A pilot study of vaginal nerve fiber and blood vessel density in postmenopausal women with genitourinary syndrome of menopause

Objective: Menopause is accompanied by decreased circulating estrogen for all people; however, only some develop genitourinary syndrome of menopause, the cause of which is unknown. In this pilot study, we measured vaginal blood vessel and nerve fiber density, as well as vaginal fluid immune markers to identify a potential cause of vaginal symptoms. Methods: This is a secondary analysis of samples from a randomized trial of vaginal estradiol or moisturizer versus placebo for moderate-severe postmenopausal vaginal discomfort. Fourteen participants were selected from the placebo tablet/vaginal moisturizer or dual placebo arms of the original study: eight with a ≥2-point reduction in most bothersome symptom severity (responders) and six with a <2-point reduction in symptom severity (nonresponders). At 0, 4, and 12 weeks, we characterized vaginal protein gene product 9.5-positive nerve fiber and CD31+ vessel length and density from vaginal wall biopsies (immunofluorescent staining) and vaginal fluid immune markers (MesoScale Discovery). We compared responders versus nonresponders at baseline and across visits using linear mixed models to evaluate associations between symptoms, nerve/vessel length and density, and immune markers. Results: There were no significant differences in baseline characteristics between responders and nonresponders. Mean CD31+ vessel length at 12 weeks was higher in responders than nonresponders ( P = 0.034), while all other measurements were similar between the two groups. No clear patterns were observed across proinflammatory or chemoattractant cytokine concentrations with biopsy measures. Conclusions: Vaginal blood supply and extent of vascularization may contribute to vaginal discomfort symptoms in postmenopausal people; however, the results of this small study need to be confirmed with a larger sample size.