The Impact of Menopause Treatments on the Vaginal Microbiome of Peri-menopausal and Post-menopausal Women

Peri- and post-menopausal women experience dysbiosis of the vaginal microbiota, characterized by a non-Lactobacillus dominant microbiome and higher microbial richness. However, there is a critical need to better characterize how the initiation and cessation of interventions used to manage menopause symptoms impact the vaginal microbiome of peri- and post-menopausal women. The overall objective of this project is to investigate the epidemiological and biological factors that influence vaginal dysbiosis and its clinical management among peri- and post-menopausal women. Our central hypothesis is that treatments for managing menopause symptoms produce significant changes to the vaginal microbiome, and that these changes are mediated by the stage of the menopause transition. In Aim 1, we will recruit a longitudinal clinical cohort of peri-menopausal, early post-menopausal, and late post-menopausal women to characterize changes in the vaginal microbiota composition and taxonomic richness following initiation of menopause treatments. In Aim 2, we will characterize longitudinal changes in the vaginal microbiome following cessation of menopause treatments. We will use 16S rRNA gene amplicon sequencing (V3-V4 hypervariable region) from self-collected vaginal swabs. These aims constitute the mentored research component of the candidate’s career development plan for this K01. In parallel with this research, the candidate will pursue training in translational microbiome science, supported by an exemplary team of renowned investigators with expertise in gynecological health (Primary Mentor, Dr. Juno Obedin-Maliver), the vaginal microbiome (Co-Mentors Drs. David Relman, Christina Muzny, and Christopher Taylor), and the impact of menopause on genital tissues (Co- Mentor Dr. Bertha Chen). Stanford University offers a world-class research infrastructure that fosters outstanding collaborative and innovative translational research. This research also leverages the expertise of Stanford’s OBGYN Department, including its Menopause and Healthy Aging Programs. In summary, the strong mentoring environment and training plan are anticipated to comprehensively prepare Dr. Tordoff to launch an independent research career. The proposed studies promise to address critical gaps in our understanding of how pharmacological treatments for menopause impact vaginal health, and the results of this research will improve decision making for clinicians and patients regarding menopause treatments.