Pubertal Blockade and Estradiol Effects on Cardiometabolic Health for Transitioning Youth (PUBERTY)

项目摘要/摘要 候选人：娜塔莉·诺科夫医生是一位儿科内分泌学家，她的研究和临床重点是 变性人青年的心脏代谢健康。她的K23提案的目标是获得批判性研究 领导高质量、以患者为中心的临床研究所需的技能。这次培训将帮助她实现自己的目标 制定成功的独立研究计划并成为国际专家的长期目标 性激素对心脏代谢健康的影响。 背景：在美国，高达1.8%的青少年认为自己是变性人。对变性女性的治疗 (男性和女性性别认同，MTF)可能包括青春期阻断(促性腺激素释放激素 类似物或GnRHa)在青春期早期，随后在青春期后期雌二醇。这些因素的影响 心脏代谢健康的治疗方法研究不足，也不清楚。服用雌二醇者MTF发生率较高 血管事件多于非变性人(顺性人)。 研究计划：青春期阻断和雌二醇对过渡青年心脏代谢健康的影响 (青春期)是一项纵向观察研究，旨在评估GnRHa和雌二醇对 血管功能和胰岛素敏感性(IS)。年轻的MTF(n=15)将在出生前和6个月前进行评估 在GnRHa之后。单独的MTF青年队列(n=40，年龄13-16岁，20名临床接受GnRHa治疗的人 和20名没有这样做的人)将在基线、雌二醇后6个月和12个月进行评估。MTF的年轻人将被比较 至顺性青年(男15例，女15例)，根据青春期和体质量进行调整。 职业发展计划：诺科夫博士的研究职业发展培训活动包括：1)收获 设计和进行临床研究的专门知识(青春期研究的实施和完成， 临床研究的课程和博士学位)；2)学习如何进行和解释血管研究；3)学习 评估IS的新方法。 环境：这个项目的环境非常特殊，有一个强大的儿科学术部门 科罗拉多大学安舒茨医学院内分泌学与科罗拉多临床医院资源 以及翻译科学研究所和妇女健康研究中心。诺科夫博士是 True Center for Gender多样性，一个综合的、多学科的诊所，为1000多名变性人提供服务 这将确保这项研究的成功招聘。具有内分泌学、胰岛素方面专业知识的导师 抵抗力、血管健康、性激素、易受感染人群的工作和临床研究 对这位候选人的未来进行了投资，并将有助于支持她的研究和职业发展。 影响：这项新研究的结果将改善变性人青年的临床护理，并提供信息 关于未来血管事件的风险因素。诺科夫博士将在研究设计方面获得宝贵的技能 评估血管和代谢健康，作为一名首席临床研究人员开启有影响力的职业生涯。

PROJECT SUMMARY/ABSTRACT Candidate: Dr. Natalie Nokoff is a Pediatric Endocrinologist whose research and clinical focus is on the cardiometabolic health of transgender youth. The goal of her K23 proposal is to acquire the critical research skills necessary to lead high-quality, patient-centered clinical research. This training will help her achieve her long-term goal of developing a successful independent research program and becoming an international expert on the impact of sex steroids on cardiometabolic health. Background: Up to 1.8% of adolescents in the U.S. identify as transgender. Treatment of transgender females (male sex and a female gender identity, MTF) may include pubertal blockade (gonadotropin-releasing hormone analogue or GnRHa) in early puberty followed by estradiol later in adolescence. The impact of these treatments on cardiometabolic health is understudied and unclear. MTF adults on estradiol have higher rates of vascular events than non-transgender (cisgender) individuals. Research Plan: Pubertal Blockade and Estradiol Effects on Cardiometabolic Health for Transitioning Youth (PUBERTY) is a longitudinal observational study to evaluate the impact of GnRHa and estradiol on vascular function and insulin sensitivity (IS). Young MTF (n=15) will be evaluated before and 6 months after GnRHa. A separate cohort of MTF youth (n=40, ages 13-16 years, 20 who clinically received a GnRHa and 20 who did not) will be evaluated at baseline, 6 and 12 months after estradiol. MTF youth will be compared to cisgender youth (n=15 males, 15 females), adjusted to pubertal stage and body mass. Career Development Plan: Dr. Nokoff’s research career development training activities include: 1) gain expertise in design and conduct of clinical studies (implementation and completion of the PUBERTY study, coursework and a PhD in Clinical Investigation); 2) lean how to perform and interpret vascular studies; 3) learn new methods for assessing IS. Environment: The environment for this project is exceptional with a strong academic Section of Pediatric Endocrinology at the University of Colorado Anschutz Medical Campus and resources of the Colorado Clinical and Translational Sciences Institute and Center for Women’s Health Research. Dr. Nokoff is faculty in the TRUE Center for Gender Diversity, a comprehensive, multidisciplinary clinic serving over 1,000 transgender youth, that will assure successful recruitment for this study. Mentors with expertise in endocrinology, insulin resistance, vascular health, sex steroids, working with vulnerable populations, and clinical investigation are invested in this candidate’s future and will be instrumental in supporting her research and career development. Impact: The results of this novel study will improve the clinical care of transgender youth and yield information on risk factors for future vascular events. Dr. Nokoff will gain invaluable skills in study design as well as assessment of vascular and metabolic health, launching an impactful career as a lead clinical investigator.