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Vaginal Estrogen for Genitourinary Syndrome of Menopause: A Systematic Review

Rahn, David D. MD; Carberry, Cassandra MD; Sanses, Tatiana V. MD; Mamik, Mamta M. MD, MS; Ward, Renée M. MD; Meriwether, Kate V. MD; Olivera, Cedric K. MD, MS; Abed, Husam MD; Balk, Ethan M. MD, MPH; Murphy, Miles MD

doi: 10.1097/AOG.0000000000000526
Contents: Review

OBJECTIVE: To comprehensively review and critically assess the literature on vaginal estrogen and its alternatives for women with genitourinary syndrome of menopause and to provide clinical practice guidelines.

DATA SOURCES: MEDLINE and Cochrane databases were searched from inception to April 2013. We included randomized controlled trials and prospective comparative studies. Interventions and comparators included all commercially available vaginal estrogen products. Placebo, no treatment, systemic estrogen (all routes), and nonhormonal moisturizers and lubricants were included as comparators.

METHODS OF STUDY SELECTION: We double-screened 1,805 abstracts, identifying 44 eligible studies. Discrepancies were adjudicated by a third reviewer. Studies were individually and collectively assessed for methodologic quality and strength of evidence.

TABULATION, INTEGRATION, AND RESULTS: Studies were extracted for participant, intervention, comparator, and outcomes data, including patient-reported atrophy symptoms (eg, vaginal dryness, dyspareunia, dysuria, urgency, frequency, recurrent urinary tract infection (UTI), and urinary incontinence), objective signs of atrophy, urodynamic measures, endometrial effects, serum estradiol changes, and adverse events. Compared with placebo, vaginal estrogens improved dryness, dyspareunia, urinary urgency, frequency, and stress urinary incontinence (SUI) and urgency urinary incontinence (UUI). Urinary tract infection rates decreased. The various estrogen preparations had similar efficacy and safety; serum estradiol levels remained within postmenopausal norms for all except high-dose conjugated equine estrogen cream. Endometrial hyperplasia and adenocarcinoma were extremely rare among those receiving vaginal estrogen. Comparing vaginal estrogen with nonhormonal moisturizers, patients with two or more symptoms of vulvovaginal atrophy were substantially more improved using vaginal estrogens, but those with one or minor complaints had similar symptom resolution with either estrogen or nonhormonal moisturizer.

CONCLUSION: All commercially available vaginal estrogens effectively relieve common vulvovaginal atrophy-related complaints and have additional utility in patients with urinary urgency, frequency or nocturia, SUI and UUI, and recurrent UTIs. Nonhormonal moisturizers are a beneficial alternative for those with few or minor atrophy-related symptoms and in patients at risk for estrogen-related neoplasia.

CLINICAL TRIAL REGISTRATION: PROSPERO International prospective register of systematic reviews,, CRD42013006656.

Approved vaginal estrogen therapies are effective in management of common, bothersome postmenopausal atrophy-related vulvovaginal and lower urinary tract symptoms.Supplemental Digital Content is Available in the Text.

University of Texas Southwestern Medical Center, Dallas, Texas; Women & Infants Hospital, Alpert Medical School of Brown University and the Center for Evidence Based Medicine, Brown University, Providence, Rhode Island; the University of Maryland School of Medicine, Baltimore, Maryland; the Icahn School of Medicine at Mount Sinai, New York, New York; Vanderbilt University Medical Center, Nashville, Tennessee; the University of New Mexico Health Sciences Center, Albuquerque, New Mexico; Henry Ford Health System, Detroit, Michigan; and the Institute for Female Pelvic Medicine and Reconstructive Surgery, North Wales, Pennsylvania.

Corresponding author: David D. Rahn, MD, Associate Professor, Department of Obstetrics & Gynecology, Division of Female Pelvic Medicine & Reconstructive Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9032; e-mail:

Presented at the 40th Annual Scientific Meeting of the Society of Gynecologic Surgeons, March 23–26, 2014, Scottsdale, Arizona.

The Society of Gynecologic Surgeons provided funding support for assistance by methods experts in systematic review and logistic support.

Financial Disclosure The authors did not report any potential conflicts of interest.

© 2014 by The American College of Obstetricians and Gynecologists.