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

项目总结/摘要 候选人：Natalie Nokoff博士是一名儿科内分泌学家，其研究和临床重点是 跨性别青年的心脏代谢健康。她的K23提案的目标是获得关键的研究， 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她的目标。 发展成功的独立研究计划并成为国际专家的长期目标 性类固醇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跨性别者。变性女性的待遇 (male性别和女性性别认同，MTF）可能包括青春期阻滞（促性腺激素释放激素 类似物或GnRHa），随后在青春期后期给予雌二醇。实体就雇员 对心脏代谢健康的治疗研究不足，也不清楚。接受雌二醇治疗的MTF成人的 与非跨性别（cisgender）个体相比， 研究计划：青春期阻滞和勃起对过渡期青年心脏代谢健康的影响 （PUBERTY）是一项纵向观察性研究，旨在评价GnRHa和雌二醇对 血管功能和胰岛素敏感性（IS）。Young MTF（n = 15）将在术前和术后6个月进行评价 在GnRHa之后一个单独的MTF青年队列（n = 40，年龄13 - 16岁，20名临床接受GnRHa治疗的患者） 20名未接受雌二醇治疗的患者）将在基线、雌二醇治疗后6个月和12个月进行评价。MTF青年将比较 顺性别青年（n = 15名男性，15名女性），调整到青春期阶段和体重。 职业发展计划：诺科夫博士的科研职业发展培训活动包括：1）收获 临床研究设计和实施方面的专业知识（PUBERTY研究的实施和完成， 课程和临床研究博士学位）; 2）学习如何执行和解释血管研究; 3）学习 评估IS的新方法。 环境：这个项目的环境是特殊的，有一个强大的儿科学术部分 科罗拉多大学安舒茨医学院内分泌学和科罗拉多临床资源 以及转化科学研究所和妇女健康研究中心。Nokoff博士是 TRUE性别多样性中心，一个综合性的多学科诊所，为1,000多名变性人提供服务 青年，这将确保成功招募这项研究。导师具有内分泌学、胰岛素 阻力，血管健康，性类固醇，与弱势群体的工作，和临床研究是 投资于这位候选人的未来，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跨性别青年的临床护理， 未来血管事件的风险因素。Nokoff博士将获得研究设计方面的宝贵技能， 评估血管和代谢健康，作为首席临床研究员开展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.