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: 8449209
• 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 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8449209
• 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; therapeutic target; tool; treatment strategy

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(申请人提供)：该研究奖将支持弗吉尼亚大学(UVA)的Christine M.Burt Solorzano医学博士的发展，她将继续在John C.Matt医学博士的指导下接受以患者为导向的研究培训，他是生殖神经内分泌学和多囊卵巢综合征(PCOS)方面的知名研究员。索罗扎诺博士是一位儿科内分泌学家，以前的研究经验主要集中在肥胖的各个方面。她的近期目标是了解多囊卵巢综合征的起源，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征研究的领导者，评估预防多囊卵巢综合征的干预措施的有效性。这一培训将使索罗扎诺博士获得成为一名独立临床研究员所需的技能。该申请概述了职业发展计划，其中包括临床试验方法学、生物统计学、流行病学、研究伦理学、分析方法学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。索罗扎诺博士的研究建议旨在确定超重女孩雄激素过剩的来源和时机，并确定减少这一群体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征的先兆，多囊卵巢综合征是一种常见的慢性内分泌疾病，与女性的不孕不育、代谢紊乱和多毛症有关。儿童肥胖是一个世界性的问题，它使女孩面临雄激素过剩的风险，即使在青春期早期也是如此。需要确定青春期雄激素过剩的来源，以阐明预防多囊卵巢综合征的目标。患有多囊卵巢综合征的妇女和年龄较大的青少年主要是卵巢分泌过量的雄激素。然而，目前尚不清楚是否肾上腺、卵巢或两者都是超重女孩在发展为完全多囊卵巢综合征之前雄激素过剩的原因。尤其是在青春期早期，卵巢功能被认为是最低限度的。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。目的2将使用小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将研究长期治疗(例如，小剂量氢化可的松、二甲双胍或螺内酯)在青春期所有阶段减少女孩肥胖相关雄激素过剩的潜在疗效。这项研究将在弗吉尼亚大学的临床研究中心进行，并将诊断工具扩展到年轻女孩，以检查肾上腺和卵巢雄激素的产生。它可能确定治疗策略的靶点，以治疗或预防青春期雄激素过剩--青春期是多囊卵巢综合征发展的关键阶段。