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: 8220192
• 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/8220192
• 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 treatment; 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. PUBLIC HEALTH RELEVANCE: Childhood obesity - an international problem - puts girls at risk for excess male hormone (androgen) production and polycystic ovary syndrome (PCOS). PCOS leads to infertility, metabolic problems, and male-pattern hair growth in women and adolescents. This project would identify sources of obesity-related androgen excess during puberty and examine the efficacy of potential therapies in reducing androgen levels in girls during all stages of puberty, with the goal of preventing PCOS.

描述（由申请人提供）：该研究奖将支持克莉丝汀M。伯特索洛尔扎诺，医学博士，弗吉尼亚大学（UVA）的，因为她继续在以病人为导向的研究约翰C。医学博士马歇尔，哲学博士、生殖神经内分泌学和多囊卵巢综合征（PCOS）的既定研究者。索洛尔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方面。她的近期目标是了解PCOS的起源并确定新的治疗策略。她的长期目标是成为儿科PCOS研究的领导者，评估干预措施预防PCOS的有效性。该培训将使索洛尔扎诺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，其中包括临床试验方法，生物统计学，流行病学，研究伦理学，分析方法和研究设计的全面指导，部分通过临床研究硕士学位。索洛尔扎诺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，并确定减少这一人群雄激素产生的潜在策略。 青春期雄激素过多是PCOS的先兆，PCOS是一种常见的慢性内分泌紊乱，与不孕、代谢紊乱和女性多毛症有关。儿童肥胖--一个国际性的问题--使女孩面临雄激素过多的风险，即使在青春期早期。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PCOS的女性和年龄较大的青少年主要是卵巢雄激素过度生产。然而，目前尚不清楚是否肾上腺，卵巢，或两者都负责雄激素过剩的超重女孩之前，发展成全面的PCOS综合征。在青春期早期，卵巢功能被认为是最小的，尤其如此。 目的1将使用肾上腺抑制/刺激试验和卵巢刺激试验来检查正常和超重女孩在整个青春期雄激素产生的来源。目标2将使用低剂量氢化可的松和亮丙瑞林治疗，以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将检查长期治疗的潜在疗效（例如，低剂量氢化可的松、二甲双胍或螺内酯），以减少青春期所有阶段女孩中与肥胖相关的雄激素过多。这项研究将在弗吉尼亚大学的临床研究中心进行，并将扩展诊断工具，以检查年轻女孩的肾上腺和卵巢雄激素产生。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-PCOS发展的关键阶段。 公共卫生相关性：儿童肥胖--一个国际性问题--使女孩面临过量雄性激素（雄激素）产生和多囊卵巢综合征（PCOS）的风险。多囊卵巢综合征导致不孕症，代谢问题，以及女性和青少年的男性模式毛发生长。该项目将确定青春期肥胖相关雄激素过多的来源，并检查潜在治疗在青春期所有阶段降低女孩雄激素水平的有效性，以预防PCOS。