Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal Symptoms: A Randomized Clinical Trial

Abstract

Importance: Nearly half of postmenopausal women report bothersome vulvovaginal symptoms, but few data support the efficacy of 2 commonly recommended treatments.

Objective: To compare the efficacy of a low-dose vaginal estradiol tablet and a vaginal moisturizer, each vs placebo, for treatment of moderate-to-severe postmenopausal vulvovaginal symptoms.

Design, setting, and participants: This 12-week multicenter randomized clinical trial enrolled postmenopausal women with moderate to severe symptoms of vulvovaginal itching, pain, dryness, irritation, or pain with penetration.

Interventions: Vaginal 10-μg estradiol tablet (daily for 2 weeks, then twice weekly) plus placebo gel (3 times a week) (n = 102) vs placebo tablet plus vaginal moisturizer (n = 100) vs dual placebo (n = 100).

Main outcomes and measures: The main outcome was decrease in severity (0-3) of most bothersome symptom (MBS) between enrollment and 12 weeks. Additional measures included a composite vaginal symptom score, Female Sexual Function Index (FSFI) score (2-36), modified Female Sexual Distress Score-Revised item 1, treatment satisfaction and meaningful benefit, Vaginal Maturation Index, and vaginal pH.

Results: The 302 women had a mean (SD) age of 61 (4) years and were primarily white (267 [88%]), college educated (200 [66%]), and sexually active (245 [81%]). Most women (294 [97%]) provided data for the primary analysis. The most commonly reported MBS was pain with vaginal penetration (182 [60%]), followed by vulvovaginal dryness (63 [21%]). Mean baseline MBS severity was similar between treatment groups: estradiol, 2.4 (95% CI, 2.3 to 2.6); moisturizer, 2.5 (95% CI, 2.3 to 2.6); placebo, 2.5 (95% CI, 2.4 to 2.6). All treatment groups had similar mean reductions in MBS severity over 12 weeks: estradiol, -1.4 (95% CI, -1.6 to -1.2); moisturizer, -1.2 (95% CI, -1.4 to -1.0); and placebo, -1.3 (95% CI, -1.5 to -1.1). No significant differences were seen between estradiol (P = .25) or moisturizer (P = .31) compared with placebo. Mean total FSFI improvement was similar between estradiol (5.4; 95% CI, 4.0 to 6.9) and placebo (4.5; 95% CI, 2.8 to 6.1) (P = .64), and between moisturizer (3.1; 95% CI, 1.7 to 4.5) and placebo (P = .17).

Conclusions and relevance: Our results suggest that neither prescribed vaginal estradiol tablet nor over-the-counter vaginal moisturizer provides additional benefit over placebo vaginal tablet and gel in reducing postmenopausal vulvovaginal symptoms.

Trial registration: clinicaltrials.gov Identifier: NCT02516202.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Mitchell is a consultant for Symbiomix Therapeutics. Dr Reed receives grant support from Bayer Pharmaceuticals. Dr LaCroix has served on a scientific advisory board for Sermonix, Inc. No other disclosures are reported.

Figures

Figure 1.. Recruitment, Enrollment, Randomization, and Follow-up of Participants

MBS indicates most bothersome symptom.

Figure 2.. Most Bothersome Symptom Severity Score Change Over 12 Weeks

Most bothersome symptom severity scores (1 indicates mild; 2, moderate; 3, severe) at 0, 4, and 12 weeks of treatment in women randomized to vaginal estradiol tablet (10 μg) + placebo gel, vaginal moisturizer + placebo tablet, or placebo gel + placebo tablet. Women chose vulvovaginal itching, pain, dryness, irritation, or pain with vaginal penetration as their most bothersome symptom at enrollment. There was no significant difference in the change from baseline in severity scores between treatment groups at 4 or 12 weeks (estradiol vs dual placebo, P = .25; moisturizer vs dual placebo, P = .31).