# Methods to Test Lifestyle, Vaginal Microenvironment, and Genitourinary Symptoms across Menopause Transition

> **NIH NIH R56** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $795,662

## Abstract

Over 50% of postmenopausal women are affected by the genitourinary syndrome of menopause (GSM), which
includes vaginal atrophy, vaginal dryness, and sexual dysfunction. Symptoms worsen if untreated and are
associated with stress and depression. Estrogen decline in menopause is thought to lead to reduced glycogen
accumulation in the vaginal epithelium and is associated with low vaginal Lactobacillus spp. levels in 50-80%
of women. Lactobacillus spp. protect the urogenital tract from pathogens in part by producing lactic acid and for
their anti-inflammatory properties, but whether lactobacilli are a marker for estrogen levels or play a functional
role in GSM is unknown. Available treatments for vulvovaginal GSM symptoms have limitations. Some women
are contraindicated for hormonal therapy or are concerned with side effects. Vaginal lubricants provide some
relief, but they may be toxic to the vaginal epithelium, reduce lactobacilli, and raise urogenital infection risk.
New therapies are needed. Vaginal microbiota are a plausible approach to treatment, however, probiotics
alone have not proven effective. Vaginal microbiota co-vary with metabolite and immune profiles, and it is
unknown how these molecular features relate to GSM. We hypothesize that core vaginal microenvironment
biomarkers (VMB; e.g., microbial, metabolite, and immune profiles) reflect vaginal biological aging (V-BA) that
is increased by menopause but may also be modifiable by other factors, such as lifestyle. Longitudinal studies
are needed to identify core age-related VMB and determine how they relate to GSM. To accomplish this task,
we will develop new statistical methods to combine complex longitudinal epidemiologic data with high-
dimensional compositional data. We will leverage 2,301 archived cervicovaginal samples collected as part of a
cohort of 812 women aged 35-60 years with visits every six months for two years (R01-CA123467). Specific
Aims are to 1) quantify V-BA using VMB; 2) evaluate the longitudinal relationship between V-BA and GSM; 3)
longitudinally assess the relationship of lifestyle factors on V-BA and VMB; 4) quantify longitudinal mediation
by V-BA and VMB between lifestyle and GSM. Microbiota are already profiled by 16S rRNA gene amplicon
sequencing (R21-AI107224). Along with clinical, demographic, and behavioral surveys, we will 1) use cervical
secretions and multiplexed bead-based immune-assays to quantify concentrations of 70 immune markers
(cytokines, chemokines, growth factors); 2) profile metabolites from vaginal swabs (GC/LC-MS). This proposal
is focused on developing and validating new statistical methods that refine and adapt modern structural
modeling and microbiota compositional analyses. The novel statistical approaches will allow identification of
vaginal microenvironment features which may lead to development of new and effective GSM treatments.
These methods will also provide a new framework to handle missing data and confounding that has limited
pr...

## Key facts

- **NIH application ID:** 10229293
- **Project number:** 1R56AG068673-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** REBECCA M. BROTMAN
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $795,662
- **Award type:** 1
- **Project period:** 2020-09-30 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229293

## Citation

> US National Institutes of Health, RePORTER application 10229293, Methods to Test Lifestyle, Vaginal Microenvironment, and Genitourinary Symptoms across Menopause Transition (1R56AG068673-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10229293. Licensed CC0.

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