Treatment of Hyperandrogenism vs. Insulin Resistance in Infertile PCOS Women

不孕 PCOS 女性高雄激素血症与胰岛素抵抗的治疗

基本信息

批准号：
8056663
负责人：
RICHARD S. LEGRO
金额：
$ 62.98万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-06-02 至 2013-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8056663
关键词：
Affect Androgens Anovulation Area Behavior Therapy Birth Birth Rate Blood Pressure Body Weight decreased Body mass index Characteristics Clinical Clinical Trials Design Clomiphene Clomiphene Citrate Conceptions Data Development Diabetes Mellitus Disease Endocrine System Diseases Face Female Fertility Funding Gestational Diabetes Glucuronides Goals Guidelines Health Healthcare Hyperandrogenism Hypertension induced by pregnancy Infertility Insulin Resistance Intervention Lead Life Style Live Birth Measures Metformin Monitor OGTT Obesity Oral Contraceptives Outcome Ovulation Ovulation Induction Pharmaceutical Preparations Phase Phenotype Polycystic Ovary Syndrome Population Pre-Eclampsia Predictive Factor Pregnancy Pregnancy Complications Pregnancy Outcome Pregnancy Rate Pregnancy loss Pregnanediol Proinsulin Randomized Randomized Controlled Trials Recruitment Activity Regimen Relative (related person)Reproductive Medicine Research Personnel Risk Role Spontaneous abortion Subfecundity Syndrome Test Result Testing United States National Institutes of Health Visit Woman arm care burden design diet and exercise effective therapy expectation experience glucose tolerance good diet improved indexing insulin sensitivity multidisciplinary neglect novel patient oriented pill pregnant prevent primary outcome programs randomized trial reproductive risk benefit ratio sibutramine urinary weight loss intervention

项目摘要

DESCRIPTION (provided by applicant): Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility among women, and women with PCOS are at increased risk for pregnancy complications such as gestational diabetes and pre-eclampsia. PCOS results in a significant health care burden to our economy with an estimated $500 million spent annually in the U.S. on infertility treatment alone. Both hyperandrogenism (HA) and obesity exacerbated insulin resistance (IR) are characteristic of the syndrome, and are targets for treatment, but which should be the predominant focus is unknown. We hypothesize that the key to improving the live birth rate in infertile women with PCOS is to correct HA, and the key to avoiding later pregnancy complications is to improve IR with an intense weight loss program. Phase I will be a randomized trial of three preconception interventions (lasting 4 mos.) in infertile women with PCOS (N=246, ~150 at Penn State and ~100 at U Penn): A) a combined intervention of medication (sibutramine), meal replacements, and lifestyle modficiation to improve IR B) continuous OCP for 4 months to improve HA and C) the combination of both to improve HA and IR. This will be followed by ovulation induction with clomiphene citrate in all subjects for up to 4 cycles (Phase II). All treatment arms will follow standardized diet and exercise regimens at this point. The primary outcome of the trial will be the cumulative live birth rates of the three treatment groups (and secondarily ovulation rates) which we propose will increase stepwise from Treatment A thru C. We will also examine changes in the PCOS phenotype during Phase I and II and will study all pregnant subjects by trimester in pregnancy for changes in glucose tolerance and blood pressure in the two treatment arms (Phase III). The goal of this trial is to establish the relative roles of HA versus IR and in combination in treating infertility and preventing pregnancy complications in women with PCOS. We will adapt existing medications and treatments with an established favorable risk benefit ratio to the treatment of infertile women with PCOS. Our trial is novel and important because we are studying women with PCOS across the continuum from pre-conception to conception to delivery. This project has assembled a unique multidisciplinary team bridging vast experience in their respective areas, and fulfills the mandates of the NIH roadmap to develop clinical interventions that improve patient oriented outcomes. PUBLIC HEALTH RELEVANCE: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women in the U.S. and is the leading cause of infertility in women. The best treatment for this disorder is unknown and this proposal will examine the effects of weight loss, reducing female androgens with the birth control pill, and using both in combination on pregnancy rates and pregnancy complication rates in women with PCOS. Our goal is to develop safe and effective treatments to improve the treatment of infertility in women with PCOS, but the findings can be generalized to all women with PCOS.

描述（由申请人提供）：多囊卵巢综合征（PCOS）是女性无排卵性不孕的最常见原因，患有 PCOS 的女性发生妊娠并发症（如妊娠糖尿病和先兆子痫）的风险增加。 PCOS 给我们的经济带来了巨大的医疗负担，据估计，美国每年仅在不孕不育治疗上就花费 5 亿美元。高雄激素血症 (HA) 和肥胖加剧的胰岛素抵抗 (IR) 都是该综合征的特征，也是治疗的目标，但尚不清楚哪一个应该成为主要焦点。我们假设，提高患有 PCOS 的不孕女性的活产率的关键是纠正 HA，而避免后期妊娠并发症的关键是通过强烈的减肥计划来改善 IR。第一阶段将是对患有 PCOS 的不孕女性（N=246，宾夕法尼亚州立大学约 150 人，宾夕法尼亚大学约 100 人）进行三种孕前干预（持续 4 个月）的随机试验：A）药物联合干预（西布曲明）、代餐和改变生活方式以改善 IR B) 连续 4 个月的 OCP 以改善 HA 和 C) 两者相结合以改善 HA 和 IR。随后，所有受试者将使用克罗米芬柠檬酸盐诱导排卵，最多 4 个周期（第二阶段）。此时，所有治疗组都将遵循标准化饮食和运动方案。该试验的主要结果将是三个治疗组的累积活产率（以及其次的排卵率），我们建议从治疗 A 到治疗 C 逐步增加。我们还将检查 I 期和 II 期 PCOS 表型的变化并将在怀孕三个月前研究所有怀孕受试者的两个治疗组的葡萄糖耐量和血压变化（第三阶段）。该试验的目的是确定 HA 与 IR 以及联合用药在治疗 PCOS 女性不孕症和预防妊娠并发症方面的相对作用。我们将采用现有的药物和治疗方法，以既定的有利风险效益比来治疗患有 PCOS 的不孕妇女。我们的试验是新颖且重要的，因为我们正在研究患有多囊卵巢综合症的女性从受孕前到受孕再到分娩的整个过程。该项目组建了一支独特的多学科团队，在各自领域积累了丰富的经验，并履行了 NIH 路线图的任务，开发临床干预措施，改善以患者为导向的结果。公共健康相关性：多囊卵巢综合征 (PCOS) 是美国女性最常见的内分泌疾病，也是女性不孕的主要原因。这种疾病的最佳治疗方法尚不清楚，该提案将研究减肥、使用避孕药减少女性雄激素以及两者联合使用对多囊卵巢综合症女性妊娠率和妊娠并发症率的影响。我们的目标是开发安全有效的治疗方法，以改善 PCOS 女性不孕症的治疗，但研究结果可以推广到所有 PCOS 女性。