Elucidating causes of vaginal symptoms using a multi-omics approach - Admin. Supplement

总结 跨性别者（Transgender）是指那些性别认同与其出生时的性别不匹配的人。 性2016年，美国约有140万成年人被认定为变性人。跨性别者可能会 或接受过性别确认生殖器手术。知之甚少 性健康检查和管理的方法，以及获得性传播疾病的风险 感染或其他生殖器疾病的发展。因此，NIH确定了一个主要的 需要进行创新研究，解决医学、社会学、心理学和结构性原因， 跨性别和性别认同的后果。大约1/4的跨性别女性（被分配到 出生时为男性但具有女性性别特征）进行了阴道成形术（手术产生新阴道， 典型地使用阴茎和阴囊皮肤），而诸如恶臭、分泌物和刺激的症状， 通常报道，很少有人知道的基本病理生理学。cis女性的阴道微生物组 是健康的关键决定因素，但我们对微生物群落的组成和作用的理解， 新生阴道是罕见的，完全缺乏免疫结果。在跨性别男性中，阴道切除术很少见（<2%）， 然而，估计有69%的人使用性别肯定睾酮治疗。男性化激素疗法 对阴道上皮产生显著影响，导致细胞增殖和糖原产生减少。 这与在cis妇女绝经期观察到的阴道萎缩相似，这会影响阴道微生物群 并对性健康和生活质量产生负面影响。关于这种关系的信息很少 阴道微生物群和炎症与阴道萎缩和症状的发展之间的关系， 男人鉴于这些未知因素，本研究的短期目标是更好地了解生殖器疾病的原因。 症状以及这些症状对跨性别女性和男性性健康和生活质量的影响。我们 将实现这些目标，建立TransBiota研究和表征免疫学和 跨性别女性和男性的阴道微环境（目标1），然后测试相关性 阴道微环境和患者特征之间的关系，包括性行为和卫生 实践（阴道暴露），以及重要的阴道症状（目标2）。我们将实施创新的 以家庭为基础的抽样策略和创新的统计策略，通过纠正 与微生物组分析相关的实验误差。了解阴道微环境及其 在跨性别女性和男性的性健康中的作用是临床最佳发展的重要前提， 目前缺乏的做法。这项研究的长期目标是改善阴道护理的反式 妇女和男子，并最终利用这一信息的发展新的干预措施，以实现 最佳的阴道健康和保护。

SUMMARY Transgender (trans) individuals are those who have a gender identity that does not match their birth-assigned sex. About 1.4 million adults in the United States identified as transgender in 2016. Trans people may take gender-affirming hormones or have undergone gender-affirming genital surgery. Little is known about approaches to sexual health screening and management, as well as risk for acquisition of sexually transmitted infections or development of other genital pathologies, in this population. The NIH has thus identified a major need for innovative research addressing the medical, sociological, psychological and structural causes and consequences of transgender and gender nonconforming identities. About ¼ of trans women (people assigned male at birth but with a female gender identity) have undergone vaginoplasty (surgical creation of a neovagina, typically using penile and scrotal skin) and while symptoms, such as malodor, discharge and irritation are commonly reported, little is known about the underlying pathophysiology. The vaginal microbiome in cis women is a critical determinant of health, yet our understanding of the composition and role of microbiota colonizing the neovagina is scarce and completely lacking for immune outcomes. In trans men, vaginectomy is rare (<2%), however an estimated 69% use gender-affirming testosterone therapy. Masculinizing hormone therapy has significant effects on the vaginal epithelium that result in reduced cellular proliferation and glycogen production. This is similar to vaginal atrophy observed during menopause in cis women, which affects the vaginal microbiota and has negative impacts on sexual health and quality of life. Little information is available on the relationship between vaginal microbiota and inflammation and the development of vaginal atrophy and symptoms in trans men. Given these unknowns, the short-term goals of this research are to better understand the causes of genital symptoms and the impact of these symptoms on sexual health and quality of life in trans women and men. We will achieve these goals establishing the TransBiota study and characterizing the immunological and microbiological vaginal microenvironments in trans women and men (Aim 1) and then testing for correlations between the vaginal microenvironment and patient characteristics, including sexual behaviors and hygiene practices (vaginal exposures), and importantly vaginal symptoms (Aim 2). We will implement an innovative home-based sampling strategy and an innovative statistical strategy that affords scientific rigor by correcting for experimental errors associated with microbiome analyses. Understanding the vaginal microenvironment and its role in sexual health in trans women and men is an important prerequisite to the development of clinical best- practices, which are currently lacking. The long-term goals of this study are to improve vaginal care for trans women and men and to ultimately leverage this information for the development of novel interventions to achieve optimal vaginal health and protection.