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：
7630483
负责人：
RICHARD S. LEGRO
金额：
$ 62.65万
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/7630483
关键词：
Affect Androgens Anovulation Area 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 Healthcare Hyperandrogenism Hypertension induced by pregnancy Infertility Insulin Resistance Intervention Lead Life Style Live Birth Measures Metformin Modification 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 Clinical Trials Randomized Controlled Trials Recruitment Activity Relative (related person)Reproductive Medicine Research Personnel Risk Role Spontaneous abortion Subfecundity Syndrome Test Result Testing Treatment Protocols United States National Institutes of Health Upper arm Visit Woman 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 public health relevance 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）是妇女发出不育的最常见原因，而患有PCOS的女性患妊娠并发症的风险增加，例如妊娠糖尿病和前宾夕法尼亚前诊所。 PCOS为我们的经济带来了巨大的医疗保健负担，仅在美国每年在美国不孕治疗上花费了5亿美元。超雄激素（HA）和肥胖症加剧的胰岛素抵抗（IR）都是综合征的特征，是治疗的靶标，但应该是主要的焦点。我们假设，提高PCOS不育女性的活产生率的关键是纠正HA，避免以后的怀孕并发症的关键是通过强烈的减肥计划来改善IR。 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.在所有受试者中，最多4个周期（II阶段）将用柠檬酸氯酸酯排卵诱导。目前，所有治疗臂都将遵循标准化的饮食和运动方案。该试验的主要结果将是我们提出的三个治疗组的累积活产率（以及第二个排卵率）将从治疗中逐步增加。我们还将检查I和II期间PCOS表型的变化，并将研究妊娠中孕妇在怀孕中的所有怀孕受试者，以实现两次治疗臂的变化和血液（阶段III阶段）的变化。该试验的目的是确定HA与IR的相对作用，并在治疗不孕症和预防PCOS女性妊娠并发症中结合使用。我们将以确定的有利风险益处比例适应现有的药物和治疗方法，以治疗对PCOS的不育妇女的治疗。我们的试验很新颖，很重要，因为我们正在研究从概念到构想再到交付的连续体的PCOS女性。该项目已经组建了一个独特的多学科团队，在各自领域弥合了丰富的经验，并履行了NIH路线图的任务，以开发临床干预措施，以改善患者面向患者的结果。公共卫生相关性：多囊卵巢综合征（PCOS）是美国女性中最常见的内分泌疾病，是女性不孕症的主要原因。该疾病的最佳治疗方法尚不清楚，该提案将检查体重减轻，通过避孕药减少雌性雄激素的影响，并在PCOS女性中使用妊娠率和妊娠并发症率的结合。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，但可以将这些发现推广到所有患有PCOS的女性。