Vaginal estradiol affects vaginal microbiota, alleviates local symptoms in postmenopausal women

Postmenopausal women with genitourinary symptoms of menopause is widely advised with vaginal estradiol or moisturizer for symptom improvement, but the impact of these treatments on the local microenvironment is poorly understood.

A recent study by Dr Sujatha Srinivasan, PhD and team in a secondary analysis of a randomized clinical trial in postmenopausal women found that women with moderate to severe vulvovaginal symptoms, women using vaginal 10 μg estradiol tablet demonstrated larger changes in the vaginal microbiota and metabolome compared with women using vaginal moisturizer or placebo, despite a decrease in pH within each intervention group.

The findings of the study are published in JAMA Network Open.

The study is a post hoc prespecified secondary analysis of a 12-week multicenter randomized clinical trial among postmenopausal women with moderate to severe genitourinary symptoms. Women were enrolled between April 2016 and February 2017; final follow-up visits occurred in April 2017. Data were analyzed from November 2018 to July 2021. Ten-μg vaginal estradiol plus placebo gel vs placebo tablet plus vaginal moisturizer vs dual placebo. The main outcome measures were changes in the diversity and composition of the vaginal microbiota, changes in the metabolome, and pH.

The results of the study were

• A total of 302 postmenopausal women from the parent trial, 144 women were included in this analysis. After 12 weeks, the microbiota was dominated with Lactobacillus and Bifidobacterium communities among 36 women (80%) in the estradiol group, compared with 16 women (36%) using moisturizer and 13 women (26%) using placebo (P < .001).

• The composition of vaginal fluid metabolites also varied after 12-weeks among women in the estradiol group with significant changes in 90 of 171 metabolites measured (53%) (P < .001), including an increase in lactate.

• The 12-week pH among women in the estradiol group was lower vs placebo pH, 5 [4.5-6.0] vs 6 [5.5-7.0]; but not the moisturizer group vs placebo pH, 6 [5.5-6.5].

• There was a decrease in pH from baseline to 12-weeks within the moisturizer pH, 7 [6.0-7.5] vs 6 [5.5-6.5] and placebo pH, 7 [7.0-7.5] vs 6 [5.5-7.0] groups.

• Women with high-diversity bacterial communities at baseline exhibited greater median change in pH compared with women with low-diversity communities −1 [−2 to −0.5] vs −0.3 [−1.1 to 0].

Researchers concluded that use of vaginal estradiol tablets resulted in substantial changes in the vaginal microbiota and metabolome with a lowering in pH, particularly in women with high-diversity bacterial communities at baseline. Low pH moisturizer or placebo did not significantly impact the vaginal microbiota or metabolome despite lowering the vaginal pH. Estradiol use may offer additional genitourinary health benefits to postmenopausal women.

Reference: 10.1001/jamanetworkopen.2022.5032