940 through 1990, the rate of increase in nonmarital childbearing slowed during the 1990s. The birthrate among unmarried women in 2007 and 2008 peaked at 51.8% per 1,000 unmarried women aged 15 to 44 years and declined to 37.8 in 2021 (Osterman et al., 2023). There were 158,043 births to females age 15 to 19, which accounted for less than 5% of births in 2020, and given the age of these mothers, in 2020 nine of every 10 (91.7%) of these births occurred outside marriage (Office of Population Affairs, n.d.). The percentage of unintended pregnancies has dropped to 45% in 2011 from 51% in 2008. The rates are higher among low-income and non-Hispanic Black women. Several goals were set by Healthy People 2030 to improve

planned pregnancy: (1) offering full range of long-acting contraceptives and (2) enhanced education on correct and consistent use of contraceptives (CDC, n.d.-i).

HEALTH STATUS INDICATORS Health status indicators, one of the simplest ways to understand health status across populations, include using data on mortality, morbidity, and access to and utilization of health services. The following health status indicators are selected primarily based on whether they had a marked impact on women’s quality of life, functioning, or well-being; affected a large proportion of women or a subgroup of women; or reflected an important emerging health issue. When data are available and differences for key health conditions are notable, we provide prevalence or incidence estimates based on race/ ethnicity and gender. Moreover, given the strong relationship between health and income, which is especially important for women who represent most of the poor in the United States, we report health measures by socioeconomic differences.

Life Expectancy Life expectancy is a key indicator of health status worldwide, and mortality rate is the measure of the number of deaths per unit of the population. Due to COVID-19, life expectancy decreased more among Hispanic and non-Hispanic Black people than non-Hispanic White people in the United States in 2020 (Figure 1.1). The life expectancy of U.S. women has

1,600

1,400 Deaths per 100,000 U.S. standard population

2019

11,399.0

2020

1,200 1,092.8 1985.0

1,000

1905.2

1903.8 1835.4

800

868.8

724.9

715.2 633.2

1703.1

627.4

1570.1

600 430.7 400

0

Total2

Male

Female Hispanic

Black male

Black female

White male

White female

Non-Hispanic

FIGURE 1.1  Age-adjusted death rates, by sex and race and ethnicity: United States, 2019 and 2020. Source: Reproduced from Murphy, S. L, Kochanek, K. D, Xu, J., & Arias, E. (2021). Mortality in the United States, 2020 (NCHS Data Brief No. 427). National Center for Health Statistics. https://doi .org/10.15620/cdc:112079

8  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS At birth 78.8 77.0

Both sexes

76.3 74.2

Male

81.4 79.9

Female At age 65 19.6 18.5

Both sexes

18.2 17.0

Male

2019 2020

20.8 19.8

Female

0

20

40

60

80

100

Life expectancy (years)

FIGURE 1.2  Life expectancy at birth and age 65, by sex: United States, 2019 and 2020. Source: Reproduced from Murphy, S. L, Kochanek, K. D, Xu, J., & Arias, E. (2021). Mortality in the United States, 2020 (NCHS Data Brief No. 427). National Center for Health Statistics. https://doi .org/10.15620/cdc:112079

nearly doubled since the turn of the 21st century, from 48 years in 1900 to a record high of 81.4 years in 2019, compared to 76.3 years for men (Figure 1.2; Murphy et al., 2021). Overall, women are expected to outlive men by an average of 5 to 6 years, and this varies by race/ethnicity. Hispanic women had the longest life expectancy (82.4 years), outliving non-Hispanic Black women (75.7 years) and non-Hispanic White women (80.2 years) in 2020 (Arias et al., 2021). Compared to 2021, Hispanic women’s life expectancy decreased to 81 years, non-Hispanic Black women decreased to 74.8 years, and non-Hispanic White women decreased to 79.2 years (Arias et al., 2022). However, by age 65 years these differences narrow, and life expectancy becomes more similar for White and Black women. Although life expectancy has increased since 1960 for both women and men, women’s life expectancy increased by 20.5 years versus 19.8 years in men (average life expectancy is 75.1 years for women vs. 70.6 years for men; WorldData.info, n.d.). Although the United States has one of the highest healthcare expenditures as a percentage of gross domestic product than other developed countries, the life expectancy for women is lower in the United States than in several other developed countries (Table 1.2; WorldData.info, 2020), specifically Canada.

Causes of Death In the 21st century, significant progress was made toward increasing the years of life for most Americans, regardless of race/ethnicity or gender. Americans live longer than ever before. Presently, the chronic conditions of heart disease, cancer, COVID-19, and unintentional injuries account for more

than half of U.S. deaths and are the leading causes of death for both men and women (Xu et al., 2022). As of 2019, the COVID-19 pandemic began to disrupt the lives of many people around the world. This unexpected pandemic made the top 10 leading causes of death in the United States, ranking No. 3 within 1 year (Figure 1.3). Although women have a longer life expectancy than men, they do not necessarily live those extra years in good physical and mental health. In 2017, Mississippi and West Virginia remained in the top five states with the highest death rates in the United States. Alabama, Kentucky, and Oklahoma were among the other three. Hawaii remained in the top five having the lowest death rates with New York, Connecticut, California, and Minnesota (Xu, 2019). As a nation we are doing well, but data support that a few states remain burdened with health status indicators of high mortality rates for men and women, calling for unique and targeted systems interventions. HIV death rates are declining globally, in both men and women, falling below the most common causes of death such as heart disease, liver disease, respiratory conditions, stroke, cancers, and Alzheimer disease as of 2016 (Murphy et al., 2021; WHO, 2020; see HIV section later in chapter). Leading causes of death vary by age, with unintentional injury the leading cause of death for women 25 to 44 years of age and the third leading cause for 45- to 65-year-olds. Suicide and homicide are the fourth and fifth most common causes for 25- to 44-year-olds, and pregnancy complications account for the ninth leading cause of death for this age group. Cancer, heart disease, and chronic lower respiratory disease are the top three causes of death for women 65 to 84 years old, but this shifts to heart disease, Alzheimer disease, and cancer beyond age 85; in both groups stroke is a close fourth (Table 1.3; Heron, 2021).

Chapter 1  Women and Their Health 9

TABLE 1.2  Life Expectancy at Birth for Selected Countries: Men and Women, 2020 COUNTRY

MEN: LIFE EXPECTANCY (YEARS)

WOMEN: LIFE EXPECTANCY (YEARS)

RANK

Hong Kong

82.9

88

1

Japan

81.6

87.7

4

Spain

79.7

85.1

19

France

79.2

85.3

23

Switzerland

81.1

85.2

8

Australia

81.2

85.3

7

Israel

80.7

84.8

11

Sweden

80.7

84.2

10

Canada

79.7

83.9

18

Greece

78.6

83.7

29

Ireland

80.4

84.1

13

Denmark

79.6

83.6

20

Costa Rica

76.8

81.9

35

Puerto Rico

73.6

82.6

50

United States

74.5

80.2

47

China

75.3

81.1

39

75

83.7

43

El Salvador

66.4

75.4

96

South Africa

62.2

68

106

India

68.6

71.8

82

Haiti

61.1

67.1

110

Afghanistan

59.9

65.4

113

Congo

57.8

61.7

120

Somalia

54

58.1

121

51.2

54.4

123

Thailand

Chad

Source: Data from WorldData.info. (2020). Life expectancy for men and women. https://www.worlddata.info/life-expectancy.php#by-population

Morbidity Morbidity is a generic measure that assesses the quantity of health in a given population and is easy to interpret and compare across populations and time. The incidence of specific outcomes such as injuries, chronic conditions, mental illness, and activity limitations are summary measures of morbidity, which are presented in this section. INJURIES

In 2020, 200,955 deaths from unintentional injuries were reported. Unintentional injuries included falls contributing 42,114, motor vehicle accidents (MVA) contributing 40,698, and poisoning contributing 87,404 (CDC, 2020). Male burden of mortality (7.6%) was higher than female (4.4%), ranking as

the third leading cause of death for men and sixth leading cause of death for women (Heron, 2021). Approximately one third of age-adjusted deaths are due to unintentional injuries. Ages 1 to 9 (31%), ages 10 to 24 (38.1%), and ages 25 to 44 (34.2%) make up the one third age-adjusted population. However, by age 45+ unintentional injuries barely make up one tenth of age-adjusted deaths. By ages 45 to 64 (9%) and ages 65 and over (2.9%) a dramatic decrease in the percentage of deaths caused by unintentional injuries is obvious (Figure 1.4; Heron, 2021). VIOLENCE AGAINST WOMEN

Violence against women is a global issue that goes beyond mortality and injuries, carrying a high burden of morbidity and health illnesses (WHO, n.d.). Violence is a term that encompasses a broad range of maltreatment against women and

10  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS 161.5 1168.2

Heart disease 146.2

Cancer

2144.1

COVID-19 *

85.0 49.3

Unintentional injuries

157.6

37.0 138.8 38.2 236.4 29.8 132.4

Stroke Chronic lower respiratory diseases Alzheimer disease

21.6 124.8

Diabetes Influenza and pneumonia

12.3 113.0

Kidney disease

12.7 12.7 0

2019 2020 30

60

90

120

150

180

Deaths per 100,000 U.S. standard population

FIGURE 1.3  Age-adjusted death rates for the 10 leading causes of death in 2020: United States, 2019 and 2020. Source: Reproduced from Murphy, S. L, Kochanek, K. D, Xu, J., & Arias, E. (2021). Mortality in the United States, 2020 (NCHS Data Brief No. 427). National Center for Health Statistics. https://doi .org/10.15620/cdc:112079

TABLE 1.3  Leading Causes of Death in Females, All Races and Origins—United States, 2017 RANK

TOTAL (%)

1–19 YEARS (%)

20–44 YEARS (%)

45–64 YEARS (%)

65–84 YEARS (%)

85+ YEARS (%)

1

Heart disease (21.8)

Unintentional injury (32.7)

Unintentional injury (30)

Cancer (34.2)

Cancer (27)

Heart disease (27.7)

2

Cancer (20.5)

Cancer (11)

Cancer (16)

Heart disease (16.3)

Heart disease (19.9)

Alzheimer disease (10.9)

3

Chronic lower respiratory disease (6.2)

Suicide (10.3)

Heart disease (9)

Unintentional injury (6.9)

Chronic lower respiratory disease (8.9)

Cancer (9.9)

4

Stroke (6.2)

Homicide (7.4)

Suicide (7.6)

Chronic lower respiratory disease (5.3)

Stroke (5.8)

Stroke (8.1)

5

Alzheimer disease (6.1)

Birth defects (6.4)

Homicide (3.8)

Diabetes (3.8)

Alzheimer disease (4.4)

Chronic lower respiratory disease (4.9)

6

Unintentional injury (4.3)

Heart disease (3.4)

Chronic liver disease (2.9)

Stroke (3.6)

Diabetes (3.3)

Flu and pneumonia (2.7)

7

Diabetes (2.7)

Flu and pneumonia (2)

Diabetes (2.4)

Liver disease (3.5)

Unintentional injury (2.3)

Unintentional injury (2.6)

8

Flu and pneumonia (2.2)

Stroke (1.4)

Stroke (2)

Suicide (2)

Kidney disease (2.1)

Hypertension (1.9)

9

Kidney disease (1.8)

Chronic lower respiratory disease (1.2)

Pregnancy complications (1.9)

Septicemia (1.8)

Flu and pneumonia (2)

Diabetes (1.8)

10

Septicemia (1.6)

Benign neoplasm (1)

Septicemia (1.2)

Kidney disease (1.6)

Septicemia (1.8)

Kidney disease (1.7)

Source: Adapted from Heron, M. (2021). Deaths: Leading causes for 2018. National Vital Statistics Report, 70(4). https://doi.org/10.15620/cdc:104186.

Chapter 1  Women and Their Health 11 Ages 1–9

Other 27.3

Ages 10–24

Unintentional injuries 31.8

Stroke 1.3 Perinatal conditions 1.3 Septicemia 1.4 CLRD 1.9 Heart disease 3.0 Influenza and pneumonia 3.1

Stroke 0.6 CLRD 0.7 Other Influenza and pneumonia 0.8 14.0 Diabetes 0.8 Congenital malformations 1.6 Heart disease 3.0 Cancer 5.5 Homicide 14.4

Cancer 11.7

Homicide 7.7

Unintentional injuries 38.3

Suicide 20.5

Congenital malformations 9.5 Ages 45–64

Ages 25–44

Other HIV disease 0.9 19.6 Influenza and pneumonia 1.0 Unintentional Stroke 1.6 injuries Diabetes 2.2 34.0 Chronic liver disease and cirrhosis 3.0 Homicide 6.1 Heart Suicide disease 11.2 10.1 Cancer 10.3

Other 20.6

Influenza and pneumonia 1.5 Septicemia 1.5 Suicide 3.1

Cancer 28.0

Stroke 3.3 Heart disease 21.0

Diabetes 4.0 Chronic liver disease and cirrhosis 4.1 CLRD 4.2 Unintentional injuries 8.7

Ages 65 and over

Other 24.6

Ages 85 and over

Other 27.1

Heart disease 25.1

Heart disease 28.6

Parkinson disease 1.6 Kidney disease 2.0 Influenza and pneumonia 2.3 Unintentional injuries 2.7 Diabetes 2.9 Alzheimer disease 5.7

Cancer 20.5 CLRD 6.5 Stroke 6.1

Hypertension 1.7 Kidney disease 1.9 Diabetes 1.9 Unintentional injuries 2.7 Influenza and pneumonia 2.8

Cancer 11.7 Stroke 7.3 CLRD 5.1

FIGURE 1.4  Percent distribution of the 10 leading causes of death by age group: United States 2019. Source: Reproduced from Heron, M. (2021). Deaths: Leading causes for 2019. National Vital Statistics Report, 70(4), 11. https://www.cdc.gov/nchs/data/nvsr/nvsr70/nvsr70-04-508.pdf

Alzheimer disease 9.1

12  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

men. As per the United Nations, violence against women is defined as “any act of gender-based violence that results in, or is likely to result in, physical, sexual or psychological harm or suffering to women, including threats of such acts, coercion or arbitrary deprivation of liberty, whether occurring in public or in private life” (1994, p. 3). Intimate partner violence (IPV) and sexual violence (SV) are common forms of violence against women. IPV (the most common form of violence experienced by women) is behavior by an intimate partner or ex-partner that causes physical, sexual, or psychological harm, including physical aggression, sexual coercion, psychological abuse, and controlling behaviors; whereas SV is “any sexual act, attempt to obtain a sexual act, or other act directed against a person’s sexuality using coercion, by any person regardless of their relationship to the victim, in any setting” (WHO, n.d.). Per the National Intimate Partner and Sexual Violence Survey (NISVS) of 2010, SV includes five types: rape, being made to penetrate someone else, sexual coercion, unwanted sexual contact, and noncontact unwanted sexual experiences. Violence against women is a broad term that can include IPV, SV, trafficking, femicide, acid attacks, genital mutilation, and forced marriages. Worldwide, women ages 15 to 49 represent 35% of the population who has reported physical or sexual IPV or nonpartner SV in their lifetime; and out of that number, 30% is specifically IPV (WHO, n.d.). In the United States alone, 35.6% of women and 28.5% of men have experienced some form of IPV. This percentage is likely higher in IPV because the woman usually knows the partner and therefore is comfortable enough to be somewhere alone with them. This is also true for women who are trafficked. Violence against women, specifically rape, does not discriminate due to a person’s age (Figure 1.5), race/ethnicity (Table 1.4), or sexual orientation (Table 1.5). Although the age range of 18 to 24 represents the highest percentage of women rape victims at 37.4%, girls age 10 and younger still represent an alarming 12.3%. Approximately 22% of Black women, 18.8% of non-Hispanic women, 14.6% of Hispanic

women, 26.9% American Indian/Alaska Native, and 33.5% of multiracial non-Hispanic women have reported rape in their lifetime (SDG, Injuries & Violence, 2018). Approximately 13.1% of lesbian women, 46.1% of bisexual women, and 17.4% of heterosexual women have been raped at some point in their lifetime. The percentages for other sexual violence acts in lesbian, bisexual, and heterosexual women are even higher (Walters et al., 2013). Globally, approximately 38% of murders are committed by intimate partners (WHO, 2021b). There are many risk factors associated with violence against women. Some factors are shared among IPV and SV,

45+ years 1.7%

25–34 years 14.2% 11–17 years 29.9%

35–44 years 4.5% 10 years and under 12.3%

18–24 years 37.4%

FIGURE 1.5  Age at time of first completed rape victimization in lifetime among female victims. Source: Reproduced from Black, M. C., Basile, K. C., Breiding, M. J., Smith, S. G., Walters, M. L., Merrick, M. T., Chen, J., & Stevens, M. R. (2011). The National Intimate Partner and Sexual Violence Survey (NISVS): 2010 summary report. National Center for Injury Prevention and Control, Centers for Disease Control and Prevention. https://www.cdc.gov/violenceprevention/pdf /nisvs_report2010-a.pdf

TABLE 1.4  Lifetime Prevalence of Sexual Violence by Race/Ethnicity—U.S. Women NON-HISPANIC HISPANIC

BLACK

WHITE

ASIAN OR PACIFIC ISLANDER

AMERICAN INDIAN OR ALASKA NATIVE

MULTIRACIAL

Rape Weighted % Estimated Number of Victims

14.6 2,202,000

22.0 3,186,000

18.8 15,225,000

*

26.9 234,000

33.5 452,000

Other sexual violence Weighted % Estimated Number of Victims

36.1 5,442,000

41.0 5,967,000

47.6 38,632,000

29.5 1,673,000

49.0 424,000

58.0 786,000

*Estimate is not reported. Source: Reproduced from Black, M. C., Basile, K. C., Breiding, M. J., Smith, S. G., Walters, M. L., Merrick, M. T., Chen, J., & Stevens, M. R. (2011). The National Intimate Partner and Sexual Violence Survey (NISVS): 2010 summary report. National Center for Injury Prevention and Control, Centers for Disease Control and Prevention. https://www.cdc.gov /violenceprevention/pdf/nisvs_report2010-a.pdf

Chapter 1  Women and Their Health 13

TABLE 1.5  Lifetime Prevalence of Sexual Violence by Any Perpetrator by Sexual Orientation—U.S. Women LESBIAN

BISEXUAL

HETEROSEXUAL

WEIGHTED %

ESTIMATED NUMBER OF VICTIMS

WEIGHTED %

ESTIMATED NUMBER OF VICTIMS

WEIGHTED %

ESTIMATED NUMBER OF VICTIMS

13.1

214,000

46.1

1,528,000

17.4

19,049,000

Completed forced penetration

*

*

36.5

1,209,000

11.4

12,490,000

Attempted forced penetration

*

*

*

*

5.1

5,590,000

Complete alcohol/drug facilitated penetration

*

*

24.4

810,000

7.6

8,263,000

Other sexual violence

46.4

756,000

74.9

2,482,000

43.3

47,325,000

*

*

29.6

981,000

12.4

13,523,000

Unwanted sexual contact

32.3

526,000

58.0

1,922,000

25.9

28,352,000

Noncontact unwanted sexual experiences

37.8

616,000

62.9

2,085,000

32.4

35,422,000

Rape

Sexual coercion

Note: Estimated numbers have been rounded to the nearest thousand. *Estimate is not reported. Source: Reproduced from Walters, M. L., Chen J., & Breiding, M. J. (2013). The National Intimate Partner and Sexual Violence Survey (NISVS): 2010 findings on victimization by sexual orientation. National Center for Injury Prevention and Control, Centers for Disease Control and Prevention. https://www.cdc.gov/violenceprevention/pdf/nisvs_sofindings.pdf

while others are specific to each (Table 1.6). Shared factors include history of family violence, history of alcohol and/ or drug abuse, lower educational levels, community norms, and gender inequality. Sadly, forms of emergencies, including epidemics and pandemics, tend to increase the amount of violence against women cases. Specifically, the COVID-19 pandemic has exacerbated violence against women, while also limiting access to services. A women’s health can be negatively affected by violence. Health consequences may include, yet are not limited to, death (by homicide or suicide), obstetric issues (unintended pregnancy; late, little, or no prenatal care), gynecologic issues, sexually transmitted infections (STIs), and psychological issues (depression, posttraumatic stress, anxiety, eating disorders, sleeping disorders, suicide ideations/attempts). Children can be affected negatively by violence against women, specifically IPV, as higher rates of infant and child mortality and morbidity have been associated. Children known to have grown up in families with history of violence may suffer from psychological and/or emotional disturbances. Unfortunately, these disturbances have been associated with being an abuser or victim of violence later in life (WHO, 2021b). Although these data indicate the high prevalence of the problem, reporting of violence against women remains inconsistent. Although some experts believe that studies overestimate the extent of violence against women, others believe that there is underestimation. To date, few national studies report on women who are immigrants, homeless, disabled, in the military, or in other institutionalized situations, which may be populations at significantly greater

TABLE 1.6 Risk Factors Associated With Violence Against Women ASSOCIATED RISK FACTORS

IPV

Past history of exposure to violence

X

Marital discord and dissatisfaction

X

Difficulties in communicating between partners

X

Male controlling behaviors toward partners

X

SV

Beliefs in family honor and sexual purity

X

Ideologies of male sexual entitlement

X

Weak legal sanctions for sexual violence

X

IPV, intimate partner violence; SV, sexual violence. Source: Adapted from World Health Organization. (2021, March 9). Violence against women. http://www.who.int/news-room/fact-sheets/detail/violence-against-women

risk of violence against women. Accurate history taking and overall assessment of girls and women is crucial in the effort to identify and report violence against women, while also providing appropriate care. EMERGING INFECTIONS

Infectious diseases continue to affect all people, regardless of gender, age, ethnic background, lifestyle, and socioeconomic status. They cause suffering and death and impose an

14  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

enormous financial burden in the United States. Many infectious diseases have been conquered by modern interventions such as vaccines and antibiotics. New diseases are constantly emerging, including Zika, Ebola, severe acute respiratory syndrome, Lyme disease, hantavirus pulmonary syndrome, and the recent COVID-19; others reemerge in drug-resistant forms, including malaria, tuberculosis, and bacterial pneumonias. Among women, populations of particular concern include pregnant women, immigrants, and refugees. For example, if a pregnant woman acquires an infection, it can increase the infant’s risk of preterm delivery, low birth weight, long-term disability, or death. Although many of these adverse birth outcomes could be prevented by prenatal care, access to and utilization of prenatal care are disparate by race/ ethnicity and socioeconomic status. For example, infants born to American Indian and Black women have the highest neonatal death rates because of infectious diseases than any other group (Ely & Driscoll, 2021). CORONAVIRUS

Coronaviruses are important human and animal pathogens. In December 2019, a cluster of cases of pneumonia of unknown cause began to emerge in Wuhan, China. On December 31, 2019, a novel coronavirus was identified as the cause of this cluster of pneumonia cases in Wuhan, a city in the Hubei Province of China. It rapidly spread, resulting in an epidemic throughout China, followed by a global pandemic. In February 2020, WHO designated the disease COVID-19, which stands for coronavirus disease 2019. The virus that causes COVID-19 is designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); previously it was referred to as 2019-nCoV (Rasmussen et al., 2020). Globally, COVID-19 confirmed cases evolved from the initial case count of 189,000 on March 17, 2019 to 300 million

confirmed cases in 2022. The reported case counts underestimated the overall burden of COVID-19, as only a fraction of acute cases were diagnosed and reported (CDC, 2022a). Direct person-to-person respiratory transmission was considered the primary means of transmission of coronavirus 2019. It was transmitted through close-range contact (within 6 feet) via respiratory particles with talking, coughing, or sneezing and at longer distances, particularly in enclosed, poorly ventilated spaces. The period of infection begins prior to development of symptoms and is highest in the early stages of illness when the viral RNA levels from upper respiratory specimens are the highest. Transmission rates are highest in household and congregate settings, but social and work gatherings increase transmission rates as well (CDC, n.d.-d; Zou et al., 2020). Like all viruses, COVID-19 evolves into different variants of concern over time. The Delta variant was first identified in India in December 2020 and had been the most prevalent, highly transmissible variant worldwide until emergence of the Omicron variant in November 2021 in South Africa. Infection with the Delta variant was associated with a higher risk of severe disease and hospitalization, but emerging data on the clinical impact of Omicron suggest that Omicron has a replication advantage over the Delta variant and evades infection and vaccine-induced humoral immunity to a greater extent than prior variants. Omicron appears to be associated with less severe disease than other variants (Iuliano et al., 2022). Measures to prevent the spread of COVID-19 have evolved since discovery of the disease and include masking, social distancing, diligent handwashing, respiratory hygiene (covering the cough and sneeze), adequate ventilation of indoor spaces, cleaning frequently touched objects and surfaces, vaccines (Table 1.7), serial testing, self-isolation with symptoms and positive testing, and monoclonal antibody preexposure and postexposure (CDC, 2022a).

TABLE 1.7  Different COVID-19 Vaccines in the United States; January 21, 2022 PFIZER-BIONTECH

MODERNA

JOHNSON & JOHNSON’S JANSSEN

Ages recommended 5+ years old

Ages recommended 18+ years old

Ages recommended 18+ years old

Primary series 2 doses Given 3 weeks (21 days) apart

Primary series 2 doses Given 4 weeks (28 days) apart

Primary series 1 dose

Booster dose Everyone ages 18 years and older should get a booster dose of either Pfizer-BioNTech or Moderna (COVID-19 vaccines) 5 months after the last dose in their primary series. Teens 12–17 years old should get a Pfizer-BioNTech COVID-19 vaccine booster 5 months after the last dose in their primary series.

Booster dose Everyone ages 18 years and older should get a booster dose of either Pfizer-BioNTech or Moderna (COVID-19 vaccines) 5 months after the last dose in their primary series.

Booster dose Everyone ages 18 years and older should get a booster dose of either Pfizer-BioNTech or Moderna (mRNA COVID-19 vaccines) at least 2 months after the first dose of J&J/ Janssen COVID-19 vaccine. You may get J&J/Janssen in some situations.

When fully vaccinated 2 weeks after 2nd dose

When fully vaccinated 2 weeks after 2nd dose

When fully vaccinated 2 weeks after 1st dose

Source: Adapted fromAdu, P., Poopola, T., Medvedev, O. N., Collings, S., Mbinta, J., Aspin, C., & Simpson, C. R. (2023). Implications for COVID-19 vaccine uptake: A systematic review. Journal of Infection and Public Health, 16(3), 441–466. https://doi.org/ 10.1016/j.jiph.2023.01.020; Centers for Disease Control & Prevention. (n.d.). Stay up to date with COVID-19 vaccines. Retrieved August 13, 2023 from https://www.cdc.gov/coronavirus/2019-ncov/vaccines/stay-up-to-date.html#recommendations; Khoury, D. S., Docken, S. S., Subbarao, K., Kent, S. J., Davenport, M. P., & Cromer, D. (2023). Predicting the efficacy of variant-modified COVID-19 vaccine boosters. Nature Medicine, 29(3), 574–578

Chapter 1  Women and Their Health 15

Burden of Disease Associated with COVID-19

The COVID-19 pandemic has changed access to healthcare worldwide, and these changes may have long-term consequences for those diagnosed with cancer. Screening for cancer, STIs, pregnancy, and IPV may have been delayed, leading to patients getting diagnosed and managed later and not having the same outcomes pre-COVID. COVID also disrupted treatment plans and altered patient outcomes. Telemedicine use improved during COVID and increased ability to connect with patients remotely and provided another opportunity for access to healthcare while decreasing risk of COVID exposure. Telemedicine increased access to experts who may not have been accessible in person at this time as well. Children faced disruption in their daily routines with quarantines, social isolation, and education via Zoom with increased rates of anxiety, depression, and eating disorders. Children were impacted by the pandemic both physically and mentally with long-term sequelae. By 2021, a greater than 30% increase in mental health presentations to the EDs with children having high levels of suicidal ideation, aggression with self-harm, higher rates of substance abuse, and more instances of eating disorders were noted. Vaccines have been slowly approved by the FDA for use in specific age groups and are an important measure in primary prevention. In the United States, COVID vaccines are available to people by groups, ages 5 to 11, ages 12 to 17, and ages 18 and older. Pfizer Biotech is approved for ages 5 to 17 with Johnson & Johnson’s Janssen, Pfizer-BioNTech, and Moderna for ages 18 and older (CDC, 2022b). One particularly rare and serious side effect of COVID-19 is multisystem inflammatory system in children (MIS-C). Almost all children who have contracted MIS-C have been unvaccinated. A child who has been vaccinated but later gets sick is much less likely to become sick enough to be hospitalized or die. Some of the side effects of COVID-19 can affect children for years. It is estimated that over 140,000 children in the United States have lost one parent to COVID-19. Case counts of pregnant women with COVID-19 were analyzed from 1/22/2020 to 7/25/2022 with 225,656 total cases, 306 total deaths, and 34,693 total hospitalized (CDC, 2022a). Currently research is underway regarding long-term effects of COVID-19 with lingering symptoms, and longterm effects of PTSD, anxiety, depression, suicide, and IPV. COVID-19 impacted how prenatal care was delivered and birth locations due to restrictions on support people and family with limitations on the presence or number of support people present during labor and birth. Many were separated from their newborns and were limited in options for pharmacologic and nonpharmacologic pain relief during labor. The 2019 pandemic helped highlight existing health system weaknesses and revealed a need for health system corrections redefining normal functioning. ZIKA VIRUS

The Zika virus has a potential impact on sexual and reproductive health of women in the United States. Brazil and Colombia were first to report instances of Zika in the United States. Zika was first isolated in Uganda. Zika, named for a forest in Uganda, is a single-stranded RNA virus. The Zika virus is common in areas of Africa, Asia, and Pacific Islands

(CDC, 2016; Foy et al., 2011). Dissemination of accurate and current information is critical to prevent panic and myths. A single-stranded RNA virus, Zika, was first isolated in 1947 from a monkey in the Zika forest (CDC, 2016; Foy et al., 2011). The Zika virus has been isolated in sperm, urine, and blood (CDC, 2016). It is spread primarily by mosquito bite, and transmitted by pregnant women to fetus, through blood and sexual contact. The illness is usually mild with symptoms lasting for several days to a week (CDC, 2016; Foy et al., 2011). Common symptoms are fever, rash, joint pain, and conjunctivitis. There is no specific antiviral agent; treatment consists of symptom management (e.g., rest, fluids, analgesics, and antipyretics; Foy et al., 2011). Healthcare providers are encouraged to report suspected cases to their state or local health departments to facilitate diagnosis and mitigate the risk of local transmission. Birth defects such as microcephaly, seizure, intellectual difficulty, and developmental delays have resulted in the babies of women affected during pregnancy. Close monitoring for growth and development is the current management of such infants. Prevention is the primary way of combating the spread of the virus by avoidance of mosquito bites, postponement of travel to areas with Zika, and avoidance of exposure to the virus before, during, and after conception. HUMAN PAPILLOMAVIRUS

Human papillomavirus (HPV) is the most common sexually transmitted infection (STI). It is so common that most sexually active people will acquire the virus within a lifetime. Approximately 150 types of HPV strain have been identified with 40 infecting the genital area. Currently more than 42 million Americans are infected with HPV and it is estimated that roughly 13 million Americans will become infected yearly (Boersma & Black, 2020). The only HPV vaccine available in the United States since 2016 is Gardasil-9. Gardasil-9 protects against nine HPV types including 6, 11, 16, and 18. HPV types 6 and 11 (low risk) cause >90% of genital warts, while HPV types 16 and 18 (high risk) contribute to 66% of cervical cancers. Routine vaccination is recommended at ages 11 or 12 years yet may start as early as age 9 years. The recommended cutoff age is 26 years, yet some adults ages 27 to 45 years may benefit from the vaccination, which should be discussed with their healthcare professional (Boersma & Black, 2020). Generally, when people talk about HPV, the focus is on women, but HPV affects men as well. More than half of men who are sexually active in the United States will have HPV at some time in their lives. About 1% of sexually active men in the United States have genital warts at any one time. The 400 men who get HPV-related cancer of the penis, 1,500 men who get HPV-related cancer of the anus, and 5,600 men who get cancers of the oropharynx (back of the throat) have been exposed to a high-risk strain of HPV (Boersma & Black, 2020). The HPV can remain dormant for months or years before showing signs and symptoms. Low-risk strains of HPV can cause genital warts in both men and women. Genital warts are the first symptom seen in low-risk HPV strains. However, high-risk HPV rarely causes initial symptoms. Genital warts appear as small bumps in the genital area or around the anus. They can be small or large, raised or flat, and even shaped like cauliflower. Pregnant women with genital warts should be

16  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

counseled concerning the low risk for warts on the larynx (recurrent respiratory papillomatosis) in their infants or children. In 90% of HPV infections the virus is self-limiting, without any clinical symptoms, and usually resolves on its own within 2 years, therefore a person does not realize they are a carrier prior to passing it along. This contributes to the rapid infection rates and highlights the importance of safe sex practice discussions during office visits, no matter the chief complaint (Boersma & Black, 2020; CDC, n.d.-d). However, when the virus is persistent, lasting longer than 6 to 8 months, or when it is joined by other HPV genotypes, there is a greater likelihood of developing cervical cancer precursor cells or an invasive epithelial lesion. HPV is a major etiologic factor in the development of benign cervical papilloma as well as cervical cancer. Ten percent of HPV cases become persistent and cause more severe health problems ranging from genital warts to cervical cancer. Ninety percent of all cervical cancer cases are caused by a high-risk type of HPV (see Chapter 32, Human Papillomavirus). HUMAN IMMUNODEFICIENCY VIRUS

HIV death rates are declining globally, in both men and women, falling below most common causes of death such as heart disease, liver disease, respiratory conditions, stroke, cancers, and Alzheimer disease as of 2016 (WHO, 2019). HIV incidence has decreased by 73% from the highest number of infections (130,400) in 1984 and 1985 to 34,800 in 2019. Most infections continue to be attributed to male with male sexual contact (63% in 1981 and 66% in 2019). Over time the proportion of HIV infections have increased among Black people from 29% in 1981 to 41% in 2019 and among Hispanic/ Latinx persons (from 16% in 1981 to 29% in 2019). The CDC (n.d.-g) estimated at the end of 2019 that 1.2 million people had HIV in the United States. In 2020, 30,635 people received a new HIV diagnosis (Table 1.8). In 2020, the age range with the highest number of diagnoses was 25 to 29 years (6,103), with 30 to 34 years (5,233) and 20 to 24 years (4,867) a close second and third (CDC, n.d.-g). As it relates to TABLE 1.8  New HIV Diagnoses Among Adults and Adolescents in the United States and Dependent Areas by Race/Ethnicity, 2020 RACE OR ETHNICITY

NUMBER OF DIAGNOSES

American Indian/Alaska Native

200

Asian

635

Black/African American

12,827

Hispanic/Latinx

7,999

Native Hawaiian and other Pacific Islander White Multiracial

65 7,831 792

Source: Reproduced from Centers for Disease Control and Prevention. (n.d.). HIV: Statistics overview. U.S. Department of Health and Human Services. Retrieved March 31, 2023, from https://www.cdc.gov/hiv/statistics/overview/index.html

race/ethnicity, the annual diagnosis per 1,000 persons most dramatically persists among Black (15,340) and Hispanic women (10,502) while White women (9,018) closely trail. All other race/ethnicity groups listed were less than 1,000 diagnosis per year (CDC, n.d.-e). This is an obvious contribution to the healthcare disparity gap issue. CHRONIC CONDITIONS

Six in 10 adults in the United States have a chronic disease and four in 10 adults have two or more conditions. Chronic conditions are often debilitating and contribute significantly to key causes of death among women. Chronic diseases are defined broadly as conditions that last 1 year or more and require ongoing medical attention or limit activities of daily living (ADLs) or both. There is a complex and long-term interplay between chronic conditions and health across a woman’s life span. Although women live longer than men, women also experience greater morbidity at younger ages and utilize health services at higher rates than men. The nation’s $4.1 trillion in annual healthcare costs are driven by three specific chronic conditions: heart disease, cancer, and diabetes (CDC, n.d.-h). As women progress from childbearing ages through menopause and to postmenopause years, the prevalence of chronic conditions increases, with an associated shift to conditions linked to environmental factors. Overall, the pattern and magnitude of chronic conditions vary markedly by gender. Women were more likely to report arthritis, cataracts, orthopedic impairment, goiter or thyroid disease, diabetes, hypertension, varicose veins, chronic bronchitis, asthma, and chronic sinusitis; men were more likely to report visual impairment, hearing impairment, and heart disease. Chronic diseases such as heart disease, cancer, chronic lung disease, stroke, Alzheimer disease, diabetes, and chronic kidney disease occurs disproportionately among poor women. Based on National Health Interview Survey (NHIS) data, low income was correlated with the occurrence of diabetes, asthma, hypertension, and thyroid disease (National Center for Health Statistics [NCHS], 2021). Additionally, the differences in chronic conditions by racial/ethnic populations can differ dramatically. For example, American Indians/Alaska Natives were three times more likely to have had diabetes and end-stage renal disease than Asians/Pacific Islanders and six times more likely to have had these conditions than Whites. Blacks were twice as likely as Asians/Pacific Islanders to have diabetes and end-stage renal disease and four times more likely to have these conditions than Whites (American Immigration Council, 2020). Pain conditions are also common in women, especially low back pain and migraine or severe headache. Arthritis is the most common cause of disability among U.S. adults. Although osteoarthritis is the most common, types of arthritis that primarily affect women are lupus, fibromyalgia, and rheumatoid arthritis. Cancers can be a chronic condition with persistent pain and should not be excluded from this section. In the United States in 2018 there were close to 1.8 million new cancer cases resulting in approximately 600,000 deaths (Figure 1.6). Arthritis is more common among women than among men (23.5% vs. 18.1%) and increases with age (Figure 1.7). Arthritis affects more adults who are inactive (23.6%) compared to active (18.1%) and is more common in adults with fair/poor health (40.5%) in comparison to excellent/very

Chapter 1  Women and Their Health 17 Male

Female

466.6

White

489.1

Black American Indian and Alaska Native

259.6

Asian and Pacific Islander

279.1

Hispanic

384.4

Black American Indian and Alaska Native

262.8

Asian and Pacific Islander

418.0

White

292.8

Hispanic

350.5

331.0

FIGURE 1.6  Rate (per 100,000 people) of all types of new cancers by sex and race and ethnicity. Source: Data from U.S. Cancer Statistics Working Group. (2021). U.S. Cancer Statistics Data Visualizations Tool, based on 2020 submission data (1999–2018). U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute. https://www.cdc.gov/cancer/dataviz ARTHRITIS will INCREASE as the population grows and ages Diagnosed and future projections* 90 80

People (millions)

70 60 50

67

63 46

50

53

72

75

78

54

40 30 20

Diagnosed

10

Projected

0 2000

2005

2010

2015

2025

2020

2030

2035

2040

2045

Year

FIGURE 1.7  National arthritis prevalence projections. Source: Reproduced from Centers for Disease Control and Prevention. (n.d.). Arthritis: National statistics. U.S. Department of Health and Human Services. Retrieved February 16, 2023, from https://www .cdc.gov/arthritis/data_statistics/national-statistics.html

good health (15.4%). Arthritis diagnoses are expected to increase in the coming decades, suggesting an estimated 78.4 million adults age 18 or older will have arthritis by 2040 and 34.6 million of the adults will report the arthritis affecting their ADLs. Out of the 78.4 million, two thirds of the population are expected to be women (CDC, n.d.-c).

Vision loss and hearing loss are both sources of disability for women. Trouble seeing affects approximately 10% of women, whereas hearing difficulty or deafness affects approximately 1.5% (NCHS, 2014b). Heart disease and stroke are the first and third most common causes of death for women in the United States.

18  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

Although much attention has focused on the diagnosis and treatment of women with heart disease, an important aspect to understand is the disability associated with these two diseases. Both heart disease and stroke are associated with increasing age, but like other diseases, these vary with socioeconomic status and race/ethnicity. Although similar proportions of non-Hispanic Black and White women experience heart disease, a higher proportion of non-Hispanic American Indian/Alaska Native and non-Hispanic multiracial women experience heart disease. Stroke incidence increases with age; the lifetime risk for women age 55 to 75 is one in five in the United States. Hispanic and non-Hispanic Black women are more likely to suffer from a stroke than non-Hispanic White women. As a healthcare provider, it is important to know prevention is key, as four in five strokes are preventable. Chronic obstructive pulmonary disease (COPD) also is an important source of chronic illness and disability for women, as well as the fourth leading cause of death among U.S. women age 18 years and older. Approximately 6% of women report having COPD and its prevalence increases with age (11% of women age 65–74 years and 10.4% of women age 75 and older). COPD varies with race/ethnicity and poverty level. It is most common among non-Hispanic American Indian/ Alaska Natives (8.6%) and non-Hispanic women of multiple races (9.9%), followed by non-Hispanic White women (7%), non-Hispanic Black women (6%), Hispanic women (4.9%), and non-Hispanic Asian women (2.6%). Women living with incomes less than 100% of the poverty level are twice as likely to report COPD as those with an income of 400% of the poverty level (10% vs. 4.6%; U.S. Cancer Statistics Working Group, 2021). Hypertension is common among women, with 17.6% of women age 20 to 44, 55.8% of women age 45 to 64, 74.3% of women age 65 to 74, and 86% of women age 75 and over having been diagnosed with high blood pressure. There is a trend showing that hypertension increases with age. Racial/ ethnic variation is evident; more than 55% of non-Hispanic Black women and 45.1% of Hispanic or Latina women have hypertension compared with 37% of non-Hispanic Whites. As of 2015–2018 data, the percentage of Asian women has also surpassed non-Hispanic Whites at 42.8% (NCHS, 2021). Osteoporosis is more prevalent among women than men and increases with age. Approximately 18.8% of women have been diagnosed with osteoporosis who are over the age of 50 versus 4.2% in men. One in four women 65 years and older reports having been diagnosed. Non-Hispanic White and Mexican American women 65 years and older were more likely to have been diagnosed with osteoporosis than non-Hispanic Black women. Risk of bone fractures among older women is often associated with osteoporosis and may lead to disability or even death (CDC, 2021). In 2017–2018 the prevalence of obesity in the United States was 42.4% which is an increase from 30.5% back in 1999–2000. Obesity is now considered a costly chronic disease contributing to an annual medical cost of nearly $173 billion in 2019. Obesity is associated with increased risk of numerous diseases, including hypertension, type 2 diabetes, cardiovascular and liver diseases, arthritis, some types of cancer, and reproductive health risks. There is little racial/ ethnic variation in being underweight, but approximately

41.4% of non-Hispanic white adults are considered obese (body mass index [BMI], >30) compared with 49.9% of non-Hispanic Black adults and 45.6% Hispanic adults, and 16.1% of non-Hispanic Asian adults. Obesity prevalence is at minimum 40% among all age groups (20 to 39 years, 40 to 59 years, and 60 and older; CDC, n.d.-b). REPRODUCTIVE AND GYNECOLOGIC CONDITIONS

Both reproductive and gynecologic conditions affect a considerable proportion of women. Dysmenorrhea and vulvodynia cause discomfort that interferes with some women’s normal activities, but other conditions, such as endometriosis, uterine fibroids (leiomyomas), and ovarian cysts, affect fertility and reproductive functioning. Infertility is estimated to affect 10% of all U.S. women 15 to 44 years of age (CDC, n.d.-j). Endometriosis affects approximately 10% of girls and reproductive-age women (WHO, 2023b), and uterine fibroids are the most common (more than 3 million cases annually) benign tumors among women, especially those in childbearing ages (CDC, n.d.-e). The prevalence increases with age in both; however, uterine fibroids are usually detected in 80% of women by the age of 50 (De La Cruz & Buchanan, 2017). Racial/ethnic differences are noteworthy, with 12.3% of non-Hispanic Black women, 5.6% of white women, and 4.2% of Hispanic women experiencing uterine fibroids. Non-Hispanic white women are most likely to experience endometriosis (6.9%) compared with 3.4% of Black and 3.9% of Hispanic women. These two conditions are most often responsible for hysterectomy. Uterine fibroids account for 39% of all hysterectomies within the US annually (De La Cruz & Buchanan, 2017). In addition to endometriosis and uterine fibroids, age, obesity, and polycystic ovary syndrome are associated with infertility. MENTAL ILLNESS

Mental illnesses affect women and men differently. Scientists are only beginning to understand the contribution of various biological and psychosocial factors to mental health and mental illness in both women and men. Research on women’s health—which has grown substantially in the last 30 years— helps to clarify the risk and protective factors for mental disorders in women and to improve women’s mental health treatment outcomes. Depressive disorders include major depression, postpartum depression, dysthymic disorder (a less severe but more chronic form of depression), and bipolar disorder (manic-depressive illness). Globally, 280 million people (5%) have depression (WHO, 2023a). Within the United States in 2019, 18.5% of adults had some form of depressive symptoms (whether mild, moderate, or severe) within the previous 2 weeks (Figure 1.8). Of that percentage, 2.8% experienced severe, 4.2% experienced moderate, and 11.5% experienced mild symptoms (Villarroel & Terlizzi, 2020). Notably, at its worst, depression can lead to suicide. Although depression is not the only mental illness that affects women more often than men, it is significant because of its common occurrence, recurrence, and effects on functioning (WHO, 2023a). Trying to become pregnant, pregnancy loss, being pregnant, and giving birth increase risk for depression in women. The prevalence of depressive ­symptoms also

Chapter 1  Women and Their Health 19 Severe 2.8% Moderate 4.2%

Mild 11.5%

Mental issues such as schizophrenia, depression, bipolar disorders, Alzheimer disease, and obsessive-compulsive disorders affect nearly one in five Americans each year. Nearly 70% of adults with a diagnosed mental disorder do not receive treatment. Among all areas of healthcare, the mental health field is beset by disparities in the availability of and access to services occurring by means of financial barriers and stigmatization (Reeves et al., 2011). WOMEN’S PERCEPTION OF THEIR HEALTH AND LIMITATIONS IN FUNCTIONING

None-minimal 81.5%

Many women who experience chronic illness, whether mental or physical, also experience limitation of activity related to their conditions. About 17% of women report limitations related to chronic illness: Nearly 10% report fair or poor health, by their own assessment and self-assessed health status, that leads to severe psychological distress, and 3.7% report serious psychological distress (NCHS, 2021). ACTIVITY LIMITATIONS

FIGURE 1.8 Percent distribution of severity of depression symptoms in the past 2 weeks among adults age 18 and over: United States, 2019. Source: Reproduced from Villarroel, M. A., & Terlizzi, E. P. (2020). Symptoms of depression among adults: United States, 2019 (NCHS Data Brief No. 379). National Center for Health Statistics. https:// cdc.gov/nchs/data/databriefs/db379-H.pdf

varies with age groups and race/ethnicity (Figure 1.9). Hispanic, non-Hispanic White, and non-Hispanic Black women were most likely to report depressive symptoms during the past 2 weeks. Non-Hispanic Asian women were the least likely to experience any form of depression compared to other ethnic groups. Age influences the prevalence of depressive symptoms and severity as those in the younger age range (18–29 years) experience a higher percentage of mild symptoms, and there is a significant decrease in moderate and severe symptoms (Villarroel & Terlizzi, 2020). The important influences of income, education, and marital status, as well as age and race/ethnicity, need to be considered in studies of depression. The main risk factor for developing Alzheimer disease—a dementing brain disorder that leads to the loss of mental and physical functioning and eventually to death—is increased age. Although the number of new cases of Alzheimer disease is similar in older adult women and men, the number of existing cases is twice as high among women as among men, with women older than 65 years constituting 3.2 million diagnosed cases. Alzheimer disease death rates increased between 2000 and 2010 by about 40%, from 141.2 to 196.9 deaths per 100,000 people. The greater prevalence and mortality among women appear to be related to their longevity rather than to an increased sex-specific disease risk (DHHS, 2013). The chronic stress often associated with caregiving for someone with dementia can contribute to mental health problems for the caregiver (see Chapter 18, Health Considerations for Women Caregivers). Because women in general are at greater risk of depression than men, and as caregivers are much more likely to suffer from depression than the average person, women caregivers of people with Alzheimer disease may be particularly vulnerable to depression.

Women’s quality of life is affected by their ability to carry out daily activities at work, at home, and in the community. Adverse health effects all aspects of women’s lives, particularly their ability to engage in daily activities. Activity limitation caused by a physical, mental, or emotional health problem is a broad measure of health functioning for women. Women were nearly twice as likely as men to report activity limitation in 2011 to 2012 (17% compared with 9%). Activity limitation caused by chronic conditions such as arthritis was substantially higher among women.

Healthcare Access and Utilization In the first half of 2022, 8.36% (27.4 million) of people all ages were uninsured and 12.1% of people age 18 to 64 were uninsured (Figure 1.10; Cohen & Cha, 2022). Women in the United States obtain healthcare services through a variety of sources. Numerous factors, including affordability and availability of services and information about how and why it is important to access and utilize such services, affect their access to these services. Given the consolidation of the healthcare system, the shift to managed care, and decreased public funding of healthcare and health-related programs, the changes in healthcare delivery have serious implications for women’s healthcare utilization. Although women commonly enter the healthcare delivery system for pregnancy prevention or pregnancy-related services, these reproductive health services are typically provided separately from other aspects of women’s healthcare. Health services organizations for women include private- and public-sector groups. For women, the fragmentation of care, lack of coordination of services, and discontinuities in the healthcare delivery system contribute to higher costs to individual women and both deficiencies and excesses in care. Access to healthcare is important for preventive care and for prompt treatment of illness and injuries. Indicators of healthcare access and utilization include use of preventive services, outpatient care, and inpatient care, and access to these varies by health insurance status, poverty status, and race/ethnicity (Figure 1.11). Hispanic adults were less likely to have health insurance coverage. Women’s access to healthcare services is seriously compromised by inadequate health insurance, and

20  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS 25

21.8 Men

Percent

20 115.0

15

Women

13.4 19.6

10

13.4

5 0

Mild

Any severity

4.9 12.1

Moderate

3.5

Severe

25 21.0

Percent

20

16.8

18–29

18.4 18.4 13.9

15

10.3 10.7

10

4.4

Any severity1

45–64

65 and over

12.0

5 0

30–34

Mild1

3.8

4.5

3.8

Moderate2

2.7

2.7

3.1

2.6

Severe

25

Percent

20

Hispanic

319.3 319.3

Non-Hispanic black

1,2,316.9

15 10.2

10

Non-Hispanic white

1,2,310.2

312.0

312.2

7.9 34.0 34.4 34.6

5

1.2 0

Non-Hispanic Asian

Any severity

Mild

Moderate

32.7 32.9 3 2.5

1.2

Severe

FIGURE 1.9  Depressive symptoms across age groups and race/ethnicity. Source: Reproduced from Villarroel, M. A., & Terlizzi, E. P. (2020). Symptoms of depression among adults: United States, 2019 (NCHS Data Brief No. 379). National Center for Health Statistics. https:// cdc.gov/nchs/data/databriefs/db379-H.pdf

women without health insurance generally cannot obtain appropriate healthcare. Although little is known about how women obtain basic healthcare in the United States, national survey data report that women are more likely than men to have a usual source of care, have more outpatient visits, have more hospital stays (even excluding maternity stays), use home health services, and use nursing homes (Table 1.9). PUBLICLY FUNDED HEALTH PROGRAMS

In 2021, 21.7% of adults age 18 to 64 and 44.3% of children age 0 to 17 had publicly funded healthcare coverage (Cohen et al., 2022). The two major publicly funded health programs are Medicare and Medicaid. Medicare is funded by the federal government and reimburses older adults and those who

are disabled for their healthcare. Medicaid is funded jointly by federal and state governments to provide healthcare for the poor. Although Medicaid eligibility and benefits vary by state, Medicare and Medicaid healthcare utilization and costs often vary dramatically by state. Medicare spending grew 8.4% to $900.8 billion in 2021 while Medicaid spending grew 9.2% to $734 billion (Centers for Medicare & Medicaid Services, 2023). Women are more likely to qualify for Medicaid given their disproportionate share of poverty. The Patient Protection and Affordable Care Act promises to have dramatic effects on women’s access to healthcare as well as to a variety of preventive services. See Chapter 3, Women and Healthcare, for a more detailed discussion of this coverage for women.

Chapter 1  Women and Their Health 21 9.6

All people Children 0–17 Adult 18–64 Adult 65 and over

4.4

Uninsured

14.0 0.6 39.5 44.7

Public coverage

21.6 96.0 60.1 53.1

Private coverage

66.3 47.4 0

20

40

60

80

100

Percent

FIGURE 1.10  Percentage of people who were uninsured or had public or private coverage, by age group: United States, January–June 2022. Source: Reproduced from Cohen, R. A., & Cha, A. E. (2022, December). Health insurance coverage: Early release of estimates from the National Health Interview Survey, January–June 2022. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics. https://www.cdc.gov/nchs/data/nhis/earlyrelease/insur202111.pdf

40 2019

Percent

30

29.7 29.3

2020

2021 (January–June)

31.4

20 14.7 14.6 14.7 10.5

10

0

Hispanic

9.2

9.0

Non-Hispanic White

7.5

Non-Hispanic Black

8.8 6.1

Non-Hispanic Asian

FIGURE 1.11  Percentage of adults age 18 to 64 who were uninsured, by race and ethnicity and year: United States, January–June 2022. Source: Reproduced from Cohen, R. A., Terlizzi, E. P., Cha, A. E., & Martinez, M. E. (2021). Health insurance coverage: Early release of estimates form the National Health Interview Survey, 2020. National Center for Health Statistics, National Health Interview Survey Early Release Program. https:// www.cdc.gov/nchs/data/nhis/earlyrelease/insur202108-508.pdf

PRIVATELY FUNDED HEALTHCARE

Approximately 64% of U.S. women younger than 65 years have some form of private health insurance (Cohen & Cha, 2022), most of which is obtained through the workplace. As the health insurance marketplace continues to rapidly change as new types of managed care products emerge, the share of an employee’s total compensation for health insurance and

the use of traditional fee-for-service medical care continues to decline markedly. Approximately 30% of women had public insurance and 8% were uninsured (Table 1.9). Health insurance coverage varies by race/ethnicity, with non-Hispanic whites having coverage (76.7%), but less than 50% of non-Hispanic Blacks and Hispanics (49.7 and 44.7%, respectively) having coverage. Although women and men report

22  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

TABLE 1.9  Women and Men Health Insurance Status: January–June 2022 AGE GROUP (FEMALE)

UNINSURED (%)

PUBLIC COVERAGE (%)

PRIVATE COVERAGE (%)

Under 65

7.9

30.2

63.9

18–64

9.5

25.0

67.5

0–17

3.3

45.0

53.9

AGE GROUP (MALE)

UNINSURED (%)

PUBLIC COVERAGE (%)

PRIVATE COVERAGE (%)

Under 65

12.0

25.0

65.1

18–64

14.8

18.5

68.7

0–17

4.6

42.0

55.7

Source: Adapted from Cohen, R. A., & Cha, A. E. (2022, December). Health insurance coverage: Early release of estimates from the National Health Interview Survey, January–June 2022. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics. https://www.cdc.gov/nchs/data/nhis /earlyrelease/insur202212.pdf

similar levels of enrollment for private insurance, enrollment varies significantly by race/ethnicity and poverty status ­ (Cohen & Cha, 2022). HEALTHCARE PAYMENT AND EXPENDITURES

Major sources of payment for healthcare in the United States include the government and employers. The United States continues to spend more on healthcare than any other industrialized country, and health spending is increasing rapidly (Cohen & Cha, 2022). The expenditures for prescription drugs increased more rapidly than any other type of health expenditure. The United States continues to spend a larger proportion of its gross national product on healthcare than any other major industrialized country. Much of U.S. healthcare spending is directed to care for chronic diseases and conditions that reflect the aging population. PREVENTION SERVICES

The use of prevention services has substantial positive effects on the long-term health status of women. The use of several different types of preventive services has been increasing; however, disparities in their use according to income and by race/ethnicity persist among all persons. The importance of promoting wellness and preventing illness among women involves screening for conditions such as breast, cervical, and colorectal cancer. Regular mammographic screening for women age 50 years and older is effective in reducing deaths from breast cancer. In 2013, approximately 65% of women age 65 years and older had had a mammogram within the previous 2 years. Among those 40 years and older, the proportion of women receiving mammograms was 64% or greater for all racial/ethnic groups except multiracial women. The proportion of women receiving mammograms was higher among those with greater levels of education (53% for those who had not completed high school) and much lower (36%) for women who were uninsured than for those with private insurance (74%) or Medicaid (64%). The percentage of women 18 to 44 years of age and 45 to 64 years was relatively high (80% and 77%, respectively), but the proportion older than 65 years dropped

to 47%, consistent with changing guidelines about screening. Women who reported having Pap tests within the previous 3 years differed by race/ethnicity. The reported prevalence was as follows: non-Hispanic Black women, 78%; non-Hispanic White women, 73%; Hispanic women, 74%; American Indian/Alaskan Native women, 73%; and Asian women, 68%. Finally, colorectal cancer is the third leading cause of cancer-related deaths among women after lung and breast cancer. Early detection and treatment can substantially reduce the risks associated with colorectal cancer for people age 50 years and older. Other preventive strategies relevant to women include the HPV vaccine to prevent cervical cancer, anal cancer, and genital warts The preventive care provisions of the Patient Protection and Affordable Care Act should improve access to these preventive services by expanding health insurance access and requiring new plans to cover U.S. Preventive Services Task Force (USPSTF)–recommended preventive services and well-woman visits without copayments required (DHHS, 2013). OUTPATIENT CARE

Important changes in the delivery of healthcare in the United States are driven in large part by the need to contain rising costs. One significant change has been a decline in the use of inpatient services and an increase in outpatient services such as outpatient surgery and hospice care. From 2009 to 2011, nearly 87% of women had a usual source of care, a place where they could go when sick, such as an office for health professionals or health center, but not an ED. More than 90% of women who have private or public insurance coverage had a usual source of care compared with only 56% who were uninsured. In addition to varying health insurance coverage, having access to a usual source of care varies with race/ethnicity. Nearly 89% of non-Hispanic White women, 85% of non-Hispanic Black women, 85% of American Indian/Alaska Natives, 85.7% of Asians, 85% of Native Hawaiian/Pacific Islanders, and 82% of multiracial women but only 78.6% of Hispanics reported a usual source of care (DHHS, 2013). Having a usual source of care is more commonly experienced by older women who are most likely to have health insurance;

Chapter 1  Women and Their Health 23

nearly 97% of those older than 65 years had a usual source of care compared with nearly 79% of women 18 to 34 years of age (DHHS, 2013). Although women frequently enter the healthcare delivery system with reproductive health concerns, they seldom can benefit from primary care that is comprehensive and coordinated. Regardless of the type of provider or reason for accessing care, women’s healthcare delivery in the United States remains fragmented. An estimated 80% of women report that they have a usual source of care, which is predominately in physician offices. Among physician providers, family practitioners, general internists, and OB/GYNs provide most basic healthcare to women; however, women may rely on multiple providers (DHHS, 2013). For example, 33% of women age 18 years and older reported seeing an OB/GYN and an additional primary care provider for their regular care. Women who used two or more physicians for regular care were more likely to be younger, have private insurance, and have higher income than women who used only one physician. Also, these women were more likely to have more annual visits and to receive more clinical preventive services. Among women who relied on only one physician, 39% reported using a family practitioner or an internist, 16% used an OB/GYN, 3% used a specialist, and 10% had no regular physician. Finally, despite estimates that more than 100,000 APRNs deliver primary healthcare, less than 2% of women report using nonphysician providers as a regular source of care. Women made much of their healthcare visits to physicians’ offices, with the number increasing as women aged. A similar pattern with age was found for EDs, with the latter especially pronounced for women 75 years and older (Table 1.10). In 2007, an estimated 1,459,000 women received home healthcare, with 31% of patients younger than 65 years. Of the remainder of women patients, 18% were 65 to 74 years, 29% 75 to 84 years, and 22% older than 85 years (DHHS, 2013).

TABLE 1.10  Women’s Visits to Physician Offices and Emergency Departments, 2018: Per 100 Persons

In addition, 1,045,100 women received hospice care during that same year in the United States. Hospice care is defined as a program of palliative and supportive care services that provides physical, psychological, social, and spiritual care for dying persons, their families, and loved ones. Of the patients enrolled in hospice care, 17% were younger than 65 years, with the remainder accounting for hospice care divided among those 65 to 74 years (15%), 75 to 84 years (29%), and 85 years and older (38%). There is a striking increase in the use of each service as women age. The most common admission diagnoses for home healthcare include malignant neoplasms; diabetes; diseases of the nervous system and sense organs and circulatory, respiratory, and musculoskeletal systems; decubitus ulcers; and fractures. Primary admission diagnoses for hospice care include malignant neoplasms and diseases of the heart and respiratory system. The proportion of women living in nursing homes is also noteworthy. More than 1,061,000 women resided in nursing homes during 2007, with only 6.4 per 100,000 younger than 65 years of age. Of women 65 to 74 years of age, 98 per 100,000 resided in nursing homes, and of those 75 to 84 years old about 423 per 100,000 resided in nursing homes, increasing after age 85 years to 1,651 per 100,000 (Cohen et al., 2021; Miller et al., 2023; Ne’eman et al., 2022). Differences in marital status between older women and men are reflected in both their living arrangements, such as in a nursing home, and in their relationship to their informal caregivers. Women tend to care for their spouses or partners, and as they age, they find themselves living alone (about 30%). Although most men were cared for by a spouse, lived with family members, and had a primary caregiver with whom they lived, women were more likely to live alone or with nonfamily members. Notably, the primary caregiver of most women was a relative other than a spouse—most often a child or child-in-law. As more people live to the oldest ages and because the incidence of many debilitating illnesses such as diabetes, dementia, and osteoporosis increases with age, the number of older nursing home residents will continue to grow and issues surrounding long-term care will become increasingly important. The majority of nursing home residents were White, widowed, and functionally dependent women. The leading admission diagnoses for older nursing home residents (both men and women) were diseases of the circulatory system, followed by mental disorders.

AGE

PHYSICIAN OFFICES

EMERGENCY DEPARTMENTS

Younger than 15 years

165.6

41.4

INPATIENT CARE

15–24 years

189.3

48.8

25–44 years

263.9

47.4

45–64 years

346.5

37.8

65–74 years

508.9

35.8

75 and over

617.0

62.2

Hospitalization is dependent not only on a woman’s medical condition, but also on her ability to access and use ambulatory healthcare. Delaying or not receiving timely and appropriate care for chronic conditions and other health problems may lead to the development of more serious health conditions that require hospitalization. Utilization of inpatient services has declined, as has the number of beds in community hospitals. The National Hospital Discharge Survey is the principal source of national data on the characteristics of patients discharged from nonfederal short-stay hospitals. Hospital costs are the highest of any type of healthcare service. For example, in 2010, mean healthcare expenses of women older than 18 years who had an expense were greatest for hospital inpatient services at $15,792 per person,

Sources: Data from National Center for Health Statistics. (2021, September 30). National Ambulatory Medical Care Survey: 2018 national summary tables. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. https://www .cdc.gov/nchs/data/ahcd/namcs_summary/2018-namcs-web-tables-508.pdf; National Center for Health Statistics. (2021, May 17). National Hospital Ambulatory Medical Care Survey: 2018 emergency department summary tables. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. https://www.cdc.gov /nchs/data/nhamcs/web_tables/2018-ed-web-tables-508.pdf

24  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

compared with home health services at $5,066, hospital outpatient services at $2,529, and office-based services at $1,645. Prescription medications cost women an average of $1,617 per person and ED services cost $1,461 on average. Dental services cost an average of $677 per woman (DHHS, 2013). The average cost of total healthcare services per woman was $6,066 in 2010. Women paid approximately 14.4% of these expenses out of pocket. When they are hospitalized, women have shorter average lengths of stay than men (4.5 vs. 5.5 days in 2010), but the pattern of diagnoses and procedures varied between women and men in large part because of hospitalizations for pregnancy-related causes (including deliveries and diagnoses associated with pregnancy). For women younger than 18 years of age, pneumonia, asthma, injuries, and fractures account for the major reasons for hospitalization. For women 18 to 44 years, HIV infection, childbirth, alcohol and drug problems, serious mental illness, diseases of the heart, intervertebral disc disorders, injuries, and fractures constitute major reasons for hospitalization. For women 45 to 64 years, major reasons for hospitalization are cancer, diabetes, alcohol and drug problems, diseases of the heart, stroke, pneumonia, injuries, and fractures. For those 65 to 74 years old, major causes of hospitalization are cancer, diabetes, serious mental illness, disease of the heart, stroke, pneumonia, osteoarthritis, injuries, and hip fracture. For those 75 years and older, primary causes of hospitalization include cancer, diabetes, serious mental illness, diseases of the heart, stroke, pneumonia, osteoarthritis, injuries, and hip fracture. ORAL CARE

Dental healthcare is essential for oral health and for the prevention and treatment of tooth decay and infection. As of 2021, there were 201,927 professional active dentists in the United States. There are 60.84 dentists per 100,000 U.S. population (American Dental Association, 2022). The percentage of adults age 18 and over who had a dental visit in 2020 was 63.0% compared to 85.9% of children ages 2 to 17. Between 2015 and 2018, women (23.5%) had fewer untreated dental caries than men (28.4%), which suggests women were more likely than men to have a dental visit (American Immigration Council, 2020). Dental visits were more common among women with household incomes 400% of the poverty level (82%) compared with women with incomes less than 100% of the poverty level (42.6%). Cost represents a significant barrier for women in accessing dental care. Only 20% of adults have dental insurance. In 2011, 16% of women did not obtain needed care because they could not afford it. The rate for women not getting needed care was greater for women with public insurance (23%) and for those who were uninsured (36%; Shrider et al., 2021).

Health Behaviors All people engage in behaviors that are either helpful or harmful to themselves and others, with consequences to their health and well-being that will have both immediate and long-term effects. Many of these patterns of behavior are associated with morbidity and mortality. Exercising, not smoking, not using drugs, drinking alcohol in moderation, and good nutrition can improve or maintain women’s general

health and well-being and can also reduce the risk of selected morbidities and the consequences of such morbidities. PHYSICAL ACTIVITY

The 1996 Surgeon General’s report on physical activity and health reported that three quarters of U.S. adults exercise during their leisure time (DHHS, 1996). Despite the implementation of the Title IX, Education Amendments of 1972, which provides for equal opportunity for women in school sporting activities, one third of women report no leisure-time physical activity. Women’s multiple roles in the workplace and at home compete with leisure-time physical activity. The 2008 Physical Activity Guidelines for Americans (DHHS, 2008) recommends that adults should engage in at least 2.5 hours of moderate-intensity or 1.25 hours of vigorous-intensity aerobic activity (e.g., jogging) per week or a combination of both plus muscle-strengthening activities on at least 2 days per week (see Chapter 14, Healthy Practices: Physical Activity). According to Behavioral Risk Factor Surveillance System (BRFSS) 2019 data, in the United States, the crude prevalence among adults age 18 and older who reported meeting recommendations for weekly aerobic activity was 50.7% (Bennie et al., 2019; Fluetsch et al., 2019). Women were a lot less likely to meet muscle-strengthening activity recommendations compared with aerobic activity (19.8% vs. 43.9%). Physical activity varied with education and race/ethnicity. Some unintended adverse health consequences can result from physical activity. For example, exercise undertaken incorrectly can lead to musculoskeletal injuries and metabolic abnormalities. Also, excessive exercise among girls during puberty can result in the female athlete triad: disordered eating, amenorrhea, and osteoporosis (see Chapter 14, Healthy Practices: Physical Activity). NUTRITION

Given the established relationship between nutrition and health, many health promotion behavior changes are nutrition related. The nutritional status of adult women is the culmination of nutrient intake, metabolism, and utilization over their life span. Although the link between nutrition and good health is established (see Chapter 13, Nutrition for Women), women’s eating patterns are affected by numerous societal factors that reflect the cultural and socioeconomic landscape of the 21st century. These factors include increased employment outside the home, consumption of convenience foods, meals eaten away from home, single woman–headed households, and tobacco use. For many reasons such as professional fulfillment, economic necessity, and TANF, women of all age groups are employed and thus burdened by the multiple responsibilities of employment, child care, and home management, which leaves minimal time and energy to prepare well-balanced, home-cooked meals for themselves and their families. According to BRFSS 2019 data, in the United States, the crude prevalence among adults age 18 and older who reported consuming fruit less than once per day was 39.1% (CDC, 2021). Because nutrition is a modifiable factor for numerous chronic diseases, the Healthy People 2030 nutritional initiative includes objectives that concern weight gain, obesity, dietary intake, and nutrients (folate, calcium, and iron),

Chapter 1  Women and Their Health 25

which directly impact women’s health. In 2015–2019, only one in 10 adults met recommendations for fruit and vegetable intake. From 2007 to 2010, 43% of women reported that they had consumed fast food. On average, those who did consumed about 25% of their total daily calories from these items. Fast food consumption declined with age, such that 59% of women age 18 to 24 years consumed fast food compared with 22.9% of women age 65 years and older. More than half of non-Hispanic Black women consumed fast food (55.5%), followed by 47.8% of Mexican American women and 41.4% of non-Hispanic White women. Consumption of sugar-sweetened beverages varied with household income, with 60% of women with incomes less than 200% of the poverty level compared with 36.3% of women with incomes of 400% of the poverty level. Sugar-drink consumption ranged from 43% among non-Hispanic White women to 66.1% of non-Hispanic Black women (DHHS, 2013). Federal programs of the U.S. Department of Agriculture provide help to low-income families in obtaining food. The Supplemental Nutrition Assistance Program (SNAP), formerly the Federal Food Stamp Program, provides benefits for purchasing foods to individuals and families with incomes usually below 130% of the poverty level. In 2011, SNAP served a record high of 44.1 million people per month, about one in seven Americans. Among households that relied on SNAP, 5.1 million (24.5%) were female-headed households with children. They accounted for 52% of all SNAP households with children. In addition, the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) also serves low-income women and families by providing supplementary nutritious foods, nutrition education, breastfeeding support, and referrals to health and social services. In 2012, WIC served nearly 2.1 million pregnant women and mothers, accounting for 23.5% of WIC participation. In addition, more than 75% of the 8.9 million individuals receiving WIC benefits were infants and children. Food security, always having access to enough food for an active, healthy life, is becoming a more prevalent issue in the United States. Households with low food security have multiple food access issues, but little if any reduced food intake. Those with very low food security have reduced food intake and disrupted eating patterns. In 2011, nearly 18 million households experienced food insecurity for one or more members at some point in the year. Very low food security increased from 5.4% to 5.7% in 2011, returning to levels seen in 2008 and 2009 during the recession. Food security varies with household composition. Women and men living alone had similar rates of food insecurity (15%), but female-headed households with children and no spouse were more likely than male-headed households with no spouse to experience food insecurity (36.8% vs. 24.9%). SUBSTANCE ABUSE

Substance abuse may have a profound impact on the current and future health of women. Women who use illicit substances are more likely to have poor nutrition and serious morbidity and to die from drug overdose, suicide, and violence. Use of selected substances in the past month among persons 12 and older was 11.7% in 2018 with drug overdose deaths from using any opioid per 100,000 population was 20.8% (CDC,

2023; Mattson et al., 2021). Rates of substance use and choice of substance vary by gender, age, race/ethnicity, educational attainment, and poverty status. Federal law defines illicit drugs as marijuana, cocaine, heroin, hallucinogens, stimulants, inhalants, and nonmedical use of prescription-type psychotherapeutic drugs, such as pain medications, and sedatives. The number of poisoning deaths, most of which are drug related, has increased, including those tracked to use of prescription pain medications, and have surpassed MVA as the leading cause of fatal injury in the United States. From 2009 to 2011, 6.7% of women (vs. 11% of men) age 18 years and older used an illicit drug within the previous month. Most commonly used were marijuana (4.9% for women) and psychotherapeutic drugs (nonmedical use, 2.3%). Less than 1% of women used cocaine, heroin, hallucinogens, or inhalants. Among women, 17% of those 18 to 25 years of age reported using an illicit drug during the previous month compared with less than 5% of women 50 years and older. Non-Hispanic Asian women and Hispanic women were less likely than women of other racial/ethnic groups to report using illicit drugs in the previous month. Illicit drug use was more common among non-Hispanic women of multiple races (9%) and non-Hispanic White women (97.5%) than among non-Hispanic Black women (6.7%; DHHS, 2013). Although women are more likely than men to be lifetime abstainers, women appear to suffer more severe consequences than men do after shorter duration of less alcohol intake. From 2009 to 2011, 21% of women reported consuming four or more drinks on a single occasion over the course of about 2 hours (binge drinking) and 7.3% reported heavy drinking (consuming on average more than one drink per day). Drinking patterns are related to both household income and age and race/ethnicity. At incomes of 200% of the poverty level, women and men were equally likely to drink heavily (8.2%), and binge drinking tended to increase with income. Nearly 38% of women age 18 to 25 years reported binge drinking in the previous month compared with 6.2% of those 65 years and older. Heavy drinking was also more common among young women (11.4%) and decreased to less than 7% of women age 35 years and older. Binge drinking ranged from 9% among non-Hispanic Asian women to about 25% of non-Hispanic White and native Hawaiian/other Pacific Islander women (DHHS, 2013). Cigarette smoking is the major preventable cause of death among adult women and leads to an increased risk of cancer, heart disease, stroke, reproductive health problems, and pulmonary conditions. Once women start smoking, they continue to smoke for several reasons, including nicotine addiction, stress management, struggles against depression, and weight management. Women are less likely to report smoking than men (11.0% vs. 14.1%; CDC, n.d.-f). In 2021, the prevalence of smoking was highest among American Indian women (20.9%) and lowest among non-Hispanic Asian women (7.2%; Table 1.11). Notably, the prevalence of smoking was lower among more education (4.0% of those with graduate degree) versus 21.6% of those with no diploma (Table 1.12). Smoking cessation is an important way to reduce the risk of poor health. The proportions of adults who quit smoking vary with education attainment.

26  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

TABLE 1.11  Percentage of Persons Age 18 Years and Older Who Reported Cigarette Use “Every Day” or “Some Days” at Time of Survey and Reported Smoking at Least 100 Cigarettes During Their Lifetime, by Race/ Ethnicity, 2020 BY RACE/ETHNICITY

PERCENTAGE

White, non-Hispanic

13.3%

Black, non-Hispanic

14.4%

Asian, non-Hispanic

8.0%

American Indian/Alaska Native, non-Hispanic

27.1%

Hispanic

8.0%

Other, non-Hispanic

19.5%

BIOLOGICAL AND ENVIRONMENTAL FACTORS

The last decade of the 21st century was a time of significant advances in women’s health. Prompted by the feminist movement of the 1960s and 1970s, increasing attention to women’s health brought changes in health services, such as freestanding birth centers, development of academic coursework in women’s health for professionals and the public, and advances in research about women’s health. Each of these changes foreshadows enhanced possibilities for women’s health during the 21st century. The consequences of advanced understanding of women’s health through research may be the most dramatic in the decades ahead. THE HUMAN GENOME

Source: Adapted from Centers for Disease Control and Prevention. (n.d.). Current cigarette smoking among adults in the United States. U.S. Department of Health and Human Services. Retrieved February 16, 2023, from https://www.cdc.gov/tobacco /data_statistics/fact_sheets/adult_data/cig_smoking/index.htm

TABLE 1.12  Percentage of Persons Age 25 Years and Older Who Reported Cigarette Use, by Education, 2020 BY EDUCATION (ADULTS AGE >/25 YRS)

Changing Women’s Health

PERCENTAGE

0–12 (no diploma)

21.5%

GED

32.0%

High school diploma

17.6%

Some college, no degree

14.4%

Associate degree (academic or technical/ vocational)

12.7%

Undergraduate degree (bachelor’s)

5.6%

Graduate degree (master’s, doctoral or professional)

3.5%

Source: Adapted from Centers for Disease Control and Prevention. (n.d.). Current cigarette smoking among adults in the United States. U.S. Department of Health and Human Services. Retrieved February 16, 2023, from https://www.cdc.gov/tobacco /data_statistics/fact_sheets/adult_data/cig_smoking/index.htm

Overall, the profile of health-promoting behaviors for women shows that activity levels decrease with age and that only about 20% of young adult women engage in regular physical activity that meets guidelines for aerobic and muscle-strengthening activity. Fat and carbohydrate intake remains relatively stable at 50% and 33%, respectively, across the life span, but total number of kilocalories taken in decreases with age (National Institute of Diabetes and Digestive and Kidney Diseases, 2021).

Research focused on the human genome has revealed new understandings about sex differences that may have profound implications on health of the nation. Not only have new insights about sex differences in the genetic bases for phenotypic differences between men and women revolutionized this field, but also some genetic discoveries have been made that may drive health consequences for women. Being male or female is linked to differences in health and illness, and these differences are influenced by genetic, physiologic, environmental, and experiential factors (Farrell, 2022). Although in many instances sex differences can be traced to the effects of reproductive hormones, hormones are no longer a universal explanation for these differences. Research on understanding the human genome has provided a basis for learning about the molecular and cellular mechanisms that underlie sex-specific differences in phenotype. Many of these new understandings warrant further investigation (Allen et al., 2021). Sexual genotype (XX in females and XY in males) has effects far beyond elaboration of reproductive hormones. Genes on sex chromosomes can be expressed differently in females and males. Single or double copies of the genes, meiotic effects, X-chromosome inactivation, and genetic imprinting are a few of the phenomena involved. X-chromosome inactivation is the random silencing of one or the other X chromosome that takes place during early embryonic development. X-chromosome inactivation, which occurs about the time of implantation, is a unique biochemical process in that it occurs only in females. Females inherit a paternally imprinted X chromosome, unlike males, who inherit only a maternally imprinted X chromosome. A subset of genes on the X chromosome may escape inactivation. As a result, females can get double doses of certain genes. The Y chromosome has a host of actively transcribed genes that are expressed throughout the male body but are absent from the female body (Abashishvili et al., 2022). Although the new biological discoveries are important to the understanding of women’s health, it remains important to recall that these sex differences are not the same as gender differences. Sex differences refer to differences that are biologically driven, whereas gender refers to differences that are socially influenced: self-representation as male or female and social responses to one’s phenotype. There are many differences between males and females in basic cellular

Chapter 1  Women and Their Health 27

biochemistries that can affect health, and many do not arise only because of hormonal differences between the sexes. Research is in progress on the functions and effects of X-chromosome– and Y-chromosome–linked genes in somatic as well as germ cells. Mechanisms of influence of genetic sex differences in biological organization (cell, organ, organ system, and organism), effects of genes versus the effects of hormones, and sex differences across the life span remain to be fully understood. ENVIRONMENTS FOR WOMEN’S HEALTH

The effects of women’s environmental exposures on their health have gained scientific attention (Garcia et al., 2021; Haynes et al., 2017). As a basis for its work, the Federal Interagency Working Group on Women’s Health and the Environment of the DHHS defined environment to include the home, school, indoor and outdoor workplaces, public and private facilities and outdoor spaces, and healthcare services and recreational settings. Women’s health can be affected by the products women use in these settings as well as by contact with physical, chemical, and biological toxicants in air, water, soil, food, and other organisms. In addition, early life exposures of mothers and children, substances ingested, and economic circumstances can influence health. There are multiple mechanisms by which environmental exposures can influence public health through the life stages of women and their children (Bolte et al., 2022). For example, environmental chemicals may increase or decrease signaling molecules by mimicking or blocking effector molecule signals that disrupt signal pathways. How populations differ in their susceptibility and how susceptibility changes over time may be explained in part by focusing on the intersection of genetic and environmental influences—for example, understanding how environmental agents with estrogenic-like activity interact with genes. Study of endocrine disruptors and their potentially adverse health effects could contribute significantly to improving women’s health through curtailment of environmental exposures. In addition, studies of genetic susceptibility to environmental exposures—for example, the NATZ gene, which determines slow acetylation among smokers and its effect on breast cancer—may help reduce risk if these biological indicators become readily available to women. Finally, as we have come to appreciate the disparities in health experienced by many populations of women, we are understanding and addressing the utility of the concept of gender disparities. Health disparities exist when there are differences in the incidence, prevalence, mortality, and burden of disease and other adverse health outcomes when compared with the general population. Sociocultural environments form the context for women’s lives and have profound effects on their health and that of future generations. The critical intersection of gender, race/ethnicity, class, and age shapes the environments that influence women’s chances for health. Consequently, it is difficult to attribute gender disparities in health to biology, environments, physiology, or human experience. The intersection of gender with other characteristics often determines the following for women: ● Exposures to toxins ● Social relations such as those linked to low social and economic status

Racism Sexism ● Heterosexism ● Stress ● Tobacco/alcohol/other substance use Sociocultural as well as physical and toxic environments thus form the context for women’s lives and have profound effects on their health and that of future generations (Bolte et al., 2022). It is therefore critical to consider women’s health from an integrative perspective and to move beyond research describing the nature of women’s health problems to that which engages women in the study of solutions to their health problems (Meleis et al., 2016). Likewise, it is critical to consider both the individual experience of health, providers of healthcare to women, as well as the community’s health. A multilevel approach to health is important to institute the kinds of programs that are likely to be successful in improving women’s chances for improved and sustained health. ● ●

GLOBALIZATION

A final important factor influencing women’s health is globalization. As economic forces move women into a global economy, some would point out that the world continues to be an unsafe place for girls and women. Meleis (2005) and Meleis et al. (2016) asserted that the gender divide compromises the safety of women. Women are at risk for violence, rape, trafficking, and abuse. Their mortality and injury rates reflect the limited definition of the nature and type of work they do. Conditions expose them to infections such as HIV/AIDS, pregnancy and birthing cycles, and unsafe abortions owing to the inadequacy and inaccessibility of health services. Meleis urges providers and recipients of services to enhance safe womanhood, not just safe motherhood by addressing health risks associated with women’s work, marriage, violence, reproductive rules, and access to resources (Meleis et al., 2016). The education of young girls sets their horizons by determining their options for work. How work is defined limits consideration of the nature, burden of double and triple shifts, and hazards of work that are not currently considered in the economic and labor statistics or health studies. Marriage defines many women and obligates them to provide services and resources to husbands and families, as well as shoulder the burdens of multiple roles. Battering and abuse of girls and women, trafficking, and access to income through sex work all put women at great health risk, including for HIV/ AIDS. Wars and terrorism increase women’s chances of rape. Pregnancy, birth, and motherhood also escalate the risk of poor health for women. Finally, healthcare services that are fragmented, inaccessible, and focused on disease rather than prevention and health promotion become a source of overload for women. The invisibility of women’s healthcare issues on national and international agendas intensifies the risk for women. Meleis proposes that a fundamental change is necessary in the conceptual framework for women’s health. She recommends using a human rights framework that is guided by a focus on women’s life situations and experiences as a starting point for considering health. Stigma, exploitation, and oppression are key concepts in understanding women’s

28  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

health. Second, she urges redefinition of women’s work from employment to a multidimensional framework that includes the amount of energy, activity, and space occupied; the amount and quality of time; the resources for their work; and the results, values, and meaning of their work. Third, she recommends development of policies that acknowledge women’s perspectives, experiences, and life context, as well as give women a platform and advocacy to have their voices heard in the policy arena. Finally, Meleis recommends that societies consider women the center of the family and the community, expecting them to be the agents for continuity of values, gatekeepers, integrators, and guardians of social capital. This implies placing women’s health at the forefront of foreign policy and international consciousness in war and peace. (This discussion is continued in Chapter 3, Women and Healthcare.)

THE FUTURE DIRECTIONS OF WOMEN’S HEALTH Notable advances have been achieved in the scope and depth of women’s health and healthcare research in the last century. However, major challenges continue to emerge; these challenges are influenced by socioeconomic and environmental trends; racism, agism, genetic, hormonal, and biological determinants; globalization; and other social issues. Future and emerging issues for women’s health in the next century need to address the effects of demographic and sociocultural change on women’s health and focus on the impact of such changes on the healthcare system and the ability of women to access appropriate high-quality, equity care. The need to broaden research topics and to consider populations that have been inadequately studied is essential. In general, although healthcare providers are committed to doing everything possible to promote women’s health, the range of clinical and public health interventions is often limited, access to healthcare is inequitable, and the research evidence specific to women remains incomplete. Therefore, when considering future directions in research, one should ask whether study results will advance the ability to improve women’s health and whether healthcare providers are being educated adequately to promote women’s health!

REFERENCES Abashishvili, L., Gogolashvili, A., Keratishvili, D., & Pestvenidze, M. (2022). Influence of gender in developing autoimmune diseases. Experimental and Clinical Medicine Georgia, (2). https://doi.org/10.52340/jecm.2022.02.13 Allen, C. G., Peterson, S., Khoury, M. J., Brody, L. C., & McBride, C. M. (2021). A scoping review of social and behavioral science research to translate genomic discoveries into population health impact. Translational Behavioral Medicine, 11(4), 901–911. https://doi.org/10.1093/tbm/ibaa076 American Immigration Council. (2020, September 24). Immigrant women and girls in the United States: A portrait of demographic diversity. https://www .americanimmigrationcouncil.org/research/immigrant-women-and-girls -united-states

Arias, E., Tejada-Vera, B., Ahmad, F., & Kochanek, K. D. (2021, July). Provisional life expectancy estimates for 2020 (Vital Statistics Rapid Release No. 15). National Center for Health Statistics. https://www.cdc.gov/nchs/data/vsrr /vsrr015-508.pdf Arias, E., Tejada-Vera, B., Kochanek, K. D., & Ahmad, F. (2022, August). Provisional life expectancy estimates for 2021 (Vital Statistics Rapid Release No. 23). National Center for Health Statistics. https://www.cdc.gov/nchs/data /vsrr/vsrr023.pdf Arsitio, K. B., & Gutierrez, M. V. (2023). The integration of women in the military: A case study. International Journal of Research and Innovation in Social Science, 7(4), 195–210. https://doi.org/10.47772/IJRISS.2023.7416 Balbus, J. (2022). Observations from COP27: Health care is becoming a bigger part of the climate change solution. Environmental Health Perspectives, 130(12), 121001. https://doi.org/10.1289/EHP12549 Bennie, J. A., De Cocker, K., Teychenne, M. J., Brown, W. J., & Biddle, S. J. (2019). The epidemiology of aerobic physical activity and muscle-strengthening activity guideline adherence among 383,928 US adults. International Journal of Behavioral Nutrition and Physical Activity, 16, 1–11. https://doi.org/10.1186 /s12966-019-0797-2 Betancourt, J. A., Dolezel, D. M., Shanmugam, R., Pacheco, G. J., Stigler Granados, P., & Fulton, L. V. (2023). The health status of the US veterans: A longitudinal analysis of surveillance data prior to and during the COVID-19 pandemic. Healthcare, 11(14), 2049. https://doi.org/10.3390 /healthcare11142049 Boersma, P., & Black, L. I. (2020). Human papillomavirus vaccination among adults aged 18–26, 2013–2018 (NCHS Data Brief No. 354). National Center for Health Statistics. https://www.cdc.gov/nchs/data/databriefs/db354-h.pdf Bolte, E. E., Moorshead, D., & Aagaard, K. M. (2022). Maternal and early life exposures and their potential to influence development of the microbiome. Genome Medicine, 14(1), 1–29. https://doi.org/10.1186/s13073-021-01005-7 Borelli, G. (2023). About six-in-ten Americans say legalization of same-sex marriage is good for society. https://www.pewresearch.org/short-reads /2022/11/15/about-six-in-ten-americans-say-legalization-of-same-sex -marriage-is-good-for-society/ Brady, E., & Keller, M. F. (2023). Women in combat need a collaborative culture shift. Military Medicine, 188(Suppl. 4), 3–8. https://doi.org/10.1093/milmed /usac405 Brown, A. (2022). More than twice as many Americans support than oppose the #MeToo movement. https://www.pewresearch.org/social-trends/2022/09/29/more -than-twice-as-many-americans-support-than-oppose-the-metoo-movement/ Brown, S., Herr, J., Roy, R., & Klerman, J. A. (2020). Employee and worksite perspectives of the family and medical leave act: Supplemental results from the 2018 surveys. https://www.dol.gov/sites/dolgov/files/OASP/evaluation/pdf /WHD_FMLA2018SurveyResults_Appendices_Aug2020.pdf Brown, T. H., & Homan, P. (2023). The future of social determinants of health: Looking upstream to structural drivers. The Milbank Quarterly, 101(S1), 36–60. https://doi.org/10.1111/1468-0009.12641 Catalyst. (2022, August 29). Women in the workforce: United States (quick take). https://www.catalyst.org/research/women-in-the-workforce-united-states Centers for Disease Control and Prevention. (n.d.-a). Adolescent and school health: Health disparities. U.S. Department of Health and Human Services. Retrieved February 16, 2023, from https://www.cdc.gov/healthyyouth/disparities Centers for Disease Control and Prevention. (n.d.-b). Adult obesity facts. U.S. Department of Health and Human Services. Retrieved February 16, 2023, from https://www.cdc.gov/obesity/data/adult.html Centers for Disease Control and Prevention. (n.d.-c). Arthritis: National statistics. U.S. Department of Health and Human Services. Retrieved February 16, 2023, from https://www.cdc.gov/arthritis/data_statistics/national-statistics.html Centers for Disease Control and Prevention. (n.d.-d). Cervical cancer statistics. U.S. Department of Health and Human Services. Retrieved February 16, 2023, from http://www.cdc.gov/cancer/cervical/statistics Centers for Disease Control and Prevention. (n.d.-e). Common reproductive health concerns for women. U.S. Department of Health and Human Services. Retrieved February 16, 2023, from https://www.cdc.gov/reproductivehealth /womensrh/healthconcerns.html Centers for Disease Control and Prevention. (n.d.-f). Current cigarette smoking among adults in the United States. U.S. Department of Health and Human Services. Retrieved February 16, 2023, from https://www.cdc.gov/tobacco /data_statistics/fact_sheets/adult_data/cig_smoking/index.htm Centers for Disease Control and Prevention. (n.d.-g). HIV: Statistics overview. U.S. Department of Health and Human Services. Retrieved March 17, 2023, from https://www.cdc.gov/hiv/statistics/overview/index.html Centers for Disease Control and Prevention. (n.d.-h). National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP): About chronic diseases. U.S. Department of Health and Human Services. Retrieved February 16, 2023, from https://www.cdc.gov/chronicdisease/about/index.htm

Centers for Disease Control and Prevention. (n.d.-i). Unintended pregnancy. U.S. Department of Health and Human Services. Retrieved February 16, 2023, from https://www.cdc.gov/reproductivehealth/contraception /unintendedpregnancy/index.htm Centers for Disease Control and Prevention. (n.d.-j). Women’s reproductive health. U.S. Department of Health and Human Services. Retrieved February 16, 2023, from https://www.cdc.gov/reproductivehealth/womensrh/index.htm Centers for Disease Control and Prevention. (2016). Zika virus: Sexual transmission and prevention. U.S. Department of Health and Human Services. http:// www.cdc.gov/zika/transmission/sexual-transmission.html Centers for Disease Control and Prevention. (2020). WISQARS: Causes of injury-related death: Unintentional, all injury types. https://wisqars.cdc.gov/data /explore-data/explore/selected-years Centers for Disease Control and Prevention. (2021). About chronic diseases. National Center for Chronic Disease Prevention and Health Promotion. https://www.cdc.gov/chronicdisease/about/index.htm Centers for Disease Control and Prevention. (2022a). Data on COVID-19 during pregnancy: Severity of maternal illness. U.S. Department of Health and Human Services. https://stacks.cdc.gov/view/cdc/119588 Centers for Disease Control and Prevention. (2022b, November 1). Overview of COVID-19 vaccines. U.S. Department of Health and Human Services. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines /overview-COVID-19-vaccines.html Centers for Disease Control and Prevention. (2023). Drug overdose deaths. https://www.cdc.gov/drugoverdose/deaths/index.html Centers for Medicare & Medicaid Services. (2023, February 17). NHE fact sheet. U.S. Department of Health and Human Services. https://www.cms .gov/research-statistics-data-and-systems/statistics-trends-and-reports /nationalhealthexpenddata/nhe-fact-sheet Cheng, T. C., & Lo, C. C. (2022). Citizenship status and restrictive policies affect participation in temporary assistance for needy families (TANF). Social Work Research, 46(3), 185–192. https://doi.org/10.1093/swr/svac009 Cohen, A. J., Dosa, D. M., Rudolph, J. L., Halladay, C. W., Heisler, M., & Thomas, K. S. (2022). Risk factors for veteran food insecurity: Findings from a National US Department of Veterans Affairs food insecurity screener. Public Health Nutrition, 25(4), 819–828. https://doi.org/10.1017/S1368980021004584 Cohen, R. A., & Cha, A. E. (2022, December). Health insurance coverage: Early release of estimates from the National Health Interview Survey, January–June 2022. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics. https://www .cdc.gov/nchs/data/nhis/earlyrelease/insur202111.pdf Cohen, R. A, Terlizzi, E. P., Cha, A. E., & Martinez, M. E. (2021). Health insurance coverage: Early release of estimates form the National Health Interview Survey, 2020: National Center for Health Statistics, National Health Interview Survey Early Release Program. https://www.cdc.gov/nchs/data/nhis/earlyrelease /insur202108-508.pdf Connor, L., Dean, J., McNett, M., Tydings, D. M., Shrout, A., Gorsuch, P. F., Hole, A., Moore, L., Brown, R., Melnyk, B. M., & Gallagher-Ford, L. (2023). Evidence‐based practice improves patient outcomes and healthcare system return on investment: Findings from a scoping review. Worldviews on Evidence‐Based Nursing, 20(1), 6–15. https://doi.org/10.1111/wvn.12621 Creamer, J., Shrider, E. A., Burns, K., & Chen, F. (2022, September 13). Poverty in the United States: 2021. U.S. Department of Commerce, U.S. Census Bureau. https://www.census.gov/library/publications/2022/demo/p60-277.html De La Cruz, M. S. D., & Buchanan, E. M. (2017). Uterine fibroids: Diagnosis and treatment. American Family Physician, 95(2), 100–107. https://www.aafp .org/pubs/afp/issues/2017/0115/p100.html Duffin, E. (2022, October 11). U.S. population by generation 2021. Statista. https://www.statista.com/statistics/797321/us-population-by-generation Eichler, M. (2022). Making military and veteran women (in)visible: The continuity of gendered experiences in military-to-civilian transition. Journal of Military, Veteran and Family Health, 8(S1), 36–45. https://doi.org/10.3138 /jmvfh-2021-0077 Ely, D. M., & Driscoll, A. K. (2021). Infant mortality in the United States, 2019: Data from the period linked birth/infant death file. National Vital Statistics Reports, 70(14). National Center for Health Statistics. https://dx.doi .org/10.15620/cdc:111053 Family and Medical Leave Act, 29 U.S.C. §§ 2601–2654 (1993). Farrell, R. M. (2022). Women, children, families and the translation of genomics in reproductive medicine. In M. A. Allyse & M. Michie (Eds.), Born well: Prenatal genetics and the future of having children (pp. 3–13). Springer Verlag. Fluetsch, N., Levy, C., & Tallon, L. (2019). The relationship of physical activity to mental health: A 2015 behavioral risk factor surveillance system data analysis. Journal of Affective Disorders, 253, 96–101. https://doi.org/10.1016/j .jad.2019.04.086

Foy, B. D., Kobylinski, K. C., Foy, J. L. C., Blitvich, B. J., Travassos da Rosa, A., Haddow, A. D., Lanciotti, R. S., & Tesh, R. B. (2011). Probable non–vector-borne transmission of Zika virus, Colorado, USA. Emerging Infectious Diseases, 17(5), 880–882. https://doi.org/10.3201/eid1705.101939 Fusaro, V. A., & Gewirtz, R. (2022). Temporary assistance for needy families (TANF) still matters: A social work perspective. Social Work, 67(4), 394–397. https://doi.org/10.1093/sw/swac034 Garcia, O., Slavish, D. C., Dietch, J. R., Messman, B. A., Contractor, A. A., Haynes, P. L., Pruiksma, K. E., Kelly, K., Ruggero, C., & Taylor, D. J. (2021). What goes around comes around: Nightmares and daily stress are bidirectionally associated in nurses. Stress and Health, 37(5), 1035–1042. https:// doi.org/10.1002/smi.3048 Hamilton, B. E., Martin, J. A., & Ventura, S. J. (2010). Births: Preliminary data for 2008. National Vital Statistics Report, 58(16). https://www.cdc.gov/nchs /data/nvsr/nvsr58/nvsr58_16.pdf Hamilton, B. E., Martin, J. A., & Osterman, M. J. K. (2022). Births: Provisional data for 2021 (Vital Statistics Rapid Release No. 20). National Center for Health Statistics. https://doi.org/10.15620/cdc:116027 Haynes, B., Suckley, L., & Nunnington, N. (2017). Workplace productivity and office type: An evaluation of office occupier differences based on age and gender. Journal of Corporate Real Estate, 19(2), 111–138. https://doi .org/10.1108/JCRE-11-2016-0037 Heron, M. (2021). Deaths: Leading causes for 2019. National Vital Statistics Report, 70(9), 1–115. https://www.cdc.gov/nchs/data/nvsr/nvsr70/nvsr70-09 -508.pdf Holliday, R., Holder, N., Smith, A. A., Desai, A., Hoffmire, C. A., Forster, J. E., & Monteith, L. L. (2023). Military sexual trauma among veterans using and not using VA justice-related programing: A national examination. Journal of Psychiatric Research, 164, 46–50. https://doi.org/10.1016/j .jpsychires.2023.05.067 Iuliano, A. D., Brunkard, J. M., Boehmer, T. K., Peterson, E., Adjei, S., Binder, A. M., Cobb, S., Graff, P., Hidalgo, P., Panaggio, M. J., Rainey, J. J., Rao, P., Soetebier, K., Wacaster, S., Ai, C., Gupta, V., Molinari, N.-A. M., & Ritchey, M. D. (2022). Trends in disease severity and health care utilization during the early Omicron variant period compared with previous SARS-CoV-2 high transmission periods—United States, December 2020–January 2022. Morbidity and Mortality Weekly Report, 71, 146–152. https://doi.org/10.15585 /mmwr.mm7104e4 Kerns-D’Amore, K., McKenzie, B., & Locklear, L. S. (2023). Migration in the United States: 2006 to 2019 (American Community Survey Reports, ACS53). U.S. Census Bureau. Laughlin, L., & Wisniewski, M. (2021, March 23). Women represent majority of workers in several essential occupations. U.S. Census Bureau. https:// www.census.gov/library/stories/2021/03/unequally-essential-women-and -gender-pay-gap-during-covid-19.html Lleras, C. (2008). Employment, work conditions, and the home environment in single-mother families. Journal of Family Issues, 29(10), 1268–1297. https:// doi.org/10.1177/0192513X08318842 Lowdermilk, D. L., Cashion, M. C., Perry, S. E., Alden, K. R., & Olshansky, E. (Eds.). (2020). Maternity and women’s health care (12th ed.). Elsevier. Martin, J. A., Hamilton, B. E., & Osterman, M. J. K. (2022, August). Births in the United States 2021 (NCHS Data Brief 442). U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics. https://doi.org/10.15620/cdc:119632 Mattson, C. L., Tanz, L. J., Quinn, K., Kariisa, M., Patel, P., & Davis, N. L. (2021). Trends and geographic patterns in drug and synthetic opioid overdose deaths—United States, 2013–2019. Morbidity & Mortality Weekly Report, 70(6), 202–207. http://dx.doi.org/10.15585/mmwr.mm7006a4 McPhail, R., Chan, X. W., May, R., & Wilkinson, A. (2023). Post-COVID remote working and its impact on people, productivity, and the planet: An exploratory scoping review. The International Journal of Human Resource Management, 1–29. https://doi.org/10.1080/09585192.2023.2221385 Meleis, A. (2005). Safe womanhood is not safe motherhood: Policy implications. Health Care for Women International, 26, 464–471. https://doi .org/10.1080/07399330590962825 Meleis, A. I., Caglia, J., & Langer, A. (2016). Women and health: Women’s dual roles as both recipients and providers of healthcare. Journal of Women’s Health, 25(4), 329–331. https://doi.org/10.1089/jwh.2015.5717 Melnyk, B. M., & Fineout-Overholt, E. (Eds.). (2019). Evidence-based practice in nursing and healthcare: A guide to best practice (4th ed.). Wolters Kluwer. Miller, K. E., Chatterjee, P., & Werner, R. M. (2023). Trends in supply of nursing home beds, 2011–2019. JAMA Network Open, 6(3), e230640. https://doi .org/10.1001/jamanetworkopen.2023.0640 Murphy, S. L, Kochanek, K. D, Xu, J., & Arias, E. (2021). Mortality in the United States, 2020 (NCHS Data Brief No. 427). National Center for Health Statistics. https://doi.org/10.15620/cdc:112079

National Center for Health Statistics. (2021). 2019 trend tables: Table 22. Hypertension among adults aged 20 and over, by selected characteristics: United States, selected years 1988–1994 through 2015–2018. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. https://www.cdc.gov/nchs/data/hus/2019/022-508.pdf National Institute of Diabetes and Digestive and Kidney Diseases. (2021). Overweight and obesity statistics. https://www.niddk.nih.gov/health-information /health-statistics/overweight-obesity. Ne’eman, A., Stein, M., & Grabowski, D. C. (2022). Nursing home residents younger than age sixty-five are unique and would benefit from targeted policy making: Study examines policies that could benefit nursing home residents younger than sixty-five. Health Affairs, 41(10), 1449–1459. https://doi .org/10.1377/hlthaff.2022.00548 Office of Population Affairs. (n.d.). Trends in teen pregnancy and childbearing. U.S. Department of Health and Human Services, Office of Public Health and Science. Retrieved March 30, 2023, from https://opa.hhs.gov/adolescent-health /reproductive-health-and-teen-pregnancy/trends-teen-pregnancy-and -childbearing Osterman, M. J. K., Hamilton, B. E., Martin, J. A., Driscoll, A. K., & Valenzuela, C. P. (2023). Births: Final data for 2021. National Vital Statistics Report, 72(1). https://www.cdc.gov/nchs/data/nvsr/nvsr72/nvsr72-01.pdf Park, H., & Choi, S. (2023). Understanding the perceptions of low-income American working mothers in rural areas: Exploratory analysis of relative care. Journal of Family Studies, 29(3), 1154–1179. https://doi.org/10.1080 /13229400.2022.2032797 Pathak, S. K., & Dev, G. (2023). The evolution of same-sex marriage laws and their impact on the traditional family structure. Indian Journal of Law and Legal Research, 5(2), 1. Patient Protection and Affordable Care Act of 2010, Pub. L. No. 111-148, 124 Stat. 119 (2010). https://www.congress.gov/111/plaws/publ148/PLAW-111publ148.pdf  Personal Responsibility and Work Opportunity Reconciliation Act, Pub. L. No. 104-196, 110 Stat. 2105 (1996). https://www.congress.gov/104/plaws /publ193/PLAW-104publ193.pdf Pew Research Center. (2023). Second-generation Americans: A portrait of the adult children of immigrants. https://www.pewresearch.org /social-trends/2013/02/07/second-generation-americans/ Rasmussen, S. A., Smulian, J. C., Lednicky, J. A., Wen, T. S., & Jamieson, D. J. (2020). Coronavirus disease 2019 (COVID-19) and pregnancy: What obstetricians need to know. American Journal of Obstetrics and Gynecology, 222(5), 415–426. https://doi.org/10.1016/j.ajog.2020.02.017 Reeves, W. C., Strine, T. W., Pratt, L. A., Thompson, W., Ahluwalia, I., Dhingra, S. S., McKnight-Eily, L. R., Harrison, L., D’Angelo, D. V., Williams, L., Morrow, B., Gould, D., & Safran, M. A. (2011). Mental illness surveillance among adults in the United States. MMWR Supplements, 60(3), 1–29. https://www .cdc.gov/mmwr/preview/mmwrhtml/su6003a1.htm Scherer, Z. (2022, November 22). Key demographic and economic characteristics of same-sex and opposite-sex couples differed. U.S. Census Bureau. https:// www.census.gov/library/stories/2022/11/same-sex-couple-households -exceeded-one-million.html Shrider, E. A., Kollar, M., Chen, F., & Semega, J. (2021). Income and poverty in the United States: 2020 (Report No. P60-273). U.S. Census Bureau. https://www .census.gov/library/publications/2021/demo/p60-273.html Statista. (n.d.) Poverty rate in the United States in 2021, by age and gender. Retrieved March 17, 2023, from https://www.statista.com/statistics/233154/us -poverty-rate-by-gender Toossi, M., & Morisi, T. L. (2017). Women in the workforce before, during, and after the great recession. https://www.bls.gov/spotlight/2017/women-in-the -workforce-before-during-and-after-the-great-recession/pdf/women-in -the-workforce-before-during-and-after-the-great-recession.pdf United Nations. (1994). Declaration on the elimination of violence against women. https://documents-dds-ny.un.org/doc/UNDOC/GEN/N94/095/05 /PDF/N9409505.pdf?OpenElement U.S. Bureau of Labor Statistics. (2021, April). Women in the labor force: A data book. U.S. Department of Labor. https://www.bls.gov/opub/reports/womens -databook/2020/home.htm U.S. Bureau of Labor Statistics. (2023, January 25). Labor force statistics from the Current Population Survey: Household data annual averages: 9. Employed persons by occupation, sex, and age. U.S. Department of Labor. https://www .bls.gov/cps/cpsaat09.htm U.S. Cancer Statistics Working Group. (2021). U.S. Cancer Statistics Data Visualizations Tool, based on 2020 submission data (1999–2018). U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute. https://www.cdc.gov/cancer/dataviz

U.S. Census Bureau. (n.d.). American Community Survey: B01001G sex by age (two or more races). U.S. Department of Commerce. Retrieved March 28, 2023, from https://data.census.gov/table?q=Two+or+More+Races&tid =ACSDT1Y2021.B01001G U.S. Census Bureau. (n.d.). American Community Survey: SO101 age and sex. U.S. Department of Commerce. Retrieved March 28, 2023, from https://data .census.gov/table?q=age+and+sex&tid=ACSST1Y2021.S0101 U.S. Census Bureau. (2021, November 29). Census Bureau releases new estimates on America’s families and living arrangements. U.S. Department of Commerce. https://www.census.gov/newsroom/press-releases/2021/families-and -living-arrangements.html U.S. Department of Health and Human Services. (1996). Physical activity and health: A report of the Surgeon General. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion. https://www.cdc .gov/nccdphp/sgr/index.htm U.S. Department of Health and Human Services. (2022). Trends in teen pregnancy and childbearing. https://opa.hhs.gov/adolescent-health/reproductive -health-and-teen-pregnancy/trends-teen-pregnancy-and-childbearing U.S. Department of Health and Human Services, Health Resources and Services Administration. (2013). Women’s health USA 2013. U.S. Department of Health and Human Services. https://mchb.hrsa.gov/sites/default/files/mchb /data-research/womens-health-2013.pdf U.S. Department of Homeland Security. (n.d.). Yearbook of immigration statistics. Office of Immigration Statistics. Retrieved August 5, 2023, from https:// www.dhs.gov/files/statistics/publications/yearbook.shtm. Vespa, J., Medina, L., & Armstrong, D. M. (2020, February). Demographic turning points for the United States: Population projections for 2020 to 2060 (Current Population Report P25-1144). U.S. Census Bureau. https://www.census .gov/content/dam/Census/library/publications/2020/demo/p25-1144 .pdf Villarroel, M. A., & Terlizzi, E. P. (2020). Symptoms of depression among adults: United States, 2019 (NCHS Data Brief No. 379). National Center for Health Statistics. https://cdc.gov/nchs/data/databriefs/db379-H.pdf Walters, M. L., Chen J., & Breiding, M. J. (2013). The National Intimate Partner and Sexual Violence Survey (NISVS): 2010 findings on victimization by sexual orientation. National Center for Injury Prevention and Control, Centers for Disease Control and Prevention. https://www.cdc.gov/violenceprevention /pdf/nisvs_sofindings.pdf WorldData.info. (2020). Life expectancy for men and women. https://www .worlddata.info/life-expectancy.php World Health Organization. (n.d.). Violence against women. Retrieved March 30, 2023, from http://www.who.int/news-room/fact-sheets/detail /violence-against-women World Health Organization. (1946). Constitution. Author. https://www.who.int /about/governance/constitution World Health Organization. (2008). Closing the gap in a generation: Health equity through action on the social determinants of health: Commission on Social Determinants of Health final report. Author. World Health Organization. (2020). WHO reveals leading causes of death and disability worldwide: 2000–2019. https://www.who.int/news/item /09-12-2020-who-reveals-leading-causes-of-death-and-disability -worldwide-2000-2019 World Health Organization. (2021a, September 13). Depression. https://www .who.int/news-room/fact-sheets/detail/depression World Health Organization. (2021b). Violence against women. https://www.who .int/news-room/fact-sheets/detail/violence-against-women World Health Organization. (2023a, March 31). Depressive disorder (depression). https://www.who.int/news-room/fact-sheets/detail/depression World Health Organization. (2023b, March 24). Endometriosis. http://www.who .int/news-room/fact-sheets/detail/endometriosis Xu, J. (2019). Mortality patterns between five states with highest death rates and five states with lowest death rates: United States, 2017 ((NCHS Data Brief No. 350). National Center for Health Statistics. https://www.cdc.gov/nchs /products/databriefs/db350.html Xu, J., Murphy, S. L, Kochanek, K. D, & Arias, E. (2022, December). Mortality in the United States, 2021 (NCHS Data Brief No. 456). National Center for Health Statistics. https://doi.org/10.15620/cdc:122516 Zou, L., Ruan, F., Huang, M., Liang, L., Huang, H., Hong, Z., Yu, J., Kang, M., Song, Y., Xia, J., Guo, Q., Song, T., He, J., Yen, H. L., Peiris, M., & Wu, J. (2020). SARS-CoV-2 viral load in upper respiratory specimens of infected patients. New England Journal of Medicine, 382(12), 1177–1179. https://doi .org/10.1056/NEJMc2001737

Chapter

2

Women and Healthcare Workforce: Caregivers and Consumers Meghan Eagen-Torkko, Diana Taylor,

WOMEN AND HEALTHCARE IN THE UNITED STATES Women in the United States have a dual relationship with healthcare, as the majority of the healthcare workforce and as recipients/consumers of that healthcare. The relationships between women and healthcare are further complicated by racism, ableism, homo/transphobia, and ageism that different women experience in very different ways. While it can be said that women’s healthcare, like women’s experiences in the other spheres of our lives, is impacted by institutional misogyny and sexism, Black, Indigenous, and other people of color (BIPOC); disabled people; lesbian, gay, transgender, bisexual, queer, intersex, and other sexual and gender diverse people such as asexual persons (LGBTQI+);1 and older people also are affected by racism and other systems of oppression in complex and competing ways. The intersectional nature of oppressions means that we should be very cautious as clinicians and as researchers at Udrawing conclusions about patients and best care practices when those conclusions are not centered in the lived expertise of the people most affected. Much of what we know, or believe we know, about women and healthcare in the United States is drawn from the experiences of White, straight, cisgender, nondisabled women, and may not reflect the realities of healthcare for BIPOC and others. For example, when discussing options for pregnancy-related care, providers will “package” that information differently for BIPOC women than for White women (Altman et al., 2019), which in turn calls into question the adequacy of informed consent for that care. It is critical when examining healthcare

and

Molly Altman

for women to also be critical of whose experiences are being centered in the discussion and who is considered the “norm.” In this chapter, we examine the dual role of women in healthcare. As members of the healthcare workforce, women represent the majority of employees, but are disproportionately concentrated in roles with less power and compensation within the larger healthcare workforce. As healthcare consumers, women are more likely to utilize care, particularly during the childbearing years when men of the same age are much less likely to access care, but also experience the negative impacts of sexism while accessing that care. For example, women are much more likely than men to die of cardiac arrest caused by a myocardial infarction, but not because they are more likely to experience that cardiac arrest. Rather, the “classic” signs of cardiovascular disease are much less common in women than in men, leading many women not to seek care, and women are less likely to have their symptoms treated aggressively if they do go to an ED (Aggarwal et al., 2018; Yu et al., 2019). As both workforce members and as consumers, women experience negative aspects of the healthcare system disproportionately to their representation in the general population and within healthcare. Healthcare systems, which could not survive without the labor and expertise of women, will need to evolve in the coming decades to meet the needs of not only their women consumers but also their women workers. That evolution has begun to incorporate more emphasis on population health needs (gender- and age-focused health, mental health, sexual and reproductive health, for example) as well as the workforce to care for these populations (e.g., women’s health, public health, behavioral health). The Patient Protection and Affordable Care Act (ACA, 2010; Health

In a 2020 National Academy of Sciences, Engineering, and Medicine (NASEM) report, the phrase sexual and gender diverse (SGD) is recommended to describe individuals who identify as lesbian, gay, bisexual, transgender, queer, intersex, or nonbinary, or who exhibit attractions and behaviors that do not align with heterosexual or traditional gender norms (Patterson et al., 2020). 1

29

30  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

Resources and Services Administration [HRSA], 2021a) incentivized community health for the first time in healthcare regulation and reimbursement, and while the initial promise of the ACA has somewhat faded following a number of Supreme Court decisions that limited some provisions, the SARS-CoV-2 (COVID-19) pandemic that began in January 2020 has spotlighted the need for improved public and community health systems, workforce, and funding. As discussed later in the chapter, healthcare initially began as a community-based system, and professionalization throughout the 19th and 20th centuries moved that system out of the communities where it originated. With a renewed interest in vaccination, infectious disease monitoring, and the role that public and community health workers (CHWs) play in the health of individuals and communities, the potential exists for a more powerful role for both public and community health, and for community-based health workers, both formal and informal. Historically, those workers have been women, and women are likely to reclaim some of that role given the prevalence of women in both the healthcare workforce and consumer base. One of the challenges of healthcare as we move into a postpandemic, post-ACA era is that we are inheriting a mishmash of healthcare specialties, providers, and foci. In contrast to the United Kingdom’s National Health System (discussed later), healthcare for women, trans men, nonbinary people, and other gender diverse populations is fractured between sexual and reproductive healthcare (SRH), which is often delivered via obstetrician-gynecologists (OB/GYN, a surgical specialty), and non-SRH services, including cardiovascular/ metabolic assessments, which may be delivered via family practice physicians, internists, or other providers, who may or may not also manage SRH. Confusingly, SRH providers often also deliver non-SRH services such as routine glucose checks, lipid panels, and other screenings. To add yet another layer of difficulty, the U.S. system often divides people first by body system (reproductive, pulmonary, neurology), and then may later subspecialize (urogynecology) by gender, or the gender subspecialization may come first (women’s health). Finally, specialties are highly inconsistent in how they define gender (some use a social-personal definition, while others use body parts, which can be traumatic or harmful for gender diverse people to experience). These inconsistencies and specialty-physician focused systems are in stark contrast to the more common model seen in the United Kingdom and other countries where nurses, midwives, and generalist physicians are prioritized within an organized system of primary healthcare that includes both personal (individual) and public (community or region) care. In this model of care, core services are delivered in the home or within neighborhood clinics, or by local public health districts, which is a model much closer to the community-based one the United States previously had than our current illness/specialty-focused care, delivered in centralized healthcare systems that may or may not be familiar with the community of its patients. There are many challenges that women in the healthcare system face, as patients and as caregivers, and while the U.S. model of primary/secondary/tertiary care is not the sole cause of these, the fractured nature of U.S. healthcare necessarily overemphasizes SRH potentially at the cost of holistic care, since people with uteri must often routinely interact with the

healthcare system (for contraception, routine cervical and breast cancer screenings, and sexually transmitted infection [STI] screening and treatment), but may find that their experience of that healthcare system is limited to SRH services. The U.S. specialty-care model likewise limits utilization of public health work in primary prevention and health improvement since such work is incongruent with the diagnosis-treatment norms of this system. Finally, because of the gendered nature of many specialties, people who do not fall into the category of cisgender women may be excluded or harmed by this model of care. As we discuss the existing systems, we need to actively consider how we can adapt or replace those parts of the systems that may be harmful or unnecessarily costly or inefficient. Note on language used: While many healthcare workers do not identify with the gender binary, the bulk of available data collected does use binary male/female categories. This limits our ability to directly address the issues facing trans and gender diverse healthcare workers in this chapter. The use of “women” is intended not to exclude trans and gender diverse healthcare workers, who may experience discrimination and harm related to their gender identity and their role as healthcare workers, but instead to (a) acknowledge the impacts of sexism and patriarchy on healthcare workers who present as women and make up the large majority of healthcare workers, and (b) reflect the current state of the research. It is our expectation that for the next revision of this text, there will be more information available about the experiences specific to trans and gender diverse healthcare workers. Likewise, healthcare of trans men and nonbinary people often falls under the purview of “women’s health,” and we acknowledge the limitations of this terminology. In contrast, trans women’s gender is often ignored in favor of current anatomy, particularly if they have not had gender-affirming surgery, and they may be excluded from “women’s health” despite their gender. In addition, “women’s healthcare” encompasses the whole person, and not solely gynecology/reproductive health. While we do focus on reproductive healthcare as significant in the experience of women in the United States, we reaffirm that women are not defined by our anatomy, and that women’s health is a holistic rather than specialty concept. The U.S. Bureau of Labor Statistics (BLS) collects ethnicity data as Hispanic/non-Hispanic. While Latino/Latina/Latinx are terms more often used by individuals in the United States to reflect ethnicity/identity, they are not synonymous with Hispanic, and therefore cannot be substituted. In this chapter, we use the language used by the BLS in its data, while recognizing that there is difficulty in extrapolating these findings to people who may identify as Latino/Latina/Latinx/Latine. It is our hope that governmental data collection will be reconsidered in future with input from community members.

HEALTHCARE WORKFORCE: GLOBAL AND IN THE UNITED STATES According to the World Health Organization (WHO), the definition of the health workforce includes “all people engaged in actions whose primary intent is to enhance health”

Chapter 2  Women and Healthcare Workforce: Caregivers and Consumers 31

and improve population health outcomes (WHO, 2008, 2016). This includes physicians, nurses, and midwives, but also laboratory technicians, public health professionals, CHWs, pharmacists, and all other support workers whose main function relates to delivering preventive, promotive, or curative health services (WHO, 2016). National and global efforts to achieve the health targets set by the United Nations (UN) are thwarted in many countries by shortages of health staff, their often-inequitable distribution, and gaps in their capacity and performance. The UN 2030 Agenda for Sustainable Development Goals (SDG) expands the Millennium Development Goals (2000–2015) relevant to health workforce and women’s health: SDG 4— Ensure inclusive and equitable quality education and promote lifelong learning opportunities for all; SDG 5—Achieve gender equality and empower all women and girls. Although low- and middle-income countries face the most severe challenges in ensuring a sufficient, fit-for-purpose and fit-to-practice health workforce, countries at all levels of socioeconomic development face the challenge of how to sustain the human capital required to guarantee universal access and universal health coverage (including the elimination of preventable maternal and child deaths and unsafe abortion; UN, 2015). According to the WHO Global Health Workforce Alliance, a global deficit of over 12 million skilled health professionals (midwives, nurses, and physicians) is estimated by 2035 and implies the need to rethink the traditional models of education, deployment, and remuneration of the health workforce; long-term system-building; comprehensive labor market engagement; and essential data systems (WHO, 2014b). In 2013, WHO recommended that health begins with health workers and their empowerment (voice, rights, responsibilities), which play a central role in developing and implementing sustainable strategies toward universal health coverage and the improvement of health services and population health outcomes. Some of the common challenges across all countries include current and future shortages of some categories of health workers; replacement of an aging health workforce; the insufficient use of advanced practitioners, midwives, and nurses in many settings; and the difficulty attracting and retaining workers without enabling environments (WHO, 2014b, 2016). The delivery of health services is one of the largest and fastest growing industries in the United States, with about 22 million workers (U.S. Census Bureau,2 2019) either in the health sector or in health occupations employment outside the health sector, accounting for more than 14% of the total U.S. workforce. (Indeed, even the use of the word “industry” demonstrates the problem with our fragmented health service delivery system that expands and contracts based on profit and corporate decisions, and reflects the difference between the United States and global definitions.) About 44% of all healthcare jobs are in hospitals (32%) and offices of healthcare practitioners, and one third are in nursing homes (14%) or other ambulatory or personal care facilities (U.S. Census Bureau, 2019). Of the 15 million healthcare practitioners,

technicians, and support personnel, in 2020, RNs (21%) were the single largest health occupation, followed by nursing assistants (9%), personal care aides (9%), and home health aides (4%; BLS, 2023‌‌‌‌‌‌‌‌‌‌). Despite the size and anticipated growth of the healthcare workforce, there are significant disparities within that workforce. In the United States, women are 80% of the direct-provision healthcare workforce and 86% of the nursing workforce (BLS, 2023‌‌‌‌‌‌‌‌‌‌), but men are overrepresented in roles of leadership in healthcare relative to the proportion of nurses (B. W. Smith et al., 2021). Although people of color represent 40% of the total U.S. population (U.S. Census Bureau, 2021a), over 50% of workers in almost every health occupation except personal, psychiatric, nursing, and home health aides are White (HRSA, 2017b‌‌‌‌‌‌‌‌‌‌). While the racial/ethnic proportion of counselors, social workers, laboratory technicians, and licensed practical nurses come the closest to equity in the U.S. population (37%–40% BIPOC), only 24% of 18 professional categories are filled by those who are BIPOC (HRSA, 2017b‌‌‌‌‌‌‌‌‌‌). Furthermore, women of color are overrepresented relative to their workforce proportion in lower-paying support work like home health aides, where they experience both less economic stability and increased risk of injury and interpersonal violence (Dill et al., 2020). Rapid changes in economic, demographic, and healthcare system factors are driving reform in the U.S. health workforce. There are imbalances among geographic and functional health workforce shortages, healthcare reform, and development of healthcare workers to meet the population and health service needs. These health workforce imbalances intersect with continuing systems of oppression and inequities across gender, race, and economic status. Given these changes and inequities, the future healthcare workforce will be increasingly female, young, racially/ethnically diverse, not U.S. born, at or below the poverty level, and less educated. This has implications for relative power and safety of the BIPOC healthcare workforce and demonstrates a need for systems-level protections for healthcare workers in these roles. In addition to the long-standing issues of equity in the U.S. healthcare workforce, the SARS-CoV-2 pandemic (COVID-19) has both exacerbated and created workforce issues (Khan et al., 2021). Now in its third year as of this writing, the pandemic increased the intended departure of healthcare workers from the bedside (Labrague & de Los Santos, 2021), worsened the mental and physical health of those who remained (Hennein et al., 2021; Shaukat et al., 2020; Sim, 2020), and created a profound relational rupture between workers and institutions, workers and patients, and workers and the public (Eagen-Torkko et al., 2021). Recovery from that rupture will require focused attention from every level of government, as well as from healthcare systems. In this chapter, we provide an overview of the current U.S. healthcare workforce; trends for the future; and critical drivers, disparities, and challenges to ensure an adequate supply and distribution of well-prepared health workers to meet the nation’s healthcare needs. Since women dominate the current and future healthcare workforce, we focus on how gender, and

The data from the U.S. Census Bureau’s 2019 American Community Survey (ACS) are more up to date than the Health Resources and Services Administration (HRSA) total workforce data analysis of the ACS Public Use Microdata Sample (PUMS) 2011–2015 data (HRSA, 2017a). 2

32  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

other elements that intersect with gender, shapes, strengthens, and empowers women as the primary healthcare workforce to meet current and future population and health service needs.

eral segments (American Hospital Association [AHA], 2022‌‌‌‌‌‌‌; Centers for Disease Control and Prevention [CDC], n.d.-a, n.d.-b, n.d.-c, n.d.-e‌‌‌‌‌‌)3: ●

U.S. HEALTH WORKFORCE: OCCUPATIONS AND PROVIDERS Definitions of healthcare providers (people and places) are rooted in history; their evolution is shaped by social, economic, and political forces. Historically, healthcare was provided by community members who trained in informal or formal apprenticeships, or by family members of the person needing care. The “professionalization” of both nursing and medicine that occurred in the United States in the 19th century, along with the rapid expansion of regulation of both healthcare practice and education, profoundly changed both who were healthcare providers and how they practiced (Matthews, 2012). Medical and nursing education reflected the segregation and exclusion of Black, Indigenous, and people of color (BIPOC) common to many professions, and this gatekeeping led to a healthcare workforce that reflected racist and sexist norms, rather than the communities served by that workforce (Jeffries, 2020). The informal/unlicensed healthcare workforce (home health workers, etc.) continues to represent more diversity in race and class, but with an increasing loss of power, income, and authority. With the rapid and massive changes in the U.S. healthcare system, badly needed system redesign is occurring along with a redefinition of healthcare workers’ roles. These changes are influenced by multiple determinants: the form of government involvement, definitions of health, social values, costs, society’s expectations for the healthcare system, the privatization of health delivery systems, and the political power of various stakeholders. Research increasingly supports the need for culturally congruent care, including care providers who reflect the patients they care for, as essential to improving health disparities (Marcelin et al., 2019; Williams et al., 2016). Understanding the historical exclusion of BIPOC and other marginalized groups (whether by religion, sexual orientation/gender identity, or disability, for example) is foundational to creating lasting and meaningful change to the current systems. The term healthcare provider here refers to people who provide care to patients and the settings or systems in which health services are provided. More than 100,000 establishments make up the health services industry with four gen-

●

● ●

Hospitals (public and private; AHA, 2022) Nursing and personal care facilities (excluding residential, mental health, substance abuse, and other residential care facilities; CDC, n.d.-c) Home healthcare (CDC, n.d.-b) Ambulatory care settings (excluding home healthcare, but including medical and diagnostic laboratories, offices and clinics of doctors of medicine, offices and clinics of dentists, offices and clinics of other health practitioners [chiropractors, optometrists, podiatrists, occupational/physical therapists, psychologists, speech/hearing therapists, nutritionists, and alternative medicine practitioners], outpatient care centers [kidney dialysis centers, substance use disorder (SUD) treatment clinics, mental health centers, and rehabilitation centers], medical and diagnostic laboratories, and other ambulatory health services [ambulance and helicopter transport services, blood and organ banks, pacemaker monitoring services, and nonhospital surgical centers]; CDC, n.d.-a)

Among the U.S. working-age population, the federal government defines the health workforce as the "occupations [that] include all healthcare providers with direct patient care and support responsibilities" (U.S. Department of Health and Human Services [DHHS], n.d., “Strategies”). This definition is inclusive of workforce occupations defined within the U.S. Department of Labor (DOL), Bureau of Labor Statistics Standard Occupational Classification (SOC) system.4 The BLS Occupational Employment Statistics categories/groupings, updated most recently by the 2018 SOC system (BLS, 2018), represents the majority of health ‌‌‌‌‌‌‌‌‌‌ workforce occupations.5 The SOC is used by federal statistical agencies to classify workers into occupational categories for the purpose of data collection and analysis, with cross-references with the U.S. BLS (fastest growing occupations), the BLS Occupational Employment Statistics (employment and wage estimates), and the U.S. Census Bureau’s American Community Survey (ACS; current demographic data).6 In addition to the U.S. BLS, the National Center for Health Workforce Analysis (NCHWA), a unit of the HRSA of the DHHS, uses these labor and census data to estimate the current and future supply and demand for U.S.

More detailed information on the work settings can be found on the U.S. Census Bureau website: www.census.gov/eos/www/naics. Variation in definitions reflects the changes in standards and measurement. The BLS estimates occupational employment statistics every 2 years using the classifications developed by the SOC system. However, the SOC is revised about every 10 years, although an update was published in 2018. 5 These occupational categories have limitations. Before 2010, for example, registered nursing made no distinction between nurse practitioners, nurse midwives, and RNs. The nursing aides, orderlies, and attendants occupational category also includes multiple job titles, levels of training, and certifications and were separated into separate job categories in 2010. Some job titles in a healthcare setting may not necessarily reflect similar Occupational Employment Statistics (OES) occupational classifications, which may cause some problems in reporting. For example, confusion may result from the differences in defining a home health aide as any individual providing services in the home or as one who completes home health aide certification requirements (https://www.bls.gov/soc/2018/soc_2018_manual.pdf). 6 For more detailed information on the data sources, definitions, methods, and SOC categories, see HRSA (2017a). See also the U.S. Census Bureau website: www.census.gov/eos/www/naics. 3 4

Chapter 2  Women and Healthcare Workforce: Caregivers and Consumers 33

health workers in order to produce a health workforce of sufficient size and skill to meet the nation’s healthcare needs (HRSA, 2018a, 2018b, 2020). The NCHWA regularly publishes a summary of data on the size and characteristics of U.S. health occupations based ‌‌‌‌‌‌‌‌‌‌ on the U.S. government’s SOC system.7 The most recent summary in The U.S. Health Workforce Chartbook, published in September 2018, is based on U.S. Census Bureau data from the ACS Public Use Microdata Sample (PUMS) 2011–2015 (HRSA, 2018b). The U.S. Health Workforce Chartbook estimates the total number of individuals in the occupation or occupational grouping, the percentage of women, the percentage of health workers older than age 55, and the highest and lowest number of workers per 100,000 in the working-age population across the 50 states. HRSA’s Health Workforce Simulation Model (HWSM) uses a microsimulation approach to link multiple data elements that incorporate behavioral as well as structural changes impacting workforce supply and demand, including population needs for health provider occupations (e.g., women’s health, behavioral health, and primary care providers; HRSA, 2021b).‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌ In The U.S. Health Workforce Chartbook, health occupation titles are grouped into four categories for ease of reporting (HRSA, 2018b): Part I comprises clinicians (physicians; physician assistants [PAs]; RNs including nurse anesthetists (CRNAs), nurse-midwives (CNMs), and nurse practitioners (NPs); LPN/LVNs; pharmacists; and oral health professions, including dentists, dental hygienists, and dental assistants). Part II includes additional clinician categories (chiropractors, veterinarians, and vision health professionals, including optometrists and dispensing opticians) and occupations concerned with healthcare administration duties (medical/ health service managers and medical secretaries). Part III reports on health-related technologists and technicians as well as aides and assistants; and Part IV describes behavioral (psychologists, counselors, and social workers) and allied health (physical therapists and assistant/aides, dietitians/nutritionists, occupational therapists, respiratory therapists [RTs], speech-language pathologists, and massage therapists) occupations. While the grouping of occupations makes the data easier to report and analyze, it must be regarded with some caution, as it eludes the degree to which healthcare functions on a teamwork model, as incentivized by aspects of the ACA, and the reality that the roles of each profession often overlap in any given patient’s care. In the reports from the Census Bureau’s 2019 ACS, there were 22 million workers in the healthcare industry, which represents approximately 14% of the U.S. workforce (Laughlin et al., 2021). In the HRSA’s The U.S. Health Workforce Chartbook, the largest health occupations or groupings were RNs (approximately 3,067,000); nursing, psychiatric, and home health aides (2,845,000); behavioral/allied health practitioners (2,219,000); personal care aides (1,649,000); phy-

sicians (961,000); medical assistants and other healthcare support occupations (1,249,000); and LPN/LVNs (852,000). Almost‌‌‌‌‌‌‌‌‌‌ half of the 34 occupations or occupational groupings (HRSA, 2018a) are greater than 75% female, with dental hygienists, medical secretaries, and speech-language pathologists being more than 95% female (HRSA, 2018a). There are significant variations in age across occupations, from dentists and psychologists (more than 35% being older than 55 years) to emergency medical technicians and paramedics, dental assistants, and physical therapist assistants and aides (fewer than 10% being older than 55 years). More recent data show a significant change in health workforce expansion. The finding that 30% of health workforce left their jobs or were laid off in 2021—driven largely by the pandemic, insufficient pay or opportunities, and burnout—has implications for the entire healthcare system, both in the short term as the country struggles to overcome the COVID-19 pandemic and beyond as the U.S. population continues to age (Galvin, 2021).

WOMEN IN THE U.S. WORKFORCE In 2020, women were 51.6% of the total U.S. paid labor force, and 57.4% of U.S. women are now in the labor force (BLS, 2020a, 2020b; DOL, 2010a, 2020b). Despite equal opportunity laws, women have not achieved parity with men’s earnings, and many continue to be crowded into female “employment ghettos” such as factories and hospitals. BIPOC women often experience the intersection of both racism and sexism in the workforce; in 2019, Hispanic women were paid 55.4% of the earnings of White non-Hispanic men, and Black women were paid 63.0% of the earnings of White non-Hispanic men (DOL, 2020a). The SARS-CoV-2 pandemic that began in early 2020 profoundly changed workforce participation for women in and out of healthcare (Albanesi & Kim, 2021; Landivar et al., 2020). With the closure of many segments of the service economy for pandemic control, women were disproportionately impacted by the economic stressors of the pandemic, and the closure of schools and day care centers overwhelmingly impacted women’s ability to return to work when those sectors reopened, as well as to continue working at jobs that had not been interrupted (Collins et al., 2021). Because women are so disproportionately represented in healthcare, and because as essential workers healthcare providers continued employment throughout the pandemic, the emotional and logistical burden of providing healthcare in a pandemic fell largely on women. As the immediate and delayed effects of chronic understaffing, workplace trauma, and persistent stress ripple through the healthcare system, healthcare workers—who are largely women—are leaving or considering leaving their roles, which has implications for future workforce fitness and capacity (Labrague & de Los Santos, 2021).

The National Center for Health Workforce Analysis (NCHWA; bhw.hrsa.gov/data-research/review-health-workforce-research), which is the data and statistics unit of the DHHS/HRSA, provides data resources for county, state, national, and global workforce estimation and analysis. In addition, the NCHWA develops the national infrastructure for workforce data management, supports state governments and organizations to improve workforce data, and supports state/regional health workforce research centers through a grant program. 7

34  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

The paid civilian workforce in the United States includes over 152 million people, of whom just under half (71 million) are women (BLS,‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌ 2021a). The official data underestimate the work performed by people in the informal economy, who do not appear in most employment data, particularly the estimated 11 million undocumented residents (Budiman, 2020), who contribute an estimated $5 trillion to the economy over 10 years (Edwards & Ortega, 2017). Using paid employment as the delineation of the workforce also omits the people whose unpaid labor enables the paid workforce, such as parents who work from home, those providing kinship care, volunteers, and others, who are disproportionately women. Therefore, any discussion of women in the paid workforce must also acknowledge the limitations of that definition, and the role that unpaid labor plays in enabling paid labor. Paid labor is also disproportionately concentrated in traditional “women’s work” (e.g., social work, nursing, teaching, administrative support). In 2018, 88.9% of nurses,8 9‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌6% of dental hygienists, 81.9% of social workers, 86.7% of special education teachers, and 70.9% of office support workers were women (BLS, 2021a). Women represent the majority of people with at least a bachelor’s degree in the workforce, but a significant pay gap persists in almost every occupation (American Association of University Women [AAUW], 2021). In 2018, White women working full-time were paid 79% of what White men were paid, and this gap worsened for BIPOC and older women (AAUW, 2021; see Table 2.1). The gender-based wage gap in the United States is more significant than in nearly every other peer nation (AAUW, 2021), and while education is often seen as a path to better employment, the wage gap persists at every educational level in the United States (BLS, 2021c). For BIPOC women, the pay gap persists across education levels (AAUW, 2021; Bleiweiser et al., 2021). Across the world, women provide the majority of paid and unpaid healthcare but earn less than men. In a study of 104 countries (Boniol et al., 2019), women represent around 70% of the health workforce, but earn on average 28% less than men. Occupational segregation (10%) and working hours (7%) can explain most of this gap, but even when considering “equal work” an “equal pay” gap of 11% remains. The trend of increasing participation of women in highly paid occupations is predicted to narrow this gap by 4% in the coming 20 years. In the United States, women are overrepresented in the health workforce compared with the total population. Although men represent a larger proportion of the overall U.S. working-age population, women represent the majority of workers in 29 of 34 health occupations, accounting for more than 80% of workers in nearly half (15 of 34) of these occupations (HRSA, 2018a‌‌‌‌‌‌‌‌‌‌). Although women are making significant advances in the traditionally “male” occupations of medicine, dentistry, pharmacy, and some highly technical health occupations, they continue to far outnumber men in the traditionally “female” health occupations: nurse, occu-

pational and physical therapist, dietitian/nutritionist, dental assistant/dental hygienist, nursing assistant, and health aide/ technician. In general, the majority of the pay gap between men and women in health occupations widens in the highest paying occupations such as medicine and dentistry. For example, women physicians and surgeons earn 75% of what their male counterparts earn, even after controlling for age, race, hours, and education (Whaley et al., 2021). However, the gender pay gap is narrower for women primary care physicians, who are paid at least 90% of men’s median annual salary for 10 of 13 internal medicine specialties (Wang et al., 2021). Except for dental hygienists who have no gender pay inequity, male dentists make 26% more, male nurses make 15% more, and male pharmacists make 6% more than their female counterparts (Trapani & Jacobs, 2020). This disparity persists when considering leadership and administration roles in nursing, which are disproportionately filled by men. The gender pay gap narrows but still exists in the lower paid health occupations such as LPNs (11%) and health support workers (10% for nursing and home health aides). And numbers don’t tell the whole story. Since women (many of whom are mothers and family breadwinners) are the majority of the healthcare workforce wage gaps compound the problem. When women aren’t paid fairly, families suffer, and the American economy suffers. Overall, the healthcare workforce is more racially diverse than the U.S. population and has increased in racial/ethnic diversity over the past decade. In 2022, the racial distribution in the United States was 59.3% non-Hispanic Whites; 13.6% Black/African American; 18.9% Hispanic; 6.1% Asian/ Pacific Islander; and 1.3% American Indian/Alaskan Native but 2.9% of the U.S. population is multiracial (U.S. Census Bureau, 2022‌‌‌‌‌‌‌‌. By 2060, these proportions will shift quite dramatically, as there will no longer be any clear racial/ethnic majority because the BIPOC population is projected to rise to 56% of the total population in 2060, compared with 38% in 2014. Less than 45% will be non-Hispanic white; 13% Black/ African American; 29% Hispanic origin; almost 10% Asian/ Pacific Islander; and less than 1% American Indian, Eskimo, and Aleut (U.S. Census Bureau, 2022). More than half of the nation’s children are part of a minority race/ethnic group. This proportion is expected to continue to grow so that by 2060, just 36% of all children (people younger than 18 years) will be single-race non-Hispanic White, compared with 52% today. By 2060, the nation’s foreign-born population would reach nearly 19% of the total population, increased from 13% in 2014 (U.S. Census Bureau, 2022). The statistics presented in Table 2.2 illustrate the racial and ethnic characteristics of selected healthcare occupations.6 In 2015, 70% of pharmacists, 67% of physicians, 73% of RNs, and 75% of dentists were White (non-Hispanic) compared with 77% White (non-Hispanic) in the U.S. working-age population and 60% in the U.S. population (in 2021; HRSA, 2018a;

Depending on the data source (BLS, 2020a, 2020b; HRSA, 2017a, 2017b; U.S. Census Bureau, 2023; U.S. Census Current Population Survey, 2021) the population of nurses may include RNs, LPNs/LVNs, and APRNs. For example, the 2020 CPS data estimated the RN population as 86% women compared to 90% women in their 2015 report (U.S. Census Bureau, 2015). The HRSA’s The Health Workforce Chartbook (using 2015 data) reports RNs as 90.3% female, CNMs and NPs as 91.8% female, CRNAs as 57.7% women, and LPN/LVNs as 90.6% female (HRSA, 2018b). 8

Chapter 2  Women and Healthcare Workforce: Caregivers and Consumers 35

U.S. Census Bureau, 2021‌‌‌‌‌‌‌‌). Overall, White and Asian workers are more represented among the occupations found within the health diagnosing and treating practitioners subcategory —occupations that often require many years of education or training and are both better-paid than in the U.S. working-age population altogether. Conversely, Hispanic workers of any race, Black/African American, American Indians/Alaska Natives, Pacific Islanders, and individuals reporting multiple or other race are, in general, far more underrepresented in this subcategory. However, Asians are underrepresented in two occupations—APRNs (4%) and speech-language pathologists (2%). Among the health technologists and technicians subcategory, Black workers have the largest representation (25%) among LPNs, nearly twice their representation in the overall U.S. workforce. However, Hispanic workers are underrepresented in all occupations in this subcategory. Similar to the health technical occupations, there is varying racial/ ethnic representation among all the healthcare support occupations—occupations that generally require fewer years of education or training. For example, Black workers have their highest proportion among nursing, psychiatric, and home health aides (32%), whereas Hispanic workers have their highest representation among medical (26%) and dental assistants (23%), both of which are a greater proportion than in the overall national workforce. In addition, multiple races, American Indians/Alaska Natives, and Pacific Islander workers have the largest proportion (2.2%, 1.1%, and 0.5%, respectively) among personal care aides (personal care and service occupation). Conversely, White healthcare workers have their lowest representation among nursing, psychiatric, and home health aides (47%; DHHS, 2017). The trends in racial/ethnic diversity vary considerably by occupation, reflecting the historical racism of healthcare systems in the United States, as well as current structural oppressions (Yearby, 2021). Black non-Hispanic healthcare workers had the largest gain in share of the overall health workforce (16.9% in 2004 to 18.2% in 2013), which is a larger increase compared with the U.S. population trends (14.0% in 2004 to 14.8% in 2013). While Latinx healthcare workers gained representation in the healthcare workforce (8.5% in 2004 to 10.9% in 2013), it was at a slightly slower rate compared with the U.S. population (14.2% in 2004 to 17.1% in 2014; Salsberg et al., 2021; Snyder et al., 2019). These trends do not reflect the racial and ethnic identities of members of all groups within the healthcare workforce, and the higher paid, more powerful positions within the healthcare hierarchy remain disproportionately White and non-Hispanic. In a more recent 2019 study of Black, Hispanic, and Native American healthcare workers, weighted data from the 2019 ACS were used to compare the diversity of 10 healthcare occupations (APRNs, dentists, occupational therapists [OTs], pharmacists, physical therapists [PTs], PAs, physicians, RNs, RTs, and speech-language pathologists) with the diversity of the U.S. working-age population, and 2019 data from the

Integrated Postsecondary Education Data System (IPEDS) were used to compare the diversity of graduates with that of the U.S. population of graduation age (Salsberg et al., 2021). Among the 10 professions assessed, the mean diversity index for Black people was 0.54 in the current workforce and in the educational pipeline (where a value of 1.0 indicates equal representation of Blacks in the current workforce or pipeline). The diversity index for the current healthcare workforce was lower than 0.50 in nine of 10 professions (all except respiratory therapy) for Hispanic health workers. For Black and Native American health workers, the diversity index for the current healthcare workforce was lower than 0.50 in five of 10 occupations (dentist, pharmacist, physician, OT, and PT). Notably, there is near equity for Black RNs and RTs in the healthcare workforce. In contrast, among graduates of programs leading to the 10 occupations reviewed, the proportion of Black individuals ranged from 3.0% for PAs to 14.2% for APRNs. The proportion of Hispanic graduates of programs leading to the 10 occupations reviewed ranged from 6.5% for pharmacists to 19% for RTs, but significantly less than 21.3% of Hispanics in the U.S. population (aged 20–35 years). The occupations listed in Tables 2.1 and 2.2 are not all those on which information is available, but they provide a good representation and clear picture of the continued effects of racism and sexism in paid healthcare roles. In Table 2.1, the occupations are listed for women in selected health occupations for 2015, 2019, and 2021, depending on the data source (BLS, 2020a, 202‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌0b, 2021d; HRS‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌A, 2017b)9 and compared with 1995 data. Notably, the large numbers of nursing aides and medical assistants, of which approximately 90% or more are women, account for the majority of women in all healthcare occupations. Clearly, women, particularly women of color, are clustered in jobs and occupations that are lower in pay, lower in status, and less autonomous than the jobs of most men in the healthcare field (BL ‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌S, 2020a; Doyal, 1995; HRSA, 2017b). This concentration in low-power roles also limits the ab‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌ility of women, particularly BIPOC women, to change the systems that harm them as healthcare workers and harm their clients. The healthcare industry has seen constant job growth over the past two decades, even during the 2008 economic recession, when healthcare added 428,000 jobs and the rest of the economy lost 7.5 million jobs (Frogner et al., 2015; Wood, 2011). Healthcare employment is expected to rise, in large part because of the growing elderly population that typically requires more healthcare services, as well as the implementation of the ACA of 2010 (Cuckler et al., 2013). Recent projections from the HRSA expect the majority of the increase in primary care demand will be caused by demographics and the remaining 20% will be caused by changes in demand under the ACA (H ‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌ RSA, 2017a). These projections, however, predate the SARS-Cov-2/COVID-19 pandemic, which seems to be significantly changing the workforce capacity, and potentially the distribution.

For the national perspective, the primary source of national data on the racial and ethnic mix of the healthcare workforce is the American Community Survey (ACS), which is an annual nationally representative household survey conducted by the U.S. Census Bureau. Data on the diversity of the pipeline of workers are available through the Integrated Postsecondary Education Data System (IPEDS) for those in occupations requiring at least a postsecondary award; however, data are not available for those with less than a postsecondary award. 9

36  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

TABLE 2.1  Women Workers in Selected Health Occupations, United States, 1995 and 2015–2020a,b HEALTH OCCUPATION

WORKERS (IN 1,000s‌‌‌‌‌‌‌‌‌‌‌)

WOMEN (%)c‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌ 1995e

2015f

>55 YEARS OLD (%)

AVERAGE WAGE, FULL-TIME WORKERSd ALL

WOMEN

MEN

Total employed, age 16 or olderg

159,825

46.1

46.9

50.3h

791

719

871

RNs

3,327.2

93.1

86.7i

25.5

1,305

1,274

1,437

APRNsj

280g

–

85.1

26.2k

1,955l

1,903

–

LPNs

894

95.4

90.2

26.1

921

918

–

Physicians

980

24.4

g

33.7

31.0

2,418

2,418

2,647

Physician assistants

165g

53.2

64.4g

14.2

1,884

1,885

–

Pharmacists

352g

36.2

57.8g

24.2

2,019

2,087

2,010

Dentists

167g

13.4

38.7g

38.2

2,492

–

–

Dental hygienists

207g

99.4

95.0g

18.2

1,269

1,264

–

Physical therapists

235

70.2

70.8

14.0

1,527

1,478

1,551

Emergency medical technicians/ paramedics

225.9

–

31.5

7.4

1,288

–

1,352

Clinical laboratory technicians

393.2

71.7

73.6

24.4

1,352

1,140

1,280

Aides: nursing, psychiatric, home health

2,846

89.4m

87.2

19.8

626

615

740

Medical assistants

571

–

92.4

9.9

676

668

980

Dental assistants

347.7

98.5

94.6

10.2

665

653

–

Bureau of Labor Statistics. (2020). Labor force statistics from the current population survey. https://www.bls.gov/cps/tables.htm#annual Health Resources and Services Administration. (2018). The U.S. health workforce chartbook—In brief. U.S. Department of Health and Human Services. https://bhw.hrsa.gov /sites/default/files/bureau-health-workforce/data-research/hrsa-us-health-workforce-chartbook-in-brief.pdf c Bureau of Labor Statistics. (2021). Current population survey, health occupations by gender. http://www.bls.gov/cps/cpsaat11.htm d Bureau of Labor Statistics. (2021). Current population survey, health occupations by average wage (full-time workers). http://www.bls.gov/cps/cpsaat39.htm e Bureau of Labor Statistics. (1995). Current population survey, health occupations by gender. http://www.bls.gov/cps/aa1995/aat11.txt f Bureau of Labor Statistics. (2019). Current population survey: Women in the labor force. Report 1092. https://www.bls.gov/opub/reports/womens-databook/2020/home.htm g Health Resources and Services Administration. (2017). Sex, race, and ethnic diversity of U.S. health occupations (2011–2015): Technical documentation. https://bhw.hrsa.gov /sites/default/files/bureau-health-workforce/data-research/diversity-us-health-occupations.pdf h Fry, R. (2021). Amid the pandemic, a rising share of older U.S. adults are now retired. Pew Research Center. https://pewrsr.ch/3BL5DIj i 2020 Current Population Survey data compared to 90% of women RNs in 2015. j Includes nurse anesthetists (CRNAs), nurse-midwives (CNMs), and nurse practitioners (NPs), but full data available for NPs. k 31% of CRNAs were older than 55 years in 2015. l Wage data available only for NPs. m Nursing aides, orderlies, and attendants included in 1995 data. a

b

Workforce supply and capacity are also cyclical. The total number of individuals working in a profession is affected both by capacity (those trained and authorized to provide services in question) and by actual supply (qualified individuals who want to work). As provider shortages become apparent, educational programs expand, producing more graduates, and legal scopes of practice may grant broader practice authority to some professions in underserved areas. (This deficit-model approach to healthcare scope is problematic and is discussed later.) At the same time, practice models shift to integrate new workers into care delivery, effectively expanding capacity. Efforts to increase capacity may coincide with economic trends producing higher-than-anticipated numbers of individuals wanting to work. Evidence of the cyclical nature of workforce supply is the recent undersupply followed by oversupply of nurses and pharmacists (Buerhaus et al., 2009; Zavadski,

2014). However, unusual events can disrupt the accustomed cycles; for example, the SARS-CoV-2/COVID-19 pandemic amplified existing demands on the healthcare workforce, and increased workforce departures while simultaneously increasing rates of mental health issues, moral injury, and burnout among healthcare workers (Pereira-Sanchez et al., 2020; Sriharan et al., 2021; Stone et al., 2021). Shortages can be created not only by a lack of providers to fill roles, but also by trauma-driven loss of capacity of those providers to perform at peak ability (Marvaldi et al., 2021), and the challenge of the healthcare system during the recovery from the pandemic will be to address the harms experienced by healthcare providers during it. One approach to address this current shortage taken by California’s HealthImpact policy and research center is to focus on six opportunities to grow the nursing workforce. The strategies range from introducing K12 students to nursing

60.1 73.5 84.0 60.8 67.0 72.7 70.4 74.8 83.4 77.8 78.9 62.0 46.8 53.6 81.1

U.S. populationd

RNs

APRNse

LPNs

Physicians

Physician assistants

Pharmacists

Dentists

Dental hygienists

Physical therapists

Emergency medical technician/paramedic

Clinical laboratory technologists

Aides: nursing, psychiatric, home health

Medical assistants

Dental assistants

22.5

26.1

13.7

9.4

10.3

4.8

7.5

6.1

3.7

10.0

6.3

9.4

4.5

5.7

18.5

18.0

HISPANIC OR LATINX

8.8

13.4

32.0

13.7

6.3

4.4

3.1

3.0

5.9

7.1

4.8

23.1

5.7

10.4

12.2

13.0

BLACK/ AFRICAN AMERICAN (NONHISPANIC)

6.9

4.2

4.0

11.8

1.9

11.1

4.2

14.3

17.9

7.3

19.6

4.0

4.1

8.4

5.6

6.0

ASIAN (NONHISPANIC)

1.0

0.5

0.8

0.5

0.6

0.2

0.2

0.1

0.2

0.6

0.1

0.7

0.2

0.4

0.7

1.0

AMERICAN INDIAN AND ALASKA NATIVE

–

0.3

0.2

0.2

0.1

0.1

–

–

–

–

0.0

0.1

–

0.1

0.2

0.5

NATIVE HAWAIIAN AND OTHER PACIFIC ISLANDER

2.2

1.9

2.1

2.2

1.9

1.6

1.5

1.7

1.8

2.2

2.1

1.9

1.3

1.5

2.8

2.0

MULTIPLE/ OTHER RACE (NONHISPANIC)

a

Health Resources and Services Administration. (2017). Sex, race, and ethnic diversity of U.S. health occupations (2011–2015): Technical documentation. U.S. Department of Health and Human Services. https://bhw.hrsa.gov/sites /default/files/bureau-health-workforce/data-research/diversity-us-health-occupations.pdf b Bureau of Labor Statistics. (2021). Labor force characteristics by race and ethnicity. Report 1095. https://www.bls.gov/opub/reports/race-and-ethnicity/2020/home.htm c Bureau of Labor Statistics. (2021). Employment status of the civilian noninstitutional population by age, sex, and race. https://www.bls.gov/cps/cpsaat05.htm d U.S. Census Bureau. (2021). Quick facts 2020. https://www.census.gov/quickfacts/fact/table/US/PST045221 e Includes nurse anesthetists, midwives and nurse practitioners.

77.0

WHITE (NONHISPANIC)

Total U.S. workforcec

HEALTH OCCUPATION

TABLE 2.2  Racial and Ethnic Diversity (%) of Workers in Selected Health Occupations, United States, 2015–2021 (Numbers in Thousands)a,b

Chapter 2  Women and Healthcare Workforce: Caregivers and Consumers 37

38  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

as a career, to improving skills in the existing nursing workforce (including transitions from unlicensed roles to licensed roles, as well as LPN-RN and RN-APRN), and improving retention and well-being among practicing nurses (Chan et al., 2021). This collection of strategies targets inflow of potential nurses, growth of the current workforce, and mitigating future workforce loss from trauma and/or burnout and can serve as a model for the multilevel approaches needed to address the complex issue of nursing workforce capacity. Other strategies to address workforce issues include expansion of the role of palliative care nurses, improving seamless transitions between secondary and postsecondary education, and increased funding for nurses and nursing students (Rosa et al., 2020). The troubled Public Service Loan Forgiveness Program, for example, which forgives up to 85% of federal loans in exchange for 10 years of work in nonprofit or government organizations, could be better leveraged to relieve the heavy loan burden of many healthcare providers, as could other loan forgiveness programs for healthcare education at the state and federal levels. These programs have the added benefit of encouraging practice in underserved communities and locations but may also contribute to a lack of investment in the community by healthcare providers who see them as a short-term commitment rather than a career choice. Critical assessment of both intended and unintended sequelae of policy approaches to reducing workforce shortage is essential to avoid reinforcing inequities in an effort to improve them. Healthcare occupations in the 21st century will have more women in them and will be more ethnically diverse than they are today in terms of the number and proportion of women occupying jobs in the health workforce. Trends in availability, accessibility, acceptability, and quality as well as other implications of gender and ethnic diversity among the health workforce will be explored further.

Historical Perspectives In prehistoric eras, both men and women shared the activities of healing—herbs and roots were gathered and dispensed to those who were ailing. However, records suggest that gender divisions began even during these early times. Women tended to fulfill the caregiver and midwifery role, and men tended to be medicine givers (Dock & Stewart, 1938). Religion and medicine were united very early, with the role of religious leader and healer often merged into a single powerful entity. Nuns, who were considered immune to the moral pollution of nudity that otherwise threatened women’s virtue, frequently served as nurses. In the United States, enslaved women and their descendants served as midwives and nurses to communities, both Black and White, and their knowledge and skill were critical to the safety and survival of large segments of the colonialist Americas, as did their descendents (Suarez, 2020). Although the majority of physicians have been men, since the 19th century, nurses in the United States and Europe have been almost exclusively women10 ‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌(Choy, 2003; D’Antonio, 2010). During the 19th century, few women received a formal education, and relatively few were formally employed outside the home, although working-class women have always contributed economically and pragmatically to their families’

survival. Middle-class, largely White women in the 1800s were struggling to define a role for themselves in society through the women’s suffrage movement of the 1840s, as well as through the early women’s health organizations of the time (Ehrenreich & English, 1973). Beginning in the mid-1800s, Florence Nightingale and other nursing reformers leveraged the accepted gender roles of the era to argue that the role of trained nurse allowed women to harness their innately feminine caring traits and contribute meaningfully to society (Reverby, 1987a). These nursing reformers, however, did not extend the role of professional nurse to all women, instead choosing to emphasize the role of White, largely middle-class women to legitimize a role previously filled by women considered unfit for marriage, whether by vows of chastity or, conversely, by a history of sex work or other moral suspicion. The goal of nurse reformers was to consolidate and legitimate the power of professional nurses within the healthcare system, rather than to ensure inclusion of diverse communities. Women who sought education as physicians also appealed to social beliefs about women’s attributes, balancing what historian Regina Morantz-Sanchez has called “sympathy and science” (Morantz-Sanchez, 1985). During this critical period of transition in U.S. medical history, urbanization, immigration, and the growth of hospitals led to a gradual replacement of family members as caregivers to reliance on professional nurses and physicians (Rosenberg, 1995). The landmark Flexner Report, released in 1910, set forth new and more “scientific” standards for medical education (e.g., increasing the number of years of education required of medical school applicants). The report consolidated and formalized ideals that had already been circulating among medical (White, upper-class) “elites,” and it resulted in the closure of many schools that had previously educated women and Black physicians. As standards of entry were tightened and the American Medical Association (AMA) and state medical organizations gained more power over the medical profession, it became more difficult for women, Jewish people, and BIPOC to access medical education (Starr, 1982). The number of women in the medical profession continued to decrease through the 1950s, but in the 1960s and beyond, the second-wave feminist movement, affirmative action programs, and women’s own determination led women to seek higher education, particularly in the traditionally male medical careers, which may have also implicitly reflected the devaluation of nursing and other traditionally “female” healthcare roles. In an effort to establish authority as physicians, many women opted to distance themselves from other female healthcare providers, including nurses, which resulted in a limitation of the power sheer numbers might have otherwise been expected to bestow. With better healthcare workforce data and private–public partnerships, the Institute of Medicine (IOM) has led a number of reports that challenge the Flexnerian paradigm in which the focus has been on degrees and specialized training rather than on aligning population needs with healthcare worker training and entry into practice. This is an evident attempt to bring U.S. healthcare more in line with the remainder of the world, including WHO, and has significant support in academia and advocacy work, although possibly less in policy implementation and durable

Chapter 2  Women and Healthcare Workforce: Caregivers and Consumers 39

policy changes. The IOM 2021 report, The Future of Nursing: Charting a Path to Health Equity thoroughly revised the priorities of the 2011 IOM Future of Nursing report to focus on social determinants of health, improving the resilience of the nursing workforce, and emphasizing the need for both financial support for and direct input from nurses in a wide variety of settings (Wakefield et al., 2021). However, the limited change in nursing roles in the decade between these two watershed reports suggests that despite the repeated calls for nurses and nursing to be centered in the U.S. healthcare system, and to play a role more analogous to that in many other countries, nursing remains stymied by regulatory and institutional barriers to full scope care. Because repeated analyses identified nurses and nursing as key healthcare roles for the transition to a more community-based and comprehensive health system, and because the vast majority of nurses are women, careful examination of nurses and nursing are essential to understanding women in the healthcare workforce. And finally, we highlight health workforce analysis that aligns population needs with workforce availability, accessibility, and quality in new reports on primary care, women’s health, behavioral and public health workforce, as well as SRH workforce capacity-building.10 In this section, we focus intentionally on nursing for two reasons: Nurses are the largest single category of healthcare providers in the United States, and the overwhelming majority of nurses (86%) are women (CPS, 2020). Additionally, nursing has a complex history in the United States and globally: while nursing as a profession has a long history of systematic data collection and analysis, as well as some of the earliest work in infection control and public health, that professionalization often occurred at the cost of BIPOC communities and healthcare workers. The formalization of nursing and midwifery pathways in the United States explicitly excluded BIPOC from these pathways and prioritized the health of White Americans. Mary Breckinridge, for example, who is often lauded as having brought midwifery and public health nursing to Appalachia, did so in an explicit effort to improve the health and fertility of White residents in the region (American College of Nurse-Midwives [AC‌ NM], 2021a). Nurse-midwifery programs that admitted Black applicants, such as at the HBCU Tuskegee University, were short-lived as governmental support for them waned (Dawley & Walsh, 2016). At the same time, regulatory changes excluded the Black grand midwives of the American South, who had largely trained in an apprentice model, and the effects of this exclusion persist to this day: of the nearly 6,500 members of the ACNM in 2019, 92% identify as White (ACNM, 2021a). Despite its troubled past and present, nursing has the potential to guide the changes in healthcare that are badly needed. As a holistic discipline that includes function and meaning, as well as pathology, in the assessment and care of patients, nursing at its best seeks to improve health in ways

that are meaningful to the individual, within their particular context. This is central to addressing the needs identified by the 2019 IOM report, the 2010 ACA, and the more recent public health crisis of COVID-19. Nurses serve clients in communities, in homes, in schools, and in other settings, as well as in inpatient settings, and because of this have an opportunity for a different perspective on health and healthcare. Next, we examine some of the specific issues affecting nursing, as well as opportunities for the future.

Nursing’s Roles in Providing HealthCare: RNS and APRNS Nurses make up the single largest health profession in the United States (HRSA, 2‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌017a). There were 3.3 million RNs, 280,000 APRNs, and 894,000 LPNs working in the field of nursing between 2015 and 2020 (BLS, 2020a; HRSA NCHWA, 2017). They perform a variety of patient care duties and are critical to the delivery of healthcare services across a wide array of settings, including schools, ambulatory care clinics, hospitals, nursing homes, public health programs, hospice, and home health agencies. Distinctions are made among different types of nurses according to their education, role, and the level of autonomy in practice. LPNs typically receive training for a year beyond high school and, after passing the national NCLEX-PN® exam, become licensed to work in patient care. LPNs provide a variety of direct care services, including administration of medication, taking of medical histories, recording of symptoms and vital signs, and other tasks as delegated by RNs, physicians, and other healthcare providers. RNs may have a bachelor’s degree in nursing, a 2-year associate degree in nursing, or a diploma from an approved nursing program and must also pass a national exam, the NCLEX-RN®, before they are licensed to practice. The scope of RN responsibilities is more complex and independent than that of LPNs. RNs provide a wide array of direct care services such as complex health assessments, care planning and coordination, administration of treatments, disease prevention, patient education, and health promotion for individuals, families, and communities. RNs may choose to obtain advanced clinical education and training to become an APRN, defined by four titles—certified nurse-midwife (CNM), certified registered nurse anesthetist (CRNA), clinical nurse specialist (CNS), and NP. APRNs usually have a master’s degree, although doctoral-level education is becoming the norm, and are certified to practice in a clinical specialty area. The changes to healthcare funding and structures that accompanied the 2010 ACA recognized some of the overlooked roles nurses play in the healthcare system (particularly in community health and care coordination) but did not change some of the important aspects of funding and reimbursement

Although the workforce necessary to care for an aging and institutionalized population is critically important, we have not included such data here. Since nurses, nursing assistants, and other health support occupations provide the majority of care to these populations, the discussion of the primary care, women’s health, behavioral health, and public health workforce overlap with the care to geriatric and long-term care populations. Please refer to Building Geriatric Workforce Enhancement Program at www.hrsa.gov/grants/find-funding/hrsa-19-008 for a more thorough discussion. 10

40  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

that impact nursing. In particular, the ACA did not mandate reimbursement parity for APRNs with physicians and did not change the 1983 Centers for Medicaid & Medicare Services regulations that prohibit reimbursement for nursing care in the inpatient setting (American Nurses Association, 2017). These regulatory decisions have impacts on the financial aspects of nursing in the healthcare setting and on the roles nurses play in those settings. About 445,000 RNs (16%) and 166,000 LPNs (24%) live in rural areas. The per capita distribution of RNs varies substantially across states (Rural Health Information Hub, 2020), with fewer RNs per 100,000 population working in the West and Southwest states (e.g., Washington, California, Idaho, Nevada, New Mexico, Oklahoma, Texas, Utah, Wyoming) and more RNs per 100,000 population working in the Northeast and Midwest states (e.g., Delaware, Iowa, Maine, Massachusetts, Montana, Nebraska, North/South Dakota, Pennsylvania). The nursing workforce grew substantially in the past decade, with the number of RNs growing by more than 500,000 (24%) and LPNs by more than 90,000 (16%) and outpaced growth in the U.S. population. Despite this, BLS projections for the next decade predict a shortage of nursing staff, in part due to the demographics of the nursing workforce and the U.S. population as a whole. The average RN is portrayed as a White, married, middle-aged mother working full-time in a hospital, and many assumptions about the workforce and RN scope of practice are derived from this “typical” RN. However, over the past decade, RNs and LPNs are becoming more diverse. The proportion of BIPOC RNs increased from 20% to 27%, a 25% increase, and the proportion of men in the RN workforce increased to almost 14%, a 29% increase. Owing to growth in new entrants, the absolute number of RNs younger than 30 has increased. However, with one third of the nursing workforce older than 50 years of age, the mean age of RNs has increased during the past decade, which has implications for workforce capacity as these RNs reach retirement age (HRSA, 2018c; HRSA, NCHWA, 2017). Currently, more than half of the RN workforce (55%) holds a bachelor’s or higher degree. The annual median wage for a RN (not APRN) was $75,330 in 2020 (BLS, 2020b). The highest paid 10% of RNs made more than $116,230, whereas the bottom 10% earned less than $53,410. The states with the highest RN employment levels also have the highest average wages, ranging from California ($120,560), New York ($89,760), Texas ($76,800), Pennsylvania ($74,170), and Florida ($69,510). The top-paying states for RNs are concentrated in the West and Northeast regions, with annual wages ranging from $96,230 (Oregon), $96,250 (Massachusetts), and $95,250 (Alaska) to $104,830 (Hawaii) and $120,560 (California). Although annual earnings of RNs are above average for all healthcare workers (approximately $41,132; HRSA,‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌2017a), they are markedly lower than physician, dentist, and pharmacist earnings (see Table 2.1) and below those for physical therapists and laboratory technicians (HRSA,‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌2017a). Work settings for nurses are changing as the Baby Boomer generation ages and requires more care, healthcare continues to shift to community settings (driven in part by ACA-incentivized care coordination efforts), and population-based nursing care gains ground in systems. One of the important

changes in health professions over the past 50 years has been the development of advanced practice nursing and the autonomous APRN roles of CNM, CNS, CRNA, and NP. APRNs are prepared by education and certification to assess, diagnose, and manage patient problems; order tests; and prescribe medications. However, many states (27)‌‌‌‌‌‌‌ limit APRN practice by requiring formal physician supervision or collaboration to practice (American Association of Nurse Practitioners [AANP], 2022). In the other states, APRNs practice independently, often in low-resource settings such as rural areas and low-income urban areas. As with RNs, boards of nursing (BONs) in each state license and regulate the practice of APRNs (National Council of State Boards of Nursing [NCSBN], n.d.). The majority of APRNs (55%) are employed in physician/other practitioner offices and outpatient care centers, with less than one third of NPs (26%), CNMs (29%), and CRNAs (30%) employed directly by hospitals (BLS, 2021b). Depending on the data source, APRNs represent approximately 9% of the national RN population. Although the number of employed APRNs have been estimated at approximately 280,000, according to the U.S. government (BL ‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌S, 2020a) in 2020, there were 246,700 employed NPs, 8,100 CNMs, and 45,200 CRNAs (Bureau of Labor Statistics, 2021e). As CNSs are not recognized by statute in all states, neither the BLS nor the HRSA provides regular reports; the National Sample Survey of Registered Nurses (NSSRN) estimated that there were nearly 60,000 CNSs in 2010 (National Association of Clinical Nurse Specialists [NACNS], 2020). According to 2015 data (HRSA, 2017b), demographic characteristics among the three groups of nurses in advanced practice are similar in terms of race (85% non-Hispanic White) but differ on gender and age. The CNM and NP groups are predominantly female (92%), whereas the CRNA group is nearly half men (44%). Of note, CRNAs are paid significantly more than other APRNs (median salary approached $185,000 in 2020, compared to $112,000 for NPs and CNMs; BLS, 2020b). APRNs are less diverse than the RN population, with 4.5% Hispanic and 6% Black/African American APRNs, although Black nurses are slightly more likely than White nurses to hold a graduate degree in nursing (Smiley et al., 2018). This disparity suggests that racism, access to employment, and factors other than education play a role in the lack of diversity among APRNs. It is particularly striking among CNMs, where almost nine out of 10 midwives are White, but almost half of their patients are BIPOC (CDC, 2021‌‌‌‌‌‌‌). This failure to reflect the communities many APRNs serve is troubling, given the research on the benefits of culturally congruent care, and will need to be a focus of nursing in the next decade and beyond. APRNs are often considered to be a lower-cost solution to a shortage of primary care providers, and many regulatory changes reflect this deficit-model framing. The need for primary care providers is well documented, particularly given the increased demands on these providers to manage care under many provisions of the ACA, and nurses in many states have been successful in arguing that independent APRN practice mitigates this shortage. Within the NP workforce, nearly half were working in primary care practices or facilities, frequently in high-need, low-resource settings such as federally qualified health centers (FQHCs), public health

Chapter 2  Women and Healthcare Workforce: Caregivers and Consumers 41

centers, Indian Health Services locations, and other relatively low-paid locations. The focus on APRNs as a cost-effective response to a provider shortage is problematic because it reinforces a healthcare hierarchy in which physicians are seen as the “gold standard” and because it makes nursing regulations vulnerable to changes in market forces rather than reflective of the research supporting APRNs as safe and effective providers. Additionally, it strengthens the fractured U.S. service model by focusing on who is providing care, rather than what care is being provided, and seeking to improve that care. The geographic distribution of APRNs varies due to multiple factors, including local practice statutes, demand, income potential. In particular, there are significant differences in permissible scope of practice for APRNs that reflect the political power and will of physician groups in a state rather than the educational preparation and national scope of practice of APRNs. Western states are most likely to have full independent practice for APRNs, with California, a state with a robust and powerful medical association, a stark outlier. In 22 states, APRNs are required to have supervisory or collaborative formal relationships with physicians, despite decades of data supporting the safety of independent practice for APRNs (AANP, 2021). States that have independent practice may have a required supervisory period for newly licensed APRNs, despite a lack of evidence for this model. In states that have independent practice licensure for APRNs, a frequent rationale given for this is the lack of access to physicians for many lowresource communities, including rural and urban areas. However, this scarcity model of licensure posits a hierarchical relationship between physicians and APRNs and reinforces the role of APRN as a next-best or stopgap measure in shortage situations, rather than as an expert provider capable of independent care and weakens the position of APRNs to continue care delivery if the existing shortage of primary care physicians eases, for example. The 2008 economic recession resulted in a temporary RN surplus because of deferred retirements and enrollment/ graduation surges in nursing programs (McMenamin, 2013). However, as noted above, the SARS-CoV-2/COVID-19 pandemic that began in late 2019 has negatively affected that surplus by increasing temporary or permanent departures from the healthcare workforce, as well as increasing demand on the healthcare system, particularly in acute care settings. Employment of CRNAs, CNMs, and NPs is expected to grow 45% from 2020 to 2030, much faster than the average for all occupations. Growth will occur because of an increase in the demand for healthcare services. Several factors, including ACA legislation and the resulting newly insured, an increased emphasis on preventive care, and the large, aging Baby Boomer population, will contribute to this demand. APRN reimbursement is also often lower than that of physicians for the same billed visits, which may lead insurance companies to encourage APRN use as a lower-cost option for care; this, of course, does not benefit the APRN, although it may benefit the insurer. The safety and efficacy of APRN care is well documented (e.g., Norton et al., 2016; Traczynski & Udalova, 2018), as is improved patient relationships and medication adherence compared to physician care (e.g., Leach et al., 2018; Muench et al., 2021; van Dusseldorp et al.,

2021). With the IOM- and ACA-driven shift to an emphasis on preventive and primary care, as well as health education and risk reduction, APRNs are well positioned to fill the need for primary care services (BLS, 2021e).

WOMEN AS PATIENTS As discussed earlier in the chapter, women have a long history as healthcare providers—and, of course, as healthcare consumers. Because of the healthcare needs specific to sexual and reproductive healthcare (SRH)—in particular, contraception and pregnancy—cisgender women are frequent consumers of healthcare at an earlier age than are most men, and because of the role many women play in family logistics, are a powerful factor in healthcare utilization for their families as well (Zimmerman & Hill, 1999). However, this familiarity with the healthcare system does not necessarily translate to better health outcomes, as women 18 to 64 years old are more likely to experience disability and report fair or poor health status than are men ([NASEM, 201‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌8a). Additionally, women are more likely to live in poverty than are men, which is a powerful predictor of health status, and more likely not to fill needed prescriptions due to cost (NASE ‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌M, 2018a). Finally, women are subject to morbidity and mortality risks specific to reproductive health and—more acutely—the politicization of reproductive healthcare. In this section, we examine some key aspects of women’s healthcare and health outcomes to illustrate how systemic issues like racism and misogyny impact the health of women in the United States.

Pregnancy and Abortion The capacity to become pregnant is not limited to women (trans men and nonbinary people with uteri can also become pregnant, and people without uteri cannot, regardless of gender), but so many aspects of pregnancy as it relates to health are intimately connected to misogyny and assumptions about women’s lives that discussions of the impacts of pregnancy and the healthcare system center on women. Pregnancy—its desirability, its acceptability, its health impacts—is also deeply connected to racism, classism, and ableism in the United States, and the disparate outcomes for pregnancy on health reflect these systemic issues. In this section, we examine a few of the factors affecting the health of women in relation to the capacity for pregnancy. Pregnancy is an extremely common experience for women in the United States. Approximately 5.6 million pregnancies occur annually in the United States, with approximately 60% of these ending in a birth (Maddow-Zimet & Kost, 2021). Of the 3.8 million births each year, 90% are attended by physicians, and 99% occur in hospitals (ACNM, 2016; Gregory et al., 2021). This is significantly different from the United Kingdom, where 54% of births are by midwives (Stephenson, 2016), and from the Netherlands, where 16% of births occur at home (Sandall, 2015). While common, pregnancy is also not without risk, particularly in the United States. In 2017, 19 women died for each

42  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

100,000 live births in the United States, compared to eight in France, five in Ireland, and two in Norway (United Nations Population Fund [UNFP], 2021). The primary causes of maternal mortality in the United States were cardiovascular disease, hemorrhage, infection, and cardiomyopathy (CDC, n.d.-d). Mortality rates in 2019 varied sharply by state, from 11.2/100K in California to 37.7/100K in Kentucky, reflecting in many cases the strength of the social and health safety net available in a given state (BLS, 2021b). Racism, however, remains the largest factor in maternal mortality in the United States; while 14.1 White women die for every 100,000 live births, 39.9 Black women die for every 100,000 live births (CDC, n.d.-d). The differences persist across income, education, and geographic location (Hill et al., 2022; Scott et al., 2019). The proposed causes for these disparities are many, and include chronic stress related to racism (Kramer et al., 2019), social factors like limited access to healthcare (or limited access to respectful, culturally congruent healthcare; Muse, 2018), and failure of providers to listen to Black women and families during the childbearing year (Wishart et al., 2021). The racial disparities in birth outcomes in the United States is an anomaly among peer nations, which strongly argues against an inherent physiologic cause for the mortality rates, and its persistence over socioeconomic status makes a single explanation like lower income or education levels unlikely. For Black women in the United States, pregnancy represents risk in a way that is less true for White women in the United States. For the nearly 3 million pregnancies each year that do not end in a birth, there is another series of issues. Spontaneous pregnancy loss (miscarriage) is extremely common and affects perhaps one in five recognized pregnancies (Linnakaari et al., 2019). While the vast majority of miscarriages occur without complications, possible outcomes include infection, hemorrhage, and, increasingly, scrutiny about whether the miscarriage was truly spontaneous. As abortion care becomes increasingly difficult to access, and legal strategies to limit it pivot more toward the pregnant person and away from the provider, miscarriages are likely to become more scrutinized and possibly criminalized, as they have been broadly in other countries and in some places in the United States (Weigel et al., 2020). In contrast to birth, abortion in the United States since 1973’s Roe v. Wade decision legalizing abortion has been extraordinarily safe. A 2012 analysis found a nearly 14-fold increase in mortality rate for birth compared to abortion in the United States, which is consistent with safety data from other settings with legal abortion (Raymond & Grimes, 2012). A 2018 NASEM analysis argued that “it [the committee] should consider how abortion’s unique regulatory environment relates to the safety and quality of abortion care” (NASEM, 2018b, p. 6). This regulatory environment has included a ban on federal funding (including Medicaid, Indian Health Services, and federal employee health coverage) for abortion care since 1976; a progressively more restrictive series of laws requiring, among other things, providers to “counsel” people seeking abortion that abortion causes mental illness and breast cancer, despite no research supporting this claim; and targeted regulations of abortion providers (TRAP laws) that included a requirement that an outpatient abortion clinic meet the requirements of a standalone surgical center, even though procedural abortions do not meet the definition of surgery and are extraordinarily

low risk. The Dobbs decision states the federal constitution does not confer a right to abortion and the authority to regulate abortion belongs to the states. Thirteen states had “trigger laws” with the intend to ban abortion if the Supreme Court struck down a federal right to abortion. Other states have attempted to or passed abortion restrictions or bans (Kaiser Family Foundation [KFF], 2022). Since the Dobbs decision, states that have banned or restricted abortion services have experienced higher rates of maternal and infant mortality, especially among women of color; greater racial inequities across their health care systems; fewer maternity care providers; and more maternity care “deserts” (Declercq et al., 2022; Supreme Court of the United States, 2022).‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌

ALIGNING POPULATION NEEDS WITH HEALTH WORKFORCE AVAILABILITY, ACCESSIBILITY, AND CAPACITY: A FOCUS ON POPULATION NEEDS—NOW AND FUTURE Until recently, most health workforce projections focused on supply and demand of health worker occupations, without acknowledging that individuals work in teams across clinical settings and with a variety of populations. In an attempt to evaluate adequacy of the health workforce to deliver care to specific populations or in specific settings, the NCHWA has estimated projections of supply, demand, and supply adequacy for Women’s Health Service Providers (HRSA, 2021c; National Center for Health Workforce Analysis [NCHWA], 2016), and Be‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌havioral Health Providers (HRSA, 2018a, 2019; SAMHSA, 2019). And in keeping with the global model of population needs built on a foundation of primary healthcare (personal healthcare and public health services), the WHO framework for an SRH workforce is described here.

Primary Care Workforce The IOM Committee on Primary Care (IOM, 1996) defined primary care as the provision of integrated, accessible healthcare services by clinicians who are accountable for addressing a large majority of personal healthcare needs, developing a sustained partnership with patients, and practicing in the context of family and community. The primary care clinician workforce includes physicians, NPs, PAs, and nurse-midwives (CNMs). This definition is distinguished from the WHO term primary healthcare, which combines personal health services and population-based, public health services (WHO, 2008, 2014a). Primary healthcare (coordination of patient care across settings, specialties, and populations) results in better health outcomes, reduced health disparities and lower spending, including on avoidable ED visits and hospital care. Primary care services include health promotion, disease prevention, health maintenance, counseling, patient education, diagnosis, and treatment of acute and chronic illnesses in a variety of healthcare settings (e.g., office, inpatient, long-term care, home care, schools, telehealth) for individuals and families across the lifespan and of diverse sexualities and genders.

Chapter 2  Women and Healthcare Workforce: Caregivers and Consumers 43

Recent evidence suggests that the current primary care team includes a generalist physician (family or internal medicine), a nurse (RN, LVN), an NP or PA, and about 25% of teams include a clinical pharmacist, a behavioral specialist, or a social worker (AAN 2016; Bodenheimer et al., 2015; Flinter et al., 2018; Jabbarpour et al., 2020; Mason, 2016; Smolowitz et al., 2015). An important team member in primary healthcare systems outside the United States, CHWs have been underutilized in primary care teams in the United States (Hartzler et al., 2018). In an analysis of 30 studies, CHWs play important roles in clinical services, community resource connections, and health education and coaching through multiple functions (i.e., care coordination, health coaching, social support, health assessment, resource linking, case management, medication management, remote care, follow-up, administration, health education, and literacy support) with potential to improve health outcomes and primary care access (Hartzler et al., 2018). The adequacy of the future primary care workforce, as defined by availability, accessibility, acceptability, and quality, to meet the needs of people in the United States has been partially estimated by HRSA (2020a). In 2018, there were approximately 256,220 full-time equivalent primary care physicians and almost 100,000 full-time NPs (64,490) and PAs (33,400) working in primary care (HRSA, 2020a). By 2030, HRSA projects a 6% to 13% increase in supply of family and general internal physicians and a 2% to 8% decrease in geriatric and pediatric physicians and a 13% to 50% increase in demand for all primary care physicians. Since the supply and demand for primary care providers varies across states and regions, HRSA projects that by 2030, the adequacy of future supply of family physicians will range from 46% to 178%. However, if nurses and NPs (along with PAs) are able to practice to the full extent of their practice ability and authority, the adequacy of the primary care workforce in 2030 could achieve 90% capacity overall (Bosse et al., 2017; HRSA, 2021d). The extent to which the national supply of primary care providers will come close to meeting the national demand in 2030 depends on several factors—effective and efficient use of teambased care, expansion of health insurance coverage under full implementation of the ACA and state Medicaid, health professional regulatory reform, and the implementation of programs and policies to address the maldistribution and diversity of the primary care workforce.

Public Health Workforce ‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌ Public health is a broad field, encompassing the protection and promotion of the public’s health domestically and globally. The complexity of the U.S. public health infrastructure, which spans 50 state health departments, 2,800 local health departments, and 300 regional and district offices, complicates workforce analysis (Association of State and Territorial Health Officials, 2020‌‌‌‌‌‌‌). In addition, much of public health has historically been funded through categorical (or vertical) financing streams for specific politically acceptable programs, disease areas, and initiatives, such as communicable disease control, family planning, and maternal and pediatric healthcare (IOM, 2012). In addition, the U.S. federal government plays a large role in the public health

system in the country. It surveys the population’s health status and health needs, sets policies and standards, passes laws and regulations, supports biomedical and health services research, helps finance and sometimes delivers personal health services, provides technical assistance and resources to state and local health systems, provides protection against international health threats, and supports international efforts toward global health. The federal government does all these mainly through two delegated powers: the power to regulate interstate commerce and the power to tax and spend for the general welfare. The federal government’s regulatory activities, such as labeling hazardous substances, are based in the power to regulate interstate commerce. Its service-oriented programs, such as the cleanup of hazardous substances or financing personal health services through Medicaid and Medicare programs, are based in its power to tax and spend for the general welfare (IOM, 1988). At present, the main federal unit with responsibility for public health is the U.S. Public Health Service in the DHHS. The second major unit is the Health Care Financing Administration, also in the DHHS. Primary care/personal health services differ from public or community health in that public health deals with health from the perspective of populations, not individuals. The clinical healthcare provider—a doctor, nurse, or dentist— helps with personal healthcare issues, or how a condition or disorder affects you individually. The public health approach is different. Public health focuses on the whole neighborhood (or city, county, state, etc.) and determines how many people have a particular disease or problem and what’s putting them at risk. Then, public health professionals work out how to reduce those exposures and cut down on the number of new cases. In effect, the “patient” in public health is the entire community. Public health is also concerned with whether the people with a problem have access to health professionals and are getting good care. If public health does its job, then the whole neighborhood, community, and society are healthier (American Public Health Association [APHA], 2021). Public health professionals try to prevent problems from happening or recurring through implementing educational programs, recommending policies, administering services, and conducting research—in contrast to clinical professionals like doctors and nurses, who focus primarily on treating individuals after they become sick or injured. Public health also works to limit health disparities. A large part of public health is promoting healthcare equity, quality, and accessibility. The U.S. public health system once had a history of robust funding and function, until the advent of Reaganomics in the 1980s drastically cut funding for many integrated social, nutritional, and health services, including community-based services for women, children, families, and vulnerable populations, and has never recovered the lost ground. It was particularly poor timing considering the advent of the HIV pandemic, and the failure of adequate public health systems in the United States may have contributed to its progression both in the United States and abroad. Without that funding, public health systems became increasingly reliant on single-focus programs and short-term funding streams from all levels of government, which significantly weakened the ability of these systems to lead sustained health improvement and workforce.

44  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

The‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌public health workforce consists of public health nurses and physicians, dentists, nutritionists, health educators, epidemiologists, sanitarians, public health technicians/engineers, CHWs, scientists, and public health administrators as well as state and local health commissioners. Over the past decade alone, the public health workforce has shrunk by more than 15% (Castrucci & Valdes Lupi 2020). By some estimates, the U.S. public health workforce will need to grow by 80% to provide a minimum set of health services in the country today. Decades of underinvestment has undermined the public health workforce. Because the “patient” in public health is by definition a broad entity rather than a single individual with a heart-tugging story of illness, cutting public health funding in times of economic distress carries relatively little political risk. With diminished funding, state and local health departments have not been able to attract, recruit, and retain the number of professionals with skills needed to respond to health threats. With shrinking numbers and reduced capacity, workforce development has fallen behind across public health, resulting in several challenges, including (1) lagging skills among workers due to changes in technology, (2) a lack of systems and data to assess and monitor workforce needs, and (3) hiring barriers that exist at federal, state, and local levels. The COVID-19 pandemic highlights the consequences of this underinvestment and the critical need for a strong and diverse public health workforce. Increased funding recently distributed to the CDC secondary to the COVID-19 pandemic—from the Public Health and Social Services Emergency Fund, American Rescue Plan, and others—expands resources for new and expanded workforce development activities (Division of Scientific Education and Professional Development [DSEPD], 2021). With this funding, state and local public health departments have a unique opportunity to invest in the public health workforce to achieve improved availability, accessibility, and quality. A recent report suggests focusing on six workforce development strategies: reassess capabilities and roles, share resources and engage partners, overhaul the recruitment process, invest in employees, cultivate strong leaders, and promote diversity and inclusion (Kumar et al., 2022). Although these strategies can be considered necessary for any part of the health workforce, they are imperative to building capacity in the public health system and its workforce.

Women’s Health Workforce11 Although all people share many healthcare needs, women also experience unique healthcare challenges and can face an array of gender-based health disparities. A group of healthcare professionals, traditionally referred to as “women’s health providers,” typically delivers obstetrics, gynecology, and other preventive and reproductive care services predominantly or solely to cisgender women, and has acquired spe-

cialized credentials in the field of women’s health. Women’s health providers may also offer these same health services to individuals who do not identify as female, although this can be problematic for these individuals as they are literally required to misgender themselves to receive care. (Trans women may experience the opposite problem and find themselves excluded from women’s health based on anatomy rather than gender.) When studied as a group, this cadre of providers often includes OB/GYN physicians, CNMs/certified midwives (CMs),12 and NPs and PAs specialized in women’s health— and hence, these provider types are the focus of a recent HRSA report. Along with family medicine physicians who provide women’s healthcare, these professionals have been the focus of two reports on these women’s health service providers from the NCHWA (2016, 2021b). The 2021 HRSA report presents projections of supply, demand, and supply adequacy for OB/GYNs, CNM/CMs, NPs, and PAs through 2030. The projections are at the national level by metropolitan/nonmetropolitan areas for all four professions and at the state level for OB/GYNs. The contribution of family medicine physicians in the delivery of women’s health services is included. The provider types included in the reports have distinct training paths yet share certain components of their scopes of practice (NCHWA, 2016). Projections extrapolate current national care use and delivery patterns to the future population, accounting for variables including geographic and temporal variation in demographics, lifestyle risk factors, and disease prevalence, which all could affect the future demand for women’s health services. This scenario facilitates evaluation of whether the future supply of women’s health services providers will be sufficient to maintain current levels of care. However, the inadequacy of the current care levels is evidenced by significant access-to-care issues and substandard health outcomes (MacDorman et al., 2016; DHHS, 2020). This report was finalized in the midst of the COVID-19 pandemic, and the full implications of the pandemic on both short-term and long-term supply and demand for women’s health services providers remain uncertain (American College of Obstetricians and Gynecologists [ACOG], 2015). As noted above, trans and gender diverse people may have difficulty accessing needed care, and data are not currently collected on providers who include trans and gender diverse clients in their practice scope. Findings from HRSA’s 2021 HWSM indicate that the nation is training an insufficient number of new OB/GYNs to offset field attrition, while demand for OB/GYN services is growing. At the same time, rapid growth in supply of CNM/ CMs and women’s health NPs and PAs is projected, which may partially alleviate the growing shortfall of OB/GYNs. CNM/CMs, NPs, and PAs can provide services related to uncomplicated pregnancy and childbirth and can treat many common gynecologic conditions. However, a more relevant

Women's health refers to the influence of sex and gender on health, illness, disability, and disease status across the lifespan. For‌‌‌‌‌‌‌‌‌‌‌‌ data on workforce projections see data.hrsa.gov/topics/health-workforce/workforce-projections#top. 12 Because of the widely varying legal status and scope of certified professional midwives (CPMs) and others who are not certified by the American Midwifery Certification Board (AMCB), it is difficult to assess the role of these providers in the national healthcare workforce. This is not a reflection on the care they provide or the important role they play in the care of pregnant people in many jurisdictions. 11

Chapter 2  Women and Healthcare Workforce: Caregivers and Consumers 45

question may be why the United States relies so heavily on obstetrics, a surgical specialty, for most of women’s healthcare. Is there truly a shortage of OB/GYNs, or are the assumptions about the best providers to care for women to blame? The declining OB/GYN specialist physician supply may mean that OB/GYN efforts could increasingly focus on high-risk pregnancies, the management of complex gynecologic conditions, and surgical procedures, which is both an appropriate use of their advanced expertise in pathology and more reflective of the role they take in most other wealthy nations, which, overwhelmingly, have better pregnancy outcomes than does the United States. Substantial barriers to care prevent many women from receiving the healthcare they need. For example, women from underrepresented racial-ethnic groups tend to use fewer indicated services than their non-Hispanic White counterparts (Child Trends, 2018). Women without health insurance also use fewer women’s health services than their insured peers. Addressing differences in healthcare access, strengthening health insurance access, and dismantling racial-ethnic disparity-related barriers may result in a total demand for women’s health services much higher than current levels. Additionally, access does not explain the crisis in Black perinatal mortality, which has multiple structural contributions, including racism in housing, education, employment, and daily life, in addition to access issues (Crear-Perry et al., 2021). Addressing this public health crisis will require not only improved access, but also reconceptualizing health delivery away from simple provider availability to address the determinants of health that occur long before the client arrives at the provider office. This in turn will need to drive a shift away from specialty providers to an increasing use of public health nurses and CHWs. Although geographic maldistribution exists, primary care providers (e.g., family physicians, NPs, and PAs) are likely to contribute to alleviating the increased women’s healthcare service demand, especially in nonmetropolitan areas. Women’s unique health needs extend well beyond just anatomy-specific reproductive health services, and primary care clinicians play a critical role in closing the many health disparities that women face. Primary care clinicians also deliver many sexual and reproductive health services, which include, among other services, the provision of birth control, cervical cancer screening, prenatal care, and the management of chronic conditions during pregnancy. Furthermore, some family medicine physicians are trained to deliver obstetric care. CNMs and women’s health NPs are classified as primary care providers for these populations as well, which OB/GYNs are not. Again, given the need for holistic care for women’s health, a pivot away from specialist surgeons to primary care providers of all varieties is logical. This holistic change will also create opportunities to decouple women’s healthcare from SRH, and to decrease the exclusivity of gendered healthcare. Because trans men and trans women, as well as nonbinary people of varying gender presentation, can experience gender-based harm and discrimination both in healthcare and in the larger society, their health needs may reflect not only anatomic health needs (Pap smear for some trans men, for example), but also potentially the effects of misogyny that are shared with cisgender women, albeit in different ways (e.g., sexual violence, wage gaps).

Rather than focusing on “women’s health” as a category of care, there is the need to evolve care that acknowledges the impacts of patriarchy and misogyny on people who are not cisgender men, and includes people based on needs, rather than gatekeeping by gender identity. One recent approach to this has come unexpectedly from the ACNM, which in 2021 expanded the midwifery scope of practice to include people of all genders seeking midwifery care (ACNM, 2021b). Although that care will differ depending on anatomic needs, an inclusive approach to gender ensures that people are able to access and benefit from midwifery-model care, which includes awareness of gender politics and power in the United States, and the effects of this on health. As the healthcare system evolves in response to the growing need for women’s health services, through demographic and geographic shifts, with the uptake of new technologies, and with delivery system and reimbursement reforms, each health provider’s role and its implications on future availability, acceptability, and accessibility for women’s health providers may change. For example, for states that allow greater practice autonomy in care delivery by CNMs, NPs, and PAs (fewer regulatory limitations on scope of practice), the HWSM might underestimate demand for these occupations while overestimating demand for OB/GYNs—and vice versa for states that offer less practice autonomy for these occupations. Although the HWSM projects that the growth in CNM, NP, and PA supply will exceed growth in demand based on current care delivery patterns, there might not be a “surplus” of these providers. Rather, the rapid growth in supply of these providers may have the following implications: (a) Some care historically provided by OB/GYNs could shift to these providers helping alleviate the projected growing shortfall of OB/GYNs. (b) These providers can help increase the comprehensiveness of women’s health services provided. (c) These providers can help increase access to services by populations that currently underutilize services, including LGBTQI+ people. In 2018, the annual number of CNM, NP, and PA graduates was relatively high, presumably in response to both a projected shortage of OB/GYNs, a perceived increase in future demand, and reimbursement incentives that encourage provision of team-based care and all team providers working at the top of their licenses. That is, dynamic market forces work to mitigate this gap. Furthermore, the supply estimations and projections for women’s health PAs are based on those PAs self-identifying as working in women’s health. Commonly, PAs are educated as generalists for their flexibility to change roles based on where they find interest or employment, with up to 8% of PAs changing practice specialties annually (Smith, 2017). As such, new entrant numbers for any given year or number of PAs continuing to practice in women’s health in any year are somewhat fluid, and more easily adaptable to market conditions than, for example, physician specialties. The HWSM assumes that the baseline number of healthcare providers choosing to practice in women’s health will continue at the same rate. The growth in demand for women’s health services as currently defined, in an era of low birth rates, is growing at a slower rate than demand for other specialties that primarily serve older patient populations and that are projected to experience faster growth in demand. The level of demand for services can have an effect on specialty choice for new healthcare workers, along with numer-

46  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

ous other factors (Yang et al., 2019). And future technological innovations (including self-collected human papillomavirus [HPV] screening in place of routine Pap smears, currently under investigation), shifts in the uptake of team-based care, and other coming trends in delivery of women’s health services (e.g., movement toward over-the-counter access to contraception) will likely affect provider supply and demand in 2030, and thus may not be fully captured in the workforce projections, outside of their current effect in the baseline study year (2018). The increased use of telemedicine in prenatal care necessitated by the COVID-19 pandemic may continue after the pandemic and may help improve care for those who have difficulties accessing in-person care, although there are potential implications for people who are otherwise not connected to community resources except through prenatal visits (Altman et al., 2021; Fryer et al., 2020). Finally, this report was prepared during the COVID-19 pandemic. While it is too early to find accurate data about the types, magnitudes, or duration of the pandemic’s effects on these projections, the dynamics created by the pandemic suggest there will be some considerable effects on the supply, demand, and delivery of women’s healthcare. Evidence from the literature suggests that preventive and routine care, needed treatments, and regular screenings were and are still being missed during the pandemic (1) because of social distancing and quarantining protocols, (2) out of fear of visiting medical facilities during the pandemic, and (3) due to the economic fallout from the pandemic, which is disproportionately impacting women (Glionna, 2020). As a result, the mix of care required until these trends resolve likely will shift toward more later stage treatments to address the issues unaddressed at earlier stages. On the supply side, the drop in business from this delayed care could have long-term implications for the viability of some practices and facilities providing women’s healthcare services (AHA, 2020; Rubin, 2020).

SRH Workforce—Integrating Population Needs With Primary Care and Public Health As mentioned earlier, the global model of primary healthcare provides services to women and men across the lifespan, with emphasis on gender diversity and health equity within an integrated system of primary care and public health. The WHO definition and conceptualization of SRH goes beyond the specialties of obstetrics, gynecology, women’s health, and maternal child healthcare to include the sexual and reproductive health of men and women throughout their life cycle, and adolescents of both sexes, and it is closely associated with sociocultural factors, gender diversity and the respect and protection of human rights.

At the 2005 World Summit, the United Nations adopted a resolution that all countries should strive to achieve universal access to SRH by 2015 calling on all national healthcare systems to increase their delivery of SRH services by a workforce that has adequate knowledge, skill, and appropriate attitudes to provide competent SRH (UN, 2005; WHO, 2010). In 2009, WHO also conducted an intercountry survey to identify SRH provision across clinician type, setting, and degree of SRH integration into primary healthcare.13 A summary of services by CHW, nurse, midwife (these are separate roles in most countries globally), and doctor across six WHO regions and across seven areas of service provision is published by WHO in The Role of Primary Health-Care Providers in Sexual and Reproductive Health (WHO, 2011a) followed by a set of core SRH competencies for interprofessional primary healthcare providers with the intent that these would be further adapted by individual countries to fit their unique national contexts (WHO, 2011b). Significantly, WHO identified SRH, including access to abortion, as included under essential health services that must continue in pandemic conditions (WHO, 2020), which emphasizes the value that public health places on SRH. According to WHO, an expanded definition and conceptualization of SRH is central to the specification of SRH standards and competencies for population health workforce capacity building. SRH extends before and beyond the years of reproduction, and services should be part of the existing healthcare system and delivered as a collection of integrated services that address the full range of SRH needs.14 The WHO 13 core competencies “reflect the attitudes, tasks, knowledge and skills that health personnel in primary health care need to protect, promote and provide SRH in the community” (WHO, 2011a, p. 1) and apply to all frontline healthcare providers, including nurses, midwives, NPs, PAs, physicians, and CHWs (WHO, 2011a, 2011b). Current and future shortages of skilled health professionals are especially critical in regions of the world that also have a high burden of unsafe abortion and related sexual and reproductive morbidity and mortality. Additionally, most countries, including many high-income ones, have subnational disparities in the availability of a skilled health workforce, with shortages being particularly high in rural areas or within the public sector. The United Kingdom’s National Health Service is an exemplar of SRH workforce capacity building that builds on the WHO framework demonstrating improved health outcomes. In the United Kingdom, SRH is provided to adults and adolescents within a coordinated system of primary care and public health services and focuses on three areas: (1) The patient experience—ensuring that patients have access to a full choice of contraceptive methods (including abortion) and can see a competent healthcare professional to discuss

SRH components: antenatal, childbirth, newborn, family planning/infertility, abortion, sexual/reproductive tract infections (STI/RTI), violence/cancer screening, and sexual health promotion/education. 14 The WHO SRH concept consists of six components: (1) improving antenatal, perinatal, postpartum and neonatal care; (2) providing high-quality services for family planning, including infertility services; (3) eliminating unsafe abortion; (4) combatting sexually transmitted infection (STI), including HIV, reproductive tract infections (RTIs), cervical cancer, and other morbidities; (5) promoting sexual health; and (6) increasing workforce capacity and program development. 13

Chapter 2  Women and Healthcare Workforce: Caregivers and Consumers 47

the full range of unintended pregnancy prevention options available to them without fear of harassment or stigma; (2) a well-trained workforce—assuring an optimum provider skill mix to cater for a wide population demand; and (3) the importance of integration—establishing clear referral pathways between services so that care can be integrated around the needs of the individual, not institutional or professional silos. Primary care and public health practitioners have a pivotal role to play in promoting high-quality SRH (Faculty of Sexual and Reproductive Healthcare [FSRH], 2015). In addition, SRH education, training, and certification have been established for RNs, APRNs, midwives, and nonspecialist physicians working in the United Kingdom. The National Health Service builds on general prevention, public health, and primary care competencies by the Royal College of Nursing (RCN), the Royal College of Obstetricians and Gynecologists (RCOG), and the FSRH (FSRH, 2012; RCN, 2009; Wilkinson & Halfnight, 2013). Currently, FSRH offers several competency-based training pathways for a variety of clinicians (FSRH, 2012). In this rational system, curriculum and training processes are coordinated across 10 components using a combination of teaching-learning and evaluation modalities for all categories of frontline primary healthcare providers in the UK national health system (FSRH, 2012).15 In the United States, most SRH services are provided in a fragmented health system, (Levi et al., 2013) and increasing the capacity of U.S. clinicians to provide high-quality SRH for all Americans has been declared an urgent public health priority (APHA, 2015). With likely shortages of primary care clinicians including OB/GYN physicians, a shrinking proportion of primary care clinicians prepared to provide women’s health, and even fewer health professionals providing services in public health, community clinics, and family planning, there is a need to consider the overall SRH workforce policy options. The ACA's (2010) focus on primary care and prevention creates an obvious framework for building capacity. In order to improve SRH workforce availability, accessibility, and quality; the areas for immediate action require development and implementation of new ways to prepare future clinicians and frontline health workers, the further development of the existing primary care workforce, the incorporation of SRH into new models of healthcare delivery and reimbursement, and the leveraging of existing professional expertise to improve SRH delivery (Nothnagle et al., 2013). A 2012 study by the RAND Corporation is the first U.S. report focusing on the SRH workforce with analysis of supply and utilization combined with proposals for policy intervention (Auerbach et al., 2012). The impact of the evolving healthcare delivery system and expanding health insurance coverage is analyzed, which offers an opportunity to integrate the currently “siloed” system and bring it closer to the comprehensive system of SRH services integrated across public health and primary care that WHO recommends. The findings and rec-

ommendations are relevant to all providers of SRH services as recommended by WHO. Short and intermediate policy options and interventions spanning education, federal/state policy, and emerging models of care delivery have the potential not only to close expected supply-demand gaps in the SRH workforce but to improve the quality and efficiency of SRH service delivery, expand the provider base delivering SRH services, and better integrate these services with other parts of the healthcare system. There are multiple challenges preventing integration of SRH information into health professions education. Some of the limitations to engaging the entire healthcare team in SRH lie with inadequate preparation at the prelicensure level, the lack of graduate and postgraduate clinical training opportunities, a failure to recognize the potential distinctive contributions of all healthcare professionals, including physicians and pharmacists, as well as political interference with the provision of SRH. The majority of providers of SRH clinical care are not physicians; they are nurses, NPs, CNM/CMs, PAs, pharmacists, as well as allied and unlicensed health workers, yet there are barriers to universal access to all of these providers, which further limits efforts to reduce unintended pregnancy and sexually transmitted infections and improve SRH promotion. These challenges have been further complicated by political challenges to government involvement in the delivery of SRH, especially the lack of adequate federal funding for unintended pregnancy prevention as well as state restrictions on abortion services. Regardless of the ultimate outcome of this political interference, preparation of and support for providers in all settings to deliver high-quality SRH remain important. In response to SRH workforce challenges and increased demand for SRH services in the United States, an interprofessional group of SRH experts from a wide range of educational, clinical, and policy backgrounds convened to develop a shared agenda to address SRH workforce issues (Nothnagle et al., 2013). At the outset, the participants agreed on fundamental tenets of SRH: comprehensive SRH that includes care of women and men throughout the life cycle with emphasis on adolescents, gender diversity, and health equity; evidence-based prevention and management of unintended pregnancy, including abortion care; public health prevention models to address health disparities; and team-based, interprofessional models of care. Vulnerable populations have historically had limited access to SRH; therefore, strategies to improve access to care for all underlie all recommendations (Cappiello & Nothnagle, 2013). As the U.S. health system pivots to focus on primary care and prevention, the need for competencies and pathways to ensure that primary care providers are able to provide quality SRH has emerged (Simmonds et al., 2017). Building on efforts spearheaded by the SRH Workforce Initiative and the WHO SRH workforce competencies, studies were conducted to identify and refine core competencies in SRH for primary

Competency-based education, training, and certification in the specialty of SRH includes competencies in 10 areas: Basic SRH services/ skills; contraception; unplanned pregnancy care; women’s health/common gynecology; assessment of specialty gynecology problems; pregnancy care; genitourinary conditions of men; sexual health promotion; public health, ethical, legal competencies; leadership, management, technology, audit competencies. 15

48  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

care providers in the United States (Cappiello et al., 2016). The 26 core competencies encompass professional ethics and reproductive justice (RJ), collaboration, SRH services and conditions affecting SRH to inform education and training across professions, as well as to fill the gap between an established standard of care necessary to meet patient needs and the outcomes of that care. Of note, in contrast to the WHO and FSRH competencies, RJ is referenced in this U.S.-focused set. In addition, competency-based educational modules have been developed for all health professional students to improve their understanding, clarify their values, and learn of ways to integrate best practices for unintended pregnancy prevention and care into clinic settings (Hewitt & Cappiello, 2015). Each module is based on essential unintended pregnancy prevention and care competencies to help students improve competency and hone their skills in defined areas—professional ethics, pregnancy options counseling, postpartum/postabortion contraception, public health, quality and safety, and global health.

Behavioral Health Workforce According to the 2019 National Survey on Drug Use and Health (NSDUH), 80% of individuals with a SUD do not get needed care; 57% of those with mental illness also do not get needed care and fully one-third of those living with serious mental illness do not get the care they need (Substance Abuse and Mental Health Services Administration [SAMHSA], 2020a). Given the SAMHSA mission to reduce the impact of mental illness and substance misuse on America’s communities, ensuring that individuals with mental illness and SUDs have access to evidence-based high-quality care is a critical focus. A major factor in achieving this goal is addressing the availability, accessibility, and quality of the behavioral health workforce. In a 2020 report by SAMHSA (2020b), the behavioral health workforce16 functions in a wide range of prevention, healthcare, and social service settings. These settings include prevention programs, community-based programs, inpatient treatment programs, primary care delivery systems, EDs, criminal justice systems, schools, or higher education institutions. This workforce includes, but is not limited to, psychiatrists, psychologists, social workers, advanced practice psychiatric nurses, marriage and family therapists, certified prevention specialists, addiction counselors, mental health/ professional counselors, psychiatric rehabilitation specialists, psychiatric aides and technicians, paraprofessionals in psychiatric rehabilitation and addiction recovery fields (e.g., case managers, homeless outreach specialists, and parent aides), peer support specialists, and recovery coaches. The identified number of behavioral health providers needed in the United States in this report are based on conservative estimates of those requiring access to mental health and SUD services. This report shows the stark contrast between providers that are currently available versus what is

needed to address the mental health issues faced by millions of Americans. The goal of this report is to provide information on evidence-based models of care for those with serious mental illness and SUDs and practitioner numbers needed to meet the behavioral health needs of the American people, and to offer a foundation on which a model for a mental health system that will address these needs can be established. Although the field is growing due to increases in insurance coverage for mental health and SUD services and the rising rate of military veterans seeking behavioral health services, serious workforce shortages exist for health professionals and paraprofessionals across the United States. The NSDUH has consistently shown that the majority of those in need of treatment for mental illness and SUDs are not served. This yearly public health surveillance instrument also showed that in 2018 there were 57.8 million Americans with mental illness and/or SUDs, while in 2019 this number increased to 61.2 million. These findings underscore the urgent need to address the over 4 million provider shortage for behavioral health services in America. The nation’s mental health and SUD providers are essential because mental illness and SUDs are key factors in disability, mortality, and healthcare costs. As the opioid crisis continues, HRSA is analyzing the size and distribution of the behavioral health workforce, both today and in future years (HRSA, 2018b). The national-level supply and demand for select behavioral occupations (psychiatrist, psychiatric NP and PA, psychologist, social worker, addiction counselor, marriage and family therapist, mental health counselor, and school counselor) are projected from 2017 through 2030 using HRSA’s HWSM. Nationally, two of the nine behavioral health occupations estimated in this report (psychiatrists and addiction counselors) are projected to experience shortages in supply by 2030, if there are no changes in behavioral healthcare utilization from today. If current supply and utilization patterns for behavioral health professionals remain the same throughout the forecast period, seven occupations (NPs, PAs, psychologists, social workers, marriage and family therapists, mental health counselors, and school counselors) will be adequate or may potentially experience an oversupply at the national level. Between 2017 and 2030, the total supply of all psychiatrists is projected to decline as retirements exceed new entrants. Rapid growth in supply of psychiatric NPs and psychiatric PAs may help blunt the shortfall of psychiatrists, but will not fully offset it. In 2030, the supply of these three types of providers will not be sufficient to provide any higher level of care than the national average in 2017, which does not fully meet need. Modeling results suggest that if current trends continue, the overall national supply of social workers will grow rapidly and through 2030 should be more than sufficient to meet demand. However, the role of social workers in care delivery continues to evolve. To the extent that the nation relies greatly on social workers in a patient-centered medical home model that better integrates behavioral health and primary

Behavioral healthcare includes care that addresses any behavioral problem, including mental health and substance abuse conditions, stresslinked physical symptoms, patient activation, and health behaviors. https://data.hrsa.gov/topics/health-workforce/workforce-projections#top‌‌‌‌‌‌‌‌‌‌‌‌ 16

Chapter 2  Women and Healthcare Workforce: Caregivers and Consumers 49

care, the increase in demand for social workers could be substantially higher than the projections in this report. The ability of Americans to access appropriate treatment and community recovery resources is critical to improving the overall population health of our citizens and reducing the impact of mental illness and SUDs on individuals, families, and communities. The discussion of the behavioral health workforce should also take into account the important role of peers in the treatment and the recovery process. Recently, there has been an emergence of recovery support centers or “recovery cafes” that encourage peers to support those in treatment. Recovery support centers may also provide critical services for individuals in recovery such as food, social support, access to housing, recovery education, and referrals to more specialized services. In order to ensure that clients remain in treatment and can fully engage in productive activities, peer support should be a critical part of the behavioral health team and represent a major workforce need. To support anticipated demands, the SAMHSA-HRSA Center for Integrated Health Solutions (HRSA-CIHS) is at the forefront of helping the behavioral health workforce implement and use new and evolving practices and technologies to better address the needs of people with mental health and substance use conditions (SAMHSA, 2021). The HRSA-CIHS also provides guidelines on how to provide culturally relevant services via the SAMHSA Office of Behavioral Health Equity (SAMHSA, 2020c). And, in 2020, the expansion of telemedicine has broadened access to Medicare telehealth services so that people can receive a wider range of services from their providers without having to travel to a healthcare facility including specialty care (Centers for Medicare & Medicaid Services [CMS], 2020). The expansion of telemedicine may facilitate access to treatment with fewer barriers related to both transportation and stigma, thereby facilitating treatment services for substance use and mental health conditions.

HEALTHCARE WORKFORCE DRIVERS AND DISPARITIES: INTERSECTIONS OF GENDER, RACE/ETHNICITY, ECONOMIC STATUS, AND POPULATION NEEDS The healthcare system is undergoing major change, which has direct implications for the healthcare workforce. We are moving from acute care treatment to ambulatory care focused on the prevention of chronic disease. With innovations in technology and communications, the professional hierarchy will need to flatten to utilize a diverse healthcare team focused on consumers and cost-effectiveness. Legislative and demographic drivers include ACA expansion and population growth that is increasingly diverse combined with an aging population. The maldistribution of primary care providers— both by type of reimbursement accepted and geographic location—appears to be a more significant problem than overall shortage. The ambulatory care sector will see the largest gain in jobs, mostly because there will be growth in home healthcare and its workers have the lowest level of education

and wages. Given these trends and projections, the healthcare workforce will be increasingly even more female, younger, racially/ethnically diverse, and non-U.S. born, with low income and low education.

Challenges Facing the Healthcare Workforce These trends point to the challenges of a mismatch across growing populations, a lack of workforce capacity, workforce shortages, and the need to develop healthcare workers. The corporatization of healthcare appears to negatively affect the nursing workforce as well. For example, a third of all nurses are unhappy with their current job, but satisfied with their career choice (George Washington University School of Business [GWU], 2021). If career choice is not a problem and current jobs frequently are, there exists a mismatch between the career and the work, not the career and the carer. This an important distinction with implications for regulation of the healthcare industry, the increasing monopolization in many markets, and public policy going forward. It will also need to factor in decisions made about recovery from the current pandemic and preparation for the next public health crisis. Challenges of the future concern staff shortages, unmet educational needs, maldistribution of services and providers, and imbalances across gender and racial diversity. Each of these is affected by multiple systems and will require multifaceted approaches to address, which is difficult within a healthcare model that often seems to be less a system and more a collection of disconnected individuals. These changes will also include shifting from a mindset of who is available to do something to what is needed to be done; overcoming long-standing convictions about who can and should do what; redesigning education and training so that incumbent healthcare workers are equipped with the skills needed to improve equity, quality, and safety; and investing in short- and long-term strategies to cultivate the necessary human capital to overcome shortages and develop a diverse healthcare workforce that represents U.S. society, that is fairly compensated, and that does not discriminate against either clients or each other. Although this chapter focuses primarily on disparities associated with gender and race, much of the impact of these inequities also apply across other population dimensions. Marked differences in the intersecting social determinants, such as poverty, low socioeconomic status (SES), and lack of access to care, exist along racial/ethnic lines and have been shown to contribute to poor health outcomes (De Lew & Sommers, 2022; MacDorman & Mathews, 2011; Sondik et al., 2010) historically linked to exclusion or discrimination. Again, however, it is important to view social determinants of health not as immutable facts or characteristics of risk, but rather as concrete outcomes of the larger systems of oppression (racism, sexism, ableism, etc.) that are built into society. Addressing health disparities requires addressing the systems that have created those disparities in the first place, both within healthcare and in the larger communities. Contrary to articulating gender, race, and class as distinct social categories, intersectionality (a theory developed by U.S. Black feminists, who challenged the notion

50  Part I  LIVES AND HEALTH FOR WOMEN AND MINORITIZED GENDER PERSONS

of a universal gendered experience) postulates that these systems of oppression are mutually constituted and work together to produce inequality (Davis, 1981; Collins, 1990; Schulz & Mullings, 2006). This has begun a shift away from a focus on the individual characteristic to the systems that differentially value that characteristic; from race to racism as the salient fact, for example (Williams & Rucker, 2000). Individuals as workers are shaped simultaneously by race-, class-, and gender-based systems of hierarchy as well as by ability/disability, sexual orientation, and age. Moreover, ecosocial theory integrates the body, mind, and society in understanding the health impact of social conditions and structural inequities, as well as the ways that gender, race, and culture become interwoven in life (Hammarström et al., 2014). Though the status for women in the workforce has improved over the past several decades, many women, particularly Black women and other women of color, still struggle for equality in many occupations. Despite high levels of education (women are earning postsecondary degrees at a faster rate than men are), and strong representation in professional and technical occupations, women still face a persistent wage and earnings gap. Although a number of factors may influence the differences in earnings between men and women in the aggregate (such as higher numbers of women in lower-paying occupations), the wage gap continues even within individual occupations. Women are also more likely than men to leave and then reenter the workforce if they have children, which may affect accrued seniority or promotions, yet even this is insufficient to explain the entire persistent gap (Department for Professional Employees [DPE], 2015). Structural racism and its effects on health is central to every facet of American life: education (Noguera & Alicea, 2020), housing (Krieger et al., 2020), employment (Gemelas et al., 2021), reproduction (Roberts, 1999), legal status (Perreira & Pedroza, 2019), chronic stress and trauma (Walters et al., 2011), institutionalized violence and the carceral state (Hayes, Sufrin, and Perritt, 2020), and healthcare (Mateo & Williams, 2021). Racism has an adverse impact on the healthcare environment and on those receiving healthcare services, but it also impacts health outcomes before an individual ever reaches the healthcare system and reduces the potential for healthcare systems to improve those outcomes once they do. Nor are healthcare workers immune to the experience of racism, sexism, or other oppressions from their colleagues and affiliated institutions. Racism exists in healthcare on an individual level (an attitude of a provider toward a client, for example) and on a systems level (healthcare research, for example; Jones, 2000), and has complex interactions with other aspects of identity, including gender (Crenshaw, 1989). In the healthcare arena, healthcare providers may be victims as well as perpetrators of sexism, racism, and other systems of discrimination and oppression. Selective mistreatment undermines the work experiences of individuals who are identified with groups that are the targets of discriminatory behaviors. Although discrimination occurs on multiple levels—job, housing, and education inequities—it is complicated for women and BIPOC, and multiply complicated for BIPOC women. Classism, racism, and gender inequalities intersect to create structural violence, whereby unequal opportunity and marginalization persist for many in the health workforce (Rhodes et al., 2012).

Gender Discrimination and Sexism Gender discrimination has been defined as any distinction, exclusion, or restriction made on the basis of socially constructed gender roles and norms that prevents a person from enjoying full human rights (WHO, 2001). While this definition also includes trans and gender diverse individuals, it is usually applied to the experiences of cisgender women and is discussed here as such. Gender discrimination can take many forms, overt and covert, such as wage discrimination, occupational gender segregation, sexual harassment, or conduct that creates an intimidating, hostile, or humiliating school or work environment. Gender discrimination can also be less overt, such as the exclusion of informal or home health workers from protective labor legislation (e.g., overtime payment requirements), reassigning pregnant workers on the basis of their pregnant status, or informally penalizing workers for using paid time off to care for family members—all of which disproportionately impact women workers. How gender discrimination has affected women in healthcare has been explored by a number of scholars (Ashley, 1976; Cleland, 1971; Doyal, 1995; Hochschild, 1983; Reverby, 1987a, 1987b; Tijdens et al., 2013; Weaver & Garrett, 1983). Most historians attribute the discrepancy in compensation between men and women in the health occupations to gender discrimination and to lack of social value on caring work (Reverby, 1987b). Ashley (1976) described the discriminatory attitudes toward women that institutionalized their servitude in hospitals and points out the far-reaching effects of sexism on the quality and delivery of healthcare in U.S. hospitals. Hochschild (1983) linked the work of “caring” with occupational activities and economics. In a classic study of women service workers, she described how women are expected to sell their “emotional labor”—to pretend to have positive feelings they are not experiencing and to deny their negative responses in order to make others feel they are being cared for in a safe environment (Hochschild, 1983). This often results in “emotional dissonance”—core stress in which the task of managing an estrangement between self and feeling and between self and behavior. Although women in jobs with the greatest responsibility reported the most stress, it was those with the least say over their working lives who suffered the worst effects. Hochschild (1983) also reported that this experience leads to burnout and a loss of self as feelings and emotions became dulled as a defense against an intolerable situation. Subsequent studies have found that women workers with the least autonomy, job status, or control in their work suffered from physical and emotional disorders resulting in significant economic impact (Doyal, 1995; Hochschild, 1983). Marini (1989) first described wage gaps in segregated occupations: The more an occupation is female-identified, the lower the wages for that occupation. A more recent study (Tijdens et al., 2013) found that “female” tasks and skills are devalued in the labor market, supporting the links among occupational segregation/composition, gender–wage gap, and discrimination. Moreover, even when women choose the same jobs as men, the wage gap persists. For example, male surgeons earn almost 40% more per week than their female counterparts. In real terms, this means that in 2015, a female surgeon earned $756 less per week than her male colleague, which added up

Chapter 2  Women and Healthcare Workforce: Caregivers and Consumers 51

to nearly $40,000 over the course of 1 year (Baxter, 2015). Research on nurses found that they experienced moral distress associated with perceived poor ethical climate, such as the dissonance between a lack of respect for colleagues or patients and the nurse’s perceived lack of decision-making power (Lamiani et al., 2015). This sense of moral distress was amplified during the SARS-CoV-2/COVID-19 pandemic (Silverman et al., 2021), and is associated with long-term mental health impacts (Lake et al., 2021).

Racism and Xenophobia Racial/ethnic disparities and discrimination in healthcare occur in the context of broader historical and contemporary social, structural, and economic inequality, with evidence of persistent racial/ethnic discrimination in many sectors of American life. Black, Hispanic/Latinx, American Indian, and Pacific Islander communities, and some Asian American subgroups, are disproportionately represented in the lower socioeconomic ranks, in lower-quality schools, and in poorer-paying jobs (Nelson, 2002). These disparities can be traced to many factors, including historical patterns of legalized segregation, structural racism, and discrimination. Although some institutionalized discrimination and harm have been removed from the official legal systems of the United States, their impacts remain, as does the fallout from a lifetime of experiencing racism-related stress and/or trauma. The effects of racism persist even when SES is controlled for in analyses, which suggests that health outcomes previously ascribed solely to differences in education and income require closer analysis to repair. For example, Black women with university degrees have 1.6 times the risk of perinatal mortality than White women without a high school diploma (Petersen et al., 2019). Examples like these make it clear that health disparities cannot be simply explained by differences in income or education, or even access to care. Indeed, in addition to the structural racism encountered in daily life, healthcare may not in fact be as good at caring for BIPOC patients and may instead create a new source of harm. Reviews of hundreds of studies conducted in different parts of the country indicate significant differences in healthcare received by persons of different racial/ethnic backgrounds. Differential treatment and access to care in most studies could not be explained by such factors as SES, insurance coverage, stage or severity of disease, comorbidities, type and availability of healthcare services, and patient preferences (e.g., Prather et al., 2018; Schut, 2021; A. C. Smith et al., 2021). Despite efforts to address diversity of the healthcare workforce over the past 30 years, entrenched structural inequities exist in healthcare professional education and within healthcare institutions (e.g., Bell, 2021; Coleman, 2020; Legha et al., 2021; Romano, 2018). Although institutions focus on promoting cultural competence within the health professional workforce, power, White supremacy, and racism/antiracism are not systematically addressed either in education or in practice. Current evidence suggests that if institutionalized racism is addressed by healthcare systems (including education programs), other levels of racism, such as internalized and personally mediated racism, will resolve or have a reduced impact (Altman et al., 2021; Jones, 2000; O’Connor et al., 2019; Taylor, 2021). How-

ever, this requires healthcare systems, including educational systems for providers, to accept responsibility for actively combating that racism. The evidence that systems are doing so in an effective way is to date scanty. Most of the healthcare workforce data on racial discrimination comes from health professions literature on physicians and nurses, who also are less diverse and relatively more powerful than members of other occupational groups, such as home health workers and nursing assistants. Because of the intersections of classism and racism, impacts of racism are likely to be felt even more strongly among workers in these occupations. Even for physicians and nurses, discrimination is a common experience, but via different routes. A recent qualitative study of Black physicians, nurses, and technicians found that relative power in an organization made a difference in how the respondents experienced workplace racism, with physicians noting few instances of individual racism but significant organizational racism, technicians reporting the opposite, and nurses in the middle (Wingfield & Chavez, 2020). One early national study, conducted in 1993 and 1994 among female physicians, found that approximately 60% of BIPOC respondents reported racial/ethnic discrimination at work (Palepu et al., 1998). Despite significant promises made by governmental agencies and healthcare organizations, there is little evidence that the experiences of BIPOC healthcare workers have changed substantially since this early work. The proportion of physicians who reported that they had experienced racial/ethnic discrimination “sometimes, often, or very often” during their medical career was substantial among BIPOC physicians (71% of Black, 45% of Asian, 63% of “other” race, and 27% of Hispanic/Latinx, compared with 7% of white physicians, all p 65 and at risk Covers if at risk for Hep B Covers if at risk for Hep C from IV drug use (annually), had a blood transfusion prior to 1992 (annually), or born between 1945 and 1965 (if not at other risk, covers only once)

Obesity screening/ counseling

Screening and face-to-face counseling

BMI >30 kg/m2

Osteoporosis

Bone density test/BMD every 2 years if criteria met.

Risk criteria: ● Estrogen-deficient and at risk for osteoporosis, based on medical history and/or other findings ● X-rays show possible osteoporosis, osteopenia, or vertebral fractures ● On prednisone or steroid-type drugs ● Primary hyperparathyroidism ● For monitoring response to drug therapy

Tobacco use cessation

Up to eight face-to-face counseling sessions per year

However, recommend smoking cessation at every office visit for primary prevention

Vaccinations

Flu/pneumoccal/hepatitis B

All flu, COVID-19 vaccinations and boosters If at risk for Hep B 65 years and older adults receive PCV13 followed by PPSV23 6 months to 1 year later; for adults age 65 years and older who have already received PPSV23 but not PCV13, they can receive one dose of PCV13 at least 1 year after PPSV23 vaccination

BMD, bone mineral density; BMI, body mass index; FIT, fecal immunochemical test; FOBT, fecal occult blood test; Hep, hepatitis; HPV, human papillomavirus; IV, intravenous; PCV, pneumococcal conjugate vaccine; PPSV, pneumococcal polysaccharide vaccine; USPSTF, U.S. Preventive Services Task Force. Sources: Adapted from American Cancer Society. (2022). Cancer facts & figures 2022. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics /annual-cancer-facts-and-figures/2022/2022-cancer-facts-and-figures.pdf; Centers for Disease Control and Prevention. (2020). Breast cancer: Things you should know. https://www.cdc.gov/cancer/breast/pdf/breast-cancer-fact-sheet-508.pdf; Centers for Medicare & Medicaid Services. (2022). Preventive & screening services: Part B. https://www.medicare.gov/coverage/preventive-screening-services; Reuben, D., Herr, K., Pacala, J., Pollock, B., Potter, J., & Semla, T. (2022). Geriatrics at your fingertips. American Geriatrics Society; U.S. Preventive Services Task Force. (2018b). Cervical cancer: Screening. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation /cervical-cancer-screening

Chapter 10  Older Women’s Health 213

Weight Control

Prevention of Falls

Obesity, described as an epidemic in the United States today, has increased among older women in recent decades, yet it is a key modifiable risk factor for disease, morbidity from chronic disease, and death. The prevalence of severe obesity is lowest in the over-60 age category, although the prevalence is affected by gender, race, and ethnicity. Severe obesity is highest in non-Hispanic Black women and lowest among non-Hispanic Asian women (Stierman et al., 2021). Obesity is associated with an increased risk of CHD, hypertension, diabetes, some cancers, osteoarthritis, and disability, among other chronic conditions. Obese older women can derive multiple health benefits from weight loss; however, careful ongoing health assessments are warranted during weight loss to evaluate the impact on lean muscle mass, fracture risk, and other health parameters. It is important in the older adult to avoid losing muscle mass with weight loss. There appears to be a consensus that a moderate weight loss of 5% to 10% results in significant health benefits, and that to counteract muscle loss due to aging, the American College of Sport Medicine guidelines recommend resistance training with muscle-strengthening exercise twice a week (Fiataraone Singh et al., 2019). The Women’s Preventive Services Initiative (WPSI) has recommended counseling midlife women age 40 to 60 years with normal or overweight body mass index (BMI) to maintain or limit weight gain through healthy eating and physical activity to prevent obesity as women age (Health Resources and Services Administration [HRSA], 2022). HRSA has approved this recommendation, and insurance plans must cover weight counseling in this age group beginning in 2023.

Because fall-related fractures increase the risk for further decline, the prevention of falls is a top priority. Hip fractures and most other nonvertebral fractures in older women occur because of a fall (North American Menopause Society, 2021), making fall prevention a key safety concern for older women. Falls can have a major impact on women’s morbidity and mortality (Burns & Kakara, 2018; Florence et al., 2018). The most recent Cochrane Review of fall-prevention interventions showed that programs likely to be beneficial included multidisciplinary and multifactorial programs with both health and environmental risk factor screening and modification in the community and residential facilities; home hazard assessment and modification; muscle strengthening and balance retraining programs; and withdrawal of psychotropic medications (Gillespie et al., 2012).

Sleep Older adults do not always report problems with sleep to their healthcare providers because the common wisdom has held that sleep disturbances are to be expected as one grows older. Sleep architecture changes—decreased rapid eye movement and slow wave sleep, increased awakenings at night, and a “phase advance” in circadian rhythms (becoming sleepy earlier)—are seen with aging and contribute to sleep changes. More prominent in sleep disturbances are comorbidities such as depression, anxiety, chronic respiratory illnesses, CVD, gastroesophageal reflux disease (GERD), chronic pain, neurodegenerative disorders, and movement disorders (e.g., restless legs syndrome), which affect sleep quality. Medication side effects and interactions and primary sleep disorders, lifestyle patterns, psychosocial factors, and late life stressors also affect sleep quality. Geriatric pharmacotherapy guidelines can aid the clinician in cautious prescribing: to avoid prescribing certain medications or to prescribe only under specific conditions (American Geriatrics Society Beers Criteria Update Expert Panel, 2019). Self-managed approaches to better sleep hygiene include consistent bedtime and awaking, 7 to 9 hours of sleep each night, exercise prior to 3 hours before bedtime, avoidance of large meals close to bedtime, and reducing screen time prior to sleep (National Institute on Aging, n.d.-b).

Vaccinations Because of immune system changes with aging (e.g., immunosenescence) and an increased prevalence of multiple chronic illnesses, older adults can be particularly vulnerable to infectious conditions, associated profound morbidity with complications, and increased risk of mortality. Therefore, older adults will particularly benefit from vaccinations. Annual influenza, two-dose pneumococcal (after age 65 years), and two-dose herpes zoster (after age 50 years) vaccinations are recommended for older adults (CDC, n.d.-d). It is imperative for clinicians to discuss the benefits of vaccinations with their clients. Vaccination against COVID-19 may become part of the routine vaccination schedule as recent data have shown that the highest impact of vaccination against infection and death includes booster doses among the older adult population (Johnson et al., 2022).

Medication Management Prescription drug use has increased dramatically over the years as more and more new medications are introduced. Polypharmacy, can be defined as taking five or more medications while hyperpolypharmacy, also becoming more common, is defined as 10 or more medications (Masnoon et al., 2017). Polypharmacy increases with age, and remains a significant safety issue for older adults, particularly older women who consume the majority of prescription medications. In fact, a recent large study involving nearly 2 million older adults showed the prevalence of polypharmacy among this population to be approximately 44% (Khezrian et al., 2020; Sheikh-Taha & Asmar, 2021). With the higher number of chronic illnesses with age, the drug burden, along with the potential for drug interactions, increases. Optimal medication management occurs with appropriate prescription given the goals of the older woman, coupled with evidence-based guidelines that take comorbid conditions into account. Adherence can be improved by addressing both health literacy and financial considerations, as well as the deployment of enabling technology for reminding and tracking medications.

214  Part II  HEALTH PROMOTION AND PREVENTION

Social Relationships Connection with others is core to healthy aging. Women often survive spouses and friends, resulting in changes in their social network, with losses and opportunities to develop new relationships. Women more readily form and nurture relationships and commonly possess skills and abilities to sustain and develop meaningful connections across the life span. Compared with most men, women play a key role in ensuring family connectivity, sustaining friendships over longer periods of time and actively engaging in friendships throughout life. Women without social connections will benefit from suggestions and referrals to community social activities.

Sexuality Older women are sexual beings who are capable of meaningful sexual relationships. Normal changes with age do not need to affect women’s sexual desires and the ability to experience an orgasm; however, about 50% to 70% of postmenopausal women do experience symptoms of genitourinary syndrome of menopause (GSM; Angelou et al., 2020). Physiologic changes associated with lowered estrogen and other sex steroid hormones affecting vaginal blood flow can make sexual activity uncomfortable. The estrogen changes lead to thinning of vulvar tissue; narrowing, shortening, and loss of elasticity of the vaginal walls; and a reduction of glandular secretions with an increase in vaginal pH. A number of additional factors influence sexual function for older women: established behavioral patterns and preferences, illness, certain medications such as SSRIs (selective serotonin reuptake inhibitors), relationship quality, self-esteem, life stressors, and societal values. Vaginal dryness is the most bothersome GSM symptom, affecting up to 93% of older women with irritation, burning, and itching of vulva/vagina experienced by 63% whether sexually active or not (Moral et al., 2018). Loss of a partner has been reported to be the main reason older women are no longer sexually active, with older women identifying emotional intimacy as an important reason for sexual activity (Granville & Pregler, 2018). The prevalence of sexual activity declines as widowhood increases with age. More than 60% of older women between ages 57 and 64 years are sexually active, 40% among those between 65 and 74 years are active, and less than 20% of women between 75 and 85 years remain active. Among those who are sexually active, approximately half report issues that are bothersome to them, most commonly low desire (43%), difficulty with vaginal lubrication (39%), and inability to have an orgasm (34%). These concerns are more likely among women with chronic health conditions (Merghati-Khoei et al., 2016). Discussion of sexual concerns remains limited, with only 22% of women older than 50 years having conversations about their sexuality with healthcare providers, and usually it is the patient who will initiate the discussion rather than the clinician (Granville & Pregler, 2018). The low rate of sexual health discussions highlights the need for clinicians to initiate such dialogue. A thorough sexual history will guide possible treatments, such as lubricants, vaginal moisturizers, or estrogen creams to reduce physical discomfort or counseling for issues

of relationship quality. If a healthy older woman has remained sexually active, is not inhibited by societal stereotypes and myths against sex with advanced age, and has a partner who has maintained sexual interest and ability to engage in sexual activity, it is likely that she will have continued satisfactory sexual relationships (see Chapter 19, Women’s Sexual Health, for a comprehensive life span discussion of sexuality).

SUMMARY This chapter focuses on older women and their experiences of aging, shaped by the sociopolitical context of women’s lives and the disparities in access to healthcare and services that are related to gender, race, and class. The economic lives of older women are improving, but their economic disadvantages compared with older men are expected to continue; this is particularly true for women of color who experience the triple effects of gender, age, and ethnicity. Transgender people continue to face discrimination as they age. The diversity of the older population is growing, and the coming wave of baby boomers represents a challenge for policy makers, private enterprises, families, and healthcare providers (Thorpe & Whitfield, 2017). As baby boomers attain their eighth decade of life in large numbers, it is highly likely that aging in our culture will be redefined and new solutions and innovations will proliferate in the coming decades. A woman’s experience of aging depends on her personal characteristics and history, access to resources that promote health, and ability to develop strategies for coping with loss and change. Coping with the changes that accompany aging involves some losses that may not be anticipated, but many of the normal psychological and physiologic changes that affect older women may be predicted. Improving outcomes for older women starts with primary prevention to improve general health, delay the onset of disability, and increase productivity and well-being; it continues with health promotion to minimize the effects of chronic conditions and optimize quality of life and functional capacity. If women are educated about age-related changes and given time to assimilate and plan for the process of transition from one phase of life to the next, the potential for optimal aging will be enhanced. Sensitivity to the needs and issues of older women and advocacy for appropriate access and service are essential for promoting the health and well-being of this significant population.

REFERENCES AARP & National Alliance for Caregiving. (2020). Caregiving in the United States 2020. https://www.aarp.org/content/dam/aarp/ppi/2020/05/full-report-caregiving-in-the-united-states.doi.10.26419-2Fppi.00103.001.pdf Administration on Aging. (2021, May). 2020 profile of older Americans. U.S. Department of Health and Human Services. https://acl.gov/sites/default/files/ Profile%20of%20OA/2020ProfileOlderAmericans_RevisedFinal.pdf Ahn, H., Kwon, J., & Kang, J. (2020). Supporting aging-in-place well: Findings from a cluster analysis of the reasons for aging-in-place and perceptions of well-being. Journal of Applied Gerontology, 39(1), 3–15. https://doi .org/10.1177/073346481774877 Alzheimer’s Association. (2022). Alzheimer’s disease facts and figures. Alzheimer’s and Dementia, 18(4), 700–789. https://doi.org/10.1002/alz.12638

American Association of University Women. (2019). The simple truth about the gender pay gap: Fall 2019 update. https://www.aauw.org/app/uploads /2020/02/Simple-Truth-Update-2019_v2-002.pdf American Cancer Society. (2022). Cancer facts & figures 2022. https://www.cancer .org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual -cancer-facts-and-figures/2022/2022-cancer-facts-and-figures.pdf American Geriatrics Society. (2022). AGS guidelines, recommendations, and position statements. Geriatrics Healthcare Professionals. https://www .americangeriatrics.org/publications-tools American Geriatrics Society Beers Criteria Update Expert Panel. (2019). American Geriatrics Society updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society, 67(4), 674–694. https://doi.org/10.1111/jgs.15767 American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). https://doi.org/10.1176/appi.books.9780890425596 American Society of Pension Professionals & Actuaries. (2022). A deeper dive into COVID’s impact on retirement saving. https://www.asppa.org/news /deeper-dive-covid%E2%80%99s-impact-retirement-saving Amutah-Onukagha, N. N., Doamekpor, L. A., & Gardner, M. (2017). An examination of the sociodemographic and health determinants of major depressive disorder among black women. Journal of Racial and Ethnic Health Disparities, 4(6), 1074–1082. https://doi.org/10.1007/s40615-016-0312-2 Anderson, K. M., Davis, K., & Flynn, B. J. (2015). Urinary incontinence and pelvic organ prolapse. Medical Clinics, 99(2), 405–416. Angelou, K., Grigoriadis, T., Diakosavvas, M., Zacharakis, D., & Athanasiou, S. (2020). The genitourinary syndrome of menopause: An overview of the recent data. Cureus, 12(4), Article e7586. https://doi.org/10.7759/cureus.7586 Apesoa-Varano, E., Tang-Feldman, Y., Reinhard, S., Choula, R., & Young, H. (2015–2016). Multi-cultural caregiving and caregiver interventions: A look back and a call for future action. Generations, 39(4), 39–48. Armitage, R., & Nellums, L. B. (2020). COVID-19 and the consequences of isolating the elderly. Lancet Public Health, 5(5), Article e256. https://doi .org/10.1016/S2468-2667(20)30061-X Baker, L., Cotman, C., Thomas, R., Jin, S., Shadyab, A., Pa, J., Rissman, R., Brewer, J., Zhang, J., Jung, Y., La Croix, A., Messer, K., & Feldman, H. (2022). Topline results of EXERT: Can exercise slow cognitive decline in MCI? Proceeding of the Alzheimer’s Association International Conference, San Diego, CA. https://alz.confex.com/alz/2022/meetingapp.cgi/Paper/69700 Balcázar-Hernández, L., Martínez-Murillo, C., Ramos-Peñafiel, C., Pellón Tellez, K., Li, B., Manuel-Apolinar, L., & Basurto, L. (2021). Women and COVID-19: Severity and mortality in hospitalized middle-aged and older patients. Journal of the International Menopause Society, 24(3), 313–315. https://doi.org/10.1080/13697137.2020.1868424 Batmani, S., Jalali, R., Mohammadi, M., & Bokaee, S. (2021). Prevalence and factors related to urinary incontinence in older adults women worldwide: A comprehensive systematic review and meta-analysis of observational studies. BMC Geriatrics, 21, Article 212. https://doi.org/10.1186/s12877-021-02135-8 Bertoluci, M. C., & Rocha, V. Z. (2017). Cardiovascular risk assessment in patients with diabetes. Diabetology & Metabolic Syndrome, 9, Article 25. https://doi .org/10.1186/s13098-017-0225-1 Bond, T., Saad-Lessler, J., & Weller, C. (2020). Still shortchanged: An update on women’s retirement preparedness. National Institute on Retirement Security. https:// www.nirsonline.org/wp-content/uploads/2020/04/Still-Shortchanged-Final.pdf Bone Health and Osteoporosis Foundation. (2022). Bone source for clinicians healthcare professionals toolkit. https://www.bonesource.org/s/HCP-Toolkit -with-graphics.pdf Bukowski, L. A., Hampton, M. C., Escobar-Viera, C. G., Sang, J. M., Chandler, C. J., Henderson, E., Creasy, S. L., & Stall, R. D. (2019). Intimate partner violence and depression among Black transgender women in the USA: The potential suppressive effect of perceived social support. Journal of Urban Health, 96, 760–771. https://doi.org/10.1007/s11524-019-00355-3 Burnes, D., Sheppard, C., Henderson, C. R., Jr., Wassel, M., Cope, R., Barber, C., & Pillemer, K. (2019). Interventions to reduce ageism against older adults: A systematic review and meta-analysis. American Journal Public Health, 109(8), e1–e9. https://doi.org/10.2105/AJPH.2019.305123 Burns, E., & Kakara, R. (2018). Deaths from falls among persons aged ≥65 years—United States, 2007–2016. MMWR Morbidity & Mortality Weekly Report, 67(18), 509–514. https://doi.org/10.15585/mmwr.mm6718a1 Calasanti, T., Carr, D., Homan, P., & Coan, V. (2021). Gender disparities in life satisfaction after retirement: The roles of leisure, family, and finances. Gerontologist, 61(8), 1277–1286. https://doi.org/10.1093/geront/gnab015 Centers for Disease Control and Prevention. (n.d.-a). Alzheimer’s disease and healthy aging: For caregivers, family and friends. U.S. Department of Health and Human Services. Retrieved April 23, 2023, from https://www.cdc.gov /aging/caregiving/caregiver-brief.html

Centers for Disease Control and Prevention. (n.d.-b). Alzheimer’s disease and healthy aging: Minorities and women are at greater risk for Alzheimer’s disease. U.S. Department of Health and Human Services. Retrieved April 24 2023, from https://www.cdc.gov/aging/publications/features/Alz-Greater-Risk.html Centers for Disease Control and Prevention. (n.d.-c). Healthy tribes: Diabetes within American Indian and Alaska Native populations. U.S. Department of Health and Human Services. Retrieved April 23, 2023, from https://www .cdc.gov/healthytribes/native-american-diabetes.html Centers for Disease Control and Prevention. (n.d.-d). Immunization schedules: Adult immunization schedule by age. U.S. Department of Health and Human Services. Retrieved April 23, 2023, from https://www.cdc.gov/vaccines /schedules/hcp/imz/adult.html Centers for Disease Control and Prevention. (n.d.-e). Violence prevention: Fast facts: Preventing elder abuse. U.S. Department of Health and Human Services. Retrieved April 23, 2023, from https://www.cdc.gov/vaccines/schedules /hcp/imz/adult.html Chang, S.-C., Crous-Bou, M., Prescott, J., Rosner, B., Simon, N. M., Wang, W., De Vivo, I., & Okereke, O. I. (2018). Relation of long-term patterns in caregiving activity and depressive symptoms to telomere length in older women. Psychoneuroendocrinology, 89, 161–167. https://doi.org/10.1016/j.psyneuen.2018.01.005 Ching Lim, S. (2017). Managing the elderly with urinary incontinence and dementia. International Archives of Urology and Complications, 3(2), Article 027. https://doi.org/10.23937/2469-5742/1510027 Corbière, S., & Tettenborn, B. (2021). Stroke in women: Is it different? Clinical and Translational Neuroscience, 5(1), Article 2514183. https://doi .org/10.1177/2514183X211014514 Cubanski, J., Koma, W., Damico, A., & Neuman, T. (2019). How much do Medicare beneficiaries spend out of pocket on health care? (Appendix Table 1: Average Out-of-Pocket Spending on Services and Premiums by Traditional Medicare Beneficiaries, 2016). Kaiser Family Foundation. https://files.kff. org/attachment/Appendix-Table-How-Much-Do-Medicare-Beneficiaries -Spend-Out-of-Pocket-on-Health-Care Cubanski, J., Neuman, T., Damico, A., & Smith, K. (2018, January 26). Medicare beneficiaries’ out-of-pocket health care spending as a share of income now and projections for the future. Kaiser Family Foundation. https://www.kff.org/ medicare/report/medicare-beneficiaries-out-of-pocket-health-care-spending-as-a-share-of-income-now-and-projections-for-the-future Cummings, J., Lee, G., Ritter, A., Sabbagh, M., & Zhong, K. (2019). Alzheimer’s disease drug development pipeline: 2019. Alzheimer’s and Dementia, 5(1), 272–293. https://doi.org/10.1016/j.trci.2019.05.008 Daniel, H., Erickson, S. M., & Bornstein, S. S. (2018). Women’s health policy in the United States: An American College of Physicians position paper for the Health and Public Policy Committee of the American College of Physicians. Annals of Internal Medicine, 168(12), 874–875. https://doi.org/10.7326/M17-3344 Der Ananian, C., Winham, D. M., Thompson, S. V., & Tisue, M. E. (2018). Perceptions of heart-healthy behaviors among African American adults: A mixed methods study. International Journal of Environmental Research and Public Health, 15(11), Article 2433. https://doi.org/10.3390/ijerph15112433 Dowell, E. K. P. (2022, January 27). Women consistently earn less than men. U.S. Census Bureau. https://www.census.gov/library/stories/2022/01/genderpay-gap-widens-as-women-age.html Erikson, E. H., Erikson, J. M., & Kivnick, H. Q. (1986). Vital involvement in old age: The experience of old age in our time. W. W. Norton. Fadiga, L., Saraiva, J., Catarino, D., Frade, J., Melo, M., & Paiva, I. (2020). Adult-onset autoimmune diabetes: Comparative analysis of classical and latent presentation. Diabetology & Metabolic Syndrome, 12, Article 107. https://doi.org/10.1186/s13098-020-00616-1 Farrés-Godayol, P., Jerez-Roig, J., Minobes-Molina, E., Yildirim, M., Molas-Tuneu, M., Escribà-Salvans, A., Rierola-Fochs, S., Romero-Mas, M., Torres-Moreno, M., Coll-Planas, L., Booth, J., & Giné-Garriga, M. (2022). Urinary incontinence and its association with physical and psycho-cognitive factors: A cross-sectional study in older people living in nursing homes. International Journal of Environmental Research & Public Health, 19(3), Article 1500. https://doi.org/10.3390/ijerph19031500 Federal Interagency Forum on Aging-Related Statistics. (2020). Older Americans 2020: Key indicators of well-being. U.S. Government Printing Office. https:// agingstats.gov/docs/LatestReport/OA20_508_10142020.pdf Fiataraone Singh, M., Hackett, D., Schoenfeld, B., Vincent, H., & Wescott, W. (2019, July 31). Resistance training for health. American College of Sports Medicine. https://www.acsm.org/news-detail/2019/08/01/new!-resistance-training -for-health-infographic Florence, C. S., Bergen, G., Atherly, A., Burns, E., Stevens, J., & Drake, C. (2018). Medical costs of fatal and nonfatal falls in older adults. Journal of American Geriatrics Society, 66(4), 693–698. https://doi.org/10.1111/jgs.15304 Fraser, S., Lagacé, M., Bongué, B., Ndeye, N., Guyot, J., Bechard, L., Garcia, L., Taler, V., CCNA Social Inclusion and Stigma Working Group, Adam, S., Beaulieu, M., Bergeron, C. D., Boudjemadi, V., Desmette, D., Donizzetti, A.

R., Éthier, S., Garon, S., Gillis, M., Levasseur, M., . . . Tougas, F. (2020). Ageism and COVID-19: What does our society’s response say about us? Age and Ageing, 49(5), 692–695. https://doi.org/10.1093/ageing/afaa097 Gallagher, S., & Wetherell, M. (2020). Risk of depression in family caregivers: Unintended consequence of COVID-19. BJPsych Open, 6(6), Article E119. https://doi.org/10.1192/bjo.2020.99 Gammack, J. K. (2017). Physical activity in older persons. Missouri Medicine, 114(2), 105–109. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140016 Gaugler, J., James, B., Johnson, T., Reimer, J., Solis, M., & Weuve, J. (2022). Alzheimer’s disease facts and figures. More than normal aging: Understanding mild cognitive impairment (Alzheimers Dement, Special Report no. 18). https:// www.alz.org/alzheimers-dementia/what-is-dementia/related_conditions /mild-cognitive-impairment Gillespie, L. D., Robertson, M. C., Gillespie, W. J., Sherrington, C., Gates, S., Clemson, L. M., & Lamb, S. E. (2012). Interventions for preventing falls in older people living in the community. Cochrane Database of Systematic Reviews, 2012(9), Article CD007146. https://doi.org/1002/14651858.CD007146.pub3 Goldberg, E. M., Jiménez, F. N., Chen, K., Davoodi, N. M., Li, M., Strauss, D. H., Zou, M., Guthrie, K., & Merchant, R. C. (2021). Telehealth was beneficial during COVID-19 for older Americans: A qualitative study with physicians. Journal of the American Geriatrics Society, 69(11), 3034–3043. https://doi .org/10.1111/jgs.17370 Gordon, E. H., & Hubbard, R. E. (2020). Differences in frailty in older men and women. Medical Journal of Australia, 212(4), 183–188. https://doi .org/10.5694/mja2.50466 Grami, N., Tuazon, J. R., Kalia, S., Lawson, A., Li, J., Savage, R. D., & Rochon, P. A. (2022). Promoting healthy aging in older women: A call to action. Journal of the American Geriatrics Society, 70(3), 928–931. https://doi.org/10.1111/jgs.17614 Granville, L., & Pregler, J. (2018). Women’s sexual health and aging. Journal of the American Geriatrics Society, 66(3), 595–601. https://doi.org/10.1111/jgs.15198 Hamm, J. M., Heckhausen, J., Shane, J., & Lachman, M. E. (2020). Risk of cognitive declines with retirement: Who declines and why? Psychology and Aging, 35(3), 449–457. https://doi.org/10.1037/pag0000453 Hanna, C., & Goldman, T. (2017). Issue brief: Women and social security. American Academy of Actuaries. https://www.actuary.org/content/women-and-social-security-1 Health Resources and Services Administration. (2022, December). Women’s preventive services guidelines. U.S. Department of Health and Human Services. Retrieved April 23, 2023, from https://www.hrsa.gov/womens-guidelines Health Resources and Services Administration, Office of Health Equity. (2018). Health equity report 2017. U.S. Department of Health and Human Services. https://www.hrsa.gov/sites/default/files/hrsa/health-equity/2017-HRSA-health-equity-report.pdf Hidalgo, J. L., Sotos, J. R., & DEP-EXERCISE Group. (2021). Effectiveness of physical exercise in older adults with mild to moderate depression. Annals of Family Medicine, 19(4), 302–309. https://doi.org/10.1370/afm.2670 Hornbuckle, L. M. (2021). Running while Black: A distinctive safety concern and barrier to exercise in White neighborhoods. Preventive Medicine Reports, 22, Article 101378. https://doi.org/10.1016/j.pmedr.2021.101378 Hua, D., Xu, Y., Zhang, X., He, T., Chen, C., Chen, Z., & Xing, Y. (2021). Retinal microvascular changes in hypertensive patients with different levels of blood pressure control and without hypertensive retinopathy. Current Eye Research, 46(1), 107–114. https://doi.org/10.1080/02713683.2020. 1775260 Institute for Healthcare Improvement. (2021, December ). Using the age-friendly 4Ms to better advocate for older adults (and geriatric care). https://www.ihi.org/communities/blogs/using-the-age-friendly-4ms-to-better-advocate-for-older -adults-and-geriatric-care Jabson Tree, J. M., Patterson, J. G., Beavers, D. P., & Bowen, D. J. (2021). What is successful aging in lesbian and bisexual women? Application of the aging-well model. Journals of Gerontology Series B, Psychological Sciences and Social Sciences, 76(7), 1371–1387. https://doi.org/10.1093/geronb/gbaa130 Jerez-Roig, J., Booth, J., Skelton, D. A., Giné-Garriga, M., Chastin, S. F. M., & Hagen, S. (2020). Is urinary incontinence associated with sedentary behaviour in older women? Analysis of data from the National Health and Nutrition Examination Survey. PLoS One, 15, Article e0227195. https://doi.org/10.1371/journal .pone.0227195 Johnson, A. G., Amin, A. B., Ali, A. R., Hoots, B., Cadwell, B. L., Arora, S., Avoundjian, T., Awofeso, A. O., Barnes, J., Bayoumi, N. S., Busen, K., Chang, C., Cima, M., Crockett, M., Cronquist, A., Davidson, S., Davis, E., Delgadillo, J., Dorabawila, V., . . . Scobie, H. M. (2022). COVID-19 incidence and death rates among unvaccinated and fully vaccinated adults with and without booster doses during periods of Delta and Omicron variant emergence—25 U.S. jurisdictions, April 4–December 25, 2021. MMWR Morbidity & Mortality Weekly Report, 71(4), 132–138. https://doi.org/10.15585/mmwr.mm7104e2

Kaeberlein, M. R., & Martin, G. M. (Eds.). (2016). Handbook of the biology of aging (8th ed.). Academic Press. Kaiser Family Foundation. (2022, June). The facts about Medicare spending. https://www.kff.org/interactive/medicare-spending/ Kane, R., Ouslander, J., & Abrass, I. (2003). Essentials of clinical geriatrics (5th ed.). McGraw-Hill. Kang, C. (2019). Senolytics and senostatics: A two-pronged approach to target cellular senescence for delaying aging and age-related diseases. Molecules and Cells, 42(12), 821–827. https://doi.org/10.14348/molcells.2019.0298 Khezrian, M., McNeil, C. J., Murray, A. D., & Myint, P. K. (2020). An overview of prevalence, determinants and health outcomes of polypharmacy. Therapeutic Advances in Drug Safety, 11, Article 2042098620933741. https://doi. org/10.1177/2042098620933741 Kiely, A. (2018). Why is dementia different for women? Alzheimer’s Society United Against Dementia. https://www.alzheimers.org.uk/blog/why-dementia -different-women Kiesswetter, E., Sieber, C. C., & Volkert, D. (2020). Protein intake in older people: Why, how much and how? Zeitschrift für Gerontologie und Geriatrie, 53(4), 285–289. https://doi.org/10.1007/s00391-020-01723-4 Kim, Y. J., Soto, M., Branigan, G. L., Rodgers, K., & Diaz Brinton, R. (2021). Association between menopausal hormone therapy and risk of neurodegenerative diseases: Implications for precision hormone therapy. Alzheimer’s and Dementia, 7, Article e12174. https://doi.org/10.1002/trc2.12174 King, B. M., Carr, D. C., & Taylor, M. G. (2019). Depressive symptoms and the buffering effect of resilience on widowhood by gender. The Gerontologist, 59(6), 1122–1130. https://doi.org/10.1093/geront/gny115 Kirkland, J. L., & Tchkonia, T. (2017). Cellular senescence: A translational perspective. EBioMedicine, 21, 21–28. https://doi.org/10.1016/j.ebiom.2017.04.013 Koma, W., Cubnaski, J., & Neuman, T. (2021). A snapshot of sources of coverage among medicare beneficiaries in 2018. Kaiser Family Foundation. https://www .kff.org/medicare/issue-brief/a-snapshot-of-sources-of-coverage-among -medicare-beneficiaries-in-2018/ Ladin, K., Porteny, T., Perugini, J. M., Gonzales, K. M., Aufort, K. E., Levine, S. K., Wong, J. B., Isakova, T., Rifkin, D., Gordon, E. J., Rossi, A., Koch-Weser, S., & Weiner, D. E. (2021). Perceptions of telehealth vs in-person visits among older adults with advanced kidney disease, care partners, and clinicians. JAMA Network Open, 4(12), Article e2137193. https://doi.org/10.1001 /jamanetworkopen.2021.37193 Laramie, J. A. (2021). Issues in the lives of older lesbian, gay, bisexual, transgender, and/or queer women. Clinics in Geriatric Medicine, 37(4), 579–591. https://doi.org/10.1016/j.cger.2021.05.005 LeBoff, M. S., Chou, S. H., Ratliff, K. A., Cook, N. R., Khurana, B., Kim, E., Cawthon, P. M., Bauer, D. C., Black, D., Gallagher, J. C., Lee, I. M., Buring, J. E., & Manson, J. E. (2022). Supplemental vitamin D and incident fractures in midlife and older adults. New England Journal of Medicine, 387(4), 299–309. https://doi.org/10.1056/NEJMoa2202106 Leggett, A. N., Strominger, J., Robinson-Lane, S. G., & Maust, D. T. (2022). Disparities in health care task participation and provider communication by family caregiver race. Journal of General Internal Medicine, 37, 1321–1324. https://doi.org/10.1007/s11606-021-06766-w Livingston, G., Huntley, J., Sommerlad, A., Ames, D., Ballard, C., Banerjee, S., Brayne, C., Burns, A., Cohen-Mansfield, J., Cooper, C., Costafreda, S. G., Dias, A., Fox, N., Gitlin, L. N., Howard, R., Kales, H. C., Kivimäki, M., Larson, E. B., Ogunniyi, A., . . . Mukadam, N. (2020). Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet, 396(10248), 413–446. https://doi.org/10.1016/S0140-6736(20)30367-6 Lu, P., Oh, J., Leahy, K. E., & Chopik, W. J. (2021). Friendship importance around the world: Links to cultural factors, health, and well-being. Frontiers in Psychology, 11, Article 570839. https://doi.org/10.3389/fpsyg.2020.570839 MacGuire, F. (2020). Reducing health inequalities in aging through policy frameworks and interventions. Frontiers in Public Health, 8, Article 315. https://doi.org/10.3389/fpubh.2020.00315 Madsen, T. E., Howard, G., Kleindorfer, D. O., Furie, K. L., Oparil, S., Manson, J. E., Liu, S., & Howard, V. J. (2019). Sex differences in hypertension and stroke risk in the REGARDS study: A longitudinal cohort study. Hypertension, 74(4), 749–755. https://doi.org/10.1161/HYPERTENSIONAHA.119.12729 Madsen, T. E., Howard, V. J., Jiménez, M., Rexrode, K. M., Acelajado, M. C., Kleindorfer, D., & Chaturvedi, S. (2018). Impact of conventional stroke risk factors on stroke in women: An update. Stroke, 49, 536–542. https://doi .org/10.1161/STROKEAHA.117.018418 Martin, G. (1992). Biological mechanisms of aging. In J. G. Evans & T. F. Williams (Eds.), Oxford textbook of geriatric medicine (pp. 41–48). Oxford University Press. Masnoon, N., Shakib, S., Kalisch-Ellett, L., & Caughey, G. E. (2017). What is polypharmacy? A systematic review of definitions. BMC Geriatrics, 17(1), Article 230. https://doi.org/10.1186/s12877-017-0621-2

Matthews, K. A., Xu, W., Gaglioti, A. H., Holt, J. B., Croft, J. B., Mack, D., & McGuire, L. C. (2019). Racial and ethnic estimates of Alzheimer’s disease and related dementias in the United States (2015–2060) in adults aged ≥65 years. Alzheimer’s and Dementia, 15(1), 17–24. https://doi.org/10.1016/j .jalz.2018.06.3063 Medicare Payment Advisory Commission & Medicaid and CHIP Payment and Access Commission. (2022). Data book: Beneficiaries dually eligible for Medicare and Medicaid. https://www.macpac.gov/wp-content/uploads/2022/02/Beneficiaries-Dually-Eligible-for-Medicare-and-Medicaid-February-2022.pdf Merghati-Khoei, E., Pirak, A., Yazdkhasti, M., & Rezasoltani, P. (2016). Sexuality and elderly with chronic diseases: A review of the existing literature. Journal of Research in Medical Sciences, 21, Article 136. https://doi.org/10.4103/1735 -1995.196618 Moral, E., Delgado, J. L., Carmona, F., Caballero, B., Guillán, C., González, P. M., Suárez-Almarza, J., Velasco-Ortega, S., Nieto, C., & the writing group of the GENISSE study. (2018). Genitourinary syndrome of menopause. Prevalence and quality of life in Spanish postmenopausal women. The GENISSE study. Climacteric: Journal of the International Menopause Society, 21(2), 167–173. https://doi.org/10.1080/13697137.2017.1421921 Mozaffarian, D., Benjamin, E. J., Go, A. S., Arnett, D. K., Blaha, M. J., Cushman, M., Das, S. R., de Ferranti, S., Després, J. P., Fullerton, H. J., Howard, V. J., Huffman, M. D., Isasi, C. R., Jiménez, M. C., Judd, S. E., Kissela, B. M., Lichtman, J. H., Lisabeth, L. D., Liu, S., . . . Turner, M. B. (2016). Heart disease and stroke statistics—2016 update: A report from the American Heart Association. Circulation, 133, e38–e360. https://doi.org/10.1161 /CIR.0000000000000350 National Association of Chronic Disease Directors. (2018). Caregiving for family and friends—A Public health issue. https://www.cdc.gov/aging/agingdata /docs/caregiver-brief-508.pdf National Center for Health Statistics. (2019). Health, United States, 2018. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. https://www.ncbi.nlm.nih.gov/books/NBK551095 National Center on Elder Abuse. (2022). Research, statistics, and data. https:// ncea.acl.gov/What-We-Do/Research/Statistics-and-Data.aspx National Institute on Aging. (n.d.-a). Aging and your eyes. U.S. Department of Health & Human Services, National Institutes of Health. https://www.nia .nih.gov/health/aging-and-your-eyes#tips National Institute on Aging. (n.d.-b). Getting a good night’s sleep. U.S. Department of Health & Human Services, National Institutes of Health. https:// www.nia.nih.gov/health/infographics/getting-good-nights-sleep National Institute on Deafness and Other Communication Disorders. (2021, March 25). Quick statistics about hearing. U.S. Department of Health & Human Services, National Institutes of Health. https://www.nidcd.nih.gov /health/statistics/quick-statistics-hearing Newcomb, B. (2021, February 26). Perspectives of African-American women missing from aging-in-place research. https://gero.usc.edu/2021/02/26 /perspectives-of-african-american-women-missing-from-aging-in-place -research Noel-Miller, C. (2021, December 15). Medicare beneficiaries’ out-of-pocket spending for health care. AARP Public Policy Institute. https://www.aarp.org /ppi/info-2021/medicare-beneficiaries-out-of-pocket-spending-for-health -care.html North American Menopause Society. (2021). Management of osteoporosis in postmenopausal women: The 2021 position statement of the North American Menopause Society. Menopause, 28(9), 973–997. https://doi.org/10.1097 /GME.0000000000001831 Ochida, K. M., & Lachs, M. S. (2015). Not for doctors only: Ageism in healthcare. Generations, 39(3), 46–57. Office of Health Equity. (2020). Health Equity Report 2019–2020: Special feature on housing and health inequalities. U.S. Department of Health and Human Services, Health Resources and Services Administration. https://www.hrsa .gov/sites/default/files/hrsa/health-equity/HRSA-health-equity-report.pdf Officer, A., & de la Fuente-Núñez, V. (2018). A global campaign to combat ageism. Bulletin of the World Health Organization, 96(4), 295–296. https://doi .org/10.2471/BLT.17.202424 Ohrn, A. M., Nielsen, C. S., Schirmer, H., Stubhaug, A., Wilsgaard, T., & Lindekleiv, H. (2016). Pain tolerance in persons with recognized and unrecognized myocardial infarction: A population-based, cross-sectional study. JAMA, 5, Article e003846. https://doi.org/10.1161/JAHA.116.003846 Okoro, C. A., Hollis, N. D., Cyrus, A. C., & Griffin-Blake, S. (2018). Prevalence of disabilities and health care access by disability status and type among adults—United States, 2016. MMWR Morbidity & Mortality Weekly Report, 67, 882–887. https://doi.org/10.15585/mmwr.mm6732a3 Öngel, M. E., Yıldız, C., Akpınaroğlu, C., Yilmaz, B., & Özilgen, M. (2021). Why women may live longer than men do? A telomere-length regulated and

diet-based entropic assessment. Clinical Nutrition, 40(3), 1186–1191. https:// doi.org/10.1016/j.clnu.2020.07.030 Orellano-Colón, E. M., Suárez-Pérez, E. L., Rivero-Méndez, M., Boneu-Meléndez, C. X., Varas-Díaz, N., Lizama-Troncoso, M., Jiménez-Velázquez, I. Z., León-Astor, A., & Jutai, J. W. (2021). Sex disparities in the prevalence of physical function disabilities: A population-based study in a low-income community. BMC Geriatrics, 21(1), Article 419. https://doi.org/10.1186/ s12877-021-02362-z Pignolo, R. J., Law, S. F., & Chandra, A. (2021). Bone aging, cellular senescence, and osteoporosis. JBMR Plus, 5(4), Article e10488. https://doi.org/10.1002/ jbm4.10488 Pillemer, K., Burnes, D., Riffin, C., & Lachs, M. S. (2016). Elder abuse: Global situation, risk factors, and prevention strategies. Gerontologist, 56(Suppl. 2), S194–S205. https://doi.org/10.1093/geront/gnw004 Proietti, M., & Cesari, M. (2020). Frailty: What is it? Advances in Experimental Medicine and Biology, 1216, 1–7. https://doi.org/10.1007/978-3-030-33330-0_1 Reinert, M., Nguyen, T., & Fritze, D. (2021). 2021: The state of mental health in America. Mental Health America. Rivera-Torres, S., Fahey, T. D., & Rivera, M. A. (2019). Adherence to exercise programs in older adults: Informative report. Gerontology & Geriatric Medicine, 5. https://doi.org/10.1177/2333721418823604 Roberts, A. W., Ogunwole, S. U., Blakeslee, L., & Rabe, M. A. (2018a). A snapshot of the fast-growing U.S. older population. U.S. Census Bureau. https:// www.census.gov/library/stories/2018/10/snapshot-fast-growing-us-older -population.html Roberts, A. W., Ogunwole, S. U., Blakeslee, L., & Rabe, M. A. (2018b). The population 65 years and older in the United States: 2016. American Community Survey Reports, ACS-38. U.S. Census Bureau. https://www.census.gov /content/dam/Census/library/publications/2018/acs/ACS-38.pdf Roberts, E. T., & Mehrotra, A. (2020). Assessment of disparities in digital access among Medicare beneficiaries and implications for telemedicine. JAMA Internal Medicine, 180, 1386–1389. https://doi.org/10.1001/jamainternmed .2020.2666 Rock, C., Thomson, C., Gansler, T., Gapstur, S., McCullough, M., Patel, A., Andrews, K., Bandera, E., Spees, C., Robien, K., Hartman, S., Sullivan, K., Grant, B., Hamilton, K., Kushi, L., Caan, B., Kibbe, D., Black, J., Wiedt, T., . . . Doyle, C. (2020). American Cancer Society guideline for diet and physical activity for cancer prevention. CA: A Cancer Journal for Clinicians, 72(4) 245–271. https://doi.org/10.3322/caac.21591 Rodolfo, J., De Araújo, T., Maria, L., Macedo, D. B., Jerez-roig, J., & De Lima, K. C. (2021). Mobility limitation in older adults residing in nursing homes in Brazil associated with advanced age and poor nutritional status: An observational study. Journal of Geriatric Physical Therapy, 45(3), E137–E144. https:// doi.org/10.1519/JPT.0000000000000301 Rossiello, F., Jurk, D., Passos, J. F., & d’Adda di Fagagna, F. (2022). Telomere dysfunction in ageing and age-related diseases. Nature Cell Biology, 24(2), 135–147. https://doi.org/10.1038/s41556-022-00842-x Rowe, J., & Kahn, R. (1998). Successful aging. Pantheon Books. Sánchez-González, J. L., Sánchez-Rodríguez, J. L., Martín-Vallejo, J., Martel-Martel, A., & González-Sarmiento, R. (2021). Effects of physical exercise on cognition and telomere length in healthy older women. Brain Sciences, 11(11), Article 1417. https://doi.org/10.3390/brainsci11111417 Sheikh-Taha, M., & Asmar, M. (2021). Polypharmacy and severe potential drug-drug interactions among older adults with cardiovascular disease in the United States. BMC Geriatrics, 21, Article 233. https://doi.org/10.1186/ s12877-021-02183-0 Shock, N., Gruelich, R. C., Andres, R., Arenberg, G., Costa, P. T., Jr., Lakatta, E. G., & Tobin, J. D. (1984). Normal human aging: The Baltimore longitudinal study of aging (NIH Publication No. 84-2450). U.S. Department of Health and Human Services. Sobhani, A., Fadayevatan, R., Sharifi, F., Kamrani, A. A., Ejtahed, H.-S., Hosseini, R. S., Mohamadi, S., Fadayevatan, A., & Mortazavi, S. (2021). The conceptual and practical definitions of frailty in older adults: A systematic review. Journal Diabetes & Metabolic Disorders, 20(2), 1975–2013. https:// doi.org/10.1007/s40200-021-00897-x Spillman, B., Allen, E., & Favreault. (2020). Informal caregiver supply and demographic changes: Review of the literature. Office of Assistant Secretary for Planning and Evaluation (ASPE), Urban Institute. https://aspe.hhs.gov /reports/informal-caregiver-supply-demographic-changes-review-literature-0 Statista. (2020). Resident population of the United States by sex and age as of July 1, 2020. https://www.statista.com/statistics/241488/population-of-the-us -by-sex-and-age Stetson, B., Minges, K. E., & Richardson, C. R. (2017). New directions for diabetes prevention and management in behavioral medicine. Journal of Behavioral Medicine, 40(1), 127–144. https://doi.org/10.1007/s10865-016 -9802-2

Stierman, B., Afful, J., Carroll, M., Chen, T., Davy, O., Fink, S., Fryar, C., Gu, Q., Hales, C., Hughes, J., Ostchega, Y., Storandt, R., & Akinbami, L. (2021). National Health and Nutrition Examination Survey 2017–March 2020 prepandemic data files—Development of files and prevalence estimates for selected health outcomes (National Health Statistics Reports, No. 158). National Center for Health Statistics. https://stacks.cdc.gov/view/cdc/106273 Struijk, E. A., Hagan, K. A., Fung, T. T., Hu, F. B., Rodríguez-Artalejo, F., & Lopez-Garcia, E. (2020). Diet quality and risk of frailty among older women in the Nurses’ Health Study. The American Journal of Clinical Nutrition, 111(4), 877–883. https://doi.org/10.1093/ajcn/nqaa028 Sund, M., Fonseca-Rodríguez, O., Josefsson, A., Welen, K., & Fors Connolly, A. M. (2022). Association between pharmaceutical modulation of oestrogen in postmenopausal women in Sweden and death due to COVID-19: A cohort study. BMJ Open, 12(2), Article e053032. https://doi.org/10.1136/bmjopen-2021-053032 Sutphin, G. L., & Korstanje, R. (2016). Longevity as a complex genetic trait. In M. R. Kaeberlein & G. M. Martin (Eds.), Handbook of the biology of aging (8th ed., pp. 3–54). Academic Press. Tai, H., Liu, S., Wang, H., & Tan, H. (2021). Determinants of urinary incontinence and subtypes among the elderly in nursing homes. Frontiers in Public Health, 9, Article 788642. https://doi.org/10.3389/fpubh.2021.788642 Thorpe, R. J., Jr., & Whitfield, K. E. (2017). Advancing minority aging research. Research on Aging, 39(4), 471–475. https://doi.org/10.1177/0164027516672779 Tuttle, C., Tanem, J., Lahr, M., Schroeder, J., Tuttle, M. S., & Henning-Smith, C. (2020). Rural-urban differences among older adults. University of Minnesota Rural Health Research Center. https://rhrc.umn.edu/publication/rural-urban -differences-among-older-adults U.S. Bureau of Labor Statistics. (2021, September). Highlights of women’s earnings in 2020 (BLS Report 1094). U.S. Department of Labor. https://www.bls.gov /opub/reports/womens-earnings/2020/home.htm U.S. Census Bureau. (2021). Quick facts, United States. U.S. Department of Commerce. https://www.census.gov/quickfacts/fact/table/US/PST045221 U.S. Department of Agriculture & U.S. Department of Health and Human Services. (2020, December). Dietary guidelines for Americans, 2020–2025 (9th ed.). https://www.dietaryguidelines.gov/sites/default/files/2020-12 /Dietary_Guidelines_for_Americans_2020-2025.pdf U.S. Department of Health and Human Services. (2018). Physical activity guidelines for Americans (2nd ed.). Author. https://health.gov/paguidelines /second-edition/pdf/Physical_Activity_Guidelines_2nd_edition.pdf U.S. Environmental Protection Agency. (2022, December 12). Heat islands and equity. https://www.epa.gov/heatislands/heat-islands-and-equity U.S. Preventive Services Task Force. (2018a). Vitamin D, calcium, or combined supplementation for the primary prevention of fractures in community-dwelling adults: U.S. Preventive Services Task Force Recommendation Statement. JAMA, 319(15), 1592–1599. https://doi.org/10.1001/jama.2018.3185 U.S. Preventive Services Task Force. (2018b). Cervical cancer: Screening. https:// www.uspreventiveservicestaskforce.org/uspstf/recommendation/cervical -cancer-screening Vahia, I. V., Jeste, D. V., & Reynolds, C. F. (2020). Older adults and the mental health effects of COVID-19. JAMA, 324(22), 2253–2254. https://doi .org/10.1001/jama.2020.21753 Valenti, K. G., Janssen, L. M., Enguidanos, S., & de Medeiros, K. (2021). We speak a different language: End-of-life and bereavement experiences of older lesbian, gay, and bisexual women who have lost a spouse or partner. Qualitative Health Research, 31(9), 1670–1679. https://doi.org/10.1177/10497323211002823

van der Ende, M. Y., Juarez-Orozco, L. E., Waardenburg, I., Lipsic, E., Schurer, R. A. J., van der Werf, H. W., Benjamin, E. J., van Veldhuisen, D. J., Snieder, H., & van der Harst, P. (2020). Sex-based differences in unrecognized myocardial infarction. JAMA, 9(13), Article e015519. https://doi.org/10.1161 /JAHA.119.015519 Vyas, C. M., Donneyong, M., Mischoulon, D., Chang, G., Gibson, H., Cook, N. R., Manson, J. E., Reynolds, C. F., 3rd, & Okereke, O. I. (2020). Association of race and ethnicity with late-life depression severity, symptom burden, and care. JAMA Network Open, 3(3), Article e201606. https://doi.org/10.1001 /jamanetworkopen.2020.1606 Wang, L., Yang, L., Di, X., & Dai, X. (2020). Family support, multidimensional health, and living satisfaction among the elderly: A case from Shaanxi Province, China. International Journal of Environmental Research & Public Health, 17(22), Article 8434. https://doi.org/10.3390/ijerph17228434 Wanka, A. (2019). Continuity and change in the transition to retirement: How time allocation, leisure practices and lifestyles evolve when work vanishes in later life. European Journal of Ageing, 17(1), 81–93. https://doi.org/10.1007 /s10433-019-00526-w Weller, C. E., & Karakilic, E. (2020). Wealth inequality, precariousness, household debt, and macroeconomic instability. Journal Economic Issues, 56(2), 599–606. https://doi.org/10.1080/00213624.2022.2065864 Whiteman, A., Wang, A., McCain, K., Gunnels, B., Toblin, R., Lee, J. T., Bridges, C., Reynolds, L., Murthy, B. P., Qualters, J., Singleton, J. A., Fox, K., Stokley, S., Harris, L., Gibbs-Scharf, L., Abad, N., Brookmeyer, K. A., Farrall, S., Pingali, C., . . . Barbour, K. E. (2021). Demographic and social factors associated with COVID-19 vaccination initiation among adults aged ≥65 Years—United States, December 14, 2020–April 10, 2021. MMWR Morbidity & Mortality Weekly Report, 70(19), 725–730. https://doi.org/10.15585/mmwr.mm7019e4 Wolff, J. L., Freedman, V. A., Mulcahy, J. F., & Kasper, J. D. (2020). Family caregivers’ experiences with health care workers in the care of older adults with activity limitations. JAMA Network Open, 3(1), Article e1919866. https://doi .org/10.1001/jamanetworkopen.2019.19866 World Health Organization. (2018). Ageism. http://www.who.int/health-topics /ageism World Health Organization. (2019). A society is measured by how it cares for its elderly citizens. https://www.who.int/news-room/feature-stories/detail/a-society -is-measured-by-how-it-cares-for-its-elderly-citizens Yelton, B., Friedman, D. B., Noblet, S., Lohman, M. C., Arent, M. A., Macauda, M. M., Sakhuja, M., & Leith, K. H. (2022). Social determinants of health and depression among African American adults: A scoping review of current research. International Journal of Environmental Research and Public Health, 19(3), Article 1498. https://doi.org/10.3390/ijerph19031498 Yiannopoulou, K. G., & Papageorgiou, S. G. (2020). Current and future treatments in Alzheimer disease: An update. Journal Central Nervous System Disease, 12, Article 1179573520907397. https://doi.org/10.1177/1179573520907397 Yon, Y., Mikton, C., Gassoumis, Z. D., & Wilber, K. H. (2019). The prevalence of self-reported elder abuse among older women in community settings: A systematic review and meta-analysis. Trauma Violence Abuse, 20(2), 245–259. https://doi.org/10.1177/1524838017697308 Zamarro, G., & Prados, M. J. (2021). Gender differences in couples’ division of childcare, work and mental health during COVID-19. Review of Economics of the Household, 19(1), 11–40. https://doi.org/10.1007/s11150-020 -09534-7

Chapter

11

Well Women’s Health* Eldora Lazaroff, Lynn M. Gaddis,

The practice of well women’s health‌‌‌‌‌‌‌‌is not of a reactive healthcare system that responds to acute and urgent needs, but rather one that nurtures health, well-being, and minimized health risk (American College of Obstetricians and Gynecologists [ACOG], 2018; National Women’s Law Center [NWLC], 2022). The modern approach to addressing the physical and mental healthcare needs of women from adolescence to older age is a team approach. Providers of sexual and reproductive health (SRH) services to women range from gynecologic care to geriatric services. Healthcare professionals nurture the optimal health and well-being of women at significant stages of their lives. This chapter offers suggestions and new evidence-based research, clinical updates, drug information, clinical guidelines, information related to COVID-19, racism and health disparities, emerging topics in women’s health, and expanded information on the care of transgender individuals as well as enhanced information on pregnancy and related issues as these clients are increasingly treated in primary care settings. Healthcare providers educated in primary care specialties, such as family, adult/gerontology, and pediatrics, are knowledgeable to provide SRH care services to women. The Agency for Healthcare Research and Quality (AHRQ) supports the National Academy of Medicine (NAM) assessment of possible gaps in evidence expressed by the U.S. Preventive Services Taskforce (USPSTF; Institute of Medicine [IOM], 2011). The Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital developed resources for consumers, healthcare providers, and policy makers to help women navigate the SRH preventive services available to them under the Patient Protection and Affordable Care Act (ACA; IOM, 2011; NWLC, 2022). Clients come from varied cultural and socioeconomic backgrounds with a host of personal beliefs regarding their health. The NAM provides resources on transgender and gender diverse inclusivity, sex as a biological variable, and sex-specific illnesses and vulnerabilities (IOM, 2011‌‌‌) Furthermore, clients are surfing the web, reading medical literature, and becoming self-educated in mainstream medicine along with alternative and complementary medicine. Women entering the clinician’s office often have thought-out questions and suggestions for their plans of care.‌‌‌‌‌‌‌‌

and

Versie Johnson-Mallard

COMPONENTS OF A WELL-WOMAN VISIT The yearly well-woman visit is an opportunity to promote health by addressing health concerns and educating women about health risks and disease prevention across a lifespan. A woman’s health history should be collected while she is clothed. The healthcare provider should sit at eye level and face the woman. If language is a barrier for the client, a qualified, professional translator may be necessary to collect health information correctly. Begin the history with social conversation. Asking sensitive questions in front of family or friends may result in incomplete answers and missed information. Interview your client alone, if possible. If unable to interview the woman alone, attempt to contact her later to fill in any important missing information. The well-woman visit, at minimum, should include: ● ● ● ●

● ● ●

Review of health history Assessment of physical and psychosocial well-being Primary and secondary screening Review of prescription and over-the-counter medications, vitamins, and supplements Counseling/education Preconception, prenatal, and interconception care Updates on risk factors and immunizations (Women’s Preventive Services Initiative [WPSI], 2022)

Health History The health history is a fundamental part of the annual visit and may vary depending on age, risk factors, and the woman’s and/or her healthcare provider’s preferences (ACOG, 2018; WPSI, 2022). The best time to begin establishing a relationship with a woman is during your interview to collect her and her family’s health history. An annual visit for an established female client may consist of: ● ●

Counseling about health maintenance Risk assessment

*This chapter is a revision of the chapter that appeared in the second edition of this textbook, coauthored with Barbara B. Cochrane and Heather M. Young, and we thank them for their original contribution.

215

216  Part II  HEALTH PROMOTION AND PREVENTION ● ● ●

Body mass index (BMI) assessment Screening Immunizations

An established client will require a thorough review and update of her past medical history and social history, as well as a three-generation family history (if known, see Table 11.1). Updating a woman’s health history is the opportune time to, together, determine what healthcare needs may be indicated and how the woman views her personal health. The health history is an investigation of current health, real and potential risks, and discovery of knowledge gaps and is a time to gather information to support any indicated referrals. Developing a rapport with the woman may decrease any discomfort that might occur when asking personal and often difficult questions such as drug use, sexual history, and abuse. Asking the question does not imply judgment when asked in a respectful manner and without criticism. Active TABLE 11.1  Components of Client History PAST MEDICAL HISTORY

SOCIAL HISTORY

Medical Medications ● Allergies ● Surgery ● Immunizations

Occupation Diet ● Exercise ● Tobacco ● Alcohol ● Illicit drugs ● Sexual history ● Last menstrual period ● Last Pap smear

●

●

●

●

FAMILY HISTORY

Mother—e.g., HTN, alive‌‌‌‌‌‌‌ ● Father—e.g., healthy, alive ● Siblings ●

OBSTETRIC HISTORY ‌‌‌‌‌‌‌

HTN, hypertension (high blood pressure).

listening skills, such as leaning forward, nodding, and encouraging further description while saying tell me more or go on all indicate interest and serve to instill a sense of trust in the client–healthcare provider professional relationship. It is critical to listen to the woman’s response while paying attention to the language and words she uses, as well as her facial expressions and body language. Furthermore, it is important to do everything possible to avoid interruptions while the woman is explaining her concerns and reasons for her health visit. It is very important that the healthcare provider maintain good eye contact with the woman (not the computer screen) while addressing her. If necessary, the typing of information into the electronic medical chart should be kept to a minimum.

Routine Health Screening LIPID PROFILE ASSESSMENT

A lipid profile provides healthcare providers with a risk assessment for morbidity related to coronary heart disease (CHD; Table 11.2). CHD is the most common cause of death in adults in the United States (Bays et al., 2014). Women considered to be at high risk are those with a family history of premature cardiovascular disease, previous personal history of CHD, a BMI greater than 30, a personal and/or family history of peripheral vascular disease, and diabetes mellitus (Bays et al.,2014; USPSTF, 2014). The recommended timing for dyslipidemia screening in women ages 20 to 45 years with increased risk for CHD is every 5 years (Fitzgerald et al., 2015; USPSTF, 2014). ENDOCRINE SCREENING

The endocrine system is a complex system using hormones that target organs throughout the body. Hormones affect the development of sexual characteristics, fertility, fluid balance, and maintenance of blood pressure (BP). Disorders of the endocrine system are categorized as:

‌‌‌‌‌TABLE 11.2  Lipid Profile Components and Levels LIPID PROFILE

COMPONENTS

LEVELS

Total cholesterol

Measures all of the cholesterol

Desirable: 1,000 copies/mL and not breastfeeding (Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission, 2012). Pregnant women with HIV should be linked to comprehensive HIV medical and psychosocial care as well as prenatal and postpartum care (Andrews et al., 2018). Many women are diagnosed with HIV at a slightly older age than are men (CDC, 2021b). Furthermore, the prevalence of HIV is higher in African American or Hispanic women, and factors contributing to this disparity include oversampling, poverty, lack of health insurance, limited access to care, discrimination, and racism (Agénor et al., 2021; Bosh et al., 2021; Relf et al., 2019; Scott et al., 2023). Thus, a comprehensive plan of care that takes into consideration the multiplicity of stressors that women with HIV experience has a greater chance at making a healthy impact on their lives.

TREATMENT OF HIV IN WOMEN Women with undiagnosed HIV often seek care for routine gynecologic services including treatment for candidiasis, which presents an opportunity to recommend HIV testing. Recurrent vulvovaginal candidiasis is one common symptom of HIV infection in women, and treatment is the same for a woman with or without HIV (CDC, 2021c). Furthermore, prevalence rates for vulvovaginal candidiasis are higher in women with

590  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

HIV, and symptoms can be worse in those with deteriorating immune function (CDC, 2021c). In addition, some gynecologic infections and conditions affect women with HIV differently than women without HIV. Women with HIV are also more likely than women without HIV to have abnormal cervical cytology and human papillomavirus infection, which have results in the development of cervical cancer screening guidelines for women with HIV (Moscicki et al., 2019). Other common infections such as pelvic inflammatory disease, genital herpes, and bacterial vaginosis can be more severe and difficult to treat in women with HIV compared to women without HIV; thus, refer to the special considerations section of the STI treatment guidelines (Cameron et al., 2020; CDC, 2021c). While not all women seeking gynecologic services for conditions such as recurrent vaginal candidiasis and abnormal cervical cytology have HIV infection, providers should consider testing undiagnosed women who are experiencing similar symptoms and assessing immune function in women with HIV. Individuals with a new diagnosis of HIV infection should be informed about (a) the importance of prompt linkage to HIV care and what to expect when they begin healthcare of HIV infection, and (b) the effectiveness of HIV treatments, as well as the goal of treatment including reduced risk of HIV transmission and mortality (Panel on Antiretroviral Guidelines for Adults and Adolescents, 2022). The care of a person with HIV should be supervised by an expert in HIV and/or infectious diseases. All women newly diagnosed with HIV should undergo an extensive medical history review, physical examination, and laboratory evaluation. The initial encounter should be nonjudgmental and focus on establishing rapport. The medical history (Table 31.4) should include inquiries related to sexual behaviors, STIs, and chronic illnesses unrelated to but affected by HIV and its treatments, such as heart disease and diabetes mellitus. The history also should include inquiries about illnesses and conditions associated with immunosuppression, such as tuberculosis; herpes zoster and genital herpes; acute and chronic skin disorders, such as fungal infections and molluscum contagiosum; severe and repeated episodes of vaginal candidiasis; diarrhea associated with various fungi or bacteria; and frequent bouts of pneumonia and sinusitis (Panel on Antiretroviral Guidelines for Adults and Adolescents, 2022; Thompson et al., 2021). The presence or frequency of these infections not typically found in persons with normal immunologic status may help pinpoint the time of infection. In addition, women with HIV should be asked about their gynecologic and obstetric history, including birth control method and plans for future childbearing. The physical examination for patients with HIV should be very thorough. Vital signs should be carefully monitored, especially temperature and weight. The wide-scale and subtle effects of HIV on various body systems require careful examination, especially of the mouth, eyes, skin, lungs, heart, lymph nodes, abdomen, genitourinary system, rectum, and nervous system. HIV may cause subtle or obvious changes in each of these systems. Clinical abnormalities in these systems will give the practitioner evidence of the level of immune system compromise in the patient with HIV. In addition, certain laboratory tests (Table 31.5) should be included in the initial examination of the woman with HIV. In addition, all patients should be tested for tuberculosis initially and annually

TABLE 31.4  Medical History for Women With HIV TOPIC

SPECIFIC POINTS TO ADDRESS

HIV diagnosis

Date/year of first test; reason for being tested; mode of transmission

HIV treatment history

Nadir CD4 count; most recent and highest viral load Specific antiretroviral treatment history including prior resistance testing, reasons for regimen changes

Sexually transmitted infections and other infection history

Syphilis; gonorrhea; herpes simplex; pelvic inflammatory disease; anogenital warts; tuberculosis; hepatitis A, B, or C; prior vaccinations; history of chickenpox or shingles

Obstetric and gynecologic history

Pregnancies and their resolution, menstrual disorders, anovulation, perimenopause, uterine fibroids or polyps, abnormal vaginal discharge, cancer, genital tract infections

Other medical diagnoses

Hypertension, type 2 diabetes mellitus, cardiovascular disease, premalignant or malignant conditions, thyroid disease

Sexual practices

Condom use; other birth control methods; number of current partners; sexual activity with men, women, or both; history of transactional sex for drugs or money; history of anal sex

HIVassociated signs and symptoms

Bacterial pneumonia, thrush, severe headache, midline substernal discomfort with swallowing, visual changes including flashes of light, floaters, or visual field deficits

Mental health history

Past and current problems, evidence of depression (change in appetite, trouble sleeping, loss of interest in usual activities, anhedonia)

Family history

Age and health of children, including HIV tests if done; HIV in other family members; hypertension; type 2 diabetes; cardiovascular disease; malignancy

Medications

Prescription and over the counter; history of and attitude toward regular medication use; use of complementary and alternative therapies; drug allergies

Social history

Place of birth, where raised, who woman has lived with, child care responsibilities, housing status, history of interpersonal violence, education and occupational history, travel history, substance use or abuse, illicit drug use

Sources of support

Who has the woman told of her diagnosis, and what were their reactions? Does she have friends and family members she can talk to? Does she have a job? Does she have health insurance?

Patient education Source: Panel on Antiretroviral Guidelines for Adults and Adolescents. (2022). Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Department of Health and Human Services. https://clinicalinfo.hiv.gov/sites/default /files/guidelines/documents/adult-adolescent-arv/guidelines-adult-adolescent-arv.pdf; Thompson, M. A., Horberg, M. A., Agwu, A. L., Colasanti, J. A., Jain, M. K., Short, W. R., Singh, T., & Aberg, J. A. (2021). Primary care guidance for persons with human immunodeficiency virus: 2020 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clinical Infectious Diseases, 73(11), e3572–e3605. https:// doi.org/10.1093/cid/ciaa1391

Chapter 31  Women and HIV/AIDS 591

TABLE 31.5  Baseline HIV Laboratory Tests Serology

HIV antibody testing CD4 T lymphocyte count (T cell or CD4 cell count) ● Plasma HIV RNA (viral load) ● Genotypic resistance testing (testing may not be successful for patients with an HIV RNA level or viral load of ≤100 copies/mL) ● HLA B*5701 in patient being considered for abacavir therapy ● Complete blood count, including white blood cell count and differential ● Chemistry panel, including liver and renal function ● Lipid profile ● Syphilis ● Varicella-zoster virus if no history of chickenpox or shingles; immunity to measles, mumps, and rubella in persons born in 1957 or after ● Toxoplasmosis IgG, cytomegalovirus IgG, and cryptococcal antigen if the patient is symptomatic or CD4 count 500,000; Panel on Antiretroviral Guidelines for Adults and Adolescents, 2022). Refer to the Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV for a more detailed list of initial combination regimens for treatment-naïve persons. Preferred alternatives consist of two NRTIs plus an NNRTI or a PI boosted by cobicistat or ritonavir. Combination ART medications work together effectively to reduce the circulating viral load. With two different points of disruption of the replication cycle, concurrent use of these medications represents the best hope of managing HIV infection as a chronic illness. ART medications have demonstrated a high level of effectiveness in reducing viral load in persons who are adherent. Optimal adherence to ART can be challenging for some

persons with HIV as a result of several multilevel factors (e.g., stigma, mental health issues, and lack of access to care, health insurance, transportation, and social support). Poor adherence can result in detectable viral load, virologic failure, and ultimately drug resistance. Managing persons with resistance is complex and may require consultation with an HIV expert. Disparities are well documented. Compared to other persons with HIV, women with HIV have lower viral suppression rates (CDC, 2023). Disparities are even more evident among Black or African American women with HIV with lower rates of adherence and viral suppression compared to the White and Hispanic female counterparts (Geter et al., 2019). Reasons for poor adherence and viral suppression among Black/ African American women include stigma, discrimination, lack of child care and transportation, limited access to care, and low levels of resilience (Geter et al., 2019). Intense patient counseling to ensure maximal adherence to HAART is one crucial component of care for persons with HIV to prevent development of resistant virus and to maximize viral suppression. Identifying barriers and implementing evidence-based strategies to address social and structural barriers are also important components of care to maximize viral suppression. Patients on ART may have other chronic conditions requiring medications and frequent monitoring of lab values. For any patient for whom ART is initiated, the interactions between HIV medications and other medications the patient takes regularly must be examined. Furthermore, scheduling of medications to minimize untoward interactions is a critical component of care for these patients. Occupational and nonoccupational postexposure prophylaxis (PEP) with ART is recommended for people who are HIV-negative who have an exposure to HIV during sex, persons who were sexually assaulted, persons who shared needles or other equipment to inject drugs, and healthcare workers exposed through a needlestick injury or cut with a contaminated object, contact of a mucous membrane or nonintact skin with potentially infectious material or body fluids, or prolonged exposure (several minutes or more) of intact skin to potentially infectious materials (Workowski et al., 2015). PEP must be started within 72 hours after an exposure and taken daily for 28 days. Clinicians should consult an expert prior to starting ART for PEP. Clinicians may contact the National Clinician Consultation Center for PEP consultation (CDC, 1992).

Adherence to Antiretroviral Therapy Adherence to ART is crucial. A critical nursing challenge is to teach and counsel persons with HIV in adhering to the prescribed medication regimen. Failure to adhere to an ART protocol results in a rapid increase in viral load with concurrent immune system damage. The likelihood of developing AIDS is directly related to viral load. Simply, the presence of more virus means more immune system damage and a worsening ability to fend off aggressive opportunistic infections. The development of ART-resistant strains of virus is a primary concern in treatment failure and represents a serious sequela of nonadherence. Cross-resistance among treatment options limits the availability of effective therapy. Furthermore, the transmission of resistant strains complicates therapies for treatment-naïve patients, who may have few options available from the onset of the infection. Patients who fail to

594  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

follow their ART regimen as prescribed face the risk of developing a resistant strain of virus. The danger of nonadherence is dual: First, an increased viral load with a resistant virus is an alarming clinical situation associated with a poor outcome for the patient. Second, additional treatments for opportunistic infections, with their concomitant side effects, will be necessary as symptoms of advancing disease manifest themselves. Nurse practitioners have a distinct role in the preparation of patients as they begin ART. Effective nursing care must take into consideration the following issues related to the initiation of a treatment protocol that demands careful adherence: ●

●

●

●

What is the patient’s understanding of HIV? Nurse practitioners in settings that see HIV patients regularly may take for granted that patients have a more thorough understanding of HIV than they really do. With much of the knowledge about HIV filtered through rumor, innuendo, and incomplete or misleading media reports, patients may be woefully lacking in substantive knowledge of their disease. Recent developments in ART have allowed the healthcare professional to understand HIV as a chronic and manageable disease; however, this understanding has not reached all segments of the public. Emphasizing the chronic rather than fatal nature of the infection may help patients to reframe their understanding of the illness. Basic to the establishment of an effective nursing care plan is the thorough assessment of the patient’s understanding of the disease, including its meaning to the patient. Can the patient understand how the medications are to be taken? The patient may have a limited ability to understand the issues surrounding ART and adherence. It is incumbent on the nurse practitioner to ensure that the patient or the patient’s caregiver understands the importance of taking the medications as ordered. The nurse practitioner may have to be creative in devising charts, journals, pill boxes, or other reminders for the patient and the caregiver to enhance the chances of successful adherence. What is the patient’s daily schedule, and how does ART fit into the schedule? The nurse practitioner must consider shift work, sleep–wake patterns, mealtimes, and family responsibilities in assisting the patient in establishing a medication schedule to which the patient can adhere. If is it clear that the patient is likely to fail in following a complex schedule of medications in the context of a busy and active life, the nurse should consult with the physician or nurse practitioner in identifying alternative medications that may be more suitable for the patient. For example, the nurse or nurse practitioner can assess if the patient is eligible to switch to a single-tablet regimen. Are there any social constraints on the patient related to taking ART? ART represents the constant presence of HIV, an incurable infection that is fraught with social implications in addition to its health implications. Some persons find that the frequent reminder of the infection through taking ART is onerous and psychologically painful, lessening the likelihood of long-term adherence.

Many women keep their HIV infection a secret from their closest family members and friends. The presence of ART

medications in the home increases the risk that someone will discover the patient’s diagnosis. The patient must be counseled about that possibility and encouraged to think about the social implications if the HIV is discovered. Beginning ART represents a small step in going public with the diagnosis. The patient must understand that the pharmacist filling the prescriptions will know the patient’s diagnosis. The patient may prefer to have prescriptions filled in a place that is likely to offer more anonymity, such as a hospital pharmacy, HIV clinic pharmacy, or a discount store pharmacy with a high volume of business. Finances may be an important consideration for the patient, who may have to seek outside sources of funds to enable the purchase of ART. The goal for nurse practitioners is always the same; patients will adhere to their ART schedules as evidenced by decreasing and ultimately nondetectable viral loads, maintaining that level for as long as possible. Simply handing a patient several prescriptions for expensive medications requiring complicated schedules and having a number of uncomfortable and potentially serious side effects is likely to result in treatment failure. Nurse practitioners are in a unique position to make a substantial positive impact on the lives of persons living with HIV by spending time in careful assessment, planning, intervening, and goal setting.

Prevention of Opportunistic Infections In the 40 years since the identification of HIV/AIDS, great improvements have been made in the prevention of opportunistic infections that ravaged the earliest victims of the HIV pandemic. Increasingly, aggressive use of ART has helped in maintaining the immune systems of persons with HIV, reducing the need for routine chemoprophylaxis against opportunistic infections. Furthermore, infections such as Pneumocystis pneumonia (PCP), toxoplasmosis, and other bacterial diseases have been effectively prevented in patients requiring chemoprophylaxis. A single daily dose of double-strength trimethoprim-sulfamethoxazole (Septra, Bactrim) has reduced the incidence of PCP, toxoplasmosis, and bacterial infections (Panel on Antiretroviral Guidelines for Adults and Adolescents, 2022). This is a particularly useful medication because it is effective, generally well tolerated, simple to take, and inexpensive. However, for those who are sensitive to or allergic to trimethoprim-sulfamethoxazole, dapsone is an effective alternative. Persons with HIV should follow some specific, although not overly restrictive, guidelines regarding minimizing exposure to potential sources of opportunistic infection. For women who are likely to be managing the care of the home and children, understanding how to preserve and maintain her own health while fulfilling her household and parenting obligations is very important. Nurse practitioners should counsel women in basic good hygiene practices that can minimize the risk of many exposures. These practices include: ●

Thorough handwashing with water and soap after toileting, after assisting children in toileting, and at intervals throughout the day. Paper towels in the bathroom provide a more sanitary means of drying hands than a hand towel that stays damp and may be used by others.

Chapter 31  Women and HIV/AIDS 595 ●

●

●

●

●

Minimizing exposure to animal or human waste by using disposable gloves. This includes wearing disposable gloves when doing yard work and when changing a baby’s diaper. Drinking water only from sources known to be dependable and clean; avoiding ingestion of water from lakes, rivers, and recreational swimming pools. Avoiding contact with animals in specific circumstances: ❍ Pets younger than 6 months old (increased likelihood of exposure to parasites) ❍ Any animal with diarrhea ❍ All reptiles: turtles, lizards, snakes, iguanas (risk of salmonella exposure) ❍ Situations that may expose the patient to bird droppings Treating cats with special care: ❍ Adopting cats that are more than 1 year old (risk of exposure to bacteria and parasites) ❍ Daily cleaning of litter box, preferably by a person without HIV ❍ Keeping the cat indoors, not allowing the cat to hunt ❍ Avoiding cat scratches or bites and washing scratches or bites thoroughly and immediately ❍ Controlling fleas on cats Avoiding raw or undercooked eggs, poultry, meat, or seafood, and preventing cross-contamination by using separate kitchen utensils and cutting boards when processing these foods. Cutting boards should be thoroughly scrubbed after each use. Careful kitchen and cooking practices can decrease greatly the risk of foodborne infection.

In addition, HIV-positive patients should be counseled to consult with a healthcare provider before traveling to developing countries that may result in exposure to opportunistic pathogens. The CDC website (https://wwwnc.cdc.gov/travel) provides travelers with up-to-date information regarding endemic diseases and recommendations regarding vaccinations before travel. Basic health practices, such as family planning (Table 31.7), adequate sleep and rest, good nutrition, exercise, smoking cessation, and avoidance of stress should not be overlooked in counseling HIV-positive persons. Family planning choices and possible birth control options should be discussed. Vertical transmission and medical interventions should be addressed. Seven to 8 hours of sleep a night is ideal for most adults. This amount may be difficult to achieve; however, nurse practitioners can assist the patient in developing a sleep schedule that allows adequate rest. Principles of good nutrition apply to persons with HIV and, in fact, are especially necessary to provide adequate vitamins, minerals, electrolytes, and protein. Persons with HIV who are significantly under- or overweight should be encouraged to improve their nutritional status through support groups, nutritional counseling, or other means of weight management. Persons with a high intake of alcohol should be counseled to decrease their intake, because alcohol does not have any significant nutritional value, can interfere with vitamin absorption, and contains excess calories. Furthermore, chronic alcohol abuse can exacerbate liver problems. It is important to note

TABLE 31.7  Contraception for Women With HIV METHOD

BENEFITS

DISADVANTAGES

Male condom

Protects against STIs and HIV; protects partner

Partner cooperation required

Female condom

Protects against STIs and HIV; protects partner

Partner cooperation helpful

Oral contraceptive

Effective when used consistently

Some HIV medications may reduce the effectiveness of hormonal contraceptives No HIV protection for partner No STI protection Risk of cervical ectopy Possible interaction with antibiotics and antiretrovirals

Depo-Provera injection

Effective Limited compliance needed

No STI protection No HIV protection for partner

Intrauterine device

Effective

No HIV protection for partner No STI protection

Diaphragm

Effective Female controlled

Leave in 6–8 hours after ejaculation May increase risk of urinary tract infection

Patch

Avoids first-pass metabolism Easy to use

No STI protection No HIV protection for partner

Tubal ligation

One-time procedure Permanent

No STI protection No HIV protection for partner

STIs, sexually transmitted infections. Source: HIV.gov. (2023). Recommendations for the use of antiretroviral drugs during pregnancy interventions to reduce perina­tal HIV transmission in the United States. https://clinicalinfo.hiv.gov/en/guidelines/perinatal/whats-new; Cotter, A., Potter, J. E., & Tessler, N. (2006). Management of HIV/AIDS in women. In J. Beal, J. J. Orrick, & K. Alfonso (Eds.), HIV/AIDS primary care guide (pp. 533–546). Crown House.

that excessive alcohol intake will impair one’s ability to make good judgments regarding health and sexual behaviors and to adhere to the ART regimen. Exercise improves muscle tone and cardiovascular health and reduces stress—all important factors in maintaining a state of health. HIV-positive persons should be encouraged to engage in some form of exercise on a regular basis. Nurse practitioners can assist the patient in identifying simple means of increasing activity, even if the patient is somewhat debilitated or reluctant to engage in regular workouts. Walking is a simple form of exercise that is within the abilities of most persons and can be incorporated into one’s daily routine with little effort. Patients should be encouraged and supported in their efforts to stop smoking. In addition to the well-documented negative effects of smoking on health, the propensity of

596  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

HIV-positive persons to pulmonary infections makes smoking cessation imperative. Nurse practitioners should be cognizant of the difficulty of stopping smoking and support any efforts the patient makes to decrease the number of cigarettes per day. However, the nurse practitioner is also in an excellent position to help the patient find therapies, group support, and other means to stop smoking. Stress reduction plays an important role in health maintenance. Nurse practitioners can assist patients in identifying changeable stressors and in developing strategies to decrease overall stress. Many persons with HIV have significant social stressors related to poverty and other sociocultural issues that may be difficult to ameliorate. Nurse practitioners can help these patients understand management of their HIV infection to lessen the effects of HIV on their lives. An important nursing intervention, then, is to help HIV patients understand the chronic, manageable aspects of the infection. Careful planning with patients in terms of making regular clinic visits, initiating and adhering to an ART regimen, and improving general health behaviors can be an effective means of reducing some of the HIV-related stresses for these patients.

SPECIAL POPULATIONS Women With HIV of Childbearing Age Special considerations must be taken into account when managing HIV in women of childbearing age. The goals of their treatment include improving overall health and quality of life, minimizing disease progression, minimizing unwanted pregnancies, preventing heterosexual transmission, and avoiding prescribing medical treatments with teratogenic potential. Comprehensive reproductive and sexual health counseling are essential for women with HIV. There are benefits and drawbacks of various contraceptives. Some HIV medications may reduce the effectiveness of hormonal contraceptives (see Table 31.7). Barrier methods are necessary for HIV and STI prevention. The effect of hormonal contraceptives on viral shedding is not clear, and the bioavailability of ethinyl estradiol in hormonal contraceptives may be significantly reduced by some antiretroviral medications, including ritonavir, cobicistat, or ritonavir-boosted protease inhibitors. Women using oral contraceptive methods, an intrauterine device, or tubal ligation should be counseled to use a barrier method as well to reduce the risk of contracting an STI or transmitting HIV or an STI to her partner. It is essential that APRNs be aware of the drug interactions between oral contraceptives and ART, because some of the interactions may compromise the effectiveness of either the contraceptive method by lowering oral contraceptive drug levels (e.g., nevirapine, ritonavir) or lowering the effectiveness of the ART (Panel on Antiretroviral Guidelines for Adults and Adolescents, 2022). Clinicians should refer to Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States (HIV.gov, 2023).

HIV in Pregnancy Childbearing in women with HIV is a complex issue to be addressed carefully and thoroughly by clinicians working with this population. Reproduction is a major life activity and refusing to help someone based solely on their HIV status is considered illegal discrimination. Couples with HIV or serodiscordant couples should not be denied assisted reproductive techniques based solely on their seropositive status (Chambers et al., 2021; Jaideep et al., 2021). Preconception counseling for women known to have HIV is an important means of optimizing maternal health before pregnancy. Elements of preconception counseling for women with HIV should include appropriate contraceptive methods to reduce unintended pregnancy; safer sex practices; avoidance of alcohol, illicit drug use, and cigarette smoking; risk factors of perinatal transmission and effective strategies to reduce and prevent transmission; and potential effects of HIV on pregnancy and maternal health (Panel on Antiretroviral Guidelines for Adults and Adolescents, 2022). Elements to be considered in providing care to women with HIV considering pregnancy include avoiding antiretroviral agents with a potential for teratogenicity, achieving and sustaining suppressed HIV-1 RNA, evaluating the need for prophylaxis or preconception immunizations (influenza, pneumococcal, hepatitis B), optimizing nutritional status and folic acid supplementation, evaluating for opportunistic infections and initiating appropriate treatments or prophylactic regimens, screening for psychiatric and substance abuse disorders and domestic violence, standard genetic and reproductive health screening, and planning for pediatric and perinatal consultation (Panel on Antiretroviral Guidelines for Adults and Adolescents, 2022). Protection of the health of the pregnant woman and the fetus is the primary therapeutic goal in all prenatal and perinatal care, and this goal is the same for all women regardless of their HIV status. For women with HIV, minimizing the risk of vertical transmission is an additional therapeutic goal. Without intervention, HIV is effectively transmitted from mother to child. Before antiretroviral prophylaxis use, vertical transmission rates ranged from 13% to 32% in industrialized countries. Transmission can occur at any time during a pregnancy; however, without any prevention measures, most transmission occurs during the intrapartum period (HIV. gov, 2023). Factors affecting vertical transmission are found in Table 31.8. Perinatal transmission of HIV to the fetus has decreased significantly in the past decade to less than 1% in the United States because of the prophylactic administration of antiretroviral prophylaxis to pregnant women in the prenatal and perinatal periods. Healthcare providers should follow the same guidelines used for women who are not pregnant (CDC, 2022a). During labor, women take HIV medicines to reduce the risk of mother-to-child transmission. The newborn infant then receives HIV medicines from birth up to 6 weeks of life, beginning within 6 hours after birth (Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission, 2012). Breastfeeding is not recommended in the United States (Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission, 2022).

Chapter 31  Women and HIV/AIDS 597

TABLE 31.8  Factors Affecting Vertical HIV Transmission DISEASE-RELATED FACTORS

Maternal HIV-1 RNA (plasma and genital tract) Maternal CD4+ count Viral genotype and phenotype Viral resistance mutations

MATERNAL HEALTH AND SOCIAL FACTORS

Clinical stage STIs during pregnancy Vitamin A deficiency Ongoing intrauterine device Tobacco and substance use Multiple sexual partners during pregnancy

OBSTETRIC FACTORS

Duration of ruptured membranes Chorioamnionitis from use of invasive antenatal procedures Mode of delivery

INFANT FACTORS

Prematurity Breastfeeding Developing immune system Gastrointestinal factors

STIs, sexually transmitted infections. Source: Amin, O., Powers, J., Bricker, K. M., & Chahroudi, A. (2021). Understanding viral and immune interplay during vertical transmission of HIV: Implications for cure. Frontiers in Immunology, 12, 757400. https://doi.org/10.3389/fimmu.2021.757400

Use of ART during pregnancy involves two aims: (1) improve maternal health and (2) reduce mother-to-child transmission. As with nonpregnant women, decisions regarding therapy initiation and selection should be based on standard clinical criteria, applicable to all adults with HIV. Balancing potentially conflicting needs of mother and infant health may be challenging because data regarding the safety, efficacy, and pharmacokinetics of ART in pregnancy may be limited, particularly with newer drugs. Women who are pregnant or considering pregnancy must be counseled regarding the potential short- and long-term risks and benefits associated with antiretroviral management strategies. Clinicians should refer to Recommendations for Use of Antiretroviral Drugs During Pregnancy (Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission, 2012). Before the widespread use of HAART, elective cesarean was routinely recommended as the preferred delivery method for women with HIV. Whether cesarean delivery continues to be the optimal method of delivery today, given that current transmission rates are very low and multiagent chemoprophylaxis is the norm, has not been established (Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission, 2012). The Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission (2012) advise that women with HIV-1 RNA greater than 1,000 copies/mL in the third trimester should be counseled regarding the potential benefits of elective cesarean delivery. Breastfeeding has been implicated in the transmission of HIV. The current recommendation is that HIV-positive mothers in the United States formula-feed their infants to avoid possible transmission of the virus (Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission, 2012). However, in developing countries, women may not have access to safe alternatives to breast milk for their infants. Mothers face the difficult issue regarding guardianship of their children in the event of their death. Women with HIV are more likely to be poor and may have limited financial and social support. A single mother may have little or no contact with the father of her children, or he may be a poor candidate for parenting the children full-time. Making choices regarding her children’s welfare may be difficult at best, and impossible if she has severely limited familial or social support. She may face the possibility that her children will be placed into foster care if she becomes very ill or dies. Nurse practitioners

can assist HIV-infected mothers in expressing fear and grief over this possible, if not likely, scenario. Furthermore, nurse practitioners can assist the woman in seeking community services dedicated to managing the legal affairs of persons with HIV if those services are available. HIV case managers at the local level can also assist HIV-infected women in making decisions about the eventual care of their children. Women who address this issue early after their diagnosis may feel relieved that the issue of guardianship is resolved and formalized.

Incarcerated Women Incarcerated women are 15 times more likely to be HIV infected than women in the general population because the behaviors for which they are incarcerated place them at higher risk (CDC, 2015a, 2015c). They are often victims of substance abuse including injection drugs, have partners who are IDUs, have experienced intimate partner violence, or have been forced to have unprotected sex and/or trade sex for food or housing. Often, they have few or no marketable job skills, have little or no access to HIV prevention methods, and are afraid to ask their partners to use protection. Prevention challenges include a lack of awareness about HIV and lack of resources for HIV testing and treatment in prisons. Although prisons are more likely to have HIV programs, most incarcerated individuals are detained in jails (Workowski et al., 2015). Most jail inmates are released within 72 hours and the rapid turnover in jail populations contributes to a lack of testing and connection with treatment. Additionally, inmate concerns regarding privacy and fear of stigma lead to a lack of disclosure of high-risk behaviors.

Transgender Women Persons who are transgender identify as a gender that is not the same as the sex assigned to them at birth. Transgender women identify as women but were born with male anatomy. Transgender women account for 2% of HIV infection in the United States and most new infections are among Black/African American transgender women and transgender women living in the U.S. South (CDC, 2021a). Transgender persons are more likely to access care when services are provided in a gender-affirming environment (e.g., use of chosen name and pronoun). Providers caring for transgender women should

598  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

have knowledge of their patients’ current anatomy and patterns of sexual behavior before counseling them about STI/ HIV prevention. For transgender women with HIV, clinicians should provide comprehensive care based on the personalized needs of the individual.

SUMMARY HIV is associated with multifaceted dimensions of morbidity, mortality, and societal costs that are often disproportionately experienced by women and their infants. The need for prevention is critical, and nurse practitioners must assume a primary role in helping women decrease risky behaviors and increase protective practices as well as HIV testing.

FUTURE DIRECTIONS To decrease the burden of HIV on women, screening, early detection, and treatment are essential. Again, nurse practitioners are a first-line defense in providing these services. Finally, treatment of HIV can lessen the impact of the disease. Education and counseling are essential to ensure that women obtain the maximum benefit from treatment.

REFERENCES Agénor, M., Koma, J. W., Pérez, A. E., McDowell, A., & Gonzales, G. (2023). Differences in health insurance and usual source of care among racial/ethnic and sexual orientation subgroups of US women and men. Population Research and Policy Review, 42(3), 33. https://doi.org/10.1007/s11113-023 -09774-2 Andrews, M. M., Storm, D. S., Burr, C. K., Aaron, E., Hoyt, M. J., Statton, A., & Weber, S. (2018). Perinatal HIV service coordination: Closing gaps in the HIV care continuum for pregnant women and eliminating perinatal HIV transmission in the United States. Public Health Reports, 133(5), 532–542. https://doi.org/10.1177/0033354918789912 Bennett, B. (2006). HIV testing. In J. Beal & J. J. Orrick (Eds.), HIV/AIDS primary care guide (pp. 9–16). Crown House. Bhatia, M. S., & Munjal, S. (2014). Prevalence of depression in people living with HIV/AIDS undergoing ART and factors associated with it. Journal of Clinical and Diagnostic Research, 8(10), WC01–WC04. https://doi.org/10.7860 /JCDR/2014/7725.4927 Bordogna, A. L., Coyle, A. C., Nallamothu, R., Manko, A. L., & Yen, R. W. (2023). Comprehensive sexuality education to reduce pregnancy and STIs in adolescents in the United States: A systematic review and meta-analysis. American Journal of Sexuality Education, 18(1), 39–83. https://doi.org/10.1080/15546128 .2022.2080140 Bosh, K. A., Hall, H. I., Eastham, L., Daskalakis, D. C., & Mermin, J. H. (2021). Estimated annual number of HIV infections—United States, 1981–2019. Morbidity and Mortality Weekly Report, 70(22), 801. https://doi .org/10.15585/mmwr.mm7022a1 Cameron, J. E., Dennis, D. A. C., Herrel, N. R., Chapple, A. G., & Hagensee, M. E. (2020). Risk of abnormal cervical cytology in HIV-infected women testing positive for both human papillomavirus and Epstein-Barr virus in genital tract specimens. Cancer Causes & Control, 31, 365–375. https://doi .org/10.1007/s10552-020-01287-z Centers for Disease Control and Prevention. (1981). Pneumocystis pneumonia—Los Angeles. MMWR Morbidity and Mortality Weekly Report, 30(21), 250–252. https://www.cdc.gov/mmwr/preview/mmwrhtml/june_5.htm

Centers for Disease Control and Prevention. (1992). 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Morbidity and Mortality Weekly Report Recommendations and Reports, 41(RR-17), 1–19. https://www.cdc.gov /mmwr/preview/mmwrhtml/00018871.htm Centers for Disease Control and Prevention. (2007). HIV/AIDS surveillance report, 2005 (Vol. 17, Rev. ed., pp. 1–54). U.S. Department of Health and Human Services. https://www.cdc.gov/hiv/pdf/statistics_2005_hiv_surveillance _report_vol_17.pdf Centers for Disease Control and Prevention. (2012). HIV transmission risk. http://www.cdc.gov/hiv/law/pdf/Hivtranmsmision.pdf Centers for Disease Control and Prevention. (2015a). HIV among incarcerated populations. https://www.cdc.gov/hiv/group/correctional.html Centers for Disease Control and Prevention. (2015b). HIV in the United States: At a glance. https://www.cdc.gov/hiv/statistics/overview/ataglance.html Centers for Disease Control and Prevention. (2016). Leading causes of death— Females—Non-Hispanic black—United States, 2016. https://www.cdc.gov /women/lcod/2016/nonhispanic-black/index.htm Centers for Disease Control and Prevention. (2018). Standard precautions. https:// www.cdc.gov/oralhealth/infectioncontrol/summary-infection-prevention -practices/standard-precautions.html Centers for Disease Control and Prevention. (2019a). HIV and occupational exposure. https://www.cdc.gov/hiv/workplace/healthcareworkers.html Centers for Disease Control and Prevention. (2019b). HIV and women. https://www .cdc.gov/hiv/group/gender/women/index.html Centers for Disease Control and Prevention. (2019c). HIV in the Southern United States. https://www.cdc.gov/hiv/pdf/policies/cdc-hiv-in-the-south-issue -brief.pdf Centers for Disease Control and Prevention. (2021a). HIV prevention. https:// www.cdc.gov/hiv/basics/prevention.html Centers for Disease Control and Prevention. (2021b). HIV surveillance supple­ mental report: Estimated HIV incidence and prevalence in the United States, 2015–2019 (Vol. 26, No. 1). https://www.cdc.gov/hiv/library/reports/hiv -surveillance.html Centers for Disease Control and Prevention. (2021c). STI treatment guidelines: 2021 recommendations now available. https://www.cdc.gov/std/treatment -guidelines/default.htm Centers for Disease Control and Prevention. (2022a). HIV and women: HIV incidence. https://www.cdc.gov/hiv/group/gender/women/incidence.html Centers for Disease Control and Prevention. (2022b). HIV in the United States and dependent areas. https://www.cdc.gov/hiv/statistics/overview/ataglance .html Centers for Disease Control and Prevention. (2022c). HIV in the United States by region. https://www.cdc.gov/hiv/statistics/overview/geographicdistribution .html Centers for Disease Control and Prevention. (2022d). Protecting others. https:// www.cdc.gov/hiv/basics/livingwithhiv/protecting-others.html Centers for Disease Control and Prevention. (2022e). STDs and HIV—CDC detailed fact sheet. https://www.cdc.gov/std/hiv/stdfact-std-hiv-detailed.htm Centers for Disease Control and Prevention. (2023). HIV and women: Viral suppression and barriers to care. https://www.cdc.gov/hiv/group/gender /women/viral-suppression.html Chakraborty, H. (2016). Determinants of intimate partner violence among HIV-positive and HIV-negative women in India. Journal of Intimate Partner Violence, 31(3), 515–530. https://doi.org/10.1177/0886260514555867 Chambers, G. M., Dyer, S., Zegers-Hochschild, F., de Mouzon, J., Ishihara, O., Banker, M., Mansour, R., Kupka, M. S., & Adamson, G. D. (2021). International committee for monitoring assisted reproductive technologies world report: Assisted reproductive technology, 2014. Human Reproduction, 36(11), 2921–2934. https://doi.org/10.1093/humrep/deab198 Chipphindale, S., & French, L. (2001). HIV counselling and the psychosocial management of patients with HIV or AIDS. British Medical Journal, 322(7301), 1533–1535. https://doi.org/10.1136/BMJ.322.7301.1533 Derose, K. P., Griffin, B. A., Kanouse, D. E., Bogart, L. M., Williams, M. V., Haas, A. C., Flórez, K. R., Collins, D. O., Hawes-Dawson, J., Mata, M. A., Oden, C. W., & Stucky, B. D. (2016). Effects of a pilot church-based intervention to reduce HIV stigma and promote HIV testing among African Americans and Latinos. AIDS and Behavior, 20(8), 1692–1705. https://doi.org/10.1007 /s10461-015-1280-y DesLauriers, N., Sambai, B., Mbogo, L., Ludwig-Barron, N., Kingston, H., Chohan, B., Gitau, E., Sinkele, W., Masyuko, S., Herbeck, J., Bukusi, D., Guthrie, B. L., Farquhar, C., & Monroe-Wise, A. (2023). Alcohol use among people who inject drugs living with HIV in Kenya is associated with needle sharing, more new sex partners, and lower engagement in HIV care. AIDS and Behavior, 1–11. https://doi.org/10.1007/s10461-023-04113-0

Dickson, M. F., Tillson, M., Calvert, J. M., & Staton, M. (2023). Transactional sex among rural, justice‐involved Appalachian women who use drugs. The Journal of Rural Health. https://doi.org/10.1111/jrh.12741 Dong, M., Dong, Y., Bai, J., Li, H., Ma, X., Li, B., Wang, C., Li., H., Qi, W., Wang, Y., Fan, A., Han, C., & Xue, F. (2023). Interactions between microbiota and cervical epithelial, immune, and mucus barrier. Frontiers in Cellular and Infection Microbiology, 13, 1124591. https://doi.org/10.3389/fcimb.2023.1124591 Geter, A., Sutton, M. Y., Armon, C., Buchacz, K., & HIV Outpatient Study Investigators. (2019). Disparities in viral suppression and medication adherence among women in the USA, 2011–2016. AIDS and Behavior, 23(11), 30153023. https://doi.org/10.1007/s10461-019-02494-9 Ghosh, M., Rodriguez-Garcia, M., & Wira, C. R. (2013). Immunobiology of genital tract trauma: Endocrine regulation of HIV acquisition in women following sexual assault or genital tract mutilation. American Journal of Reproductive Immunology, 69, 51–60. https://doi.org/10.1111/AJI.12027 Glaubius, R., Kothegal, N., Birhanu, S., Jonnalagadda, S., Mahiane, S. G., Johnson, L. F., Brown, T., Stover, J., Mangal, T. D., Pantazis, N., & Eaton, J. W. (2021). Disease progression and mortality with untreated HIV infection: Evidence synthesis of HIV seroconverter cohorts, antiretroviral treatment clinical cohorts and population‐based survey data. Journal of the International AIDS Society, 24, e25784. https://doi.org/10.1002/jia2.25784 Grant, R. M., Anderson, P. L., McMahan, V., Liu, A., Amico, K. R., Mehrotra, M., Mosquera, C., Casapia, M., Montoya, O., Buchbinder, S., Veloso, V. G., Mayer, K., Chariyalertsak, S., Bekker, L. G., Hosek, S., Kallas, E. G., Schechter, M., Glidden, D., & iPrEx study team (2014, July 20–25). Results of the iPrEx open-label extension (iPrEx OLE) in men and transgender women who have sex with men: PrEx uptake, sexual practices, and HIV incidence. 20th International AIDS Conference. Melbourne, Australia. https://www.mdlinx. com/infectious-disease/conference-abstract.cfm/18761 Grossman, H. (2017). The overlooked secondary benefits of PrEP. TheBodyPro. https://www.thebodypro.com/article/the-overlooked-secondary-benefits -of-prep Hatcher, R. A., Trussell, J., Nelson, A., Cates, W., Kowal, D., & Policar, M. (2011). Contraceptive technology. Springer Publishing Company. Herbeck, J., Mittler, J., Gottlieb, G., Goodreau, S., Murphy, J., Cori, A., Pickles, M., & Fraser, C. (2016). Evolution of HIV virulence in response to widespread scale up of antiretroviral therapy: A modeling study. Virus Evolution, 2(2), vew028. https://doi.org/10.1093/ve/vew028 Hessol, N. A., Gandhi, M., & Greenblatt, R. M. (2005). Epidemiology and natural history of HIV infection in women. In J. R. Anderson (Ed.), A guide to the clinical care of women with HIV (pp. 1–34). Department of Health and Human Services, HIV/AIDS Bureau. HIV.gov. (2022). Impact on racial and ethnic minorities. https://www .hiv.gov/hiv-basics/overview/data-and-trends/impact-on-racial-and-ethnic -minorities HIV.gov. (2023). Recommendations for the use of antiretroviral drugs during pregnancy interventions to reduce perina­tal HIV transmission in the United States. https://clinicalinfo.hiv.gov/en/guidelines/perinatal/whats-new HIVinfo. (2021a). HIV and women. National Institutes of Health. https://hivinfo .nih.gov/understanding-hiv/fact-sheets/hiv-and-women HIVinfo. (2021b). HIV treatment: The basics. National Institutes of Health. https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-treatment-basics Hutchinson, M., Cosh, S. M., & East, L. (2023). Reproductive and sexual health effects of intimate partner violence: A longitudinal and intergenerational analysis. Sexual & Reproductive Healthcare, 35, 100816. https://doi .org/10.1016/j.srhc.2023.100816 Jaideep, M., Malhotra, K., Talwar, P., Kannan, P., Singh, P. P., Kumar, Y., Chimote, N., Joshi, C., Bawle, S., Agarwal, R. B., Agarwal, S., Prakash, V., Awashti, P., Shukla, S., Prakash, R., & Adiga, S. K. (2021). ISAR consensus guidelines on safety and ethical practices in in vitro fertilization clinics. Journal of Human Reproductive Sciences, 14(Suppl. 1), S48–S68. https://doi .org/10.4103/0974-1208.330504 Kaiser Family Foundation. (2021). The HIV/AIDS epidemic in the United States: The basics. https://www.kff.org/hivaids/fact-sheet/the-hivaids-epidemic-in -the-united-states-the-basics Kalibala, S., Oweya, E., & Phiri, L. (2016). Relationship between socio demographic characteristics and HIV indicators among women in Kenya, Tanzania, Uganda, Rwanda, Zambia and Malawi based on DHS data. International Journal of Women’s Health Wellness, 2, 024. https://doi .org/10.23937/2474-1353/1510024 Kwakwa, H. A., & Ghobrial, M. W. (2003). Female-to-female transmission of human immunodeficiency virus. Clinical Infectious Diseases, 36, e40–e41. https://doi.org/10.1086/345462 Lacombe-Duncan, A. (2016). An intersectional perspective on access to HIV-related healthcare for transgender women. Transgender Health, 1(1), 137–141. https://doi.org/10.1089/trgh.2016.0018

Landovitz, R. J. (2016). Optimizing delivery of preexposure prophylaxis— The next frontier. JAMA Internal Medicine, 176(1), 85–86. https://doi .org/10.1001/jamainternmed.2015.6530 Lunn, M. R., Cui, W., Zack, M. M., Thompson, W. W., Blank, M. B., & Yehia, B. R. (2017). Sociodemographic characteristics and health outcomes among lesbian, gay, and bisexual US adults using healthy people 2020 leading health indicators. LGBT Health, 4(4), 283–294. https://doi.org/10.1089/lgbt.2016.0087 Maman, S., Campbell, J., Sweat, M. D., & Gielen, A. C. (2000). The intersections of HIV and violence: Directions for future research and interventions. Social Science & Medicine, 50(4), 459–478. https://doi.org/10.1016/s0277 -9536(99)00270-1 Migueles, S. A., & Connors, M. (2010). Long-term nonprogressive disease among untreated HIV-infected individuals: Clinical implications of understanding immune control of HIV. JAMA, 304(2), 194–201. https://doi.org/10.1001 /jama.2010.925 Miller, W. C., Rosenberg, N. E., Rutstein, S. E., & Powers, K. A. (2010). The role of acute and early HIV infection in the sexual transmission of HIV. Current Opinion in HIV and AIDS, 5(4), 277–282. https://doi.org/10.1097/COH .0B013E32833A0D3A Minkin, M. J. (2016). Sexual health and relationships after age 60. Maturitas, 83, 27–32. https://doi.org/10.1016/j.maturitas.2015.10.004 Moscicki, A. B., Flowers, L., Huchko, M. J., Long, M. E., MacLaughlin, K. L., Murphy, J., Spiryda, L. B., & Gold, M. A. (2019). Guidelines for cervical cancer screening in immunosuppressed women without HIV infection. Journal of Lower Genital Tract Disease, 23(2), 87–101. https://doi.org/10.1097/LGT .0000000000000468 Nabayinda, J., Namirembe, R., Kizito, S., Nsubuga, E., Nabunya, P., Sensoy Bahar, O., Magorokosho, N., Kiyingi, J., Nattabi, J., Tozan, Y., Jennings Mayo-Wilson, L., Mwebembezi, A., Witte, S. S., & Ssewamala, FM. (2023). Correlates of intimate partner violence among young women engaged in sex work in southern Uganda. Journal of Interpersonal Violence. https://doi .org/10.1177/08862605231175908 National Institutes of Health. (2021a). HIV and mental health. https://hivinfo .nih.gov/understanding-hiv/fact-sheets/hiv-and-mental-health National Institutes of Health. (2021b). The stages of HIV infection. https://hivinfo .nih.gov/understanding-hiv/fact-sheets/stages-hiv-infection Panel on Antiretroviral Guidelines for Adults and Adolescents. (2022). Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Department of Health and Human Services. https://clinicalinfo.hiv.gov /sites/default/files/guidelines/documents/adult-adolescent-arv/guidelines -adult-adolescent-arv.pdf Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. (2012). Recommendations for use of antiretroviral drugs in pregnant HIV-1 infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States (pp. 1–235). https://npin .cdc.gov/publication/recommendations-use-antiretroviral-drugs-pregnant -hiv-1-infected-women-maternal-health Pilcher, C. D., Tien, H. C., Eron, J. J., Vernazza, P. L., Leu, S. Y., Stewart, P. W., Goh, L. E., & Cohen, M. S. (2004). Brief but efficient: Acute HIV infection and the sexual transmission of HIV. Journal of Infectious Diseases, 189, 1785–1792. https://doi.org/10.1086/386333 Relf, M. V., Pan, W., Edmonds, A., Ramirez, C., Amarasekara, S., & Adimora, A. A. (2019). Discrimination, medical distrust, stigma, depressive symptoms, antiretroviral medication adherence, engagement in care, and quality of life among women living with HIV in North Carolina: A mediated structural equation model. Journal of Acquired Immune Deficiency Syndromes, 81(3), 328–335. https://doi.org/10.1097/QAI.0000000000002033 Scott, S. B., Knopp, K., Yang, J. P., Do, Q. A., & Gaska, K. A. (2023). Sexual minority women, health care discrimination, and poor health outcomes: A mediation model through delayed care. LGBT Health, 10(3), 202–210. https://doi.org/10.1089/lgbt.2021.0414 Smith, D. K., Koenig, L. J., Martin, M., Mansergh, G., Heneine, W., Ethridge, S., Morgan, M., Mermin, J., Fenton, K., & CDC PrEP Guidelines Writing Team. (2014). Pre-exposure prophylaxis for the prevention of HIV infection in the United States—2014. A clinical practice guideline (pp. 1–67). https:// www.sfdph.org/dph/files/newsMediadocs/2014PR/PrEPguidelines2014.pdf Thompson, M. A., Horberg, M. A., Agwu, A. L., Colasanti, J. A., Jain, M. K., Short, W. R., Singh, T., & Aberg, J. A. (2021). Primary care guidance for persons with human immunodeficiency virus: 2020 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clinical Infectious Diseases, 73(11), e3572–e3605. https://doi.org/10.1093/cid /ciaa1391 Tran, B. X., Ho, R. C. M., Ho, C. S. H., Latkin, C. A., Phan, H. T., Ha, G. H., Vu, G. T., Ying, J., & Zhang, M. W. B. (2019). Depression among patients with HIV/ AIDS: Research development and effective interventions (GAPRESEARCH).

International Journal of Environmental Research and Public Health, 16(10), 1772. https://doi.org/10.3390/IJERPH16101772 U.S. Food and Drug Administration. (2021, December). Highlights of prescribing information: Apretude. https://www.accessdata.fda.gov/drugsatfda_docs /label/2021/215499s000lbl.pdf

Woolweaver, A. B., Drescher, A., Medina, C., & Espelage, D. L. (2023). Leveraging comprehensive sexuality education as a tool for knowledge, equity, and inclusion. Journal of School Health, 93(4), 340–348. https://doi.org/10.1111 /josh.13276

Chapter

32

Human Papillomavirus Elizabeth A. Kostas-Polston,* Versie Johnson-Mallard,

ANOGENITAL HUMAN PAPILLOMAVIRUS–RELATED DISEASE There was a time when our understanding of the human papillomavirus (HPV) and its role in anogenital disease was limited. The discovery of the Pap smear 75 years ago by Dr. George Papanicolaou led to the subsequent discovery made by Dr. Harald zur Hausen regarding HPV as the necessary cause of cervical cancer and other anogenital diseases. Clinical evidence supporting cervical cancer screening guidelines—perhaps the most successful cancer screening model in the United States (National Cancer Institute [NCI], 2014)— have helped to make great strides in our understanding of the natural history of HPV, its association with sexual transmission, and the role it plays in anogenital disease and cancer. HPV infection may lead to disease and cancer in primarily anogenital sites (e.g., cervix, vulva, vagina, anus, and penis). HPV has more recently been associated with oropharyngeal and other head and neck diseases and cancer. This chapter focuses on anatomic sites where HPV infection wreaks much of its havoc in women, namely, the cervix and the anus.

Definition and Scope According to the Centers for Disease Control and Prevention (CDC), HPV infection is the most common sexually transmitted infection (STI) in the United States (CDC, 2015, 2021). It is estimated that in 2015 there were 79 million individuals in the United Stated infected with HPV. It is estimated that each year in the United States approximately 37,300 new cases of HPV-related cancers are diagnosed (CDC, 2021). Additionally, 14 million people will become infected yearly with HPV (CDC, 2015, 2021). In fact, it is postulated that greater than 90% of sexually active individuals will develop an HPV infection during their lifetime (CDC, 2015; Chesson et al., 2014).

and

Naomi Jay

HPV-associated morbidity includes external genital warts (EGWs) and cancer precursors. Cancer precursors may lead to HPV-associated cancer. A necessary requisite for transformation to occur (from a precursor to carcinoma) is persistent infection, which is not a common occurrence (~10% persistence; CDC, 2021). The female anatomic sites infected by HPV and leading to carcinogenesis are provided in Table 32.1.

Etiology Once cervical cancer was the leading cause of cancer death in U.S. women until cervical cancer screening was initiated as standard for women. It is widely accepted that HPV infection is the cause of almost all cases of precancerous and cancerous lesions of the cervix. There are more than 200 genotypes of HPV, of which 14 genotypes are associated with cervical cancer (high-risk oncogenic genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68; NCI, 2022). The more than 200 genotypes include low-risk or nononcogenic types that often cause benign changes and mild cellular abnormality, and the high-risk or oncogenic types that have the potential to cause neoplasia and cancer. Although most HPV cases are subclinical, present no physical symptoms, and clear spontaneously within 2 years, others develop into benign papilloma or malignant cancers (Markowitz et al., 2014). HPV 16 and HPV 18 are particularly of interest, as 70% of HPV­-associated cervical cancers are associated with at least one of the two strains (Uyar & Rader, 2014). HPV infection is epidemic, but cancer is a rare occurrence; the infection is usually transient and clears as a result of an individual’s immune response (Moscicki et al., 2012). Progression to cancer occurs when an HPV infection with a high-risk HPV type persists over time. Persistent infection is defined as the detection of the same HPV type two or more times within a given interval of time. The HPV type affects both the likelihood of persistence and the risk of progression to precancer. HPV 16 persists

*The opinions and assertions expressed herein are those of the author(s) and do not necessarily reflect the official policy or position of the Uniformed Services University or the Department of Defense.

599

600  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

TABLE 32.1  U.S. Annual Human Papillomavirus Cancer Cases in Women: Anatomic Site LOCATION

CASES IN WOMEN

Oropharynx

2,300

Cervix

11,100

Anus

4,700

Vulva

2,900

Vagina Total

700 21,700

Source: Adapted from Centers for Disease Control and Prevention. (n.d.). How many cancers are linked with HPV each year? Retrieved July 8, 2023, from https://www.cdc .gov/cancer/hpv/statistics/cases.htm

longer than other types and also is especially carcinogenic, with a risk of cervical intraepithelial neoplasia (CIN)-3 of 40% at 5 years (Moscicki et al., 2006). High-risk HPV can cause neoplastic changes of other lower genital tract sites (e.g., vagina, vulva, anus, and penis) as well as nongenital sites (e.g., oral cavity, esophagus, and oropharynx). We still have much to learn about the impact of oncogenic HPV in the carcinogenesis of nongenital cancers. HUMAN PAPILLOMAVIRUS TYPES

The most common anogenital low-risk (nononcogenic) HPV types are 6 and 11 (which cause 90% of genital warts), and types 40, 42, 43, 44, 53, 54, 61, 72, 73, and 81. Most low-risk HPV infections clear spontaneously within the first year after infection; however, some may take up to 2 years to clear. As previously mentioned, high-risk (oncogenic) HPV genotypes are associated with cervical neoplasia and cancer. HPV 16 is most commonly associated with cervical high-grade squamous intraepithelial lesions (HSIL) and invasive cancers. Although women infected with HPV 16 are at greater risk for developing cervical HSIL, most HPV 16 infections will not develop into abnormal cellular changes. HPV 18 is most commonly associated with cervical adenocarcinoma. This type of cervical cancer is more difficult to detect on cytology because it occurs in the upper portion of the endocervical canal. For the same reason, it is also more difficult to detect adenocarcinoma using colposcopy-directed biopsies.

Risk Factors Many decades of data support that HPV is a skin cell virus and is transmitted through skin-to-skin contact (Hogenwoning et al., 2003; Manhart & Koutsky, 2002; Winer et al., 2006). It is important for healthcare providers to remember that there is no way to determine when or by whom an individual was infected with HPV.

Clinical Presentation In most cases, HPV infection is transient and has no clinical manifestations or sequelae. In cases of condylomata acuminata (genital warts), lesions may be visible. However, it is important for healthcare providers to note that this may not always be the

case. Condylomas develop because of exposure to HPV types 6 and 11, which are low risk or nononcogenic, and may appear as flat, fleshy, or exophytic; cauliflower-like in appearance; and/or pink or hyperpigmented lesions in either squamous epithelium and/or on mucous membranes (Hogenwoning et al., 2003; Manhart & Koutsky, 2002; Winer et al., 2006). Most often, HPV infection is detected through cervical cancer screening—specifically, because of an abnormal Pap smear or positive, high-risk HPV DNA test, which is now considered the primary screening tool for cervical cancer prevention.

Evaluation and Assessment Collecting a thorough medical and sexual health history is the first step in evaluating risk. Smoking and the use of immunosuppressive medications, for example, significantly increase the likelihood of HPV infection persistence. Inquiring as to whether an individual has a history of abnormal cervical cytology and treatment is also an important data gathering point. The healthcare provider must become proficient and comfortable when conducting a complete sexual history. Sexual health history questions are sensitive and may be perceived to be invasive by the woman. Healthcare provider sensitivity is needed.

Physical Examination GENITAL LESIONS

Although usually benign, genital warts are highly infectious. As a result, infection with HPV types 6 and/or 11 creates a significant amount of morbidity and healthcare costs related to treatment. Furthermore, a diagnosis of genital warts, especially in younger women, often carries with it psychological distress. Women with extensive disease are likely to have an alteration in the integrity of their immune system. This can be seen during times of pregnancy, when a woman’s immune response is physiologically altered; if the HIV status of a woman changes; or if a woman begins smoking. Smoking carries a significant risk for persistent or recurrent HPV disease. Genital warts may be self-limiting and clear on their own, or may clear as a result of treatment. The development of new warts is not necessarily indicative of new infection or even reinfection, but rather may be caused by active disease that develops as a result of a persistent HPV infection. Occasionally, a lesion with the appearance of a genital wart may be cancerous. In order to avoid missing a rare diagnosis of verrucous carcinoma or squamous cell carcinoma, healthcare providers should biopsy all atypical lesions and send for histologic evaluation. Missing such a diagnosis would be detrimental by leading to a delay in treatment, thereby leading to needless morbidity or even death. Differential Diagnosis

Disease caused by HPV infection, unless an overt genital wart, does not usually cause visible changes that can readily be noted on inspection and physical examination. It is important to differentiate a woman’s normal anatomy from physical changes that may suggest HPV infection or disease. Physical findings which may suggest current infection or disease include all of the following:

Chapter 32  Human Papillomavirus 601 ●

● ●

● ● ● ● ●

Micropapilliferous and microfilamentous changes of the micropapillomatosis labialis Skin tags, hymenal remnants Raised pigmented red, dark, or white, or cauliflower-like lesions on the external genitalia Nevi Dermatoses (e.g., lichen sclerosus) Melanomas Molluscum contagiosum Verrucous carcinoma

CERVICAL CANCER

In 2023, it is estimated that 13,960 new cases of cervical cancer will be diagnosed in American women. Further, it is estimated that 4,310 women will die in the United States due to cervical cancer (American Cancer Society [ACS], 2023). These statistics are most unfortunate as cervical cancer is a preventable and curable cancer. What is more, most of the women who will succumb to cervical cancer have never undergone cervical screening. In fact, the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) has put into place strategies to help low-income, uninsured, and underinsured women gain access to timely cervical cancer screening and diagnostic services. The goal of cervical cancer screening is to identify high-grade disease early and treat for the purpose of preventing the development of cervical cancer.

Cervical Cancer Screening The overall goal of cervical cancer screening is to identify disease early and with certainty before cervical precancerous

disease develops into cancer. Cervical cancer screening is guided by two principles: (1) risk stratification—identifying who is at risk and what their risk is; and (2) disease stratification—identifying who will actually benefit from intervention. This goal is accomplished by (a) identifying, treating, and surveilling high-grade cervical cancer precursors (cervical HSIL), thereby reducing a woman’s risk of developing invasive cancer; and (b) avoiding unnecessary treatment or overtreatment of benign and transient HPV infections and cancer precursor lesions that most likely will regress. Loop electrosurgical excision procedure (LEEP) and cold knife conization (CKC) are associated with adverse obstetric outcomes, which include preterm delivery and perinatal death (Khan & Smith-McCune, 2014). Currently, international and U.S. national cervical screening guidelines differ (see Table 32.2). More and more, primary HPV testing plays a more important role in cervical cancer screening as it is significantly more sensitive in detecting high-grade cervical dysplasia than cytologic specimens collected on a Pap smear. At the time of print of this edition, the U.S. Preventive Services Task Force (USPSTF) cervical screening guidelines were “under revision for updates.”

Diagnostic Tests There are FDA (U.S. Food and Drug Administration)approved screening tests available for use when screening for cervical cancer: cytology alone (conventional Pap smear or liquid-based Pap smear) and/or high-risk (HR) HPV DNA testing (Cobas HPV test, APTIMA HPV Assay, Hybrid

TABLE 32.2  Cervical Cancer Screening Guidelines The American Cancer Society ● www.cancer.org/cancer/cervical-cancer/detectiondiagnosis-staging/screening-tests/hpv-test.html

The U.S. Preventive Services Task Force (USPSTF) www.uspreventiveservicestaskforce.org/uspstf/ recommendation/cervical-cancer-screening   Endorsed by: The American College of Obstetricians and Gynecologists (ACOG) www.acog.org/clinical/clinical-guidance/ practice-advisory/articles/2021/04/ updated-cervical-cancer-screening-guidelines The American Society for Colposcopy and Cervical Pathology (ASCCP) www.asccp.org/screening-guidelines Society of Gynecologic Oncology (SGO) ● www.sgo.org/news/sgo-endorses-acog-new-practiceadvisory-of-uspstf-cervical-cancer-screeningrecommendations World Health Organization ● https://www.who.int/publications/i/ item/9789240040434

The preferred test for cervical cancer screening for women ages 25–65 years is primary HPV testing ● Because some HPV tests are approved by the FDA as part of a cotest, primary HPV testing may not be an option. In those instances, a cotest every 5 years or a Pap test every 3 years is recommended ●

Ages 21–29 ❍ Cytology alone every 3 years ● Ages 30–65 ❍ Cytology alone every 3 years, or ❍ FDA-approved primary HR HPV testing alone every 5 years ❍ Cotesting (HR HPV testing and cytology) every 5 years ● Ages ≥66 ❍ No screening after adequate negative prior screening results ●

General population of women: ❍ Primary screening method is HPV DNA detection, beginning at age of 30, with regular testing every 5–10 years ❍ HPV DNA detection in a screen, triage and treat approach starting at the age of 30 years with regular screening every 5 to 10 years ● Women living with HIV: HPV DNA detection in a screen, triage and treat approach starting at the age of 25 years with regular screening every 3 to 5 years ●

FDA, Food and Drug Administration; HPV, human papillomavirus; HR, high risk.

602  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

TABLE 32.3  Human Papillomavirus (HPV) DNA Tests Approved by the Food and Drug Administration TEST

PURPOSE

Cobas HPV test (Roche Molecular Systems)

Identifies DNA from 14 high-risk genital HPV types commonly associated with cervical cancer

APTIMA HPV Assay (Gen-Probe)

Identifies RNA from 14 high-risk genital HPV types commonly associated with cervical cancer

Hybrid Capture 2 High Risk HPV DNA test (Digene)

Identifies genetic DNA from HPV in cervical cells

Cervista HPV HR and Genfind DNA Extraction (Hologic)

Identifies DNA from 14 high-risk genital HPV types commonly associated with cervical cancer

Cervista HPV 16/18 (Hologic)

Identifies HPV genotypes 16 and 18 in cervical samples

INTENDED USE

Provides information about a woman’s risk for developing cervical cancer ● In women ≥30 years of age or women ≥21 years of age with borderline cellular results to assess indication for follow-up and/or diagnostic procedures ●

Provides information about a woman’s risk for developing cervical cancer ● Used for women ≥30 years of age or any age with borderline cytology results to determine any need for follow-up procedures ●

● ●

●

● ●

Detection of high-risk HPV (HR HPV) Follow-up test when a Pap smear is mildly abnormal Determines a woman’s risk for developing cervical cancer

Determines a woman’s risk for developing cervical cancer Used for women ≥30 years of age or any age with borderline cytology results to determine indication for any follow-up procedures

Source: Adapted from LabCE. (n.d.). FDA-approved HPV tests. https://www.labce.com/spg761630_fda_approved_hpv_tests.aspx

Capture 2 High Risk HPV DNA test, and Cervista HPV HR and Genfind DNA Extraction, or Cervista HPV 16/18). Recommended screening modalities are as follows: cytology alone, HR HPV DNA testing alone, and finally cotesting using both cytology and HR HPV DNA testing (Table 32.3). CERVICAL CYTOLOGY

Historically, cervical cytology has been the mainstay of cervical cancer prevention screening. Cervical cytology consists of two collection methods: conventional Pap (exfoliated cells are smeared onto a slide and fixed with preservative) and liquid-based thin layer (exfoliated cells are collected using an endocervical brush and then transferred into a liquid preservative). Most healthcare providers use liquid-based cytology as its sensitivity is greater when compared with conventional cytology. Liquid-based cytology is often most preferred as it allows for reflex HPV testing as well as gonorrhea and chlamydia testing. Regardless of method, a low-grade squamous intraepithelial lesion (LSIL) cytology triages many women into a low-risk category. An LSIL cytology result is typically translated to be an active HPV infection, of which most are self-limiting. In contrast, HSIL cytology identifies women who are at the greatest risk of developing an invasive cancer. Treatment of this cancer precursor is indicated to prevent transformation into invasive cancer. HUMAN PAPILLOMAVIRUS DNA TESTING

We have identified HPV as a necessary cause of cervical cancer. What is more, women infected with HPV types 16 and 18 have a 10-fold increased risk of developing cervical cancer (Khan et al., 2005). HPV DNA testing uses advanced molecular biological methodologies for the detection of high-risk HPV. It is important that healthcare providers only use HPV DNA tests that are approved by the FDA.

COTESTING

Cotesting with cervical cytology and HPV DNA testing has been shown to increase sensitivity, thereby increasing early detection rates. An increased sensitivity translates into greater clinical confidence in the lengthening of screening intervals. In turn, lengthening screening intervals allows for transient HPV infection clearance and minimizes opportunities to overtreat. Positive HPV DNA testing allows for risk stratification and identification in women who, for example, cytology alone was reported as normal. In these cases, a woman with a negative cytology result and a positive high-risk HPV result will require additional evaluation (e.g., colposcopy). When requesting an HPV DNA test, the healthcare provider may also request HPV genotyping (either at initial collection or after the HPV DNA test results are reported). Positive HPV types 16 and 18 genotyping results help guide the healthcare provider in further stratifying a woman’s risk of developing a cancer precursor and invasive cancer.

Treatment and Management CONDYLOMATA ACUMINATA (GENITAL WARTS)

Although the primary purpose for treating EGWs is cosmetic, it is not uncommon for individual’s to experience psychological and emotional distress related to learning of their diagnosis and also side effects associated with treatment, for example, skin irritation, mild pain and mild pruritus, and reddening of the skin. For this reason, it is important for the healthcare provider to establish a trusting relationship, establish good communication, educate, and when indicated, refer for psychological evaluation (Lawrence et al., 2009; Nahidi et al., 2018). During pregnancy, when it is physiologically normal for an individual’s immune system to be suppressed, shifts in hormone levels may cause preexisting genital warts to proliferate.

Chapter 32  Human Papillomavirus 603

TABLE 32.4  Treatment Regimens for Genital Warts RECOMMENDED REGIMENS FOR EXTERNAL GENITAL WARTS

Patient self-applied

Podofilox 0.5% solution or gel Imiquimod 5% cream Sinecatechins 15% ointment

Healthcare provider administered

Cryotherapy with liquid nitrogen or cryoprobe; repeat applications every 1–2 weeks TCA or BCA 80%–90% Surgical removal either by scissor excision, shave excision, curettage, or electrosurgery

ALTERNATIVE REGIMENS (MORE SIDE EFFECTS, LESS DATA ON EFFICACY)

Recommended regimen for cervical warts

For those with exophytic cervical warts, a biopsy evaluation to exclude high-grade SIL must be performed before treatment is initiated. Management of exophytic cervical warts should include consultation with a specialist.

Recommended regimens for vaginal warts

Cryotherapy with liquid nitrogen. The use of a cryoprobe in the vagina is not recommended because of the risk for vaginal perforation and fistula formation. TCA or BCA 80%–90% applied to warts. A small amount should be applied only to warts and allowed to dry, at which time a white frosting develops. If an excess amount of acid is applied, the treated area should be powdered with talc, sodium bicarbonate, or liquid soap preparations to remove unreacted acid. This treatment can be repeated weekly, if necessary.

Recommended regimens for urethral meatus warts

Cryotherapy with liquid nitrogen

Recommended regimens for anal warts

Cryotherapy with liquid nitrogen (perianal only) TCA or BCA 80%–90% applied to warts (intra- or perianal). A small amount should be applied only to warts and allowed to dry, at which time a white frosting develops. If an excess amount of acid is applied, the treated area should be powdered with talc, sodium bicarbonate, or liquid soap preparations to remove unreacted acid. This treatment can be repeated weekly, if necessary. Combination of liquid nitrogen and TCA may allow for more rapid regression Office-based ablation with electrocautery Surgical removal (for extensive warts)

BCA, bichloroacetic acid; SIL, squamous intraepithelial lesion; TCA, trichloroacetic acid. Source: Adapted from Centers for Disease Control and Prevention. (n.d.). Genital HPV infection: Basic fact sheet. http://www.cdc.gov/std/hpv/stdfact-hpv.htm

In cases in which EGWs begin to grow, surgical removal and sometimes cesarean section may be indicated (in rare cases when they obstruct the birth canal). The recommended period of gestation for treatment is around 32-weeks’ gestation. Post-treatment, obstetric patients should be monitored as recurrence may occur. During pregnancy, EGWs are to be treated as per CDC recommended treatment guidelines (see Table 32.4). Treatment of genital warts includes both healthcare provider–administered and patient-administered therapies. When contemplating a treatment plan, healthcare providers should consider all of the following: genital wart size, number, location, morphology, woman’s choice, healthcare provider experience, convenience, and adverse effects.

Increasing Severity of Squamous Intraepithelial Lesions and Treatment Modalities Two treatment modalities are used to address the increasing severity of SIL: ablative therapy and excisional therapy. ABLATIVE THERAPY

This treatment modality includes the use of cryotherapy and laser vaporization. When performing cryotherapy or laser vaporization, it is important to note that no surgical

specimen will be available for histologic testing. For this reason, many healthcare providers prefer using excisional therapies. Advantages of cryotherapy include ease to perform in an outpatient setting, minimal healthcare provider training, affordability, and minimal long-term fertility issues. Significant cramping and watery, malodorous vaginal drainage for up to 3 weeks are the most commonly reported disadvantages to cryotherapy. Laser vaporization is also readily performed in the outpatient setting with minimal risk to the individual. The most common reason this procedure is not preferred by healthcare providers has to do with the necessary additional training and the additional cost of the equipment. Women tolerate laser vaporization well, and often receive some type of sedative prior to the procedure to help with any discomfort/pain and to minimize patient movement during the procedure. The biggest advantage of laser vaporization is the precision at which the tissue/area of concern is destroyed. EXCISIONAL THERAPY

Excisional therapy includes LEEP and CKC biopsy. The result of these procedures is a tissue specimen, which is sent to pathology for histologic evaluation and diagnosis. Individuals are most often treated with a local anesthetic during these procedures and with nonsteroidal anti-inflammatory medication for postprocedure cramping. Vaginal bleeding

604  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

and discharge are common and may last for up to 2 weeks. Thermal artifacts are evident on the margins of a specimen, and care must be taken by both the healthcare provider and pathologist to ensure that the margins are clear; this indicates that there is evidence that no high-grade lesions were missed during the procedure. Typically, a CKC biopsy procedure is typically performed when there is evidence and concern for an increased possibility of invasive cancer. The biggest advantage of a CKC procedure versus a LEEP procedure has to do with the fact that the biopsy specimen collected via CKC will not have undergone any thermal damage to the tissue margins. Because more tissue is collected during a CKC procedure, the individual is at greater risk for developing acute bleeding, and long-term cervical stenosis and cervical insufficiency, which may lead to, for example, premature delivery.

Current Approaches to Cervical Cancer Prevention Current approaches to cervical cancer prevention include (1) HPV vaccination, (2) cervical cancer screening, (3) follow-up evaluation using colposcopy and cervical biopsy, and (4) treatment for biopsy-confirmed high-grade cervical cancer precursors. Approaches 2 and 4 have previously been discussed. In the following section, we discuss HPV vaccination as a means of prevention.

Human Papillomavirus Vaccination Since 2017, the 9-valent vaccine is the only HPV vaccine available in the United States (KFF Women’s Health Policy, 2021). Unfortunately, uptake of the vaccine in the United States continues at less than hoped-for rates. As of 2019, only 54% of women and less than 49% of men in the recommended age groups had received all recommended doses. Decreasing persistent HPV infection rates, disease, and cancer burden will be achieved if HPV cancer prevention vaccine uptake increases through the implementation of interventions that are successful at improving vaccine uptake. Widespread, HPV cancer prevention vaccination will sharply reduce genital warts and anogenital cancers; cervical, vaginal, vulvar, and anal dysplasia and cancer; and EGWs. The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination at age 11 to 12 and may begin as early as age 9 years (Meites et al., 2016). The vaccine is most effective at early age before exposure to the HPV through sexual activity and provides antibody levels equivalent to those who received three doses of the HPV vaccine. The HPV vaccination is also recommended as catchup for females ages 13 to 26 years and for males ages 13 to 21 years, for those who have not been previously vaccinated, or who have not completed the three-dose vaccine series. Males age 22 to 26 years may be vaccinated. In October 2018, the FDA approved the expanded use of the 9-valent HPV vaccine in individuals ages 27 to 45. It is recommended that individuals ≥27 years of age, and up to 45, together with their healthcare provider, determine risk for new HPV infection acquisition through shared decision-making to determine benefit of vaccine uptake (American College of Obstetricians and Gynecologists [ACOG], 2020). See Table 32.5 for the 9-valent vaccine schedule.

HUMAN PAPILLOMAVIRUS VACCINE UPTAKE AND THE FIGHT AGAINST CANCER IN AMERICA

In 2012, the President’s Cancer Panel determined that low rates of adolescent HPV vaccine uptake were a threat to America’s progress against cancer (President’s Cancer Panel, 2014). At that time, the CDC estimated that increasing current low vaccination rates up to 80% (a Healthy People 2020 target) would prevent an additional 53,000 future cervical cancer cases in the United States in adolescent girls 12 years old or younger over the course of their lifetimes (CDC, 2013). Barriers to vaccine uptake were identified. They included (a) missed clinical opportunities, (b) misinformation, (c) mistrust, (d) lack of knowledge, (e) insufficient access and/or system gaps, and (f) cost concerns (President’s Cancer Panel, 2014). In an effort to address these barriers, the Panel recommended three critical goals that must be achieved to increase HPV vaccine uptake in the United States. The overall goal is completion of the vaccine series by all vaccine-eligible adolescents for whom the vaccine is not contraindicated. Critical goals include the following: (a) reduce missed clinical opportunities to recommend and administer the vaccines; (b) increase parents’, caregivers’, and adolescents’ acceptance of the vaccine; and (c) maximize access to HPV vaccination services (President’s Cancer Panel, 2014). MISSED CLINICAL OPPORTUNITIES

Often, adolescents receive other recommended vaccines during well-child visits, but not HPV vaccines. Healthcare providers should strongly encourage HPV vaccination whenever other vaccines are administered and healthcare organizations should use electronic health records and immunization information systems to avoid missed opportunities for HPV vaccination. Precounseling patients to expect mild local discomfort after inoculation is a reinforcer of vaccine safety. Mild local discomfort is not a cause for alarm, nor an adverse event. Healthcare providers should not test for HPV DNA before vaccination and pregnancy testing is not recommended. The HPV vaccination is safe during breastfeeding. There is no need to revaccinate individuals who previously completed some but not all the vaccine series. Healthcare providers should recommend HPV vaccination as early as possible in children and adolescents with a history of child abuse. Although, overall, the United States is experiencing an uptake of HPV vaccination, there remain socioeconomic disparities in the United States. These disparities are seen in adolescents living at or above the poverty level as well as in those living in rural America, as they are less likely to participate in well-child visits (CDC, 2023). Participating in few well-child visits results in fewer opportunities for healthcare providers to recommend and administer the vaccine. KNOWLEDGE, ATTITUDES, AND BELIEFS

Parental and caregiver knowledge, attitudes, and beliefs affect whether children receive any vaccine, including HPV vaccines. Most parents believe that vaccines protect their children from potentially life-threatening diseases, but some refuse one or more recommended vaccines based on concerns, such as safety. The most important predictor of vaccination in the clinical setting is a strong recommendation

Chapter 32  Human Papillomavirus 605

TABLE 32.5  Human Papillomavirus Vaccine Schedule in the United States 9-VALENT HPV VACCINE

Manufacturer

Merck & Co., Inc.

Target age

9-yearsa 11–12 years target ageb 13–26 years as catch upc 27–45 years in some women

Sex

Boys and girls

HPV genotypes

6, 11, 16, 18, 31, 33, 45, 52, 58 SCHEDULE

9–14 years If vaccinated before age 15, two doses are needed; 0 (baseline) and 6–12 months. The 6-month interval is critical for adequate immune titers. If the interval between doses is 25 kg/m2. ● Advise adequate water intake. ● Assess for stress and stress management. ● Ensure that antihypertensives are being taken correctly. ● Consider reducing, changing, or discontinuing estrogen. ● Monitor blood pressure; if consistently elevated, consider discontinuing HT. ●

Rash

● ●

Consider adding testosterone (off-label use). Assess sexual function, social factors, and relationship; make recommendations (see Chapter 19, Women’s Sexual Health and Chapter 29, Urologic and Pelvic Floor Health Problems).

Advise limiting salt, caffeine, and alcohol use. Assess for stress and stress management (see Chapter 12, Mental Health and Chapter 40, Mental Health Challenges). ● Ensure adequate daily water intake. ● Consider change to continuous combined EPT regimen to reduce hormone fluctuations. ● Consider change to transdermal estrogen. ● Consider decreasing estrogen and/or progestogen. ● ●

Ensure that patch is applied over clean, dry area. ● Ensure that patch location is rotated. ● If urticaria develops, stop medication and assess for allergic response. ●

See prescribing reference for full information on side effects, cautions, and contraindications for estrogen, progestogens, and testosterone hormone therapy products. EPT, estrogen-progestogen therapy; HT, hormone therapy; BMI, body mass index. Source: Adapted from ePocrates. (n.d.). Computerized pharmacology and prescribing reference (updated daily). www.epocrates.com; The North American Menopause Society. (2019). Menopause practice: A clinician’s guide (6th ed.). Author. a

Chapter 34  Menopause 651

The need for HT is reevaluated at least annually; if symptom control is still necessary, then HT may be continued for the shortest period possible. If symptoms are well controlled using a specific dose, then reducing the dose to determine if symptom control continues is appropriate. Some will have symptoms for a few years, whereas others continue with moderate to severe symptoms for many years (NAMS, 2019, 2022). The decision to discontinue HT is made collaboratively with the patient and based on their individual risks, needs, and QOL. The discussion on discontinuation of HT needs to include the newest findings from ongoing research regarding cardiovascular, breast cancer, and venous thromboembolic event risks. (NAMS, 2019, 2022). NONHORMONE PRESCRIPTION MEDICATIONS

Although ET, EPT, and estrogen + bazedoxifene are superior for VMS management (NAMS, 2019, 2022), those who are unwilling or unable to take hormones may benefit from using alternative prescription options (Table 34.6). These may be added to lifestyle changes and/or some CAM therapies. Many of the studies evaluating efficacy of nonhormonal oral prescription medications for HF management were conducted with breast cancer survivors who were experiencing HFs. Clinicians need to consider whether the results apply to those who have not had breast cancer and also whether treatment options need to be tailored because some nonhormonal

medications may interfere with breast cancer therapies (NAMS, 2019, 2022).

Considerations for Special Populations Because hormonal fluctuations and ovulation are possible, perimenopausal persons with a uterus who engage in sexual intercourse with males can become pregnant. Almost half (45%) of all pregnancies are unintended (Guttmacher Institute, 2019). Although data specifying unintended pregnancy rates among perimenopausal women are lacking, the CDC reported that 2.7 abortions were performed for every 1,000 women over age 40 years between 2010 and 2019 (Kortsmit et al., 2021). Thus, it is important to discuss contraception with perimenopausal persons who may become pregnant (see Chapter 21, Fertility Self-Management and Shared Management). Premature or temporary menopause (see Box 34.1) causes early loss of fertility and potentially more severe symptoms than natural menopause. There is a higher risk for osteoporosis and CVD because of the comparatively earlier reduction in estrogen and progesterone. Other significant health concerns may arise related to underlying disease processes (NAMS, 2019, 2022). Likewise, menopause generally occurs earlier following hysterectomy, most likely attributable to the reduced circulation to the remaining ovaries following surgical interruption of the uterine blood supply, which also partially feeds the ovaries.

TABLE 34.6  Nonhormonal Pharmacologic Optionsa for Vasomotor Symptom Management CATEGORY

DRUG

DOSAGEa

COMMENTa

COMMON SIDE EFFECTSa

CONTRAINDICATIONSa

Anticonvulsants

Gabapentin (Neurontin)

Initial dose 300 mg/day Increase at 3- to 4-day intervals to 300 mg three times daily as needed

Avoid abrupt cessation Effective in two out of two trials

Ataxia, dizziness, fatigue, somnolence

No antacids within 2 hours of use Alcohol potentiates CNS depression

Antihypertensives

Clonidine

0.05–0.1 mg twice daily

Available as a patch Less effective than SSRIs/SNRIs or gabapentin Avoid abrupt cessation

Agitation, arrhythmias, constipation, dizziness, drowsiness, dry mouth, hypotension, impotence, insomnia, myalgia, nausea, orthostatic hypotension, rash, urticaria, weakness

Antagonized by tricyclic antidepressants Potentiates CNS depressants

Asthenia, chest pain, decreased libido, dyspepsia, edema, fever, hyperglycemia, hypertension, insomnia, intestinal disturbance, rash, urinary frequency, weight gain

Use with caution in women with diabetes or history of thromboembolic disease

Methyldopa and Bellergal Breast cancer agent (progestin)

Megestrol (Megace)

Not recommended because of toxicity 20 mg daily (divided doses)

May increase insulin requirements

(continued)

652  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

TABLE 34.6  Nonhormonal Pharmacologic Optionsa for Vasomotor Symptom Management (continued) CATEGORY

SSRIs/SNRIsb

DRUG

DOSAGEa

COMMENTa

COMMON SIDE EFFECTSa

CONTRAINDICATIONSa

Avoid concomitant use of MAO inhibitors or thioridazine Use with caution with warfarin Avoid use with alcohol Use with caution in women with diabetes, diseases that affect metabolism, or heart disease

Fluoxetine (Prozac)

Start at 20 mg/day Titrate up as needed

Avoid abrupt cessation Monitor weight

Anorgasmia, asthenia, GI upset, reduced libido, somnolence, insomnia, sweating

Paroxetine (Brisdelle)

7.5 mg/day

Only SSRI with FDA approval for treatment of HFs Avoid abrupt cessation

See fluoxetine

Desvenlafaxine (Pristiq)

Start at 50 mg/day Titrate up to max dose of 400 mg/ day as needed

Avoid abrupt cessation

See fluoxetine

Venlafaxine (Effexor XR)

Start at 37.5 mg/ day Titrate up as needed

Avoid abrupt cessation

See fluoxetine

See prescribing reference for full information on doses, side effects, contraindications, and cautions; except for paroxetine 7.5 mg (Brisdell), use of these products for vasomotor symptom relief is off-label; efficacy for HF management with these products is less than that with estrogen. b Effective in four out of six trials in meta-analysis. CNS, central nervous system; FDA, Food and Drug Administration; GI, gastrointestinal; HFs, hot flashes; MAO, monoamine oxidase; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor. Source: Adapted from ePocrates. (n.d.). Computerized pharmacology and prescribing reference (updated daily). www.epocrates.com; The North American Menopause Society. (2019). Menopause practice: A clinician’s guide (6th ed.). Author. a

FUTURE DIRECTIONS Much has been learned about managing menopause-related symptoms over the past several decades. Landmark research studies have clarified risks and benefits of HT, nonhormonal therapy, and various CAMs for managing menopause-related symptoms, and the importance of maintaining a high QOL has been underscored. Current research is evaluating various other methodologies, such as alternative hormones, novel nonhormone therapies, other CAM therapies, and unique delivery options, to evaluate their effectiveness in mitigating VMS while retaining a strong safety profile for health. These new therapies are likely to provide important relief in the future.

REFERENCES Afonso, R. F., Hachul, H., Kozasa, E. H., de Souza Oliveira, D., Goto, V., Rodrigues, D., Tufik, S., & Leite, J. R. (2012). Yoga decreases insomnia in postmenopausal women: A randomized clinical trial. Menopause, 19(2), 186–193. https://doi.org/10.1097/gme.0b013e318228225f Alexander, I. M. (2006). Bioidentical hormones for menopause therapy: Separating the myths from the reality. Women’s Health Care, 5(1), 7–17.

Alexander, I. M. (2011). Hormone therapy and incidence of breast cancer. Climacteric, 14, 299–300. Alexander, I. M. (2012). The history of hormone therapy use and recent controversy related to heart disease and breast cancer arising from prevention trial outcomes. Journal of Midwifery & Women’s Health, 57(6), 547–557. https:// doi.org/10.1111/j.1542-2011.2012.00247.x Alexander, I. M., Ruff, C., Rousseau, M. E., White, K., Motter, S., McKie, C., & Clark, P. (2003). Menopause symptoms and management strategies identified by black women. Menopause, 10(6), 601. American College of Obstetricians and Gynecologists. (2017). Practice Bulletin No. 179. Breast cancer risk assessment and screening in average-risk women. Obstetrics & Gynecology, 130(1), e1–e16. https://doi.org/10.1097/AOG .0000000000002158 Anderson, G. L., Limacher, M., Assaf, A. R., Bassford, T., Beresford, S. A., Black, H., Bonds, D., Brunner, R., Brzyski, R., Caan, B., Chlebowski, R., Curb, D., Gass, M., Hays, J., Heiss, G., Hendrix, S., Howard, B. V., Hsia, J., Hubbell, A., . . . Women’s Health Initiative Steering Committee. (2004). Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women’s Health Initiative randomized controlled trial. Journal of the American Medical Association, 291(14), 1701–1712. https://doi.org/10.1001/jama.291.14.1701 Antonijevic, I. A., Stalla, G. K., & Steiger, A. (2000). Modulation of the sleep electroencephalogram by estrogen replacement in postmenopausal women. American Journal of Obstetrics and Gynecology, 182(2), 277–282. https://doi .org/10.1016/s0002-9378(00)70211-0 Avis, N. E., Stellato, R., Crawford, S., Bromberger, J., Ganz, P., Cain, V., & Kagawa-Singer, M. (2001). Is there a menopausal syndrome? Menopausal status and symptoms across racial/ethnic groups. Social Science & Medicine, 52(3), 345–356. https://doi.org/10.1016/s0277-9536(00)00147-7 Bacon, J. (2017). The menopausal transition. Obstetrics and Gynecology Clinics of North America, 44, 285–296. https://doi.org/10.1016/j.ogc.2017.02.008 Bagger, Y. Z., Tankó, L. B., Alexandersen, P., Qin, G., & Christiansen, C. (2005). Early postmenopausal hormone therapy may prevent

cognitive impairment later in life. Menopause, 12(1), 12–17. https://doi.org/10 .1097/00042192-200512010-00005 Barnard, N. D., Kahleova, H., Holtz, D. N., del Aguila, F., Neola, M., Crosby, L. M., & Holubkov, R. (2021). The Women’s Study for the Alleviation of Vasomotor Symptoms (WAVS): A randomized, controlled trial of a plant-based diet and whole soybeans for postmenopausal women. Menopause, 28(10), 1150–1156. https://doi.org/10.1097/GME.0000000000001812 Beck, V., Unterrieder, E., Krenn, L., Kubelka, W., & Jungbauer, A. (2003). Comparison of hormonal activity (estrogen, androgen and progestin) of standardized plant extracts for large scale use in hormone replacement therapy. Journal of Steroid Biochemistry and Molecular Biology, 84(2–3), 259–268. https://doi.org/10.1016/s0960-0760(03)00034-7 Bentzen, J. G., Forman, J. L., Larsen, E. C., Pinborg, A., Johannsen, T. H., Schmidt, L., Friis-Hansen, L., & Nyboe Andersen, A. (2013). Maternal menopause as a predictor of anti-Mullerian hormone level and antral follicle count in daughters during reproductive age. Human Reproduction, 28(1), 247–255. https:// doi.org/10.1093/humrep/des356 Breen, N., Cronin, K. A., Meissner, H. I., Taplin, S. H., Tangka, F. K., Tiro, J. A., & McNeel, T. S. (2007). Reported drop in mammography: Is this cause for concern? Cancer, 109(12), 2405–2409. https://doi.org/10.1002/cncr.22723 Brincat, M., Kabalan, S., Studd, J. W., Moniz, C. F., de Trafford, J., & Montgomery, J. (1987). A study of the decrease of skin collagen content, skin thickness, and bone mass in the postmenopausal woman. Obstetrics & Gynecology, 70(6), 840–845. https://journals.lww.com/greenjournal/abstract/1987/12000/a_ study_of_the_decrease_of_skin_collagen_content,.6.aspx Brincat, M. P. (2000). Hormone replacement therapy and the skin: Beneficial effects: The case in favor of it. Acta Obstetricia et Gynecologica Scandinavica, 79(4), 244–249. https://obgyn.onlinelibrary.wiley.com/doi/pdf/10.1034 /j.1600-0412.2000.079004244.x Butts, S. F., Freeman, E. W., Sammel, M. D., Queen, K., Lin, H., & Rebbeck, T. R. (2012). Joint effects of smoking and gene variants involved in sex steroid metabolism on hot flashes in late reproductive-age women. Journal of Clinical Endocrinology and Metabolism, 97(6), E1032–E1042. https://doi .org/10.1210/jc.2011-2216 Butts, S. F., Sammel, M. D., Greer, C., Rebbeck, T. R., Boorman, D. W., & Freeman, E. W. (2014). Cigarettes, genetic background, and menopausal timing: The presence of single nucleotide polymorphisms in cytochrome P450 genes is associated with increased risk of natural menopause in European-American smokers. Menopause, 21(7), 694–701. https://doi.org/10.1097 /GME.0000000000000140 Carmody, J. F., Crawford, S., Salmoirago-Blotcher, E., Leung, K., Churchill, L., & Olendzki, N. (2011). Mindfulness training for coping with hot flashes: Results of a randomized trial. Menopause, 18(6), 611–620. https://doi .org/10.1097/gme.0b013e318204a05c Cayan, F., Dilek, U., Pata, O., & Dilek, S. (2008). 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, 5(1), 132–138. https://doi.org/10.1111/j .1743-6109.2007.00635.x Centers for Disease Control and Prevention. (n.d.). Sleep and sleep disorders. https://www.cdc.gov/sleep/index.html Chen, C. T., Liu, C. T., Chen, G. K., Andrews, J. S., Arnold, A. M., Dreyfus, J., Franceschini, N., Garcia, M. E., Kerr, K. F., Li, G., Lohman, K. K., Musani, S. K., Nalls, M. A., Raffel, L. J., Smith, J., Ambrosone, C. B., Bandera, E. V., Bernstein, L., Britton, A., . . . Rajkovic, A. (2014). Meta-analysis of loci associated with age at natural menopause in African-American women. Human Molecular Genetics, 23(12), 3327–3342. https://doi.org/10.1093/hmg/ddu041 Chen, L. R., Ko, N. Y., & Chen, K. H. (2019). Isoflavone supplements for menopausal women: A systematic review. Nutrients, 11(11), 2649. https://doi .org/10.3390/nu11112649 Chen, M. N., Lin, C. C., & Liu, C. F. (2015). Efficacy of phytoestrogens for menopausal symptoms: A meta-analysis and systematic review. Climacteric, 18(2), 260–269. https://doi.org/10.3109/13697137.2014.966241 Chlebowski, R. T., Anderson, G., Pettinger, M., Lane, D., Langer, R. D., Gilligan, M. A., Walsh, B. W., Chen, C., McTiernan, A., & Women’s Health Initiative Investigators. (2008). Estrogen plus progestin and breast cancer detection by means of mammography and breast biopsy. Archives of Internal Medicine, 168(4), 370–377; quiz 345. https://doi.org/10.1001/archinternmed.2007.123 Chlebowski, R. T., Kuller, L. H., Prentice, R. L., Stefanick, M. L., Manson, J. E., Gass, M., Aragaki, A. K., Ockene, J. K., Lane, D. S., Sarto, G. E., Rajkovic, A., Schenken, R., Hendrix, S. L., Ravdin, P. M., Rohan, T. E., Yasmeen, S., & Anderson, G. (2009). Breast cancer after use of estrogen plus progestin in postmenopausal women. New England Journal of Medicine, 360(6), 573–587. https://doi.org/10.1056/NEJMoa0807684 Choi, J. I., Han, K. D., Lee, D. W., Kim, M. J., Shin, Y. J., & Lee, H. N. (2017). Relationship between alcohol, consumption and age at menopause: The Korea National Health and Nutrition Examination Survey. Taiwan Journal

of Obstetrics and Gynecology, 56(4), 482–486. https://doi.org/10.1016/j.tjog .2017.05.002 Clarke, C. A., Glaser, S. L., Uratsu, C. S., Selby, J. V., Kushi, L. H., & Herrinton, L. J. (2006). Recent declines in hormone therapy utilization and breast cancer incidence: Clinical and population-based evidence. Journal of Clinical Oncology, 24(33), e49–e50. https://doi.org/10.1200/JCO.2006.08.6504 Cohen, L. S., Joffe, H., Guthrie, K. A., Ensrud, K. E., Freeman, M., Carpenter, J. S., Learman, L. A., Newton, K. M., Reed, S. D., Manson, J. E., Sternfeld, B., Caan, B., Freeman, E. W., LaCroix, A. Z., Tinker, L. F., Booth-Laforce, C., Larson, J. C., & Anderson, G. L. (2014). Efficacy of omega-3 for vasomotor symptoms treatment: A randomized controlled trial. Menopause, 21(4), 347–354. https://doi.org/10.1097/GME.0b013e31829e40b8 Coombs, N. J., Taylor, R., Wilcken, N., & Boyages, J. (2005). Hormone replacement therapy and breast cancer: Estimate of risk. British Medical Journal, 331(7512), 347–349. https://doi.org/10.1136/bmj.331.7512.347 Coombs, N. J., Taylor, R., Wilcken, N., Fiorica, J., & Boyages, J. (2005). Hormone replacement therapy and breast cancer risk in California. Breast Journal, 11(6), 410–415. https://doi.org/10.1111/j.1075-122X.2005.00132.x Cosman, F., de Beur, S. J., LeBoff, M. S., Lewiecki, E. M., Tanner, B., Randall, S., Lindsay, R., & National Osteoporosis Foundation. (2014). Clinician’s guide to prevention and treatment of osteoporosis. Osteoporosis International, 25(10), 2359–2381. https://doi.org/10.1007/s00198-014-2794-2 Craig, M. C., Fletcher, P. C., Daly, E. M., Picchioni, M. M., Brammer, M., Giampietro, V., Rymer, J., McGuire, P. K., Maki, P. M., & Murphy, D. G. (2008). A study of visuospatial working memory pre- and post-gonadotropin hormone releasing hormone agonists (GnRHa) in young women. Hormonal Behavior, 54(1), 47–59. https://doi.org/10.1016/j.yhbeh.2008.01.012 Cramer, D. W., Xu, H., & Harlow, B. L. (1995). Family history as a predictor of early menopause. Fertility and Sterility, 64(4), 740–745. https://doi.org/10.1016 /s0015-0282(16)57849-2 Dasgupta, D., & Ray, S. (2017). Is menopausal status related to women’s attitudes towards menopause and aging? Women & Health, 57 (3), 311–328. https:// doi.org/10.1080/03630242.2016.1160965 Dennerstein, L., Dudley, E., & Burger, H. (2001). Are changes in sexual functioning during midlife due to aging or menopause? Fertility and Sterility, 76(3), 456–460. https://doi.org/10.1016/s0015-0282(01)01978-1 Dennerstein, L., Dudley, E. C., Hopper, J. L., Guthrie, J. R., & Burger, H. G. (2000). A prospective population-based study of menopausal symptoms. Obstetrics & Gynecology, 96(3), 351–358. https://doi.org/10.1016 /s0029-7844(00)00930-3 Dillaway, H., Byrnes, M., Miller, S., & Rehan, S. (2008). Talking “among us”: How women from different racial-ethnic groups define and discuss menopause. Health Care for Women International, 29, 766–781. https://doi .org/10.1080/07399330802179247 Ding, X., Tang, R., Zhu, J., He, M., Huang, H., Lin, Z., & Zhu, J. (2020). An appraisal of the role of previously reported risk factors in the age at menopause using mendelian randomization. Frontiers in Genetics, 11(507), 1–10. https://doi.org/10.3389/fgene.2020.00507 Edwards, A. L., Shaw, P. A., Halton, C. C., Bailey, S. C., Wolf, M. S., Andrews, E. N., & Cartwright, T. (2021). “It just makes me feel a little less alone”: A qualitative exploration of the podcast Menopause: Unmuted on women’s perceptions of menopause. Menopause, 28(12), 1374–1384. https://doi .org/10.1097/GME.0000000000001855 Ee, C., French, S. D., Xue, C. C., Pirotta, M., & Teede, H. (2017). Acupuncture for menopausal hot flashes: Clinical evidence update and its relevance to decision making. Menopause, 24(8), 980–987. https://doi .org/10.1097/GME.0000000000000850 El Khoudary, S., Greendale, G., Crawford, S., Avis, N., Brooks, M., Thurston, R., Karvonen-Gutierrez, C., Waetjen, L., & Matthews, K. (2019). The menopause transition and women’s health at midlife: A progress report from the Study of Women’s Health Across the Nation (SWAN). Menopause, 26(10), 1213–1227. https://doi.org/10.1097/GME.0000000000001424 Elkins, G. R., Fisher, W. I., Johnson, A. K., Carpenter, J. S., & Keith, T. Z. (2013). Clinical hypnosis in the treatment of postmenopausal hot flashes: A randomized controlled trial. Menopause, 20(3), 291–298. https://doi.org/10.1097 /gme.0b013e31826ce3ed ePocrates. (n.d.). Computerized pharmacology and prescribing reference (updated daily). https://www.epocrates.com/ Espeland, M. A., Shumaker, S. A., Leng, I., Manson, J. E., Brown, C. M., LeBlanc, E. S., Vaughan, L., Robinson, J., Rapp, S. R., Goveas, J. S., Wactawski-Wende, J., Stefanick, M. L., Li, W., Resnick, S. M., & WHIMSY Study Group. (2013). Long-term effects on cognitive function of postmenopausal hormone therapy prescribed to women aged 50 to 55 years. JAMA Internal Medicine, 1723(15), 1429–1436. https://doi.org/10.1001/jamainternmed.2013.7727 Fairfield, K. M., & Fletcher, R. H. (2002). Vitamins for chronic disease prevention in adults: Scientific review. Journal of the American Medical Association, 287(23), 3116–3126. https://doi.org/10.1001/jama.287.23.3116

Fait, T., Sailer, M., & Regidor, P. A. (2019). Prospective observational study to evaluate the efficacy and safety of the pollen extract Sérélys in the management of women with menopausal symptoms. Gynecological Endocrinology, 35(4), 360–363. https://doi.org/10.1080/09513590.2018.1538347 Forman, M. R., Mangini, L. D., Thelus-Jean, R., & Hayward, M. D. (2013). Lifecourse origins of the ages at menarche and menopause. Adolescent Health, Medicine and Therapeutics, 4, 1–21. https://doi.org/10.2147/AHMT.S15946 Fortmann, S. P., Burda, B. U., Senger, C. A., Lin, J. S., & Whitlock, E. P. (2013). Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the US Preventive Services Task Force. Annals of Internal Medicine, 159(12), 824– 834. https://doi.org/10.7326/0003-4819-159-12-201312170-00729 Frame, K., & Alexander, I. M. (2013). Mind-body therapies for sleep disturbances in women at midlife. Journal of Holistic Nursing, 31(4), 276–284. https://doi.org/10.1177/0898010113493504 Freedman, R. R., & Blacker, C. M. (2002). Estrogen raises the sweating threshold in postmenopausal women with hot flashes. Fertility and Sterility, 77(3), 487–490. https://doi.org/10.1016/s0015-0282(01)03009-6 Freedman, R. R., & Woodward, S. (1992). Behavioral treatment of menopausal hot flushes: Evaluation by ambulatory monitoring. American Journal of Obstetrics and Gynecology, 167(2), 436–439. https://doi.org/10.1016 /s0002-9378(11)91425-2 Freeman, E. W., Sammel, M. D., Boorman, D. W., & Zhang, R. (2014). Longitudinal pattern of depressive symptoms around natural menopause. JAMA Psychiatry, 71(1), 36–43. https://doi.org/10.1001/jamapsychiatry.2013.2819 Fulan, H., Changxing, J., Baina, W. Y., Wencui, Z., Chunqing, L., Fan, W., Dandan, L., Dianjun, S., Tong, W., Da, P., & Yashuang, Z. (2011). Retinol, vitamins A, C, and E and breast cancer risk: A meta-analysis and meta-regression. Cancer Causes and Control, 22(10), 1383–1396. https://doi.org/10.1007 /s10552-011-9811-y Gaudet, T. W. (2004). CAM approaches to menopause management: Overview of the options. Menopause Management: Women’s Health Through Midlife & Beyond, 13(Suppl. 1), 48–50. Genazzani, A., Panay, N., Simoncini, T., Depypere, H., Mueck, A., Egarter, C., Biglia, N., Fait, T., Birkhaeuser, M., Skouby, S. O., Brincat, M., Goldstein, S., Ruan, X., Celis-Gonzales, C., & Palacios, S. (2020). Purified and specific cytoplasmic pollen extract: A non-hormonal alternative for the treatment of menopausal symptoms. Gynecological Endocrinology, 36(3), 190–196. https://doi.org/10.1080/09513590.2020.1722994 Gleason, C. E., Dowling, N. M., Wharton, W., Manson, J. E., Miller, V. M., Atwood, C. S., Brinton, E. A., Cedars, M. I., Lobo, R. A., Merriam, G. R., Neal-Perry, G., Santoro, N. F., Taylor, H. S., Black, D. M., Budoff, M. J., Hodis, H. N., Naftolin, F., Harman, S. M., & Asthana, S. (2015). Effects of hormone therapy on cognition and mood in recently postmenopausal women: Findings from the randomized, controlled KEEPS-Cognitive and Affective Study. PLoS Medicine, 12(6), e1001833. https://doi.org/10.1371 /journal.pmed.1001833 Gold, E. B., Colvin, A., Avis, N., Bromberger, J., Greendale, G. A., Powell, L., Sternfeld, B., & Matthews, K. (2006). Longitudinal analysis of the association between VMS and race/ethnicity across the menopausal transition: Study of Women’s Health Across the Nation. American Journal of Public Health, 96(7), 1226–1235. https://doi.org/10.2105/AJPH.2005.066936 Gold, E. B., Crawford, S. L., Avis, N. E., Crandall, C. J., Matthews, K. A., Waetjen, L. E., & Harlow, S. D. (2013). Factors related to age at natural menopause: Longitudinal analyses from SWAN. American Journal of Epidemiology, 178(1), 70–83. https://doi.org/10.1093/aje/kws421 Gold, E. B., Crawford, S. L., Shelton, J. F., Tepper, P. G., Crandall, C. J., Greendale, G. A., Matthews, K. A., Thurston, R. C., & Avis, N. E. (2017). Longitudinal analysis of changes in weight and waist circumference in relation to incident VMS: The Study of Women’s Health Across the Nation (SWAN). Menopause, 24(1), 9–26. https://doi.org/10.1097/GME.0000000000000723 Gold, E. B., Sternfeld, B., Kelsey, J. L., Brown, C., Mouton, C., Reame, N., & Stellato, R. (2000). Relation of demographic and lifestyle factors to symptoms in a multi-racial/ethnic population of women 40–55 years of age. American Journal of Epidemiology, 152(5), 463–473. https://doi.org/10.1093 /aje/152.5.463 Goodman, N. F., Cobin, R. H., Ginzburg, S. B., Katz, I. A., Woode, D. E., Camacho, P. M., Manson, J. E., & Petak, S. M. (2011). American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of menopause. Endocrine Practice, 17(Suppl. 6), 1–25. https://doi.org/10.4158/ep.17.s6.1 Gracia, C. R., & Freeman, E. W. (2018). Onset of the menopause transition: The earliest signs and symptoms. Obstetrics and Gynecology Clinics of North America, 45, 585–597. https://doi.org/10.1016/j.ogc.2018.07.002 Gracia, C. R., Sammel, M. D., Freeman, E. W., Lin, H., Langan, E., Kapoor, S., & Nelson, D. B. (2005). Defining menopause status: Creation of a new

definition to identify the early changes of the menopausal transition. Menopause, 12(2), 128–135. https://doi.org/10.1097/00042192-200512020-00005 Grady, D., Herrington, D., Bittner, V., Blumenthal, R., Davidson, M., Hlatky, M., Hsia, J., Hulley, S., Herd, A., Khan, S., Newby, L. K., Waters, D., Vittinghoff, E., & Wenger, N. (2002). Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). Journal of the American Medical Association, 288(1), 49–57. https://doi.org/10.1001/jama.288.1.49 Greendale, G. A., Huang, M. H., Wight, R. G., Seeman, T., Luetters, C., Avis, N. E., Johnston, J., & Karlamangla, A. S. (2009). Effects of the menopause transition and hormone use on cognitive performance in midlife women. Neurology, 72(21), 1850–1857. https://doi.org/10.1212/WNL .0b013e3181a71193 Greendale, G. A., Wight, R. G., Huang, M. H., Avis, N., Gold, E. B., Joffe, H., Seeman, T., Vuge, M., & Karlamangla, A. S. (2010). Menopause-associated symptoms and cognitive performance: Results from the Study of Women’s Health Across the Nation. American Journal of Epidemiology, 171(11), 1214– 1224. https://doi.org/10.1093/aje/kwq067 Greene, J. G. (1976). A factor analytic study of climacteric symptoms. Journal of Psychosomatic Research, 20, 425–430. https://doi.org/10.1016/ 0022-3999(76)90005-2 Grodstein, F., Lifford, K., Resnick, N. M., & Curhan, G. C. (2004). Postmenopausal hormone therapy and risk of developing urinary incontinence. Obstetrics & Gynecology, 103(2), 254–260. https://doi.org/10.1097/01 .AOG.0000107290.33034.6f Grodstein, F., Manson, J. E., & Stampfer, M. J. (2006). Hormone therapy and coronary heart disease: The role of time since menopause and age at hormone initiation. Journal of Women’s Health, 15(1), 35–44. https://doi.org/10.1089 /jwh.2006.15.35 Guttmacher Institute. (2019). Unintended pregnancy in the United States. Fact Sheet. https://www.guttmacher.org/fact-sheet/unintended-pregnancy-united-states Hansen, K. R., Knowlton, N. S., Thyer, A. C., Charleston, J. S., Soules, M. R., & Klein, N. A. (2008). A new model of reproductive aging: The decline in ovarian non-growing follicle number from birth to menopause. Human Reproduction, 23(3), 699–708. https://doi.org/10.1093/humrep/dem408 Harlow, S. (2018). Menstrual cycle changes as women approaches the final menses. Obstetrics and Gynecology Clinics of North America, 45(4), 599–611. https://doi.org/10.1016/j.ogc.2018.07.003 Harlow, S. D., Cain, K., Crawford, S., Dennerstein, L., Little, R., Mitchell, E. S., & Yosef, M. (2006). Evaluation of four proposed bleeding criteria for the onset of late menopausal transition. Journal of Clinical Endocrinology and Metabolism, 91(9), 3432–3438. https://doi.org/10.1210/jc.2005-2810 Harlow, S. D., Gass, M., Hall, J. E., Lobo, R., Maki, P., Rebar, R. W., Sherman, S., Sluss, P. M., & de Villiers, T. J. (2012). Executive summary of the Stages of Reproductive Aging Workshop + 10: Addressing the unfinished agenda of staging reproductive aging. Menopause, 19(4), 387–395. https://doi .org/10.1097/gme.0b013e31824d8f40 Harris, M. T. (2008). Aging women’s journey toward wholeness: New visions and directions. Health Care for Women International, 29(10), 962–979. http://doi .org/10.1080/07399330802269659 He, C., & Murabito, J. M. (2014). Genome-wide association studies of age at menarche and age at natural menopause. Molecular and Cellular Endocrinology, 382(1), 767–779. https://doi.org/10.1016/j.mce.2012.05.003 Hefler, L. A., Grimm, C., Bentz, E. K., Reinthaller, A., Heinze, G., & Tempfer, C. B. (2006). A model for predicting age at menopause in white women. Fertility and Sterility, 85(2), 451–454. https://doi.org/10.1016/j.fertnstert.2005.07.1300 Heiss, G., Wallace, R., Anderson, G. L., Aragaki, A., Beresford, S. A., Brzyski, R., Chlebowski, R. T., Gass, M., LaCroix, A., Manson, J. E., Prentice, R. L., Rossouw, J., & Stefanick, M. L. (2008). Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. Journal of the American Medical Association, 299(9), 1036–1045. https://doi.org/10.1001 /jama.299.9.1036 Henderson, K. D., Bernstein, L., Henderson, B., Kolonel, L., & Pike, M. C. (2008). Predictors of the timing of natural menopause in the Multiethnic Cohort Study. American Journal of Epidemiology, 167(11), 1287–1294. https://doi .org/10.1093/aje/kwn046 Henderson, V. W., & Popat, R. A. (2011). Effects of endogenous and exogenous estrogen exposures in midlife and late-life women on episodic memory and executive functions. Neuroscience, 191, 129–138. https://doi.org/10.1016/j .neuroscience.2011.05.059 Henderson, V. W., St John, J. A., Hodis, H. N., McCleary, C. A., Stanczyk, F. Z., Shoupe, D., Kono, N., Dustin, L., Allayee, H., & Mack, W. J. (2016). Cognitive effects of estradiol after menopause: A randomized trial of the timing hypothesis. Neurology, 87(7), 699–708. https://doi.org/10.1212 /WNL.0000000000002980 Herber-Gast, G. C., & Mishra, G. D. (2013). Fruit, Mediterranean-style, and high-fat and -sugar diets are associated with the risk of night sweats and hot

flushes in midlife: Results from a prospective cohort study. American Journal of Clinical Nutrition, 97, 1092–1099. https://doi.org/10.3945/ajcn.112.049965 Hogervorst, E., De Jager, C., Budge, M., & Smith, A. D. (2004). Serum levels of estradiol and testosterone and performance in different cognitive domains in healthy elderly men and women. Psychoneuroendocrinology, 29(3), 405–421. https://doi.org/10.1016/s0306-4530(03)00053-2 Hsia, J., Langer, R. D., Manson, J. E., Kuller, L., Johnson, K. C., Hendrix, S. L., Pettinger, M., Heckbert, S. R., Greep, N., Crawford, S., Eaton, C. B., Kostis, J. B., Caralis, P., Prentice, R., & Women’s Health Initiative Investigators. (2006). Conjugated equine estrogens and coronary heart disease: The Women’s Health Initiative. Archives of Internal Medicine, 166(3), 357–365. https://doi .org/10.1001/archinte.166.3.357 Huber, A., Grimm, C., Huber, J. C., Schneeberger, C., Leodolter, S., Reinthaller, A., Tempfer, C. B., & Hefler, L. A. (2006). A common polymorphism within the steroid 5-alpha-reductase type 2 gene and timing of menopause in Caucasian women. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 125(2), 221–225. https://doi.org/10.1016/j.ejogrb.2005.10.012 Hulley, S., Furberg, C., Barrett-Connor, E., Cauley, J., Grady, D., Haskell, W., Knopp, R., Lowery, M., Satterfield, S., Schrott, H., Vittinghoff, E., & Hunninghake, D. (2002). Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). Journal of the American Medical Association, 288(1), 58–66. https://doi.org/10.1001/jama.288.1.58 Hulley, S., Grady, D., Bush, T., Furberg, C., Herrington, D., Riggs, B., & Vittinghoff, E. (1998). Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/ Progestin Replacement Study (HERS) Research Group. Journal of the American Medical Association, 280(7), 605–613. https://doi.org/10.1001/jama.280.7.605 Hunter, M. S. (2014). Beliefs about hot flashes drive treatment benefit. Menopause, 21(8), 909. https://doi.org/10.1097/GME.0000000000000297 InterLACE Study Team. (2019). Variations in reproductive events across life: A pooled analysis of data from 505 147 women across 10 countries. Human Reproduction, 34(5), 881–893. https://doi.org/10.1093/humrep/dez015 Irvin, J. H., Domar, A. D., Clark, C., Zuttermeister, P. C., & Friedman, R. (1996). The effects of relaxation response training on menopausal symptoms. Journal of Psychosomatic Obstetrics and Gynecology, 17(4), 202–207. https://doi .org/10.3109/01674829609025684 Jenabi, E., & Poorolajal, J. (2015). The association between hot flushes and smoking in midlife women: A meta-analysis. Climacteric, 18(6), 797–801. https://doi.org/10.3109/13697137.2015.1080236 Johnson, A., Roberts, L., & Elkins, G. (2019). Complementary and alternative medicine for menopause. Journal of Evidence-Based Integrative Medicine, 24, 1–14. https://doi.org/10.1177/2515690X19829380 Kargozar, R., Azizi, H., & Salary, R. (2017). A review of effective herbal medicines in controlling menopausal symptoms. Electronic Physician, 9(11), 5826–5833. https://doi.org/10.19082/5826 Kaufert, P., Boggs, P. P., Ettinger, B., Woods, N. F., & Utian, W. H. (1998). Women and menopause: Beliefs, attitudes, and behaviors. The North American Menopause Society 1997 Menopause Survey. Menopause, 5(4), 197–202. Kortsmit, K., Mandel, M. G., Reeves, J. A., Clark, E., Pagano, H. P., Nguyen, A., Petersen, E. E., & Whiteman, M. K. (2021). Abortion surveillance—United States, 2019. MMWR Morbidity and Mortality Weekly Report Surveillance Summaries, 70(9), 1–29. https://doi.org/10.15585/mmwr.ss7009a1 LeBoff, N. S., Greenspan, S. L., Insogna, K. L., Lewiecki, E. M., Saag, K. G., Singer, A. J., & Siris, E. S. (2022). The clinician’s guide to prevention and treatment of osteoporosis. Osteoporosis International, 33, 2049–2102. https:// doi.org/10.1007/s00198-022-06479-8 Lehert, P., Villaseca, P., Hogervorst, E., Maki, P. M., & Henderson, V. W. (2015). Individually modifiable risk factors to ameliorate cognitive aging: A systematic review and meta-analysis. Climacteric, 18(5), 678–689. https://doi.org /10.3109/13697137.2015.1078106 Lethaby, A. E., Marjoribanks, J., Kronenberg, F., Roberts, H., Eden, J., & Brown, J. (2013). Phytoestrogens for menopausal vasomotor symptoms. Cochrane Database of Systematic Reviews, 2013(12), CD001395. https://doi .org/10.1002/14651858.CD001395.pub4 Li, C. I., Malone, K. E., Porter, P. L., Lawton, T. J., Voigt, L. F., Cushing-Haugen, K. L., Lin, M. G., Yuan, X., & Daling, J. R. (2008). Relationship between menopausal hormone therapy and risk of ductal, lobular, and ductal-lobular breast carcinomas. Cancer Epidemiology, Biomarkers and Prevention, 17(1), 43–50. https://doi.org/10.1158/1055-9965.EPI-07-0558 Liao, L., Lunn, S., & Baker, M. (2015). Midlife menopause: Male partners talking. Sexual and Relationship Therapy, 30(1), 167–180. https://doi.org/10.1080/14 681994.2014.893290 Loprinzi, C. L., Levitt, R., Barton, D., Sloan, J. A., Dakhil, S. R., Nikcevich, D. A., Bearden, J. D., 3rd, Mailliard, J. A., Tschetter, L. K., Fitch, T. R., & Kugler, J. W. (2006). Phase III comparison of depomedroxyprogesterone acetate to venlafaxine for managing hot flashes: North Central Cancer Treatment

Group Trial N99C7. Journal of Clinical Oncology, 24(9), 1409–1414. https:// doi.org/10.1200/JCO.2005.04.7324 Lu, Y., Liu, P., Recker, R. R., Deng, H. W., & Dvornyk, V. (2010). TNFRSF11A and TNFSF11 are associated with age at menarche and natural menopause in white women. Menopause, 17(5), 1048–1054. https://doi.org/10.1097 /gme.0b013e3181d5d523 Lujan-Barosso, L., Gibert, K., Obón-Santacana, M., Chirlaque, M. D., Sánchez, M. J., Larrañaga, N., Barricarte, A., Quirós, J. R., Salamanca-Fernández, E., Colorado-Yohar, S., Gómez-Pozo, B., Agudo, A., & Duell, E. J. (2018). The influence of lifestyle, diet, and reproductive history on age at natural menopause in Spain: Analysis from the EPIC-Spain sub-cohort. American Journal of Human Biology, 30(6), 1–10. https://doi.org/10.1002/ajhb.23181 Lund, K., Siersma, V., Brodersen, J., & Waldorff, F. B. (2019). Efficacy of a standardized acupuncture approach for women with bothersome menopausal symptoms: A pragmatic randomized study in primary care (the ACOM study). BMJ Open, 9(1), e023637. https://doi.org/10.1136/bmjopen-2018-023637 Marvan, M. L., Islas, M., Vela, L., Chrisler, J. C., & Warren, E. A. (2008). Stereotypes of women in different stages of their reproductive life: Data from Mexico and the United States. Health Care for Women International, 29, 673–687. https://doi.org/10.1080/07399330802188982 McConnell, D. S., Stanczyk, F. Z., Sowers, M. R., Randolph, J. F., Jr., & Lasley, B. L. (2012). Menopausal transition stage-specific changes in circulating adrenal androgens. Menopause, 19(6), 658–663. https://doi.org/10.1097 /gme.0b013e31823fe274 Meissner, H. I., Breen, N., Taubman, M. L., Vernon, S. W., & Graubard, B. I. (2007). Which women aren’t getting mammograms and why? Cancer Causes and Control, 18(1), 61–70. https://doi.org/10.1007/s10552-006-0078-7 Mishra, G. D., Chung, H. F., Cano, A., Chedraui, P., Goulis, D. G., Lopes, P., Mueck, A., Rees, M., Senturk, L. M., Simoncini, T., Stevenson, J. C., Stute, P., Tuomikoski, P., & Lambrinoudaki, I. (2019). EMAS position statement: Predictors of premature and early natural menopause. Maturitas, 123, 82–88. https://doi.org/10.1016/j.maturitas.2019.03.008 Mohammady, M., Janani, L., Jahanfar, S., & Mousavi, M. S. (2018). Effect of omega-3 supplements on vasomotor symptoms in menopausal women: A systematic review and meta-analysis. European Journal of Obstetrics & Gynecology and Reproductive Biology, 228, 295–302. https://doi.org/10.1016/j .ejogrb.2018.07.008 Mosca, L., Benjamin, E. J., Berra, K., Bezanson, J. L., Dolor, R. J., Lloyd-Jones, D. M., Newby, L. K., Piña, I. L., Roger, V. L., Shaw, L. J., Zhao, D., Beckie, T. M., Bushnell, C., D’Armiento, J., Kris-Etherton, P. M., Fang, J., Ganiats, T. G., Gomes, A. S., Gracia, C. R., . . . Wenger, N. K. (2011). Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update: A guideline from the American Heart Association. Journal of the American College of Cardiology, 57(12), 1404–1423. https://doi.org/10.1016/j .jacc.2011.02.005 Nasto, L. A., Fusco, A., Colangelo, D., Mormando, M., Di Giacomo, G., Rossi, B., De Marinis, L., Logroscino, C. A., & Pola, E. (2012). Clinical predictors of vertebral osteoporotic fractures in post-menopausal women: A crosssectional analysis. European Review for Medical and Pharmacological Sciences, 16(9), 1227–1234. Newhart, M. R. (2013). Menopause matters: The implications of menopause research for studies of midlife health. Health Sociology Review, 22(4), 365–376. https://doi.org/10.5172/hesr.2013.22.4.365 North American A+Menopause Society. (2023). Menopause Health Questionnaire. https://www.menopause.org/publications/clinical-practice-materials /menopause-health-questionnaire North American Menopause Society. (2019). Menopause practice: A clinician’s guide (6th ed.). Author. North American Menopause Society. (2022). The 2022 hormone therapy position statement of the North American Menopause Society. Menopause, 29(7), 767–794. https://doi.org/10.1097/GME.0000000000002028 Pastore, L. M., Carter, R. A., Hulka, B. S., & Wells, E. (2004). Self-reported urogenital symptoms in postmenopausal women: Women’s Health Initiative. Maturitas, 49(4), 292–303. https://doi.org/10.1016/j.maturitas.2004.06.019 Prior, J. C. (2018). Progesterone for treatment of symptomatic menopausal women. Climacteric, 21(4), 358–365. https://doi.org/10.1080/13697137.201 8.1472567 Ravdin, P. M., Cronin, K. A., Howlader, N., Berq, C. D., Chlebowski, R. T., Feuer, E. J., Edwards, B. K., & Berry, E. D. (2007). The decrease in breast-cancer incidence in 2003 in the United States. New England Journal of Medicine, 356(16), 1670–1674. https://doi.org/10.1056/NEJMsr070105 Reed, S. D., Guthrie, K. A., Newton, K. M., Anderson, G. L., Booth-LaForce, C., Caan, B., Carpenter, J. S., Cohen, L. S., Dunn, A. L., Ensrud, K. E., Freeman, E. W., Hunt, J. R., Joffe, H., Larson, J. C., Learman, L. A., Rothenberg, R., Seguin, R. A., Sherman, K. J., Sternfeld, B. S., & LaCroix, A. Z. (2014). Menopausal quality of life: RCT of yoga, exercise, and omega-3 supplements.

American Journal of Obstetrics and Gynecology, 210(3), 244.e1–244.e11. https://doi.org/10.1016/j.ajog.2013.11.016 Resnick, S. M., Maki, P. M., Golski, S., Kraut, M. A., & Zonderman, A. B. (1998). Effects of estrogen replacement therapy on PET cerebral blood flow and neuropsychological performance. Hormones and Behavior, 34(2), 171–182. https://doi.org/10.1006/hbeh.1998.1476 Roberts, A., & Lethaby, A. (2014). Phytoestrogens for menopausal vasomotor symptoms: A Cochrane review summary. Maturitas, 78, 79–81. https://doi .org/10.1016/j.maturitas.2014.04.004 Rossouw, J. E., Anderson, G. L., Prentice, R. L., LaCroix, A. Z., Kooperberg, C., Stefanick, M. L., Jackson, R. D., Beresford, S. A. A., Howard, B. V., Johnson, K. C., Kotchen, J. M., & Ockene, J. (2002). Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women’s Health Initiative randomized controlled trial. Journal of the American Medical Association, 288(3), 321–333. https://doi.org/10.1001 /jama.288.3.321 Rossouw, J. E., Prentice, R. L., Manson, J. E., Wu, L., Barad, D., Barnabei, V. M., Ko, M., LaCroix, A. Z., Margolis, K. L., & Stefanick, M. L. (2007). Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. Journal of the American Medical Association, 297(13), 1465–1477. https://doi.org/10.1001/jama.297.13.1465 Salpeter, S. R., Walsh, J. M., Greyber, E., Ormiston, T. M., & Salpeter, E. E. (2004). Mortality associated with hormone replacement therapy in younger and older women: A meta-analysis. Journal of General Internal Medicine, 19(7), 791–804. https://doi.org/10.1111/j.1525-1497.2004.30281.x Sapre, S., & Thakur, R. (2014). Lifestyle and dietary factors determine age at natural menopause. Journal of Mid-Life Health, 5(1), 3–5. https://doi.org/10 .4103/0976-7800.127779 Schiff, I., Regestein, Q., Schinfeld, J., & Ryan, K. J. (1980). Interactions of oestrogens and hours of sleep on cortisol, FSH, LH, and prolactin in hypogonadal women. Maturitas, 2(3), 179–183. https://doi .org/10.1016/0378-5122(80)90002-x Shaywitz, S. E., Naftolin, F., Zelterman, D., Marchione, K. E., Holahan, J. M., Palter, S. F., & Shaywitz, B. A. (2003). Better oral reading and short-term memory in midlife, postmenopausal women taking estrogen. Menopause, 10(5), 420–426. https://doi.org/10.1097/01.GME.0000060241.02837.29 Shumaker, S. A., Legault, C., Rapp, S. R., Thal, L., Wallace, R. B., Ockene, J. K., Hendrix, S. L., Jones, B. N., 3rd, Assaf, A. R., Jackson, R. D., Kotchen, J. M., Wassertheil-Smoller, S., Wactawski-Wende, J. (2003). Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: The Women’s Health Initiative Memory Study: A randomized controlled trial. Journal of the American Medical Association, 289(20), 2651–2662. https://doi.org/10.1001/jama.289.20.2651 Sievert, L. L. (2014). Anthropology and the study of menopause: Evolutionary, developmental, and comparative perspectives. Menopause, 21(10), 1151–1159. https://doi.org/10.10.97/gme.0000000000000341 Smith, R. L., Flaws, J. A., & Gallicchio, L. (2015). Does quitting smoking decrease the risk of midlife hot flashes? A longitudinal analysis. Maturitas, 82(1), 123–127. https://doi.org/10.1016/j.maturitas.2015.06.029 Soares, C. N., Almeida, O. P., Joffe, H., & Cohen, L. S. (2001). Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: A double-blind, randomized, placebo-controlled trial. Archives of General Psychiatry, 58(6), 529–534. https://doi.org/10.1001/archpsyc.58.6.529 Sood, R., Sood, A., Wolf, S. L., Linquist, B. M., Liu, H., Sloan, J. A., Satele, D. V., Loprinzi, C. L., & Barton, D. L. (2013). Paced breathing compared with usual breathing for hot flashes. Menopause, 20(2), 179–184. https://doi .org/10.1097/gme.0b013e31826934b6 Spencer, K. L., Malinowski, J., Carty, C. L., Franceschini, N., Fernández-Rhodes, L., Young, A., Cheng, I., Ritchie, M. D., Haiman, C. A., Wilkens, L., Chunyuanwu, Matise, T. C., Carlson, C. S., Brennan, K., Park, A., Rajkovic, A., Hindorff, L. A., Buyske, S., & Crawford, D. C. (2013). Genetic variation and reproductive timing: African American women from the Population Architecture using Genomics and Epidemiology (PAGE) Study. PloS One, 8(2), e55258. https://doi.org/10.1371/journal.pone.0055258 Stanczyk, F. Z., Matharu, H., & Winer, S. A. (2021). Bioidentical hormones. Climacteric, 24(1), 38–45. https://doi.org/10.1080/13697137.2020.1862079 Stanzel, K. A., Hammarberg, K., & Fisher, J. (2017). Experiences of menopause, self-management strategies for menopausal symptoms and perceptions of health care among immigrant women: A systematic review. Climateric, 21(2), 101–110. https://doi.org/10.1080/13697137.2017.1421922 Sternfeld, B., Guthrie, K. A., Ensrud, K. E., LaCroix, A. Z., Larson, J. C., Dunn, A. L., Anderson, G. L., Seguin, R. A., Carpenter, J. S., Newton, K. M., Reed, S. D., Freeman, E. W., Cohen, L. S., Joffe, H., Roberts, M., & Caan,

B. J. (2014). Efficacy of exercise for menopausal symptoms: A randomized controlled trial. Menopause, 21(4), 330–338. https://doi.org/10.1097 /GME.0b013e31829e4089 Sydenham, E., Dangour, A. D., & Lim, W. S. (2012). Omega 3 fatty acid for the prevention of cognitive decline and dementia. Cochrane Database of Systematic Reviews, 2012(6), CD005379. https://doi.org/10.1002/14651858. CD005379.pub3 Tepper, P. G., Brooks, M. M., Randolph, J. F., Jr., Crawford, S. L., El Khoudary, S. R., Gold, E. B., Lasley, B. L., Jones, B., Joffe, H., Hess, R., Avis, N. E., Harlow, S., McConnell, D. S., Bromberger, J. T., Zheng, H., Ruppert, K., & Thurston, R. C. (2016). Characterizing the trajectories of VMS across the menopausal transition. Menopause, 23(10), 1067–1074. https://doi.org/10.1097 /GME.0000000000000676 Thompson, J. J., Ritenbaugh, C., & Nichter, M. (2017). Why women choose compounded bioidentical hormone therapy: Lessons from a qualitative study of menopausal decision-making. BMC Women’s Health, 17(1), 97. https://doi .org/10.1186/s12905-017-0449-0 Thurston, R. C., & Joffe, H. (2011). Vasomotor symptoms and menopause: Findings from the Study of Women’s Health Across the Nation. Obstetrics and Gynecology Clinics of North America, 38(3), 489–501. https://doi .org/10.1016/j.ogc.2011.05.006 Thurston, R. C., Sowers, M. R., Chang, Y., Sternfeld, B., Gold, E. B., Johnston, J. M., & Matthews, K. A. (2008). Adiposity and reporting of VMS among midlife women: The Study of Women’s Health Across the Nation. American Journal of Epidemiology, 67(1), 78–85. https://doi.org/10.1093 /aje/kwm244 Unfer, V., Casini, M. L., Costabile, L., Mignosa, M., Gerli, S., & Di Renzo, G. C. (2004). Endometrial effects of long-term treatment with phytoestrogens: A randomized, double-blind, placebo-controlled study. Fertility and Sterility, 82(1), 145–148. https://doi.org/10.1016/j.fertnstert.2003.11.041 U.S. Census Bureau. (2019). Age and sex composition in the United States: 2019. https://www.census.gov/data/tables/2019/demo/age-and-sex/2019-age-sex -composition.html U.S. Department of Health and Human Services, & U.S. Department of Agriculture. (2015, December). 2015-2020 dietary guidelines for Americans (8th ed.). https://health.gov/dietaryguidelines/2015/resources/2015-2020_Dietary _Guidelines.pdf U.S. Food and Drug Administration. (2008). FDA takes action against compounded menopause hormone therapy drugs. https://www.fiercebiotech.com/biotech /fda-takes-action-against-compounded-menopause-hormone-therapy-drugs van Meurs, J. B., Dhonukshe-Rutten, R. A., Pluijm, S. M., van der Klift, M., de Jonge, R., Lindemans, J., de Groot, L. C., Hofman, A., Witteman, J. C., van Leeuwen, J. P., Breteler, M. M., Lips, P., Pols, H. A., & Uitterlinden, A. G. (2004). Homocysteine levels and the risk of osteoporotic fracture. New England Journal of Medicine, 350(20), 2033–2041. https://doi.org/10.1056/NEJMoa032546 Versi, E., Harvey, M. A., Cardozo, L., Brincat, M., & Studd, J. W. (2001). Urogenital prolapse and atrophy at menopause: A prevalence study. International Urogynecology Journal and Pelvic Floor Dysfunction, 12(2), 107–110. https:// doi.org/10.1007/s001920170074 Williams, J. W., Plassman, B. L., Burke, J., Holsinger, T., & Benjamin, S. (2010). Preventing Alzheimer’s disease and cognitive decline. Evidence Report/Technology Assessment No. 193. Agency for Healthcare Research and Quality. https://www.ncbi.nlm.nih.gov/books/NBK47456 Wilson, R. A., Marino, E. R., & Wilson, T. A. (1966). Norethynodrel-mestranol (Enovid) for prevention and treatment of the climacteric. Journal of the American Geriatrics Society, 14(10), 967–985. https://doi.org/10.1111/j .1532-5415.1966.tb02880.x Woods, N. F., Mitchell, E. S., & Adams, C. (2000). Memory functioning among midlife women: Observations from the Seattle Midlife Women’s Health Study. Menopause, 7(4), 257–265. Wu, A.-M., Huang, C.-Q., Lin, Z.-K., Tian, N.-F., Ni, W.-F., Wang, X.-Y., Xu, H.-Z., & Chi, Y.-L. (2014). The relationship between vitamin A and risk of fracture: Meta-analysis of prospective studies. Journal of Bone and Mineral Research, 29(9), 2032–2039. https://doi.org/10.1002/jbmr.2237 Zandi, P. P., Carlson, M. C., Plassman, B. L., Welsh-Bohmer, K. A., Mayer, L. S., Steffens, D. C., & Breitner, J. C. (2002). Hormone replacement therapy and incidence of Alzheimer disease in older women: The Cache County Study. Journal of the American Medical Association, 288(17), 2123–2129. https:// doi.org/10.1001/jama.288.17.2123 Zava, D. T., Groves, M. N., & Stanczyk, F. Z. (2014). Percutaneous absorption of progesterone. Maturitas, 77, 91–92. https://doi.org/10.1016/j.maturitas .2013.10.006

Chapter

35

Osteoporosis*

Ivy M. Alexander, Matthew Witkovic, Kara Vignati,

Osteoporosis (OP) is the most common bone disease in humans, representing a major public health problem (Sarafrazi et al., 2021; LeBoff et al., 2022; North American Menopause Society [NAMS], 2021). Fracture attributable to OP is a significant health problem that affects all genders, especially those experiencing menopause (LeBoff et al., 2022; NAMS, 2021). As estrogen and progesterone levels fall, bone strength also declines. OP is a disorder of the skeletal system characterized by a reduction in bone strength and increased risk for fracture (Camacho et al., 2020; Sarafrazi et al., 2021; LeBoff et al., 2022; NAMS, 2021). Low bone mass (LBM; previously identified as osteopenia) is like OP except that there is a lesser amount of bone lost. Two factors contribute to bone strength: bone mineral density (BMD) and bone quality. BMD refers to the thickness and volume of the bone. Bone quality refers to the bone architecture, mineralization, rate of turnover, and accumulated damage (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). BMD is easily measured using densitometry testing such as the dual-energy x-ray absorptiometry (DXA). Bone quality is more difficult to assess as simple measurement devices are not readily available. OP is a silent condition in that it is not evident until a fracture occurs or kyphosis is recognized. Even with fracture, OP is often missed. For these reasons, national organizations have initiated programs to increase awareness and recommend prevention early in life as well as routine screening to identify and manage bone loss before fractures occur. The goal for preventing, identifying, and managing OP is to prevent fractures, which are associated with extensive negative sequelae. A note about language: The authors attempt to use inclusive language throughout this chapter. The need to accurately represent data from research sometimes requires the use of specific terms such as woman and women. Additionally, because bone remodeling is greatly influenced by endogenous female or male hormones, the terms female and male are used to represent biological sex when appropriate. Bone remodeling in a transgender person who does not take

and

Daniela LaRosa Karanda

gender-affirming hormone therapy (GAHT) or a nonbinary person is the same as that in persons of the same biological sex. Bone remodeling is thought to remain stable across the lifespan for transgender persons who do take GAHT since the endogenous decreases in hormones are overridden by their exogenous GAHT.

DEFINITION OP is defined by BMD at the hip or lumbar spine that is 2.5 or more standard deviations below the mean BMD of a young adult reference population. When the score is compared to the average young adult reference population matched by sex and ethnicity, the score is referred to as a T-score (Alexeeva et al., 1994). OP is a skeletal disorder characterized by a loss of bone matrix and reduced bone integrity and strength. It predisposes patients to an increased risk for fracture (Dolan & Walsh, 2022). OP is a risk factor for fracture, just as hypertension is a risk factor for stroke. The disease causes over 2 million fractures annually in the United States, exceeding the combined number of new cases of breast cancer, myocardial infarction, and prostate cancer (LeBoff et al., 2022). Fracture incidence is projected to increase to approximately 3.2 million annually by the year 2040 (LeBoff et al., 2022). Primary OP is due to bone loss related to age, gender, family history, and other factors. Bone loss accelerates in females with the decline of estrogen and progestogen hormones after menopause. One large modifiable risk factor for OP is nutritional deficiency including low intake of calcium, vitamin D, dietary protein, and fruits and vegetables, or high consumption of alcohol. Other modifiable risk factors include a sedentary lifestyle, low body mass index (BMI), cigarette smoking, stress, and air pollution. Nonmodifiable risk factors include history of falls, older age, sex, White ethnic background, prior fractures, and genetic predisposition (Pouresmaeili et

*This chapter is a revision of the chapter that appeared in the second edition of this textbook, coauthored by Emily Miesse, and we thank her for her original contribution.

653

654  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

al., 2018). Among postmenopausal persons, low BMD at the femoral neck (T-score of −1.0 or below) is found in 10% of Black Americans, 16% of Mexican Americans, and 21% of White Americans. More than 20% of postmenopausal persons have prevalent vertebral fractures (VFs). In the United States, as many as 8 million females and 2 million males have OP (Lindsay & Cosman, 2018), and more than 40 million people have bone mass levels that increase their risk for contracting OP. Secondary OP results from medical conditions or pharmacologic treatments that hinder attaining peak bone mass and/ or interfere with bone turnover or predispose to accelerated bone loss (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). Secondary causes of OP include chronic use of some medications, especially corticosteroids, as well as an array of conditions that interfere with bone modeling or remodeling such as hypogonadism, hyperparathyroidism, chronic liver disease, inflammatory diseases, renal disease, cardiovascular disease, diabetes mellitus, and dementia (Pouresmaeili et al., 2018). OP affects approximately 10 million U.S. adults, and about 43 million more have LBM (Sarafrazi et al., 2021; Lindsay & Cosman, 2018). LBM is defined as a BMD T-score of −1.0 to −2.5, meaning the person’s BMD is between 1 and 2.5 standard deviations below that of an average young person of the same sex and ethnicity. Despite the high prevalence of OP and LBM, only a small fraction of these cases are diagnosed and treated (Camacho et al., 2020; LeBoff et al., 2022; Lindsay & Cosman, 2018; NAMS, 2021). OP and LBM increase a person’s risk for fracture (Camacho et al., 2020; LeBoff et al., 2022; Lindsay & Cosman, 2018; NAMS, 2021). At age 50, the lifetime risk of developing fractures is estimated to be 40% to 50% for White U.S. females (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). The lifetime risk for a hip fracture is estimated at 6% among American Blacks, 14% among American Hispanics, and 17% among American Whites. Yearly incidence of OP-related fracture is projected to increase by 68% by 2040 (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). The real concerns related to bone loss are related to fracture. OP-related fractures are often associated with devastating sequelae. Hip fracture conveys extraordinary morbidity and mortality outcomes. Up to one out of every four patients die in the year following a hip fracture (25% mortality rate), 25% need long-term (nursing home) care, and half (50%) never return to their prefracture level of mobility. Hip fractures are also associated with an increased incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE; Lindsay & Cosman, 2018). VFs frequently cause substantial acute and chronic pain, loss of height, and kyphosis. Kyphosis can advance to restrict movement, interfere with gastrointestinal and other abdominal organ function, and limit lung capacity (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). Physical disability and inability to enjoy previous activities add to the burden of the disease by causing isolation and depression, factors that can increase risks for additional bone loss and falls through inactivity. Enormous costs result from OP-related fractures, both personally and economically. Annual costs of $57 billion are projected to exceed $95 billion by 2040. The current annual

financial toll accounts for hospital admissions (currently over 432,000), long-term care facility admissions (over 180,000), and around 2.5 million outpatient healthcare visits (NAMS, 2021).

ETIOLOGY Peak bone mass is usually attained by about age 30 years (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). When peak bone mass is achieved, bone remodeling continues. Osteoclast cells secrete enzymes that digest bone and create microscopic holes, called resorption cavities, along the surface of the bone. Osteoblasts then migrate to the surface and secrete collagen to fill the resorption cavities with newly formed osteoid material. The osteoblasts are eventually replaced with lining cells, and the process repeats. Bone formation and remodeling are regulated by multiple endocrine and hormonal mechanisms. During childhood, when bone mass increases rapidly, osteoblasts act independently and in response to growth hormones. However, in adulthood, osteoblasts act in response to osteoclast activity and functional load stress that is exerted on bone, such as the stress caused by physical exercise. LBM and OP are caused when the normal processes of bone remodeling are unbalanced and resorption rates exceed bone formation, resulting in reduced bone quality and strength (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). Primary OP is associated with aging for both females and males. It affects females more than males because of the rapid increase in bone loss that accompanies the decline in estrogen and progesterone levels during the transition to postmenopause (TPM; Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). The rate of bone turnover and bone loss accelerates during the 3- to 5-year span preceding menopause. On average, bone loss of 2% occurs annually during the 1 to 3 years prior to menopause and over 5 to 10 years after, resulting in bone loss of 10% to 12% across the TPM (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). Secondary OP is bone loss caused by disease processes or medications (Box 35.1) that interfere with the normal process of bone formation (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). Secondary OP can affect males or females at any age and may be considered if the Z-score identified on a DXA scan is low. Z-score compares the patient BMD to that of the average same-aged reference population matched by sex and ethnicity. Low Z-scores may also be seen in females or males who never achieved peak bone mass levels when growing up. Fracture risk is also affected by disease processes or medications that increase risk for fracture (Box 35.1).

RISK FACTORS Some risk factors for OP can be controlled; others cannot (Box 35.2). Risk factors for fracture and falls are distinct from the risk factors for bone loss (Box 35.3).

Chapter 35  Osteoporosis 655

Box 35.1  Medicationsa and Medical Conditionsa Associated With Bone Loss or Increased Fracture Risk Medications Associated With Bone Loss or Increased Fracture Risk

Medical Conditions Associated with Bone Loss or Increased Fracture Risk

Aluminum-containing antacids (e.g., Amphojel, Maalox, Mylanta) Androgen deprivation therapy Anticoagulants (unfractionated heparin) Anticonvulsants (e.g., carbamazepine [Carbatrol, Tegretol], divalproex [Depakote], phenobarbital, phenytoin [Dilantin], valproate [Depacon]) Aromatase inhibitors Barbiturates Cholestyramine (e.g., Questran) Chemotherapy/immunosuppressors (e.g., methotrexate [Trexall]) Cytotoxic agents Glucocorticosteroids (e.g., prednisone [Deltasone, Sterapred]) Gonadotropin-releasing hormone (GnRH) agonist or antagonist Immunosuppressive agents Insulin with hypoglycemia Lithium (e.g., Eskalith, Lithobid) Medroxyprogesterone acetate intramuscular injection (e.g., Depo-Provera) Methotrexate Parenteral nutrition Proton pump inhibitors (PPIs, e.g., rabeprazole [AcipHex], esomeprazole [Nexium], lansoprazole [Prevacid], omeprazole [Prilosec]) Selective norepinephrine-reuptake inhibitors (SNRIs, e.g., duloxetine [Cymbalta]) Selective serotonin reuptake inhibitors (SSRIs, e.g., citalopram [Celexa], sertraline [Zoloft]) SGLT2 inhibitors (gliflozins) Tamoxifen (premenopausal for breast cancer) Thiazolidinediones (e.g., pioglitazone [Actos], rosiglitazone [Avandia]) Thyroid hormone (in excess; e.g., levothyroxine [Levoxyl, Levothroid, Synthroid]) Warfarin (e.g., Coumadin)

Alcoholism AIDS/HIV Bone disorders (e.g., acromegaly, ankylosing spondylitis, osteogenesis imperfecta, posttransplant bone disease) Chronic liver disease, cholestatic liver disease, primary biliary cirrhosis Chronic renal failure, end-stage renal disease, renal tubular acidosis Connective tissue diseases (e.g., lupus, multiple sclerosis, rheumatoid arthritis, sarcoidosis) Depression Eating disorders (e.g., anorexia nervosa, vitamin D deficiency, calcium deficiency, obesity) Endocrine disorders (e.g., diabetes [type 1, type 2], gonadal insufficiency [primary, secondary], hypercortisolism [e.g., Cushing syndrome], hyperparathyroidism, hyperthyroidism, hypothyroidism [overtreated], thyrotoxicosis) Gastrointestinal disorders (e.g., celiac disease, malabsorption syndromes, gastrectomy, gastric bypass surgery, inflammatory bowel disease, pancreatic disease) Genetic disorders (e.g., cystic fibrosis, Gaucher disease, hemochromatosis, hypophosphatasia, Klinefelter syndrome, Marfan syndrome, osteogenesis imperfecta, sickle cell, thalassemia, Turner syndrome) Hematologic disorders (e.g., hemophilia, leukemia) HIV/AIDS Liver disease, chronic, cirrhosis Neuromuscular disorders (muscular dystrophy, paraplegia, quadriplegia, proximal myopathy) Prolonged immobility Renal disease, chronic Respiratory disorders (e.g., cystic fibrosis, chronic obstructive pulmonary disease) Rheumatologic disease Seizure disorders (e.g., epilepsy)

Representative list, not exhaustive. Source: Adapted from Camacho, P. M., Petak, S. M., Binkley, N., Diab, D. L., Eldeiry, L. S., Farooki A, Harris, S. T., Hurley, D. L., Kelly, J., Lewiecki, E. M., Pessah-­Pollack, R., McClung, M., Wimalawansa, S. J., & Watts, N. B. (2020). American Association of Clinical Endocrinologists/American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis—2020 update. Endocrine Practice, 26(Suppl. 1), 1–46. https://doi.org/10.4158/GL-2020-0524SUPPL; LeBoff, M. S., Greenspan, S. L., Insogna, K. L., Lewiecki, E. M., Saag, K. G., Singer, A. J., & Siris, E. S. (2022). The clinician’s guide to prevention and treatment of osteoporosis. Osteoporosis International, 33(10), 2049–2102. https://doi.org/10.1007/s00198-021-05900-y; North American Menopause Society. (2021). Management of osteoporosis in postmenopausal women: The 2021 position statement of the North American Menopause Society. Menopause, 28(9), 973–997. https://doi.org/10.1097/GME.0000000000001831 a

SYMPTOMS OP itself is asymptomatic. A person cannot tell that their bones are losing density. OP may be recognized when a person loses 1.5 inches in height (usually due to silent or

painless VFs) or due to the pain associated with a clinically evident fracture related to the bone loss (Cosman et al., 2014). Kyphosis, usually due to VFs, causes a permanently stooped appearance and may be first noted when there is a documented loss of height (Camacho et al., 2020; LeBoff

656  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

Box 35.2  Osteoporosis Risk Factors

Box 35.3  Risk Factors for Falls and Fracturea

Potentially Modifiable Risk Factors

Evaluated in the FRAX Algorithm

Amenorrhea (caused by eating disorder or excessive exercise) Body weight less than 127 lb, body mass index less than 21 kg/m2 Chronic diseases (see Box 35.1) Cigarette smoking (active or passive) Falls Frailty Low estrogen level (e.g., menopause) Medications (see Box 35.1) Nulliparity Poor nutrition (e.g., excessive vitamin A, excessive alcohol or caffeine intake, excessive soda intake, excessive sodium intake, inadequate calcium/vitamin D intake, protein deficiency) Sedentary lifestyle/immobility

Age (especially older than 65 years, fracture risk doubles with each 7–8 years after age 50 years) Body mass index (BMI) less than 21 kg/m2 Current smoking Femoral neck raw bone mineral density (BMD) in g/cm2 Gender (female sex at greater risk than male sex) Glucocorticoid use Ingestion of three or more units of alcohol per day Parent history of hip fracture (increases risk ~130%) Personal prior fracture (risk for future fracture doubles) Rheumatoid arthritis Secondary osteoporosis Selected Other Risk Factors

Nonmodifiable Risk Factors

Depression/anxiety/decreased cognitive function Environmental (poor lighting, trip hazards, etc.) Frailty History of falls, fainting, off balance Impaired mobility Low vitamin D levels Neurologic disease Neuropathy, especially lower extremities Orthostatic hypotension Poor vision Sedentary lifestyle Use of medications or substances that cause drowsiness, dizziness, lightheadedness, or imbalance; use of multiple medications Vertigo Weakness

Advanced age Dementia Delayed puberty Endocrine disorders (Cushing syndrome, thyrotoxicosis, diabetes mellitus) Family history of osteoporosis Female gender First-degree relative with history of fracture Fracture history (fracture at 40–45 years or older is associated with an increased risk for osteoporosis) Genetic factors (variations in or absence of genes that regulate protein receptors or enzymes needed for bone development) Race (Caucasian and Asian women at greatest risk, then Hispanic and African American) Source: Adapted from Camacho, P. M., Petak, S. M., Binkley, N., Diab, D. L., Eldeiry, L. S., Farooki A, Harris, S. T., Hurley, D. L., Kelly, J., Lewiecki, E. M., Pessah-Pollack, R., McClung, M., Wimalawansa, S. J., & Watts, N. B. (2020). American Association of Clinical Endocrinologists/American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis—2020 update. Endocrine Practice, 26(Suppl. 1), 1–46. https://doi.org/10.4158/GL-2020-0524SUPPL; LeBoff, M. S., Greenspan, S. L., Insogna, K. L., Lewiecki, E. M., Saag, K. G., Singer, A. J., & Siris, E. S. (2022). The clinician’s guide to prevention and treatment of osteoporosis. Osteoporosis International, 33(10), 2049–2102. https://doi.org/10.1007/s00198-021-05900-y; North American Menopause Society. (2021). Management of osteoporosis in postmenopausal women: The 2021 position statement of the North American Menopause Society. Menopause, 28(9), 973–997. https://doi.org/10.1097 /GME.0000000000001831

et al., 2022; NAMS, 2021). Kyphosis also causes the rib cage to slump downward. With progression of bone loss, the ribs eventually come to rest on the ischial spines, thus minimizing thoracic and abdominal cavity space for organs. This restriction frequently leads to gastrointestinal problems, such as gastric reflux, anorexia, and constipation, and to

Risk factors have variable influences on fracture or fall risk. In the FRAX algorithm, all variables except age, height, weight, and gender are binary (entered as yes/no). This limits the weighting of some variables that would carry a higher risk for fracture if values were entered on a continuum. For example, a woman with a history of two prior fractures and taking 30 mg of oral steroid daily is at greater risk than a woman with one prior fracture who is taking 5 mg of steroid daily. The FRAX does calculate fracture risk using all the variables noted in the upper half of Box 35.3; therefore, the presence of multiple risks in one person is recognized. FRAX, fracture risk assessment. Source: Adapted from Camacho, P. M., Petak, S. M., Binkley, N., Diab, D. L., Eldeiry, L. S., Farooki A, Harris, S. T., Hurley, D. L., Kelly, J., Lewiecki, E. M., Pessah-Pollack, R., McClung, M., Wimalawansa, S. J., & Watts, N. B. (2020). American Association of Clinical Endocrinologists/American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis—2020 update. Endocrine Practice, 26(Suppl. 1), 1–46. https://doi.org/10.4158/GL-2020-0524SUPPL; LeBoff, M. S., Greenspan, S. L., Insogna, K. L., Lewiecki, E. M., Saag, K. G., Singer, A. J., & Siris, E. S. (2022). The clinician’s guide to prevention and treatment of osteoporosis. Osteoporosis International, 33(10), 2049– 2102. https://doi.org/10.1007/s00198-021-05900-y; North American Menopause Society. (2021). Management of osteoporosis in postmenopausal women: The 2021 position statement of the North American Menopause Society. Menopause, 28(9), 973–997. https://doi.org/10.1097/GME .0000000000001831 a

Chapter 35  Osteoporosis 657

respiratory disorders, such as shortness of breath (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). Self-image can also be negatively affected because of body changes and difficulty in finding clothing that fits properly over the kyphotic hump.

EVALUATION/ASSESSMENT Office assessment for OP includes a thorough history to identify personal and familial risk factors for bone loss. Possible causes of secondary OP (Box 35.3) are also investigated through history and physical examination to identify any negative effects on bone health that can be eliminated or reduced (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021).

History Gathering information that will enable risk stratification and identification of potential secondary causes for OP is critical when taking a history. Medications used and health habits such as diet and exercise, smoking, and daily alcohol consumption are all important in understanding risk and determining nonpharmacologic treatments (Boxes 35.1 and 35.2). Uncovering symptoms suggestive of systemic conditions that cause OP (e.g., hyperthyroidism) or increase risks for fracture or falls is also essential (Boxes 35.1, 35.2, and 35.3). Noting nonmodifiable risk factors such as age, ethnicity, history of fractures, and family history will help in determining if DXA scanning is needed earlier than standard age-related screening. Using the fracture risk assessment (FRAX) algorithm scale will help quantify these risk factors (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). A comprehensive risk assessment for falls is completed, especially in those with established OP, including hearing or vision impairments, neurologic status, and other medical problems or medications that may increase fall risk (Box 35.3).

Physical Examination The physical examination includes assessment for physical risk factors, such as low BMI (less than 21 kg/m2) or body weight (less than 127 lb), kyphosis, tooth loss, or spinal tenderness; signs of low estrogen levels; signs of thyroid abnormalities; and clues to other secondary causes for OP. Height is measured accurately using a stadiometer, not taken via patient report. Reductions in height can be an important first clue for painless (or silent) VFs (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). Fall risk can also be assessed by observing gait when the patient is entering or leaving the room. If there is concern for falls, Romberg and orthostatic blood pressure readings can provide additional information.

VFs can be painless; however, they are often associated with significant pain (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). VFs can be caused by normal activities of daily life, such as bending forward to pick up an item. The anterior edge of a vertebral bone crumbles in response to the increase in pressure exerted while bending forward, and changes into a wedge shape. Over time, having multiple wedge-shaped bones on top of one another, instead of the usual square/cube shape, forces the spine to curve forward, causing kyphosis.

DIFFERENTIAL DIAGNOSIS The diagnosis of OP is based on DXA results, physical exam findings, and laboratory results. A clinical diagnosis of OP is made when the patient has a low-trauma fracture of any type. A low-trauma fracture is a fracture sustained from relatively minor force, such as a fall from a standing height or less. Differentiating primary from secondary OP is important because some causes of secondary OP may be treatable and may rectify the bone loss. For example, a person with BMD test results that indicate OP may have disorders other than OP, such as osteomalacia or multiple myeloma, which may be treatable once identified. If serum calcium level is low, the cause needs to be identified and treated before an antiresorptive agent is administered, because it may exacerbate the problem. If vitamin D levels are low, replacement is necessary. OP can be missed in patients who sustain a low-trauma fracture. Recognition of OP is critical as medications and a multidisciplinary approach to management are most effective (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021).

DIAGNOSTIC STUDIES DXA is the gold standard for screening and diagnosing OP (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). Radiation is used to measure central BMD at the hip and lumbar spine areas. Peripheral DXA is also available; however, central DXA is the standard for diagnosing and monitoring BMD (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021; U.S. Preventive Services Task Force [USPSTF], 2018). Laboratory testing is needed to screen for secondary causes of OP (Camacho et al., 2020; Fitzgerald, 2022; LeBoff et al., 2022; NAMS, 2021). Quantitative computed tomography (QCT) can also be used to evaluate central BMD. QCT is especially useful in evaluating patients with osteoarthritis because it is less likely to detect osteophytes, which can falsely increase BMD measures identified with DXA. Other methods for evaluating bone density include peripheral DXA, single-energy x-ray absorptiometry (SXA), peripheral QCT, radiographic absorptiometry (RA), peripheral quantitative ultrasound (QUS), and radiogrammetry. QUS done at the calcaneus is often used at health fairs as it is housed in a small unit often on wheels and therefore easily moved. These methods are not used to diagnose OP;

658  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

however, they may alert a person that their peripheral BMD is low and prompt them to seek central DXA testing. OP can also be incidentally identified on x-ray studies. However, it is apparent on x-ray images only if there is bone loss of 30% to 40%; x-rays are not used to diagnose OP. When bone loss is identified with noncentral measures, the patient is referred for DXA. See Box 35.4 for the recommendations for DXA screening. DXA results for BMD are reported as T-scores and Z-scores (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). The T-score indicates the number of standard deviations the patient’s BMD falls above or below that of a young adult, sexand ethnic-matched norm. The World Health Organization determined classifications for T-score results (Alexeeva et al., 1994; Table 35.1). The Z-score indicates the number of standard deviations the BMD is above or below the mean for an age-, sex-, and ethnic-matched cohort. The Z-score is most often used for diagnosing bone loss in children or young adults, and can be helpful in identifying secondary OP. When the Z-score is low, it indicates either that the BMD is lower than the age cohort due to secondary OP causes or that peak bone mass was not achieved in young adulthood (Camacho et al., 2020; Fitzgerald, 2022; LeBoff et al., 2022; NAMS, 2021).

Box 35.4  Recommendations for DXA Screening ● ●

● ●

All females 65 years old or older Females younger than age 65 years (postmenopausal or transitioning to postmenopause) who have clinical risks for OP identified with screening Individuals who sustain a fracture after age 50 years Individuals who have a clinical condition or take medications that are associated with bone loss or decreased bone mass

DXA, dual-energy x-ray absorptiometry; OP, osteo­­porosis. Source: Adapted from LeBoff, M. S., Greenspan, S. L., Insogna, K. L., Lewiecki, E. M., Saag, K. G., Singer, A. J., & Siris, E. S. (2022). The clinician’s guide to prevention and treatment of osteoporosis. Osteoporosis International, 33(10), 2049–2102. https://doi.org/10.1007/s00198-021-05900-y

TABLE 35.1  World Health Organization T-Score Classifications T-SCORE RESULT

INTERPRETATION

Before a diagnosis of OP is confirmed, even with DXA results of −2.5 or below, a comprehensive history, physical examination, and laboratory studies are needed to identify possible causes of secondary OP or contraindications to medications (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). Initial laboratory testing should include complete blood count, albumin, calcium (albumin adjusted), renal function tests, phosphorus, magnesium, liver tests, 25(OH)-vitamin D, and parathyroid hormone (PTH), depending on the clinical picture. Additional testing to consider includes serum protein electrophoresis, serum immunofixation, serum free kappa and lambda light chains, thyroid-stimulating hormone with reflux free thyroxine (T4), tissue transglutaminase antibodies, IgA (immunoglobulin A) levels, iron, ferritin, homocysteine, prolactin, tryptase, bone turnover markers (BTMs), 24-hour urinary creatinine and calcium, and urinary histamine, protein electrophoresis (UPEP), and free cortisol (LeBuff et al., 2022; NAMS, 2021). Biochemical BTMs are not used to diagnose OP. They are serum markers that have been used in research to evaluate fracture risk and treatment response. BTMs reflect osteoclast bone resorption activity (C-terminal telopeptide of type 1 collagen) or osteoblast activity for bone formation (procollagen type 1 N-terminal propeptide or alkaline phosphatase [bone-specific]). BTMs are not currently recommended for routine use to evaluate patients with OP (LeBoff et al., 2022; NAMS, 2021). The FRAX, launched by the University of Sheffield (www .shef.ac.uk/FRAX) in 2008, uses data about 11 different risk factors as well as femoral neck BMD to provide added information to support clinical decision-making for initiating medication therapy, especially among those with osteopenia (see Pharmacotherapeutics section).

TREATMENT/MANAGEMENT OP management begins early in life with recommendations about diet and exercise tailored to develop full peak bone mass as a young adult and continues with the goal of preventing bone loss at midlife. Once bone loss has occurred, the goal continues focusing on prevention of further bone loss as well as fracture prevention. Strategies for maximizing peak bone mass and bone loss prevention include changes in diet, use of supplements, and an exercise program that includes both weight-bearing and resistive activities. Fall prevention and use of pharmacotherapeutics are the mainstays of fracture prevention. Referral to a specialist is warranted when patients do not respond to first-line pharmacotherapeutics or when comorbid disease makes management complicated.

At or above −1.0

Normal

−1.0 to −2.5

Osteopenia

At or below −2.5

Osteoporosis

Self-Management

At or below −2.5 with low-trauma fracture(s)

Severe or established osteoporosis

DIET AND SUPPLEMENTS

Source: Adapted from Alexeeva, L., Burkhardt, P., Christiansen, C., Cooper, C., Delmas, P., Johnell, O., Johnston, C., Kanis, J. A., Lips, P., Melton, L. J., Meunier, P., Seeman, E., Stepan, J., 3rd, & Tosteson, A. (1994). Assessment of fracture risk and its application to screening for postmenopausal osteoporosis (WHO Technical Report Series 843). https://apps.who.int/iris/handle/10665/39142.

OP prevention needs to start early in life by ingesting a diet rich in calcium, vitamin D, and minerals, which are necessary to achieve peak bone mass. Maintaining adequate intake of both calcium (Table 35.2) and vitamin D (800–1,000 U/day)

Chapter 35  Osteoporosis 659

TABLE 35.2  Daily Calcium Recommendations for Females at Various Ages AGE

DAILY CALCIUM RECOMMENDATION (MG)

Birth to 6 months

200

6–12 months

260

1–3 years

700

4–8 years

1,000

9–13 years

1,300

14–18 years and pregnant or lactating

1,300

19–50 years and pregnant or lactating

1,000

51–70 years >70 years

1,200 1,000 1,200

Source: Adapted from Ross, A. C., Manson, J. E., Abrams, S. A., Aloia, J. F., Brannon, P. M., Clinton, S. K., Durazo-Arvizu, R. A., Gallagher, J. C., Gallo, R. L., Jones, G., Kovacs, C. S., Mayne, S. T., Rosen, C. J., & Shapses, S. A. (2011). The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: What clinicians need to know. Journal of Clinical Endocrinology and Metabolism, 96(1), 53–58. https://doi.org/10.1210/jc.2010–2704

remains necessary with aging and throughout postmenopause. Supplementation is often needed to increase the 600 to 700 mg of calcium ingested by women over 50 in a typical diet (Ross et al., 2011). Although UV sunlight exposure to bare skin can synthesize vitamin D, this is not the recommended modality to obtain adequate levels of vitamin D, both because of the increased risk for skin cancer and because of variables that interfere with a consistent amount of vitamin D production. Thus, supplementation or ingestion of vitamin D–fortified foods is recommended. Individuals with low serum 25-(OH)vitamin D levels (less than 30 ng/mL) may require supplementation (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). Other dietary considerations include minimizing ingestion of soda and caffeinated beverages. Caffeine intake should not exceed four cups of coffee per day as caffeine limits intestinal calcium absorption (Coronado-Zarco et al., 2019). The phosphorus in soda and the caffeine in other beverages may interfere with bone formation and remodeling processes if consumed in very high quantities. More important, for most people, is that frequent ingestion of these beverages can replace ingestion of calcium-rich milk, posing a greater harm to developing and maintaining bone strength. Adequate amounts of phosphorus are needed; however, phosphorus intake must be balanced because either excessive or insufficient amounts can interfere with bone formation. Adequate citric acid, protein, and fiber are also needed for proper bone formation. Excessive protein or fiber intake can interfere with normal intestinal absorption of calcium. Alcohol consumption should be limited to two drinks per day as three or more drinks per day may be associated with an increased fracture risk (Camacho et al., 2020; LewBoff et al., 2022; NAMS, 2021).

Although supplementation with adequate amounts of calcium and vitamin D is important for general health, there is limited evidence that calcium, vitamin D, or calcium with vitamin D combinations will alone provide a reduction in fracture risk (American College of Obstetricians and Gynecologists’ Committee on Clinical Practice Guidelines– Gynecology, 2021; Barrionuevo et al., 2019). Calcium and vitamin D from dietary sources, and supplementation when dietary sources do not meet recommended daily intakes, should be initiated in conjunction with other OP treatment modalities in those with a high risk of fracture (Camacho et al., 2020; Eastell et al., 2019; LeBoff et al., 2022; NAMS, 2021). Calcium from dietary sources is preferred over supplements; however, calcium intake from dietary sources is frequently below the recommended dietary allowance. Furthermore, individuals with lactose intolerance may not tolerate dairy products that are richest in calcium, making supplementation necessary (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). The recommended dietary allowances (RDAs) for calcium are based on elemental calcium, the amount of calcium that is absorbed from a food or supplement and used in the body. To promote adequate absorption, doses should be spaced and not exceed 500 to 600 mg per dose (Coronado_Zarco et al., 2019). Most supplements now list elemental calcium levels on their labels; therefore, determining the amount of calcium that is absorbed is straightforward. Taking 1,000 mg of calcium supplement daily was not associated with increased risks for cardiovascular disease or stroke in the Nurses’ Health Study (Paik et al., 2014). However, increased calcium doses may increase kidney stone risk and may increase cardiac risk at higher doses (NAMS, 2021). Several different types of calcium supplements are available (Table 35.3). EXERCISE

Establishing an active lifestyle early in life and maintaining it throughout the older years is crucial to encourage normal bone formation and slow bone loss. The effects of exercise on bone are site specific because osteoblast activity increases locally in response to load stress caused by exercise (e.g., walking supports bone density in the hips, lower spine, and legs; hand weights benefit the arms and wrists; and overhead weights benefit the shoulders, upper arms, wrists, and upper spine; Camacho et al., 2020; LeBoff et al., 2022). Weight-bearing, resistance, and balance exercises are recommended (Camacho et al., 2020; LeBoff et al., 2022). Physical activity in which bones and muscles work against gravity, such as walking, are considered weight-bearing exercises (Cosman et al., 2014). Other examples of weight-bearing exercises include jogging, dancing, and lifting weights. Resistance training includes activities such as water aerobics, cycling, and yoga. When severe OP is present, exercises that compress forces on the spine, such as forward bending, trunk rotation, or lifting heavy weights, should be avoided to minimize fracture risk (Camacho et al., 2020). In addition to improving bone strength and providing overall fitness, exercise helps women maintain their balance, and thus reduces fall risk. Exercise and activities that carry a high risk for falls are also discouraged in women with established OP.

660  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

TABLE 35.3  Calcium Supplements TYPE

Calcium carbonate

Calcium citrate

BRAND NAMES

Caltrate, Os-Cal, Tums, Viactiv, others

Citracal

COMMENTS

Available in liquid, chewable tablet Needs to be taken with food; needs acidic environment for absorption ● Not a good choice for women taking proton pump inhibitors because of lowered gastric acidity, even with meals ● Often causes flatulence, constipation; can minimize these symptoms if taken in combination with magnesium ● May contain lead if made from bone meal, dolamite, or oyster shell; concern mainly for children, pregnant or lactating women ● ●

● ●

Calcium phosphate tribasic

Posture

● ●

Calcium gluconate

Various

● ●

Calcium glubionate Calcium lactate

Calcionate Ridactate

Available in liquid, tablet, and chewing gum forms Can be taken with or without food; easily absorbed and not affected by acid level Can be taken with or without food; absorption not affected by acid level Usual formulation added to calcium-fortified drinks Less frequently used Usually combined with calcium carbonate in vitamin or mineral supplement products

Liquid form Less frequently used Less bioavailability and taken three times a day before meals ● ●

Source: Adapted from Camacho, P. M., Petak, S. M., Binkley, N., Diab, D. L., Eldeiry, L. S., Farooki A, Harris, S. T., Hurley, D. L., Kelly, J., Lewiecki, E. M., Pessah-Pollack, R., McClung, M., Wimalawansa, S. J., & Watts, N. B. (2020). American Association of Clinical Endocrinologists/American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis—2020 update. Endocrine Practice, 26(Suppl. 1), 1–46. https://doi.org/10.4158/GL-2020-0524SUPPL; Drugs.com. (n.d.). Calcium supplement oral, parenteral advanced patient information. https://www.drugs.com/cons/calcium-acetate.html; LeBoff, M. S., Greenspan, S. L., Insogna, K. L., Lewiecki, E. M., Saag, K. G., Singer, A. J., & Siris, E. S. (2022). The clinician’s guide to prevention and treatment of osteoporosis. Osteoporosis International, 33(10), 2049–2102. https://doi .org/10.1007/s00198-021-05900-y; North American Menopause Society. (2021). Management of osteoporosis in postmenopausal women: The 2021 position statement of the North American Menopause Society. Menopause, 28(9), 973–997. https://doi.org/10.1097/GME.0000000000001831

SMOKING CESSATION

Avoiding or quitting smoking to maximize peak bone formation and prevent bone loss is crucial (Camacho et al., 2020; Cosman et al., 2014; National Institutes of Health [NIH], 2017). Smoking has adverse effects on skeletal health, may increase osteoporotic fracture risk, and is detrimental to general health (Camacho et al., 2020; Coronado-Zarco et al., 2019). Patients should be counseled about the negative effects of tobacco use and supported for cessation efforts. FALL PREVENTION

Fall prevention becomes more important in those with established bone loss who are at increased risk for fracture. A home assessment is done to determine and remedy the presence of environmental hazards including loose rugs, stairs, uneven floors and grounds, pets, or exposed cords. Poor lighting and cluttered walkways can increase fall risk, especially at night. Some patients can conduct this assessment and rectify problems themselves. In other instances, clinicians, community-based providers, or family members need to intervene. Sedating medications, such as narcotics, benzodiazepines, and alcohol, should be avoided as they can increase fall risk. Vision and hearing exams should be part of routine health maintenance. Consultation occupational or physical therapy can assist with in-home evaluations and targeted interventions to improve balance and decrease fall risk (American College of Obstetricians and Gynecologists’ Committee on Clinical Practice Guidelines–Gynecology, 2021).

Complementary and Alternative Medicine MASSAGE, RELAXATION THERAPIES, AND CHIROPRACTIC MANIPULATION

Massage may indirectly benefit bone strength because it can relax and assist in muscle flexibility, potentially increasing exercise tolerance. Chair massage is performed with caution because forward bending in those with established OP potentially increases the risk of VFs. Massage does not usually provide enough force to cause fracture with established OP and may provide relaxation that assists with pain reduction. Other complementary and alternative medicine (CAM) modalities that enhance and encourage relaxation such as aromatherapy, yoga, and meditation may be helpful for pain management in those with OP fractures. Chiropractic manipulation techniques are modified by skilled chiropractors to avoid injury or fracture of weak bones. Some chiropractors do not perform manipulations on those with OP; instead, they counsel patients about dietary needs and safe exercise techniques. There is an abundance of research supporting yoga as treatment for OP. Yoga is safe and inexpensive and includes both weight-bearing and non-weight-bearing modalities. Yoga has also been demonstrated to improve balance (Motorwala et al., 2016).

Chapter 35  Osteoporosis 661

BOTANICALS AND ACUPUNCTURE

Research evaluating the use of isoflavones to improve bone density has provided conflicting results. Although some have shown moderate benefit in preventing bone loss after menopause, they are not recommended for postmenopausal OP management or prevention (Camacho et al., 2020; NAMS, 2021). Treatment results for OP with acupuncture have been mixed. Acupuncture is more often used in combination with Chinese herbs for OP in the practice of traditional Chinese medicine (TCM; Guillaume, 1992). Acupuncture (warm acupuncture and tuina acupuncture) is recognized by some as effective treatment for OP (Pan et al., 2018). Tuina is another type of acupuncture used in China for OP treatment. TCM notes benefits for blood stasis and kidney function related to OP through acupuncture effects that nourish immune and nerve system function, promote blood circulation, alleviate pain and spasm, and dredge the meridian channel (Dong et al., 2018; Pan et al., 2018).

Herbs that might be used for OP management are intended to boost estrogen levels, such as cypress, black cohosh, sage, licorice, and ginseng. Data on efficacy of herbs for BMD are lacking, and generally herbs do not demonstrate robust benefits (Leung & Siu, 2013).

Pharmacotherapeutics Several prescription medications are available for OP management (Table 35.4). Prescription medications are recommended to treat OP in postmenopausal persons in guidelines published by the Bone Health and OP Foundation (LeBoff et al., 2022), NAMS (2021), and the American Association of Clinical Endocrinologists (AACE; Comacho et al., 2020). The focus of medication for treating OP is to reduce the risk for fracture and subsequent sequelae. NAMS (2021) also recommends prescription medications to prevent OP in their guidelines. The goal for preventive therapy is to stop postmenopausal

TABLE 35.4  Prescription Medications for Osteoporosis Treatment or Preventiona,b MEDICATION

FDA-APPROVED USE AND DOSE

Alendronate (Fosamax)

Prevention: 5 mg by mouth daily or 35 mg by mouth weekly Treatment: 10 mg by mouth daily or 70 mg by mouth weekly

Alendronate + cholecalciferol (Fosamax Plus D)

Treatment: 70 mg plus 2,800 U of vitamin D3 or 70 mg plus 5,600 units of vitamin D3 in combined tablet by mouth weekly

Risedronate (Actonel)

Prevention: 5 mg by mouth daily; 35 mg by mouth weekly; or 150 mg by mouth monthly Treatment: immediate-release: 5 mg by mouth daily; 35 mg by mouth weekly; 150 mg by mouth monthly Treatment: delayed-release: 35 mg by mouth weekly

Ibandronate (Boniva)

Prevention: 150 mg by mouth monthly Treatment: 150 mg by mouth monthly; 3 mg IV every 3 months

Zoledronic acid (Reclast)

Prevention: 5 mg IV every 2 years (24 months) Treatment: 5 mg IV yearly (12 months)

Calcitonin (calcitonin salmon nasal; Miacalcin)

Treatment: 200 IU of intranasal spray daily (calcitonin salmon nasal) or 100 IU subcutaneously every other day (Miacalcin)

Denosumab (Prolia)

60 mg subcutaneously every 6 months

CONSIDERATIONS

Before any food ingestion, take oral doses in morning with 8 oz plain water, remain upright, and ingest no food or drink for at least 30–60 minutes ● Take oral doses 2 hours before antacids/calcium ● Caution with oral forms if upper gastrointestinal disease present; clinical association with dysphagia, esophagitis, or ulceration ● Beneficial effects may last for years after medication is discontinued ● Fosamax Plus D: combined bisphosphonate and vitamin D3 in a single tablet taken weekly ● IV ibandronate and zoledronic acid are not associated with gastrointestinal side effects: no limitations on timing dose around food, water, calcium, or medication intake ● Osteonecrosis of jaw (ONJ), exposed bone in mouth for >3 months with nonhealing lesions, has been associated with high-dose IV bisphosphonate therapy among individuals with cancer-related bone disease (2%–10%); cancer patients with dental problems, gum injury, oral bony abnormalities, or taking medications that interfere with healing; and, in very rare cases, healthy individuals with similar risk factors who are taking bisphosphonates for osteoporosis (incidence estimated at 0.001%–0.002%). Consider stopping therapy for 2–3 months if invasive dental procedures are required and resume after healing is complete; encourage usual dental care (e.g., cleaning, fillings, crown work). ●

Usually administered as nasal spray Alternate nares for nasal spray ● Most often used for analgesic effect on acute pain resulting from vertebral compression fractures ● ●

Administered by a healthcare professional Calcium and vitamin D needed ● Contraindicated with hypocalcemia ● May increase risk for infection ● ONJ has been reported ● ●

(continued)

662  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

TABLE 35.4  Prescription Medications for Osteoporosis Treatment or Preventiona,b (continued) MEDICATION

FDA-APPROVED USE AND DOSE

CONSIDERATIONS

Estrogen (Alora, Climara, Estrace, Estraderm, Menest, Menostar, Premarin, Vivelle, Vivelle-Dot)

Prevention: doses and routes vary

Estrogen–progestin combination productsb (Activella, Climara Pro, FemHRT, Prefest, Premphase, Prempro)

Prevention: doses and routes vary

Estrogens conjugated/ bazedoxifene (Duavee)

Prevention: 1 tab by mouth daily (0.45 mg estrogen, conjugated/20 mg bazedoxifene

Genistein + citrated zinc bisglycinate + cholecalciferol (Fosteum Rx)

Prevention: 1 capsule twice daily (each capsule contains 27 mg of genistein, 20 mg of citrated zinc bisglycinate, 200 IU of cholecalciferol)

Raloxifene (Evista)

Prevention: 60 mg by mouth daily Treatment: 60 mg by mouth daily

b

Also effective in alleviating most symptoms related to menopause (even Menostar, which has a very low dose and was shown to effectively reduce severity and frequency of hot flashes in a 2007 study) ● Available in several forms (e.g., pills, patch, ring, cream, gel) ● Use for 2 to 3 years immediately following menopause; may provide some beneficial effects on bone health after discontinuation ●

●

Also approved for menopause-related vasomotor symptom management (no progestogen needed if intact uterus)

Medical food Meets FDA standards for GRAS (generally recognized as safe) ● Not recommended if taking hormone therapy, estrogen agonist–antagonists ● ●

May cause hot flashes Not recommended if taking ET or EPT ● Also approved for prevention of breast cancer in women at high risk for invasive breast cancer ● ●

Teriparatide (recombinant human PTH 1–34) (Forteo)

Treatment (high fracture risk): 20 mcg subcutaneously daily; two courses of 2 years of therapy in lifetime

Abaloparatide (Tymlos)

Treatment: 80 mcg subcutaneously daily, 24 months cumulative use

Romosozumab (Evenity)

Treatment: 210 mg subcutaneously monthly, 12 months

● ●

Usually second line unless very high risk for fracture Most effective when used sequentially following antiresorptive and antiresorptive resumed following PTH

See prescribing reference for full information on doses, side effects, contraindications, and cautions. Combining therapies is uncommon and generally initiated only by an osteoporosis specialist because of potential side effects, including frozen bone syndrome—a condition in which bone turnover is suppressed to the point that bone quality declines despite increasing bone density, creating increased risk for fracture. b Lowest effective dose is used; the FDA recommends considering nonestrogen osteoporotic agents when ET/EPT use is solely for the purpose of osteoporosis prevention. EPT, estrogen-progestogen therapy; ET, estrogen therapy; FDA, U.S. Food and Drug Administration; IV intravenous; PTH, parathyroid hormone. Source: Adapted from Camacho, P. M., Petak, S. M., Binkley, N., Diab, D. L., Eldeiry, L. S., Farooki A, Harris, S. T., Hurley, D. L., Kelly, J., Lewiecki, E. M., Pessah-Pollack, R., McClung, M., Wimalawansa, S. J., & Watts, N. B. (2020). American Association of Clinical Endocrinologists/American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis—2020 update. Endocrine Practice, 26(Suppl. 1), 1–46. https://doi.org/10.4158/GL-2020-0524SUPPL; ePocrates. (n.d.). Computerized pharmacology and prescribing reference (updated daily). https://www.epocrates.com/; LeBoff, M. S., Greenspan, S. L., Insogna, K. L., Lewiecki, E. M., Saag, K. G., Singer, A. J., & Siris, E. S. (2022). The clinician’s guide to prevention and treatment of osteoporosis. Osteoporosis International, 33(10), 2049–2102. https://doi.org/10.1007/s00198-021 -05900-y; North American Menopause Society. (2021). Management of osteoporosis in postmenopausal women: The 2021 position statement of the North American Menopause Society. Menopause, 28(9), 973–997. https://doi.org/10.1097/GME.0000000000001831 a

bone loss before skeletal architecture damage progresses to the point of increased risk for fracture. Medications approved for OP prevention and treatment are included in Box 35.5. The FRAX algorithm was developed to identify 10-year fracture probabilities to assist in determining best practices for initiating medication therapy among patients with T-score BMDs in the LBM range (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). The FRAX algorithm is accessible online (www.shef.ac.uk/FRAX) and initially was developed for use in patients who are naïve to OP pharmacotherapy. It is specific to country and in the United States is also categorized according to ethnicity. Ten-year fracture risk probability for hip fracture and any major osteoporotic fracture (e.g., forearm, hip, humerus, or vertebrae) is calculated using 10 risk factors for fracture (Box 35.3) and the femoral neck BMD. The calculated FRAX fracture probabilities are

now printed on BMD DXA results in the United States. Eight of the variables are dichotomous, and thus limit the ability to fully specify calculations to individuals. Additionally, the use of ethnicity as a risk factor has been called into question. Despite these limitations, FRAX does identify level of risk across populations well. Its ability to identify risk for a single person is more limited (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). The U.S. FRAX algorithm adapted to clinical scenarios provides the basis for clinical recommendations for initiating medication therapy among those with LBM (Box 35.5; Camanche et al., 2020; LeBoff et al., 2022; NAMS, 2021). Another online FRAX tool, called QFracture, was released in 2009 and updated in 2016. It may have some improved discrimination over FRAX; however, it was based on data from England and Wales and is only applicable to these patient populations (Hippisley-Cox & Coupland, 2009).

Chapter 35  Osteoporosis 663

Box 35.5  Recommendations for Initiating Medication Therapy to Treat Bone Loss/ Osteoporosis Medication therapy is recommended for postmen­ opausal persons if: 1.  THe T-score BMD at the femoral neck, spine, or hip is −2.5 or below 2.  A hip fracture or vertebral fracture is sustained (regardless of BMD T-score) 3.  THe BMD T-score is −1 to −2.5 (LBM) AND a.  A fracture of the pelvis, hip, or distal forearm is sustained

OR

b.  THe FRAX 10-year risk for major OP-related fracture is ≥20% or hip fracture is ≥3% 4.  Multiple fractures are sustained (not at femoral neck, spine, hip) BMD, bone mineral density; FRAX, fracture risk assessment; LBM, low bone mass; OP, osteoporosis. Source: Adapted from Camacho, P. M., Petak, S. M., Binkley, N., Diab, D. L., Eldeiry, L. S., Farooki A, Harris, S. T., Hurley, D. L., Kelly, J., Lewiecki, E. M., Pessah-Pollack, R., McClung, M., Wimalawansa, S. J., & Watts, N. B. (2020). American Association of Clinical Endocrinologists/American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis—2020 update. Endocrine Practice, 26(Suppl. 1), 1–46. https://doi.org/10.4158/GL-2020-0524SUPPL; LeBoff, M. S., Greenspan, S. L., Insogna, K. L., Lewiecki, E. M., Saag, K. G., Singer, A. J., & Siris, E. S. (2022). The clinician’s guide to prevention and treatment of osteoporosis. Osteoporosis International, 33(10), 2049–2102. https://doi.org/10.1007 /s00198-021-05900-y; North American Menopause Society. (2021). Management of osteoporosis in postmenopausal women: The 2021 position statement of the North American Menopause Society. Menopause, 28(9), 973–997. https://doi.org/10.1097/GME.0000000000001831

Several medication therapies are currently approved by the Food and Drug Administration (FDA) for OP management, which includes both prevention and treatment. These medications work by modulating—either inhibiting or activating—bone metabolism. There are two general categories among these medications. Antiresorptive or antiremodeling agents are in the first category and include bisphosphonates, estrogens, estrogen agonists/antagonists (EAAs; formerly known as selective estrogen receptor modulators [SERMs]), tissue-selective estrogen complex, RANKL (receptor activator of nuclear factor kappa-Β ligand) inhibitor, and calcitonin (rarely used). These medications maintain or increase BMD and reduce fracture risk primarily by inhibiting bone resorption and have some effects on bone formation. Specifically, they inhibit osteoclast function, thus reducing bone resorption and increasing bone density by allowing osteoblast activity to surpass osteoclast activity. However, they do not repair or improve trabecular bone disruptions that occur with OP. In the second category are osteoanabolic agents including PTH and analog of PTH-related peptide. The mechanism of action of anabolic agents is to increase osteoblast activity and

thereby stimulate formation of new bone. They improve bone structure (both trabecular and/or cortical) and increase BMD significantly, which reduces fracture risk more quickly than the antiresorptives. Also available is the fully human monoclonal antibody to sclerostin, which has a novel mechanism to act with both antiresorbtive and osteoanabolic properties. Finally, one other prescription agent, a medical food, is available. Medical foods meet the FDA standard for GRAS, which means “generally regarded as safe.” Fosteum Plus meets this standard and includes a combination of genistein (an isoflavone that is purified from soy), vitamin D, and zinc (www. fosteumplus.com/assets/pdfs/prescribing-information/fosteum-pi.pdf). Studies evaluating Fosteum show that it does improve BMD; however, no data on fracture rates are available. Agent selection for initial treatment is guided by BMD T-score and fracture risk level prior to treatment (Table 35.5). First-line therapies for persons with high risk include those that have demonstrated efficacy for reducing spine, hip, and nonvertebral fractures and include denosumab, zoledronate, alendronate, and risedronate (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021). DXA testing is used to monitor efficacy of OP or LBM treatment. DXA testing is done every 1 to 2 years until stability is achieved, and then every 3 years. Patients should be treated to meet target outcomes of BMD total hip T-scores between −2.0 to −1.5. BMD has been demonstrated as an effective surrogate marker for fracture risk; as BMD rises, fracture risk falls. If goal T-score is not met, consider changing therapy (e.g., from bisphosphonate to RANKL inhibitor) or initiating sequential therapy with an osteoanabolic agent or human monoclonal antibody to sclerostin (Camacho et al., 2020; LeBoff et al., 2022, NAMS, 2021). Referral or consultation is appropriate prior to changing or initiating second-line medications for clinicians who are not managing OP on a regular basis. In those with normal bone mass at baseline, repeat DXA testing is done in 5 years. Repeat testing is done earlier if the patient’s risk factors for OP change (Camacho et al., 2020; LeBoff et al., 2022; NAMS, 2021).

Considerations for Special and Minoritized Populations Temporary secondary bone loss can affect persons receiving Depo-Provera injections for contraception and during pregnancy and lactation when calcium is leached from the bone. Bone mass usually reverts to prepregnancy and pre-Depo-Provera levels following birth, cessation of breastfeeding, or discontinuation of Depo-Provera. A low-dose estrogen patch can be prescribed to preserve bone mass for those using Depo-Provera while they are taking the medication. Increasing calcium intake before pregnancy and maintaining appropriate calcium intake during pregnancy and lactation are critical (Ross, 2011). In 2020, Vyas et al., published a paper that proposed eliminating the use of algorithms that make guideline recommendations based on race. Given data that demonstrate disproportionate risks for bone loss and OP among varied ethnic groups, use of algorithms like FRAX continues. However, clinicians must consider other factors that pose risks to patients— – considerations must include existing health

664  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

TABLE 35.5  Selection of Initial Medication for Osteoporosis Based on Fracture Risk FRACTURE RISK LEVEL

SUGGESTED CRITERIA

Very high

●

High

●

FIRST-LINE MEDICATIONS

Prior fractures: recent, multiple, while on OP medication, while taking medications that cause bone loss ● T-score: very low, e.g., 30%, hip >4.5%

Osteoanabolic, human monoclonal antibody to sclerostin

T-score: demonstrates OP, ≤−2.5 Fracture: possibly parent, one prior fracture at earlier age, or not high probability on FRAX ● Falls: not at increased risk

RANKL inhibitor, bisphosphonate

T-score: demonstrates LBM with elevated FRAX, or demonstrates OP ● No other risk factors

Bisphosphonate, estrogen agonists/ antagonists, estrogen*, tissue-selective estrogen complex*

●

Moderate

●

*For OP prevention, used for those also experiencing menopause-related vasomotor symptoms. FRAX, fracture risk assessment; LBM, low bone mass; OP, osteoporosis; RANKL, receptor activator of nuclear factor kappa-Β ligand. Source: Adapted from Camacho, P. M., Petak, S. M., Binkley, N., Diab, D. L., Eldeiry, L. S., Farooki A, Harris, S. T., Hurley, D. L., Kelly, J., Lewiecki, E. M., Pessah-Pollack, R., McClung, M., Wimalawansa, S. J., & Watts, N. B. (2020). American Association of Clinical Endocrinologists/American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis—2020 update. Endocrine Practice, 26(Suppl. 1), 1–46. https://doi.org/10.4158/GL-2020-0524SUPPL; LeBoff, M. S., Greenspan, S. L., Insogna, K. L., Lewiecki, E. M., Saag, K. G., Singer, A. J., & Siris, E. S. (2022). The clinician’s guide to prevention and treatment of osteoporosis. Osteoporosis International, 33(10), 2049–2102. https://doi.org/10.1007/s00198-021-05900-y; North American Menopause Society. (2021). Management of osteoporosis in postmenopausal women: The 2021 position statement of the North American Menopause Society. Menopause, 28(9), 973–997. https://doi.org/10.1097/GME.0000000000001831

disparities and co-morbidities faced by certain populations, specifically Black, Asian, and Hispanic people. Culturally competent healthcare interventions must be provided that address their health concerns and reduce disparities. The International Osteoporosis Foundation and the American Society for Bone and Mineral Research have recommendations to better address OP management for various populations (Kanis et al., 2020). The clinician’s role is to diagnose, treat, manage, and provide education. Importantly, informing minoritized populations of both modifiable and non-modifiable risks of fracture and bone loss (Kanis et al., 2020). isare critical for patients to be able to make informed decisions about their lifestyle activities and treatment.

FUTURE DIRECTIONS Bone health is a critical issue across the lifespan. Attending to building maximum bone mass during childhood and young adulthood will provide a strong foundation for fracture prevention with aging. Bone loss during midlife is managed for all through diet, supplementation, and exercise. The FRAX algorithm can assist with providing some information on who may benefit from pharmacologic therapy. Multiple pharmacotherapeutic options are available, making it realistic to tailor a medication plan for an individual. Future research is evaluating new delivery methods for existing pharmacotherapeutics as well as additional pharmacotherapeutic agents for bone health.

REFERENCES Alexeeva, L., Burkhardt, P., Christiansen, C., Cooper, C., Delmas, P., Johnell, O., Johnston, C., Kanis, J. A., Lips, P., Melton, L. J., Meunier, P., Seeman, E., Stepan, J., 3rd, & Tosteson, A.. (1994). Assessment of fracture risk and its application to screening for postmenopausal osteoporosis (WHO Technical Report Series 843). https://apps.who.int/iris/handle/10665/39142 American College of Obstetricians and Gynecologists’ Committee on Clinical Practice Guidelines–Gynecology. (2021). Osteoporosis prevention, screening, and diagnosis. Obstetrics & Gynecology, 138(3), 494–506. https://doi.org/10 .1097/aog.0000000000004514 Barrionuevo, P., Kapoor, E., Asi, N., Alahdab, F., Mohammed, K., Benkhadra, K., Almasri, J., Farah, W., Sarigianni, M., Muthusamy, K., Al Nofal, A., Haydour, Q., Wang, Z., & Murad, M. H. (2019). Efficacy of pharmacological therapies for the prevention of fractures in postmenopausal women: A network meta-analysis. Journal of Clinical Endocrinology & Metabolism, 104(5), 1623–1630. https://doi.org/10.1210/jc.2019-00192 Camacho, P. M., Petak, S. M., Binkley, N., Diab, D. L., Eldeiry, L. S., Farooki A, Harris, S. T., Hurley, D. L., Kelly, J., Lewiecki, E. M., Pessah-Pollack, R., McClung, M., Wimalawansa, S. J., & Watts, N. B. (2020). American Association of Clinical Endocrinologists/American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis—2020 update. Endocrine Practice, 26(Suppl. 1), 1–46. https://doi.org/10 .4158/GL-2020-0524SUPPL Coronado-Zarco, R., Olascoaga-Gómez de León, A., García-Lara, A., Quinzaños-Fresnedo, J., Nava-Bringas, T. I., & Macías-Hernández, S. I. (2019). Nonpharmacological interventions for osteoporosis treatment: Systematic review of clinical practice guidelines. Osteoporosis and Sarcopenia, 5(3), 69–77. https://doi.org/10.1016/j.afos.2019.09.005 Cosman, F., de Beur, S. J., LeBoff, M. S., Lewiecki, E. M., Tanner, B., Randall, S., & Lindsay, R. (2014). Clinician’s guide to prevention and treatment of osteoporosis. Osteoporosis International, 25, 2359–2381. https://doi.org/10.1007 /s00198-014-2794-2 Dolan, B., & Walsh, J. (2022). Osteoporosis prevention in women. In M. A. Papadakis, S. J. McPhee, M. W. Rabow, & K. R. McQuaid (Eds.), Current medical diagnosis & treatment 2022. McGraw Hill.

Dong, Y., Zhao, R., Wang, C., & Guo, T. (2018). Tuina for osteoporosis: A systematic review protocol. Medicine, 97(8), E9974. https://doi.org/10.1097 /MD.0000000000009974 Eastell, R., Rosen, C. J., Black, D. M., Cheung, A. M., Murad, M. H., & Shoback, D. (2019). Pharmacological management of osteoporosis in postmenopausal women: An Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology & Metabolism, 104(5), 1595–1622. https://doi.org/10.1210/jc .2019-00221 ePocrates. (n.d.). Computerized pharmacology and prescribing reference (updated daily). https://www.epocrates.com/ Fitzgerald, P. A. (2022). Osteoporosis. In M. A. Papadakis, S. J. McPhee, M. W. Rabow, & K. R. McQuaid (Eds.), Current medical diagnosis & treatment 2022. McGraw Hill. Guillaume, G. (1992). Postmenopausal osteoporosis and Chinese medicine. American Journal of Acupuncture, 20, 105–111. Hippisley-Cox, J., & Coupland, C. (2009). Predicting risk of osteoporotic fracture in men and women in England and Wales: Prospective derivation and validation of QFractureScores. British Medical Journal, 339, b4229. https:// doi.org/10.1136/bmj.b4229 Kanis, J. A., Cooper, C., Dawson-Hughes, B., Harvey, N. C., Johansson, H., Lorentzon, M., McCloskey, E. V., Reginster, J. Y., Rizzoli, R., & International Osteoporosis Foundation. (2020). FRAX and ethnicity. Osteoporosis International, 31(11), 2063–2067. https://doi.org/10.1007/s00198-020-05631-6 LeBoff, M. S., Greenspan, S. L., Insogna, K. L., Lewiecki, E. M., Saag, K. G., Singer, A. J., & Siris, E. S. (2022). The clinician’s guide to prevention and treatment of osteoporosis. Osteoporosis International, 33(10), 2049–2102. https://doi.org/10.1007/s00198-021-05900-y Leung, P.-C., & Siu, W.-S. (2013). Herbal treatment for osteoporosis: A current review. Journal of Traditional Complementary Medicine, 3(2), 82–87. https:// doi.org/10.4103/225-4110.110407 Lindsay, R., & Cosman, F. (2018). Osteoporosis. In J. Jameson, A. S. Fauci, D. L. Kasper, S. L. Hauser, D. L. Longo, & J. Loscalzo (Eds.), Harrison’s principles of internal medicine (20th ed.). McGraw-Hill. Motorwala, Z., Kolke, S., Panchal, P., Bedekar, N., Sancheti, P., & Shyam, A. (2016). Effects of yogasanas on osteoporosis in postmenopausal women. International Journal of Yoga, 9(1), 44–48. https://doi.org/10.4103/0973-6131 .171717 National Institutes of Health. (2017). The Surgeon General’s report on bone health and osteoporosis: What it means to you. https://www.niams.nih .gov/health-topics/surgeon-generals-report-bone-health-and-osteoporosis -what-it-means-you

North American Menopause Society. (2021). Management of osteoporosis in postmenopausal women: The 2021 position statement of the North American Menopause Society. Menopause, 28(9), 973–997. https://doi.org/10.1097 /GME.0000000000001831 Paik, J. M., Curhan, G. C., Sun, Q., Rexrode, K. M., Manson, J. E., Rimm, E. B., & Taylor, E. N. (2014). Calcium supplement intake and risk of cardiovascular disease in women. Osteoporosis International, 25(8), 2047–2056. https://doi.org /10.1007/s00198–014-2732–3 Pan, H., Jin, R., Li, M., Liu, Z., Xie, Q., & Wang, P. (2018) The effectiveness of acupuncture for osteoporosis: A systemic review and meta analysis. American Journal of Chinese Medicine, 46(3), 489–513. https://doi.org/10.1142 /S0192415X18500258 Pouresmaeili, F., Kamalidehghan, B., Kamarehei, M., & Goh, Y. M. (2018). A comprehensive overview on osteoporosis and its risk factors. Therapeutics and Clinical Risk Management, 14, 2029–2049. https://doi.org/10.2147 /TCRM.S138000 Ross, A. C. (2011). The 2011 report on dietary reference intakes for calcium and vitamin D. Public Health Nutrition, 14(5), 938–939. https://doi.org/10.1017 /s1368980011000565 Ross, A. C., Manson, J. E., Abrams, S. A., Aloia, J. F., Brannon, P. M., Clinton, S. K., Durazo-Arvizu, R. A., Gallagher, J. C., Gallo, R. L., Jones, G., Kovacs, C. S., Mayne, S. T., Rosen, C. J., & Shapses, S. A. (2011). The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: What clinicians need to know. Journal of Clinical Endocrinology and Metabolism, 96(1), 53–58. https://doi.org/10.1210/jc.2010–2704 Sarafrazi, N., Wambogo, E. A., & Shepherd, J. A. (2021). Osteoporosis or low bone mass in older adults: United States, 2017–2018 (NCHS Data Brief, No. 405). https://doi.org/10.15620/cdc:103477 U.S. Preventive Services Task Force. (2018, June 26). Osteoporosis to prevent fractures: Screening. https://www.uspreventiveservicestaskforce.org /uspstf/recommendation/osteoporosis-screening Vyas, D. A., Eisenstein, L. G., & Jones, D. S. (2020). Hidden in plain sight— Reconsidering the use of race correction in clinical algorithms. New England Journal of Medicine, 383(9), 874–882. https://doi.org/10.1056 /NEJMms2004740 World Health Organization. (2004, May). WHO scientific group on the assessment of osteoporosis at primary health care level. Author. https://www .dur-a-avaler.com/wp-content/uploads/2015/04/WHO-2004-Osteoporosis .pdf

CHAPTER

36

Pregnancy Decision-Making and Supportive Care* Katherine Simmonds

Throughout history, people have employed various techniques and technologies to prevent or increase their chances of becoming pregnant (Schneider & Schneider, 1995). For many, deciding when to become pregnant is crucial to their sense of personal well-being (Frost & Lindberg, 2013; Klann & Wong, 2020). For some, an unwanted or mistimed pregnancy can threaten their or their family’s survival; for others, failure to achieve a pregnancy can lead to shame, ostracization, and in some cases, even death. People’s decisions about whether, when, and how to become—or not become—pregnant are unique, and central to their very existence and identities. In this chapter, we focus on how clinicians can support people who present for healthcare related to a pregnancy diagnosis. Before describing some approaches and best practices for clinical care in this area, we provide an overview of pertinent terms, concepts, and demographic data. In addition, because it is common among health researchers and clinicians to classify pregnancies as “intended” or “unintended,” we briefly describe the debate that has emerged about this dichotomous categorization of pregnancy. Though we do use the terminology of intent to describe epidemiologic trends, we acknowledge the concept is deeply flawed and useful only at the population level, if at all. Because most clinical care takes place between clinicians and individuals, this chapter focuses primarily on interventions at this level. Finally, a few words about language and guiding frameworks for this chapter. First, we recognize that language about gender and sex is in flux, and this is likely to continue to change in the future. In this chapter, we strive to use currently accepted gender-neutral terms (e.g., people with the capacity for pregnancy, they/them/theirs); however, given that much of the available research uses binary categories with respect to sex/gender (female/male, women/men), we repeat these terms when reporting on findings of a given study. Second,

and

Joyce D. Cappiello

in considering the care of people who are deciding about, presenting for care, and engaging in actions related to a pregnancy, we ascribe to the tenets of reproductive justice and principles of trauma-informed care. For more about these frameworks, see Chapter 21, Fertility Self-Management and Shared Management, and Chapter 22, Preconception Counseling. While full discussion is beyond the scope of this chapter, clinicians are encouraged to learn about and incorporate these frameworks into their clinical practice as they care for people experiencing pregnancy.

DEFINITIONS AND EPIDEMIOLOGY Demographers and public health researchers define unintended pregnancy as “a pregnancy that is mistimed, unplanned, or unwanted at the time of conception” (Centers for Disease Control and Prevention [CDC], 2021). Within this framework, if a person did not want to become pregnant at the time they did or at any time in the future, the pregnancy is considered “unwanted.” If they wanted to become pregnant at some point in the future but not at the time they did, it is classified as “mistimed.” Large-scale population surveys like the National Survey of Family Growth (NSFG) and the Pregnancy Risk Assessment Monitoring System (PRAMS) are the most commonly cited sources of data on unintended pregnancy in the United States. According to the NSFG, 38% of all pregnancies were unintended in the years from 2017 to 2019, continuing a general trend of decline observed over the past few decades that has largely been attributed to increases in use and efficacy of contraception (Finer & Zolna, 2016). Healthy People 2030 has established a goal of further decreasing the proportion of unintended pregnancies in the United States to 36.5% (Office of Disease Prevention and Health Promotion, 2020).

*This chapter is a revision of the chapter that appeared in the second edition of this textbook, coauthored with Lisa Stern, and we thank her for her original contribution.

665

666  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

Disparities in Unintended Pregnancy Unintended pregnancy rates vary by select geographic, personal, and population characteristics. Globally, 48% of pregnancies are estimated to be unintended (Samankasikorn et al., 2019); however, this figure obscures wide variations in rates from country to country as well as intranationally. Overall, unintended pregnancies are more frequent in low- as compared to high-income countries, a reflection of global inequities in access to sexual and reproductive health services. Similarly, geographic disparities in unintended pregnancy rates are present within the United States, with states in the South tending to have the highest rates. In 2019, Mississippi (47.1%) and Florida (42.1%) had the highest proportions overall, while Vermont (20%) and New Hampshire (20.8%) were lowest (America’s Health Rankings, 2019). Economic factors and insurance coverage are partial explanations for these observed variations across states. At the population level, unintended pregnancy has been associated with certain demographic and socioeconomic factors. According to the NSFG, women with low incomes and living in poverty, and those who are not married—especially those who live with their partner—experience disproportionate rates of unintended pregnancy. Racial and ethnic disparities are also evident: Black and Hispanic women are more likely than White women to have unintended pregnancies. Education and age are also factors, as women without a high school degree, and those between ages 18 and 24 are more likely to experience unintended pregnancies than those who attend or graduate from college or are age 25 or older (Finer & Zolna, 2016). Intimate partner violence and reproductive coercion have also been implicated as contributors to disproportionately higher rates of unintended pregnancy (Samankasikorn et al., 2019). Social determinants of health, including income inequality and racism, underlie disparities in unintended pregnancy. Encouraging people to individually plan for pregnancy is an inadequate response for overcoming the effects of structural forces on health outcomes, including those related to reproduction. Social and reproductive justice offers a framework for clinical care providers to contextualize unintended pregnancy and promote the health of individuals, families, communities, and populations. Nursing scholars have called for a public health approach to unintended pregnancy that broadens the focus beyond individual patient encounters and toward access to high-quality, evidence-based sexuality education and broad preventive health services that empower people and their families to attain healthy pregnancy outcomes (Taylor et al., 2010). For people who do become pregnant, high-quality, accessible obstetric and abortion services are essential. Clinicians and public health experts play an important role in advocating for public policies that increase access to healthcare and health education, decrease racism and other forms of oppression, and enhance the economic power of women, transgender, and gender nonbinary people. Although this chapter—intended for a clinical audience—focuses primarily on clinical interventions at the individual level, to truly advance reproductive justice, structural barriers to reproductive healthcare must be dismantled and health equity must be broadly promoted (Klann & Wong, 2020).

Outcomes and Clinical Implications of Unintended Pregnancy Excluding miscarriages, 42% of unintended pregnancies in the United States ended in abortion, and 58% in live births, reflecting a continuing downward trend in the abortion rate since its peak in the 1980s (Finer & Zolna, 2016). Over the past 30 years, abortions have declined in United States, although an 8% upswing has been noted from 2017 to 2020 (Guttmacher Institute, 2022a). Globally from 2015 to 2019, an estimated 61% of unintended pregnancies ended in abortion, a rise of approximately 10% from previous years (Bearak et al., 2020). In pregnancies that end in live births, children may go on to be raised by biological or adoptive parents, or within kinship networks. Studies of the relationship between pregnancy intent and maternal and child health outcomes have yielded mixed results in the past; however, the results of the first prospective, longitudinal study of women who did and did not receive an abortion as requested produced informative data. The Turnaway Study found that women receiving an abortion did not experience harm to their health and well-being (Biggs et al., 2017), but being denied an abortion resulted in worse financial, health, and family outcomes (Foster, Ralph et al., 2018). Being denied an abortion had serious implications for the child, with higher rates of poor maternal bonding and living in poverty (Foster, Biggs et al., 2018), while existing children experienced negative developmental and socioeconomic consequences (Foster, Raifman et al., 2018). Although it is difficult to obtain precise numbers, approximately 18,000 to 20,000 domestic-born infants were adopted in the United States (0.5% of annual births; Sisson, 2022). Clinicians need to be prepared to provide unbiased information, decision support, and referrals about each of these options to patients who present with an initial positive pregnancy test. General information and resources as well as principles and specific techniques for fulfilling this clinical role are discussed later in this chapter. ISSUES IN THE MEASUREMENT OF UNINTENDED PREGNANCY

Intention is a complex and highly subjective concept. In order to enhance the validity and stability of the measure of pregnancy intent, typically researchers have not asked directly whether a pregnancy was intended or unintended, but rather posed a series of related questions (Klerman, 2000). In the NSFG, women were asked about each pregnancy they have had as to whether they wanted to have a baby at the time they conceived; further questions were then based on this initial response (Hayford & Guzzo, 2016). This retrospective approach to measurement of pregnancy intention is problematic; survey participants are asked about their desire to have become pregnant before it occurred, but many are responding months or even years after its occurrence. This leads to potential recall bias, which threatens the validity of the findings (Joyce et al., 2002). Additionally, substantial evidence has demonstrated that people’s views on intent may change over time, even during the course of a pregnancy (Aiken et al., 2015; O’Donnell et al., 2018; Rocca et al., 2019). Recently, greater interest in men’s role in pregnancy decision-making has emerged. Although the initial survey upon which the NSFG is based (known as the Indianapolis Survey)

Chapter 36  Pregnancy Decision-Making and Supportive Care 667

attempted to capture pregnancy intent by querying married, heterosexual couples, most subsequent studies have only engaged female participants. However, in recent years more researchers have sought to understand men’s attitudes toward pregnancy and the relationship to outcomes (Guzzo & Hayford, 2020; Lee et al., 2018; Li et al., 2022). Though public health has long assumed the position that unintended pregnancy is a problem, recent research suggests some people may not view pregnancy planning as meaningful, feasible, or a priority. Rather, many women express feelings of ambivalence about pregnancy or regard it as something that “just happens” (Arteaga et al., 2019; Hernandez et al., 2020; O’Donnell et al., 2018). Some suggest this supports a need for more widespread preconception planning, while others argue it reveals misplaced assumptions underlying the framework of pregnancy “intention” or “planning.” Regardless of an individual’s personal stance on pregnancy intention or planning, upholding and promoting reproductive decision-making that includes high-quality comprehensive reproductive health services as part of a full spectrum of patient-centered healthcare is an established responsibility of clinical care providers (Klann & Wong (2020).

ASSESSMENT All clinicians who provide care to people of reproductive age must be prepared to assess whether a patient desires a given pregnancy. In her seminal guide to pregnancy options counseling, Baker (1995) describes three distinct but related types of patient encounters clinicians may be involved in: (1) pregnancy testing; (2) pregnancy options counseling; and (3) abortion counseling. In the first, a person may suspect pregnancy but seek confirmation or, less commonly, are unaware they may be pregnant until the clinician suggests the possibility. In either case, the clinician proceeds with a pregnancy test, physical examination (if indicated), and delivery of test results (discussed later). If assessment confirms the person is pregnant, the clinician engages in the second type of encounter, pregnancy options counseling. In other cases, a person may present for care already certain they are pregnant but seeking education and counseling about their options. Suggested steps for clinicians for such visits are discussed in the section in this chapter on pregnancy options counseling. Finally, some people present for care with a confirmed pregnancy and have already decided how they want to proceed. In those cases, the clinical visit may just be to initiate desired service (abortion or prenatal care) or to obtain a referral. Abortion counseling is provided when a person has decided to end their pregnancy but is seeking support and information about this option specifically. This type of counseling is discussed further in the section on abortion. Approaches to self-sourcing and self-managing abortion outside the formal health system are also discussed.

History As with all patient encounters, obtaining a relevant history is the first step when assessing a person who might be or knows they are pregnant. Beginning the visit with openended questions to determine why they have come in often

reveals important information about the possibility of pregnancy as well as their feelings about it. If a reproductive age person reports symptoms commonly associated with early pregnancy, such as nausea, breast tenderness, fatigue, irregular vaginal bleeding, and/or amenorrhea, the clinician should rule out the possibility of pregnancy by asking for additional information about sexual activity and contraceptive use. In some clinical encounters, a patient’s presenting complaint may have nothing to do with pregnancy, but the possibility emerges during a review of systems or routine evaluation for another issue (e.g., before ordering x-rays or as part of a preoperative examination). If a person indicates they suspect or are already sure they are pregnant, eliciting additional information can yield important data to inform clinical assessment and management. For example, recent unprotected vaginal-penile intercourse may have prompted the visit, but it may be too early for a pregnancy test (if less than 7–10 days from fertilization). If a person is not currently seeking pregnancy and had unprotected sex less than 120 hours (5 days) ago, the clinician should recommend emergency contraception (see Chapter 21, Fertility Self-Management and Shared Management). If the sexual encounter was between 4 and 5 days prior to the visit, ulipristal acetate (Ella), or—if the patient is interested in and eligible for long-acting reversible contraception—a Copper-T intrauterine device (IUD; Paragard) can be offered, as these methods are more effective than levonorgestrel-containing methods. Before proceeding with a pregnancy test, the clinician should confirm the first day of the patient’s last menstrual period (LMP) and if it was normal (usual amount of flow, duration, etc.) in order to accurately determine the estimated gestational age (EGA) of the pregnancy. If the LMP is unknown or unsure, a pelvic examination and/or ultrasound can be performed to establish the gestational age. Patient reports of any spotting, bleeding, pain, or other early pregnancy warning signs also warrant further evaluation (see Chapter 23, Prenatal Care and Anticipating Birth, for further discussion). Screening for intimate partner violence and reproductive coercion should be a standard component of assessing patients for pregnancy. If a patient reports a positive home pregnancy test, the clinician should determine if they have already decided whether to continue or end the pregnancy, or if they would like additional information or counseling. Nobel et al. (2022) found that patients with a positive pregnancy test were more likely to report a positive experience if their provider discussed all their options. If a patient indicates they have made their decision, the clinician can assist them with obtaining desired services; if they are unsure about their decision or need additional information, education and counseling about their options is the next step.

Physical Examination and Diagnosis If a patient’s history suggests pregnancy is possible, a qualitative, immunometric urine test for human chorionic gonadotropin (hCG) should be performed. The clinician may also decide to perform a physical examination including a pelvic examination, ultrasound, and/or a quantitative beta-hCG test based on the patient’s history and clinical presentation. The presence of probable signs of pregnancy on physical exam,

668  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

including Chadwick (bluish hue of the vagina and cervix), Goodell (softening of the cervix), and Hegar (softening of the uterine isthmus) signs, as well as enlargement of the uterus, can contribute to a diagnosis of pregnancy; however, these signs may not be present in early pregnancy or may be too subtle for the clinician to detect. Physical examination findings should correlate with pregnancy test results and EGA; any discrepancy warrants further investigation, including review of the menstrual and gynecologic history to confirm accuracy of the LMP. If a discrepancy persists, a quantitative hCG and/or transvaginal ultrasound are typically the next steps in management (see Chapter 22, Preconception Counseling).

MANAGEMENT Providing Pregnancy Test Results Once pregnancy has been ruled out or confirmed, the patient should be informed. Use of neutral language, such as “the pregnancy test is positive, which means you are pregnant” is recommended. If the pregnancy test is negative, possible reasons for the result should be explained to the patient, including that it may be too early for the test to be positive or that they are not actually pregnant. If review of the menstrual and sexual history reveal it may be too early for a positive result, the patient can be instructed to repeat the test in 1 to 2 weeks. When performed correctly, 98% of people will have a positive test result within 7 days of implantation (Baldwin & Edelman, 2018). With immunometric tests, the type used in most clinical settings, false negative results are possible, but extremely rare. These rare false negatives are associated with elevated lipids, high immunoglobulin levels, and low serum protein associated with severe kidney disease. If a clinician doubts the accuracy of a negative result, they can order a quantitative beta subunit radioimmunoassay (Baldwin & Edelman, 2018). Following a negative pregnancy test, if a person does not want to become pregnant and anticipates future sexual activity that could lead to pregnancy (i.e., with a person with a penis), the clinician should initiate a discussion about contraceptive options, including a review of previous methods used, what has or has not worked for the person in the past, and about their desire for future pregnancies. Using a shared decision-making approach, together the patient and clinician can establish a contraceptive plan that includes follow-up. If the pregnancy test is positive, or pregnancy is otherwise confirmed, the clinician needs to determine the EGA and relay it to the patient, as it may be a factor in their decision about how to proceed, and in what options are available to them. This is discussed further in the next section, which focuses on providing pregnancy options counseling.

Pregnancy Options Counseling After confirming pregnancy or delivering a positive pregnancy test result, the clinician must determine whether a patient wants or needs additional information and support about the

options available to them. As previously mentioned, Noble et al. (2022) studied 14 family planning clinics in the southern United States and found patients’ satisfaction with care was higher when all options were discussed by the provider. This study offers evidence that people prefer to receive complete, unbiased information from providers so they can make fully informed decisions about their reproductive options. Though every patient encounter should be tailored to the individual, Simmonds et al. (2022) suggest four general steps for delivering options counseling: (1) explore how the patient feels about the pregnancy, including assessing their knowledge and providing education about each option; (2) help identify support systems and assess for risks; (3) assist with decision-making as needed; and (4) provide or refer for desired service. Each of these steps are discussed next. EXPLORE FEELINGS

Pregnancy can precipitate an abrupt change in a person’s life, relationship(s), living arrangements, financial stability, or self-concept. Baker (1995) suggests that for some, it may represent a crisis and lead to uncomfortable emotions or physical symptoms that interfere with a person’s ability to function. Awareness of these possibilities can help a clinician deliver nonjudgmental, patient-centered care. Asking open-ended questions such as “How do you feel about the pregnancy (or pregnancy test result)?” at the start of a visit can help the pregnant person feel comfortable sharing their concerns and experience. Finding out if they have considered or have already made up their mind about how to proceed allows the clinician to assess their decision-making process, as well as understanding available options. Some patients will report they have already decided, while others may not have decided yet; some may not feel comfortable sharing their thoughts with the clinician. Nondirective statements that indicate support for a person’s decision—no matter what it is—can help create an environment in which they feel comfortable expressing their emotions and asking questions. For example, the clinician can say, “I want to be sure you know what all your options are, and I’ll help you get good care no matter what you decide about the pregnancy.” It is important to ascertain whether a person understands their options, particularly those from certain vulnerable populations (such as adolescents or people who have recently immigrated to the United States). Because of stigma associated with abortion and adoption, clinicians need to assess patients’ knowledge about these options in particular. The 2022 Supreme Court decision (Dobbs v. Jackson Women’s Health Organization, 2022) has blocked access to abortion for many people in the state where they reside, and some may not be aware that abortion is still legally available in other states. See the section on abortion in this chapter for further discussion of these barriers. Some individuals may need time to accept a new or confirmed diagnosis of pregnancy. Clinicians should allow the time to reflect before discussing options or making specific plans; some individuals may prefer to do this outside the clinical setting, in which case a follow-up plan should be established. Follow-up can consist of a telephone call or return visit when further counseling and education can be delivered, or simply a confirmation that the person decided and knows how to arrange the next step of their care. Social and

Chapter 36  Pregnancy Decision-Making and Supportive Care 669

economic barriers that could interfere with follow-up, such as adolescents who do not plan to tell their parent or guardian that they are pregnant or a person with unstable housing, should be taken into consideration when establishing the follow-up plan. If a patient is ready and wants to discuss options, the clinician can proceed with counseling and education. In order to provide high-quality care, it is essential for clinicians to be current in their knowledge about available resources pertinent to all of the options (childrearing, adoption, abortion), as well as the legal landscape. Assessing a patient’s baseline knowledge and perceptions about each option can be accomplished by asking a question such as “Tell me, what you have heard about adoption/abortion?” or “Do you have any questions about what it would be like to be a parent/place a child for adoption/have an abortion?” Strategies and tools for assisting people with decision-making are discussed in the following paragraphs. IDENTIFY SUPPORT SYSTEMS AND ASSESS FOR RISK

In addition to discussing feelings about the pregnancy and, if the patient desires, providing education about their options, the clinician should inquire about their support systems and assess risk for violence or other personal harm that could be further exacerbated by the pregnancy. Asking if they have told others they are or might be pregnant can provide insight into the patient’s relationships and help identify those who may need more support, including additional follow-up or referral for social/mental health services. All people should be screened for risk of violence, abuse, or coercion at some point during a pregnancy options counseling visit. Reproductive coercion, at the intersection of violence and reproductive

health, is a specific form of gender-based, intimate partner violence (Basile et al., 2021). Reproductive coercion encompasses contraceptive coercion, pregnancy coercion, and abortion coercion. For some, reproductive coercion may result in pregnancy, and/or be an important factor in their decision-making, as partners, parents, or other influential people in their social network may exert excessive pressure or control regarding the decision. These situations can be ethically and legally complex in clinical practice. Resources to assist with identifying and managing such cases are available for clinicians (American College of Obstetricians and Gynecologists [ACOG], 2013). If coercion seems to be a factor in a person’s pregnancy decision-making, additional counseling and follow-up are warranted. (See Chapter 42, Gender-Based Violence and Women’s Health, for further discussion. ASSIST WITH DECISION-MAKING

Many people who know or strongly suspect they are pregnant may have already decided how they would like to proceed before presenting for clinical care; others may seek information or decision support from a clinician before making their final decision. For a person who has not decided how to proceed, it is important to contextualize their decision in relation to the gestational age of the pregnancy, and include education that early entry into prenatal care and early abortion are advised because they are both associated with better health outcomes. Furthermore, clinicians need to inform patients that abortion can be logistically difficult or impossible to obtain at advanced gestational ages, and that a delay in decision-making may preclude this option altogether. For people who are unsure whether to continue a pregnancy or have an abortion, tools to assist with decision-

TABLE 36.1  Resources for People and Providers on Abortion in the Post-Roe Era ADOPTION

Open Adoption & Family Services

www.openadopt.org

Prochoice, child-centered open adoptions including ongoing and lifelong services.

All-Options

www.all-options.org

Peer-based talk line to discuss pregnancy options or past/current experiences with abortion, adoption, parenting, infertility, or pregnancy loss.

Pregnancy Options Workbook

www.pregnancyoptions.info /pregnant.htm

A guide for those facing a pregnancy decision. LEGAL/POLICY ISSUES

If/When/How

www.reprolegalhelpline.org

Helpline to answer questions about legal rights with self-managed abortion.

Guttmacher Institute

www.guttmacher.org/state-policy /explore/overview-abortion-laws

Abortion laws by state.

Center for Reproductive Rights

https://reproductiverights.org/maps /abortion-laws-by-state

Abortion laws by state.

Kaiser Family Foundation

www.kff.org/womens-health-policy/ issue-brief/interactive-how-statepolicies-shape-access-to-abortion -coverage

State policies on abortion coverage in Medicaid, private insurance, and Affordable Care Act (ACA) Exchange Plans.

(continued)

670  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

TABLE 36.1  Resources for People and Providers on Abortion in the Post-Roe Era (continued) LEGAL/POLICY ISSUES

Reproductive Rights.gov

https://reproductiverights.gov

U.S. Department of Health and Human Services website with accurate, up-to-date information about access to and coverage of reproductive healthcare and resources.

INFORMATION ON SELF-MANAGED ABORTION PILLS

Plan C

www.plancpills.org

Provides information on how to access abortion pills online for selfmanaged abortions depending on your state.

www.mahotline.org

Proabortion clinicians with years of experience in caring for miscarriage and abortion provide advice on self-managing a miscarriage or abortion, do not provide medications.

Ineedana

www.ineedana.com/about

Provides information on closest clinics, parental consent laws, abortion funds plus other financial resources and telehealth or abortion pills by mail if allowed in your state.

Aid Access

https://aidaccess.org/en

An online source of abortion pills from outside the United States, provided by trained clinicians.

Reprocare Healthline

https://abortionhotline.org

Anonymous healthline provides peer-based emotional support, medical information, information on abortion funds, and referrals to people having self-managed abortions at home with pills.

Miscarriage + Abortion Hotline

FINANCIAL RESOURCES FOR ABORTIONS

National Network of Abortion Funds

https://abortionfunds.org

Network of >80 organizations with goal to remove financial and logistical barriers to abortion access; for example, assistance with paying for abortion, support such as transportation, child care, translation, doula services, and housing if traveling to get an abortion. POSTABORTION SUPPORT

Connect & Breathe

www.connectandbreathe.org/about.html

Peer-based, postabortion nonjudgmental talk line.

Exhale

https://exhaleprovoice.org

Peer-based talk line for nonjudgmental support after abortion.

Abortion Resolution Workbook

www.pregnancyoptions.info

Free download of Abortion Resolution Workbook: A Guide for Those Seeking Emotional and Spiritual Resolution.

RESOURCES FOR CLINICIANS

Abortion Provider Toolkit

https://aptoolkit.org

The Toolkit helps clinicians compile evidence to support the integration of early abortion care into their practice: (1) documenting education, knowledge, and training, (2) utilizing clinical and professional standards/ competencies to provide safe care, and (3) understanding roles of state and national professional organizations and state licensing boards.

Values Clarification Workshop Curriculum (RHAP)

www.reproductiveaccess.org /resource/values-clarification -workshop

Two-hour curriculum for healthcare staff who want to explore their attitudes and beliefs regarding issues surrounding abortion.

The Safety and Quality of Abortion Care in the United States (2018)

https://nap.nationalacademies.org /read/24950/chapter/1

The National Academies of Sciences, Engineering, and Medicine confirmed the safety and quality of abortion care in the United States, concluding “advanced practice clinicians (physician assistants, certified nurse-midwives, and nurse practitioners) can safely and effectively provide medication and aspiration abortions.”

Society of Family Planning Interim Clinical Recommendations: Selfmanaged abortion

www.smfm.org/publications /442-sfp-interim-clinical -recommendations-self-managed -abortion

Expert clinical guidelines

National Abortion Federation Clinical Policy Guidelines for Abortion Care, 2022

https://prochoice.org/providers/ quality-standards

Expert guidelines for clinician-provided procedural and medication abortion.

Chapter 36  Pregnancy Decision-Making and Supportive Care 671

making may be helpful. See Table 36.1 for a list of resources developed for use during a clinical visit or given to a patient to use after the visit. Another suggested strategy to support decision-making is to have the pregnant person make a list of pros and cons of each option. The Ottawa Personal Decision Guide is an evidence-supported, theory-based tool that has been designed to help patients with making health or social decisions (O’Connor et al., 2015). Though there are no published studies on its use among people facing a pregnancy decision, it may be a helpful aid in pregnancy options counseling. The Reproductive Health Access Project (2022c) has also developed a model for options counseling with people who are ambivalent about pregnancy. PROVIDE DESIRED SERVICE OR REFER TO APPROPRIATE PROVIDER

The final step of a pregnancy options counseling visit is establishing a plan with the pregnant person for obtaining desired care. If a patient is not ready to make their decision, a plan for follow-up should be discussed that considers their current EGA. Timely initiation of prenatal or abortion care should be encouraged, as this is considered standard of care. If a person is considering adoption, referral to a social worker or agency that can provide accurate information and supportive counseling about this option is recommended. See Table 36.1 for adoption resources. Depending on state-level APRN scope-of-practice regulations, type of certification, and clinical protocols, some clinicians may be able provide the services a patient desires (prenatal care and/or abortion), while others may need to refer to another provider or facility. Given the dynamic nature of abortion policy at the time of this writing, readers are directed to the section on abortion in this chapter for further discussion of providing or referring for this option. With appropriate education and certification, many primary care clinicians are able to provide routine prenatal care. Personal preference and availability of services in a particular area, as well as insurance plans or public assistance programs, may influence the type(s) of clinician (e.g., midwife, obstetrician, other) a patient selects for their prenatal and delivery care provider. Clinicians who do not or cannot provide a patient with the pregnancy-related service(s) they seek must refer to another provider or site. Developing relationships with individual providers and/or referral sites can give clinicians better understanding of the setting and quality of care delivered, which may be helpful when referring patients, especially for allaying anxiety that may arise when there is a break in continuity of care. Once a decision and plan of care have been made, the pregnancy options counseling encounter is over. Unless a clinician will also provide the subsequent prenatal or abortion care, a person may not return until they resume routine primary care. As with other referrals, if the patient will be obtaining services in a different facility, it is the referring providers’ responsibility to assist with securing an appointment, verify they were successful in accessing services in a timely manner, and follow up to determine satisfaction with care.

SPECIAL CONSIDERATIONS WHEN PROVIDING OPTIONS COUNSELING

Clinicians may experience conflicts between their personal feelings and professional responsibilities when providing care to a person who has recently discovered they are pregnant or are deciding whether to continue or end a pregnancy. Regardless of personal beliefs, health professionals are bound to uphold patient rights to autonomy and deliver care that is respectful and nonjudgmental by professional codes of ethics. The American Nurses Association (ANA) Code of Ethics for Nursing With Interpretive Statements (ANA, 2015) is one such guiding document. Although health professionals have certain rights to refuse to provide care that violates their personal beliefs, if a patient faces a life-threatening situation, or is otherwise at risk of not receiving needed care, conscientious objection cannot be invoked. Conversely, Harris (2012) suggests that some clinicians may choose to invert this concept of conscience, and instead use it to assert their willingness to provide certain types of care, such as abortion. Ideally, before providing options counseling, clinicians should engage in a process of values clarification to reflect on how their personal beliefs about parenting, adoption, abortion, and related reproductive health issues may influence their interactions with patients. Tools and workshops to assist healthcare providers in exploring these personal and professional intersections have been developed. If a clinician’s personal values threaten or interfere with delivery of unbiased, nondirective counseling or referrals, the patient’s care should be transferred to another provider. Every effort should be made to minimize delays and limit burdens to patients in obtaining care from another provider. The political landscape surrounding abortion in the United States demands clinicians to engage in a new level of reflection in considering their role in upholding patients’ reproductive autonomy.

ABORTION Induced abortion—or the practice of ending a pregnancy before viability—has been practiced throughout history and across cultures. Extensive historical and anthropological evidence indicates induced abortion has been practiced for thousands of years with a variety of means. Sociologist Carole Joffe asserts that in times and places when abortion has been forbidden, people have continued to seek it, and a culture of illegal provision has proliferated (Joffe, 2009). Until about 1880, abortion was legal in the United States. After that time, most states banned it, except to save the life of the mother. In 1973, following the U.S. Supreme Court ruling on the case of Roe v. Wade, the decision to end a pregnancy “before viability” became a constitutionally protected right. Before that ruling, many people still had abortions (estimates range from 200,000 to 1.2 million per year), including through legal channels in some cases, but more often by self-induction, underground, or “back alley” providers, as well as traveling outside the continental United States for services (Steinkopf-Frank, 2019). As a result, many people died from sepsis, hemorrhage, or other complications from abortions that were poorly performed. In 1930, 18% of maternal

672  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

deaths in the United States were attributed to induced abortion. By 1965, the absolute number of abortion-related deaths had dropped considerably (to less than 200 per year), largely as a result of the discovery of antibiotics in the 1940s. Rates for abortion deaths are now 75 mmHg Daytime mean systolic >130 mmHg, diastolic >80 mmHg Nighttime systolic mean >110 mmHg or diastolic >65 mmHg Source: Basile, J., & Bloch, M. J. (2023). Overview of hypertension in adults. UpToDate. https://www.uptodate.com/contents/overview-of-hypertension-in-adults; Whelton, P., Carey, R., Aronow, W., Casey, D. E., Jr., Collins, K. J., Himmelfarb, C. D., DePalma, S. M., Gidding, S., Jamerson, K. A., Jones, D. W., MacLaughlin, E. J., Muntner, P., Ovbiagele, B., Smith, S. C. Jr., Spencer, C. C., Stafford, R. S., Taler, S. J., Thomas, R. J., Williams, K. A., Sr., . . . Wright, J. T., Jr. (2017). ACC/AHA/ AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults. Journal of the American College of Cardiology, 71(19), e127–e248. https://doi .org/10.1016/j.jacc.2017.11.006

Lifestyle Modifications

Lifestyle modifications should be prescribed for all patients with elevated BP or HTN. Not all patients require pharmacologic therapy. Routine exercise is recommended, consisting of three to four sessions per week or more of moderate-intensity aerobic activity for approximately 40 minutes. Limiting alcohol intake is recommended; women who consume two or more alcoholic beverages per day have a significantly increased incidence of HTN compared to nondrinkers. Women with a diagnosis of HTN should not consume more than one alcoholic drink daily. Limited intake of sweets, sugar-sweetened beverages, and red meats is advised. Limiting sodium intake to an optimal goal of 2 mg/L) and LDL-C levels 40% when it was previously ≤40% (Heidenreich et al., 2022). Etiologies for HF include MI, ischemic heart disease, valvular heart disease (VHD), genetic or familial cardiomyopathies, amyloidosis, cardiotoxicity with substance abuse (cocaine, alcohol, or methamphetamine) or with cancer or other treatments, tachycardia, stress-induced or right ventricular (RV) pacing cardiomyopathies, peripartum cardiomyopathy, myocarditis, autoimmune causes, sarcoidosis, iron overload (including hemochromatosis), thyroid disease, and other endocrine metabolic and nutritional causes (Heidenreich et al., 2022). Many cardiomyopathies are unique to women and can result in HF. Peripartum cardiomyopathy presents with left ventricular diastolic dysfunction early after delivery but may also occur during pregnancy or after delivery (DeFilippis et al., 2021). Hypertropic cardiomyopathy is genetic and is usually diagnosed when clinical symptoms arise. Women, compared with men, are more likely to have obstructive physiology and a greater mortality rate (DeFilippis et al., 2021). Cardiac sarcoidosis is identified by endomyocardial biopsy or a combination of clinical cardiac symptoms in the setting of a biopsy-confirmed extracardiac sarcoid (DeFilippis et al., 2021). Cardiac amyloidosis is an infiltrative myocardial disease that results in cardiomyopathy by the deposition of misfolded amyloid fibrils within the heart muscle (DeFillipis et  al., 2021). The two most common types are monoclonal immunoglobulin amyloid light chain cardiomyopathy (ALCM) and transthyretin amyloidosis (ATTR-CM; Heidenreich et al., 2022). AL cardiac amyloidosis‌‌‌‌‌‌‌‌‌‌ has a slightly increased predominance in males and usually presents from the fifth to seventh decade of life. ATTR-CM is no longer considered a rare disease entity. ATTR can result from pathogenic variants in the transthyretin gene TTR (variant transthyretin amyloidosis, ATTRv) or wild-type transthyretin (wild-type transthyretin amyloidosis, ATTRwt). Sex differences in ATTR-CM are most significant in ATTRwt, in which there is an 80% to 90% predominance of men versus women. Although in a prospective screening study in patients over 60 years of age, admitted with HFpEF and left ventricular wall thickness greater than 12 mm, it was found that there was an equal proportion of men and women who were identified as having ATTR-CM by scintigraphy. In addition, a prospective endomyocardial biopsy study that

822  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

consisted of 108 patients with HFpEF (61% of these patients being women), 40% of the patients with ATTR-CM were women (DeFilippis et al., 2021). HF is a major cause of death and morbidity in women. Women tend to develop HF at an older age compared with men. HFpEF is responsible for half the cases of HF in women. HFpEF is more prevalent in women than in men (Bozkurt & Khalaf, 2017). Women with HFpEF have more of a predisposition to HTN as opposed to CAD. However, once a woman develops CAD, the risk for HF development is high. In a Framingham cohort, after having an MI, women had an increased risk of symptomatic HF when compared to men. DM and HTN increase the risk for developing CAD more for women than for men, and this in turn can result in the development of HF in women (Bozkurt & Khalaf, 2017). HFpEF (LVEF ≥55%) is twice as common in women than men. This is due to the physiologic differences in men and women (Eisenberg et al., 2018). Women have greater LV (left ventricular) contractility, lower LV mass, LV mass that is more preserved with aging, smaller coronary vessels, a lower rate of myocyte apoptosis, less catecholamine-mediated vasoconstriction, and a faster resting heart rate (Bozkurt & Khalaf, 2017). In the United States, HF is a growing health and economic burden mostly due to the aging population. The total deaths caused by HF in the United States have increased from 275,000 in 2009 to 310,000 in 2014 (Heidenreich et al., 2022). Noted in the 2017 AHA Heart Disease and Stroke Statistics Update, HF prevalence has increased to 6.5 million among Americans who are ≥20 years old. It is estimated that by 2030, the incidence of HF will increase by 46%, which will affect more than 8 million individuals. HF equally affects both males and females and is the leading cause of morbidity and death (Bozkurt & Khalaf, 2017). HF hospitalizations in the United States had decreased until about 2012. However, from 2013 to 2017, there has been a 26% increase in HF hospitalizations with 1.2 million hospitalizations among the 924,000 persons with HF (Heidenreich et al., 2022). While the number of patients with HF has grown because of the increasing number of older adults, the incidence of HF has decreased. However, the incidence of HFpEF is increasing and the incidence of HFrEF is decreasing. Deaths due to cardiomyopathies have increased globally as a result of increased recognition, diagnosis, and documentation of specific cardiotoxicity and cardiomyopathies (Heidenreich et al., 2022). EVALUATION/ASSESSMENT

The diagnosis of HF is made clinically and is based on one or more clinical symptoms of volume overload, including elevated jugular venous pressure, hepatojugular reflux, lung crackles, and lower-extremity edema (Box 43.5; Bristow & Lowes, 2005). Signs and symptoms of HF are similar for women and men (Box 43.5), although women have increased frequency with difficulty exercising, dyspnea upon exertion, and edema in comparison to men. Women also tend to have a worse quality of life than men for social activity and intermediate activities of daily living. In people who have HF, depression is more common in women than men. Women usually present with HF at an older age in comparison with men and develop a left bundle branch block on an EKG more

Box 43.5  Signs to Evaluate in Patients ‌‌‌‌‌‌‌With Heart Failure Elevated cardiac filling pressures and fluid overload Elevated jugular venous pressure S3 gallop Rales Hepatojugular reflux Ascites Edema Cardiac enlargement Laterally displaced or prominent apical impulse Murmurs that suggest valvular dysfunction Reduced cardiac output Narrow pulse pressure Cool extremities Tachycardia with pulsus alternans Arrhythmia Irregular pulse Source: Adapted from Lindenfeld, J., Albert, N. M., Boehmer, J. P., Collins, S. P., Ezekowitz, J. A., Givertz, M. M., Katz, S. D., Klapholz, M., Moser, D. K., Rogers, J. G., Starling, R. C., Stevenson, W. G., Tang, W. H., Teerlink, J. R., & Walsh, M. N. (2010). HFSA 2010 comprehensive heart failure practice guideline. Journal of Cardiac Failure, 16(6), e46. https://doi.org/10.1016/j.cardfail.2010.04.004

frequently than men. In addition, women are less likely than men to be referred for diagnostic testing or specialty care, and they undergo fewer procedures including revascularization, cardiac resynchronization therapy (CRT), implantable cardioverter defibrillators (ICDs), and mechanical circulatory support (Bozkurt & Khalaf, 2017). Patients are classified based on functional capacity. The New York Heart Association (NYHA) classification system relates symptoms to everyday activities and to the woman’s quality of life (Young & Mills, 2001). This system categorizes the severity of congestive HF by functional classes that depend on the degree of effort required to elicit symptoms. Class I patients have no limitation of physical activity: Ordinary activities do not produce symptoms of angina, dyspnea, or undue fatigue. Class II patients have a slight limitation of physical activity: Ordinary activities do produce cardiac symptoms. Class III patients have a marked limitation of physical activity: Although these patients are comfortable at rest, less-than-ordinary activities do produce cardiac symptoms. Those in Class IV have severe, persistent symptoms with any physical activity, and they can also have symptoms while at rest. DIAGNOSTIC STUDIES

It is important that the specific cause of HF be identified because certain conditions require disease-specific therapies. Laboratory evaluation including urinalysis, serum

Chapter 43  Cardiovascular Disease in Women 823

electrolytes, blood urea nitrogen, serum creatinine, complete blood count, fasting lipid profile, thyroid-stimulating hormone levels, liver function tests, and iron studies including ferritin, serum iron, and transferrin saturation should be performed on initial evaluation of the patient to help provide information regarding the patient's comorbidities, potential causes of HF, eligibility for and adverse effects of treatments, and degree and prognosis of HF. Laboratory tests are repeated with changes in treatment or in clinical conditions (Heidenreich et al., 2022). The measurement of B-type natriuretic peptide (BNP) or N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) should be obtained and can be useful in supporting or excluding the diagnosis of HF in an individual. In patients with chronic HF, measurements of NT-proBNP or BNP levels are recommended to stratify risk. In hospitalized patients, BNP or NT-proBNP levels are recommended on admission to establish prognosis. In addition, a BNP or NT-proBNP level is useful predischarge in helping to plan the patient's course and postdischarge prognosis. It is important to note that obesity is associated with lower levels of BNP and NT-proBNP, which can decrease diagnostic sensitivity. There also needs to be consistency in obtaining either BNP or NT-proBNP; they are not interchangeable (Heidenreich et al., 2022). An EKG should be obtained for the initial evaluation. It should be repeated when a clinical indication arises such as ischemia or myocardial injury, suspicion for an arrhythmia, conduction abnormality, or other cardiac abnormalities (Heidenreich et al., 2022). The EKG often reveals LVH. Tachycardia, rapid atrial fibrillation (AF), ischemic EKG changes, and evidence of atrioventricular and intraventricular conduction blocks and changes in voltage can be present (Madias, 2006). A chest radiograph should be obtained to assess for pulmonary congestion, to determine heart size, and to detect an alternative pulmonary, cardiac, or other disease process that may be contributing to symptoms (Heidenreich et  al., 2022). A chest radiograph often shows increased intravascular markings, frank pulmonary edema, or pleural effusions; cardiomegaly is a common finding as well (Madias, 2006). DIFFERENTIAL DIAGNOSIS Systolic Versus Diastolic Heart Failure

A transthoracic echocardiogram (TTE) has become an integral part of the evaluation of the woman with HF. It is helpful for making the diagnosis of diastolic HF by identifying LVH, which is the leading cause of diastolic HF (Jessup et al., 2009; Vasan & Levy, 2000). It provides important clues regarding the etiology of HF by assessing the cardiac structure and function of the heart and identifying abnormalities of the heart valves, myocardium, and pericardium (Heidenreich et al., 2022). The various etiologies of HF that may be found include ischemia, HTN, valvular disease, regurgitation, pericardial effusion, cardiomyopathy, cardiac amyloidosis, or a combination. Results of the TTE also help guide management because the test provides a measurement of the EF (Yancy et al., 2013). At times, the TTE may not accurately evaluate the cardiac structure and function of the heart, or more information may be necessary to determine the cause for cardiac dysfunction.

TABLE 43.4  Heart Failure Classifications CLASSIFICATION

DEFINITION

HFrEF (heart failure with reduced ejection fraction)

Ejection fraction ≤40%

HFimpEF (heart failure with improved EF [with an EF that had previously been ≤40%])

EF >40%

HFmrEF (heart failure with mildly reduced ejection fraction)

EF 41% to 49%

HFpEF (heart failure with preserved ejection fraction)

EF ≥50%

Source: Heidenreich, P. A., Bozkurt, B., Aguilar, D., Allen, L. A., Byun, J. J., Colvin, M. M., Deswal, A., Drazner, M. H., Dunlay, S. M., Evers, L. R., Fang, J. C., Fedson, S. E., Fonarow, G. C., Hayek, S. S., Hernandez, A. F., Khazanie, P., Kittleson, M. M., Lee, C. S., Link, M. S., . . . Yancy, C. W. (2022). 2022 AHA/ACC/ HFSA guideline for the management of heart failure. Journal of the American College of Cardiology, 79(17), e263–e421. https://doi.org/10.1016/j.jacc.2021.12.012

Therefore, other imaging modalities are utilized to clarify the initial diagnosis of congestive HF and to provide a more accurate assessment of cardiac structure and function. These other imaging modalities may include stress echocardiography, SPECT imaging, CMR, cardiac CT, radionuclide ventriculography, invasive coronary angiography, or PET (Heidenreich et al., 2022). HF is often separated into two diagnostic categories, depending on the left ventricular systolic function. Systolic HF refers to a LVEF 40%), HFmrEF (LVEF 41% to 49%), and HFpEF (LVEF ≥50%). All patients with prior HF history or current HF, despite measurement of LVEF, should be considered for guideline-directed medical therapy (GDMT; Colvin, 2022). Diuretics are used to improve symptoms, relieve congestion, and prevent worsening HF. The goal is to use the lowest dose of diuretic to maintain euvolemia. The preferred diuretic medications in most HF patients are loop diuretics such as furosemide, torsemide, and bumetanide. Furosemide is most commonly used. In those patients with HTN, HF, and mild fluid retention, thiazide diuretics may be considered. In those patients who have persistent edema and are unresponsive to loop diuretics alone, metolazone or chlorothiazide may be added to the loop diuretic. However, these patients must be monitored closely as this combination can put patients at increased risk for hyponatremia, hypokalemia, worsening renal function, and death, whereas higher doses of loop diuretics alone did not adversely affect survival. There are limited randomized data that compare these two approaches, although the DOSE (Diuretic Optimization Strategies Evaluation) trial did favor the use of high-dose intravenous loop diuretics (Heidenreich et al., 2022).

Chapter 43  Cardiovascular Disease in Women 825

The effects of diuretics on mortality and morbidity are uncertain with the exception of MRAs (mineralocorticoid receptor antagonists). Data obtained recently from the nonrandomized registry called Optimize-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) showed reduced 30-day hospitalization for HF and a lower all-cause mortality rate with the use of diuretics compared with no diuretic use after a hospital discharge for HF (Heidenreich et al., 2022). GDMT now consists of four classes of medications: (1) renin–angiotensin system inhibition (RASi) with the use of angiotensin receptor–neprilysin inhibitors (ARNi), ACE inhibitors (ACEi), or ARB alone; (2) beta-blockers; (3) MRAs; and (4) SGLT2 inhibitors (SGLT2i; Colvin, 2022). ARNi is now recommended as the first-line RASi to reduce morbidity and mortality in HFrEF (class 1a recommendation; Colvin, 2022). When an ARNi is not appropriate, an ACEi is recommended. If an individual cannot tolerate an ACEi and an ARNi is not appropriate, an ARB is recommended. If an individual has been on an ACEi or ARB, it is recommended to discontinue the ACEi or ARB and initiate an ARNi for increased reduction in morbidity and mortality (Colvin, 2022). It is recommended that an ARNi be utilized before discharge as de novo treatment in patients hospitalized with acute HF if they have had a reduction in NT-proBNP, improvement in health status, and improvement of LV remodeling parameters compared with an ACEi or ARB (Heidenreich et al., 2022). ARBs are indicated when women are intolerant to ACE inhibitors. For women who cannot take an ACE inhibitor or an ARB (e.g., women with renal disease), the combination of hydralazine and a nitrate is an acceptable alternative (Lindenfeld et al., 2010; Yancy et al., 2013). Beta-blockers, which were formerly absolutely contraindicated for women with HF, have become one of the cornerstone therapies (Lindenfeld et al., 2010; Yancy et al., 2013). Because beta-blockers were a later addition to the treatment of congestive HF, women have not been adequately studied (Wenger, 2002). Beta-blockers are equally effective for reducing morbidity and mortality rates in both women and men (CIBIS-II Investigators and Committees, 1999; Ghali et al., 2002; Packer et al., 2001). In patients with HFrEF, with either previous or current symptoms, the use of one of three beta-blockers has been proved to reduce mortality (Heidenreich et  al., 2022). These three beta-blockers are metoprolol (extended release, Toprol XL) and bisoprolol (Cardicor), which are both cardioselective agents, and carvedilol (Coreg), which is a noncardioselective beta-blocker with alpha-blocking properties. It is recommended that one of these beta-blockers be used to reduce hospitalizations and mortality risk. The benefits of beta-blockers were seen in patients with or without CAD, older patients, patients with or without DM, in women, and across ethnic and racial groups but not in those individuals with atrial fibrillation (Heidenreich et  al., 2022). Moreover, these drugs are effective for the treatment of both ischemic and nonischemic forms of congestive HF (Yancy et al., 2013). For Black individuals who remain symptomatic despite the use of beta-blockers, ACE inhibitors or ARB therapy, and MRAs, adding a combination of hydralazine (Unipres) and isosorbide dinitrate (Isordil) can be considered. This

combination has been shown to improve symptoms and reduce morbidity and mortality among Black people. There are no significant data for the use of hydralazine and isosorbide dinitrate when taken with an ARNi. It is recommended as a part of standard therapy for Black people. It is unknown if there is any benefit in utilizing hydralazine and isosorbide dinitrate in non-Black people with HFrEF (Heidenreich et al., 2022). MRAs, spironolactone (Aldactone) or eplerenone (Inspra), are recommended to reduce morbidity and mortality if the potassium is 30 mL/minute. This category of medications has shown improvements in HF hospitalizations, all-cause mortality rate, and sudden cardiac death in HFrEF patients (Heidenreich et al., 2022). Spironolactone and eplerenone have been found to improve mortality rates among women with class III and IV HF. This is primarily a result of these drugs’ neurohormonal blockage effects and not because of their diuretic effects (Yancy et al., 2013). For symptomatic chronic HFrEF, regardless of the presence or absence of type 2 DM, SGLT2 inhibitors are now a class 1A recommendation to decrease HF hospitalizations. In addition, SGLT2 inhibitors have also been found to be beneficial in HFpEF and HFmrEF (class 2a recommendation) in decreasing cardiovascular mortality risk and HF hospitalizations. In prespecified subgroup analyses, it was found that both men and women have similar benefits from SGLT2 inhibitors (Khan et al., 2022). In patients with HFmrEF (LVEF 41%–49%), current or previously symptomatic, it is recommended to treat the patient with evidence-based GDMT (including beta-blockers for HFrEF, ARNi, ACEi, or ARB, and MRAs to reduce the risk of cardiovascular death and HF hospitalization, especially with those patients who have an LVEF on the lower end of the range. Data for this group of patients are either subsets of analyses or post hoc from previous HF trials with patients who would now be classified as HFmrEF. When the data were assessed, patients who were on the lower end of the LVEF spectrum seem to respond to medical therapies as patients with HFrEF. Thus, it was felt reasonable to treat these patients with the same GDMT (Heidenreich et al., 2022). A small, randomized trial ‌‌‌‌‌‌‌‌‌(TRED-HF) showed that there was a high rate of relapse of dilated cardiomyopathy (44%) within 6 months in patients who had discontinued GDMT. Therefore, it is now recommended that GDMT be continued in patients with HFimpEF even in those who are asymptomatic, to prevent LV dysfunction and relapse of heart failure (Colvin, 2022). The 2022 AHA/ACC/HFSA guidelines for management of HF also made recommendations for other drug treatments in HF once GDMT has been optimized. In patients with class II to IV HF symptoms, it may be reasonable to add an omega-3 polyunsaturated fatty acid supplementation to a patient's medication regimen to reduce cardiovascular hospitalizations and mortality risk (class 2b recommendation). In those patients who are taking a renin–angiotensin–aldosterone system inhibitor (RAASi) who develop hyperkalemia, gastrointestinal potassium binders (patiromer [RLY5016] and sodium zirconium cyclosilicate [SZC]) may be an option for treatment to allow patients to continue/titrate their GDMT medications

826  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

(class 2b recommendation). In those patients with symptomatic, NYHA class II to III, stable HFrEF, chronic, with LVEF ≤35%, receiving GDMT, inclusive of a beta-blocker at maximum tolerated dose, in normal sinus rhythm with a heart rate ≥70 bpm at rest, ivabradine may be a reasonable option to add to their medication regimen to reduce cardiovascular death and HF hospitalizations (class 2a recommendation). Vericiguat, an oral soluble guanylate cyclase stimulator, can be considered in high-risk patients with HFrEF with recent worsening HF, already on GDMT, and may reduce risks of cardiovascular death and HF hospitalization (class 2b recommendation). It can result in improvement in endothelial function, vasodilation, and decrease in fibrosis and remodeling of the heart (Heidenreich et al., 2022). Digoxin (Lanoxin), which is one of the oldest pharmacologic agents available, is currently indicated only for women with systolic dysfunction who are still symptomatic despite conventional therapies (Lindenfeld et al., 2010; Yancy et al., 2013). One important caveat with digoxin use in women is the higher risk of digoxin toxicity at low doses. The Heart Failure Society of America (HFSA) guidelines of 2013 recommend digoxin levels of less than 1.0 ng/mL (Yancy et  al., 2013). Digoxin can also help with the management of heart rate in women with AF (Lindenfeld et al., 2010; Yancy et al., 2013). In patients with symptomatic HFrEF despite being on GDMT or in those who are unable to tolerate GDMT, the utilization of digoxin can be considered to decrease hospitalizations for HF (class 2b recommendation; Heidenreich et al., 2022). DIASTOLIC DYSFUNCTION

HFpEF (LVEF ≥50%) accounts for 50% of all patients with HF and is associated with significant mortality and morbidity rates. It is a disorder that is contributed to by comorbid conditions including DM, obesity, HTN, CAD, CKD, and specific causes such as cardiac amyloidosis. Therefore, treatment for these comorbid conditions is extremely important (Heidenreich et al., 2022). HFpEF has a much greater prevalence in women than men. Before women present with HF, they are more likely to develop arterial stiffness, diastolic dysfunction, and coronary microvascular dysfunction with aging, all of which predispose them to HFpEF. A comparison of men and women found that women have higher LV filling pressures with exercise and poor diastolic reserve than men. Women also have a higher predisposition to coronary microvascular dysfunction than men (Khan et al., 2022). Women with HFpEF have lower natriuretic peptide levels in comparison with men. This lower natriuretic peptide level plays an important role in the pathophysiologic mechanism in HFpEF in women, especially in those with obesity. Following menopause, the loss of estrogen as well as systemic inflammation caused by comorbidities such as obesity can lead to reduced signaling of cGMP (cyclic guanosine monophosphate)-protein kinase G. Sacubitril/valsartan (Entresto) increases cGMP-protein kinase G signaling, which is felt to possibly benefit postmenopausal women, especially those with metabolic comorbidities such as DM and obesity (Khan et al., 2022). As with systolic HF, diuretics are used to control symptoms of fluid overload and reduce congestion (Heidenreich et al., 2022). However, managing fluid balance with diastolic

HF can be more challenging. Patients with diastolic HF are more dependent on preload to maintain cardiac output as a result of the stiffened left ventricle (Barnard, 2005). The 2022 ACC/AHA/HFSA guidelines regarding diastolic HF recommend the treatment of any underlying causative conditions (e.g., HTN). Patients with HFpEF and HTN should strive to keep BP well controlled in accordance with HTN guidelines to prevent morbidity. In addition, the guidelines recommend the following treatment options. SGLT2 inhibitors are useful in decreasing cardiovascular mortality and heart failure hospitalizations (class 2a recommendation). Management of AF in these patients can aid in the improvement of symptoms (class 2a recommendation). In select patients with HFpEF, especially those with an LVEF on the lower end of the spectrum, consideration for the use of MRAs, ARBs, and ARNi is recommended to decrease hospitalizations (class 2b recommendation; Heidenreich et  al., 2022). Beta-blockers are important for the treatment of diastolic dysfunction to control HTN and tachycardia, thereby increasing diastolic LV filling time. Furthermore, measures to restore and maintain the sinus rhythm among women with AF who are symptomatic despite heart rate control can also be considered (Yancy et al., 2013). ACE inhibitors and ARBs have been shown to reduce myocardial fibrosis and LVH; however, they have not been studied exclusively in the presence of diastolic HF. Even so, patients with diastolic dysfunction (as with systolic dysfunction) appear to have activation of the renin–angiotensin– aldosterone system, which makes these medications logical choices for the treatment of HF that results from diastolic dysfunction (Yancy et al., 2013). Many cardiomyopathies are unique to women. These cardiomyopathies may be in either category of HFpEF or HFrEF. Peripartum cardiomyopathy is an idiopathic cardiomyopathy presenting with LV systolic dysfunction, usually early after delivery but can occur during pregnancy or up to a few months after the delivery (DeFilippis et al., 2021). Hypertrophic cardiomyopathy is a genetic cardiomyopathy that is more likely to be diagnosed in women after they present with clinical symptoms. Women compared with men are more likely to have obstructive physiology and a higher mortality rate (DeFilippis et al., 2021). Device Therapy for Heart Failure

Mortality rates among patients with HF and severely impaired LV systolic function (≤30%) are high (Yancy et  al., 2013). Regrettably, HF represents a sentinel prognostic event in patients with a high risk for readmission (50% in 6 months) and a high 1-year mortality rate of 30% (Giamouzis et  al., 2011; Kociol et al., 2010). Death is attributable to arrhythmia, MI, progressive HF, pulmonary or systemic emboli, electrolyte disturbances, and other vascular events (Lindenfeld et al., 2010). The risk of sudden cardiac death is decreased with appropriate pharmacologic therapy, as described previously. However, certain women may benefit from the implantation of an ICD. The 2022 AHA/ACC/HFSA guidelines for device therapy recommend the implantation of an ICD in patients with an EF of 35% or less, who are NYHA class II or III, with nonischemic dilated cardiomyopathy or ischemic heart disease, at least 40

Chapter 43  Cardiovascular Disease in Women 827

days post MI, on chronic GDMT, whose survival is anticipated to be greater than 1 year. In addition, ICD implantation is also recommended for primary prevention of sudden cardiac death to reduce mortality in patients with an EF ≤30%, who are at least 40 days post MI, with NYHA class I symptoms, currently on GDMT, whose survival is expected to be greater than 1 year (Heidenreich et al., 2022). These devices are not recommended or appropriate for the woman with end-stage (class D) disease with progressive and irreversible HF symptoms or with a limited life expectancy as a result of other disease states; such devices are unlikely to affect the overall prognosis of these women (Tracy et al., 2012; Yancy et al., 2013). Sex differences in ICD implantation have been found. Based on many studies, women who are eligible for an ICD are less likely than men to have a device implanted. It remains questionable if an ICD prevents sudden death in women because landmark primary ICD trials included very few women. In meta-analyses, it was found that there was no survival benefit for women with an ICD. In addition, women were also less likely to receive appropriate ICD therapies in comparison to men. It is thought that the sex difference benefits of ICDs for primary prevention may be due to the cause of death. One study showed that there was 32% lower risk of sudden death in women than men and there was no sex difference in pump failure (DeFilippis et al., 2021). CRT is another treatment option for patients with HF that can reduce hospitalizations, reduce total mortality, and improve symptoms and quality of life (Heidenreich et  al., 2022). Biventricular pacing improves hemodynamic measurements such as cardiac index and systemic vascular resistance (Blanc et  al., 1997). Furthermore, medication therapy using ACE inhibitors, ARBs, and beta-blockers along with CRT can slow and even partially reverse LV remodeling (Lindenfeld et al., 2010). Criteria for CRT include symptomatic HF, NYHA class II to IV, with EF ≤35%, in normal sinus rhythm (NSR), left bundle branch block (LBBB) with a QRS complex ≥150 ms (class I indication). CRT may also be advantageous in (1) those individuals with an EF ≤35%, normal sinus rhythm, LBBB, QRS 120–149 ms, (2) individuals with an EF ≤35%, non-LBBB pattern, with QRS ≥150 ms, and (3) those individuals with significant pacemaker dependency despite what their underlying rhythm is. These three criteria are class IIa recommendations (DeFilippis et al., 2022). CRT is underutilized in women compared to men even though women appear to have greater benefit. Women with HFrEF who are eligible for CRT are less likely than men to receive this therapy. This disparity has increased over time in United States. In the MASCOT ‌‌‌‌‌‌‌‌‌(Management of Atrial Fibrillation Suppression in AF-HF Comorbidity Therapy) study, women with CRT in comparison to men had a greater decrease in LV end-diastolic dimension, increased improvement in quality of life, and fewer hospitalizations for HF. In another study, women had a greater increase in LVEF and greater reduction in LV end-diastolic dimension compared with men (DeFilippis et al., 2021). Wilcox et al. (2014) found that the use of guideline-directed CRT and ICD therapy was associated with substantially reduced 24-month mortality rate in eligible men and women with HF and reduced EF. Device therapies should be offered to all patients.

Critical to decision-making for device implantation is the woman’s overall prognosis and her functional capacity at baseline. Women with HF have been found to have poorer health-related quality of life than men (Heo et al., 2007; Lesman-Leegte et  al., 2009). In addition, many women need a great deal of psychological support because the implantation of such a device can be unnerving, impeding patient recovery and return to daily life—now with an ICD. Cultivation of social support networks can cushion the impact of stress through support and online chat groups.

Arrhythmias Until recently, women have been underrepresented in electrophysiologic and most cardiovascular clinical trials. This underrepresentation has significant implications for understanding and treating female patients as guideline-directed therapies emerge from such clinical trials (Zeitler et  al., 2022). The National Institutes of Health have taken aim at addressing this disparity more recently by adding a requirement to grant applications that they include sex differentiation (Legato et al., 2016). Understanding that gender differences exist in the cardiac electrical system is paramount in guiding our assessment, treatment, and understanding the etiology behind cardiac electrical disturbances in women. In addition to understanding sex differences in the etiology of the electrophysiologic system, we must also address sex differences in device therapies and the effects of drugs and pregnancy (Zeitler et al., 2022). In addition to sex differences, we also must take into consideration changes with aging and how that affects the heart and how it may be different in women. Aging is associated with many changes in the cardiovascular system that include decreased compliance of blood vessels, mild concentric LVH, increased atrial contraction contribution to LV filling, and a higher incidence of many cardiac arrhythmias and conduction disorders (Chow et al., 2012). Some alterations in cardiac rhythm do not produce symptoms, whereas others cause hemodynamic changes requiring treatment. The prognostic significance of any conduction abnormality or rhythm disturbance is dependent primarily on the presence and severity of any accompanying cardiac disease (Chow et al., 2012). ETIOLOGY

Early research regarding the pharmacologic management of arrhythmias included few, if any, women. Recent studies have recognized this data gap and have described differences in electrophysiologic properties and cardiac substrate between men and women that can be attributed to several factors including circulating sex hormones, sex hormones affecting cell development, and autonomic function (Zeitler et  al., 2022). The cardiac action potential is affected by sex hormone levels as they affect protein synthesis and affect the ion channels. This effect on ion channels changes the susceptibility to arrhythmias and EKG findings (such as the QT interval). Differences in the conduction system between males and females are noted in several studies. The resting heart rate of a female is about 3.5 bpm ‌‌‌‌‌‌‌‌‌ higher than that of an age-matched

828  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

male (Taneja et al., 2001). This difference by gender is thought to be a result of a known shorter sinus node recovery time in women (Connolly et al., 2009; Zeitler et al., 2022). Heart rate variability is a product of autonomic function and is thereby sensitive to hormonal changes (Brar et al., 2015). In an analysis of EKGs dating back to 1920, Bazett observed and documented that women have an inherently longer QT interval than men (Bazett, 1997). This difference occurs after males enter puberty due to the increasing testosterone levels and by the time the male reaches middle age and testosterone levels decrease, the difference in QT interval is no longer observed (Bidoggia et al., 2000). The degree of autonomic variability in women, which suggests that women have a higher vagal tone, also contributes to the difference in how women may respond to certain therapies and medications (Ryan et  al., 1994). Therefore, there may be more complexity in diagnosing and treating arrhythmias in women over the life cycle. Lastly, women may also respond differently to treatments for arrhythmias, especially pharmacologic management (Hongo & Scheinman, 2005). DIFFERENTIAL DIAGNOSIS Supraventricular Arrhythmias Definition and Etiology

The term supraventricular arrhythmia (SVA) encompasses rhythms that originate at or above the sinoatrial (SA) node and includes arrhythmias such as atrioventricular nodal reentrant tachycardia (AVNRT), atrial tachycardia (AT), atrial fibrillation (AF), atrial flutter, and supraventricular tachycardia (SVT; DeSimone et al., 2018). Symptoms

Regardless of gender, these arrhythmias can cause patients uncomfortable symptoms. Women with SVA in addition to AF and ventricular arrhythmias can present with a variety of symptoms, including palpitations, heart racing, heart flutters, chest discomfort, lightheadedness, dizziness, presyncope, and fatigue. However, frank syncope is uncommon with SVA, occurring in only about 15% of patients (Blomström-Lundqvist et al., 2003). Diagnostic Studies

A TTE may be used to evaluate structural heart disease, including valvular heart disease, that will increase the risk of arrhythmias. Twenty-four-hour Holter monitoring is helpful for evaluating the woman with frequent symptoms, but if the symptoms do not occur within that 24-hour time span, an alternative diagnostic monitoring device should be considered. An event recorder or loop recorder is indicated for less frequent symptoms and is used for longer than 24 hours. Implantable loop recorders are a third option for the patient whose symptoms may be less frequent or of short duration and are therefore difficult to capture on a loop recorder. Exercise testing can be helpful if the symptoms are brought on by stress or exercise. Laboratory examination of the woman with palpitations and a suspected arrhythmia includes electrolyte, magnesium, and thyroid function tests. A complete blood

count may be indicated if anemia or infection is suspected because both conditions may precipitate tachyarrhythmias (Blomström-Lundqvist et  al., 2003). Additionally, findings from these studies help the clinician to differentiate between SVA and ventricular tachycardia. Treatment/Management

For women who have no evidence of preexcitation on the 12-lead EKG, who have normal LV function, and who tolerate the arrhythmia well, no specific therapy may be required, especially if the episodes are infrequent. Precipitating factors should be reviewed during the initial assessment, and if there is a history of excessive intake of alcohol, caffeine, or nicotine (which are stimulants); use of recreational drugs; or hyperthyroidism, these factors should be discussed and eliminated (Blomström-Lundqvist et  al., 2003). Treatment of regular, stable SVT is aimed at symptom alleviation and prevention by utilizing agents to slow conduction through the AV node. Vagal manuevers can be attempted by the patient during an episode, but pharmacologic management is frequently required (DeSimone et  al., 2018). Treatment with pharmacologic agents such as beta-blockers and calcium channel blockers are first-line medication therapy (Ahmad et al., 2021). Digoxin (Lanoxin) is less effective for the prevention of SVA. For women with SVT and no evidence of structural heart disease, propafenone (Rythmol), and flecainide (Tambocor) are effective for the prevention of recurrence, and they may be prescribed by cardiologists who specialize in arrhythmia management (Blomström-Lundqvist et al., 2003). Radiofrequency catheter ablation has also been very successful for the treatment of SVA (especially SVT) in both males and females. Success of ablation does not seem to differ by sex; however, what does appear to differ is the time to treatment. Women tend to have a longer time between symptoms onset to diagnosis and ablation of their SVT arrhythmia. This discrepancy is not due to referral pattern but is due to female preference for medication trials before invasive intervention. The major common theme in reasons for the delay is the female patients’ perception or role as caregiver (Zeitler et al., 2022). Ablation is now considered first-line therapy (Page et al., 2016). Atrial Flutter Etiology, Symptoms, and Evaluation/Assessment

Women with atrial flutter can present with symptoms similar to those of SVT, and the diagnostic workup is identical (Blomström-Lundqvist et al., 2003). However, these women often have more comorbidities and are more likely to have symptoms of fatigue, shortness of breath, and chest discomfort, as well as palpitations. HF and pulmonary disease are commonly seen among these women, who are typically older than women with SVT (Scheinman & Huang, 2003). Treatment/Management

Guidelines regarding the pharmacologic management of atrial flutter are often combined with those of AF. Beta-blockers and nondihydropyridine calcium channel blockers can be used for initial rate control; this is a class I

Chapter 43  Cardiovascular Disease in Women 829

TABLE 43.5  CHA2DS2-VASc Score CONDITION

POSSIBLE POINTS

C

Congestive heart failure

+1

H

Hypertension

+1

A

Age (older than 75 years)

+2

D

Diabetes mellitus

+1

S

Prior stroke or transient ischemic attack or thromboembolic event

+2

V

Vascular disease of any kind

+1

Sc

Sex category (female sex)

+1

Source: Lip, G. Y., Nieuwlaat, R., Pisters, R., Lane, D. A., & Crijns, H. J. (2010). Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: The Euro Heart Survey on Atrial Fibrillation. Chest, 137, 263–272. https://doi.org/10.1378/chest.09-1584

indication. However, the most common side effect is hypotension. Catheter ablation is also class I indication and considered first-line therapy for patients presenting with atrial flutter. Amiodarone, dofetilide, or sotalol are class IIa options for rhythm control strategy. Flecainide and propafenone are class IIb indicated for rhythm control in the absence of structural heart disease (Page et al., 2016). For atrial flutter stroke risk is assessed in the same manner as for AF. Although the mechanism is different than AF, the atrial flutter patient carries the risk of systemic embolization due to ineffective atrial squeeze and also carries a high coexistent prevalence of AF (January et al., 2019). CHA2DS2-VASc score (see Table 43.5) risk assessment and anticoagulation management recommendations should be followed. Patients who present with 48 hours or greater or unknown duration of atrial flutter can be considered for direct current cardioversion (DCCV) or pharmacologic cardioversion if a transesophageal echocardiogram is negative for thrombus or if the patient has been on uninterrupted anticoagulation for a minimum of 3 weeks prior to DCCV and will remain on anticoagulation for at least 4 weeks post cardioversion. Recommendations for anticoagulation of patients with nonvalvular AF include direct oral anticoagulants (DOACs) or vitamin K agonist (warfarin). DOACs are the preferred choice if not contraindicated as studies show superiority or lower bleeding risk compared to warfarin. For those patients requiring anticoagulation who have valvular atrial arrhythmia, vitamin K agonist (warfarin) is indicated (January, 2019). Atrial Fibrillation Definition and Scope, Etiology

AF is a common arrhythmia and the risk of developing AF increases with age. Obesity, DM, HTN, obstructive sleep apnea, European descent, ischemic heart disease, CKD, alcohol abuse/overuse, and smoking are among the list of additional risk factors for developing AF. AF is the primary diagnosis upon hospitalization in the United States in more than 454,000 cases per year. One out of every seven strokes

is caused by AF, and these strokes tend to be more severe in nature in comparison to other stroke etiologies (Centers for Disease Control and Prevention [CDC], 2021). By the year 2030, it is estimated that 12.1 million people in the United States will be diagnosed with AF (CDC, 2021). Patients with AF are hospitalized twice as often as those without AF and are three times more likely to have multiple admissions. It is estimated that caring for patients with AF adds $26 billion to U.S. healthcare expenses (January et  al., 2014). The increase in hospitalizations for AF occur for many reasons, including aging of the population, the rising prevalence of chronic heart disease, and more frequent diagnosis as a result of increased monitoring and awareness of the condition by practitioners and patients. The prevalence is higher among men than women (Feinberg et  al., 1995); however, because the incidence of AF increases overwhelmingly with aging and because there are more women in the population older than 75 years, the total number of women and men with AF in this age group is equal (Humphries et al., 2001). Males have an overall larger left atrial size than females, which may partially account for the higher prevalence of AF in men; however, the etiology is not completely understood. In the landmark Women's Health Initiative program, those subjects who received hormone replacement therapy (HRT) had greater incidence of AF than those who received placebo. This indicates that postmenopausal HRT increases the woman’s risk of developing AF and is important to consider in management (Perez et al., 2012). Women are more symptomatic than men, possibly because of faster heart rates and smaller body size, and unfortunately, women have experienced more problems when the heart rate is controlled (Michelena et al., 2010). AF can occur in the presence or absence of heart disease. However, as with atrial flutter, individuals with AF often have HTN, valvular heart disease, and/or CVD. AF is associated with an increased risk of stroke, HF, and all-cause mortality, especially among women (Stewart et al., 2002). Furthermore, perioperative AF is associated with an increased long-term risk of ischemic stroke, especially after noncardiac surgery (Gialdini et al., 2014). The prognosis of those with AF is most benign among individuals who are younger than 60 years with no known heart disease; these patients are often referred to as having lone AF. Most individuals move out of this category over time as they age and develop other heart diseases and HTN (Alpert et al., 2014). Evaluation/Assessment and Diagnostic Studies

Women who present with AF can have the same symptoms as previously mentioned for women with SVA. The initial diagnostic workup is similar as well. The hemodynamic consequences of AF include the loss of atrial kick, which can add up to 30% of cardiac output; this loss is particularly important to those with reduced heart function. In addition, the tachycardia itself can lead to a tachycardia-mediated cardiomyopathy (Fuster et al., 2006). Treatment/Management

The first goal of AF management is rate control with either a beta-blocker or a calcium channel blocker. As with the other tachyarrhythmias, if hemodynamic instability exists, referral

830  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

for electrical cardioversion is the preferred management strategy. As long as the patient is hemodynamically stable, the rate may be controlled with beta-blockers, nondihydropyridine calciumchannel blockers, or amiodarone (Pacerone). Digoxin can also be used to slow the ventricular rate in AF; however, it is rarely useful as monotherapy. Digoxin (Lanoxin) is not effective for controlling increased heart rate during times of exertion or exercise (Fuster et al., 2006). Rate versus rhythm control is a difficult choice that most often requires referral to a cardiologist or an electrophysiology specialist. Most concerning with the diagnosis of AF is the risk of ischemic stroke, which averages 5% per year among patients with nonvalvular AF. Rates of ischemic stroke are two to seven times higher among women with AF than among those without AF (Cabin et al., 1990; Wolf et al., 1991) and in comparison to male patients, women have a greater overall stroke risk in AF, especially if they over age 75 years (Zeitler et al., 2022). Some investigators have demonstrated a worse outcome and a higher rate of recurrence after cardioversion. The most effective treatment currently for the restoration of sinus rhythm in those with AF is catheter ablation. Females do tend to have higher recurrence of AF post ablation compared to males. This may be due to delayed ablation consultation referral, older age at time of referral relative to later age of onset, and less aggressive ablation technique by the operator for fear of increased procedural complication rate in women (Kummer et al., 2015). AF affects the current risks and the long-term prognosis of women differently than of men. An analysis from the Euro Heart Survey on Atrial Fibrillation found that women with AF have more than double the thromboembolism risk of men with AF (Lip et al., 2010). In addition, a Swedish study found that the rate of ischemic stroke in AF patients younger than 65 years was 47% higher in women than men (Friberg et al., 2012). Last, women overall have a significantly higher risk of AF-related stroke than men and are more likely to live with stroke-related disability, which in turn leads to a significantly lower quality of life (Volgman et  al., 2009). The diagnosis, symptoms, and treatments of AF can differ for women, too. A potential deadly difference in women 20 to 79 years old is that the risk of stroke is 4.6-fold greater in women than in men (Schnohr et al., 2006). In addition, mortality rate for women with AF is up to 2.5 times greater than that for men (Michelena et al., 2010). The decision to place patients with AF on anticoagulation therapy is based on a number of factors. The choice of agent to use is dependent on balancing the risk of stroke or thromboembolic event with the risk of bleeding. Current guidelines recommend using the CHA2DS2-VASc score to determine the appropriateness of anticoagulation (January et al., 2014). It is a 10-point scale found to be a clinical predictor for estimating stroke risk in patients with nonrheumatic AF (Lip et al., 2010; Table 43.5). Individuals scoring 2 or higher on the CHA2DS2VASc are considered at high risk for thromboembolic events and should have anticoagulation therapy, unless contraindicated (January et al., 2014). Those scoring less than 2 (0 or 1) are candidates for aspirin therapy with either 81 or 325 mg (January et al., 2014). For many years, the standard of therapy for anticoagulation was vitamin K antagonists, namely, warfarin (Fuster et al., 2006). Warfarin therapy has been demonstrated to be

superior to aspirin therapy (Fuster et al., 2006), alone or in combination with clopidogrel, for stroke prevention (Connolly et  al., 2009). The risk of intracerebral hemorrhage (ICH) with the use of warfarin occurred in individuals with an international normalized ratio (INR) greater than 4.0. The advantages of warfarin include its ability to be quickly reversed by parenteral vitamin K or fresh frozen plasma (Mookadam et al., 2015). However, there are many disadvantages to warfarin therapy. INR monitoring is critical to the success of balancing this medication’s anticoagulant effect with the risk for bleeding. It can take 5 days or longer for some individuals to reach the recommended therapeutic INR of 2.0 to 3.0. Warfarin’s significant food and drug interactions affect the INR, and therefore, guidelines recommend monitoring at least every 30 days (Mookadam et al., 2015). These factors discourage providers from prescribing anticoagulation and patients accepting their recommendations (Hohnloser, 2011). Warfarin therapy is highly unpredictable (Macedo et  al., 2015). A population-based data analysis of 140,078 patients with AF in their first year of warfarin therapy in the United Kingdom found that only 44% had optimal INRs more than 70% of the time (Macedo et al., 2015). The search for more predictable anticoagulation has led to the development of DOACs. The four available agents are all indicated for use in patients with nonvalvular AF and cannot be used in patients with prosthetic heart valves. These agents have the advantage of fixed dosing and do not require blood test monitoring. In addition, they do not have dietary precautions, as they are not vitamin K antagonists. Most require adjustment for renal dysfunction (Mookadam et al., 2015). Dabigatran is an oral direct thrombin inhibitor prescribed twice daily. It is superior to warfarin in the prevention of the primary outcomes of stroke or systemic embolism (Connolly et al., 2009). A lower dose is approved for use in patients with renal dysfunction, but it should be avoided in patients with severe renal dysfunction (Mookadam et al., 2015). A risk of major bleeding was found, similar to warfarin, in the analysis of all patients, and in subgroup analysis the risk of intracranial bleeding was lower in patients older than 75 years (Connolly et  al., 2009). The main concern with direct thrombin inhibitors is the lack of a direct antidote. However, the FDA is currently reviewing the drug idarucizumab as an antidote to dabigatran, which showed good effect in the reversal of the anticoagulant effects of dabigatran in patients needing urgent surgery (Pollack et al., 2015). Rivaroxaban, apixaban, and the newest approved edoxaban are factor Xa inhibitors approved for use in patients with nonvavular AF. All the factor Xa agents are fixed-dose agents that do not require blood testing of anticoagulation levels. Rivaroxaban is a direct factor Xa inhibitor approved in 2011. It is administered once daily and requires dose adjustment in patients with renal dysfunction. The ROCKET-AF trial demonstrated the noninferiority of rivaroxaban compared with warfarin in the prevention of stroke and embolism in patients with nonvalvular AF; rivaroxaban had no significant differences in rates of major bleeding and less risk of intracranial and fatal bleeding when compared with warfarin (Patel et al., 2011). Apixaban is a direct factor Xa inhibitor that was approved for use in 2012. It is administered twice daily. The ARISTOTLE

Chapter 43  Cardiovascular Disease in Women 831

study compared apixaban to warfarin in patients with AF. Apixaban was found to be superior to warfarin (p =.01), and rates for major bleeding were found to be less than with warfarin therapy (Granger et al., 2011). Moreover, apixaban therapy reduced rates of all-cause mortality (Granger et al., 2011). Apixaban is approved in 2.5- and 5-mg doses. The 2.5-mg dose is recommended for patients with two of the three following factors: age more than 80 years, body weight less than 60 kg, and serum creatinine higher than 1.5 mg/dL (Granger et al., 2011). Edoxaban is a direct factor Xa inhibitor approved for use in 2015 for anticoagulation in AF. It is a once-daily medication and has a dose adjustment with renal impairment. The ENGAGE-AF TIMI 48 trial studied edoxaban versus warfarin in the prevention of thromboembolic events in patients with nonvalvular AF (Giugliano et al., 2013). Edoxaban was found to be equal to warfarin in the prevention of stroke and embolism. There were lower rates of fatal bleeding and intracranial bleeding. However, significantly higher rates of gastrointestinal bleeding were noted (Giugliano et al., 2013). The decision to withhold or stop anticoagulation therapy in women who are at high risk for bleeding can be difficult. The decision to initiate anticoagulation is individualized and discussed with the woman and her family as well as with all members of the healthcare team. Strategies to limit bleeding risk when prescribing anticoagulation have been studied. The European Society of Cardiology guidelines for the treatment of AF include utilization of a scoring system to assess patients at high risk for bleeding, called the HAS-BLED score (Lane & Lip, 2012). At the very least, patients at high bleeding risk require more frequent monitoring and follow-up (Mookadam et al., 2015). Sinus Tachycardia Definition and Scope

By definition, sinus tachycardia is a regular cardiac rhythm with rate faster than 100 bpm (Yusuf & Camm, 2005). Sinus tachycardia is a physiologic response to stress, anxiety, or exercise but is concerning or warrants further investigation when it occurs at rest. In many instances, women with symptoms of palpitations or heart racing will have a sinus tachycardia. Approximately 90% of patients with inappropriate sinus tachycardia are women (Blomström-Lundqvist et  al., 2003; Krahn et al., 1995). Evaluation/Assessment

In the case of sinus tachycardia, it is most appropriate to find and treat the underlying disorder. Before medication is prescribed, a history is obtained to check for possible precipitating factors, such as excessive caffeine, alcohol, nicotine intake, recreational drugs, or hyperthyroidism. The condition, such as hyperthyroidism, is treated or the precipitating agents eliminated first before proceeding to medical management. Treatment/Management

A beta-blocker is indicated for symptom management in many instances, especially in the case of hyperthyroidism. If a betablocker is contraindicated or not tolerated, a nondihydropyridine calcium channel blocker (e.g., diltiazem [Cardizem] or

verapamil [Calan]) can be considered. Close monitoring is required because less rate-controlling medication is needed when the underlying condition has been successfully treated; often the medication can be tapered off completely (Blomström-Lundqvist et al., 2003). Ventricular Arrhythmias

The presentation of ventricular arrhythmias ranges from single premature ventricular contractions (PVCs) of little or no hemodynamic significance to life-threatening ventricular tachycardia or ventricular fibrillation. These arrhythmias can occur in women with and without heart disease or cardiac disorders. Differential Diagnosis and Treatment/Management

The primary goal for managing life-threatening ventricular arrhythmias is the prevention of sudden cardiac death. Referral to an arrhythmia specialist is appropriate. Management is based on the etiology of arrhythmia. Possible treatments are medications, ablation, ICD placement, and sometimes a short-term intervention involving a wearable defibrillator in the form of a vest. Long QT syndrome is a disorder that is more common in postpubertal women than in postpubertal men. In addition, women with long QT syndrome have an increased risk of arrhythmia for 9 to 12 months postpartum (Seth et  al., 2006). Beta-blocker therapy should be continued during pregnancy and in the postpartum period. Long QT syndrome often goes undiagnosed, although 90% of these patients have experienced the condition by age 40 years. The problem arises from the ion channels in the heart muscle causing conduction defects, which predispose patients to torsades de pointes, which then can proceed to syncope and sudden cardiac death. A prolonged QT interval can be caused by some medications as well as hypokalemia and other nutritional and endocrine disorders. Long QT syndrome should be suspected in patients who have recurrent syncope during exertion and those with family histories of sudden, unexpected death (Meyer et al., 2003). A thorough history is key to protecting patients at risk. Arrhythmias and Pregnancy

Pregnancy can predispose women to arrhythmias due to the many physiologic changes that the body undergoes during this time, including autonomic changes, systemic fluid variations, and systemic hemodynamic changes (Massari et  al., 2018). Fortunately, most arrhythmias during pregnancy are benign. In addition, most arrhythmias in the pregnant woman arise in the setting of a structurally normal heart and are therefore tolerated well (Shotan et al., 1997). In women with a history of arrhythmia, ectopy may increase. Premature atrial contractions and PVCs are relatively common during pregnancy and generally do not require pharmacologic management. Often the heart rate increases by 25% in women who are pregnant; therefore, sinus tachycardia, especially in the third trimester is common. Ectopic beats and nonsustained arrhythmia are found in more than 50% of pregnant women assessed for palpitations, whereas sustained tachycardias are uncommon in 2 to 3/1,000 (Blomström-Lundqvist et al., 2003; Shotan et al.,

832  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

1997). The avoidance of triggers such as caffeine and emotional stress can be helpful. SVT episodes may increase during pregnancy. Women with frequent SVT who are contemplating becoming pregnant may want to consider ablation therapy before conception to avoid medications while pregnant (Oakley et al., 2003). All antiarrhythmic medications cross the placenta, and pharmacokinetics can be altered during pregnancy, thereby necessitating more frequent monitoring of drug levels (Oakley et al., 2003). Therapeutic drug levels can be affected by an increase in intravascular volume requiring an increase in loading dose, a reduction of plasma proteins contributing to lower drug concentrations, increased renal blood flow with an increase in the clearance of drugs, increased hepatic metabolism of drug resulting from progesterone also increasing clearance, and changes in gastric absorption of medication, making serum drug concentrations variable (Perez-Silva & Merino, 2011). For women who develop SVT during pregnancy, management is similar to that of the nonpregnant patient but does vary depending on the trimester of pregnancy (Ibetoh et al., 2021). Concerns related to treatment are related to potential pharmacotherapy contraindications and side effects and radiation to the unborn fetus (Kaspar et al., 2018). Regardless of trimester or pregnancy status, vagal maneuvers are attempted first to break the arrhythmia (Oakley et  al., 2003). If vagal maneuvers are not successful, adenosine is the drug of choice for terminating a sustained SVT during all three trimesters and labor (Ibetoh et al., 2021). If the condition is recurrent and suppression is necessary, cardioselective beta-blockers (e.g., metoprolol) are recommended. Atenolol and verapamil are contraindicated during the first trimester; however, they can be used during the second and third trimesters (Ibetoh et al., 2021). Some experts recommend avoiding beta-blockers altogether during the first trimester, if possible; however, others contend that beta-blockers are acceptable during pregnancy (Hongo & Scheinman, 2005). Sotalol is more likely to cause fetal bradycardia because it more readily crosses the placenta (Oakley et  al., 2003). Flecainide and propafenone have been safely used during pregnancy for the treatment of refractory SVT (Cox & Gardner, 1993). Direct current cardioversion with anesthesia can be performed safely for treatment of hemodynamically unstable or refractory SVT during all trimesters including labor, but it has triggered early preterm labor when performed during the third trimester (Ibetoh et al., 2021). Fluoroless radiofrequency catheter ablation with the use of echocardiography-guided catheters can be performed safely during pregnancy to treat SVT refractory to other treatment strategies (Curry & Quintana, 1970; Kaspar et al., 2018; Perez-Silva & Merino, 2011). AF is relatively rare (2.2%) during pregnancy in patients with no known heart disease or dysfunction but, when present, poses a challenge not only for rhythm versus rate control management but from an anticoagulation perspective as well (Pachariyanon et al., 2019). Unfortunately, many of these women may be previously undiagnosed, and the increased intravascular volume of pregnancy triggers a symptomatic arrhythmia. These patients typically are discovered to have an undiagnosed underlying etiology driving the atrial fibrillation. This includes hyperthyroidism or hypothyroidism, structural anomalies, pulmonary embolism, drug toxicity, and

electrolyte disturbances (DiCarlo-Meacham & Dahlke, 2011). Digoxin, beta-blockers, and calcium channel blockers are all appropriate for the rate control of AF during pregnancy; in women with underlying heart disease, beta-blockers or calcium channel blockers are safer in comparison to digoxin (Fuster et al., 2006; January et al., 2014; Oakley et al., 2003). Pregnancy induces a prothrombotic state for the patient but unfortunately data regarding stroke risk assessment and anticoagulation guidelines are lacking (Zeitler et al., 2022). Most women do not require anticoagulation during pregnancy unless they are at high risk for a thromboembolic event (e.g., women with valvular heart disease; Fuster et al., 2006). Warfarin crosses the placenta and has been implicated in fetal hemorrhage and death; therefore, it is contraindicated during pregnancy. Low-molecular-weight heparin is the anticoagulant of choice in pregnancy (Fuster et  al., 2006). Bradycardia that requires permanent pacemaker implantation is also uncommon during pregnancy; however, uterine compression of the inferior vena cava can rarely causes reflex bradycardia (Oakley et  al., 2003). In addition, congenital heart block can become symptomatic during pregnancy. Permanent pacemaker implantation is safe during pregnancy if abdominal lead shielding is used (Oakley et al., 2003). Ventricular tachycardia can occur during any term during pregnancy. It can present in women with congenital long QT interval syndrome or valvular heart disease, or it may be idiopathic. Most instances of ventricular tachycardia that occurs in pregnancy in the absence of structural heart disease are benign (Kotchetkov et  al., 2010). If ventricular tachycardia presents during the last 6 weeks of pregnancy or after birth, postpartum cardiomyopathy must be ruled out. Because ventricular tachycardia during pregnancy can be exacerbated by increased catecholamines, beta-blockers are used as firstline therapy. Amiodarone is strictly reserved for emergent treatment of hemodynamically unstable and life-threatening ventricular arrhythmias secondary to its known fetal toxicity (Stec et al., 2013). Any hemodynamically unstable rhythm can seriously compromise blood flow to the fetus and is considered a medical emergency. Electrical cardioversion can be used to convert any hemodynamically unstable tachyarrhythmia. Very little electrical energy reaches the fetus, and it is advisable to convert the rhythm quickly rather than to risk decreased blood flow to the fetus (Curry & Quintana, 1970; Ogburn et al., 1982; Zipes et al., 2006).

Valvular Heart Disease DEFINITION AND SCOPE

In the United States, the prevalence of valvular heart disease is estimated at 2.5% (CDC, 2014).‌‌‌‌‌‌‌‌Valvular disease due to rheumatic fever has dramatically declined in the past few decades; however, age-related degenerative changes are becoming more common (DesJardin et  al., 2022). Because of the increase in degenerative etiologies, the prevalence of valve disease increases after the age of 65 years, especially with aortic stenosis (AS) and mitral regurgitation (MR), which is responsible for three of four cases of valve disease (Iung & Vahanian, 2014). Valvular heart disease has contributed to increasing cardiac

Chapter 43  Cardiovascular Disease in Women 833

mortality and morbidity rates in the United States for the last several decades (Shoob et al., 2006). Despite these trends, there have been advances in noninvasive cardiac monitoring, minimally invasive surgical techniques, and appropriate timing of surgical interventions, along with sophisticated prosthetic valves; these have improved the overall prognosis for acute and chronic valvular disorders. The etiology and pathophysiologic consequences, evaluation, treatment, and continual care of women with valvular heart disease and consequent cardiac dysfunction necessitate a methodic approach to the efficient and practical use of a wide choice of diagnostic procedures, medical and surgical interventions, and long-term follow-up. ETIOLOGY

The four heart valves normally regulate unidirectional blood flow through the heart’s atria and ventricles and into the systemic circulation. Their structural and functional characteristics allow for efficient cardiac muscle contractility and relaxation and for optimal cardiac perfusion (Guyton & Hall, 2006). Valvular diseases and the resultant changes in normal circulatory physiology are caused by either a forward flow through a narrow or irregular orifice (stenosis) or a regurgitant flow through an incompetent valve (insufficiency). Each of these structural abnormalities leads to hemodynamic changes that directly affect myocardial structure and function as well as coronary blood flow. With the widespread use of echocardiography to both diagnose and plot the trajectory of valve dysfunction, the guidelines for the management of specific valvular lesions have incorporated noninvasive and surgical interventions for patients with acute and chronic valve disease. EVALUATION/ASSESSMENT

In general, patients with valve disease may present with a heart murmur, symptoms, or incidental findings of valvular abnormalities on chest imaging or noninvasive testing. Regardless, all patients with known or suspected valve disease should undergo an initial history and physical examination. Cardiac auscultation as a screening method for valvular disease is an essential aspect of the cardiac evaluation. Murmurs are classified according to location, intensity, pitch, radiation, and duration on the basis of the timing of events during the cardiac cycle (Shipton & Wahba, 2001). Specific details of cardiac auscultation–associated physical examination findings that aid in the diagnosis of valvular dysfunction are provided in the ACC/AHA 2014 practice guidelines for the management of patients with valvular heart disease (Nishimura et al., 2014). DIAGNOSTIC STUDIES

In evaluating patients with valvular heart disease, it is important to correlate the history and physical examination findings with the results of the EKG, chest radiograph, and TTE. Further testing, such as CT, CMRI, and stress testing, may be needed if there is a discrepancy between the physical examination findings and initial testing results. Invasive testing, including transesophageal echocardiography and cardiac catheterization, is often needed to determine an optimal treatment plan. There is a classification system to note the progression of valvular disease with four stages (A–D), similar to that

of the HF guidelines (see earlier section). The stages range from A (at  risk) through B (progressive), C (asymptomatic severe), and D (symptomatic severe). These stages are based on valve anatomy, valve hemodynamics, the hemodynamic consequences, and symptoms (Nishimura et al., 2014, Otto et al. 2021). DIFFERENTIAL DIAGNOSIS Mitral Valve Prolapse Definition, Scope, and Etiology

The term mitral valve prolapse (MVP) refers to the displacement of abnormally thickened redundant mitral valve leaflets that extend into the left atrium during systole and that may or may not be associated with MR. Other associated features of this syndrome may include left atrial dilatation, left ventricular enlargement, consequent SVA, and abnormalities that involve other valves as well. It is estimated that 1% to 3% of the U.S. population is afflicted with MVP (Bonow et  al., 2006), although the true prevalence is difficult to determine. MVP may have a much lower prevalence than previously estimated, and the prevalence may be similar among different ethnic groups (Theal et al., 2004). From a population perspective, the prevalence of serious cardiovascular complications associated with MVP is low. It is more commonly diagnosed in women than in men and is thought to be associated with either familial (e.g., Marfan syndrome or other connective tissue diseases) or acquired disorders (e.g., CAD). The health trajectory of a patient with MVP is variable, ranging from a benign hemodynamic state and a normal life expectancy to severe comorbid complications and the need for surgical intervention. Evaluation/Assessment

Although a formal diagnosis is made with the use of echocardiography, a routine physical examination reveals an abnormal auscultatory sound that prompts further workup. The salient auscultatory characteristic of MVP is a high-pitched midsystolic “click” that is best heard at or medial to the apex of the heart. A subsequent late-systolic crescendo murmur indicates mild MR. Changes in the patient’s body position, which affects ventricular blood volume, can alter auscultatory findings: Standing to decrease the end-diastolic volume causes an earlier click during systole, whereas squatting to increase ventricular volume causes a delay in the click. Diagnostic Studies

Noninvasive two-dimensional Doppler echocardiography provides the most specific and quantitative information to help define the degree of valve abnormality. For symptomatic women, TTE is performed to help with the determination of the need for cardiac catheterization; transesophageal echocardiography is performed when surgical repair is being considered (Bonow et al., 2006; Nishimura et al., 2014). Treatment/Management

The ACC and AHA guidelines have approached the evaluation and management of women with MVP on the basis of the presence or absence of symptoms, although some indications

834  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

overlap (Bonow et al., 2006; Nishimura et al., 2014). Surgical treatment is the intervention of choice when that patient has severe and symptomatic mitral stenosis, but not all patients will be a surgical candidate. In those cases, the patient may be a candidate for percutaneous balloon mitral valvuloplasty (PBMV; Yoon et al., 2017). Monitoring and Surgical Management

Most women with MVP have a benign course. However, potential associated complications include embolic events, infective endocarditis, and MR that eventually requires surgery. Symptomatic women who develop severe MR require valve repair or replacement to prevent complications such as HF, cerebrovascular events, arrhythmias, and death (Bonow et al., 2006). Mitral valve repair is preferred whenever possible over replacement (Nishimura et al., 2014). Mitral Regurgitation Etiology

MR is a dysfunction of the mitral valve causing retrograde blood flow from the left ventricle to the left atrium, which is the opposite of the proper direction. MR is characterized as either primary or secondary, which is categorized by the cause of the MR. Primary MR is also called degenerative or organic MR. This classification of MR results from a structural deformity or leaflet, chordae tendinea, or papillary muscle damage. Secondary MT is a result of left ventricular dysfunction with normal mitral valve leaflets and chords (Zhang et al., 2020). One of the initial hemodynamic changes that takes place with MR is an increase in the end-diastolic volume. An incompetent mitral valve allows for increased blood flow (and subsequent increased pressure) into the left atrium, which reduces afterload (thus decreasing the end-systolic volume). In a more chronic state, the heart compensates for changes in pressure and volume by increasing in size and becoming hypertrophied. A reduction in cardiac output with severe MR can result in pulmonary congestion, shock, and death (Chirillo et al., 2006). Evaluation/Assessment and Diagnostic Studies

For the purpose of designing a treatment algorithm, the progression of MR can be categorized into three stages: (a) the asymptomatic patient with hemodynamically significant regurgitation, (b) the asymptomatic patient with decreased left ventricular function, and (c) the symptomatic patient with decreased left ventricular function (Carabello & Crawford, 1997; Nishimura et  al., 2014). For women with chronic MR, cardiac enlargement with displacement of the left ventricular apical impulse can be appreciated during the physical examination. A holosystolic murmur can be auscultated and may also be accompanied by an S3 or early diastolic flow rumble with or without the presence of HF. TTE provides a baseline evaluation of the severity of the MR. Treatment/Management

Medical therapy is limited, although vasodilating agents such as nitroprusside are used to reduce afterload. For women who develop symptoms in the presence of acute and severe MR, surgery is recommended, particularly if left

ventricular function is preserved. Surgical options include mitral valve repair, mitral valve replacement with the preservation of the valve apparatus, and mitral valve replacement with the removal of the valve apparatus (Bonow et al., 2006; Nishimura et al., 2014). Valve repair is preferred over valve replacement to avoid the need for chronic anticoagulation. The European Heart Survey showed that women with severe MR were referred for surgery at a more advanced clinical state than men were; also, MV repair was performed less often in women and conferred a higher mortality rate than it did in men (Carabello & Crawford, 1997). Mitral Stenosis Etiology

Mitral stenosis (MS) generally traces back to a case of rheumatic fever, although this presentation is becoming rarer as developing countries achieve access to healthcare. It is typically latent for an average of 20 years before symptoms appear, and it is the most common valvular disease discovered during pregnancy (Elkayam & Bitar, 2005). A funnel-shaped structure develops from both chordae and commissural fusions, and in conjunction with a thickening and calcification of the leaflets, it produces a narrowed orifice between the left atrium and the left ventricle. Other potential complications associated with MS are AF and embolization as a result of an increase in left atrial pressure and enlargement. MS affects women four times as often as men in developing countries. However, with the decline in the incidence of rheumatic fever in the United States and Europe, the ratio of women to men who present with MS is 2:1 (Bonow et al., 2006). Patients are generally 60 years old or older when they present with symptoms, and more than one third of patients who require surgical repair are more than 65 years old (Shoob et al., 2006). Symptoms, Evaluation/Assessment, and Diagnostic Studies

Women may present early during the course of MS with fatigue, dyspnea, orthopnea, new-onset AF, pulmonary edema, or an embolic event (e.g., stroke). Symptomatic women with MS require evaluation of the extent of their valve disease, as well as an assessment of their NYHA functional class status. The ACC/AHA guidelines categorize MS severity as mild, moderate, or severe on the basis of hemodynamic data and symptom history (Nishimura et al., 2014). Patient history, physical examination, and noninvasive studies, including chest radiography, EKG, and echocardiography, facilitate the diagnosis. During the cardiac examination, the characteristic “opening snap” during early diastole, a lowpitched rumbling diastolic murmur, and an accentuated S1 are indicative of MS. Findings with worsening valve disease include signs of right ventricular overload, such as distended neck veins, a right ventricular heave, ascites, and peripheral edema. On chest radiography, left atrial enlargement may be noted. Both the pulmonary arterial and venous circulations may be distorted, and there may be evidence of interstitial edema that is consistent with congestion. Echocardiography is the most sensitive and specific noninvasive test used to assess the degree of restricted opening of the mitral valve leaflets; leaflet mobility, flexibility, thickness, and calcification; and suitability of valvotomy (Bonow et al., 2006; Nishimura

Chapter 43  Cardiovascular Disease in Women 835

et al., 2014). Because women with MS can remain clinically stable for years, there is generally no need for further immediate testing if the documented valve area is greater than 1.5 cm2 and the mean gradient is less than 5 mmHg.

3 years. Two-dimensional Doppler echocardiography is used to confirm the diagnosis.

Treatment/Management

Although the progression rate of AS is slow, the individual rate of progression to hemodynamic consequences varies, thus necessitating the close monitoring of both symptomatic and asymptomatic women by a specialist. No medical therapy has been shown to effectively treat AS. Lipid-lowering therapy may slow the progression of the mechanisms associated with atherosclerosis; however, because symptoms can quickly progress, surgical intervention is considered if diagnostic testing reveals moderate to severe AS (Bonow et  al., 2006; Nishimura et al., 2014).

Medical therapy cannot correct mechanical obstruction of the mitral valve. Women who develop more severe MS can remain free of symptoms if they are educated to limit strenuous physical activity. Women are counseled to seek immediate evaluation if a sudden increase in shortness of breath occurs. Disease progression is monitored with an annual history and physical examination, EKG, and chest radiography. Surgical intervention generally correlates with clinical symptoms or with evidence of pulmonary HTN or ventricular dysfunction (Bonow et al., 2006; Nishimura et al., 2014). Recommendations for the treatment of conditions associated with MS (e.g., AF) include anticoagulation, heart rate control, and chemical or electrical cardioversion. Long-term anticoagulation is warranted to prevent systemic embolic events. Without surgical intervention, mitral valve disease results in an 85% mortality rate at 20 years after symptom onset (Bonow et al., 2006). Aortic Stenosis Definition, Scope, and Etiology

Nonrheumatic AS has been described as a calcific disease in which there is an accumulation of lipids, smooth muscle cells, collagen inflammatory cells, and platelet adherence that produces plaque-laden areas along the leaflets and valve cusps; this imitates the atherosclerotic process that accompanies CAD (Carabello & Crawford, 1997). This generally idiopathic process results in the obstruction of blood flow through a narrowed orifice. Fewer women present with AS as a result of exposure to rheumatic fever. AS is the most common valvular lesion in the United States, affecting approximately 25% of individuals who are more than 65 years old, and it is associated with cardiovascular risk factors such as HTN, DM, gender, smoking, and dyslipidemia (Bonow et al., 2006). Furthermore, investigators pooled together databases and calculated an estimated prevalence of 12.4% for AS and 3.4% for severe AS as the burden of disease among older adults. Using these calculations, approximately 290,000 older patients with severe AS are potential candidates for transcatheter aortic valve replacement (TAVR; Osnabrugge et al., 2013). Evaluation/Assessment and Diagnostic Studies

During the cardiac examination, the most common sign of AS is a late-systolic ejection murmur heard in the aortic area. The murmur can frequently be heard radiating to the neck. The murmur can mimic MR in that it may also be auscultated over the apex; it may also be associated with a thrill. As the AS worsens, pulsus parvus et tardus may be elicited; when this occurs, the carotid upstrokes diminish in amplitude and are delayed during the cardiac cycle, and the clinician may also detect a paradoxically split S2 as a result of delayed ventricular emptying. The development of symptoms such as angina, HF, or syncope indicates a poor shortterm prognosis with a high risk for sudden death within 2 to

Treatment/Management

Aortic Regurgitation Etiology

Aortic regurgitation (AR) is caused by disease that involves at least one of the aortic leaflets (e.g., infective endocarditis, rheumatic fever) or the aortic root (e.g., collagen vascular disease, annuloaortic ectasia). Acute AR, which is usually a complication of an invasive procedure, aortic dissection, or chest trauma, is a rare and life-threatening event. Chronic AR is more prevalent and imposes a cardiac trajectory with an initial compensatory increase in left ventricular mass, a low EF, and subsequent HF symptoms. The prevalence of AR increases with age and is detected more often in men than in women (Carabello & Crawford, 1997; DesJardin et al., 2022). Evaluation/Assessment

Multiple examination findings suggest regurgitant flow and increased systolic stroke volume. The classic murmur is a high-frequency decrescendo diastolic murmur heard at the left sternal border. An S3 is sometimes noted, and S2 may be absent altogether. With severe AR, women may present with bounding carotid pulses, head bobbing (de Musset sign), a pulsating uvula (Miller sign), and pistol-shot sounds heard over a compressed femoral artery (Traube sign). Treatment/Management

Referral to a specialist is appropriate for women with AR to manage resultant HF or to provide surgical intervention. The guidelines recommend (class I) that the management of patients with severe heart valve disease is best achieved by a heart valve team composed minimally of a cardiologist and a cardiac surgeon but potentially including cardiologists, structural valve interventionalists, cardiovascular imaging specialists, cardiovascular surgeons, anesthesiologists, and nurses, all of whom have expertise in the management and outcome of patients with severe heart valve disease. Often, heart valve centers of excellence have a valve clinic with a valve team. The guidelines recommend (class IIa) that consultation with or referral to a heart valve center of excellence is reasonable for asymptomatic patients with severe valve disease. Surgical risk is evaluated through the Society of Thoracic Surgeons (STS), where surgeons predict the risk of death by assessing the patient's fragility (e.g., Katz Index of Independence in Activities of Daily Living; Bach, 2014).

836  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS Infective Endocarditis Prevention

The ACC/AHA 2008 guideline update regarding valvular heart disease revised the recommendations for infective endocarditis prophylaxis (Wilson et al., 2007). Infective endocarditis is less likely to be caused by a procedure than by random exposure to bacteria, such as when brushing teeth, chewing gum, or other oral hygiene procedures, and it was also found that prophylactic antibiotic treatment prevents only a very small number of cases of infective endocarditis. Thus, prophylactic antibiotics are reserved for women who are at the highest risk of an adverse outcome from acquiring infective endocarditis (Wilson et al., 2007). The 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease by Nishimura et al. (2014) recommends the same approach to care. Considerations for Special Populations

The normal physiologic changes related to a woman’s cardiovascular system during pregnancy become more critical in the setting of valvular disease. There is a 50% increase in blood volume and a consequent 25% increase in cardiac output that influences valvular function such that stenotic valve murmurs are accentuated and regurgitant murmurs may become nearly inaudible. Ideally, the management of women with known valvular lesions begins before conception. The 2006 ACC/AHA Guidelines for the Management of Patients with Valvular Heart Disease provide recommendations such as anticoagulation therapies, exercise restrictions, and prophylaxis endocarditis treatment for each specific valve condition (Bonow et al., 2006).

Cardiomyopathy

associated with a risk of recurrent HF (Givertz, 2013). Additionally, women with significant left ventricular dysfunction are at increased risk for future cardiovascular events (McNamara et al., 2015). Cardiomyopathies have a genetic component, and this is relevant to practice. Current practice guidelines include the use of genetic testing in patients with cardiomyopathies as part of our management strategy. Our evolving knowledge of cardiomyopathies provides evidence that understanding genetic testing will help to personalize care and risk stratify not only the patient but the patient's family members (Pelliccia et al., 2019). DIFFERENTIAL DIAGNOSIS Stroke Definition, Scope, and Etiology

According to the 2015 AHA statistics, cardiovascular health encompasses several clinical conditions, including cerebrovascular disease and stroke. Stroke is currently the fifth leading cause of death and the leading cause of disability in adults in the United States; it is the third leading cause of death among women. Because of several important treatment modalities for acute stroke and because there has been a nationwide surge in establishing certified stroke centers, more patients are surviving their first stroke; there are currently 7 million stroke survivors, a majority of which are women. An additional 3.6 million people are projected to survive a stroke within the next two decades, and more than half of those individuals will be women. With a projected larger aging population, older women are expected to make up a majority of the stroke survivor population (Mozaffarian et al., 2015). The reasons for these statistics are multifold and include some of the following stark facts: ●

DEFINITION, SCOPE, AND ETIOLOGY

The AHA classified cardiomyopathies as primary (genetic, mixed, or acquired) or secondary (e.g., infiltrative, toxic, or inflammatory). The four major types are dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy (Pelliccia et al., 2019). Dilated cardiomyopathy, the most common form and affects 5 in 100,000 adults and 0.57 in 100,000 children. It is the third leading cause of HF in the United States after CAD and HTN (Wexler et al., 2009). The causes of cardiomyopathies are varied. Dilated cardiomyopathy in adults is most commonly caused by CAD (ischemic cardiomyopathy) and HTN, although viral myocarditis, valvular disease, and genetic predisposition may also play a role (Wexler et al., 2009). Peripartum cardiomyopathy (PPCM) is associated with pregnancy; the heart dilates and weakens, leading to symptoms of HF. PPCM can be difficult to diagnose because symptoms of HF can mimic those of pregnancy. PPCM can be a major cause of maternal morbidity and mortality, especially in some minority groups such as Africans and African Americans (Givertz, 2013). Most affected women recover normal heart function; however, some will progress to severe HF requiring mechanical support or heart transplantation. Even when the heart recovers, another pregnancy may be

●

●

●

●

●

●

Women live longer than men and therefore have a higher lifetime stroke risk than men. Women tend to have gaps in knowledge about stroke symptoms and stroke treatment options and therefore do not seek acute stroke care. Older women have a poorer functional recovery from stroke than men, as they frequently lack a support system to assist with rehabilitation and lifestyle and stroke-prevention strategies. Women have a higher rate of recurrent stroke compared with men. Stroke mortality rate is higher among women and is likely related to longer life expectancy. Women have been underrepresented in clinical trials related to stroke treatment and prevention and, as a result, may not be afforded gender-specific, evidence-based treatment. Women have sex-specific stroke risk factors, including pregnancy, gestational HTN, oral contraceptive pill use, menopause, and higher rates of other cardiovascular conditions.

In 2014, the AHA Stroke Association in collaboration with the Council on Cardiovascular and Stroke Nursing, the Council on Clinical Cardiology, the Council on Epidemiology and Prevention, and the Council for High Blood Pressure Research endorsed the first guideline dedicated to stroke risk

Chapter 43  Cardiovascular Disease in Women 837

and prevention in women. The AHA Science Advisory and Coordinating Committee approved a Healthcare Statement that summarized data on stroke risk factors unique to women and proposed a female-specific risk score to better capture adult women’s stroke risk (Bushnell et al., 2014). Given that the majority of the population will be older women with multiple cardiovascular and cerebrovascular risk factors, this guideline provides an excellent reference for clinicians who prescribe both primary and secondary stroke-prevention strategies. Stroke has been defined as a sudden death of brain cells due to the lack of oxygen caused by a blockage of blood flow (resulting in an ischemic stroke) or rupture of an artery in the brain (resulting in a hemorrhagic stroke). Approximately 87% of strokes are ischemic in nature, and 13% are hemorrhagic. Hemorrhagic stroke is further divided into intracerebral hemorrhage (ICH; 10%) and subarachnoid hemorrhage (SAH; 3%; Sacco et al., 2013). Although women have an overall lower incidence of ischemic stroke than men, older women (older than 85 years) have a similar or higher incidence of ischemic stroke. Longevity and survival after their index stroke give women

both a higher lifetime stroke risk and a higher stroke mortality rate. Risk Factors

Table 43.6, taken from the 2014 AHA Guidelines, ‌‌‌‌‌‌‌highlights stroke risk factors and the unique sex-specific factors, including those that are more prevalent in women than in men. Symptoms

Strokes usually present as a syndrome in which patients experience the sudden onset of neurologic deficits; the constellation of symptoms helps to localize the region in the central nervous system that has been injured. Public awareness campaigns have highlighted the most common symptoms by using the acronym F.A.S.T., which stands for Facial weakness or drooping, weakness in the Arm, Speech problems, and Time, emphasizing the importance of calling 911 and seeking medical help immediately. Clinicians are familiar with the five‌‌‌‌‌‌‌‌‌ “suddens”: unilateral numbness/weakness in face/arm/leg, confusion, trouble speaking, severe headache, trouble seeing

TABLE 43.6  Stroke Risk Factors, Categorized by Sex-Specific Features RISK FACTOR

SEX-SPECIFIC RISK FACTORS

Pregnancy

X

Preeclampsia

X

Gestational diabetes

X

Oral contraceptive use

X

Postmenopausal hormone use

X

Changes in hormonal status

X

RISK FACTORS THAT ARE STRONGER OR MORE PREVALENT IN WOMEN

Migraine with aura

X

Atrial fibrillation

X

Diabetes mellitus

X

Hypertension

X

RISK FACTORS WITH SIMILAR PREVALENCE IN MEN AND WOMEN BUT UNKNOWN DIFFERENCE IN IMPACT

Physical inactivity

X

Age

X

Prior cardiovascular disease

X

Obesity

X

Diet

X

Smoking

X

Metabolic syndrome

X

Depression

X

Psychosocial stress

X

838  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

in one or both eyes, and trouble walking/lack of coordination. These “suddens” highlight symptoms that indicate further evaluation is needed. Patients may also present with symptoms of sudden onset of vertigo with vomiting, unexplained syncope, or altered mental status that precedes the symptoms already discussed and heightens suspicion for a cerebrovascular event. Evaluation/Assessment

Although there are some common features to symptom presentation that may be indicative of stroke type, the diagnosis requires a detailed history, rapid imaging, and comprehensive neurologic exam. Differential Diagnosis ISCHEMIC STROKE

Definition, Scope, and Etiology

The classifications of ischemic stroke are generally divided into five subtypes. These classifications reflect a proposed etiology of ischemic stroke and serve as a guide for the appropriate treatments for secondary stroke prevention. Approximately 30% of patients who present with an ischemic stroke are diagnosed with large vessel disease, referring to atherosclerosis leading to stenosis or occlusion of a major artery in the brain or artery leading to the brain (including the carotid or vertebral arteries). An additional 20% of ischemic strokes are thought to be cardioembolic in nature, in which patients with vessel occlusions may have had an embolus travel from the heart (such as in AF). Approximately 15% of patients are diagnosed with small vessel disease, which refers to stenoses of the smaller vessels (deeper in the brain) typically related to long-standing DM or HLD. Stroke patients who fall into the category of “other” are patients for whom their stroke may result from vasculopathies or hypercoagulable states. Nearly 30% of patients have a final diagnosis of cryptogenic stroke such that despite a comprehensive diagnostic workup, there is no identified cause for their stroke. Evaluation/Assessment and Diagnostic Studies

In addition to a careful medical history, diagnostic imaging (such as an MRI) and other studies (such as an echocardiogram) help to identify a suspected stroke etiology and guide secondary stroke prevention therapies. TRANSIENT ISCHEMIC ATTACK

Definition

The term transient ischemic attack (TIA) is frequently used to describe stroke symptoms that are transient in nature and thus are too often mistakenly considered a less urgent medical issue. Traditionally, TIAs have been defined as events in which focal neurologic symptoms last less than 24 hours; however, the more routine use of neuroimaging studies such as a head CT scan or MRI have demonstrated that even patients with stroke symptoms lasting just several hours have evidence of infarction on CT or MRI. This has led to a more current definition of TIA, which is “a brief episode of neurological dysfunction caused by focal brain or retinal ischemia, with clinical symptoms typically lasting less than one hour, and without evidence of acute infarction” (Easton et al., 2009, p. 2277).

Evaluation/Assessment

A valuable risk assessment tool called the ABCD2 score used to predict short-term stroke risk after a TIA was developed by Johnston et al. (2007) and considered five items that were assigned points to determine the 2-, 7-, 30-, and 90-day stroke risk. The seven-point scoring scale is based on age, blood pressure, clinical features, duration of symptoms, and history of DM. Based on the patient’s score, practitioners can make clinical decisions regarding the benefit of recommending hospital admission for urgent workup and treatment (see Figure 43.5). Intracerebral Hemorrhage.  Spontaneous, nontraumatic ICH

is the most common of the hemorrhages in which blood vessel rupture causes bleeding into the brain parenchyma. Uncontrolled HTN is the principal cause; other secondary causes include cerebral amyloid angiopathy (CAA), intracranial aneurysm rupture, vasculitis, and hemorrhagic transformation after an ischemic stroke. The incidence of ICH and mortality resulting from ICH in women is reportedly lower than in men, but after the age of 65 years, there were similar mortality risks. Subarachnoid Hemorrhage.  SAH occurs when an intracranial

aneurysm ruptures and blood enters the spaces around the brain tissue. The incidence of SAH is higher in women and is noted after the age of 55 years. Women have a higher risk of SAH resulting primarily from the prevalence and location of cerebral aneurysms (Algra et  al., 2012). These statistics underscore the fact that women in all age groups can be at risk for any one or more of these ischemic stroke subtypes, so a thorough health history and gender-specific risk factor profile help direct therapies for both primary and secondary ischemic stroke prevention. Treatment/Management

In the primary care setting, it is critical to recognize the symptoms of stroke and quickly have the patient transported to an emergency care facility. In the emergency facility, the goal is to stabilize, assess, and image the patient within 60 minutes of presentation (Adams et al., 2007). Rapid identification, diagnosis, and initiation of treatment are the key to minimizing the residual effects of stroke. After patient discharge from the acute care setting, management focuses on rehabilitation. Rehabilitation programs are interdisciplinary with physical therapy, speech therapy, and a number of others as needed to minimize an individual’s residual effects. Secondary Prevention

After a stroke that is not cardioembolic, the AHA and American Stroke Association recommend antiplatelet agents to decrease the risk for a second stroke or other cardiac events. Specifically, aspirin (50–325 mg/day) alone or in combination with dipyridamole extended release or clopidogrel alone (Adams et al., 2008) are prescribed. Consistent evaluation for adherence and encouragement to continue with therapy are important, as approximately 25% of patients stop taking their medications within 3 months after their stroke (Bushnell et al., 2010).

Chapter 43  Cardiovascular Disease in Women 839

ABCD2 Score The ABCD2 score is a risk-assessment tool designed to improve the prediction of short-term stroke risk after a TIA. The score is optimized to predict the risk of stroke within 2 days after a TIA but also predicts stroke risk within 90 days. The ABCD2 score is calculated by summing up points for five independent factors. RISK FACTOR Age $60 years

POINTS

SCORE

1

Blood pressure Systolic BP $ 140 mmHg OR Diastolic BP $ 90 mmHg

1

Clinical features of TIA (choose one) Unilateral weakness with or without speech impairment OR Speech impairment without unilateral weakness

2 1

Duration TIA duration $ 60 minutos TIA duration 10–59 minutes

2 1

Diabetes

1

Total ABCD2 score

0–7

Using the ABCD2 Score Higher ABCD2 scores are associated with a greater risk of stroke during the 2, 7, 30, and 90 days after a TIA (figure). The authors of the ABCD2 score made the following recommendations for hospital observation

Hospital observation justified in most situations

4–5

4.1%

6–7

8.1% Hospital observation worthwhile

2-day risk 7-day risk 30-day risk 90-day risk

20% Stroke Risk

2-Day ABCD2 Stroke Comment Score Risk Hospital observation may be 0–3 1.0% unnecessary without another indication (e.g., now atrial fibrillation)

25%

15% 10% 5% 0%

0

1

2

3 4 5 ABCD2 Score

6

7

FIGURE 43.5 ABCD2 risk assessment tool used to predict stroke risk after a transient ischemic attack (TIA): prognosis and key management considerations. Source: Johnston, S. C., Rothwell, P. M., Nguyen-Huynh, M. N., Giles, M. F., Elkins, J. S., Bernstein, A. L., & Sidney, S. (2007). Validation and refinement of scores to predict very early stroke risk after transient ischemic attack. Lancet, 369, 283–292. https://doi.org/10.1016/S0140-6736(07)60150-0. Copyright © 2007, used with permission from Elsevier.

FUTURE DIRECTIONS Much has been learned about women and heart disease during the past several years, and there is now clear evidence that CVD in women is indeed different from CVD in men. Clinicians need to continue to advocate for women who are at risk for heart disease and strive to provide best practices for preventing, identifying, and treating heart disease in women. Future research will provide more data regarding unique symptoms and presentations among women, as well as

treatment modalities that have superior outcomes for women. In the interim, aggressive preventive measures, early recognition, and aggressive management are critical.

REFERENCES Adams, H. P., Jr., del Zoppo, G., Alberts, M. J., Bhatt, D. L., Brass, L., Furlan, A., Grubb, R. L., Higashida, R. T., Jauch, E. C., Kidwell, C., Lyden, P. D., Morgenstern, L. B., Qureshi, A. I., Rosenwasser, R. H., Scott, P. A., & Wijdicks, E. F.

(2007). Guidelines for the early management of adults with ischemic stroke: A guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke, 38(5), 1655–1711. https://doi .org/10.1161/STROKEAHA.107.181486 Adams, R. J., Albers, G., Alberts, M. J., Benavente, O., Furie, K., Goldstein, L. B., Gorelick, P. B., Halperin, J., Harbaugh, R. E., Johnston, C., Katzan, I., Kelly-Hayes, M., Kenton, E. J., Marks, M., Sacco, R. L., & Schwamm, L. H. (2008). Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke, 39(5), 1647–1652. https://doi.org/10.1161/STROKEAHA.107.189063 Agabiti-Rosei, E., & Muiesan, M. L. (2002). Left ventricular hypertrophy and heart failure in women. Journal of Hypertension Supplement, 20(2), S34–S38. Ahmad, F., Abu Sneineh, M., Patel, R. S., Rohit Reddy, S., Llukmani, A., Hashim, A., Haddad, D. R., & Gordon, D. K. (2021). In the line of treatment: A systematic review of paroxysmal supraventricular tachycardia. Cureus, 13(6), e15502. https://doi.org/10.7759/cureus.15502 Alam, M., Bandeali, S. J., Kayani, W. T., Ahmad, W., Shahzad, S. A., Jneid, H., Birnbaum, Y., Kleiman, N. S., Coselli, J. S., Ballantyne, C. M., Lakkis, N., & Virani, S. S. (2013). Comparison by meta-analysis of mortality after isolated coronary artery bypass grafting in women versus men. American Journal of Cardiology, 112(3), 309–317. https://doi.org/10.1016/j.amjcard.2013.03.034 Alberti, K. G., Eckel, R. H., Grundy, S. M., Zimmet, P. Z., Cleeman, J. I., Donato,  K.  A., Fruchart, J. C., James, W. P., Loria, C. M., & Smith, S. C. Jr. (2009). Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation, 120(16), 1640–1645. https://doi.org/10.1161/CIRCULATIONAHA.109.192644 AlGhurair, S. A., Hughes, C. A., Simpson, S. H., & Guirguis, L. M. (2012). A systematic review of patient self-reported barriers of adherence to antihypertensive medications using the world health organization multidimensional adherence model. Journal of Clinical Hypertension, 14(12), 877–886. https:// doi.org/10.1111/j.1751-7176.2012.00699.x Algra, A. M., Klijn, C. J., Helmerhorst, F. M., Algra, A., & Rinkel, G. J. (2012). Female risk factors for subarachnoid hemorrhage: A systematic review. Neurology, 79(12), 1230–1236. https://doi.org/10.1212/WNL .0b013e31826aace6 Alpert, M. A., Lavie, C. J., Agrawal, H., Aggarwal, K. B., & Kumar, S. A. (2014). Obesity and heart failure: Epidemiology, pathophysiology, clinical manifestations, and management. Translational Research, 164(4), 345–356. https:// doi.org/10.1016/j.trsl.2014.04.010 Alzahrani, T., Nguyen, T., Ryan, A., Dwairy, A., McCaffrey, J., Yunus, R., Forgione, J., Krepp, J., Nagy, C., Mazhari, R., & Reiner, J. (2019). Cardiovascular disease risk factors and myocardial infarction in the transgender population. Circulation: Cardiovascular Quality and Outcomes, 12(4), e005597. https://doi.org/10.1161 /CIRCOUTCOMES.119.005597 American College of Sports Medicine. (1991). Guidelines for exercise testing and prescription (4th ed.). Lea & Febiger. American Diabetes Association. (2016). Cardiovascular disease and risk  management. Diabetes Care, 39(Suppl. 1), S60–S71. https://doi.org/10.2337/ dc16-S011 American Diabetes Association. (2020). Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes—2020. Diabetes Care, 43(Suppl. 1), S14–S31. https://doi.org/10.2337/dc20-S002 American Heart Association. (n.d.). Medication adherence: Importance, issues and policy: A policy statement from the American Heart Association. https:// www.heart.org/-/media/Files/About-Us/Policy-Research/Policy-Positions /Clinical-Care/Med-Adherence-Exec-Summary.pdf Ammirati, E., Frigerio, M., Adler, E. D., Basso, C., Birnie, D. H., Brambatti, M., Friedrich, M. G., Klingel, K., Lehtonen, J., Moslehi, J. J., Pedrotti, P., Rimoldi, O. E., Schultheiss, H. P., Tschöpe, C., Cooper, L. T., & Camici, P. G. (2020). Management of acute myocarditis and chronic inflammatory cardiomyopathy. Circulation: Heart Failure, 13(11), e007405. https://doi.org/10.1161 /circheartfailure.120.007405 Anderson, M., Peterson, E. D., Brennan, J. M., Raol, S. V., Dail, D., Anstrom, K. J., Piana, R., Popescu, A., Sedrakyan, A., Messenger, J. C., & Douglas, P. S. (2012). Short- and long-term outcomes of coronary stenting in women versus men: Results from the National Cardiovascular Data Registry Centers for Medicare & Medicaid Services cohort. Circulation, 126(18), 2190–2199. https://doi.org/10.1161/CIRCULATIONAHA.112.111369

Andersson, C., Nayor, M., Tsao, C. W., Levy, D., & Vasan, R. S. (2021). Framingham heart study: JACC focus seminar, 1/8. Journal of the American College of Cardiology, 77(21), 2680–2692. https://doi.org/10.1016/j.jacc.2021.01.059 Antithrombotic Trialists Collaboration. (2002). Collaborative meta-analysis of randomized trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. British Medical Journal, 324, 71–86. https://doi.org/10.1136/bmj.324.7329.71 Ashley, E. A., Raxwal, V., & Froelicher, V. (2001). An evidence-based review of the resting electrocardiogram as a screening technique for heart disease. Progress in Cardiovascular Diseases, 44(1), 55–67. https://doi.org/10.1053 /pcad.2001.24683 Bach, D. (2014). 2014 AHA/ACC guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Summary. http:// www.acc.org/latest-in-cardiology/journal-scans/2014/03/17/13/59/2014-aha -acc-guideline-for-the-management-of-patients-with-vhd Bairey Merz, C. N., Shaw, L. J., Reis, S. E., Bittner, V., Kelsey, S. F., Olson, M., Johnson, B. D., Pepine, C. J., Mankad, S., Sharaf, B. L., Rogers, W. J., Pohost, G. M., Lerman, A., Quyyumi, A. A., Sopko, G., & WISE Investigators. (2006). Insights from the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE) Study. Part II: Gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular coronary disease. Journal of the American College of Cardiology, 47(Suppl. 3), S21–S29. https://doi .org/10.1016/j.jacc.2004.12.084 Ballantyne, C. M., O’Keefe, J. H., & Gotto, A.M. (2005). Dyslipidemia essentials. Physicians Press. Barnard, D. D. (2005). Heart failure in women. Current Cardiology Reports, 7(3), 159–165. https://doi.org/10.1007/s11886-005-0071-x Baroletti, S., & Dell’Orfano, H. (2010). Medication adherence in cardiovascular disease. Circulation, 121(12), 1455–1458. https://doi.org/10.1161 /CIRCULATIONAHA.109.904003 Basile, J., & Bloch, M. J. (2023). Overview of hypertension in adults. UpToDate. https://www.uptodate.com/contents/overview-of-hypertension-in-adults Bazett, H.C. (1997). An analysis of the time-relations of electrocardiograms. Annals of Noninvasive Electrocardiology, 2, 177–194. https://doi.org/10.1111 /j.1542-474X.1997.tb00325.x Bell, D. S. (1995). Diabetic cardiomyopathy: A unique entity or a complication of coronary artery disease? Diabetes Care, 18(5), 708–714. https://doi.org/10.2337 /diacare.18.5.708 Bentley-Lewis, R., Koruda, K., & Seely, E. W. (2007). The metabolic syndrome in women. Nature Clinical Practice Endocrinology & Metabolism, 3(10), 696–704. https://doi.org/10.1038/ncpendmet0616 Bhardwaj, S., Selvarajah, S., & Schneider, E. B. (2013). Muscular effects of statins in the elderly female: A review. Clinical Interventions in Aging, 8, 47–59. https://doi.org/10.2147/CIA.S29686 Bidoggia, H., Maciel, J. P., Capalozza, N., Mosca, S., Blaksley, E. J., Valverde, E., Bertran, G., Arini, P., Biagetti, M. O., & Quinteiro, R. A. (2000). Sex-dependent electrocardiographic pattern of cardiac repolarization. American Heart Journal, 140(3), 430–436. https://doi.org/10.1067/mhj.2000.108510 Blanc, J. J., Etienne, Y., Gilard, M., Mansourati, J., Munier, S., Boschat, J., Benditt,  D. G., & Lurie, K. G. (1997). Evaluation of different ventricular pacing sites in patients with severe heart failure: Results of an acute hemodynamic study. Circulation, 96(10), 3273–3277. https://doi.org/10.1161/01 .cir.96.10.3273 Blomström-Lundqvist, C., Scheinman, M. M., Aliot, E. M., Alpert, J. S., Calkins, H., Camm, A. J., Campbell, W. B., Haines, D. E., Kuck, K.-H., Lerman, B., Miller, D. D., Shaeffer, C. W., Stevenson, W. G., Tomaselli, G. F., Antman, E. M., Smith, S., Faxon, D. P., Fuster, V., Gibbons, R. J., . . . NASPE-Heart Rhythm Society. (2003). ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias—Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients with Supraventricular Arrhythmias) developed in collaboration with NASPE-Heart Rhythm Society. Journal of the American College of Cardiology, 42(8), 1493–1531. https://doi.org/10.1016/j.jacc.2003.08.013 Bonow, R. O., Carabello, B. A., Chatterjee, K., de Leon, A. C., Faxon, D. P., Freed, M. D., Gaasch, W. H., Lytle, B. W., Nishimura, R. A., O’Gara, P. T., O’Rourke, R. A., Otto, C. M., Shah, P. M., Shanewise, J. S., Smith, S. C., Jacobs, A. K., Adams,  C. D., Anderson,  J. L., Antman, E. M., . . . Riegel, B. (2006). ACC/AHA 2006 guidelines for the management of patients with valvular disease: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 Guidelines for the Management of Patients with Valvular Heart Disease). Journal of the American College of Cardiology, 48(3), e1– e148. https://doi.org/10.1016/j.jacc.2006.05.021

Bozkurt, B., & Khalaf, S. (2017). Heart failure in women. Methodist DeBakey Cardiovascular Journal, 13(4), 216–223. https://doi.org/10.14797/mdcj-13-4-216 Brar, T. K., Singh, K. D., & Kumar, A. (2015). Effect of different phases of menstrual cycle on heart rate variability (HRV). Journal of Clinical and Diagnostic Research, 9(10), CC01–CC04. https://doi.org/10.7860/JCDR/2015/13 795.6592 Bristow, M. R., & Lowes, B. D. (2005). Management of heart failure. In D. P. Zipes, P. Libby, R. O. Bonow, & E. Braunwald (Eds.), Braunwald’s heart disease (7th ed.). Elsevier Saunders. Bugiardini, R., & Bairey Merz, C. N. (2005). Angina with “normal” coronary arteries: A changing philosophy. Journal of the American Medical Association, 293(4), 477–484. https://doi.org/10.1001/jama.293.4.477 Bugiardini, R., Ricci, B., Cenko, E., Vasiljevic, Z., Kedev, S., Davidovic, G., Zdravkovic, M., Miličić, D., Dilic, M., Manfrini, O., Koller, A., & Badimon, L. (2017). Delayed care and mortality among women and men with myocardial infarction. Journal of the American Heart Association, 6(8), e005968. https:// doi.org/10.1161/JAHA.117.005968 Burke, A. P., Kolodge, F., Farb, A., & Virmani, R. (2003). Gender differences in coronary plaque morphology in sudden coronary death. Circulation, 108, IV165. Bushnell, C., McCullough, L. D., Awad, I. A., Chireau, M. V., Fedder, W.  N., Furie,  K. L., Howard, V. J., Lichtman, J. H., Lisabeth, L. D., Piña, I. L., Reeves, M. J., Rexrode, K. M., Saposnik, G., Singh, V., Towfighi, A., Vaccarino, V., & Walters, M. R. (2014). Guidelines for the prevention of stroke in women: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke, 45(5), 1545–1588. https:// doi.org/10.1161/01.str.0000442009.06663.48 Bushnell, C. D., Zimmer, L. O., Pan, W., Olson, D. M., Zhao, X., Meteleva, T., Schwamm, L., Ovbiagele, B., Williams, L., Labresh, K. A., Peterson, E. D., & Adherence Evaluation After Ischemic Stroke–Longitudinal Investigators. (2010). Persistence with stroke prevention medications 3 months after hospitalization. Archives of Neurology, 67(12), 1456–1463. https://doi.org/10.1001 /archneurol.2010.190 Cabin, H. S., Clubb, K. S., Hall, C., Perlmutter, R. A., & Feinstein, A. R. (1990). Risk for systemic embolization of atrial fibrillation without mitral stenosis. American Journal of Cardiology, 65(16), 1112–1116. https://doi .org/10.1016/0002-9149(90)90323-s Cannon, R. O., Quyyumi, A. A., Mincemoyer, R., Stine, A. M., Gracely, R. H., Smith, W. B., Geraci, M. F., Black, B. C., Uhde, T. W., & Waclawiw, M. A. (1994). Imipramine in patients with chest pain despite normal coronary angiograms. New England Journal of Medicine, 330(20), 1411–1417. https://doi .org/10.1056/NEJM199405193302003 Carabello, B. A., & Crawford, F. A. (1997). Valvular heart disease. New England Journal of Medicine, 337(1), 32–41. https://doi.org/10.1056 /NEJM199707033370107 Centers for Disease Control and Prevention. (2021). Atrial fibrillation. https:// www.cdc.gov/heartdisease/atrial_fibrillation.htm Cesaro, A., Schiavo, A., Moscarella, E., Coletta, S., Conte, M., Gragnano, F., Fimiani, F., Monda, E., Caiazza, M., Limongelli, G., D’Erasmo, L., Riccio, C., Arca, M., & Calabrò, P. (2021). Lipoprotein(a): A genetic marker for cardiovascular disease and target for emerging therapies. Journal of Cardiovascular Medicine, 22(3), 151–161 https://doi.org/10.2459/JCM.0000000000001077 Chan, D. C., Heidenreich, P. A., Weinstein, M. C., & Fonarow, G. C. (2008). Heart failure disease management programs: A cost-effectiveness analysis. American Heart Journal, 155(2), 332–338. https://doi.org/10.1016/j.ahj.2007.10.001 Charlton, F., Tooher, J., Rye, K., & Hennessy, A. (2014). Cardiovascular risk, lipids and pregnancy: Preeclampsia and the risk of later life cardiovascular disease. Heart Lung and Circulation, 23(3), 203–212. https://doi.org/10.1016/j .hlc.2013.10.087 Chirillo, F., Salvador, L., & Cavallini, C. (2006). Medical and surgical treatment of chronic mitral regurgitation. Journal of Cardiovascular Medicine, 7(2), 96–107. https://doi.org/10.2459/01.JCM.0000199793.09608.14 Cho, G. J., Lee, J. H., Park, H. T., Shin, J. H., Hong, S. C., Kim, T. K., Hur, J. Y., Lee, K. W., Park, Y. K., & Kim, S. H. (2008). Postmenopausal status according to years since menopause as an independent risk factor for the metabolic syndrome. Menopause, 15(3), 524–529. https://doi.org/10.1097 /gme.0b013e3181559860 Cho, L., Davis, M., Elgendy, I., Epps, K., Lindley, K. J., Mehta, P. K., Michos, E. D., Minissian, M., Pepine, C., Vaccarino, V., Volgman, A. S., & ACC CVD Women’s Committee Members. (2020). Summary of updated recommendations for primary prevention of cardiovascular disease in women: JACC state-of-the-art review. Journal of the American College of Cardiology, 75(20), 2602–2618. https://doi.org/10.1016/j.jacc.2020.03.060 Chobanian, A. V., Bakris, G. L., Black, H. R., Cushman, W. C., Green, L. A., Izzo, J. L., Jones, D. W., Materson, B. J., Oparil, S., Wright, J. T., Jr., Roccella, E. J., & National High Blood Pressure Education Program Coordinating Committee. (2003). Seventh report of the Joint National Committee on prevention,

detection, evaluation, and treatment of high blood pressure. Hypertension, 42(6), 1206–1252. https://doi.org/10.1161/01.HYP.0000107251.49515.c2 Chow, G. V., Marine, J. E., & Fleg, J. L. (2012). Epidemiology of arrhythmias and conduction disorders in older adults. Clinics in Geriatric Medicine, 28(4), 539–553. https://doi.org/10.1016/j.cger.2012.07.003 CIBIS-II Investigators and Committees. (1999). The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II). Lancet, 353(9146), 9–13. https://doi.org/10.1016 /S0140-6736(98)11181-9 Cicero, A. F., Fogacci, F., Zambon, A., Toth, P. P., & Borghi, C. (2022). Efficacy and safety of inclisiran a newly approved FDA drug: A systematic review and pooled analysis of available clinical studies. American Heart Journal Plus: Cardiology Research and Practice, 13, 100127. https://doi.org/10.1016/j .ahjo.2022.100127 Colvin, M. M. (2022). AHA/ACC/HFSA heart failure guideline: Key perspectives (pp. 1–4). American College of Cardiology. https://www.acc.org/ Latest-in-Cardiology/ten-points-to-remember/2022/03/29/19/53/2022 -AHA-ACC-HFSA-Heart-Failure-Guideline-gl-hf Concannon, T. W., Griffith, J. L., Kent, D. M., Normand, S. L., Newhouse, J. P., Atkins, J., Beshansky, J. R., & Selker, H. P. (2009). Elapsed time in emergency medical services for patients with cardiac complaints: Are some patients at greater risk for delay? Circulation: Cardiovascular Quality and Outcomes, 2(1), 9–15. https://doi.org/10.1161/CIRCOUTCOMES.108.813741 Connolly, S. J., Ezekowitz, M. D., Yusuf, S., Eikelboom, J., Oldgren, J., Parekh, A., Pogue, J., Reilly, P. A., Themeles, E., Varrone, J., Wang, S., Alings,  M., Xavier, D., Zhu, J., Diaz, R., Lewis, B. S., Darius, H., Diener, H. C., Joyner, C. D., . . . RE-LY Steering Committee and Investigators. (2009). Dabigatran versus warfarin in patients with atrial fibrillation. New England Journal of Medicine, 361(12), 1139–1151. https://doi.org/10.1056/NEJMoa0905561 Cox, J. L., & Gardner, M. J. (1993). Treatment of cardiac arrhythmias during pregnancy. Progress in Cardiovascular Diseases, 36(2), 137–178. https://doi .org/10.1016/0033-0620(93)90005-x Curry, J. J., & Quintana, F. J. (1970). Myocardial infarction with ventricular fibrillation during pregnancy treated by direct current defibrillation with fetal survival. Chest, 58(1), 82–84. https://doi.org/10.1378/chest.58.1.82 DeFilippis, E. M., Henderson, J., Axsom, K. M., Costanzo, M. R., Adamson, P. B., Miller, A. B., Brett, M. E., & Givertz, M. M. (2021). Remote hemodynamic monitoring equally reduces heart failure hospitalizations in women and men in clinical practice: A sex-specific analysis of the CardioMEMS post-approval study. Circulation: Heart Failure, 14(6), e007892. https://doi.org/10.1161 /circheartfailure.120.007892 DeFilippis, E. M., Beale, A., Martyn, T., Agarwal, A., Elkayam, U., Lam, C. S. P., & Hsich, E. (2022). Heart failure subtypes and cardiomyopathies in women. Circulation Research, 130(4), 436–454. https://doi.org/10.1161 /CIRCRESAHA.121.319900 DeSimone, C. V., Naksuk, N., & Asirvatham, S. J. (2018). Supraventricular arrhythmias: Clinical framework and common scenarios for the internist. Mayo Clinic Proceedings, 93(12), 1825–1841. https://doi.org/10.1016/j.mayocp.2018.07.019 DesJardin, J. T., Chikwe, J., Hahn, R. T., Hung, J. W., & Delling, F. N. (2022). Sex differences and similarities in valvular heart disease. Circulation Research, 130(4), 455–473. https://doi.org/10.1161/CIRCRESAHA.121.319914 Devabhaktuni, S. R. (2020). Cardiac syndrome X: Background, pathophysiology, epidemiology. Medscape. https://emedicine.medscape.com/article /1967073-overview DiCarlo-Meacham, L. T., & Dahlke, L. J. (2011). Atrial fibrillation in pregnancy. Obstetrics & Gynecology, 117(2), 489–492. https://doi.org/10.1097 /AOG.0b013e31820561ef DiMatteo, M. R. (2004). Variations in patients’ adherence to medical recommendations: A quantitative review of 50 years of research. Medical Care, 42(3), 200–209. https://doi.org/10.1097/01.mlr.0000114908.90348.f9 Drazen, J. M., Jarcho, J. A., Morrissey, S., & Curfman, G. D. (2008). Cholesterol lowering and ezetimibe. New England Journal of Medicine, 358, 1507–1508. https://doi.org/10.1056/NEJMe0801842 Easton, J. D., Saver, J. L., Albers, G. W., Alberts, M. J., Chaturvedi, S., Feldmann, E., Hatsukami, T. S., Higashida, R. T., Johnston, S. C., Kidwell, C. S., Lutsep, H. L., Miller, E., & Sacco, R. L. (2009). Definition and evaluation of transient ischemic attack: A scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Stroke, 40(6), 2276−2293. https://doi.org/10.1161 /STROKEAHA.108.192218 Eckel, R. H., Jakicic, J. M., Ard, J. D., de Jesus, J. M., Houston Miller, N., Hubbard, V. S., Lee, I.-M., Lichtenstein, A. H., Loria, C. M., Millen, B. E., Nonas, C. A., Sacks, F. M., Smith, S. C., Jr., Svetkey, L. P., Wadden, T. A., & Yanovski, S. Z. (2014). 2013 AHA/ACC guideline on lifestyle management

to reduce cardiovascular risk. Circulation, 63(25 Pt. B), 2960–2984. https:// doi.org/10.1016/j.jacc.2013.11.003 Eisen, A., Kumbhani, D. J., & Bhatt, D. L. (2021). IMProved reduction of outcomes: Vytorin efficacy international trial—IMPROVE-IT. American College of Cardiology. Latest in Cardiology. https://www.acc.org/Latest-in -Cardiology/Clinical-Trials/2014/11/18/16/25/IMPROVE-IT Eisenberg, E., Di Palo, K. E., & Piña, I. L. (2018). Sex differences in heart failure. Clinical Cardiology, 41(2), 211–216. https://doi.org/10.1002/clc.22917 Elder, P., Sharma, G., Gulati, M., & Michos, E. D. (2020). Identification of female-specific risk enhancers throughout the lifespan of women to improve cardiovascular disease prevention. American Journal of Preventive Cardiology, 2, 100028. https://doi.org/10.1016/j.ajpc.2020.100028 Elkayam, U., & Bitar, F. (2005). Valvular heart disease and pregnancy. Journal of the American College of Cardiology, 46(2), 223–230. https://doi.org/10.1016/j .jacc.2005.02.085 Feinberg, W. M., Blackshear, J. L., Laupacis, A., Kronmal, R., & Hart, R. G. (1995). Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications. Archives of Internal Medicine, 155(5), 469– 473. https://doi.org/10.1001/archinte.1995.00430050045005 Finn, A. V., Nakano, M., Narula, J., Kolodge, F. D., & Virmani, R. (2010). Concept of vulnerable/unstable plaque. Arteriosclerosis, Thrombosis, and Vascular Biology, 30, 1282–1292. https://doi.org/10.1161/ATVBAHA.108.179739 Fraker, T. D., Jr., & Fihn, S. D. (2007). Chronic angina focused update of the ACC/AHA 2002 Guidelines for the Management of Patients with Chronic Stable Angina: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Group to develop the focused update of the 2002 Guidelines for the Management of Patients with Chronic Stable Angina). Journal of the American College of Cardiology, 50(23), 2264–2274. https://doi.org/10.1016/j.jacc.2007.08.002 Friberg, L., Benson, L., Rosenqvist, M., & Lip, G.Y. (2012). Assessment of female sex as a risk factor in atrial fibrillation in Sweden: Nationwide retrospective cohort study. British Medical Journal, 344, e3522. https://doi.org/10.1136 /bmj.e3522 Fuster, V., Ryden, L. E., Cannom, D. S., Crijns, H. J., Curtis, A. B., Ellenbogen, K. A., Halperin, J. L., Le Heuzey, J., Kay, G. N., Lowe, J. E., Olsson, S. B., Prystowsky, E. N., Tamargo, J. L., & Wann, S. (2006). ACC/AHA/ ESC 2006 guidelines for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation). Journal of the American College of Cardiology, 48, e149–e246. https://doi.org/10.1016/j .jacc.2006.07.018 Gandhi, P. U., & Pinney, S. (2014). Management of chronic heart failure: Biomarkers, monitors, and disease management programs. Annals of Global Health, 80, 46–54. https://doi.org/10.1016/j.aogh.2013.12.005 Gao, Z., Chen, Z., Sun, A., & Deng, X. (2019). Gender differences in cardiovascular disease. Medicine in Novel Technology and Devices, 4, 100025. https://doi .org/10.1016/j.medntd.2019.100025 Garcia, M., Mulvagh, S. L., Merz, C. N., Buring, J. E., & Manson, J. E. (2016). Cardiovascular disease in women: Clinical perspectives. Circulation Research, 118(8), 1273–1293. https://doi.org/10.1161/CIRCRESAHA.116.307547 Gast, A., & Mathes, T. (2019). Medication adherence influencing factors—An (updated) overview of systematic reviews. Systematic Reviews, 8(1), 112. https://doi.org/10.1186/s13643-019-1014-8 Gaudino, M., Di Franco, A., Alexander, J. H., Bakaeen, F., Egorova, N., Kurlansky, P., Boening, A., Chikwe, J., Demetres, M., Devereaux, P. J., Diegeler, A., Dimagli, A., Flather, M., Hameed, I., Lamy, A., Lawton, J. S., Reents, W., Robinson, N. B., Audisio, K., . . . Benedetto, U. (2021). Sex differences in outcomes after coronary artery bypass grafting: A pooled analysis of individual patient data. European Heart Journal, 43(1), 18–28. https://doi.org/10.1093/eurheartj /ehab504 Ghali, J. K., Pina, I. L., Gottlieb, S. S., Deedwania, P. C., & Wikstrand, J. C. (2002). Metoprolol CR/XL in female patients with heart failure: Analysis of the experience in Metoprolol Extended-Release Randomized Intervention Trial in Heart Failure (MERIT-HF). Circulation, 105, 1585–1591. https://doi .org/10.1161/01.cir.0000012546.20194.33 Gialdini, G., Nearing, K., Bhave, P. D., Bonuccelli, U., Iadecola, C., Healey, J. S., & Kamel, K. (2014). Perioperative atrial fibrillation and the long-term risk of ischemic stroke. Journal of the American Medical Association, 312(6), 616–622. https://doi.org/10.1001/jama.2014.9143 Giamouzis, G., Kalogeropoulos, A., Georgiopoulou, V., Laskar, S., Smith, A. L., Dunbar, S., Triposkiadis, F., & Butler, J. (2011). Hospitalization epidemic in patients with heart failure: Risk factors, risk prediction, knowledge gaps, and future directions. Journal of Cardiac Failure, 17, 54–75. https://doi .org/10.1016/j.cardfail.2010.08.010

Giardina, E. V., Sciacca, R. R., Foody, J. M., D’Onofrio, G., Villablanca, A. C., Leatherwood, S., Taylor, A. L., & Haynes, S. G. (2011). The DHHS office on women’s health initiative to improve women’s heart health: Focus on knowledge and awareness among women with cardiometabolic risk factors. Journal of Women’s Health, 20, 6, 893–890. https://doi.org/10.1089/jwh,2010.2448 Giugliano, R. P., Ruff, C. T., Braunwald, E., Murphy, S. A., Wiviott, S. D., Halperin, J. L., Waldo, A. L., Ezekowitz, M. D., Weitz, J. I., Špinar, J., Ruzyllo, W., Ruda, M., Koretsune, Y., Betcher, J., Shi, M., Grip, L. T., Patel, S. P., Patel, I., Hanyok, J. J., . . . Antman, E. M. (2013). Edoxaban versus warfarin in patients with atrial fibrillation. New England Journal of Medicine, 369, 2093–2104. https://doi.org/10.1056/NEJMoa1310907 Givertz, M. M. (2013). Peripartum cardiomyopathy. Circulation, 127, e622–e626. https://doi.org/10.1161/CIRCULATIONAHA.113.001851 Goetsch, M. R., Tumarkin, E., Blumenthal, R. S., & Whelton, S. P. (2021). New guidance on blood pressure management in low-risk adults with stage 1 hypertension. American College of Cardiology. https://www.acc.org/Latest -in-Cardiology/Articles/2021/06/21/13/05/New-Guidance-on-BP-Manage​ ment-in-Low-Risk-Adults-with-Stage-1-HTN Golden, K. E., Chang, A. M., & Hollander, J. E. (2013). Sex preferences in cardiovascular testing: The contribution of the patient-physician discussion. Academic Emergency Medicine, 20(7), 1–14. https://doi.org/10.1111/acem.12169 Gopalakrishnan, P., Ragland, M. M., & Tak, T. (2009). Gender differences in coronary artery disease: Review of diagnostic challenges and current treatment. Postgraduate Medicine, 121(2), 60–68. https://doi.org/10.3810 /pgm.2009.03.1977 Gotto, A., & Pownall, H. (1999). Manual of lipid disorders (2nd ed.). Lippincott Williams & Wilkins. Grana, R., Benowitz, N., & Glantz, S. A. (2014). Contemporary reviews in cardiovascular medicine, e-cigarettes: A scientific review. Circulation, 129, 1972– 1986. https://doi.org/10.1161/CIRCULATIONAHA.114.007667 Granger, C. B., Alexander, J. H., McMurphy, J. J., Lopes, R. D., Hylak, E. M., Hanna, M., Al-Khalidi, H. R., Ansell, J., Atar, D., Avezum, A., Bahit, M. C., Diaz, R., Easton, J. D., Ezekowitz, J. A., Flaker, G., Garcia, D., Geraldes, M., Gersh, B. J., Golitsyn, S., . . . Wallentin, L. (2011). Apixaban versus warfarin in patients with atrial fibrillation. New England Journal of Medicine, 365, 981–992. https://doi.org/10.1056/NEJMoa1107039 Greenland, P., Blaha, M. J., Budoff, M. J., Erbel, R., & Watson, K. E. (2018). Coronary calcium score and cardiovascular risk. Journal of the American College of Cardiology, 72(4), 434–447. https://doi.org/10.1016/j .jacc.2018.05.027 Greenland, P., Smith, S. C., & Grundy, S. M. (2001). Improving coronary heart disease risk assessment in asymptomatic people: Role of traditional risk factors and noninvasive cardiovascular tests. Circulation, 104, 1863–1867. https://doi.org/10.1161/hc4201.097189 Grundy, S. M., Stone, N. J., Bailey, A. L., Beam, C., Birtcher, K. K., Blumenthal, R. S., Braun, L. T., de Ferranti, S., Faiella-Tommasino, J., Forman, D. E., Goldberg, R., Heidenreich, P. A., Hlatky, M. A., Jones, D. W., Lloyd-Jones, D., Lopez-Pajares, N., Ndumele, C. E., Orringer, C. E., Peralta,  C.  A., . . . Yeboah, J. (2019a). 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/ AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. Journal of the American College of Cardiology, 73(24), e285–e350. https://doi.org/10.1016/j.jacc.2018.11.003 Grundy, S., Stone, N., Bailey A., Beam, C., Birtcher, K. K., Blumenthal,  R.  S., Braun, L. T., de Ferranti, S., Faiella-Tommasino, J., Forman, D. E., Goldberg, R., Heidenreich, P. A., Hlatky, M. A., Jones, D. W., Lloyd-Jones, D., Lopez-Pajares, N., Ndumele, C. E., Orringer, C. E., Peralta, C. A., . . . Yeboah, J. (2019b). 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/ AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: Executive summary. Journal of the American College of Cardiology, 73(24), 3168–3209. https://doi.org/10.1016/j.jacc.2018.11.002 Gulati, M., Levy, P. D., Mukherjee, D., Amsterdam, E., Bhatt, D. L., Birtcher, K. K., Blankstein, R., Boyd, J., Bullock-Palmer, R. P., Conejo, T., Diercks, D. B., Gentile, F., Greenwood, J. P., Hess, E. P., Hollenberg, S. M., Jaber, W. A., Jneid, H., Joglar, J. A., Morrow, D. A., . . . Shaw, L. J. (2021). 2021 AHA/ACC/ ASE/CHEST/SAEM/SCCT/SCMR guideline for the evaluation and diagnosis of chest pain. Journal of the American College of Cardiology, 78(22), e187– e285. https://doi.org/10.1016/j.jacc.2021.07.053 Gulati, M., Shaw, L. J., & Bairey Merz, C. N. (2012). Myocardial ischemia in women—Lessons from the NHLBI WISE Study. Clinical Cardiology, 35(3), 141–148. https://doi.org/10.1002/clc.21966 Gunderson, E. P., Lewis, C. E., Wei, G. S., Whitmer, R. A., Quesenberry, C. P., & Sidney, S. (2007). Lactation and changes in maternal metabolic risk factors. Obstetrics & Gynecology, 109(3), 729–738. https://doi.org/10.1097/01.AOG .0000252831.06695.03 Guyton, A. C., & Hall, J. E. (2006). Textbook of medical physiology (11th ed.). Elsevier Saunders.

Haider, A., Bengs, S., Luu, J., Osto, E., Siller-Matula, J. M., Muka, T., & Gebhard, C. (2019). Sex and gender in cardiovascular medicine: Presentation and outcomes of acute coronary syndrome. European Heart Journal, 41(13), 1328–1336. https://doi.org/10.1093/eurheartj/ehz898 Harjai, K. J. (1999). Potential new cardiovascular risk factors: Left ventricular hypertrophy, homocysteine, lipoprotein(a), triglycerides, oxidative stress, and fibrinogen. Annals of Internal Medicine, 131, 376–386. https://doi .org/10.7326/0003-4819-131-5-199909070-00009 Heart Protection Study Collaborative Group. (2002). MRC/BRF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: A randomised placebo-controlled trial. Lancet, 360(9326), 7–22. https:// doi.org/10.1016/S0140-6736(02)09327-3 Heer, T., Schiele, R., Schneider S., Git, A. K., Wienbergen, H., Gottwik, M., Gieseler, U., Voigtländer, T., Hauptmann, K. E., Wagner, S., & Senges, J. (2002). Gender differences in acute myocardial infarction in the era of thrombolytic reperfusion (the MITRA registry). American Journal of Cardiology, 89, 511–517. https://doi.org/10.1016/s0002-9149(01)02289-5 Heidenreich, P. A., Bozkurt, B., Aguilar, D., Allen, L. A., Byun, J. J., Colvin,  M.  M., Deswal, A., Drazner, M. H., Dunlay, S. M., Evers, L. R., Fang, J. C., Fedson,  S.  E., Fonarow, G. C., Hayek, S. S., Hernandez, A. F., Khazanie, P., Kittleson, M. M., Lee, C. S., Link, M. S., . . . Yancy, C. W. (2022). 2022 AHA/ACC/HFSA guideline for the management of heart failure. Journal of the American College of Cardiology, 79(17), e263–e421. https://doi .org/10.1016/j.jacc.2021.12.012 Heo, S., Moser, D. K., & Widener, J. (2007). Gender differences in the effects of physical and emotional symptoms on health-related quality of life in patients with heart failure. European Journal of Cardiovascular Nursing, 6, 146–152. https://doi.org/10.1016/j.ejcnurse.2006.06.008 Hernesniemi, J. A., Seppälä, I., Lyytikäinen, L. P., Mononen, N., Oksala, N., Hutri-Kähönen, N., Juonala, M., Taittonen, L., Smith, E. N., Schork, N. J., Chen, W., Srinivasan, S. R., Berenson, G. S., Murray, S. S., Laitinen, T., Jula, A., Kettunen, J., Ripatti, S., Laaksonen, R., . . . Lehtimäki, T. (2012). Genetic profiling using genome-wide significant coronary artery disease risk variants does not improve the prediction of subclinical atherosclerosis: The Cardiovascular Risk in Young Finns Study, the Bogalusa Heart Study and the Health 2000 Survey: A meta-analysis of three independent studies. PLoS One, 7, e28931. https://doi.org/10.1371/journal .pone.0028931 Hillis, L. D., Smith, P. K., Anderson, J. L., Bittl, J. A., Bridges, C. R., Byrne, J. G., Cigarroa, J. E., Disesa, V. J., Hiratzka, L. F., Hutter, A. M., Jessen, M. E., Keeley, E. C., Lahey, S. J., Lange, R. A., London, M. J., Mack, M. J., Patel, M. R., Puskas, J. D., Sabik, J. F., . . . Winniford, M. D. (2011). 2011 ACCF/AHA guideline for coronary artery bypass graft surgery: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation, 124, e652–e735. https://doi.org/10.1161 /CIR.0b013e31823c074e Hohnloser, S. H. (2011). Stroke prevention versus bleeding risk in atrial fibrillation: A clinical dilemma. Journal of the American College of Cardiology, 57, 181–183. https://doi.org/10.1016/j.jacc.2010.09.026 Holmes, M. V., Harrison, S., Talmud, P. J., Hingorani, A. D., & Humphries, S. E. (2011). Utility of genetic determinants of lipids and cardiovascular events in assessing risk. Nature Reviews Cardiology, 8, 207–221. https://doi.org /10.1038/nrcardio.2011.6 Hongo, R. H., & Scheinman, M. M. (2005). Arrhythmia and arrhythmia management. In N. K. Wenger & P. Collins (Eds.), Women and heart disease (2nd ed., pp. 523–536). Taylor & Francis Group. Humphries, K. H., Kerr, C. R., Connolly, S. J., Klein, G., Boone, J. A., Green, M., Sheldon, R., Talajic, M., Dorian, P., & Newman, D. (2001). New-onset atrial fibrillation: Sex differences in presentation, treatment and outcome. Circulation, 103, 2365–2370. https://doi.org/10.1161/01.cir.103.19.2365 Huxley, R. R., & Woodward, M. (2011). Cigarette smoking as a risk factor for coronary heart disease in women compared with men: A systematic review and meta-analysis of prospective cohort studies. Lancet, 378, 1297–1305. https://doi.org/10.1016/S0140-6736(11)60781-2 Ibetoh, C. N., Stratulat, E., Liu, F., Wuni, G. Y., Bahuva, R., Shafiq, M. A., Gattas, B. S., & Gordon, D. K. (2021). Supraventricular tachycardia in pregnancy: Gestational and labor differences in treatment. Cureus, 13(10), e18479. https://doi.org/10.7759/cureus.18479 Iung, B., & Vahanian, A. (2014). Epidemiology of acquired valvular heart disease. Canadian Journal of Cardiology, 30(9), 962–970. https://doi.org/10.1016/j .cjca.2014.03.022 Jackevicius, C. A., Ping, L., & Tu, J. V. (2008). Prevalence, predictors, and outcomes of primary nonadherence after acute myocardial infarction. Circulation, 117, 1028–1036. https://doi.org/10.1161/CIRCULATIONAHA.107 .706820

Jackevicius, C. A., Tu, J. V., Ross, J. S., Ko, D. T., & Krumholtz, H. M. (2008). Use of ezetimibe in the United States and Canada. New England Journal of Medicine, 358, 1819–1828. https://doi.org/10.1056/NEJMsa0801461 Jackson, G. (2005). Stable angina pectoris (recognition and management). In N. K. Wenger & P. Collins (Eds.), Women and heart disease (2nd ed., pp. 195–204). Taylor & Francis Group. Jakubisin Konicki, A. (2019). Promoting cardiovascular health in midlife women. Section current approaches to managing menopause. Current Obstetrics and Gynecology Reports, 8(4), 145–151. https://doi.org/10.1007 /s13669-019-00275-8 January, C., Wann, S. L., Alpert, J. S., Calkins, H., Cigarroa, J. E., Cleveland, J. C., Jr., Conti, J. B., Ellinor, P. T., Ezekowitz, M. D., Field, M. E., Murray, K. T., Sacco, R. L., Stevenson, W. G., Tchou, P. J., Tracy, C. M., & Yancy, C. W. (2014). 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: Executive summary. Journal of the American College of Cardiology, 64, 2246–2280. https://doi.org/10.1016/j.jacc.2014.03.021 January, C. T., Wann, L. S., Calkins, H., Chen, L. Y., Cigarroa, J. E., Cleveland, J., Ellinor, P. T., Ezekowitz, M. D., Field, M. E., Furie, K. L., Heidenreich, P. A., Murray, K. T., Shea, J. B., Tracy, C. M., & Yancy, C. W. (2019). 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Journal of the American College of Cardiology, 74(1), 104–132. https://doi.org/10.1016/j .jacc.2019.01.011 Jessup, M., Abraham, W. T., Casey, D. E., Feldman, A. M., Francis, G. S., Ganiats, T. G., Konstam, M. A., Mancini, D. M., Rahko, P. S., Silver, M. A., Stevenson, L. W., & Yancy, C. W. (2009). 2009 focused update ACCF/AHA guidelines for the diagnosis and management of heart failure in adults. Journal of the American College of Cardiology, 53(15), 1343–1382. https://doi .org/10.1016/j.jacc.2008.11.009 Jneid, H., Anderson, J. L., Wright, R. S., Adams, C. D., Bridges, C. R., Casey, D. E., Ettinger, S. M., Fesmire, F. M., Ganiats, T. G., Lincoff, A. M., Peterson, E. D., Philippides, G. J., Theroux, P., Wenger, N. K., & Zidar, J. P. (2012). 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non–ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology, 60, 645–681. https://doi.org/10.1016/j.jacc.2012.06.004 Johnson, B. D., Shaw, L. J., Buchthal, S. D., Bairey Merz, C. N., Kim, H. W., Scott, K. N., Doyle, M., Olson, M. B., Pepine, C. J., den Hollander, J., Sharaf, B., Rogers, W. J., Mankad, S., Forder, J. R., Kelsey, S. F., & Pohost, G. M. (2004). Prognosis in women with myocardial ischemia in the absence of obstructive coronary disease: Results from the National Institutes of Health–National Heart, Lung, and Blood Institute–Sponsored Women’s Ischemia Syndrome Evaluation (WISE). Circulation, 109, 2993–2999. https://doi.org/10.1161/01 .CIR.0000130642.79868.B2 Johnston, S. C., Rothwell, P. M., Nguyen-Huynh, M. N., Giles, M. F., Elkins, J. S., Bernstein, A. L., & Sidney, S. (2007). Validation and refinement of scores to predict very early stroke risk after transient ischemic attack. Lancet, 369, 283–292. https://doi.org/10.1016/S0140-6736(07)60150-0 Joshi, P. H., & de Lemos, J. A. (2021). Diagnosis and management of stable angina. Journal of the American Medical Association, 325(17), 1765–1778. https://doi.org/10.1001/jama.2021.1527 Kannel, W. B., & Abbott, R. D. (1986). A prognostic comparison of asymptomatic left ventricular hypertrophy and unrecognized myocardial infarction: The Framingham Study. American Heart Journal, 111, 391–397. https://doi .org/10.1016/0002-8703(86)90156-0 Kaski, J. C. (2006). Cardiac syndrome X in women: The role of oestrogen deficiency. Heart, 92(Suppl. 3), iii5–iii9. https://doi.org/10.1136/hrt.2005.070318 Kaspar, G., Sanam, K., Gundlapalli, S., & Shah, D. (2018). Successful fluoroless radiofrequency catheter ablation of supraventricular tachycardia during pregnancy. Clinical Case Reports, 6(7), 1334–1337. https://doi.org/10.1002 /ccr3.1623 Kastelein, J. J., Akdim, F., Stroes, E. S., Zwinderman, A. H., Bots, M. L., Stalenhoef, A. F., & Visseren, F. L. (2008). Simvastatin with or without ezetimibe in familial hypercholesterolemia. New England Journal of Medicine, 358, 1431–1443. https://doi.org/10.1056/NEJMoa0800742 Kern, M. J. (2005). Coronary blood flow and myocardial ischemia. In D. P. Zipes, P. Libby, R. O. Bonow, & E. Braunwald (Eds.), Braunwald’s heart disease (7th ed., pp. 1103–1128). Elsevier Saunders. Khan, S. S., Beach, L. B., & Yancy, C. W. (2022). Sex-based differences in heart failure. Journal of the American College of Cardiology, 79(15), 1530–1541. https://doi.org/10.1016/j.jacc.2022.02.013 Khera, R., Valero-Elizondo, J., Das, S. R., Virani, S. S., Kash, B. A., de Lemos, J. A., Krumholz, H. M., & Nasir, K. (2019). Cost-related medication

nonadherence in adults with atherosclerotic cardiovascular disease in the United States, 2013 to 2017. Circulation, 140(25), 2067–2075. https://doi.org /10.1161/CIRCULATIONAHA.119.041974 Kienreich, K., Tomaschitz, A., Verheyen, N., Pieber, T., Gaksch, M., Grübler, M. R., & Pilz, S. (2013). Vitamin D and cardiovascular disease. Nutrients, 5(8), 3005– 3021. https://doi.org/10.3390/nu5083005 Klocke, F. J., Baird, M. G., Lorell, B. H., Bateman, T. M., Messer, J. V., Berman, D. S., O’Gara, P. T., Carabello, B. A., Russell, R. O., Cerqueira, M. D., St John Sutton, M. G., DeMaria, A. N., Udelson, J. E., Kennedy, J. W., Verani, M. S., Williams, K. A., Antman, E. M., Smith, S. C., Alpert, J. S., . . . Russell, R. O. (2003). ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging—Executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to revise the 1995 guidelines for the clinical use of cardiac radionuclide imaging). Circulation, 108, 1404– 1418. https://doi.org/10.1161/01.CIR.0000080946.42225.4D Kociol, R. D., Hammill, B. G., Fonarow, G. C., Klaskala, W., Mills, R. M., Hernandez, A. F., & Curtis, L. H. (2010). Generalizability and longitudinal outcomes of a national heart failure clinical registry: Comparison of Acute Decompensated Heart Failure National Registry (ADHERE) and non-ADHERE Medicare beneficiaries. American Heart Journal, 160, 885–892. https://doi.org/10.1016/j.ahj.2010.07.020 Koelling, T. M., Chen, R. S., Lubwama, R. N., L’Italien, G. J., & Eagle, K. A. (2004). The expanding national burden of heart failure in the United States: The influence of heart failure in women. American Heart Journal, 147, 74–78. https://doi.org/10.1016/j.ahj.2003.07.021 Konstam, M. A. (2012). Home monitoring should be the central element in an effective program of heart failure disease management. Circulation, 125(6), 820–827. https://doi.org/10.1161/CIRCULATIONAHA.111.031161 Kotalczyk, A., Imberti, J. F., Lip, G. Y. H., & Wright, D. J. (2022). Telemedical monitoring based on implantable devices—The evolution beyond the CardioMEMS technology. Current Heart Failure Reports, 19(1), 7–14. https:// doi.org/10.1007/s11897-021-00537-8 Kotchetkov, R., Patel, A., & Salehian, O. (2010). Ventricular tachycardia in pregnant patients. Clinical Medicine Insights: Cardiology, 4, 39–44. https://doi .org/10.4137/CMC.S4755 Kothawade, K., & Bairey Merz, C. N. (2011). Microvascular coronary dysfunction in women: Pathophysiology, diagnosis, and management. Current Problems in Cardiology, 36(8), 291–318. https://doi.org/10.1016/j.cpcardiol.2011.05.002 Krahn, A. D., Yee, R., Klein, G. J., & Morillo, C. (1995). Inappropriate sinus tachycardia: Evaluation and therapy. Journal of Cardiovascular Electrophysiology, 6, 1124–1128. https://doi.org/10.1111/j.1540-8167.1995.tb00391.x Kravitz, R. L., Hays, R. D., Sherbourne, C. D., DiMatteo, M. R., Rogers, W. H., Ordway, L., & Greenfield, S. (1993). Recall of recommendations and adherence to advice among patients with chronic medical conditions. Archives of Internal Medicine, 153, 1869–1878. https://doi.org/10.1001/archinte.1993.00410160029002 Krumholz, H. M., Anderson, J. L., Bachelder, B. L., Fesmire, F. M., Fihn, S. D., Foody, J. M., Ho, P. M., Kosiborod, M. N., Masoudi, F. A., & Nallamothu, B. K. (2008). ACC/AHA 2008 performance measures for adults with ST-elevation and non–ST-elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Performance Measures (Writing Committee to Develop Performance Measures for ST-Elevation and Non–ST-Elevation Myocardial Infarction). Circulation, 118, 2596–2648. https://doi.org/10.1161 /CIRCULATIONAHA.108.191099 Kummer, B. R., Bhave, P. D., Merkler, A. E., Gialdini, G., Okin, P. M., & Kamel, H. (2015). Demographic differences in catheter ablation after hospital presentation with symptomatic atrial fibrillation. Journal of the American Heart Association, 4, e002097. https://doi.org/10.1161/JAHA.115.002097 Kurth, T., Rist, P. M., Ridker, P. M., Kotler, G., Bubes, V., & Buring, J. E. (2020). Association of migraine with aura and other risk factors with incident cardiovascular disease in women. JAMA, 323(22), 2281–2289. https://doi .org/10.1001/jama.2020.7172 Lane, D. A., & Lip, G. Y. (2012). Use of the CHA(2)DS(2)VASc and HASBLED scores to aid decision making for thromboprophylaxis in nonvalvular atrial fibrillation. Circulation, 126, 860–865. https://doi.org/10.1161 /CIRCULATIONAHA.111.060061 Lawler, P. R., Bhatt, D. L., Godoy, L. C., Lüscher, T. F., Bonow, R. O., Verma, S., & Ridker, P. M. (2021). Targeting cardiovascular inflammation: Next steps in clinical translation. European Heart Journal, 42(1), 113–131. https://doi .org/10.1093/eurheartj/ehaa099 Lawton, J. S., Tamis-Holland, J. E., Bangalore, S., Bates, E. R., Beckie, T. M., Bischoff, J. M., Bittl, J. A., Cohen, M. G., DiMaio, J. M., Don, C. W., Fremes,  S. E., Gaudino, M. F., Goldberger, Z. D., Grant, M. C., Jaswal, J. B., Kurlansky, P. A., Mehran, R., Metkus, T. S., Nnacheta, L. C., . . . Zwischenberger, B. A. (2022). 2021 ACC/AHA/SCAI Guideline for Coronary

Artery Revascularization. Journal of the American College of Cardiology, 79(2), e21–e129. https://doi.org/10.1016/j.jacc.2021.09.006 Legato, M. J., Johnson, P. A., & Manson, J. E. (2016). Consideration of sex differences in medicine to improve health care and patient outcomes. JAMA, 316(18), 1865–1866. https://doi.org/10.1001/jama.2016.13995 Lerner, D. J., & Kannel, W. B. (1986). Patterns of coronary heart disease morbidity and mortality in the sexes: A 26-year follow-up of the Framingham population. American Heart Journal, 111, 383–390. https://doi.org/10.1016 /0002-8703(86)90155-9 Lesman-Leegte, I., Jaarsma, T., Coyne, J. C., Hillege, H. L., Van Veldhuisen, D. J., & Sanderman, R. (2009). Quality of life and depressive symptoms in the elderly: A comparison between patients with heart failure and age- and gender-matched community controls. Journal of Cardiac Failure, 15, 17–23. https://doi.org/10.1016/j.cardfail.2008.09.006 Li, S., Fonarow, G. C., Mukamal, K., Xu, H., Matsouaka, R. A., Devore, A. D., & Bhatt, D. L. (2018). Sex and racial disparities in cardiac rehabilitation referral at hospital discharge and gaps in long-term mortality. Journal of the American Heart Association, 7(8), e008088. https://doi.org/10.1161/JAHA .117.008088 Lindenfeld, J., Albert, N. M., Boehmer, J. P., Collins, S. P., Ezekowitz, J. A., Givertz, M. M., Katz, S. D., Klapholz, M., Moser, D. K., Rogers, J. G., Starling, R. C., Stevenson, W. G., Tang, W. H., Teerlink, J. R., & Walsh, M. N. (2010). HFSA 2010 comprehensive heart failure practice guideline. Journal of Cardiac Failure, 16(6), e1–e194. https://doi.org/10.1016/j.cardfail .2010.04.004 Lip, G. Y., Nieuwlaat, R., Pisters, R., Lane, D. A., & Crijns, H. J. (2010). Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: The Euro Heart Survey on Atrial Fibrillation. Chest, 137, 263–272. https://doi.org/10.1378 /chest.09-1584 Lloyd-Jones, D. M., Elkind, M., & Albert, M. A. (2021). American Heart Association’s 2024 Impact goal: Every person deserves the opportunity for a full, healthy life. Circulation, 144(18), e277–e279. https://doi.org/10.1161 /CIRCULATIONAHA.121.057617 Lloyd-Jones, D. M., Leip, E. P., Larson, M. G., D’Agostino, R. B., Beiser, A., Wilson, P. W., Wolf, P. A., & Levy, D. (2006). Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age. Circulation, 113, 791–798. https://doi.org/10.1161/CIRCULATIONAHA.105.548206 Lloyd-Jones, D. M., Nam, B. H., D’Agostino, R. B., Sr., Levy, D., Murabito, J. M., Wang, T. J., Wilson, P. W., & O’Donnell, C. J. (2004). Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: A prospective study of parents and offspring. Journal of the American Medical Association, 291, 2204–2211. https://doi.org/10.1001/jama.291.18.2204 Lobelo, F., Rohm Young, D., Sallis, R., Garber, M. D., Billinger, S. A., Duperly, J., Hutber, A., Pate, R. R., Thomas, R. J., Widlansky, M. E., McConnell, M. V., & Joy, E. A. (2018). Routine assessment and promotion of physical activity in healthcare settings: A scientific statement from the American Heart Association. Circulation, 137(18), e495–e522. https://doi.org/10.1161/CIR .0000000000000559 Loscalzo, J., Weinfeld, M., Fless, G. M., & Scanu, A. M. (1990). Lipoprotein(a), fibrin binding, and plasminogen activation. Arteriosclerosis, 10, 240–245. https://doi.org/10.1161/01.atv.10.2.240 Lowery, J., Hopp, F., Subramanian, U., Wiitala, W., Welsh, D. E., Larkin, A., Stemmer, K., Zak, C., & Vaitkevicius, P. (2012). Evaluation of a nurse practitioner disease management model for chronic heart failure: A multi-site implementation study. Congestive Heart Failure, 18, 64–71. https://doi .org/10.1111/j.1751-7133.2011.00228.x Macedo, A. F., Bell, J, McCarron, C., Conroy, R., Richardson, J., Scowcroft, A., Sunderland, T., & Rotheram, N. (2015). Determinants of oral anticoagulation control in new warfarin patients: An analysis using data from Clinical Practice Research Datalink. Thrombosis Research, 136, 250–260. https://doi .org/10.1016/j.thromres.2015.06.007 Madias, J. E. (2006). ECG changes and voltage attenuation in congestive heart failure. Hospital Chronicles, Supplement, 27–30. Maffei, S., Guiducci, L., Cugusi, L., Cadeddu, C., Deidda, M., Gallina, S., Sciomer, S., Gastaldelli, A., & Kaski, J. C. (2019). Women-specific predictors of cardiovascular disease risk—New paradigms. International Journal of Cardiology, 286, 190–197. https://doi.org/10.1016/j.ijcard.2019.02.005 Mann, J. F. E., & Hilgers, K. F. (2022). Goal blood pressure in adults with hypertension. UpToDate. https://www.uptodate.com/contents/goal-blood -pressure-in-adults-with-hypertension Marrs, J. C., & Anderson, S. L. (2020). Bempedoic acid for the treatment of dyslipidemia. Drugs in Context, 9, 1–9. https://doi.org/10.7573/dic.2020-6-5 Massari, F., Scicchitano, P., Potenza, A., Sassara, M., Sanasi, M., Liccese, M., Ciccone, M. M., & Caldarola, P. (2018). Supraventricular tachycardia, pregnancy, and water: A new insight in lifesaving treatment of rhythm

disorders. Annals of Noninvasive Electrocardiology, 23(3), e12490. https://doi .org/10.1111/anec.12490 McEvoy, J. W., Daya, N., Rahman, F., Hoogeveen, R. C., Blumenthal, R. S., Shah, A. M., Ballantyne, C. M., Coresh, J., & Selvin, E. (2020). Association of isolated diastolic hypertension as defined by the 2017 ACC/AHA blood pressure guideline with incident cardiovascular outcomes. JAMA, 323(4), 329–338. https://doi.org/10.1001/jama.2019.21402 McNamara, D. M., Elkayam, U, Alharethi, R., Damp, J., Hsich, E., Ewald, G., Modi, K., Alexis, J. D., Ramani, G. V., Semigran, M. J., Haythe, J., Markham, D. W., Marek, J., Gorcsan, J., Wu, W. C., Lin, Y., Halder, I., Pisarcik, J., Cooper, L. T., & Fett, J. D. (2015). Clinical outcomes for peripartum cardiomyopathy in North America. Results of the IPAC Study (Investigations of Pregnancy-Associated Cardiomyopathy). Journal of the American College of Cardiology, 66(8), 905–914. https://doi.org/10.1016/j .jacc.2015.06.1309 McSweeney, J. C., Cleves, M. A., Zhaom W., Lefler, L. L., & Yang, S. (2010). Cluster analysis of women’s prodromal and acute myocardial infarction symptoms by race and other characteristics. Journal of Cardiovascular Nursing, 25(4), 311–322. https://doi.org/10.1097/JCN.0b013e3181cfba15 Mehran, R., Chandrasekhar, J., Urban, P., Lang, I. M., Windhoevel, U., Spaulding, C., Copt, S., Stoll, H. P., & Morice, M. C. (2020). Sex-based outcomes in patients with a high bleeding risk after percutaneous coronary intervention and 1-month dual antiplatelet therapy. JAMA Cardiology, 5(8), 939–947. https://doi.org/10.1001/jamacardio.2020.0285 Meyer, J. S., Mehdirad, A., Salem, B. I., Kulikowska, A., & Kulikowski, P. (2003). Sudden arrhythmia death syndrome: Importance of the long QT syndrome. American Family Physician, 68(3), 483–488. Michelena, H. I., Powell, B. D., Brady, P. A., Friedman, P. A., & Ezekowitz, M. D. (2010). Gender in atrial fibrillation: Ten years later. Gender Medicine, 7(3), 206–217. https://doi.org/10.1016/j.genm.2010.06.001 Mieres, J. H., Shaw, L. J., Arai, A., Budoff, M. J., Flamm, S. D., Hundley, W. G., Marwick, T. H., Mosca, L., Patel, A. R., Quinones, M., Redberg, R. F., Taubert, K., Taylor, A., Thomas, G. S., & Wenger, N. K. (2005). Role of noninvasive testing in the clinical evaluation of women with suspected coronary artery disease: Consensus statement from the Cardiac Imaging Committee, Council on Clinical Cardiology, and the Cardiovascular Imaging and Intervention Committee, Council on Cardiovascular Radiology and Intervention, American Heart Association. Circulation, 111, 682–696. https://doi .org/10.1161/01.CIR.0000155233.67287.60 Mieres, J. H., Shaw, L. J., Hendel, R. C., Miller, D. D., Bonow, R. O., Berman, D. S., & Heller, G. V. (2003). A report of the American Society of Nuclear Cardiology Task Force on women and heart disease (writing group on perfusion imaging in women). Journal of Nuclear Cardiology, 10, 95–101. https://doi .org/10.1067/mnc.2003.130362 Mookadam, M., Shamoun, F. E., & Mookadam, F. (2015). Novel anticoagulants in atrial fibrillation: A primer for the primary physician. Journal of the American Board of Family Medicine, 28, 510–522. https://doi.org/10.3122 /jabfm.2015.04.140297 Mora, S., Glynn, R. J., Hsia, J., MacFadyen, J. G., Genest, J., & Ridker, P. M. (2010). Statins for the primary prevention of cardiovascular events in women with elevated high-sensitivity C-reactive protein or dyslipidemia: Results from the Justification for the Use of statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) and meta-analysis of women from primary prevention trials. Circulation, 121, 1069–1077. https://doi.org/10.1161 /CIRCULATIONAHA.109.906479 Morris, D. C. (2005). Acute coronary syndromes. In N. K. Wenger & P. Collins (Eds.), Women and heart disease (2nd ed., pp. 237–249). Taylor & Francis Group. Mosca, L., Benin, E. J., Berra, K., Benzanon, J. L., Dolor, R. J., LloydJones, D. M., Newby, L. K., Piña, I. L., Roger, V. L., Shaw, L. J., Zhao, D., Beckie, T. M., Bushnell, C., D’Armiento, J., Kris-Etherton, P. M., Fang, J., Ganiats, T. G., Gomes, A. S., Gracia, C. R., . . . Wenger, N. K. (2011). Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update. Circulation, 123, 1243–1262. https://doi.org /10.1161/CIR.0b013e31820faaf8 Mosca, L., Hammond, G., Mochari-Greenberger, H., Towfighi, A., & Albert, M. A. (2013). Fifteen-year trends in awareness of heart disease in women: Results of a 2012 American Heart Association National Survey. Circulation, 127(11), 1254–1263. https://doi.org/10.1161/CIR.0b013e318287cf2f Mosca, L., Linfante, A. H., Benjamin, E. J., Berra, K., Hayes, S. N., Walsh, B. W., Fabunmi, R. P., Kwan, J., Mills, T., & Simpson, S. L. (2005). National study of physician awareness and adherence to cardiovascular disease prevention guidelines. Circulation, 111, 499–510. https://doi.org/10.1161/01.CIR .0000154568.43333.82 Mozaffarian, D., Benjamin, E. J., Go, A. S., Arnett, D. K., Blaha, M. J., Cushman, M., de Ferranti, S., Després, J. P., Fullerton, H. J., Howard, V. J., Huffman, M. D., Judd, S. E., Kissela, B. M., Lackland, D. T., Lichtman, J. H.,

Lisabeth, L. D., Liu, S., Mackey, R. H., Matchar, D. B., . . .Turner, M. B. (2015). Heart disease and stroke statistics—2015 update: A report from the American Heart Association. Circulation, 131, e29–e322. https://doi.org/10.1161 /CIR.0000000000000152 Mukamal, K. J., Maclure, M., Muller, J. E., & Mittleman, M. A. (2008). An exploratory prospective study of marijuana use and mortality following acute myocardial infarction. American Heart Journal, 155(3), 465–470. https://doi .org/10.1016/j.ahj.2007.10.049 Mulders, T. A., Meyer, Z., van der Donk, C., Kroon, A. A., Ferreira, I., Stehouwer, C. D., & Pinto-Sietsma, S. J. (2011). Patients with premature cardiovascular disease and a positive family history for cardiovascular disease are prone to recurrent events. International Journal of Cardiology, 153(1), 64–67. https:// doi.org/10.1016/j.ijcard.2010.08.040 National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). (2002). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation, 106, 3143–3421. https://doi.org/10.1161 /circ.106.25.3143 Newby L. K., LaPointe, N. M., Chen, A. Y., Kramer, J. M., Hammill, B. G., DeLong,  E.  R., Muhlbaier, L. H., & Califf, R. M. (2006). Long-term adherence to evidence-based secondary prevention therapies in coronary artery disease. Circulation, 113, 203–212. https://doi.org/10.1161 /CIRCULATIONAHA.105.505636 Nishimura, R. A., Otto, C. M., Bonow, R. O., Carabello, B. A., Erwin, J. P., Guyton, R. A., O’Gara, P. T., Ruiz, C. E., Skubas, N. J., Sorajja, P., Sundt, T. M., & Thomas, J. D. (2014). AHA/ACC guideline for the management of patients with valvular heart disease: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation, 129(23), 2440–2492. https://doi.org/10.1161 /CIR.0000000000000029 Novella, S., Dantas, A. P., Segarra, G., Medina, P., & Hermenegildo, C. (2012). Vascular aging in women: Is estrogen the fountain of youth? Frontiers in Physiology, 3, 1–8. https://doi.org/10.3389/fphys.2012.00165 Oakley, C., Child, A., Jung, B., Prespitaro, P., Tornos, P., Klein, W., Garcia, M. A., Blom­ström-Lundqvist, C., de Backer, G., Dargie, H., Deckers, J., Flather, M., Hradec, J., Mazzotta, G., Oto, A., Parkhomenko, A., Silber, S., Torbicki, A., Trappe, H. J., . . . Poumeyrol-Jumeau, D. (2003). Expert consensus document of management of cardiovascular diseases during pregnancy. The Task Force on the Management of Cardiovascular Diseases During Pregnancy of the European Society of Cardiology. European Heart Journal, 24, 761–781. https://doi.org/10.1016/s0195-668x(03)00098-8 Oberman, R., & Bhardwaj, A. (2022). Physiology, cardiac. In StatPearls. StatsPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK526089 O’Gara, P. T., Kushner, F. G., Ascheim, D. D., Casey, D. E., Chung, M. K., de Lemos  J. A., Ettinger, S. M., Fang, J. C., Fesmire, F. M., Franklin, B. A., Granger, C. B., Krumholz, H. M., Linderbaum, J. A., Morrow, D. A., Newby, L. K., Ornato, J. P., Ou, N., Radford, M. J., Tamis-Holland, J. E., . . . Zhao, D. X. (2013). 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation, 127, 529–555. https://doi.org/10.1161/CIR.0b013e3182742c84 Ogburn, P. L., Schmidt, G., Linman, J., & Cefalo, R. C. (1982). Paroxysmal tachycardia and cardioversion during pregnancy. Journal of Reproductive Medicine, 27, 359–362. Osnabrugge, R. L. J., Mylotte, D., Head, S. J., Van Mieghem, N. M., Nkomo, V. T., LeReun, C. M., Bogers A. J. J. C., Piazza, N., & Kappetein, A. P. (2013). Aortic stenosis in the elderly: Disease prevalence and number of candidates for transcatheter aortic valve replacement: A meta-analysis and modeling study. Journal of the American College of Cardiology, 62(11), 1002–1012. https://doi .org/10.1016/j.jacc.2013.05.015 Ostchega, Y., Fryar, C. D., Nwankwo, T., & Nguyen, D. T. (2020). Hypertension prevalence among adults aged 18 and over: United States, 2017–2018 (NCHS Data Brief, No. 364). National Center for Health Statistics. https://www.cdc .gov/nchs/products/databriefs/db364.htm Otto, C. M., Nishimura, R. A., Bonow, R. O., Carabello, B. A., Erwin, J. P. 3rd, Gentile, F., Jneid, H., Krieger, E. V., Mack, M., McLeod, C., O’Gara, P. T., Rigolin, V. H., Sundt, T. M. 3rd, Thompson, A., & Toly, C. (2021). 2020 ACC/AHA guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Journal of the American College of Cardiology, 77(4), e25–e197. https://doi.org/10.1016/j .jacc.2020.11.018 Pachariyanon, P., Cheungpasitporn, W., Bathini, T., O’Corragain, O. A., Thongprayoon, C., & Chokesuwattanaskul, R. (2019). Incidence of atrial fibrillation during pregnancy and its impacts on maternal and fetal outcomes:

A meta-analysis. Journal of the American College of Cardiology, 73(9), 356. https://doi.org/10.1016/S0735-1097(19)30964-7 Packer, M., Coats, A. J. S., Fowler, M. B., Katus, H. A., Krum, H., Mohacsi, P., Rouleau, J. L., Tendera, M., Castaigne, A., Roecker, E. B., Schultz, M. K., DeMets, D. L., & DeMets, D. L. (2001). Effect of carvedilol on survival in severe chronic heart failure. New England Journal of Medicine, 344(22), 1651–1658. https://doi.org/10.1056/NEJM200105313442201 Page, R. L., Joglar, J. A., Caldwell, M. A., Calkins, H., Conti, J. B., Deal, B. J., Estes, N. A., 3rd, Field, M. E., Goldberger, Z. D., Hammill, S. C., Indik, J. H., Lindsay, B. D., Olshansky, B., Russo, A. M., Shen, W. K., Tracy, C. M., & Al-Khatib, S. M. (2016). 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation, 133(14), e471–e505. https://doi.org/10.1161/CIR.0000000000000310 Paraskevas, K. I., Veith, F. J., Eckstein, H. H., Ricco, J. B., & Mikhailidis, D. P. (2020). Cholesterol, carotid artery disease and stroke: What the vascular specialist needs to know. Annals of Translational Medicine, 8(19), 1265. https:// doi.org/10.21037/atm.2020.02.176 Pasternak, R. C., Smith, S. C., Jr., Bairey-Merz, C. N., Grundy, S. M., Cleeman, J. I., & Lenfant, C. (2002). ACC/AHA/NHLBI Clinical advisory on the use and safety of statins. Circulation, 106(8), 1024–1028. https://doi.org/10.1161/01 .cir.0000032466.44170.44 Patel, M. R., Mahaffey, K. W., Garg, J., Pan, G., Singer, D. E., Hacke, W., Breithardt,  G., Halperin, J. L., Hankey, G. J., Piccini, J. P., Becker, R. C., Nessel, C. C., Paolini, J. F., Berkowitz, S. D., Fox, K. A., & Califf, R. M. (2011). Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. New England Journal of Medicine, 365, 883–891. https://doi.org/10.1056/NEJMoa1009638 Pelliccia, F., Limongelli, G., Autore, C., Gimeno-Blanes, J., Basso, C., & Elliott, P. (2019). Sex-related differences in cardiomyopathies. International Journal of Cardiology, 286, 239–243. https://doi.org/10.1016/j.ijcard.2018.10.091 Perez, M. V., Wang, P. J., Larson, J. C., Virnig, B. A., Cochrane, B., Curb, J. D., Klein, L., Manson, J. E., Martin, L. W., Robinson, J., Wassertheil-Smoller, S., & Stefanick, M. L. (2012). Effects of postmenopausal hormone therapy on incident atrial fibrillation: The Women’s Health initiative randomized controlled trials. Circulation: Arrhythmia and Electrophysiology, 5(6), 1108–1116. https://doi.org/10.1161/CIRCEP.112.972224 Perez-Silva, A., & Merino, J. L. (2011). Tachyarrhythmias and pregnancy. European Society of Cardiology, E-Journal Cardiology Practice, 9(31). https:// www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-9 /Tachyarrhythmias-and-Pregnancy Pignone, M., Fowler-Brown, A., Pletcher, M., & Tice, J. A. (2003). Screening for asymptomatic coronary artery disease: A systematic review for the U.S. Preventative Services Task Force. Systematic Evidence Review, No. 22. Agency for Healthcare Research and Quality. http://www.ahrq.gov/downloads/pub /prevent/pdfser/chdser.pdf Pollack, C. V., Reilly, P. A., Eikelboom, J., Glund, S., Verhamme, P., Bernstein, R. A., Dubiel, R., Huisman, M. V., Hylek, E. M., Kamphuisen, P. W., Kreuzer, J., Levy, J. H., Sellke, F. W., Stangier, J., Steiner, T., Wang, B., Kam, C. W., & Weitz, J. I. (2015). Idarucizumab for dabigatran reversal. New England Journal of Medicine, 373, 511–520. https://doi.org/10.1056/NEJMoa1502000 Reis, J. P., Auer, R., Bancks, M. P., Goff, D. C., Jr., Lewis, C. E., Pletcher, M. J., Rana, J. S., Shikany, J. M., & Sidney, S. (2017). Cumulative lifetime marijuana use and incident cardiovascular disease in middle age: The Coronary Artery Risk Development in Young Adults (CARDIA) study. American Journal of Public Health, 107(4), 601–606. https://doi.org/10.2105/AJPH.2017.303654 Reis, S. E., Holubkov, R., Conrad Smith, A. J., Kelsey, S. F., Sharaf, B. L., Reichek, N., Rogers, W. J., Merz, C. N., Sopko, G., & Pepine, C. J. (2001). Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: Results from the NHLBI WISE study. American Heart Journal, 141, 735–741. https://doi.org/10.1067/mhj.2001.114198 Reynolds, H. R., Bairey Merz, C. N., Berry, C., Samuel, R., Saw, J., Smilowitz, N. R., de Souza, A. C. D. A., Sykes, R., Taqueti, V. R., & Wei, J. (2022). Coronary arterial function and disease in women with no obstructive coronary arteries. Circulation Research, 130(4), 529–551. https://doi.org/10.1161/circresaha .121.319892 Ridker, P. M., Hennekens, C. H., Buring, J. E., & Rifai, N. (2000). C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. New England Journal of Medicine, 342, 836–843. https:// doi.org/10.1056/NEJM200003233421202 Ridker, P. M., Rifai, N., Rose, L., Buring, J. E., & Cook, N. R. (2002). Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. New England Journal of Medicine, 327, 1557–1565. https://doi.org/10.1056/NEJMoa021993 Rosengren, A., & Hasdai, D. (2005). Acute coronary syndromes—Thrombolysis, angioplasty. In N. K. Wenger & P. Collins (Eds.), Women and heart disease (2nd ed., pp. 225–236). Taylor & Francis.

Rosenson, R. S., Hegele, R. A., Fazio, S., & Cannon, C. P. (2018). The evolving future of PCSK9 inhibitors. Journal of the American College of Cardiology, 72(3), 314–329. https://doi.org/10.1016/j.jacc.2018.04.054 Roth, E. M., & Davidson, M. H. (2018). PCSK9 inhibitors: Mechanism of action, efficacy, and safety. Reviews in Cardiovascular Medicine, 19(S1), 31–46. https://doi.org/10.3909/ricm19s1s0002 Ryan, S. M., Goldberger, A. L., Pincus, S. M., Mietus, J., & Lipsitz, L. A. (1994). Gender- and age-related differences in heart rate dynamics: Are women more complex than men? Journal of the American College of Cardiology, 24(7), 1700–1707. https://doi.org/10.1016/0735-1097(94)90177-5 Sacco, R. L., Kasner, S. E., Broderick, J. P., Caplan, L. R., Connors, J. J., Culebras, A., Elkind, M. S., George, M. G., Hamdan, A. D., Higashida, R. T., Hoh, B. L., Janis, L. S., Kase, C. S., Kleindorfer, D. O., Lee, J. M., Moseley, M. E., Peterson, E. D., Turan, T. N., Valderrama, A. L., & Vinters, H. V. (2013). An updated definition of stroke for the 21st century: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke, 44(7), 2064−2089. https://doi .org/10.1161/STR.0b013e318296aeca Saeed, A., Kampangkaew, J., & Nambi, V. (2017). Prevention of cardiovascular disease in women. Methodist DeBakey Cardiovascular Journal, 13(4), 185– 192. https://doi.org/10.14797/mdcj-13-4-185 Sanghavi, D., George, M., Bencic, S., Bleiberg, S., Alawa, N., Shaljian, M., & McClellan, M. B. (2014). Treating congestive heart failure and the role of payment reform. Brookings. http://www.brookings.edu/research/papers/2014/05/21congestive-heart-failure-hospital-aco-case-study#recent_rr Savitz, D. A., Danilack, V. A., Elston, B., & Lipkind, H. S. (2014). Pregnancyinduced hypertension and diabetes and the risk of cardiovascular disease, stroke, and diabetes hospitalization in the year following delivery. American Journal of Epidemiology, 180(1), 41−44. https://doi.org/10.1093/aje /kwu118 Scanu, A. M., Lawn, R. M., & Berg, K. (1991). Lipoprotein(a) and atherosclerosis. Annals of Internal Medicine, 111, 209–218. https://doi.org/10.7326 /0003-4819-115-3-209 Scheinman, M. M., & Huang, S. (2003). The 1998 NASPE prospective catheter ablation registry. Pacing and Clinical Electrophysiology, 23, 1020–1028. https://doi.org/10.1111/j.1540-8159.2000.tb00891.x Schnohr, P., Lange, P., Scharling, H., & Jensen, J. S. (2006). Long-term physical activity in leisure time and mortality from coronary heart disease, stroke, respiratory diseases, and cancer: The Copenhagen City Heart Study. European Journal of Cardiovascular Prevention and Rehabilitation, 13(2), 173–179. https://doi.org/10.1097/01.hjr.0000198923.80555.b7 Sciomer, S., Moscucci, F. C., Dessalvi, C. C., Deidda, M., & Mercuro, G. (2018). Gender differences in cardiology: Is it time for new guidelines? Journal of Cardiovascular Medicine, 19(12), 685–688. https://doi.org/10.2459 /JCM.0000000000000719 Sesso, H. D., Lee, I. M., Gaziano, J. M., Rexrode, K. M., Glynn, R. J., & Buring, J. E. (2001). Maternal and paternal history of myocardial infarction and risk of cardiovascular disease in men and women. Circulation, 104, 393–398. https://doi.org/10.1161/hc2901.093115 Seth, R., Moss, A. J., McNitt, S., Zareba, W., Andrews, M. L., Qi, M., Robinson,  J.  L., Goldenberg, I., Ackerman, M. J., Benhorin, J., Kaufman, E. S., Locati, E. H., Napolitano, C., Priori, S. G., Schwartz, P. J., Towbin, J. A., Vincent, G. M., & Zhang, L. (2006). Long QT syndrome and pregnancy. Journal of the American College of Cardiology, 49(10), 1092–1098. https://doi .org/10.1016/j.jacc.2006.09.054 Shipton, B., & Wahba, H. (2001). Valvular heart disease: Review and update. American Family Physician, 63, 2201–2208. https://www.aafp.org/pubs/afp /issues/2001/0601/p2201.html Shoob, H., Croft, J., Ayala, C., & Mensah, G. (2006). Valvular heart disease surveillance in the United States, 1980–2000. Journal of the American College of Cardiology, 47(Suppl. A), 276. Short, L., La, V. T., Patel, M., & Pai, R. G. (2021). Primary and secondary prevention of CAD: A review. International Journal of Angiology, 31(1), 16–26. https://doi.org/10.1055/s-0041-1729925 Shotan, A., Ostrzega, E., Mehra, A., Johnson, J. V., & Elkayam, U. (1997). Incidence of arrhythmias in normal pregnancy and relation to palpitations, dizziness, and syncope. American Journal of Cardiology, 79(8), 1061–1064. https://doi.org/10.1016/s0002-9149(97)00047-7 Shufelt, C. L., Thomson, L. E. J., Goykham, P., Agarwal, M., Mehta, P. K., Sedlak,  T., Li, N., Gill, E., Samuels, B., Azabal, B., Kar, S., Kothawade, K., Minissian, M., Slomka, P., Berman, D. S., & Bairey Merz, C. N. (2013). Cardiac magnetic resonance imaging myocardial perfusion reserve index assessment in women with microvascular coronary dysfunction and reference controls. Cardiovascular Diagnosis and Therapy, 3(3), 153–160. https://doi .org/10.3978/j.issn.2223–3652.2013.08.02 Smith, G. N., Pudwell, J., Walker, M., & Wen, S. (2012). Ten-year, thirty-year, and lifetime cardiovascular disease risk estimates following a pregnancy

complicated by preeclampsia. Journal of Obstetrics and Gynaecology Canada, 34(9), 830–835. https://doi.org/10.1016/S1701-2163(16)35381-6 Smith, J. R., Thomas, R. J., Bonikowske, A. R., Hammer, S. M., & Olson, T. P. (2022). Sex differences in cardiac rehabilitation outcomes. Circulation Research, 130(4), 552–565. https://doi.org/10.1161/circresaha.121.319894 Smith, R., Frazer, K., Hyde, A., O’Connor, L., & Davidson, P. (2018). “Heart disease never entered my head”: Women’s understanding of coronary heart disease risk factors. Journal of Clinical Nursing, 27(21–22), 3953–3967. https://doi.org /10.1111/jocn.14589 Standbridge, K., & Reyes, E. (2016). The role of pharmacological stress testing in women. Journal of Nuclear Cardiology, 23, 997–1007. https://doi.org/10.1007 /s12350-016-0602-4 Stauffer, B. D., Fullerton, C., Fleming, N., Ogola, G., Herrin, J., Stafford,  P.  M., & Ballard, D. J. (2014). Effectiveness and cost of a transitional care program for heart failure: A prospective study with concurrent controls. Archives of Internal Medicine, 171(14), 1238–1242. https://doi.org/10.1001 /archinternmed.2011.274 Stec, S., Krynski, T., Baran, J., & Kulakowski, P. (2013). “Rescue” ablation of electrical storm in arrhythmogenic right ventricular cardiomyopathy in pregnancy. BMC Cardiovascular Disorders, 13(1), Article 58. https://doi.org/10.1186 /1471-2261-13-58 Stewart, S., Hart, C. L., Hole, D. J., & McMurray, J. J. (2002). A population-based study of the long-term risks associated with atrial fibrillation: A 20-year follow-up of the Renfrew-Paisley study. American Journal of Medicine, 113, 359–364. https://doi.org/10.1016/s0002-9343(02)01236-6 Stone, N., Robinson, J. G., Lichenstein, A. H., Bairey Merz, C. N., Blum, C. B., Eckel, R. H., & Goldberg, A. C. (2014). 2013 ACC/AHA Guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation, 129, S1–S45. https://doi.org/10.1161/01.cir.0000437738.63853.7a Taneja, T., Mahnert, B. W., Passman, R., Goldberger, J., & Kadish, A. (2001). Effects of sex an age on electrocardiographic and cardiac electrophysiological properties in adults. Pacing and Clinical Electrophysiology, 24, 16–21. https://doi.org/10.1046/j.1460-9592.2001.00016.x Thanassoulis, G., Peloso, G. M., Pencina, M. J., Hoffmann, U., Fox, C. S., Cupples, L. A., Levy, D., D’Agostino, R. B., Hwang, S. J., & O’Donnell, C. J. (2012). A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: The Framingham Heart Study. Circulation. Cardiovascular Genetics, 5, 113–121. https://doi.org/10.1161 /CIRCGENETICS.111.961342 Theal, M., Sleik, K., Anand, S., Yi, Q., Yusuf, S., & Lonn, E. (2004). Prevalence of mitral valve prolapse in ethnic groups. Canadian Journal of Cardiology, 20(5), 511–515. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2560555 Timpka, S., Fraser, A., Schyman, T., Stuart, J., Åsvold, B., Mogren, I., Franks, P. W., & Rich-Edwards, J. W. (2018). The value of pregnancy complication history for 10-year cardiovascular disease risk prediction in middle-aged women. European Journal of Epidemiology, 33(10), 1003–1010. https://doi .org/10.1007/s10654-018-0429-1 Tracy, C. M., Epstein, A. E., Darbar, D., DiMarco, J. P., Dunbar, S. B, Estes N., Ferguson, T. B., Hammill, S. C., Karasik, P. E., Link, M. S., Marine,  J.  E., Schoenfeld, M. H., Shanker, A. J., Silka, M. J., Stevenson, L. W., Stevenson,  W.  G., & Varosy, P. D. (2012). 2012 ACCF/AHA/HRS focused update of the 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: A report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology, 60, 1297–1313. https://doi.org/10.1016/j .jacc.2012.07.009 Tsang, W., Alter, D. A., Wijeysundera, H. C., Zhang, T., & Ko, D. T. (2012). The impact of cardiovascular disease prevalence on women’s enrollment in landmark randomized cardiovascular trials: A systematic review. Journal of General Internal Medicine, 27, 93–98. https://doi.org/10.1007/s11606-011-1768-8 Tsao,‌‌‌‌‌ C. W., Aday, A. W., Almarzooq, Z. I., Alonso, A., Beaton, A. Z., Bittencourt, M. S., Boehme, A. K., Buxton, A. E., Carson, A. P., Commodore-Mensah, Y., Elkind, M. S. V., Evenson, K. R., Eze-Nliam, C., Ferguson, J. F., Generoso, G., Ho, J. E., Kalani, R., Khan, S. S., Kissela, B. M., . . . Martin, S. S. (2022). Heart disease and stroke statistics—2022 update: A report from the American Heart Association.  Circulation,  145(8), e153–e639. https://doi.org/10.1161 /CIR.0000000000001052 U.S. Department of Health and Human Services. (2014). The health consequences of smoking—50 years of progress: A report of the surgeon general. Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. https://www .ncbi.nlm.nih.gov/books/NBK179276 Vaccarino, V., Shah, A. J., Rooks, C., Ibeanu, I., Nye, J. A., Pimple, P., Salerno, A., D’Marco, L., Karohl, C., Bremner, J. D., & Raggi, P. (2014). Sex differences in mental stress-induced myocardial ischemia in young survivors of an acute

myocardial infarction. Psychosomatic Medicine, 76(3), 171–180. https://doi .org/10.1097/PSY.0000000000000045 Varghese, T., & Wenger, N. K. (2018). Non-ST elevation acute coronary syndrome in women and the elderly: Recent updates and stones still left unturned. F1000Research, 7, 1865. https://doi.org/10.12688/f1000research.16492.1 Vasan, R. S., & Levy, D. (2000). Defining diastolic heart failure: A call for standardized diagnostic criteria. Circulation, 101, 2118–2121. https://doi.org /10.1161/01.cir.101.17.2118 Vidal-Almela, S., Czajkowski, B., Prince, S. A., Chirico, D., Way, K. L., Pipe, A. L., & Reed, J. L. (2021). Lessons learned from community- and home-based physical activity programs: A narrative review of factors influencing women’s participation in cardiac rehabilitation.  European Journal of Preventive Cardiology, 28(7), 761–778. https://doi.org/10.1177/2047487320907748 Virani, S. S., Alonso, A., Aparicio, H. J., Benjamin, E. J., Bittencourt, M. S., Callaway, C. W., Carson, A. P., Chamberlain, A. M., Cheng, S., Delling, F. N., Elkind, M., Evenson, K. R., Ferguson, J. F., Gupta, D. K., Khan, S. S., Kissela,  B. M., Knutson, K. L., Lee, C. D., Lewis, T. T., . . . Tsao, C. W. (2021). Heart disease and stroke statistics—2021 update: A report from the American Heart Association. Circulation, 143(8), e254–e743. https://doi .org/10.1161/CIR.0000000000000950 Volgman, A. S., Manankil, M. F., Mookherjee, D., & Trohman, R. G. (2009). Women with atrial fibrillation: Greater risk, less attention. Gender Medicine, 6(3), 419–432. https://doi.org/10.1016/j.genm.2009.09.008 Wenger, N. (1999). Should women have a different risk assessment than men for the primary prevention of coronary heart disease? Journal of Women’s Health Gender-Based Medicine, 8, 465–467. https://doi.org/10.1089/jwh.1.1999.8.465 Wenger, N. K. (2002). Women, heart failure, and heart failure therapies. Circulation, 105, 1526–1528. https://doi.org/10.1161/01.cir.0000014121.94868.81 Wexler, R., Elton, T., Pleister, A., & Feldman, D. (2009). Cardiomyopathy: An overview. American Family Physician, 79(9), 778–784. Whelton, P., Carey, R., Aronow, W., Casey, D. E., Jr., Collins, K. J., Himmelfarb, C. D., DePalma, S. M., Gidding, S., Jamerson, K. A., Jones, D. W., MacLaughlin, E. J., Muntner, P., Ovbiagele, B., Smith, S. C., Jr., Spencer, C. C., Stafford, R. S., Taler, S. J., Thomas, R. J., Williams, K. A., Sr. . . . Wright, J. T., Jr. (2017). ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/ PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults. Journal of the American College of Cardiology, 71(19), e127–e248. https://doi.org/10.1016/j.jacc.2017.11.006 Wilcox, J. E., Fonarow, G. C., Zhang, Y., Albert, N. M., Curtis, A. B., Gheorghiade, M., Heywood, J. T., Mehra, M. R., O’Connor, C. M., Reynolds, D., Walsh, M. N., & Yancy, C. W. (2014). Clinical effectiveness of cardiac resynchronization and implantable cardioverter-defibrillator therapy in men and women with heart failure: Findings from IMPROVE HF. Circulation: Heart Failure, 7(1), 146– 153. https://doi.org/10.1161/CIRCHEARTFAILURE.113.000789 Wilmot, K. A., O’Flaherty, M., Capewell, S., Ford, E. S., & Vaccarino, V. (2015). Coronary heart disease mortality declines in the United States from 1979 through 2011: Evidence for stagnation in young adults, especially women. Circulation, 132(11), 997–1002. https://doi.org/10.1161 /CIRCULATIONAHA.115.015293 Wilson, W., Taubert, K. A., Gewitz, M., Lockhart, P. B., Baddour, L. M., Levison,  M., Bolger, A., Cabell, C. H., Takahashi, M., Baltimore, R. S., Newburger, J. W., Strom, B. L., Tani, L. Y., Gerber, M., Bonow, R. O., Pallasch,  T., Shulman, S. T., Rowley, A. H., Burns, J. C., . . . Durack, D. T. (2007). Prevention of infective endocarditis: Guidelines from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation, 116(15), 1736–1754. https://doi.org/10.1161 /CIRCULATIONAHA.106.183095 Wolf, P. A., Abbott R. D., & Kannel, W. B. (1991). Atrial fibrillation as an independent risk factor for stroke: The Framingham Study. Stroke, 22, 983–988. https://doi.org/10.1161/01.str.22.8.983 World Health Organization. (2021, June 11). Cardiovascular diseases (CVDs). https://www.who.int/en/news-room/fact-sheets/detail/cardiovascular​ -diseases-(cvds) Yancy, C. W., Jessup, M., Bozkurt, B., Butler, J., Casey, D. E., Jr., Drazner, M. H., Fonarow, G. C., Geraci, S. A., Horwich, T., Januzzi, J. L., Johnson, M. R., Kasper, E. K., Levy, W. C., Masoudi, F. A., McBride, P. E., McMurray, J. J., Mitchell, J. E., Peterson, P. N., Riegel, B., . . . Wilkoff, B. L. (2013). 2013 ACCF/AHA guideline for the management of heart failure: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation, 128, e240–e327. https://doi .org/10.1161/CIR.0b013e31829e8776 Yoon, S., Whisenant, B. K., Bleiziffer, S., Delgado, V., Schofer, N., Eschenbach, L., Fujita, B., Sharma, R., Ancona, M., Yzeiraj, E., Cannata, S., Barker, C., Davies, J. E., Frangieh, A. H., Deuschl, F., Podlesnikar, T., Asami, M., Dhoble, A.,

Chyou, A., . . . Makkar, R. R. (2017). Transcatheter mitral valve replacement for degenerated bioprosthetic valves and failed annuloplasty rings. Journal of the American College of Cardiology, 70(9), 1121–1131. https://doi.org/10.1016/j .jacc.2017.07.714 Young, J. B., & Mills, R. M. (2001). Clinical management of heart failure. Professional Communications. Young, W., Gofman, J. W., Tandy, R., Malamud, N., & Waters, E. S. G. (1960). The quantitation of atherosclerosis III: The extent of correlation of degrees of atherosclerosis within and between the coronary and cerebral vascular beds. American Journal of Cardiology, 6(2), 300–308. https://doi .org/10.1016/0002–9149(60)90319–2 Yusuf, S., & Camm, A. J. (2005). Deciphering the sinus tachycardias. Clinical Cardiology, 28(6), 267–276. https://doi.org/10.1002/clc.4960280603 Yusuf, S., Hawken, S., Ôunpuu, S., Dans, T., Avezum, A., Lanas, F., McQueen, M., Budaj, A., Pais, P., Varigos, J., & Lisheng, L. (2004). Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): Case-control study. Lancet, 364(9438), 937–952. https://doi.org/10.1016/S0140–6736(04)17018-9 Zeitler, E. P., Poole, J. E., Albert, C. M., Al-Khatib, S., Ali-Ahmed, F., Birgersdotter-Green, U., Cha, Y. M., Chung, M. K., Curtis, A. B., Hurwitz,  J.  L., Lampert, R., Sandhu, R. K., Shaik, F., Sullivan, E., Tamirisa,

K. P., Santos Volgman, A., Wright, J. M., & Russo, A. M. (2022). Arrhythmias in female patients: Incidence, presentation and management. Circulation Research, 130(4), 474–495. https://doi.org/10.1161 /CIRCRESAHA.121.319893 Zhang, B., Li, M., Kang, Y., Xing, L., & Zhang, Y. (2020). Comparison of different transcatheter interventions for treatment of mitral regurgitation: A protocol for a network meta-analysis. Medicine (Baltimore), 99(50), e23623. https:// doi.org/10.1097/MD.0000000000023623 Zipes, D. P., Camm, A. J., Borggrefe, M., Buxton, A., Chaitman, B., Fromer, M., Gregoratos, G., Klein, G., Myerburg, R. J., Quinones, M. A., Roden, D. M., Silka, M. J., Tracy, C., Smith, S. C., Jacobs, A. K., Adams, C. D., Anderson, J. L., Hunt, S. A., Halperin, J. L., . . . Antman, E. M. (2006). ACC/AHA/ESC guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death—Executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients with Ventricular Arrhythmia and the Prevention of Sudden Cardiac Death). Journal of the American College of Cardiology, 48(5), 1064–1108. https://doi.org/10.1016/j.jacc.2006.07.010

Chapter

44

Endocrine-Related Problems*

Traci Sharkey-Wells

The endocrine system and nervous system control all physiologic processes in the body. The endocrine system acts as a chemical communication network that coordinates physiologic function through hormones that are released into the bloodstream from specific cells within ductless glands. Like other communication systems, the endocrine system is composed of transmitters (hormone-producing cells), signals (hormones), and receptors. Once in the circulation and extracellular fluid, hormones affect the function of target tissues. Hormonal mechanisms of action are generally described by the effects they have on target cells. Table 44.1 depicts the effects of common endocrine disorders on target organs. Endocrine hormones are secreted into the bloodstream and bind to distant target cells. Paracrine hormones are those that exert an effect on cells of the organ from which they are released. Autocrine hormones affect the same cells from which they are produced. Hormones can be peptides or proteins (e.g., prolactin, ACTH, insulin); steroids that are derived from cholesterol (e.g., sex hormones, adrenal steroids); amino acid derivatives (e.g., epinephrine, norepinephrine, thyroid hormones); or fatty acid derivatives (e.g., prostaglandins, leukotrienes). All hormones bind selectively to receptors either in or on the surface of target cells. Intracellular receptors interact with hormones that modulate genetic function (e.g., corticosteroids, thyroid hormone). Hormones that bind with receptors on the target cell surface control enzyme activity or regulate ion channels (e.g., growth hormone, thyrotropin-releasing hormone). Throughout this chapter the terms woman and women are used to refer to cisgender women and those born with a uterus, ovaries, and fallopian tubes. Due to limited research about endocrinologic health problems among nonbinary and transgender persons, the language used reflects the research available, generally done with women. Caring for transgender women and transgender men is not different and the use of gender-affirming hormone therapy (GAHT) is not known to change treatment guidelines.

HYPOTHALAMIC–PITUITARY RELATIONSHIPS Endocrine organ functions within the body are modulated by pituitary hormones. An exception is secretion of insulin by the pancreas, which is primarily controlled by blood glucose level. Pituitary hormone secretion is controlled by the hypothalamus. The hypothalamic–pituitary axis is the feedback system that controls interaction between the hypothalamus and pituitary gland. Input from all areas of the central nervous system is received by the hypothalamus to feed information back to the pituitary, which then releases specific hormones that stimulate endocrine glands throughout the body. The hypothalamus detects changes in circulating levels of hormones produced by these endocrine glands and either increases or decreases its stimulation of the pituitary to maintain homeostasis.

THYROID DISORDERS The thyroid gland is one of the largest endocrine glands. It secretes thyroid hormone in response to signals received from the hypothalamus through the pituitary and functions through a negative feedback mechanism (Figure 44.1). Patients may present with signs of either thyroid excess or deficiency.

Hypothyroidism DEFINITION AND SCOPE

Hypothyroidism results when the thyroid gland is unable to produce sufficient levels of thyroid hormone (triiodothyronine [T3] and thyroxine [T4]). Primary hypothyroidism

*This chapter is a revision of the chapter that appeared in the second edition of this textbook, authored by Adrienne Berarducci, and we thank her for her original contribution.

841

842  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

TABLE 44.1  Clinical Manifestations of Endocrine Disorders SIGNS AND SYMPTOMS

Anterior pituitary

POSSIBLE DISORDER

Anemia

Adrenal problems, thyroid problems

Anorexia/nausea

Adrenal problems, diabetes (DKA and HHS), thyroid disorders

Menstrual changes

Adrenal problems, PCOS, thyroid conditions, menopause, hyperprolactinemia

Nervousness

Adrenal and thyroid problems

Weakness/ fatigue

Common with multiple endocrine problems BOWEL CHANGES

Constipation

Diabetic neuropathy, hypothyroidism

Hyperdefecation

Hyperthyroidism (frequent/increased bowel movements) HAIR CHANGES

Hirsutism

PCOS, Cushing syndrome

Hair loss

Hypothyroidism THERMAL CHANGES

Fever

Adrenal and thyroid problems

Decreased temperature

Diabetes, thyroid problems WEIGHT CHANGES

weight loss

Adrenal problems (AI), thyroid problems (hyperthyroidism), diabetes

weight gain

Cushing syndrome, thyroid problems (hypothyroidism), PCOS

AI, adrenal insufficiency; DKA, diabetic ketoacidosis; HHS, hyperosmolar hyperglycemia; PCOS, polycystic ovary syndrome. Source: Data from Gardner, D., & Shoback, D. (2011). Greenspan’s basic and clinical endocrinology (9th ed.). Lange Medical Books/McGraw-Hill.

is relatively common, with incidence increasing with age. About 4.6% of the United States population 12 years of age and older have hypothyroidism (Lee, 2015). The exact prevalence varies by causative factors and is influenced by both geographic location and environmental factors. The incidence of Hashimoto thyroiditis ranges from 0.3 to 5 per 1,000 and is 10 to 20 times more common in women than in men (Gardner & Shoback, 2011). Subclinical hypothyroidism is present in about 2% of the adult population and progresses to overt hypothyroidism in about 5% to 18% of patients (Baskin et al., 2002).

Increased metabolic rate Tissues TSH in blood

Inhibition

Stimulation

Thyroid gland

Stimulation

Thyroid hormones in blood

FIGURE 44.1  Thyroid negative feedback system. TSH, thyroid-stimulating hormone.

due to loss of functional thyroid tissue or a defect in hormone synthesis. It may also occur in response to pathology of the pituitary gland or hypothalamus. Autoimmune thyroid disease (Hashimoto thyroiditis) is the most common cause of hypothyroidism in the United States and other geographic areas where iodine intake is adequate. Worldwide, however, iodine deficiency remains the leading cause. Iatrogenic hypothyroidism can occur postpartum, following partial or complete surgical removal of the thyroid gland, or from radioactive iodine (RAI) ablation, or it may be drug-induced (e.g., lithium, alpha interferon, amiodarone, iodine). Secondary hypothyroidism is rare and occurs with disorders of the pituitary and hypothalamus that cause alterations in thyroid-stimulating hormone (TSH) production (e.g., pituitary adenoma). Congenital hypothyroidism occurs in infants born with a thyroid that is not fully developed or does not function properly. If untreated, congenital hypothyroidism can lead to mental dysfunction and growth failure. Newborns in the United States are generally screened for hypothyroidism as early detection and treatment can prevent these sequelae (Park & Chatterjee, 2005). RISK FACTORS

Numerous risk factors are associated with hypothyroidism (Table 44.2). They include previous history of a thyroid disorder (e.g., goiter); partial or total thyroidectomy; radiation to the thyroid, neck, or chest; family history of thyroid disease; history of other autoimmune diseases (e.g., Sjögren syndrome, rheumatoid arthritis, lupus); pernicious anemia; type 1 diabetes; Turner syndrome; age greater than 60 years; or having been pregnant or delivered a baby within the past 6 months (Golden et al., 2009).

ETIOLOGY

SYMPTOMS

Hypothyroidism is a common endocrine disorder resulting from thyroid hormone deficiency. Most commonly, this is

Clinical manifestations of hypothyroidism result from reduced metabolic activity and metabolic rate (Bhuvana

Chapter 44  Endocrine-Related Problems 843

TABLE 44.2  Risk Factors for Primary and Secondary Hypothyroidism TYPE OF HYPOTHYROIDISM

SELECT CAUSES AND RISK FACTORS

Primary

Older than 60 years Female History of hyperthyroidism or goiter (involving treatment with radioactive iodine) Family history of hypothyroidism History of radiation therapy to neck or chest Surgical removal of partial/complete thyroid Radioactive iodine ablation

Iatrogenic

Secondary

Congenital

Use of lithium Use of amiodarone Use of exogenous iodine Use of alpha interferon Interleukin 2, tyrosine kinase inhibitors, and checkpoint inhibitor immunotherapy (e.g., ipilimumab, pembrolizumab, and nivolumab) Pituitary adenoma Pituitary ablative therapy Peripheral thyroid hormone resistance Immature/underdeveloped thyroid gland

Source: Data from Gardner, D., & Shoback, D. (2011). Greenspan’s basic and clinical endocrinology (9th ed.). Lange Medical Books/McGraw Hill; Park, S. M., & Chatterjee, V. K. (2005). Genetics of congenital hypothyroidism. Journal of Medical Genetics, 42(5), 379–389. https://doi.org/10.1136/jmg.2004.024158

et al., 2002). Thyroid hormone deficiency can cause multiple symptoms that can vary greatly from person to person and affect several systems: central nervous, cardiovascular, musculoskeletal, and reproductive. Common symptoms include fatigue; weight gain; a puffy face and/or eyelids; dull facial expression; cold intolerance; joint and muscle pain; constipation; dry skin; dry, thinning hair and eyebrows, decreased sweating; heavy or irregular menstrual periods and impaired fertility; hoarseness; slow speech; blurred vision; decreased hearing; carpal tunnel syndrome; depression; confusion; and bradycardia (Box 44.1). However, hypothyroidism develops slowly, and many patients do not notice symptoms. Symptoms more specific to Hashimoto disease are painless thyroid enlargement, subjective fullness in the throat, and exhaustion and transient neck pain with or without sore throat. Hypothyroidism is a contributor to hypercholesterolemia; therefore, individuals with hypercholesterolemia should be screened for hypothyroidism. In rare instances, severe, untreated hypothyroidism may lead to myxedema, an extreme form of hypothyroidism that results in altered mental status, hypothermia, bradycardia, hypercarbia, and hyponatremia. Ascites, pericardial effusion, and cardiomegaly may be present and can lead to cardiogenic shock. This life-threatening condition occurs most commonly in individuals with hypothyroidism in whom the condition has not been diagnosed and who are exposed to physical stress, such

Box 44.1  Common Symptoms Associated With Hypothyroidism Fatigue Weight gain Puffy face and/or eyelids Dull facial expression Cold intolerance Joint and muscle pain Constipation Dry skin and hair Decreased sweating Heavy or irregular menstrual periods Impaired fertility Hoarseness and/or slow speech Blurred vision Decreased hearing Carpal tunnel syndrome Depression Confusion Bradycardia

as hypothermia, infection, myocardial infarction, stroke, or medical intervention (e.g., surgery or hypnotic drugs). Myxedema requires immediate hospitalization and intensive treatment. EVALUATION/ASSESSMENT History

Symptoms of hypothyroidism are generally very subtle and gradual and may be mistaken for symptoms of depression and other illnesses. With suspected hypothyroidism and health maintenance encounters, providers need to take a detailed, deliberate approach in evaluating risk factors and symptoms as the obscure presentation may make them unnoticeable in some patients. Physical Examination

Evaluation of the patient with hypothyroidism may reveal subtle changes, and detection requires careful physical assessment. Physical signs may include weight gain, slow speech and movements, xerosis, pallor, coarse and brittle hair, alopecia of varying degrees and patterns, dull and/or coarse facial expression, periorbital puffiness, macroglossia, simple or nodular goiter, bradycardia, hoarseness, edema, decreased systolic and increased diastolic blood pressure, and hyporeflexia with delayed relaxation phase. Other clinical manifestations can be related to different causes of hypothyroidism

844  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

such as pituitary enlargement or adenoma and with diffuse or multinodular goiter (‌‌‌‌‌‌‌‌‌‌‌Garber et al., 2012).

Box 44.2  Patients With Hypothyroidism Who May Require Referral to Endocrinology

DIFFERENTIAL DIAGNOSIS

Differential diagnosis can be extensive as many of the symptoms of hypothyroidism are nonspecific. Special consideration should be given to the possible presence of ischemic heart disease, liver abnormalities, and depression. Patients presenting with menstrual irregularity and/or infertility may also have underlying metabolic disease. Other possible causes of the symptoms include eating disorders, HIV infection, sepsis, diabetes, and renal failure (Gardner & Shoback, 2011).

Patients younger than 18 years Patients who are unresponsive to therapy Patients who are pregnant Patients with cardiovascular disease Patients with other endocrine disorders Patients with thyroid nodules

DIAGNOSTIC STUDIES

Third-generation TSH serum assays are considered the most sensitive screening tool for primary hypothyroidism. In the presence of TSH levels elevated above the reference range, measurement of serum-free T4 or the free thyroxine index (FTI), which serves as a surrogate of the free hormone level, should be obtained. Measurement of T3 is not recommended. Elevated TSH with decreased T4 or FTI indicates hypothyroidism. Elevated TSH (usually 4.5–10.0 mIU/L) with normal free T4 or FTI is considered mild disease or subclinical hypothyroidism (Garber et  al., 2012). Symptoms of subclinical hypothyroidism are sometimes present after a patient has been acutely ill. In this situation it is referred to as euthyroid sick syndrome and usually resolves spontaneously without treatment in 6 weeks. The complete blood count and metabolic profile may also exhibit abnormalities in patients with hypothyroidism, such as anemia, dilutional hyponatremia, hyperlipidemia, reversible increased creatinine, and elevated transaminases and creatinine kinase (Kreisman & Hennessey, 1999). Although no universal screening guidelines exist for thyroid disease in adults, the American Thyroid Association (ATA) recommends screening at age 35 years and every 5 years thereafter, with closer attention to high-risk individuals, such as pregnant persons, persons older than 60 years, individuals with type 1 diabetes or other autoimmune disorders, and those with a history of neck irradiation (Ladenson et al., 2000).

TABLE 44.3  Clinical Findings in Hypothyroidism SYSTEM

General

SIGNS

Fatigue/lethargy

Periorbital edema

Weakness

Pallor

Swelling of thyroid

Goiter

Menorrhagia

Galactorrhea

Cold intolerance

Hypothermia

Weight gain

Obesity

Psychiatric

Depression

Depression

Musculoskeletal

Arthralgia, myalgia

Skin

Decreased perspiration

Brittle nails

Hair loss

Reduced skin turgor, alopecia/coarse hair, carotenemia

Constipation

Megacolon

Endocrine

Metabolic

Gastrointestinal

Decreased appetite

TREATMENT/MANAGEMENT OF PRIMARY HYPOTHYROIDISM

The goal of hypothyroidism treatment is to restore a state of euthyroidism, accomplished with thyroid replacement therapy. As with all treatment, it should be tailored to the individual. Education should provide an understanding of the disease and its treatment. Referral to an endocrinologist is appropriate for those in whom euthyroidism is difficult to achieve (Box 44.2). Self-Management Measures

Self-management measures are most often geared toward managing the many symptoms that patients can experience with hypothyroidism (Table 44.3). Patients who experience significant fatigue need to be cautioned to pace their activities and achieve adequate rest, especially until a euthyroid state is achieved. Measures for managing constipation may include increasing fluids, increasing dietary fiber, and using stool softeners.

SYMPTOMS

Respiratory

Snoring

Hypoventilation, sleep apnea

Cardiovascular‌‌‌‌‌‌

Dyspnea

Hypertension (diastolic), pericardial effusion, cardiomegaly/CHF, bradycardia

Nervous system

Paresthesia

Bradykinesia

Numbness

Distal sensory loss

Unsteadiness

Ataxia

Reduced mentation

Dementia, hyporeflexia, pseudomyotonia, visual disturbancesa

Findings in secondary hypothyroidism. CHF, congestive heart failure. Source: Reprinted with permission from Guha, B., Krishnaswamy, G., & Peiris, A. (2002). The diagnosis and management of hypothyroidism. Southern Medical Journal, 95(5), 475–480. a

Chapter 44  Endocrine-Related Problems 845

Complementary and Alternative Medicine

The extant scientific literature does not recommend complementary and alternative medicine (CAM) modalities specifically for hypothyroidism. Some patients use CAM therapies to manage symptoms of the disorder such as fatigue, weight changes, and hair and skin changes; however, their use should be discussed with their clinician. Pharmacotherapeutics

Updated guidelines from Jonklaas et al. (2014) indicate that levothyroxine (LT4) as monotherapy remains the treatment of choice for hypothyroidism. LT4 produces stable levels of both T3 and T4. The dosage is approximately 1.6 mcg/kg/day, taken every morning on an empty stomach. When initiating LT4, the patient’s weight, lean body mass, pregnancy status, etiology of thyroid disorder, degree of TSH elevation, age, and comorbidities, including the presence of cardiac disease, are considered. Patients should avoid taking biotin 48 hours prior to having serum T4, T3, and TSH testing due to interference in the assay causing false elevations. Patients who are ingesting 5 to 10 mg of biotin (marketed over the counter to prevent hair loss) can have spurious results in these assays. Biotin may cause falsely low values in assays used to measure TSH, and falsely high values in competitive binding assays used to measure free T4, T3, free T3, and TSH receptor-binding inhibitor immunoglobulin. Clinical benefits of LT4 replacement can begin to be appreciated in as little as 3 to 5 days and generally plateau at 6 weeks. Until TSH levels are within target range (1.0 to 2.0 U/ mL), LT4 dosing changes are made every 6 to 8 weeks. Serum TSH levels within the normal reference range commonly require several months of monitoring and dose titration. Dosing aspects of LT4 treatment are depicted in Table 44.4. Once the LT4 dose is stabilized, annual monitoring of serum TSH and clinical evaluation are maintained. Overtreatment must be monitored, and dose reductions initiated promptly. Patients need to be aware of symptoms of overtreatment to avoid potential health threats, such as tachycardia, TABLE 44.4  Dosing Aspects of Levothyroxine Treatment POPULATION

DOSING OF LEVOTHYROXINE

Young, healthy patients

Start at anticipated full replacement dose

Older patients

One fourth to one half of the anticipated full replacement dose and titrate slowly after no less than 4 to 6 weeks

Known ischemic heart disease

One fourth to one half of the anticipated full replacement dose and titrate slowly after no less than 4 to 6 weeks

Mild to moderate hypothyroidism

Start at 50 to 75 mcg daily

Source: Data from Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman K. D., Cappola, A. R., Celi, F., Cooper, D. S., Kim, B. W., Peeters, R. P., Rosenthal, M. S., & Sawka, A. M. (2014). Guidelines for the treatment of hypothyroidism: Prepared by the American Thyroid Association Task Force on THyroid Hormone Replacement. Thyroid, 24(12), 1670–1751. https://doi.org/10.1089/thy.2014.0028

palpitations, angina, increased sweating, nervousness, atrial fibrillation, increased nervousness, fatigue, headache, irritability, insomnia, and tremors. Excessive LT4 can also cause bone loss over time. Consideration should be given to causes other than hypothyroidism in patients who remain symptomatic despite normalization of their TSH level. This may indicate dysfunctional conversion of T4 to T3 in the brain. Combination LT4/ liothyronine (LT3) therapy may benefit these individuals; however, this is rarely observed. Considerations for Special and Minoritized Populations

The bioequivalence of various brands of LT4 can also be problematic. Because bioequivalence has been based on total T4 measurements instead of TSH levels, bioequivalence does not equal therapeutic equivalence. Patients should be maintained on a consistent brand of LT4. If the brand is changed for any reason, then TSH levels should be repeated in 4 to 6 weeks and the dose adjusted as needed to maintain euthyroidism (Jonklaas et al., 2014). Several conditions may require special dosing and monitoring of therapy for hypothyroidism. If dosage of LT4 is much higher than anticipated to maintain normal range TSH, consider evaluation for gastrointestinal disorders that may interfere with absorption. These include disorders such as Helicobacter pylori–related peptic ulcer disease and gastritis, gastroparesis, and celiac disease. Significant weight changes should also prompt closer patient monitoring. TSH and LT4 monitoring requirements may increase when initiating or discontinuing estrogen because exogenous estrogen may affect LT4 requirements. Numerous other pharmacotherapeutics can interfere with thyroxine metabolism and require closer monitoring of symptoms and TSH levels upon initiation, maintenance, and discontinuation, such as calcium supplements, phenytoin, phenobarbital, sertraline, carbamazepine‌‌‌‌‌, rifampin, proton pump inhibitors, tyrosine kinase inhibitors, bile acid sequestrants, selective estrogen receptor modulators, and cytoprotective agents. Untreated hypothyroidism in pregnancy increases maternal and fetal risks, such as hypertension, preeclampsia, anemia, cardiac dysfunction, spontaneous abortion, low birth weight, and fetal death (see Chapter 38, High-Risk Childbearing). Even mild, untreated maternal hypothyroidism has been associated with cognitive dysfunction in the child. Thyroid hormone demand increases by 30% to 50% during pregnancy and will likely require an increased dose of LT4. LT4 has been assigned pregnancy category A by the Food and Drug Administration and replacement, when warranted, should be maintained during pregnancy. A naturally occurring hormone, it is normally found in both maternal and fetal circulation. LT4 is excreted into human milk in small amounts. In replacement doses, it is not expected to cause adverse effects in the nursing infant. The manufacturer recommends that caution be used when administering LT4 to nursing persons. However, adequate replacement doses of LT4 are needed to maintain normal lactation. Current recommendations indicate that pregnant persons should receive LT4 replacement therapy with the dose titrated to achieve a TSH concentration within the trimester-specific

846  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

reference range. During the first half of pregnancy, serum TSH should be monitored every 4 months with LT4 dosing adjustments to maintain the trimester-specific TSH range. TSH should be reevaluated during the second half of pregnancy. For patients already taking LT4 for hypothyroidism, two additional doses of their current LT4 dose per week with several days’ separation may be started as soon as pregnancy is confirmed (Stagnaro-Green et al., 2011). Older adults with new-onset hypothyroidism should start at a dose of 25 to 50 mcg daily that is increased slowly by 12.5 to 25 mcg every 6 to 8 weeks. Reference ranges of serum TSH levels are higher in older populations (e.g., above 65 years), and so higher serum TSH targets may be appropriate for older people (Jonklaas et al., 2014). TREATMENT/MANAGEMENT OF SUBCLINICAL HYPOTHYROIDISM

Significant controversy persists regarding the treatment of subclinical hypothyroidism (Cooper & Biondi, 2012). Studies have suggested that treatment of these patients reduces symptoms, prevents progression to overt hypothyroidism, and may be cardioprotective. However, an evidence-based consensus statement issued by the AACE, the ATA, and the Endocrine Society (Gharib et al., 2004) recommends against routine treatment if the TSH is between 4.5 and 10 mU/L. In a separate statement, they recommended measuring thyroid antibodies in the presence of elevated TSH without symptoms. If antibodies are present and the TSH is above 5 mU/L, treatment should be considered. Although patients are usually asymptomatic, there are potential associated risks. Thus, these patients should be followed every 3 months until they are stable, as evidenced by both clinical and laboratory evaluation. Individualized care was recommended in both statements (Gharib et al., 2005).

Hyperthyroidism DEFINITION AND SCOPE

Hyperthyroidism is characterized by overproduction of T3 and/or T4. Symptoms develop in response to the effects of the excessive circulating thyroid hormone levels. The prevalence in the general population is low with peak incidence between the ages of 20 to 40 years (Baskin et al., 2002; Gardner & Shoback, 2011). Subclinical hyperthyroidism affects about 2% of the adult population and is thought to be related to oversensitivity of the pituitary gland in responding to minor elevations in T3 and T4. The clinical significance relates to progression to overt hyperthyroidism and possible effects on the cardiac and skeletal systems. In the older patient with subclinical hyperthyroidism, the risk of atrial fibrillation is increased threefold (Baskin et al., 2002; Gardner & Shoback, 2011). ETIOLOGY

The most common causes include Graves disease (an autoimmune disorder, accounts for 70% to 80% of cases), toxic multinodular goiter, and toxic adenoma. A variety of other disorders can also cause hyperthyroidism (Box 44.3). More

Box 44.3  Causes of Hyperthyroidism Graves disease (diffuse toxic goiter) Plummer disease (toxic multinodular goiter) Toxic adenoma Subacute thyroiditis (s/p viral infection) Subclinical thyroiditis Excessive pituitary production of thyroid-stimulating hormone Taking large amounts of tetraiodothyronine (through dietary supplements or medication) Tumors of the ovaries Tumors of the thyroid or pituitary gland Drugs: amiodarone, potassium iodide, intravenous contrast agent Source: Data from Gardner, D., & Shoback, D. (2011). Greenspan’s basic and clinical endocrinology (9th ed.). Lange Medical Books/McGraw-Hill.

common in women than men, hyperthyroidism tends to run in families. SYMPTOMS

Many of the presenting symptoms of hyperthyroidism are nonspecific; fatigue, nervousness, irritability, and heat intolerance with increased sweating are found in 80% to 96% of patients. Other symptoms may include weakness, weight loss, dyspnea, depression, alteration in appetite, menstrual irregularities, infertility, and increasing frequency of and changes in stool. EVALUATION/ASSESSMENT

Physical examination includes a thorough assessment of the neck and thyroid gland. About 90% of patients with Graves disease who are younger than 50 years will have a firm, diffuse goiter, and about 75% will have a bruit noted with auscultation. Any thyroid nodule should be evaluated (see discussion under Thyroid Nodule). Thyroid tenderness may indicate the presence of thyroiditis and is not usually seen in uncomplicated Graves disease (Gharib et al., 2010; Gardner & Shoback, 2011). On general inspection, the hair may be fine and silky. Nails may develop ridges and plates may have an irregular separation from the bed (onycholysis). Skin may be hyperpigmented, especially over the extensor surfaces of the elbows, knees, and small joints. Tachycardia (resting heart rate over 90 beats per minute) is found in about 96% of patients with hyperthyroidism and about 20% have atrial fibrillation, either of which may be experienced subjectively as palpitations. Increased cardiac output may be reflected by wide pulse pressure when measuring the blood pressure, and murmurs are common as well. A neurologic exam may reveal hand tremors, a fine tongue tremor, and/or hyperactive reflexes. If tremor is not readily seen, a piece of paper

Chapter 44  Endocrine-Related Problems 847

is placed on the outstretched hand; the tremors can then be seen easily (Bahn et al., 2011; Hueston, 2011; Ladenson, 2010; Mandel et al., 2011). A detailed eye examination is needed as hyperthyroidism is associated with several ocular abnormalities. The patient should be evaluated for lid lag, stare, periorbital edema, and proptosis. Ophthalmic involvement in hyperthyroidism is due to lymphocyte and fluid infiltration into the periorbital tissues, causing an inflammatory response. This compresses the optic nerve and may lead to loss of vision (Hueston, 2011; Ladenson, 2010).

referred to an endocrinologist. If surgery is the best treatment option, referral to a surgeon is warranted. Thyroid storm (Box 44.4) is a medical emergency and requires immediate referral (Bahn et al., 2011; Gardner & Shoback, 2011).

DIFFERENTIAL DIAGNOSIS

Complementary and Alternative Medicine

The main considerations in the differential diagnosis are TSH-induced hyperthyroidism, which can be caused by a pituitary adenoma secreting TSH or a problem in the feedback mechanism; euthyroid hyperthyroxinemia, caused by serum thyroid hormone-binding protein abnormalities; and low serum levels of TSH without hyperthyroidism, which may be seen in patients recovering from hyperthyroidism, and with central hypothyroidism. Of note, suppressed or low TSH can also be seen with recent corticosteroid use such as cortisone injections, prednisone, decadron, or inhaled corticosteroids. Typically, these patients have normal free T4 and free T3 and therefore do not actually have hyperthyroidism.

Chinese herbal medicines are sometimes used instead of or in combination with antithyroid medications. These medicines generally include a combination of multiple plant and root products. The herbs are intended to weaken thyroxine’s biological effects, reduce transformation of T4 to T3, and modulate the immune system or sympathetic nerve function (Chen, 2008). Although demonstrated to improve symptoms and reduce relapse rates and adverse effects (e.g., agranulocytosis) in one meta-analysis, strong evidence supporting the use of Chinese herbs for hyperthyroidism is lacking (Zeng et al., 2007).

DIAGNOSTIC STUDIES

Surgical management may be the treatment of choice for patients with a very enlarged gland or multinodular goiter, especially in the presence of dysphagia. Surgery is the treatment of choice for those with Graves ophthalmopathy as 131 I often worsens the ophthalmopathy. Patients are treated first with antithyroid hormones to reach a euthyroid state.

As with hypothyroidism, laboratory evaluation of hyperthyroidism begins with TSH levels. Hyperthyroidism is suggested when TSH levels are lower than normal, Free T3 and T4 levels should then be measured to aid in diagnosis. Findings indicative of hyperthyroidism would show suppressed TSH with elevated free T4 and/or free T3. Thyroid-stimulating immunoglobulin (TSI) and TSH receptor antibodies are typically ordered to differentiate between the diagnosis of Graves disease and thyroiditis or toxic nodule. Ultrasonography (US) is sometimes performed to measure the size of the entire thyroid gland, as well as any masses within it. US may also distinguish if the mass is solid or cystic. CT or MRI of the head is done if a pituitary tumor is suspected. Thyroid radioiodine uptake and scan can help determine the cause. Subclinical hyperthyroidism is identified in the instance of low TSH with normal T3 and T4 levels in asymptomatic patients (Bahn et al., 2011). TREATMENT/MANAGEMENT OF OVERT CLINICAL HYPERTHYROIDISM

Once diagnosed, three treatment options are available: surgery, antithyroid medications, and RAI. Treatment is determined based on the etiology and the patient’s preference. Each option carries its own set of benefits and risks (Gardner & Shoback, 2011). Several presentations require referral. Patients with ocular involvement in Graves disease require referral to an ophthalmologist for evaluation and long-term follow-up. Urgent referral is needed for those with eye pain, injected sclerae, or a change in vision. Radioactive sodium iodine-131 (131I) may exacerbate Graves ophthalmopathy; these patients should be

Self-Management Measures

Self-management measures are designed to reduce symptoms. Patients should avoid caffeine and other stimulants as these may make palpitations and tremors worse. Once therapy has been initiated, careful balancing of diet and exercise is needed as weight gain is common.

Surgery

Box 44.4  Signs of Thyroid Storm Increased temperature up to 104°F Unexplained jaundice Tachycardia CHF Atrial fibrillation CNS Symptoms Agitation Delirium Seizure/coma GI Symptoms Nausea Vomiting Diarrhea CHF, congestive heart failure; CNS, central nervous system; GI, gastrointestinal. Source: Data from Gardner, D., & Shoback, D. (2011). Greenspan’s basic and clinical endocrinology (9th ed.). Lange Medical Books/McGraw-Hill.

848  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

Potential complications include hypoparathyroidism and vocal cord injury and occur in about 1% of patients. Near total thyroidectomy is usually done and will induce hypothyroidism, requiring lifetime thyroid replacement. If too much of the thyroid gland is left behind, Graves disease can recur (Bahn et al., 2011). Pharmacotherapeutics Antithyroid Medications

Antithyroid medications are given to lower the overall thyroid level by suppressing production of thyroid hormone. The most common medications used in managing hyperthyroidism are methimazole (MMI) and propylthiouracil (PTU). The starting dose depends on the severity of the hyperthyroidism. Prior to initiating antithyroid drug therapy, a baseline complete blood count, including white blood cell count with differential, and a liver profile including bilirubin and transaminases should be evaluated. Currently, it is recommended that MMI be used for the treatment of Graves disease in most patients. PTU is not recommended for initial use except during the first trimester of pregnancy (when it is preferred), in the presence of thyroid storm, and in patients with minor reactions to MMI who refuse RAI therapy or surgery. At the initiation of MMI therapy, 10 to 20 mg daily will generally restore euthyroidism, following which the dose can be titrated to a maintenance level of 5 to 10 mg daily. Risks of major side effects are lower with MMI as compared with PTU, and MMI can be given as a single daily dose. Due to a shorter duration of action, PTU is generally administered two or three times daily. Depending on the severity of hyperthyroidism, starting doses generally range between 50 and 150 mg three times daily. Once clinical findings and thyroid function tests indicate euthyroid state, reduction of PTU dose to 50 mg two to three times daily is usually sufficient (Bahn et al., 2011). Patients need to be monitored for adverse reactions. The most common side effect is a transient skin rash that can be managed with antihistamines. Although rare, agranulocytosis is a serious side effect requiring discontinuation of the medication. Symptoms of agranulocytosis include sore throat, fever, painful mouth ulcers, anal ulcerations, depressed immune response, and increased bacterial infections, and should be evaluated with complete blood count and red blood cell indices. The patient should stop the medication and call their clinician if these symptoms develop (Bahn et al., 2011). Radioactive Iodine Therapy

The goal of RAI (131I) treatment is to ablate the thyroid tissue. Because it works quickly, RAI tends to minimize the morbidity associated with hyperthyroidism. As with surgery, pretreatment with antithyroid medications is frequently used to achieve a euthyroid state, especially in older patients. Because most patients (80%) become hypothyroid following 131I treatment, thyroid replacement for life is generally needed. A pregnancy test must be obtained within 48 hours prior to treatment in any female of childbearing age who is to be treated with RAI; verification of a negative pregnancy test prior to RAI is mandatory. Patients choosing 131I must be

counseled to avoid close contact with children younger than 8 years of age and with pregnant persons. Breastfeeding is contraindicated for at least 2 weeks after receiving treatment (Bahn et al., 2011; Gardner & Shoback, 2011). Beta-blockers may be used with 131I as adjunctive therapy to provide symptomatic relief and help stabilize the patient. Nondihydropyridine calcium channel blockers are helpful if the patient cannot tolerate beta-blockers due to side effects such as lightheadedness or drowsiness. These medications are discontinued as soon as the patient is rendered euthyroid. Considerations for Special and Minoritized Populations

Pregnancy presents some special concerns. 131I is contraindicated in both pregnancy and breastfeeding. Antithyroid medications may cross the placenta and oversuppression can adversely affect the fetus. PTU is the medication of choice and is given in the lowest possible dose to maintain euthyroidism, which is important to both maternal and fetal well-being. The need for antithyroid medications usually decreases during pregnancy and so close monitoring of TSH, T3, and T4 is advised. Hyperthyroidism in pregnant persons is usually managed in collaboration with an endocrinologist. TREATMENT/MANAGEMENT OF SUBCLINICAL HYPOTHYROIDISM

Management of subclinical hyperthyroidism is a widely debated subject as there is a paucity of long-term studies of subclinical hyperthyroidism treatment. Subclinical hyperthyroidism is defined by a low serum TSH level in the presence of normal range thyroid hormone levels. Management requires careful monitoring of thyroid function through clinical and laboratory evaluation. Treatment is currently recommended for patients 65 years of age and older, and in the presence of osteoporosis and atrial fibrillation. If treated, antithyroid drugs are usually used; however, 131I is also an option (Palacios et al., 2012).

Thyroid Nodule DEFINITION AND SCOPE

Thyroid nodules are a fairly common clinical finding in the United States. Based on palpation alone, current estimates suggest that prevalence is approximately 3% to 7% of adults (Popoveniuc & Jonklaas, 2012). Approximately 300,000 new thyroid nodules are diagnosed annually in the United States (Guo et al., 2017). It is usually found during routine physical examination or as an incidental finding during color doppler studies of the carotid artery or other imaging studies performed for unrelated reasons. ETIOLOGY

Thyroid nodules can be either benign or malignant, and hence, the major reason for evaluation is to exclude a malignant nodule. Causes of thyroid nodules include benign nodular goiter, chronic lymphocytic thyroiditis, simple or hemorrhagic cysts, follicular adenomas, subacute thyroiditis, and various histologic primary and metastatic carcinomas (Gharib et al., 2010).

Chapter 44  Endocrine-Related Problems 849

RISK FACTORS

A history of previous diseases or treatments involving the head and neck, recent pregnancy, and rapidity of onset and rate of growth of the neck mass should be documented. The malignancy rate is three- to fourfold higher for thyroid nodules found during childhood and adolescence as compared with adults. Thyroid cancer risk is also higher in males and in the older adult population. SYMPTOMS

Although clinical signs help with risk assessment, most patients with thyroid nodules experience few or no symptoms. EVALUATION/ASSESSMENT

A family history is important for the diagnosis, as both benign and malignant nodules can be familial. It is critical to ascertain family history of thyroid cancer, familial adenomatous polyposis, and multiple endocrine neoplasia syndrome as these disorders are associated with a very high risk of development of thyroid cancer. DIAGNOSTIC STUDIES

High-resolution ultrasound imaging, third-generation serum thyrotropin (TSH) assay, and fine-needle aspiration (FNA) biopsy are the basis for evaluation and management of thyroid nodules. TREATMENT/MANAGEMENT

All patients with new and/or changing nodules should be referred to an endocrinologist for further evaluation and FNA biopsy (Gharib et al., 2010).

PARATHYROID DISEASE Parathyroid hormone (PTH) is secreted from four small glands adjacent to the thyroid gland. Secretion is based on a feedback loop. PTH aids in regulating serum calcium levels. Any disruption in PTH secretion can cause serum calcium concentrations to fluctuate outside the narrow normal range of 8.5 to 10.5 mg/dL (normal range may vary by laboratory; Shoback et al., 2011). Maintaining this concentration requires the coordinated effects of multiple systems and organs such as the kidneys, intestines, and skeleton (Shoback et al., 2011). When plasma calcium levels fall, PTH secretion increases. PTH stimulates more efficient renal calcium reabsorption and intestinal calcium absorption. Excessive amounts of PTH activate bone remodeling to support extracellular fluid calcium at the expense of skeletal integrity (Moe, 2008).

Hyperparathyroidism DEFINITION, SCOPE, AND ETIOLOGY

Hyperparathyroidism (HPT), overactivity of the parathyroid glands, is the most common cause of hypercalcemia. HPT is present in about 1% of the adult population and is more common in older postmenopausal persons. Women have a two- to fourfold increased likelihood of developing HPT

over men. The most common cause is a single adenoma of the parathyroid gland. Other causes of HPT include vitamin D deficiency, chronic kidney disease, hyperplasia of one or more of the parathyroid glands, and parathyroid cancer, although this is rare and accounts for less than 1% of all cases. SYMPTOMS

The clinical manifestations of HPT involve multiple systems. The most common features are nephrolithiasis, bone fracture, constipation, abnormal cognitive function, depression, and hypertension (El-Hajj Fuleihan & Silverberg, 2023), hence the mnemonic “moans, groans, stones, bones, and thrones with psychic overtones.” EVALUATION/ASSESSMENT AND DIAGNOSTIC STUDIES

About 90% of those with HPT have an elevated PTH. Serum calcium levels are also abnormally high. Because low vitamin D levels are also associated with HPT, evaluating serum 25-hydroxyvitamin D is appropriate (Marcocci & Cetani, 2011). TREATMENT/MANAGEMENT

The treatment of choice is surgical removal of the abnormal gland, which is curative 95% to 98% of the time. Surgical complications can include laryngeal nerve damage, recurrent HPT, or permanent hypoparathyroidism. Surgery is suggested if serum calcium levels are greater than 12 mg/dL on multiple occasions or if there is a 20% rise from baseline. Serum calcium and bone mineral density are evaluated annually after surgery. Medications are not typically used to treat HPT. However, in a nonsurgical candidate, cinacalcet (Sensipar) can be used in conjunction with close monitoring of calcium levels (Bilezikian et al., 2009; El-Hajj Fuleihan & Silverberg, 2023).

Hypoparathyroidism DEFINITION AND ETIOLOGY

The most common cause of hypoparathyroidism, reduced function of the parathyroid glands, is neck surgery, such as surgery on the thyroid gland or neck neoplasms. Within hours of parathyroid gland removal, calcium concentration decreases while inorganic phosphorus increases. Urinary calcium excretion also increases. Although idiopathic disease is rare, if present, it is associated with autoimmune problems in multiple endocrine glands (Bilezikian et al., 2011; Gardner & Shoback, 2011). SYMPTOMS, EVALUATION/ASSESSMENT, AND DIAGNOSTIC STUDIES

The history seeks information about risk factors and symptoms such as muscle cramps, dermatologic problems (dry skin, brittle nails, dermatitis), and cataract development. Clinical signs of hypoparathyroidism include neuromuscular irritability such as a positive Chvostek or Trousseau sign. Diagnosis is confirmed with a low or low-normal serum PTH (Gardner & Shoback, 2011). TREATMENT/MANAGEMENT

Hypoparathyroidism is treated with calcium and vitamin D supplementation. If acute, 10% calcium gluconate can be given intravenously (Gardner & Shoback, 2011; Moe, 2008).

850  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

Long-term daily therapy is 1.5 to 3 g of oral elemental calcium with vitamin D (up to 1,000 IU). The goal is a serum calcium level between 8 and 9 mg/dL.

METABOLIC SYNDROME Definition and Scope Metabolic syndrome is a clustering of several cardiometabolic risk factors that greatly increase the risk of cardiovascular disease (CVD) and type 2 diabetes. The syndrome, as described by both the World Health Organization (WHO) and National Cholesterol Education Program (NCEP), includes a group of disorders: hyperinsulinemia/abnormal glucose tolerance, obesity, dyslipidemia, hypertension, and proinflammatory, prothrombotic state. There are an estimated 47 million individuals (age adjusted U.S. persons older than 20 years; approximately 24% ‌‌‌‌‌‌‌‌) with metabolic syndrome in the United States (Ford et al., 2002). The overall prevalence of 23.7% changes with age, affecting 6.7% of young adults (20–29 years), 43.5% of adults age 60 to 69 years, and 42% of those older than 70 years. Ethnicity is also a factor: more Hispanic American people are affected (31.9%) than non-Hispanic White people (23.8%) and Black people (21.6%). Gender differences place Black and Hispanic women at highest risk (Ford et al., 2002; Meigs, 2015).

Etiology Several explanations have been suggested that describe the etiology of the metabolic syndrome. The American Association of Endocrinology (AAE) stresses the importance of insulin resistance; however, the AAE does not recognize obesity as a component of metabolic syndrome (Einhorn et  al., 2003). Initial definition by WHO considered insulin resistance a major component of the metabolic syndrome (Alberti & Zimmet, 1998). The Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001), which developed a widely accepted definition, suggested equal weight to any of the components of the syndrome: fasting blood glucose, glucose intolerance, obesity (measured as waist circumference), hypertension, and dyslipidemia. The International Diabetic Federation (IDF) considers central obesity, insulin resistance, and a proinflammatory/prothrombotic state as important causative factors in the metabolic syndrome (Nesto, 2003). The underlying pathophysiology of metabolic syndrome is insulin resistance accompanying abnormal adipose deposition and function. Defined as a state in which the concentration of insulin is associated with an abnormal glucose response, this can lead to several pathogenic conditions (Freeman, 2006). Clinically, there is an imbalance of the amount of insulin required to maintain normal glucose levels, and the body is unable to control both hepatic glucose output and muscle glucose utilization (Masharani & German, 2011). Insulin regulation of protein and fat metabolism are disrupted. Obesity and disorders of the adipose tissue play an important role in metabolic syndrome. Fat distribution and

overall total body weight may be critical factors in pathogenesis. Obesity contributes to insulin resistance and to both hypertension and dyslipidemia. Excessive visceral adipose tissue releases several protein substances. Obesity also plays a role in endothelial dysfunction. The proinflammatory state is related to elevated C-reactive protein (CRP), fibrinogen, and other cytokines (Bentley-Lewis et al., 2007). Hypertension is also related to insulin resistance, likely through sodium reabsorption pathways. The increase in sympathetic outflow and sodium reabsorption is thought to counter the vasodilatory effect, causing elevated blood pressure (Meigs, 2015). Insulin resistance causes an abnormality in the regulation of free fatty acids. This can lead to an increase in plasma lipid levels that may be diverted to the liver, promoting fatty liver disease or nonalcoholic steatohepatitis (NASH). Lipid levels increase, especially triglycerides (TG) and very low-density lipoprotein cholesterol (VLDL-C), while high-density lipoprotein cholesterol (HDL-C) levels remain low, promoting atherogenic dyslipidemia. Several independent factors also play a role in the pathogenesis of metabolic syndrome, including age and ovarian failure. As estrogen levels decline in postmenopause, intra-abdominal fat increases, the lipid profile shifts in an atherogenic direction, and insulin resistance increases as observed by a rise in both glucose and insulin levels (Bentley-Lewis et al., 2007).

Risk Factors Risk factors for metabolic syndrome are related to each of the components and to the syndrome overall. It remains unclear whether metabolic syndrome has a single cause, although it appears that multiple risk factors precipitate the syndrome. Insulin resistance and central obesity appear to be the most important precipitating factors. In most individuals, metabolic syndrome is lifestyle mediated, with greatest risk among those following a high fat, high concentrated sugar diet and having a sedentary lifestyle. Other risk factors include genetic predisposition, increased age, ethnicity, increased weight, postmenopausal status, low household income, smoking, and soft drink consumption (Alberti et al., 2009). Conflicting evidence exists regarding alcohol consumption and metabolic syndrome. Excessive alcohol intake is associated with numerous illnesses, although studies indicate that light to moderate drinking has a cardioprotective effect. There is a need for more prospective studies to determine the relationship between alcohol consumption and metabolic syndrome (Fujita & Takei, 2011).

Evaluation/Assessment and Diagnostic Studies Several criteria have been proposed over the past decade to establish the diagnosis of metabolic syndrome. Diagnostic criteria developed by the NCEP Adult Treatment Panel III (Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, 2001) based on common clinical measures, including waist circumference, TG, HDLC, blood pressure, and fasting glucose level, continue to be used with minor modifications. Modifications to the original

Chapter 44  Endocrine-Related Problems 851

TABLE 44.5  Metabolic Syndrome Diagnostic Criteriaa PARAMETER

Fasting blood sugar

DIAGNOSTIC THRESHOLD

≥ 100 mg/dL (or receiving medication for hyperglycemia)

Blood pressure

≥ 130/85 mmHg (or receiving medication for hypertension)

Triglycerides

≥ 150 mg/dL (or receiving medication for hypertriglyceridemia)

HDL-C

< 40 mg/dL in men or < 50 mg/dL in women (or receiving medication for reduced HDL-C)

Waist circumference

≥ 102 cm (40 in.) in men or ≥ 88 cm (35 in.) in women; if Asian American, ≥ 90 cm (35 in.) in men or ≥ 80 cm (32 in.) in women

Three of the five diagnostic criteria must be met to establish a diagnosis of metabolic syndrome. HDL-C, high-density lipoprotein cholesterol. Source: Data from Grundy, S. M., Cleeman, J. I., Daniels, S. R., Donato, K. A., Eckel, R. H., Franklin, B. A., Gordon, D. J., Krauss, R. M., Savage, P. J., Smith, S. C., Jr., Spertus, J. A., & Costa, F. (2005). Diagnosis and management of the metabolic syndrome. An American Heart Association/National Heart, Lung, and Blood Institute scientific statement: Executive summary. Circulation, 112, 285–290. https://doi.org/10.1161/ CIRCULATIONAHA.105.169405

Visceral fat

Subcutaneous fat

FIGURE 44.2  Subcutaneous versus visceral fat.

a

diagnostic criteria include waist circumference adjustment to lower thresholds for individuals or ethnic groups predisposed to insulin resistance; designation of abnormal for the measures of TG, HDL-C, and blood pressure if an individual is taking pharmacotherapeutics to treat these factors; delineating a threshold for both systolic and diastolic hypertension; and in accordance with the American Diabetes Association (ADA), lowering the threshold for impaired fasting glucose level to 100 mg/dL. Metabolic syndrome is diagnosed when any three of the five diagnostic criteria exist, suggesting a multicausal etiology (Grundy et al., 2005). Diagnostic criteria for metabolic syndrome are depicted in Table 44.5.

Components of Metabolic Syndrome OBESITY Definition and Scope

Obesity, defined as a body mass index (BMI) of 30 kg/m2 or greater, contributes to several conditions associated with metabolic syndrome. It is a common, serious, and costly disorder affecting more than one third of American adults (Bray, 2014). The presence of excessive weight is important, and the distribution of fat is critical to the metabolic syndrome diagnosis. Etiology

Obesity is the accumulation of subcutaneous and visceral fat (Figure 44.2); it is the visceral fat (central obesity) that is problematic. Visceral fat is thought to be more predictive of metabolic syndrome than total body weight.

Evaluation/Assessment

Because the main concern is central obesity, measurement of waist circumference or calculation of the waist-to-hip ratio should be done. In women, central obesity is identified when waist circumference is greater than 35 inches or when the waist-to-hip ratio is greater than 0.85. To accurately measure the waist, the tape measure should be placed on the upper border of the iliac crest. Have the patient exhale and then measure without compressing the skin. The hips are measured at the widest point, again without compressing the skin. Data suggest that waist circumference is more reflective of CVD in women than is BMI and is also associated with higher risk for development of type 2 diabetes and all-cause mortality (American College of Cardiology [ACC] et al., 2014; Meigs, 2015). BMI and waist circumference are screening tools to be included in all health encounters. Decisions to treat obesity are determined by BMI, comorbidities, and waist circumference. Treatment/Management

Weight loss should be encouraged at a BMI of 25 or greater with just one comorbidity, and elevated waist circumference is considered a comorbidity. Counseling regarding dietary factors, exercise requirements, and weight management programs should be incorporated into treatment plans for all patients who are overweight or obese or at high risk for obesity. It is critical that weight management programs include individual and/or group-based psychological/behavioral interventions. Pharmacotherapy

Pharmacologic treatment (orlistat, naltrexone-bupropion, phentermine-topiramate, liraglutide, semaglutide) should be considered in adults as an adjunct to lifestyle interventions in the management of obesity (see Chapter 13, Nutrition for Women). Current recommendations suggest that patients with a BMI of 28 kg/m2 or more (with comorbidities) or BMI 30 kg/m2 or more should be considered on an individual case basis following careful assessment of risk/benefit and patient willingness to accept pharmacologic intervention.

852  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS Surgery

Bariatric surgery is an option for those in whom previous attempts at weight loss have failed or are physically unattainable when the following criteria are met: BMI 35 kg/m2 or more and/or presence of one or more severe comorbidities that are expected to improve significantly with weight reduction (e.g., immobility, arthritis, type 2 diabetes; ACC et al., 2014). ACANTHOSIS NIGRICANS Definition and Scope

Acanthosis nigricans, which is caused by an increase in melanocytes and epidermal papillomatosis, is a common finding with metabolic syndrome. This skin change is characterized by hyperpigmented, hyperkeratotic plaque-like lesions found especially in intertriginous areas such as the axillae, neck, groin, under the breast, and the vulva. The skin is also hyperplastic and has a velvety or mossy appearance. It can occur in healthy individuals as well as in numerous health disorders and with exogenous hormone therapy including growth hormone and birth control pills. It is most commonly seen in individuals of African descent, partly because it is easier to visualize on darker skin. Etiology and Risk Factors

When acanthosis nigricans develops in patients who are not obese, a diagnostic workup should be done. In rare instances, it is associated with lymphoma or malignancies of the gastrointestinal or genitourinary tract. In these cases, acanthosis nigricans may also appear on the lips, palms, and soles of feet and is generally severe. Occasionally, acanthosis nigricans is congenital or due to an endocrine disorder such as diabetes, gonadal disorders, and thyroid disease (Habif, 2009). Evaluation/Assessment and Diagnostic Studies

Acanthosis nigricans is usually diagnosed by inspection of affected areas. Skin biopsies are occasionally required for atypical cases. Treatment/Management

Treatment is cosmetic only and includes topical tretinoin, 20% urea, alpha-hydroxy acids, lactic or salicylic acid prescriptions, and laser resurfacing. HYPERTENSION

Hypertension is a critical factor in the constellation of disorders that define the metabolic syndrome. Approximately 120 million US adults (48.1%) have hypertension. About 25% have their blood pressure under control (CDC, 2023). Additionally, it is estimated that one in three adults in the United States are prehypertensive (Nwankwo et al., 2013). For a comprehensive overview of hypertension, see Chapter 43, Cardiovascular Disease in Women. IMPAIRED GLUCOSE TOLERANCE

While glucose levels may range from normal to elevated, hyperinsulinemia is always manifested. The ADA and AACE recognize the connection of diabetes to insulin resistance and the metabolic syndrome. An important part of metabolic syndrome

treatment is prevention of diabetes and CVD. The WHO criteria require glucose abnormalities to make a diagnosis of the metabolic syndrome, while the NCEP does not. In an 8-year Japanese study comparing these two definitions of metabolic syndrome, only the WHO criteria, which emphasized abnormal glucose tolerance, were predictive of developing CVD in women. These data support a link between diabetes and the metabolic syndrome; both are related to the development of CVD. DYSLIPIDEMIA

Patients with metabolic syndrome have an abnormal, atherogenic lipid profile (see Chapter 43, Cardiovascular Disease in Women). TG levels are typically elevated, and serum HDL-C levels are low. Serum low-density lipoprotein cholesterol (LDL-C) levels are increased, and the size and density of the LDL particles are reduced. The reduced particle size can lead to further development of atherosclerosis; thus, treatment is aimed at restoring the lipid profile to normal. PROINFLAMMATORY, PROTHROMBOTIC STATE

Proinflammatory, prothrombotic state abnormalities are derived largely from the secretory activity of adipose tissue, particularly visceral fat. Adipocytes release adipokines such as leptin, interleukin (IL) 6, and plasminogen activator inhibitor-1 (PAI-1), all markers for CVD risk. The clinical value of measuring these markers and CRP is unknown and should be considered for use in clinical practice only in settings that are assessing CVD risk. Both the American Heart Association (AHA) and Centers for Disease Control and Prevention (CDC) list CRP testing as optional; the decision to test is based on clinical judgment (Bray, 2015).

Differential Diagnosis The differential diagnosis involves looking at the entire constellation of problems that make up metabolic syndrome. The clinician must consider whether other causes explain the presence of hypertension, glucose abnormalities, or dyslipidemia. Other potential causes must be identified and managed. For example, in hypertensive women, secondary causes such as renovascular disease, obstructive sleep apnea, and disorders of renin and aldosterone metabolism may need exploration (Tasali & Ip, 2008). In the presence of a strong family history of dyslipidemia, hereditary dyslipidemia may need to be excluded. Hyperglycemia can present with thyroid disorders and rare endocrinopathies including pheochromocytomas and glucagonomas and, if the situation warrants, may need extensive workup. If no other causes are present, then metabolic syndrome is identified as the primary diagnosis.

Diagnostic Studies Preliminary laboratory studies in women suspected of having metabolic syndrome should include complete metabolic (chemistry) panels to evaluate serum glucose, renal function (creatinine, blood urea nitrogen [BUN], and estimated glomerular filtration rate [eGFR]), and lipid profile (TG, HDL-C, and LDL-C). In women with a family history of heart disease or other atherosclerotic disorder, consideration should be given for studies of lipoprotein(a), apolipoprotein-B100,

Chapter 44  Endocrine-Related Problems 853

high-sensitivity CRP, homocysteine, and fractionated LDL-C (Bray, 2015; Yaffe, 2007). As previously discussed, factors associated with metabolic syndrome are found in other disorders and, as such, warrant assessment. Such assessment includes thyroid function tests, liver function tests, hemoglobin A1c, and uric acid. Extant data indicate that elevated TSH is associated with a higher prevalence of metabolic syndrome (Heima et  al., 2012). Women with metabolic syndrome are more likely than the general population to have hyperuricemia, and this has been attributed to the proinflammatory nature of the syndrome (Puig & Martínez, 2008). Imaging studies may be indicated for women with symptoms or signs of the many complications of the syndrome, including CVD. Complaints of chest pain, shortness of breath, significant fatigue, dyspnea, or claudication may necessitate additional diagnostic testing with EKG (rest/stress EKG), US (vascular or rest/stress echocardiography), stress single-photon emission computed tomography (SPECT), cardiac PET, or other imaging studies. Exacerbating factors such as obstructive sleep apnea should also be investigated. Polysomnography (sleep study) should be considered in patients reporting snoring, periods of pauses in breathing, and/or daytime drowsiness (see Chapter 15, Healthy Practices: Sleep). This is critical in obese patients (Lam & Ip, 2007; Tasali & Ip, 2008). Cardiovascular risk should be assessed using the ACC/ AHA (Goff et al., 2014) calculator (available at tools.cardiosource.org/ASCVD-Risk-Estimator) to determine the risk of developing a first atherosclerotic cardiovascular disease (ASCVD) event. Risk factors used to assess the 10-year and lifetime risk of an ASCVD event are gender, age, race, total cholesterol level, HDL-C level, systolic blood pressure, treatment for hypertension, diabetes, and smoking status (see Chapter 43, Cardiovascular Disease in Women).

Treatment/Management Metabolic syndrome is managed through focused treatment of each component. The primary goal is prevention of ASCVD and type 2 diabetes, achieved through risk reduction. The goals overlap as prevention of type 2 diabetes and treatment of other conditions are important factors in the prevention of ASCVD (Bray, 2015). SELF-MANAGEMENT MEASURES

Lifestyle changes and management of obesity are the most important initial steps in treating metabolic syndrome. The major goal is lifestyle change to treat the underlying causes of obesity and physical inactivity and is essential for successful management of each metabolic syndrome component. For both long- and short-term risk reduction, therapeutic lifestyle changes (TLC) are first-line therapy for all patients with metabolic syndrome. TLC include both dietary and exercise modification and have been demonstrated to effectively reduce progression to diabetes and development of CVD. Reduction of some of the major risk factors such as smoking, stress, and sedentary lifestyle are important components of management goals and referral for appropriate intervention is indicated to support patients attempting TLC (Bray, 2015).

As with obesity, reduction in caloric intake and avoidance of high glycemic index foods and saturated fats are indicated. Not surprisingly, research indicates that the typical American diet is associated with a higher risk for developing metabolic syndrome; the opposite has been demonstrated in populations adhering to a typical Mediterranean diet (Yoneda et al., 2008). It is essential for diet modification programs to include a behavioral component as discussed in the obesity section, and referral for structured dietary modifications and weight loss may be warranted. Exercise is an essential intervention in preventing and treating metabolic syndrome and obesity. Aerobic exercise, as opposed to resistance training, is recommended at least 5 days per week (Bateman et al., 2011; Roberts et al., 2013). Exercise programs should be tailored to the individual person to achieve the best outcomes. (See Chapter 13, Nutrition for Women, and Chapter 14, Healthy Practices: Physical Activity, for details about diet and exercise modifications used for metabolic syndrome, as well as information on supporting behavior change.) PHARMACOTHERAPEUTICS

Medication therapies are used according to current authoritative guidelines for each component of the metabolic syndrome. Dyslipidemia

Many patients will require lipid-modifying medications to control dyslipidemia, even those patients who achieve success in instituting and maintaining TLC. The goal for lipid management is threefold: to lower LDL-C, raise HDL-C, and lower TG, all of which help reduce CVD risk (Stone et  al., 2014). As the goal is threefold, multiple medications may be needed. The use of multiple medications has been shown to achieve better lipid control. It is widely accepted to initiate statins (3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase inhibitors) in the presence of elevated LDL-C levels (‌‌‌‌‌‌‌‌‌‌‌Stone et al., 2014; Towne & Thara, 2008). Treatment of decreased HDL-C remains controversial, but may include niacin; however, careful monitoring is required as high doses may exacerbate hyperglycemia (Ito, 2004). Women with atherogenic dyslipidemia (elevated TG with low HDL-C), especially if overweight or obese, may benefit from fibrate medications; however, current recommendations for the treatment of cholesterol disorders emphasize statins over nonstatin medications (Stone et al., 2014). Hypertriglyceridemia is amenable to both fibrates and niacin. Caution should be employed when prescribing fibrates due to well-documented drug interactions, especially when used in combination with statins. Omega-3 fatty acids may also help in lowering TG levels (see Chapter 43, Cardiovascular Disease in Women). Hypertension

The goal of antihypertensive therapy in patients with metabolic syndrome is a blood pressure of less than 140/90 mmHg for most populations and 150/90 mmHg for patients age 60 years or older. Treatment guidelines follow the Eighth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8; James et al., 2014; see Chapter 43, Cardiovascular Disease in Women).

854  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS Insulin Resistance

Insulin resistance is first managed with TLC. There is no set limit for how long TLC alone are tried to manage insulin resistance. The patient should be evaluated with fasting glucose every 3 months; TLC have been shown to prevent metabolic syndrome more effectively than metformin or placebo (cumulative incidence of metabolic syndrome at year 3 was 51% for placebo, 45% with metformin, and 34% for TLC). TLC should be the focus of initial and ongoing education about treatment for insulin resistance and should be maintained when pharmacotherapy is initiated. The AACE recommends that clinicians use their judgment in making the decision to initiate pharmacotherapy and that pharmacotherapy should be considered when fasting blood glucose or A1c levels begin to rise. The goal of pharmacotherapy is to reduce insulin resistance, and this includes the use of metformin and/or thiazolidinediones (TZDs). Due to its proven safety record, metformin is used extensively. Titrating metformin from 500 mg once daily to 1,000 mg twice daily in increments of 500 mg every 3 to 5 days will help to avoid common gastrointestinal side effects such as abdominal discomfort, diarrhea, gas, and bloating. Liver and renal function are evaluated prior to initiating metformin and monitored at least yearly. Renal dysfunction, heart failure, current liver disease, metabolic acidosis, and current alcohol abuse are contraindications to the use of metformin (Bray, 2015). TZDs, including rosiglitazone and pioglitazone, have also been investigated for controlling insulin resistance and preventing diabetes in patients with the metabolic syndrome; however, no outcome data are yet available for CVD prevention in those with either the metabolic syndrome or diabetes. As with any medication therapy, balancing the risks and side effects with the potential benefits must be considered (Grundy et al., 2005). Proinflammatory, Prothrombotic State

No currently available pharmacotherapeutics are recommended for treatment of the proinflammatory/prothrombotic state. Preventive Cardiovascular Treatment

Along with diet, exercise, and lifestyle behavior modifications, women age 40 to 70 years without increased risk for bleeding may benefit from low-dose aspirin therapy (75–100 mg/day) (see Chapter 43, Cardiovascular Disease in Women). Surgical Considerations

Although surgical interventions for metabolic syndrome are not currently recommended, bariatric surgery referral may be considered for the morbidly obese when weight loss is not or cannot be achieved via diet and exercise (see Chapter 13, Nutrition for Women).

DIABETES Definition and Scope The ADA defines type 1 diabetes as an absolute insulin deficiency related to beta-cell dysfunction. Type 2 diabetes

mellitus is defined as a progressive insulin secretory defect related to insulin resistance. Prediabetes exists when blood glucose levels are higher than normal but not high enough to be diagnosed as diabetes. The ADA (2014) defines “gestational diabetes” as the development of diabetes during pregnancy (see Chapter 38, High-Risk Childbearing). In the United States, it is estimated that nearly 26 million Americans have diabetes and an additional 79 million are prediabetic. Diabetes affects over 8% of the U.S. population across their life span. The CDC (2011) reports that 11.3% of Americans 20 years of age and older are diabetic. In American adults 65 years of age and older, nearly 25% are affected. Alarmingly, approximately 27% ‌‌‌‌‌‌‌, or 7 million Americans, are not aware that they have diabetes. In 2010, over 200,000 Americans 20 years of age or younger had either type 1 or type 2 diabetes. Diabetes was the seventh leading cause of death in the United States in 2013 and the leading cause of disabilities. The risk of death in people with diabetes is two times as great as in those who do not have the disease (CDC, 2015). Type 2 diabetes accounts for approximately 90% to 95% of all diagnosed cases of diabetes. Current estimates suggest that approximately 40% of American adults will develop diabetes, primarily type 2. Recent data suggest that more than 50% of ethnic minorities will develop diabetes in their lifetime. The primary reason for the increased incidence of diabetes is the obesity epidemic in the United States (G ‌‌‌‌‌‌‌‌‌‌‌regg et al., 2014; Hackethal, 2014). Estimates suggest that 79 million or 35% of American adults age 20 years and older have prediabetes and will subsequently develop diabetes in their lifetime (CDC, 2011). The most common metabolic disease of childhood, type 1 diabetes affects approximately one in every 400 to 600 children and adolescents and accounts for 5% of all diagnosed cases of diabetes in adults. According to the CDC, the total incidence of type 1 diabetes is approximately 1 million Americans. CDC estimates indicate that 15,600 new cases of type 1 diabetes were diagnosed each year from 2002 to 2005 in young people. In individuals younger than 10 years of age, the annual rate of new cases was 19.7 per 100,000 population. In those older than 10 years, the annual rate of newly diagnosed cases was 18.6 per 100,000 population (CDC, 2011). In children, type 1 diabetes mellitus generally starts around age 4 years or older, with an abrupt onset. Peak incidence of onset in children is age 11 to 13 years. In adults, generally in their late 30s and early 40s, type 1 diabetes tends to present less aggressively. The slower onset form of type 1 diabetes seen in adults is referred to as latent autoimmune diabetes of the adult, or LADA (CDC, 2011).

Etiology TYPE 1 DIABETES

Type 1 diabetes mellitus occurs due to lymphocytic infiltration and destruction of insulin-secreting beta cells in the islets of Langerhans in the pancreas. The resulting decline in beta-cell mass leads to reduced insulin secretion; over time, there is insufficient available insulin to maintain normal blood glucose levels. Generally, hyperglycemia develops after destruction of 80% to 90% of the beta cells and diabetes may

Chapter 44  Endocrine-Related Problems 855

then be diagnosed. Exogenous insulin is required to reverse this catabolic condition, prevent diabetic ketosis, decrease hyperglucagonemia, normalize the metabolism of lipids and proteins, and to sustain life. Autoimmunity is currently considered the major factor in developing type 1 diabetes mellitus and may also be associated with other autoimmune diseases such as Addison disease, Hashimoto thyroiditis, and Graves disease (Borchers et  al., 2010). Less common causes of type 1 diabetes mellitus include pancreatitis, pancreatic cancer, and pancreatic surgery. TYPE 2 DIABETES

The pathophysiology of type 2 diabetes is a spectrum of metabolic process abnormalities affecting glucose metabolism; insulin resistance is central. As discussed previously (see Metabolic Syndrome), insulin resistance leads to higher levels of circulating insulin as well as hyperglycemia due to the inability of the body to use insulin in both muscle and adipose tissue. Over time, the pancreas cannot produce enough insulin to keep up with the demand, and a relative insufficiency of insulin is created, resulting in hyperglycemia. Just as with the metabolic syndrome, type 2 diabetes is usually associated with multiple metabolic comorbidities. The etiology of type 2 diabetes is multifactorial and involves both environmental and genetic factors. Extant data suggest that type 2 diabetes develops in response to excessive calorie intake without sufficient caloric expenditure and/or obesity in individuals with a susceptible genetic type. Nearly 90% of persons with type 2 diabetes are obese; however, racial and ethnic factors influence the development of type 2 diabetes. Excess weight is a recognized risk factor for developing type 2 diabetes; however, individuals of Asian ancestry are at an increased risk for diabetes at lower weight levels when compared with persons of European ancestry. A greater risk for developing type 2 diabetes is also present in White people in the presence of hypertension and prehypertension as compared with Black people (WHO Expert Consultation, 2004). Genetic variants can be attributed to only about 10% of the inheritable component in type 2 diabetes (Billings & Florez, 2010). Secondary diabetes can develop in individuals due to glucocorticoid therapy and in insulin-antagonistic disorders such as Cushing syndrome, pheochromocytoma, and acromegaly.

Risk Factors Risk factor assessment is an essential component of screening for diabetes and prediabetes. Women with any of the following risk factors should be screened at least every 3 years. In the presence of two or more risk factors, screening should occur annually (Handelsman et al., 2015). ●

●

● ● ●

Family history of type 2 diabetes in a first-degree relative (such as parent or sibling) Age greater than 45 years, although type 2 diabetes is occurring with greater frequency in younger individuals Sedentary lifestyle BMI greater than or equal to 30 kg/m2 BMI 25 to 29.9 kg/m2 in the presence of other risk factors, such as ethnicity

●

●

●

●

●

● ● ● ●

●

High-risk ethnicity including Hispanic, Native American, African American, Asian American, or Pacific Islander ancestry Prior history of impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) or metabolic syndrome Hypertension (greater than 140/90 mmHg) or on antihypertensive therapy Dyslipidemia (HDL cholesterol level less than 35 mg/ dL or TG level greater than 250 mg/dL) History of gestational diabetes or delivering a baby with a birth weight over 9 lb Polycystic ovary syndrome Nonalcoholic fatty liver disease Chronic or prolonged glucocorticoid therapy Antipsychotic drug therapy for schizophrenia or severe bipolar disorder Sleep disorders such as obstructive sleep apnea, chronic sleep deprivation, and night shift workers with glucose intolerance

Evaluation/Assessment There are many differences between type 1 diabetes and type 2 diabetes (Table 44.6), and proper diagnosis is essential for management. HISTORY

Many of the signs and symptoms of type 1 diabetes and type 2 diabetes are the same; however, their presentation is usually different (Table 44.6). Symptoms of type 1 diabetes have a rapid onset, while type 2 diabetes onset may be much slower, even insidious. In type 1 diabetes, polyuria and polydipsia are considered classic presenting signs; polyphagia with weight loss, blurred vision, and fatigue can also present. Type 2 diabetes can be largely asymptomatic; however, common presenting symptoms include fatigue, blurred vision, and Candida infections, as well as the classic symptoms of polydipsia, polyuria, polyphagia, weakness, and unexplained weight loss. Symptoms of autonomic neuropathy (dysphagia, bloating, change in bowel habits, and urinary and sexual dysfunction) as well as peripheral neuropathy (paresthesia of extremities) may be the first sign of type 2 diabetes. Chronic anovulation leading to oligomenorrhea or amenorrhea suggests an increase in the risk of type 2 diabetes, especially if accompanied by signs of hyperandrogenism. People with a history of gestational diabetes or a history of large babies (over 9 lb) are known to be at increased risk of developing type 2 diabetes (Wass et al., 2011). PHYSICAL EXAMINATION

A thorough physical examination (Table 44.7) is performed to identify presenting signs of diabetes, rule out secondary diabetes, and evaluate other problems associated with the presenting signs and symptoms. Evaluation for signs of complications and target organ damage (Table 44.8), such as peripheral neuropathy and visual changes, is done at each visit.

Differential Diagnosis The major diagnostic challenge is to differentiate between the possible causes of the patient’s presenting symptoms.

856  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

TABLE 44.6  Comparison of Type 1 and Type 2 Diabetes PARAMETER

TYPE 1

TYPE 2

Prevalence of each type

5%–10%

90%–95%

Age of diagnosis

Young, usually younger than 40 years

Older than 40 years usually

Condition in discovery

Mild to severe

Not ill, usually have mild symptoms

Cause

Absent or severely decreased insulin production

Insulin resistance or insulin secretory deficiency

None to small amount

Markedly elevated early; later may see decrease

Insulin levels

Source: Adapted from Beasler, R. S. (2014). Joslin’s diabetes deskbook: A guide for primary care providers. Joslin Diabetes Center.

Fatigue and weakness can be presenting symptoms of thyroid disorders, anemia, chronic fatigue syndrome, diabetes, depression, and other conditions. Skin problems such as pruritus and dry skin also can present with several conditions. The urinary symptoms of diabetes can mimic the presence of a urinary tract infection (UTI).

Diagnostic Studies Updated 2015 guidelines suggest differences in the diagnostic criteria for type 1 and type 2 diabetes (Handelsman et al., 2015). The criteria for diagnosing type 2 diabetes are summarized in Table 44.8 (American Diabetes Association, 2023). The final differential between the two depends on the history, presentation of symptoms, physical examination, and plasma glucose studies. Routine screening for type 2 diabetes in adults older than 45 years is recommended because of the general lack of clinical symptoms in early hyperglycemia. While past experts recommended fasting plasma glucose as the initial screen, the 2-hour oral glucose tolerance test (OGTT) is a better predictor among patients with impaired fasting glucose. Patients who have a higher-than-normal glucose level that does not meet criteria for the diagnosis of diabetes are at particularly high risk for the development of diabetes and are frequently referred to as having prediabetes. Once the diagnosis of type 2 diabetes is confirmed, several tests are done to guide management. Along with self-monitoring (see Self-Management Measures), a glycosylated hemoglobin A1c is assessed quarterly. The A1c measures the level of control during the previous 2- to 3-month period. The higher the A1c value, the poorer the glucose control. Maintaining an A1c of less than 6.5% is recommended; however, the closer to normal (5.5% or lesser) the levels are, the less likely individuals are to develop long-term sequelae. A1c results should be interpreted with caution in African Americans and in those with various anemias, hemoglobinopathies, and severe renal or hepatic disease (Handelsman et al., 2015).

TABLE 44.7  Physical Findings in Diabetes EXAMINATION

General appearance

FINDING

Altered level of consciousness

INTERPRETATION

Suggest DKA

Fruity breath Loss of subcutaneous fat and muscle wasting

Suggest insulin deficiency

Height/weight BMI

BMI >25 kg/m2

Present in 80% of type 2 diabetes

Funduscopic examination (dilated)

Retinopathy

Suggest microvascular disease

Microaneurysm Exudate, hemorrhage, macular edema Small, poorly responsive pupils

Suggest autonomic neuropathy

Oral examination

Gum disease

Suggest poor glycemic control

Thyroid examination

Wide range of findings from normal to abnormal

If abnormal, can suggest thyroidcaused symptoms or type 1 diabetes as it is associated with increased autoimmune disease

Skin

Acanthosis nigricans

Suggest type 2 diabetes

Cardiac examination

Cardiomegaly or gallop rhythm, little variation in rhythm with deep inspiration

CHF Autonomic neuropathy

Abdominal

Hepatomegaly

CHF

Pulses

Bruit (carotid/femoral) decrease/absent peripheral pulse

PVD

Atrophy of subcutaneous skin and hair loss—legs and ankle–brachial blood pressure index 0.9 Feet

Foot ulcer, unrecognized trauma, infection, neuropathic arthropathy

PVD Sensory neuropathy Neuropathy disorders

CNS

Abnormalities suggest neuropathic disease

Place and type can suggest sensory peripheral or autonomic neuropathy

BMI, body mass index; CHF, congestive heart failure; CNS, central nervous system; DKA, diabetic ketoacidosis; PVD, peripheral vascular disease. Source: Data from American Diabetes Association. (2023). Standards of care in diabetes—2023. https://professional.diabetes.org/content-page/practice-guidelines-resources.

Chapter 44  Endocrine-Related Problems 857

TABLE 44.8  Prediabetes and Diabetes Diagnostic Criteria for Nonpregnant Adults NORMAL

PREDIABETES

DIABETESa

FPG 126 mg/dL

2-hour PG 1x/week but not nightly

Daily

Ages 5–11 years

Moderate

≥2/year

Step 1

80%

>80%

Minor limitation

>2 days/week but not daily and not more than once on any day

3–4x/month

>2 days/week but not daily

Ages 0–4 years

Persistent

Consider severity and interval since last asthma exacerbation. Frequency and severity may fluctuate over time for patients in any severity category.

0–1/year

>80%

Normal FEV1 between exacerbations

>80%

Normal FEV1 between exacerbations

None

≤2 days/week

≤2x/month

≤2 days/week

Ages 5–11 years

Intermittent

FIGURE 45.2  Classification of asthma severity. * EIB, exercise-induced bronchospam; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ICS, inhaled corticosteroid; SABA, short-acting beta2-agonist. † Normal FEV1 /FVC by age: 8–19 years, 85%; 20–39 years, 80%; 40–59 years, 75%; 60–80 years, 70%. ‡ Data are insufficient to link frequencies of exacerbations with different levels of asthma severity. Generally, more frequent and intense exacerbations (e.g., requiring urgent care, hospital or intensive care admission, and/or oral corticosteroids) indicate greater underlying disease severity. For treatment purposes, patients with ≥2 exacerbations may be considered to have persistent asthma, even in the absence of impairment levels consistent with persistent asthma. Source: National Heart, Lung, and Blood Institute. (2012). Asthma care quick reference: Diagnosing and managing asthma. National Institutes of Health. http://www.nhlbi.nih.gov /files/docs/guidelines/asthma_qrg.pdf

The stepwise approach is meant to help, not replace, the clinical decisionmaking needed to meet individual patient needs.

(See “Stepwise Approach for Managing Asthma Long Term,” page 7)

Recommended Step for Initiating Therapy

Asthma exacerbations requiring oral systemic corticosteroids‡

FEV1 /FVC

FEV1 (% predicted)

Lung function

Interference with normal activity

SABA use for symptom control (not to prevent EIB )

Nighttime awakenings

Symptoms

Components of Severity

Level of severity (Columns 2–5) is determined by events listed in Column 1 for both impairment (frequency and intensity of symptoms and functional limitations) and risk (of exacerbations). Assess impairment by patient’s or caregiver’s recall of events during the previous 2–4 weeks; assess risk over the last year. Recommendations for initiating therapy based on level of severity are presented in the last row.

Impairment

Risk

876  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

exacerbations are important, such as smoking cessation. Medications are prescribed in a stepwise manner based on symptom severity (see Figure 45.2). When symptoms are increasing, the woman uses a peak flow meter to determine how limited her airflow has become (Willems et al., 2006). Short-acting bronchodilators are used, preferably with a spacer, to relieve symptoms and to reopen her airways. If home care is unsuccessful, she is educated to seek clinical care. Women are encouraged during pregnancy to continue use of medication even though safety data is limited (Pate et al., 2021).

Celiac Disease DEFINITION, ETIOLOGY, AND SYMPTOMS

Celiac disease (CD), also called celiac sprue, nontropical sprue, and gluten-sensitive enteropathy, is a common chronic condition caused by an inflammatory response to ingestion of gluten proteins. In CD, the effect of gluten causes atrophy of the villi of the small intestine, which may lead to nutrient malabsorption. The presenting symptoms are a wide array of gastrointestinal (GI) manifestations including diarrhea, weight loss, and malabsorption. CD occurs at the same frequency in both sexes; however, women are diagnosed more frequently than men (2:1). Unfortunately, women report a lower quality of life (Choung et al., 2017; Lebwohl et al., 2018). The prevalence of CD was as high in first- and second-degree relatives without symptoms as in relatives with symptoms, highlighting the importance of genetic predisposition as a risk factor for CD (Choung et al., 2017; Lebwohl et al., 2018). Black patients are less frequently diagnosed. DIFFERENTIAL DIAGNOSIS

Differential diagnosis for CD includes Crohn disease, ulcerative colitis (UC), tropical sprue, Zollinger–Ellison syndrome, autoimmune enteropathy, T-cell lymphoma, and combined immunodeficiency states. DIAGNOSTIC STUDIES

Initial diagnostic testing for CD includes serologic studies while the woman is on a gluten-containing diet. The two initial tests are immunoglobulin A (IgA) and anti-tissue transglutaminase (tTG). If CD is the primary working diagnosis, an endoscopy with intestinal biopsy should be performed

regardless of the serologic test results. Although genetic testing may be performed, it should be saved for patients with atypical presentation of the disease (Choung et al., 2017; Lebwohl et al., 2018). TREATMENT/MANAGEMENT

The gold standard of treatment for CD is nutritional consultation to guide the complete elimination of gluten from the diet. Glutens are the components found in rye, wheat, and barley grains. Patients are taught how to read food labels and to request gluten-free options when dining out (Choung et al., 2017; Lebwohl et al., 2018). Table 45.3 lists common gluten-free and gluten-containing foods.

Inflammatory Bowel Disease DEFINITION AND SCOPE

Inflammatory bowel disease (IBD), not to be confused with irritable bowel syndrome (IBS), describes chronic autoimmune diseases that cause inflammation of the GI tract. The two chronic diseases in this category are UC and Crohn disease. IBD is commonly diagnosed during women’s reproductive years. ETIOLOGY

While ongoing inflammation in the GI tract occurs in both Crohn disease and UC, there are important differences between the two diseases (Crohn’s & Colitis Foundation, n.d.). UC is a chronic, recurrent disease characterized by diffuse mucosal inflammation of the colon. Crohn disease is a chronic, recurrent disease characterized by patchy, transmural inflammation of any part of the GI mucosa from the mouth to the anus. IBD is a lifelong illness with profound psychosocial, emotional, and economic impacts. RISK FACTORS

Use of hormonal contraceptives by women with IBD may increase disease relapse and risk of other adverse health outcomes, including thrombosis. Additionally, IBD-related malabsorption might interfere with the effectiveness of oral contraceptives. Women should consider highly effective, first-line contraceptive methods, such as an IUD or implant, to avoid contraceptive failure and an unintended pregnancy when their disease may be more active (Gawron, 2018).

TABLE 45.3  Gluten-Containing and Gluten-Free Foods GLUTEN-FREE FOODS

FOODS CONTAINING GLUTEN

CHECK THE LABEL

Amaranth

Glucose syrup

Barley

Malt

Dextrin made from wheat

Arrowroot

Herbs

Some flavorings added to foods

Seitan

Tofu

Buckwheat

Lecithin

Gluten

Teriyaki sauce

Citric acid

Maltodextrin

Guar gum

Triticale

Corn

Millet Montina Quinoa Yeast

Hydrolyzed vegetable protein

Wheat—bulgur, durum, einkorn, farina, graham, kamut, semolina, and spelt

Source: Adapted from Gluten-Free Living. (2013). Ingredients index. https://www.glutenfreeliving.com/ingredient.php

Chapter 45  Chronic Illness and Women 877

SYMPTOMS, EVALUATION/ASSESSMENT

EVALUATION/ASSESSMENT

Patients with IBD can present with a variety of symptoms that need to be differentiated from other GI diseases as well as differentiated between UC and Crohn disease. Patients with mild UC present with frequent loose bowel movements associated with cramping; often there is blood and mucus in the stool. With more severe UC, the patient experiences more frequent stools (more than 10 per day and often at night) and more blood and mucus in the stool. The patient could have tachycardia, fever, weight loss, and signs of undernutrition such as hypoproteinemia and peripheral edema. The patient with Crohn disease commonly presents with abdominal cramping and tenderness, fever, anorexia, weight loss, and pain. There may be intermittent blood loss in the stool. The loss of mucosa could be sufficient to interfere with bile salt absorption, producing steatorrhea. If the bowel perforates, peritonitis will occur.

The physical exam may reveal joint erythema, warmth, and edema as well as limited range of motion and crepitus. Heberden nodes may be present at the distal interphalangeal joints. Bouchard nodes may be present at the middle interphalangeal joints. In more advanced disease muscle weakness and muscle wasting of the affected joint are apparent (Shorter et al., 2019).

TREATMENT/MANAGEMENT

Treatment for IBD is multifaceted and includes the use of medication, alterations in diet and nutrition, and sometimes surgical procedures to repair or remove affected portions of the GI tract. Aminosalicylates (5-ASA) and corticosteroids are usually the first line of treatment for IBD. If these treatments are unsuccessful, an immunomodulator or biological treatment such as a tumor necrosis factor (TNF) blocker may be indicated as an ongoing treatment to decrease the inflammatory response and ideally achieve remission. In addition, because stress is often associated with IBD “flares,” methods of stress reduction and relaxation such as meditation or yoga are often prescribed.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis for joint pain, joint edema, and fatigue includes: ● ●

● ● ● ●

DIAGNOSTIC TESTING

OA is usually diagnosed on the clinical presentation of age greater than 45 years, morning stiffness lasting less than 30 minutes, and usage-related persistent joint pain in one or a few joints. X-ray imaging is used when the diagnosis is unclear or other diagnoses or comorbid conditions are being considered (Sakellariou et al., 2017). The x-ray images typically reveal: ● ●

● ●

RHEUMATIC DISORDERS Osteoarthritis DEFINITION AND SCOPE

OA is the most common form of arthritis and is a common cause of disability among older people. Women have higher rates of OA, and it is more prominent after age 50 years. The presentation may range from incidental asymptomatic findings to a progressively disabling joint disorder. ETIOLOGY, RISK FACTORS, AND SYMPTOMS

OA of the knee is characterized by degeneration of the articular cartilage, morphologic changes to the subchondral bone, and damage to the surrounding soft tissue (Felson, 2004). These structural changes lead to joint pain, quadriceps muscle weakness, reduced range of motion, joint instability, and poor balance (Baert et al., 2014). As a result, most individuals with symptomatic knee OA report difficulty with walking, stair climbing, rising from a car, or carrying heavy loads. Early in the disease, patients may experience stiffness upon arising, which recedes with activity. As the disease progresses, stiffness and joint pain with movement become more constant. Incidence of OA increases with aging and is more common in those who have family members with the disease.

Infection Other connective tissue disorders (e.g., lupus, scleroderma) Fibromyalgia Rheumatoid arthritis (RA) Psoriatic arthritis Gout (crystalline arthritis)

Cartilage loss, joint space narrowing Increased bone density at narrowed joint spaces (in response to increased friction with cartilage loss) Osteophytes Bone erosion

TREATMENT/MANAGEMENT

Management goals for patients with OA are to optimize function, minimize pain, and if possible, to modify the process resulting in joint damage associated with the disease (Nelson et al., 2014). Chronic pain and disability are often associated with OA. Treatment encompasses both nonpharmacologic and pharmacologic approaches. Nonpharmacologic treatment may include weight loss, rest, physical therapy and structured exercise programs, assistive devices (canes, raised toilet seats, and walkers), heat and cold therapy, supportive orthotic shoes, and use of transcutaneous electrical stimulation. Other nonpharmacologic treatments may include participation in non-weight-bearing or low-impact exercise and tai chi programs and treatment with traditional Chinese acupuncture. Pharmacologic recommendations may include the following: topical capsaicin, topical nonsteroidal anti-inflammatory drugs (NSAIDs), and oral NSAIDs, including cyclooxygenase-2 (COX-2) selective inhibitors. Evaluation of intra-articular platelet-rich plasma injections have not been shown to be beneficial in the reduction of pain or altered joint structure for individuals with knee arthritis (Bennell et al., 2021).

Rheumatoid Arthritis DEFINITION AND SCOPE

RA is a chronic, inflammatory autoimmune disease and is the most common chronic inflammatory polyarticular arthritis,

878  Part III  MANAGING SYMPTOMS AND HEALTH CONSIDERATIONS

TABLE 45.4  Classification Criteria for Rheumatoid Arthritis Target population to be tested should have at least one joint with definite clinical swellinga and with the synovitis not better explained by another disease. CRITERIA

SCORE

A. THE NUMBER AND SIZE OF JOINTS THAT ARE SWOLLEN

1 Large joint

0

2–10 Large joints

1

1–3 Small joints (with or without involvement of large joints)

2

4–10 Small joints (with or without involvement of large joints)

3

>10 Joints (at least 1 small joint)

5 B. SEROLOGY

Negative RF and negative ACPA

0

Low-positive RF or low-positive ACPA

2

High-positive RF or high-positive ACPA

3 C. ACUTE PHASE REACTANTS

Normal CRP and normal ESR

0

Abnormal CRP or abnormal ESR

1 D. DURATION OF SYMPTOMS