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: 10514637
• 负责人: Christina A Muzny
• 金额: $ 28.35万
• 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 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10514637
• 关键词: 16S ribosomal RNA sequencing; Address; Applications Grants; Archives; Atopobium vaginae; Atrophic; Bacteria; Bacterial Vaginosis; Bacteriophages; Behavioral; Biological Factors; Blood; Clinical; Communities; Cross-Sectional Studies; Data; Epithelium; Estrogen deficiency; Estrogens; Evolution; Future; Gender Confirmation Surgery; Genital; Genitalia; Goals; Growth; HIV; Health Benefit; Hormonal; Hormonal Change; Knowledge; Lactobacillus; Longitudinal Studies; Menstruation; Metagenomics; 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; assigned female at birth; bacterial community; case-based; cis-female; diaries; dysbiosis; experience; fungus; gender affirming hormone therapy; health disparity; male; metagenomic sequencing; microbial community; microbiota; prevent; repository; routine Bacterial stain; sample collection; sex; 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.

抽象的： 跨性别男性（TGM）（自认为是男性但出生时被指定为女性的人）通常会放弃性别。 然而，许多人开始进行 TGM 男性化。 睾酮治疗与雌激素缺乏的顺性别女性 (CGW) 非常相似，TGM 对睾酮的治疗经验。 绝经后阴道上皮厚度减少和月经减少。 与绝经后 CGW 不同，TGM 可能会因乳酸菌丧失而导致阴道生态失调。 睾酮水平也会升高。低雌激素/高睾酮对睾酮的影响。 TGM 的阴道微生物群未知，不能从 CGW 的激素变化研究中推断。 由于使用睾酮而增加性欲，与性行为相结合可能会影响 TGM 的阴道微生物群，使她们面临细菌性阴道病 (BV) 的风险，并最终面临艾滋病毒和其他性传播感染的风险。 关于 TGM A 中睾酮注射后阴道微生物群组成的数据有限。 比较睾酮 TGM 和 CGW ≥1 年的横断面研究发现，阴道微生物群 71% 的睾酮 TGM 不太可能以乳酸菌为主，而更有可能富含 > 30 种其他细菌，其中许多与细菌性阴道炎有关。这项研究没有比较 TGM 的阴道微生物群。 睾酮启动前和后也无法识别可能发生在阴道菌群失调或之前的微生物群变化 我们认为睾酮的启动会改变阴道微生物群的组成。 在 TGM 中，与睾酮和性参与相关的性欲增加。 行为，iBV 可能是由 BV 相关细菌 (BVAB) 的性传播引起的。 目的是找出优化 TGM 中睾酮的健康益处的方法，同时减轻其潜在风险。 目标 1. 研究 TGM 启动过程中阴道微生物群组成随时间的变化 我们将从 40 个 TGM 中获取每日阴道标本和每日日记。 正常阴道微生物群（无 Amsel 标准，Nugent 评分 0-3），在开始睾酮激素治疗前 7 天开始 90 天后，将对所有 7 个前睾酮样本进行每周一次的 16S rRNA V4 测序。 随后采集样本以确定 TGM 中阴道微生物群落状态类型 (CST) 的组成。 经历阴道生态失调的转变（至少连续 2 天 Nugent 评分≥4），16S 测序 将从班前 7 天到班后 3 天对样本进行密集采样。 目标 2. 确定睾酮 TGM 中 iBV 之前阴道微生物群的变化。 目标 1 中 5 个 TGM 中发生 iBV 的标本（即至少连续 2 天 Nugent 评分≥7）（病例） 将确定 5 名未发生 iBV 的对照者，在 iBV 发生前 14 天进行每日阴道标本检查。 包括病例中 iBV 的当天以及对照的 14 天阴道标本（与基于病例的病例一致） 睾丸激素启动的那一天）将使用鸟枪法宏基因组学进行表征。