Urgency Urinary Incontinence (UUI), the hallmark of overactive bladder (OAB), is a prevalent, chronic condition disproportionately affecting postmenopausal women. The debilitating symptoms substantially degrade physical activity and quality of life, yet despite the heavy burden on public health, little is understood of the pathophysiology of UUI. Multiple epidemiologic factors implicate a microbial influence in this disease. New detection methods have revealed microbial communities within the urinary tract, once thought to be sterile, and implicated changes in these communities in UUI. The role of these alterations in the urine is unclear, but in the vagina, loss of protective Lactobacilli after menopause leads to increased vaginal pH, increased local inflammation, and impaired resistance to both vaginal and urinary infections. Early data suggest free exchange of urinary and vaginal bacteria; thus, vaginal microbiota may promote UUI via transmission of this loss of protective Lactobacilli in the urine, promoting similar changes in bladder function as seen in the vagina. In postmenopausal women, vaginal estrogen supplementation can improve UUI symptoms, but the mechanism of this improvement is unknown. As vaginal estrogen can also alter vaginal bacteria, increasing the abundance of Lactobacilli, we hypothesize that vaginal estrogen will impact urinary microbiota in a similar way to ameliorate UUI symptoms. To examine the relation between vaginal and urinary microbiota and UUI symptoms, we will conduct a pre-post pilot study in postmenopausal women with UUI, who are <10 years from menopause and estrogen-nave. We will use next-generation sequencing to define the baseline urinary and vaginal microbiota, validated OAB-specific patient-reported measures to assess the severity and impact of UUI symptoms, and vaginal cytologic indices to define vaginal epithelial quality. After a 3-month trial of standard-dose vaginal estrogen, these measures will be repeated. This proposal seeks to describe baseline vaginal features of postmenopausal women with UUI by characterizing vaginal microbiota of postmenopausal women with UUI and its concordance with urinary microbiota, and assessing vaginal epithelial quality at baseline in women with UUI. After the intervention, we will explore the effect of vaginal estrogen administration on: a) vaginal and urinary microbiota and b) vaginal quality indices in postmenopausal women with UUI and their relation to improvements in UUI symptom severity, allowing an exploration of the baseline participant characteristics positively associated with improvements in vaginal and urinary microbiota as well as the amelioration of UUI symptoms. We expect this will confirm the association of a loss of protective vaginal microbial communities and decreased vaginal epithelial quality with worsening UUI symptoms and provide evidence that local estrogen supplementation promotes symptomatic resolution by modifying vaginal microbiota and improving epithelial quality. Such findings would reveal novel approaches to treatment aimed at manipulation of the vaginal microbiome, which will provide the basis for larger, interventional trials for this underserved population.
Changes in the bacteria resident in the urine, the urinary microbiota, have been suggested to alter bladder epithelial structure to cause urgency urinary incontinence (UUI), a condition which disproportionately affects women after menopause, the physiologic estrogen-deficiency that is also associated with changes in vaginal microbiota. The neigboring bacterial communities that inhabit the vagina and urine appear interconnected, suggesting that the changes in vaginal bacteria and epithelial quality may be both a marker of and source for the bladder dysfunction in UUI. The comprehensive characterization of vaginal and urinary microbes in UUI and the correlation of vaginal changes, both microbial and histologic, with improvements in objectively-defined UUI symptoms after local treatment with estrogen suggested in this study will establish a role for vaginal health in the origin of urologic conditions, such as UUI.
