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）医学博士的Christine M. Burt Solorzano的发展，因为她继续在约翰·C·马歇尔（John C. Marshall，M.D。）的指导下培训以患者为导向的研究，该研究是医学博士学位的研究员，是一名固定的神经素质分泌学研究员，PC PC PC PC（PC）（PC）（PC）。 Solorzano博士是一位儿科内分泌学家，以前的研究经验着重于肥胖方面。她的直接目标是了解PCOS的起源并确定新的治疗策略。她的长期目标是成为小儿PCOS研究的领导者，评估干预措施防止PCOS的功效。这项培训将使Solorzano博士获得成为独立临床研究者所需的技能。该应用程序概述了一项职业发展计划，其中包括临床试验方法，生物统计学，流行病学，研究伦理学，测定方法论和研究设计的全面指导，部分通过临床研究大师。 Solorzano博士的研究建议旨在确定超重女孩中雄激素过剩的来源和时机，并确定潜在的策略来减少该人群中的雄激素产生。 青春期期间的雄激素过量是PCOS-A常见的慢性内分泌疾病的先驱，与不育，代谢性疾病和女性的毛毛学有关。儿童肥胖症 - 国际问题 - 即使在青春期初期，也使面对雄激素过剩的女孩有过多的风险。需要在青春期中识别过多的雄激素过量来源，以阐明预防PCOS的靶标。具有PCOS的妇女和年长的青少年主要对雄激素产生过多生产。但是，尚不清楚肾上腺，卵巢还是两者是在发展完整的PCOS综合征之前导致超重女孩的雄激素过量。当卵巢功能被认为是最小的时候，在青春期初期尤其如此。 AIM 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中正常和超重女孩中雄激素产生的来源。 AIM 2将使用低剂量的氢化可的松和亮脂疗法来测试短期抑制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量超重女孩的雄激素水平。 AIM 3将检查长期疗法（例如，低剂量氢化可的松，二甲双胍或螺内酯）的潜在疗效，以减少在青春期的所有阶段中与肥胖相关的雄激素过量的降低。该研究将在UVA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的产生。它可以确定青春期治疗或预防雄激素过量的治疗策略的目标 - PCOS的发展是一个关键阶段。