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

摘要： 跨性别男性（TGM）（自认为是男性但出生时被分配为女性的人）经常放弃性别- 确认手术并保留其纳塔尔生殖器（即阴道）。然而，许多TGM开始男性化， 睾酮治疗很像雌激素缺乏的顺性女性（CGW），TGM对睾酮的经验 阴道上皮厚度减少和月经减少。绝经后妇女的阴道微生物群 由于乳酸杆菌的损失，CGW可能会转向阴道生态失调。与绝经后CGW不同， 睾酮也会经历睾酮水平升高。低雌激素/高睾丸激素对 TGM的阴道微生物群是未知的，并且不能从CGW的研究中推断。荷尔蒙的变化 与性行为相结合，由于使用睾酮增加性欲可能会影响 TGM的阴道微生物群，使他们面临细菌性阴道病（BV）的风险，最终，艾滋病毒和其他性传播感染。 在TGM中开始睾酮治疗后，关于阴道微生物群组成的数据有限。一 一项比较TGM对睾酮≥1年与CGW的横断面研究发现， 71%的TGM对睾酮不太可能是乳酸杆菌为主，更可能是丰富的 >30种其他细菌物种，许多与BV相关。这项研究没有比较TGM的阴道微生物群 也不能确定阴道微生态失调之前的微生物群的变化， 事件BV（iBV）。我们假设睾酮的启动会改变阴道微生物群的组成 在TGM。在与睾酮和参与性行为相关的性欲增加的情况下， 行为，iBV可通过BV相关细菌（BVAB）的性传播引起。我们的长期目标 是确定如何优化TGM中睾酮的健康益处，同时减轻其潜在风险。 目标1。为了研究TGM启动时阴道微生物群组成随时间的变化， 睾酮治疗我们将从40例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），在开始睾酮治疗前7天开始 90天后。将对所有7份睾酮前样本进行16 S rRNA V4测序，每周一次 随后收集样本以确定随时间推移的阴道微生物群落状态类型（CST）组成。在TGM 发生阴道微生态失调的患者（至少连续2天Nugent评分≥4），16 S测序 将从轮班前7天开始至轮班后3天对标本进行密集采样。 目标二。确定TGM中睾酮iBV之前阴道微生物群的变化。阴道 来自Aim 1中5个TGM的发生iBV（即至少连续2天Nugent评分≥7）的标本（例） 并确定5名未发生iBV的对照。iBV前14天的每日阴道标本， 包括病例中iBV的当天和对照组阴道标本的14天（与基于 睾酮起始日）将使用鸟枪宏基因组学进行表征。

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.