PCOS, Sleep Apnea, and Metabolic Risk in Women

女性多囊卵巢综合征、睡眠呼吸暂停和代谢风险

基本信息

批准号：
7678042
负责人：
DAVID A EHRMANN
金额：
$ 30.1万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7678042
关键词：
Abbreviations Address Adipocytes Adrenal Glands Affect Aftercare Agonist Androgens Apnea Biological Assay Biopsy Blood specimen Body mass index Branched-Chain Amino Acids C-reactive protein Cardiovascular Diseases Cardiovascular system Chronic Collaborations Complement Confidence Intervals Continuous Positive Airway Pressure Corticotropin Data Dehydroepiandrosterone Sulfate Deterioration Development Disease Dose Double-Blind Method Dyslipidemias Elevation Endocrine Enrollment Estradiol Estrogens Excision Family Farnesyl Transferase Inhibitor Fatty acid glycerol esters Follicle Stimulating Hormone Gender Glucose Glucose Intolerance Goals Gonadal Steroid Hormones Gonadotropin Hormone Releasing Hormone HPSE gene Heritability High Density Lipoproteins High Prevalence Homeostasis Hormonal Hormones Hour Human Hydrocortisone Hydroxysteroid Dehydrogenases Hyperinsulinism Hypertension Hypertriglyceridemia Hypothalamic structure Immunoblotting In Vitro Incidence Inflammatory Insulin Insulin Resistance Interleukin-6 Interleukins Intervention Intravenous Kinetics LDL Cholesterol Lipoproteins Laboratories Lead Leuprolide Link Lipids Lipolysis Lipoproteins Low-Density Lipoproteins Luteinizing Hormone Measures Mediation Metabolic Metabolic Pathway Metabolism Methodology Methods Modeling Muscle Non-Insulin-Dependent Diabetes Mellitus Nonesterified Fatty Acids Numbers Obesity Obstructive Sleep Apnea Outcome Outcome Measure Ovarian Ovarian Ablation Pancreas Pathogenesis Pathologic Pharmaceutical Preparations Pituitary Gland Placebo Control Placebos Plasma Polycystic Ovary Syndrome Population Principal Investigator Production Progesterone Progestins Puberty Publishing REM Sleep Randomized Rate Relative (related person)Research Design Risk SHBG gene Sampling Severities Sex Characteristics Sex Hormone-Binding Globulin Sleep Sleep Apnea Syndromes Slow-Wave Sleep Steroids TNF gene Testing Testosterone Therapeutic Intervention Thinking Thyroxine Triglycerides Tumor Necrosis Factor-alpha Tumor Necrosis Factors Universities Upper arm Urine Vascular Diseases Very low density lipoprotein Very low density lipoprotein cholesterol Week Weight Woman acylcarnitine adiponectin attenuation base blood glucose regulation cardiovascular risk factor cysteine rich protein day design diabetes risk early onset ghrelin glucose tolerance glucose uptake human TNF protein hypercortisolemia hypothalamic-pituitary-adrenal axis impaired glucose tolerance improved indexing insight insulin secretion insulin sensitivity insulin signaling lipid metabolism lipoprotein cholesterol men metabolomics non rapid eye movement novel programs rapid eye movement resistin response tool

项目摘要

Obstructive sleep apnea (OSA) appears to be an underrecognized, yet significant factor in the pathogenesis of metabolic derangements in polycystic ovary syndrome (PCOS). Recent findings suggest that there may be two "subtypes" of PCOS, i.e. with or without OSA, and these two subtypes may be associated with distinct metabolic and endocrine alterations. PCOS women with OSA may be at much higher risk for diabetes and cardiovascular disease than PCOS women without OSA and may benefit from therapeutic interventions targeted to decrease the severity of OSA. Thus, a major goal of the present project is to contrast the metabolic and hormonal features of these two subtypes of PCOS, explore causative mechanisms for the high prevalence of OSA in PCOS, and test the hypothesis that continuous positive airway pressure (CPAP) treatment may decrease the risk of diabetes and other cardiovascular and metabolic abnormalities in PCOS women with OSA. In Specific Aim 1 we will determine if women with PCOS who have OSA differ from those without OSA as a consequence of differences in circulating concentrations estrogen and progesterone. We will further test our hypothesis by comparing stimulated steroid levels in response to a single dose of the GnRH agonist leuprolide in PCOS women with and those without OSA. In Specific Aim 2. we will determine if OSA improves in women with PCOS treated with estrogen or, progesterone. For these studies, we will enroll women with PCOS who have OSA. Subjects will have a detailed baseline metabolic and metabolomic profile together with a baseline polysomnogram. Subjects will then receive a single dose of depot-leuprolide in order to suppress ovarian production of estrogen, progestin, and androgen over a period of 3 months. Six weeks after administration of depot-leuprolide, subjects will have repeated assessment of metabolic, metabolomic, and sleep measures to determine if these outcomes are altered by the combined suppression of ovarian sex steroids. Subsequently, subjects will be randomized in a double-blind placebo controlled fashion to one of two treatment arms for a period of six weeks. Treatment arms are: estrogen plus placebo or progesterone plus placebo. At the end of this second six weeks, subjects will have metabolic, metabolomic, and sleep measures repeated. Primary outcome measures will be compared both within and between treatment arms. In Specific Aim 3. we will determine if metabolic disturbances present in PCOS women with OSA are ameliorated by the treatment of OSA with continuous positive airway pressure (CPAP). Results of our preliminary studies indicate that CPAP treatment of OSA results in attenuation of cortisol levels not only during sleep, but throughout waking hours as well. This aim will serve to test the hypothesis that correction of OSA in PCOS will lead to improved metabolic function which can be attributed, at least in part, to a reduction in circulating levels of cortisol.

阻塞性睡眠呼吸暂停（OSA）似乎是发病机理中未经认可但很重要的因素多囊卵巢综合征（PCOS）中的代谢异常。最近的发现表明可能是PCOS的两个“亚型”，即有或没有OSA，这两个亚型可能与独特的代谢和内分泌改变。 OSA患有OSA的PCOS女性可能会面临更高的风险糖尿病和心血管疾病比没有OSA的PCOS女性，可能会受益于治疗针对降低OSA严重程度的干预措施。因此，本项目的主要目标是对比PCOS这两个亚型的代谢和激素特征，探索因果关系 PCOS中OSA高患病率的机制，并检验了连续阳性的假设气道压力（CPAP）治疗可能会降低糖尿病和其他心血管的风险 OSA PCOS妇女的代谢异常。在特定目标1中，我们将确定是否有PCOS的女性由于循环浓度差异，其OSA与没有OSA的人不同雌激素和孕酮。我们将通过比较刺激的类固醇水平进一步检验我们的假设对具有OSA的PCOS妇女和患有PCOS女性的GNRH激动剂亮脂的单一剂量的反应。在具体目标2。我们将确定OSA是否在用雌激素治疗的PCOS的女性或孕酮。在这些研究中，我们将招募患有OSA的PCOS妇女。受试者将有一个详细的基线代谢和代谢组谱以及基线多个图。受试者会然后接收单剂量 - leuuprolide，以抑制雌激素，孕激素，孕激素的产生和雄激素在3个月内。给药后六个星期，受试者将已经重复评估代谢，代谢组和睡眠测量方法，以确定这些结果是否卵巢性类固醇的综合抑制会改变。随后，受试者将被随机化以双盲安慰剂的控制方式对两个治疗臂之一进行了六周的时间。治疗臂是：雌激素加安慰剂或孕酮加安慰剂。在第二个六个结束时几周，受试者将重复具有代谢，代谢组和睡眠度量。主要结果将在治疗臂之间和之间进行比较。在特定目标3中。我们将确定是否 OSA患有OSA的PCOS妇女中存在的代谢障碍通过使用OSA的治疗来改善连续正气道压力（CPAP）。我们的初步研究的结果表明CPAP治疗 OSA不仅会在睡眠期间而且在整个醒来的时间内都导致皮质醇水平的衰减。该目标将有助于检验以下假设：PCOS中OSA的校正将导致代谢改善可以至少部分地归因于循环水平的皮质醇水平的功能。