Neither vaginal estradiol tablet nor vaginal moisturizer were more efficacious than placebo at reducing symptom severity or improving sexual function for women with moderate-to-severe postmenopausal vulvovaginal symptoms, a study found.
To compare the efficacy of a low-dose vaginal estradiol tablet and a vaginal moisturizer, and then each to placebo, researchers conducted a 12-week, two-center, randomized clinical trial among postmenopausal women with vulvovaginal itching, pain, dryness, irritation, or pain with penetration.
Patients received vaginal 10-μcg estradiol tablet daily for two weeks, then twice weekly, plus placebo gel three times a week (n=102), a placebo tablet plus vaginal moisturizer (n=100), or dual placebo (n=100). Symptom severity was rated 0 to 3, signifying none, mild, moderate, or severe symptoms.
The main outcome was decrease in severity of most bothersome symptom (MBS) between enrollment and 12 weeks. Prespecified secondary outcomes were composite Vaginal Symptom Index (VSI), satisfaction with treatment received on a Likert scale of 0 (not satisfied) to 10 (completely satisfied), meaningful benefit from the study medications (yes or no), Female Sexual Function Index (FSFI), Female Sexual Distress Scale–Revised Item 1, Vaginal Maturation Index (VMI) that measures the effect of estrogen on the vaginal mucosa, and vaginal pH. Vaginal Symptom Index was the mean severity score of the five vulvovaginal symptoms listed as MBS choices. Results were published online March 19 by JAMA Internal Medicine.
The 302 women had a mean (SD) age of 61 years and were primarily white (88%), college educated (66%), and sexually active (81%). 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=0.25) or moisturizer (P=0.31) 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=0.64), and between moisturizer (3.1; 95% CI, 1.7 to 4.5) and placebo (P=0.17).
Although the study was not powered to make head-to-head comparisons, strengths included that its population was consistent with women presenting to primary care settings, the authors wrote. Because vaginal estradiol tablets appear not to add benefit beyond vaginal gel or moisturizer, shared decision making for treatment of postmenopausal vulvovaginal symptoms can be based on cost and patient formulation preference, they continued.
“Many postmenopausal women with moderate to severe vulvovaginal symptoms can be treated with a nonprescription vaginal lubricating gel,” the authors wrote. “However, not all gel formulations may have the same effects, and some women may prefer nongel formulations. Treatment choice should be based on individual patient preferences regarding cost and formulation.”
An invited commentary noted design limitations but highlighted the study's “striking double-negative finding for both of its placebo comparisons.” Neither low-dose vaginal estradiol nor the brand of vaginal moisturizer studied offered meaningful benefit for control of women's symptoms relative to placebo, the commentary continued.
“Based on the results of this study, women and their physicians may want to take this one step further and conclude that postmenopausal women experiencing vulvovaginal symptoms should choose the cheapest moisturizer or lubricant available over the counter—at least until new evidence arises to suggest that there is any benefit to doing otherwise,” the editorial stated.