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A systematic review of the efficacy and safety of vaginal estrogen products for the treatment of genitourinary syndrome of menopause

Biehl, Colton, BS; Plotsker, Olivia; Mirkin, Sebastian, MD

doi: 10.1097/GME.0000000000001221
Review Article

Objective: We updated a systematic review to evaluate the totality of evidence available for the efficacy and safety of vaginal estrogen products for the treatment of genitourinary syndrome of menopause (GSM) based on published randomized controlled trials.

Methods: We searched the Cochrane Library, Ovid, PubMed, Medline, Embase, and for English-language articles from database inception to June 2018. Our search consolidated 2,086 potential sources to 53 full-text articles that were reviewed and found relevant to our systematic review.

Results: We identified 53 studies that met the inclusion criteria that evaluated the efficacy and safety of vaginal estrogen versus placebo or other hormone and nonhormone controls. Compared with placebo, all vaginal estrogens demonstrated superiority in objective endpoints and subjective endpoints of GSM, whereas some trials demonstrated superiority versus placebo in urogenital symptoms. No significant difference was observed between various dosages and dosage forms of vaginal estrogen products. Vaginal estrogen showed superiority over vaginal lubricants and moisturizers for the improvement of objective clinical endpoints of vulvovaginal atrophy but not for subjective endpoints. Unopposed vaginal estrogens seemed safe, although studies were not powered to detect a long-term estrogenic side effect.

Conclusion: Estrogen products were found to be clinically effective for the treatment of GSM with doses as low as 4 μg. Vaginal estrogen products seem to be safe with few adverse effects, although there is a lack of long-term controlled clinical trial safety data. This review supports the use of commercially available vaginal estrogen therapies as an effective and safe first-line therapy for the treatment of moderate-to-severe GSM.

TherapeuticsMD, Boca Raton, FL.

Address correspondence to: Sebastian Mirkin, MD, TherapeuticsMD, 6800 Broken Sound Parkway NW, Boca Raton, FL 33487. E-mail:

Received 16 June, 2018

Revised 27 August, 2018

Accepted 27 August, 2018

Funding/support: None.

Financial disclosure/conflicts of interest: CB and OP are interns at TherapeuticsMD. SM is an employee of TherapeuticsMD with stock/stock options.

© 2019 by The North American Menopause Society.