Vaginal immune effects of testosterone in transmasculine individuals

项目总结/摘要 在美国，超过一百万人被认定为跨性别者或性别歧视者（TGNC），这意味着 他们的个人身份和性别与他们出生时的性别不符。单雄个体 出生时被指定为女性，经常寻求注射睾丸激素以获得性别确认激素的治疗 疗法性传播感染（STIs）的风险很高;至少三分之一的人 与顺性别男性发生性关系我们假设睾丸激素的产生会导致阴道萎缩， 与阴道炎症状、炎症和与STI相关的阴道细菌增加有关 采集我们建议在使用性别确认激素之前， 疗法我们将在基线和注射3个月后收集阴道拭子和阴道活检 睾丸激素的使用使用每日电子日记，我们将跟踪阴道症状，包括性交困难，干燥， 分泌物性行为和出血模式我们的首要目标是评估阴道炎症， 睾酮启动后的萎缩，并确定与阴道炎症状和性行为的关联。到 评估炎症，我们将定量细胞因子（IL-1α，IL-1β，IL-10）和趋化因子（MIP-1β，IP-10/CXCL 10，IL-10）。 8)阴道拭子中的浓度，因为这些标志物与前瞻性研究中的HIV获得相关。 队列研究我们将利用阴道活检的组织学分析来评估阴道萎缩，特别是 测量上皮厚度和糖原含量。我们将这些结果与阴道炎症状相关联 和性行为记录在日记里作为一个探索性的结果，我们将评估基因表达， 使用RNA测序进行活检。第二个目的是评估阴道微生物组的变化。我们将 进行大范围16 S rRNA基因PCR和高通量测序，以评估阴道细菌普查， 丰富度和群落多样性。该项目将解决我们的根本差距， 了解睾丸激素如何影响阴道健康和免疫力，并确定关键结果， 对设计未来临床试验评估激素治疗、HIV暴露前预防至关重要的混杂因素 和阴道用药的比例这项工作将是确定更安全的性别肯定的第一步 激素方案，将提高粘膜免疫力，减少阴道症状，并优化性健康。 我们有大量的社区参与和经验招募跨男性个体进入研究 研究和评估生殖健康成果。我们的提案结合了关键领域的协同专业知识 包括激素药物、性别确认疗法、阴道免疫和微生物组。

PROJECT SUMMARY/ABSTRACT Over one million people in the United States identify as transgender or gender nonconforming (TGNC), meaning their personal identity and gender do not correspond with their assigned sex at birth. Transmasculine individuals were assigned female at birth and often seek treatment with injectable testosterone for gender affirming hormone therapy. Transmasculine individuals are at high risk for sexually transmitted infections (STIs); at least a third have intercourse with cisgender men. We hypothesize that initiation of testosterone leads to vaginal atrophy and is associated with vaginitis symptoms, inflammation, and increases in vaginal bacteria associated with STI acquisition. We propose to enroll a cohort of 30 transmasculine individuals prior to gender-affirming hormone therapy. We will collect vaginal swabs and vaginal biopsies at baseline and after 3 months of injectable testosterone use. Using daily electronic dairies, we will track vaginal symptoms including dyspareunia, dryness, and discharge, sexual behaviors, and bleeding patterns. Our first aim is to assess vaginal inflammation and atrophy after testosterone initiation and identify associations with vaginitis symptoms and sexual behaviors. To assess inflammation, we will quantify cytokine (IL-1α, IL-1β, IL-10) and chemokine (MIP-1β, IP-10/CXCL10, IL- 8) concentrations in vaginal swabs, as these markers have been associated with HIV acquisition in prospective cohort studies. We will assess vaginal atrophy utilizing histological analysis of vaginal biopsies, specifically measuring epithelial thickness and glycogen content. We will correlate these outcomes with vaginitis symptoms and sexual behaviors recorded in daily diaries. As an exploratory outcome, we will assess gene expression in biopsies using RNA sequencing. The second aim is to assess changes in the vaginal microbiome. We will perform broad-range 16S rRNA gene PCR with high throughput sequencing to assess vaginal bacterial census, richness and community diversity on vaginal swabs. This project will address fundamental gaps in our understanding of how testosterone affects vaginal health and immunity, and identify key outcomes and confounders critical to designing future clinical trials assessing hormone therapy, HIV pre-exposure prophylaxis and vaginal drugs in this population. This work will be the first step towards identifying safer gender-affirming hormone regimens that will improve mucosal immunity, reduce vaginal symptoms, and optimize sexual health. We have substantial community engagement and experience recruiting transmasculine individuals into research studies and assessing reproductive health outcomes. Our proposal combines synergistic expertise in key areas including hormonal medications, gender affirming therapy, vaginal immunity, and the microbiome.