Excess androgen production in overweight pubertal girls--precursor to PCOS

超重青春期女孩雄激素分泌过多——多囊卵巢综合症的前兆

• 批准号: 8811858
• 负责人: Christine Michele Burt Solorzano
• 金额: $ 12.99万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8811858
• 关键词: Adolescence; Adolescent; Adrenal Blockade; Adrenal Glands; Agonist; Androgen Antagonists; Androgens; Award; Biological Assay; Biometry; Childhood; Chronic; Clinical Investigator; Clinical Research; Clinical Trials; Corticotropin; Data; Development; Development Plans; Dexamethasone; Diagnostic; Doctor of Medicine; Doctor of Philosophy; Dose; Early Intervention; Endocrine System Diseases; Endocrinologist; Epidemiologic Studies; Female; Glucocorticoids; Goals; Gonadotropin Hormone Releasing Hormone; Gonadotropins; Growth; Hair; Hirsutism; Hormones; Hydrocortisone; Hydroxyprogesterone; Hyperandrogenism; Infertility; Instruction; Insulin; International; Knowledge; Leuprolide; Marshal; Mentorship; Metabolic; Metabolic Diseases; Metformin; Methodology; Obesity; Ovarian; Ovarian Stimulations; Ovary; Overweight; Patients; Pattern; Pharmaceutical Preparations; Polycystic Ovary Syndrome; Population; Production; Puberty; Recombinant Human Chorionic Gonadotropin; Relative (related person); Research; Research Design; Research Ethics; Research Personnel; Research Proposals; Risk; Source; Spironolactone; Staging; Steroid biosynthesis; Syndrome; Testing; Time; Training; Treatment Efficacy; Universities; Virginia; Weight; Woman; career development; design; experience; girls; improved; insulin sensitizing drugs; male; obesity in children; older women; patient oriented research; premature adrenarche; prevent; reproductive neuroendocrinology; response; skills; steroid hormone; targeted treatment; therapeutic target; tool; treatment strategy; young woman

DESCRIPTION (provided by applicant): This research award will support the development of Christine M. Burt Solorzano, M.D., of the University of Virginia (UVA), as she continues to train in patient-oriented research under the mentorship of John C. Marshall, M.D., Ph.D., an established investigator in reproductive neuroendocrinology and the polycystic ovary syndrome (PCOS). Dr. Solorzano is a pediatric endocrinologist with previous research experience focusing on aspects of obesity. Her immediate goal is to understand the origins of PCOS and identify new treatment strategies. Her long-term goal is to become a leader in pediatric PCOS research, assessing the efficacy of interventions to prevent PCOS. This training will allow Dr. Solorzano to acquire skills needed to become an independent clinical investigator. The application outlines a career development plan that includes comprehensive instruction in clinical trials methodology, biostatistics, epidemiology, research ethics, assay methodology, and study design, partly via a Masters of Clinical Research. Dr. Solorzano's research proposal is designed to determine the source and timing of androgen excess in overweight girls and to identify potential strategies to reduce androgen production in this population. Androgen excess during puberty is a forerunner to PCOS-a common chronic endocrine disorder associated with infertility, metabolic disorders, and hirsutism in women. Childhood obesity - an international problem -puts girls at risk for androgen excess, even in early puberty. Identifying sources of androgen excess during puberty is needed to elucidate targets for preventing PCOS. Women and older adolescents with PCOS have predominantly ovarian overproduction of androgens. However, it is unknown whether the adrenal gland, ovary, or both are responsible for androgen excess in overweight girls prior to developing the full PCOS syndrome. This is especially true during early puberty when ovarian function is thought to be minimal. Aim 1 will use adrenal suppression/stimulation testing and ovarian stimulation testing to examine sources of androgen production in normal and overweight girls throughout puberty. Aim 2 will use low-dose hydrocortisone and leuprolide therapy to test whether short-term suppression of adrenocorticotropin or gonadotropin production can reduce androgen levels in overweight girls with androgen excess. Aim 3 will examine the potential efficacy of longer-term therapies (e.g., low-dose hydrocortisone, metformin, or spironolactone) to reduce obesity-related androgen excess in girls during all stages of puberty. The research will be performed in the Clinical Research Center at UVA and would extend diagnostic tools to examine adrenal and ovarian androgen production to young girls. It may identify targets for therapeutic strategies to treat or prevent androgen excess during puberty - a critical stage for the development of PCOS.

描述（由申请人提供）：该研究奖将支持弗吉尼亚大学 (UVA) 医学博士 Christine M. Burt Solorzano 的发展，她将在生殖神经内分泌学和多囊卵巢综合征 (PCOS) 领域知名研究者 John C. Marshall 医学博士、哲学博士的指导下继续接受以患者为导向的研究培训。 Solorzano 博士是一位儿科内分泌学家，之前有专注于肥胖方面的研究经验。她的近期目标是了解多囊卵巢综合症的起源并确定新的治疗策略。她的长期目标是成为儿科多囊卵巢综合症研究的领导者，评估预防多囊卵巢综合症的干预措施的有效性。此次培训将使 Solorzano 博士获得成为独立临床研究者所需的技能。该申请概述了职业发展计划，包括临床试验方法、生物统计学、流行病学、研究伦理、分析方法和研究设计方面的全面指导，部分通过临床研究硕士学位进行。 Solorzano 博士的研究计划旨在确定超重女孩雄激素过多的来源和时间，并确定减少该人群雄激素产生的潜在策略。 青春期雄激素过多是多囊卵巢综合症的先兆，多囊卵巢综合症是一种常见的慢性内分泌紊乱，与女性不孕、代谢紊乱和多毛症有关。儿童肥胖是一个国际问题，即使在青春期早期，也会使女孩面临雄激素过多的风险。需要确定青春期雄激素过多的来源，以阐明预防多囊卵巢综合症的目标。患有多囊卵巢综合症的女性和老年青少年主要是卵巢雄激素分泌过多。然而，尚不清楚肾上腺、卵巢或两者是否导致超重女孩在发展为完全多囊卵巢综合症之前雄激素过多。在青春期早期尤其如此，此时卵巢功能被认为是最低的。 目标 1 将使用肾上腺抑制/刺激测试和卵巢刺激测试来检查整个青春期正常和超重女孩的雄激素产生来源。目标 2 将使用低剂量氢化可的松和亮丙瑞林治疗来测试短期抑制促肾上腺皮质激素或促性腺激素的产生是否可以降低雄激素过多的超重女孩的雄激素水平。目标 3 将研究长期疗法（例如低剂量氢化可的松、二甲双胍或螺内酯）在青春期各个阶段减少女孩与肥胖相关的雄激素过多的潜在功效。该研究将在弗吉尼亚大学临床研究中心进行，并将扩展诊断工具来检查年轻女孩的肾上腺和卵巢雄激素的产生。它可以确定治疗策略的目标，以治疗或预防青春期雄激素过多——这是多囊卵巢综合症发展的关键阶段。