Sleep, Metabolic, and Cardiovascular Dysfunction in PCOS

PCOS 患者的睡眠、代谢和心血管功能障碍

基本信息

批准号：
7096585
负责人：
DAVID A EHRMANN
金额：
$ 35.49万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-30 至 2008-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Polycystic ovary syndrome (PCOS) affects 5-10% of women and may be viewed as the combination of hyperandrogenism with the classical features of the metabolic syndrome in young women. PCOS presents a unique opportunity to dissect the relationship between metabolic and cardiovascular risk and sleep disordered breathing (SDB) in a population where intrinsic effects of aging have not yet developed. Because a relationship between obstructive sleep apnea, insulin resistance and elevated testosterone levels has also been observed in men and in women without PCOS, insights gained from studies in PCOS will have broad implications. the Specific Aims of the present application are: Specific Aim 1: to test the hypothesis that sleep disturbances are caused by hyperandrogenemia and hyperinsulinemia that characterize PCOS. Following a detailed baseline evaluation of sleep, hormonal, metabolic and cardiovascular parameters, women with PCOS will be randomized to an 8-week treatment phase with pioglitazone or depot leuprolide plus estrogerdprogestin replacement or placebo. Pioglitazone will reduce insulin levels, and consequently androgen levels, in PCOS. We will compare the effects of androgen reduction alone (depot leuprolide plus estrogerdprogestin) to those of insulin plus androgen reduction achieved with pioglitazone. Primary comparisons will be the change in sleep parameters from baseline between: placebo & pioglitazone; placebo & leuprolide/estrogen/progestin; pioglitazone & leuprolide/estrogen/progestin. Specific Aim 2: to test the hypothesis that sleep disturbances cause the hormonal, metabolic and cardiovascular alterations seen in women with PCOS. PCOS women with SDB and matched control women with SDB will be evaluated at baseline and following 8 weeks of CPAP treatment. The primary comparison will be between baseline and post-treatment parameters in PCOS women. The secondary comparison will be the post-treatment change from baseline between PCOS and control women to test the hypothesis that for the same degree in improvement in SDB, the magnitude of change in metabolic and cardiovascular measures will be greater in PCOS than in controls. Specific Aim 3: to test the hypothesis that in normal young women, experimental manipulation of sleep that recapitulates the sleep disturbances characteristic of women with PCOS will result in metabolic, hormonal, and cardiovascular alterations that are typical of the metabolic syndrome. A group of healthy young women will be studied twice using a randomized cross-over design. In one study, REM sleep will be fragmented by experimentally induced microarousals for 3 consecutive nights and non- REM sleep will be left undisturbed. In the other, slow wave activity will be suppressed without awakening the subject and REM sleep will be left undisturbed. Each study will be preceded by 2 nights of basetine sleep.

描述（由申请人提供）：多囊卵巢综合征（PCOS）影响5-10％的女性，可能被视为年轻女性中代谢综合征的经典特征的结合。 PCO提供了一个独特的机会，可以剖析代谢风险和心血管风险与睡眠无序呼吸（SDB）之间的关系，而衰老的内在影响尚未发展。由于在男性和没有PCOS的女性中也观察到了阻塞性睡眠呼吸暂停，胰岛素抵抗和睾丸激素水平升高之间的关系，因此从PCOS研究中获得的见解将具有广泛的影响。本应用的具体目的是：特定目的1：测试以下假设：睡眠障碍是由PCOS表征的高狂异生血症和高胰岛素血症引起的。在对睡眠，荷尔蒙，代谢和心血管参数进行详细的基线评估之后，患有PCOS的女性将随机分为8周的吡格列酮或liuprolide deprogeride Plus Extrogerdprogestin替代或安慰剂的8周治疗阶段。吡格列酮将在PCOS中降低胰岛素水平，从而降低雄激素水平。我们将比较单独的雄激素还原（Depot Leuprolide Plus Estrogerdprogestin）与使用吡格列酮实现的胰岛素加雄激素减少的影响。主要比较将是：安慰剂和吡格列酮之间的基线与基线的睡眠参数变化；安慰剂和luprolide/雌激素/孕激素； Pioglitazone和Leuprolide/雌激素/孕激素。特定目的2：测试睡眠障碍导致PCOS女性中观察到的激素，代谢和心血管改变的假设。具有SDB和与SDB的对照妇女相匹配的PCOS妇女将在基线和CPAP治疗8周后进行评估。主要比较将是PCOS妇女的基线和治疗后参数之间的比较。次要比较将是在PCOS和对照妇女之间的基线的治疗后变化，以检验以下假设：在SDB的改善中，PCOS的代谢和心血管措施的变化幅度要大于对照组。特定目的3：为了检验以下假设：在正常的年轻女性中，对概括PCOS女性的睡眠障碍特征的睡眠操纵将导致代谢，荷尔蒙和心血管改变是代谢综合征的典型特征。一群健康的年轻女性将使用随机跨界设计进行两次研究。在一项研究中，REM睡眠将连续3个晚上通过实验诱导的微观造成的微观分散，而非REM睡眠将不受干扰。另一方面，慢波活动将在不唤醒主题的情况下被抑制，而REM睡眠将不受干扰。每项研究都将在2晚的底座睡眠之前。