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.

摘要： 变性人(TGM)(出生时自认为男性但被指定为女性的人)通常放弃性别- 确认手术并保留其出生生殖器(即阴道)。然而，许多TGM启动了男性化 睾丸激素疗法。就像雌激素缺乏的顺性女性(CGW)一样，TGM对睾酮的体验 阴道上皮厚度减少，月经减少。绝经后阴道微生物区系的研究 由于乳酸菌的丢失，CGW可能会转变为阴道生物失调。与绝经后的CGW不同，TGM 睾丸素水平也会升高。低雌激素/高睾酮对大鼠卵巢功能的影响 TGM的阴道微生物区系未知，也不能从CGW的研究中推断出来。荷尔蒙的变化 与因使用睾丸素而导致的性欲增加而导致的性行为有关，可能会影响 TGM的阴道微生物区系，使他们面临细菌性阴道病(BV)的风险，最终导致艾滋病毒和其他性传播疾病。 有关TGM中睾酮启动后阴道微生物区系组成的数据有限。一个 一项横断面研究比较了≥和CGW 1年的TGM对睾酮的影响，发现 71%的睾酮TGM不太可能是以乳酸菌为主的，更有可能富含 -gt；30种其他细菌，其中许多与BV有关。这项研究没有比较TGM的阴道微生物区系 在睾丸激素启动前后，也没有确定微生物区系中可能先于阴道生物失调或 事件BV(IBV)。我们假设睾丸激素的启动会改变阴道微生物区系的组成。 在TGM。在性欲增加的背景下，与睾丸激素和参与性行为有关 行为方面，BV相关细菌(BVAB)的性传播可诱发IBV。我们的长期目标 是找出在TGM中优化睾酮对健康有益的方法，同时降低其潜在风险。 目的1.研究TGM发病过程中阴道微生物区系组成随时间的变化 睾丸激素治疗。我们将从40个TGM获取每日阴道标本和每日日记，并提供基线 正常的阴道微生物区系(无Amsel标准，纽金特评分0-3)，在睾酮分泌前7天开始 90天后。将对所有7份睾酮前样本进行16S rRNA V4测序，并每周进行一次 然后采集标本以确定随时间推移的阴道微生物群落状态类型(CST)的组成。在TGM 谁经历了转变为阴道生物失调(纽金特评分≥为4，至少连续2天)，16S测序 将对轮班前7天至轮班后3天的样品进行密集采样。 目的2.确定TGM中IBV感染前阴道微生物区系对睾酮的影响。阴道 AIM 1中5个感染IBV的TGM样本(即连续2天以上纽金特评分≥7)(病例) 并将确定5名未患IBV的对照。从IBV前14天开始的每日阴道样本， 包括病例中的IBV日和对照的14天阴道样本(与病例相一致 睾丸激素启动的那一天)将使用鸟枪式元基因组学来描述。