Interactions between vaginal, periurethral and urinary microbiota in genitourinary syndrome of menopause and the effects of local estrogen therapy.

OBJECTIVES: Alterations to the vaginal microbiota have been investigated in genitourinary syndrome of menopause but data regarding periurethral and urinary microbiota remain limited. We aimed to characterize vaginal, periurethral, and urinary microbiota in clinically stratified postmenopausal women and to evaluate the effects of estrogen therapy. STUDY DESIGN: In this prospective study, postmenopausal women were categorized as controls without atrophy or symptoms, women with clinical atrophy without symptoms, symptomatic women, and symptomatic women receiving 12 weeks of vaginal estriol. Vaginal, periurethral, and bladder samples were collected. MAIN OUTCOME MEASURES: Microbiota composition and diversity (alpha diversity - Shannon index; and beta diversity - Bray-Curtis dissimilarity) across urogenital niches and changes in these following estrogen therapy. RESULTS: Vaginal and periurethral alpha diversity was higher in women with asymptomatic atrophy and symptomatic women at baseline than in controls and estrogen-treated women. Beta diversity analyses demonstrated separation of controls and estrogen-treated women from the atrophy groups at baseline. Controls exhibited Lactobacillus-enriched periurethral communities and Klebsiella-dominant urinary profiles. Women with asymptomatic atrophy and symptomatic women showed reduced Lactobacillus and increased anaerobic taxa in vaginal and periurethral niches, while urinary samples were characterized by Escherichia predominance. Notably, in women with asymptomatic atrophy, Lactobacillus abundance was higher in periurethral than vaginal samples. Estrogen therapy increased Lactobacillus abundance in vaginal and periurethral compartments and shifted urinary microbiota toward a control-like composition. Periurethral Streptococcus abundance correlated with sexual symptom scores. CONCLUSIONS: Microbial alterations in genitourinary syndrome of menopause are compartment-specific and extend beyond the vagina. Periurethral microbiota may contribute to symptom expression, while local estrogen therapy promotes restoration of Lactobacillus-dominant urogenital microbiota. CLINICALTRIALS: gov registration: NCT06633705.