Mitchell CM, Mitchell AJ, Wu MC, et al. - Nearly half of all postmenopausal women experience symptoms of vulvar, vaginal or urinary discomfort, which are identified to have significant impact on their sexual function and quality of life. Researchers here investigated if the vaginal microbiota and/or mucosal immune response contribute to the severity of bothersome vaginal symptoms, by performing 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. They conducted a secondary analysis of samples obtained in a 12-week randomized trial of treatment with vaginal estradiol or moisturizer vs placebo for moderate-severe postmenopausal symptoms of vaginal discomfort. Twenty women were randomly selected in each arm with ≥ 2-point reduction in most bothersome symptom (MBS) severity (responders) and 20 matched controls with ≤ 1-point reduction (non-responders). Women (n = 120) were of mean age 61 years and were primarily White (92%). Findings from this small study suggest no significant correlation of postmenopausal vaginal symptom severity with vaginal microbiota or mucosal inflammatory markers. Greater abundance of lactobacilli and lower vaginal pH were reported at the end of treatment for women receiving vaginal estradiol.