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.

项目摘要/摘要 在美国，有超过一百万的人认为跨性别或性别不合格（TGNC），含义 他们的个人身份和性别与出生时分配的性别不符。跨性别的个体 我们在出生时被分配为女性，经常寻求可注射睾丸激素的治疗​​，以确认性别 治疗。跨性别的个体有性传播感染的高风险（STIS）；至少三分之一 与sisgender男人进行性交。我们假设睾丸激素的主动性导致阴道萎缩和 与阴道症状，感染以及与STI相关的阴道细菌的增加有关 获得。我们建议在性别发表本人之前注册30个跨性别者的队列 治疗。我们将在基线和3个月后收集阴道拭子和阴道活检 睾丸激素的使用。使用每日电子乳制品，我们将跟踪阴道症状 以及出院，性行为和出血模式。我们的第一个目的是评估阴道炎症和 睾丸激素倡议后的萎缩，并确定与阴道符号和性行为的关联。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）阴道拭子的浓度，因为这些标记与预期的HIV获取有关 队列研究。我们将利用阴道活检的组织学分析评估阴道萎缩，特别是 测量上皮厚度和糖原含量。我们将将这些结果与阴道符号相关联 和每日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 活检使用RNA测序。第二个目的是评估阴道微生物组的变化。我们将 用高吞吐量测序进行宽范围16S rRNA基因PCR，以评估阴道细菌人口普查， 阴道拭子的丰富性和社区多样性。该项目将解决我们的基本差距 了解睾丸激素如何影响阴道健康和免疫学，并确定关键结果以及 混杂因素对于设计评估骑马疗法的未来临床试验至关重要，HIV暴露前预防 和该人群中的阴道药物。这项工作将是确定更安全的性别肯定的第一步 可以改善粘膜免疫学，减少阴道符号并优化性健康的骑马方案。 我们具有丰富的社区参与，并经验招募跨性别的人参与研究 研究和评估生殖健康结果。我们的建议结合了关键领域的协同专业知识 包括马雌性药物，性别确认疗法，阴道免疫和微生物组。