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： 跨性别男人（TGM）（识别为男性但出生时分配的女性的人）通常会忘记性别 确认手术并保留其出生生殖器（即阴道）。但是，许多TGM启动男性化 睾丸激素治疗。很像雌激素缺乏的scisgender妇女（CGW），TGM睾丸激素经验 阴道上皮的厚度降低和月经的损失。绝经后的阴道菌群 由于乳酸杆菌的丧失，CGW可能会转向阴道失调。与绝经后CGW，TGM不同 睾丸激素还具有升高的睾丸激素水平。低雌激素/高睾丸激素对 TGM的阴道菌群未知，不能从CGW研究中推断出来。激素变化 由于使用睾丸激素的性欲增加而与性行为的结合可能会影响 TGM的阴道菌群，使它们有阴道化细菌（BV）以及最终是HIV和其他性传播感染的风险。 在TGM中睾丸激素启动后阴道微生物群的组成的数据受到限制。一个 横断面研究比较睾丸激素的TGM≥1年与CGW的CGW发现阴道菌群的阴道菌群 睾丸激素上有71％的TGM在以乳酸杆菌为主导的可能性较小，更有可能被富含 > 30种其他细菌物种，许多物种与BV相关。这项研究没有比较TGM的阴道菌群 之前和牙菌酮的启动或确定微生物群的转变，可能是阴道营养不良或 事件BV（IBV）。我们假设睾丸激素倡议将改变阴道菌群的组成 在TGM中。在与睾丸激素相关的性欲增加并参与性的情况下 行为，IBV可以通过BV相关细菌（BVAB）的性传播引起IBV。我们的长期目标 是确定方法来优化TGM中睾丸激素的健康益处，同时减轻其潜在风险。 目的1。研究启动TGM中阴道菌群组成的变化 睾丸激素治疗。我们将从40 TGM的每日阴道规格和每日日记中获得基线 正常的阴道菌群（无AMSEL标准，Nugent得分为0-3），从睾丸激素倡议前7天开始 和90天后。 16S rRNA V4测序将在所有7个前睾丸激素标本和每周进行 此后，可以随着时间的推移确定阴道微生物群落状态类型（CST）组成。在TGM中 他们经历了阴道营养不良的转变（Nugent评分至少连续2天≥4），16S测序 换档后3天，将在样本上进行7天的样本，以进行密集采样。 目标2。确定睾丸激素上IBV之前的阴道微生物群的变化。阴道 AIM 1中5个TGM的标本（即至少连续2天nugent得分≥7）（案例）（病例） 将确定未开发IBV的5个控件。 IBV前14天的每日阴道标本， 包括IBV的当天，在对照组中的阴道标本和14天 睾丸激素倡议的日子将使用shot弹枪宏基因组学表征。