Cardiometabolic Effects of Gender-Affirming Hormonal Therapy among Transgender Women with HIV

性别肯定激素治疗对感染艾滋病毒的跨性别女性的心脏代谢影响

• 批准号: 10231178
• 负责人: Mabel Toribio
• 金额: $ 19.84万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10231178
• 关键词: 3-Dimensional; Adhesions; Adipose tissue; Affect; African American; Animals; Area; Biometry; Blood Coagulation Factor; Body Composition; Carboxypeptidase U; Cardiology; Cardiometabolic Disease; Clinical Investigator; Coagulation Process; Communicable Diseases; Complex; Coronary heart disease; Coupled; Data; Deposition; Development Plans; Diabetes Mellitus; Dyslipidemias; E-Selectin; Endothelium; Ensure; Environment; Estrogen Replacements; Estrogen Therapy; Estrogens; Face; Fatty acid glycerol esters; Funding; Future; Gender; General Hospitals; General Population; HIV; HIV Infections; Health; Heart failure; High Density Lipoprotein Cholesterol; Homeostasis; Immunology; Individual; Institution; Insulin Resistance; Knowledge; Lipids; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Malignant neoplasm of prostate; Massachusetts; Measures; Medicine; Mentors; Metabolic; Myocardial; Myocardial Infarction; Oral; Pathway interactions; Phenotype; Physicians; Physiology; Plasminogen Activator Inhibitor 1; Population; Populations at Risk; Prevention strategy; Protein S; Proteins; Prothrombin; Public Health; Research; Research Personnel; Resources; Risk; Risk Factors; Safety; Scientist; Structure; Study models; TFPI; Testing; Testosterone; Thrombophilia; Thromboplastin; Time; Training; Triglycerides; United States; Visceral; Woman; Work; antiretroviral therapy; base; blood glucose regulation; cardiometabolic risk; cardiometabolism; cardiovascular imaging; career development; cis-male; cohort; coronary fibrosis; design; experience; hormone therapy; human model; improved; inhibitor/antagonist; innovation; insulin sensitivity; monocyte; patient oriented; preservation; programs; prospective; recruit; research study; skills; standard of care; success; sudden cardiac death; thrombotic; transgender; transgender women; treatment strategy; venous thromboembolism

PROJECT SUMMARY/ ABSTRACT Around one third of transgender individuals in the United States are living with HIV. People with HIV on anti- retroviral therapy face an increased risk of cardiometabolic disease, even after controlling for traditional risk factors. Gender-affirming hormone therapy, in turn, may adversely affect the metabolic health of transgender women by increasing visceral adipose tissue and may also increase the risk of myocardial infarctions and venous thromboembolism. The increased risk for cardiometabolic disease among PWH together with the known effects of gender-affirming hormone therapy among non-HIV-infected transgender women underscores the significance of the aims of this proposal. The central hypothesis for this proposal is that gender-affirming hormone therapy in transgender WHIV will have both beneficial and adverse cardiometabolic effects, reflecting complex downstream consequences of concomitant testosterone suppression and estrogen replacement. The candidate will apply a highly innovative approach to, for the first time, prospectively investigate the effect of testosterone suppression and estrogen therapy on: aim 1 - body composition, ectopic fat deposition, insulin sensitivity, and lipid levels, aim 2 – myocardial structure and function; aim 3 – coagulation parameters (including coagulation factors and tissue factor expression on monocytes). This proposal will provide critically needed information regarding the safety of gender-affirming therapy in this population and identify possible targets for adjunctive therapies to hormone therapy which may optimize the cardiometabolic health of transgender WHIV. The candidate is an outstanding clinical investigator who is dedicated to developing her own research track centered on the cardiometabolic health of transgender individuals living with HIV. In the short term, she hopes to obtain the necessary skills to independently pursue patient-oriented physiology research in the field of transgender medicine in HIV and the preliminary data for an RO1 proposal. In the long term, she plans to utilize these skills and preliminary data to become an R01-funded clinical investigator. This proposal will be supported by an excellent team of mentors and collaborators who will provide complementary expertise in the areas of HIV-associated cardiometabolic disease, Cardiology, Infectious Disease, Immunology and Biostatistics. The institutional environment of Massachusetts General Hospital (MGH) and Harvard-affiliated institutions will provide the candidate excellent resources and opportunities for successful completion of the proposed study and her career development plan. .

项目总结/摘要 在美国，大约三分之一的变性人感染了艾滋病毒。艾滋病毒感染者服用抗- 逆转录病毒疗法面临心脏代谢疾病风险增加，即使在控制了传统风险之后 因素性别肯定激素疗法反过来可能会对变性人的代谢健康产生不利影响 增加内脏脂肪组织，也可能增加心肌梗死的风险， 静脉血栓栓塞威尔斯亲王医院患心脏代谢疾病的风险增加， 在未感染艾滋病毒的变性妇女中，性别肯定激素治疗的已知效果强调， 这一建议的目的的重要性。 这项建议的中心假设是，在跨性别WHIV中进行性别肯定激素治疗将 具有有益和不利的心脏代谢作用，反映了 伴随睾酮抑制和雌激素替代。候选人将采用高度创新的 方法，首次前瞻性地研究睾酮抑制和雌激素 治疗：目标1 -身体成分，异位脂肪沉积，胰岛素敏感性和脂质水平，目标2 - 心肌结构和功能;目标3 -凝血参数（包括凝血因子和组织 单核细胞上的因子表达）。该提案将提供有关安全性的迫切需要的信息 在这一人群中进行性别肯定疗法，并确定激素替代疗法的可能目标 这可能会优化跨性别WHIV的心脏代谢健康的治疗。 候选人是一位杰出的临床研究者，致力于发展自己的研究轨道 重点关注感染艾滋病毒的跨性别者的心脏代谢健康。在短期内，她希望 获得必要的技能，独立追求在该领域以患者为导向的生理学研究 艾滋病毒的跨性别医学和RO 1提案的初步数据。从长远来看，她计划 利用这些技能和初步数据，成为R 01资助的临床研究者。这项提案将是 由优秀的导师和合作者团队提供支持，他们将在以下方面提供互补的专业知识： 艾滋病毒相关的心脏代谢疾病，心脏病学，传染病，免疫学和 生物统计学。马萨诸塞州总医院（MGH）和哈佛附属医院的制度环境 院校将为申请人提供优质的资源和机会，让他们顺利完成 提出学习和职业发展计划。 .