Genital Health of Trans-males on Testosterone

跨性别男性的生殖健康对睾酮的影响

• 批准号: 10371144
• 负责人: Mimi Ghosh
• 金额: $ 23.23万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-15 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10371144
• 关键词: Age; Anti-Inflammatory Agents; Anus; Biological; Biological Assay; Biological Markers; Birth; Cell Cycle; Cervical; Cervix Uteri; Cervix carcinoma; Clinical; Clinical Research; DNA; Data; Detection; Development; District of Columbia; Dose; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Funding; Genital; Genitalia; Genotype; Goals; HIV; HIV/STD; HPV-High Risk; Health; High Prevalence; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Immune; Immunity; Immunologic Markers; Immunologics; Immunosuppression; Inflammation; Inflammation Mediators; Inflammatory; Knowledge; Link; Malignant Neoplasms; Malignant neoplasm of anus; Malignant neoplasm of cervix uteri; Measures; Morbidity - disease rate; Mucous Membrane; Oncogenes; Pathway interactions; Persons; Population; Predisposition; Prevalence; Prevention; Race; Research; Research Personnel; Risk; Sampling; Sexual Reassignment; Swab; Testosterone; United States National Institutes of Health; Vulnerable Populations; Walkers; antimicrobial; cisgender; comparison group; design; experience; high risk; hormonal contraception; hormone therapy; immune activation; interest; male; men; men who have sex with men; patient population; recruit; risk variant; screening guidelines; sex; transgender; transgender men; tumor-immune system interactions

Project Summary/Abstract: The prevalence of cervical and anal canceris significantly higher in the transgender populationrelative to cisgender people, yet the genital immune microenvironment that may elucidate underlying biological mechanisms of cancer development in this population remains uncharacterized. Transgender males (TM) are assigned female at birth but identify as male, and often are on long-term high doses of testosterone (T). High levels of T have been linked to greater risk of invasive cervical carcinoma in cisgender females (CF) and increased risk for detecting Human papilloma virus (HPV) 16/18 DNA in anal swabs in cisgender males who have sex with men (MSM). However, a critical gap in our knowledge exists regarding the effects of T on the cervical and anal immune microenvironment in TM. Potential mechanisms underlying susceptibility of developing HPV-associated genital cancers can include the presence of high-risk genotypes and dysregulated immune microenvironment. This goal of this proposal is to evaluate high risk HPV prevalence and characterize the genital mucosal immune microenvironment in cervical and anal compartments of TM on T. Data generated will provide valuable clinical information that would allow us to evaluate if T use, and specifically the level of T elevation, impacts genital immune dysregulation, HPV infection and HPV genotype (high vs low risk). We have unique access to this population through Dr. Goldstein, the Director of Clinical Research at Whitman Walker Health (WWH), Washington DC, who is actively involved in transgender health research and a co- investigator on this proposal. We propose to recruit 50 TM who are on T for at least 2 years and a comparison group of 50 race- and age-matched CF who are not on any hormonal therapy or contraceptives. Cervical and anal swab samples will be collected and analyzed for HR-HPV genotypes, biomarkers of inflammation and innate immune biomarkers of protection. There is a growing interest in the National Institutes of Health to fund transgender research as evidenced by the PAR-20-054 titled “Transgender People: Immunity, Prevention, and Treatment of HIV and STIs”. We are uniquely poised to respond to this PAR by virtue of our experience in the field and access to this vulnerable population. Assessment of data obtained fromthis study will provide us with baseline virological and immunological information and spur further research in understanding mechanisms in HPV-associated cancers in this population.

项目概要/摘要： 宫颈癌和肛门癌的患病率在跨性别人群中明显高于顺性别人群 人，但生殖器免疫微环境，可能阐明潜在的生物学机制的癌症 这一群体的发展仍然没有特点。 跨性别男性（TM）在出生时被指定为女性，但被识别为男性，并且通常长期服用高剂量 睾酮（T）。高水平的T与顺性别人群中浸润性宫颈癌的风险增加有关。 女性（CF）和顺性别肛门拭子中检测人乳头瘤病毒（HPV）16/18 DNA的风险增加 男男性接触者（MSM）然而，在我们的知识中存在一个关键的差距，关于T 对TM的宫颈和肛门免疫微环境的影响易感性的潜在机制 发展HPV相关生殖器癌症可能包括存在高风险基因型和失调， 免疫微环境 该提案的目的是评估高危HPV的患病率，并描述生殖器粘膜免疫的特征。 在T.生成的数据将提供有价值的临床 这些信息将使我们能够评估T使用，特别是T升高的水平，是否影响生殖器免疫 失调、HPV感染和HPV基因型（高风险vs低风险）。 我们通过惠特曼临床研究主任Goldstein博士， 步行者健康（WWH），华盛顿特区，谁是积极参与跨性别健康研究和合作， 调查这一提案。我们建议招募50名接受T治疗至少2年的TM， 一组50名种族和年龄匹配的CF，他们没有接受任何激素治疗或避孕药。宫颈和肛门 将采集拭子样本并分析HR-HPV基因型、炎症生物标志物和先天性 免疫生物标志物的保护。 美国国立卫生研究院对资助跨性别研究的兴趣越来越大，这一点可以从 PAR-20-054，题为“变性人：艾滋病毒和性传播感染的免疫、预防和治疗”。我们是唯一 凭借我们在实地的经验和接触这一弱势群体的机会，我们随时准备应对这一PAR。 本研究获得的数据评估将为我们提供基线病毒学和免疫学信息 并刺激进一步研究，以了解该人群中HPV相关癌症的机制。