Half of all postmenopausal women report symptoms of vulvar, vaginal or urinary discomfort with significant impact on sexual function and quality of life; underlying mechanisms leading to symptoms are poorly understood. To examine the possibility that the vaginal microbiota and/or mucosal immune response contribute to the severity of bothersome vaginal symptoms we conducted a substudy of samples from a randomized trial of vaginal treatment for genitourinary syndrome of menopause (GSM) to compare these features between women whose symptoms improved vs. those who did not.
This is a secondary analysis of samples collected in a 12-week randomized trial of treatment with vaginal estradiol or moisturizer versus placebo for moderate-severe postmenopausal symptoms of vaginal discomfort. We randomly selected 20 women in each arm with ≥2-point decrease in most bothersome symptom (MBS) severity (responders) and 20 matched controls with ≤1-point decrease (non-responders). At 0, 4, 12 weeks, we characterized vaginal microbiota (16S rRNA gene sequencing), vaginal fluid metabolites (broad-based metabolomic profiling), vaginal fluid soluble immune markers (MesoScale Discovery), pH and vaginal maturation index (VMI). We compared responders versus non-responders at baseline, and across all visits using linear mixed models to evaluate associations with microbiota, metabolites and immune markers, incorporating visit and participant-specific random effects while controlling for treatment arm.
Women (n=120) were mean age 61 years and primarily White (92%). At enrollment no significant differences were observed between responders and non-responders in age, MBS type or severity, microbiota composition or diversity, Lactobacillus dominance, metabolome or immune markers. There was a significant decrease in diversity of the vaginal microbiota in both responders and non-responders (p<0.001) over 12 weeks. While this change did not differ by responder status, diversity was associated with treatment arm: more women in the estradiol arm (63%) had Lactobacillus-dominant, lower diversity bacterial communities than women in the moisturizer (35%) or dual placebo (23%) arms (p=0.001) at 12 weeks. Metabolome, VMI and the measured immune markers were not associated with responder status over the 12 weeks but varied by treatment arm.
Postmenopausal vaginal symptom severity was not significantly associated with vaginal microbiota or mucosal inflammatory markers in this small study. Women receiving vaginal estradiol experienced greater abundance of lactobacilli and lower vaginal pH at end of treatment.

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References

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