The Impact of Testosterone Use on the Vaginal Microbiota in Transgender Men, including Susceptibility to Bacterial Vaginosis

睾酮的使用对跨性别男性阴道微生物群的影响，包括对细菌性阴道病的易感性

• 批准号: 10402699
• 负责人: Christina A Muzny
• 金额: $ 15.55万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-11-01 至 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10402699
• 关键词: 16S ribosomal RNA sequencing; Address; Applications Grants; Archives; Atopobium vaginae; Atrophic; Bacteria; Bacterial Vaginosis; Bacteriophages; Behavioral; Birth; Blood; Clinical; Communities; Cross-Sectional Studies; Data; Epithelial; Estrogens; Evolution; Female; Future; Gender; Gender Confirmation Surgery; Genital; Genitalia; Goals; HIV; Health Benefit; Hormonal; Hormonal Change; Knowledge; Lactobacillus; Longitudinal Studies; Masculine; Menstruation; Metagenomics; Microbiology; Participant; Persons; Pharmaceutical Preparations; Pilot Projects; Population; Postmenopause; Predisposition; Prospective cohort study; Recommendation; Research Design; Residual state; Ribosomal RNA; Risk; Risk Factors; Sampling; Serum; Sex Behavior; Sexual Transmission; Sexually Transmitted Diseases; Shotguns; Specimen; Symptoms; Testing; Testosterone; Thick; Thinness; Time; Time Study; United States National Institutes of Health; Vagina; Vaginal Douching; Vaginitis; Viral; bacterial community; base; case control; case-based; cis-female; diaries; dysbiosis; experience; fungus; health disparity; hormone therapy; male; metagenomic sequencing; microbial community; microbiota; prevent; repository; routine Bacterial stain; sample collection; sex; sexual HIV transmission; transgender men; vaginal infection; vaginal lactobacilli; vaginal microbiome; vaginal microbiota

ABSTRACT: Transgender men (TGM) (persons who identify as male but assigned female sex at birth) often forgo gender- affirming surgery and retain their natal genitalia (i.e. vaginas). However, many TGM initiate masculinizing testosterone therapy. Much like estrogen-deficient cisgender women (CGW), TGM on testosterone experience decreased thickness of the vaginal epithelium and loss of menses. The vaginal microbiota of post-menopausal CGW may shift toward a vaginal dysbiosis due to loss of lactobacilli. Unlike post-menopausal CGW, TGM on testosterone also experience elevated testosterone levels. The impact of low estrogen/high testosterone on the vaginal microbiota of TGM is unknown and cannot be extrapolated from studies of CGW. Hormonal changes in conjunction with sexual behaviors due to increased sexual desire from use of testosterone could impact the vaginal microbiota of TGM, putting them at risk for bacterial vaginosis (BV) and, ultimately, HIV and other STIs. Data are limited regarding the composition of the vaginal microbiota after initiation of testosterone in TGM. A cross-sectional study comparing TGM on testosterone for ≥1 year to CGW found that the vaginal microbiota of 71% of TGM on testosterone was less likely to be lactobacillus-dominated and more likely to be enriched with >30 other bacterial species, many associated with BV. This study did not compare the vaginal microbiota of TGM pre- and post-testosterone initiation nor identify shifts in the microbiota that could precede vaginal dysbiosis or incident BV (iBV). We hypothesize that testosterone initiation will alter the composition of the vaginal microbiota in TGM. In the setting of increased sexual desire associated with testosterone and participation in sexual behaviors, iBV could be elicited by sexual transmission of BV-associated bacteria (BVAB). Our long-term goal is to identify ways to optimize the health benefits of testosterone in TGM while mitigating its potential risks. Aim 1. To investigate changes in the composition of the vaginal microbiota over time in TGM initiating testosterone treatment. We will obtain daily vaginal specimens and daily diaries from 40 TGM with baseline normal vaginal microbiota (no Amsel criteria, Nugent score 0-3), starting 7 days prior to testosterone initiation and 90 days after. 16S rRNA V4 sequencing will be performed on all 7 pre-testosterone specimens and weekly specimens thereafter to determine vaginal microbial community state type (CST) compositions over time. In TGM who experience a shift to vaginal dysbiosis (Nugent score ≥4 on at least 2 consecutive days), 16S sequencing will be performed on specimens starting 7 days pre-shift through 3 days post-shift for intensive sampling. Aim 2. To identify changes in the vaginal microbiota that precede iBV in TGM on testosterone. Vaginal specimens from 5 TGM in Aim 1 who develop iBV (i.e. Nugent score ≥7 for at least 2 consecutive days) (cases) and 5 controls who do not develop iBV will be identified. Daily vaginal specimens from 14 days prior to iBV, including the day of iBV, in cases and 14 days of vaginal specimens from controls (aligned with cases based on the day of testosterone initiation) will be characterized using shotgun metagenomics.

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