Cardiometabolic effects of gender-affirming hormone therapy in transgender adolescents

性别肯定激素治疗对跨性别青少年的心脏代谢影响

• 批准号: 10675704
• 负责人: NINA STACHENFELD
• 金额: $ 26.61万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-02 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10675704
• 关键词: Adolescence; Adolescent; Adult; Androgen Suppression; Androgens; Appearance; Atherosclerosis; Blood Pressure; Blood Vessels; Blood flow; Body Composition; Body Weight; Cardiovascular system; Caring; Characteristics; Child; Diagnosis; Dyslipidemias; Early treatment; Endothelium; Estrogen Therapy; Estrogens; Female; Female Adolescents; Forearm; Foundations; Gender; Gender Identity; Glucose Clamp; Grant; Health; Heating; Hepatic; High Density Lipoprotein Cholesterol; Hormonal; Hormonal Change; Hormones; Hyperinsulinism; Impairment; Individual; Insulin Resistance; Intervention; Knowledge; LDL Cholesterol Lipoproteins; Laser-Doppler Flowmetry; Link; Lipids; Low-Density Lipoproteins; Male Adolescents; Measures; Mediating; Medical; Mental Health; Metabolic; Metabolic syndrome; OGTT; Obesity; Outcome; Patients; Peripheral; Persons; Professional Organizations; Risk; Risk Factors; Serum; Sex Characteristics; Skin; Techniques; Testing; Testosterone; Thrombosis; Time; Tracer; Triglycerides; United States National Institutes of Health; Vascular Endothelium; Vasodilation; Youth; blood pressure elevation; brachial artery; cardiometabolic risk; cardiometabolism; cardiovascular effects; cardiovascular risk factor; cisgender; design; effective intervention; endothelial dysfunction; gender affirming hormone therapy; improved; indexing; innovation; insulin sensitivity; male; medically necessary care; modifiable risk; novel; pediatric patients; sex; sex assigned at birth; stable isotope; standard care; time use; transgender; transgender men; transgender women; treatment strategy

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.

项目概要/摘要 在美国，大约 0.7-1.8% 或约 275,000 名青少年认为自己是跨性别者，这一数字可能还会增加 对这种情况有了更多的认识。性别肯定激素疗法（GAHT），试图更多地 使外貌与确定的性别一致，是跨性别者的主要医疗干预措施 人，并被认为是医疗上必需的。 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。虽然治疗标准已经发展到在青春期启动 GAHT，但人们对 GAHT 的了解却很少。 青春期 GAHT 发生的心脏代谢变化是跨性别青少年最佳护理的一个关键差距。 该提案首次使用最先进的技术，旨在表征代谢和 随着 GAHT 的开始，跨性别青年发生的心血管变化。我们假设改变后的 荷尔蒙环境是跨性别青少年心脏代谢风险增加的主要驱动因素。发起 睾酮或雌激素将对胰岛素抵抗、血脂、血管等指标产生特征性影响。 健康和内皮功能。跨性别受试者将接受两次检查：在开始 GAHT 之前和 六个月后，激素替代策略通常会导致激素水平与顺式相当 性别成人。使用高胰岛素-正常血糖钳夹技术和稳定同位素示踪剂，可精确 将量化和分析外周和肝脏胰岛素敏感性测量，以隔离以下因素的影响 外源激素（睾酮和雌激素）。额外的代谢指标将通过口服确定 葡萄糖耐量测试（全身胰岛素敏感性、胰岛素生成指数）和 Bod Pod（身体成分） 在基线和六个月时进行。导管水平内皮功能将通过血流介导进行评估 肱动脉的血管舒张和微血管内皮功能（皮肤血流量）将通过以下方式确定 在基线时和 GAHT 六个月后，使用激光多普勒血流计进行局部前臂皮肤加热。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 控制。这些新颖和创新的研究将阐明早期代谢和血管变化 伴随 GAHT，使跨性别青年能够更深入地了解心脏代谢风险 正在接受治疗。这是我们知识中的一个关键差距；一旦这些早期变化能够被表征， 随后的研究可以在更长的治疗轨迹上追踪这些变化，并采取有效的干预措施 可以设计和评估减少不良代谢和心血管结局的方法。