Vaginal immune effects of testosterone in transmasculine individuals

睾酮对跨男性个体的阴道免疫影响

• 批准号: 10369028
• 负责人: Florian Hladik
• 金额: $ 29.78万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-09 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10369028
• 关键词: Address; Affect; Area; Atrophic; Bacteria; Behavioral; Biological; Biological Response Modifiers; Biopsy; Birth; CXCL10 gene; Caring; Cells; Censuses; Clinical; Clinical Trials; Clinical Trials Design; Communities; Data; Dryness; Dyspareunia; Enrollment; Epithelial; Female; Future; Gender; Gene Expression; Glycogen; Goals; HIV; HIV Infections; Health; Hemorrhage; High-Throughput Nucleotide Sequencing; Histologic; Histology; Hormonal; Hormones; IL8 gene; Immune; Immunity; Immunologics; Individual; Inflammation; Injectable; Interleukin-1 alpha; Interleukin-1 beta; Interleukin-10; Knowledge; Measures; Menstruation; Mucosal Immunity; Outcome; Pattern; Persons; Pharmaceutical Preparations; Phenotype; Population; Postmenopause; Predisposition; Prospective cohort study; Public Health; Regimen; Reporting; Reproductive Health; Risk; Sampling; Sex Behavior; Sexual Health; Sexually Transmitted Diseases; Swab; Symptoms; Testosterone; Thick; United States; Vagina; Vaginitis; Vulnerable Populations; Work; base; chemokine; cis-male; cohort; community engagement; cytokine; design; diaries; experience; gender nonconforming; health disparity; high risk; hormone therapy; improved; microbial; microbiome; pre-exposure prophylaxis; primary outcome; rRNA Genes; recruit; research study; secondary outcome; sex; transcriptome sequencing; transgender; transmasculine; vaginal microbiome

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.

项目概要/摘要 美国有超过一百万人被认定为跨性别者或性别不合格者 (TGNC)，这意味着 他们的个人身份和性别与出生时指定的性别不符。跨男性个体 出生时被指定为女性，经常寻求注射睾酮治疗以获取性别肯定激素 治疗。跨男性个体感染性传播感染（STI）的风险很高；至少三分之一 与顺性别男性发生性关系。我们假设睾酮的启动会导致阴道萎缩 与性传播感染相关的阴道炎症状、炎症和阴道细菌增加有关 获得。我们建议在使用性别肯定激素之前招募 30 名跨男性个体 治疗。我们将在基线和注射 3 个月后收集阴道拭子和阴道活检 睾酮的使用。使用日常电子记录仪，我们将跟踪阴道症状，包括性交疼痛、干燥、 以及分泌物、性行为和出血模式。我们的首要目标是评估阴道炎症和 睾丸激素启动后萎缩并确定与阴道炎症状和性行为的关联。到 评估炎症，我们将量化细胞因子（IL-1α、IL-1β、IL-10）和趋化因子（MIP-1β、IP-10/CXCL10、IL- 8) 阴道拭子中的浓度，因为这些标记物已与前瞻性 HIV 感染相关 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联系起来 以及日记中记录的性行为。作为探索性结果，我们将评估基因表达 使用 RNA 测序进行活检。第二个目标是评估阴道微生物组的变化。我们将 通过高通量测序进行广泛的 16S rRNA 基因 PCR 来评估阴道细菌普查， 阴道拭子的丰富度和群落多样性。该项目将解决我们的根本差距 了解睾酮如何影响阴道健康和免疫力，并确定关键结果和 对于设计评估激素治疗、HIV 暴露前预防的未来临床试验至关重要的混杂因素 和该人群的阴道药物。这项工作将是确定更安全的性别肯定的第一步 激素疗法可改善粘膜免疫力、减轻阴道症状并优化性健康。 我们拥有大量的社区参与度和招募跨男性个体参与研究的经验 研究和评估生殖健康结果。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。