Vaginal microbiota and genitourinary syndrome of menopause in premenopausal breast cancer patients receiving endocrine therapy: a longitudinal cohort study protocol

Background Endocrine therapy with ovarian function suppression combined with aromatase inhibitors or tamoxifen is essential for hormone receptor-positive breast cancer in premenopausal women, but often induces genitourinary syndrome of menopause (GSM) via hypoestrogenism. Existing research focuses on natural menopause, with limited longitudinal data on vaginal microbiome changes in breast cancer survivors, especially amid rising cases among young Chinese women. Objectives To (1) assess temporal effects of endocrine therapy on vaginal microbiome α - and β -diversity and dominant taxa (e.g., Lactobacillus); (2) explore dose–response links between microbiome shifts and GSM severity; and (3) compare OFS + AI versus OFS + TAM impacts on vaginal microecology. Methods This single-center prospective cohort at Women’s Hospital, Zhejiang University School of Medicine, will enroll 110 premenopausal women (18–45 years) with hormone receptor-positive breast cancer, allocated to OFS + AI or OFS + TAM based on clinical regimens. Vaginal swabs collected at baseline and 1, 3, 6, 12 months undergo 16S rRNA sequencing (V3-V4 region) with DADA2-based ASV analysis via QIIME 2 for species-level resolution. Assessments include Vaginal Health Index (VHI), GSM symptoms (VAS for dryness, dyspareunia, burning), s, and urinary symptoms (ICIQ-SF). Primary outcomes: microbiome diversity (Simpson index) and Lactobacillus abundance. Secondary: VHI, VAS, urinary scores. Analyses use repeated measures ANOVA and generalized estimating equations; sample size accounts for medium effect ( d = 0.8) and 10% attrition. Ethically approved and registered in Chinese Clinical Trial Registry. Conclusion As a longitudinal study on vaginal microecology in this population, this protocol integrates molecular and clinical data to reveal GSM mechanisms, informing personalized interventions for better quality of life and adherence. Clinical trial registration http://www.chictr.org.cn/showproj.html?proj=296570 , Identifier (No. ChiCTR2500115283)