Cardiometabolic effects of gender-affirming hormone therapy in transgender adolescents

项目概要/摘要 在美国，大约0.7%-1.8%或约275，000名青年被认为是变性人，这个数字可能会增加 更好地认识到这一点。性别肯定激素疗法（GAHT），试图更多地 使身体外观与所识别的性别一致，是变性人的主要医疗干预措施。 人，并被认为是医学上必要的。GAHT与心脏代谢增加有关。 跨性别者的风险（血压升高、血脂异常、胰岛素抵抗和内皮功能障碍） 成年人了虽然治疗标准已经发展到在青春期开始GAHT，但对GAHT的治疗方法知之甚少。 心脏代谢的变化，发生与GAHT在青春期，一个关键的差距，在最佳护理的跨青年。 首次使用最先进的技术，该提案旨在表征代谢和 发生在跨性别青年与GAHT的启动心血管变化。我们假设， 荷尔蒙环境是变性青年心脏代谢风险增加的主要驱动因素。启动 睾酮或雌激素将对胰岛素抵抗、血脂谱、血管紧张素转换酶（VEGF）、血管紧张素转换酶（VEGF）、血管紧张素转换酶（VEGF）和血管紧张素转换酶（VEGF）的标志物具有特征性作用。 健康和内皮功能。跨性别受试者将接受两次检查：GAHT开始前和 6个月后，当激素替代策略通常导致激素水平与顺式- 成人性别使用稳定同位素示踪的高胰岛素-正葡萄糖钳夹技术， 将对外周和肝脏胰岛素敏感性指标进行量化和分析，以分离以下因素的影响： 外源激素（睾酮和雌激素）。其他代谢指标将通过口服 葡萄糖耐量试验（全身胰岛素敏感性、胰岛素生成指数）和Bod Pod（身体成分） 在基线和6个月时进行。将通过血流介导的内皮细胞功能测定来评估内皮细胞功能。 肱动脉的血管舒张和微血管内皮功能（皮肤血流量）将通过以下方法确定： 局部前臂皮肤加热激光多普勒血流仪，在基线和6个月后的GAHT。随着时间的推移， 我们将比较跨性别受试者与顺性别男性和女性的心脏代谢变化， 对照这些新的和创新的研究将阐明早期代谢和血管变化 伴随着GAHT，使跨性别青年的心脏代谢风险有了更深入的了解 正在接受治疗这是我们知识中的一个关键空白;一旦这些早期的变化可以被描述， 随后的研究可以在更长的治疗轨迹上跟踪这些变化，并采取有效的干预措施， 减少不良代谢和心血管结果的方法可以被设计和评估。

PROJECT SUMMARY / ABSTRACT In the US, approximately 0.7-1.8% or ~ 275,000 youth identify as transgender, a number that is likely to increase with greater recognition of this condition. Gender affirming hormone therapy (GAHT), which attempts to more align the physical appearance with the identified gender, is the primary medical intervention for transgender people and is recognized as medically necessary. GAHT has been associated with increased cardiometabolic risk (increased blood pressure, dyslipidemia, insulin resistance, and endothelial dysfunction) in transgender adults. While treatment standards have evolved to initiate GAHT in adolescence, little is known about the cardiometabolic changes that occur with GAHT in adolescence, a critical gap in the optimal care of trans youth. For the first time using state-of-the-art techniques, this proposal aims to characterize the metabolic and cardiovascular changes that occur in trans youth with the initiation of GAHT. We hypothesize that the altered hormonal milieu is the major driver of increased cardiometabolic risk in transgender youth. The initiation of testosterone or estrogen will have characteristic effects on markers of insulin resistance, lipid profiles, vascular health, and endothelial function. Transgender subjects will be examined twice: prior to the initiation of GAHT and again six months later when hormone replacement strategies typically result in hormonal levels comparable to cis- gender adults. Using the hyperinsulinemic-euglycemic clamp technique with stable isotope tracers, precise peripheral and hepatic insulin sensitivity measures will be quantified and analyzed to isolate the effects of exogenous hormones (testosterone and estrogen). Additional metabolic metrics will be determined from oral glucose tolerance tests (whole-body insulin sensitivity, insulinogenic index) and Bod Pod (body composition) performed at baseline and six months. The conduit-level endothelial function will be assessed by flow-mediated vasodilation of the brachial artery, and microvascular endothelial function (skin blood flow) will be determined by local forearm skin heating with laser Doppler flowmetry, at baseline and after six months of GAHT. Over time, we will compare the cardiometabolic changes in transgender subjects to those of cisgender male and female controls. These novel and innovative studies will illuminate the early metabolic and vascular changes accompanying GAHT, enabling a more informed understanding of the cardiometabolic risks in trans youth undergoing treatment. This is a critical gap in our knowledge; once these early changes can be characterized, subsequent studies can track these changes over longer treatment trajectories, and effective interventions to reduce adverse metabolic and cardiovascular outcomes can be designed and evaluated.