Sleep, Metabolic, and Cardiovascular Dysfunction in PCOS

PCOS 患者的睡眠、代谢和心血管功能障碍

• 批准号: 6707054
• 负责人: DAVID A EHRMANN
• 金额: $ 36.13万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6707054
• 关键词: REM sleep; adolescence (12-20); androgens; arousal; cardiovascular disorder risk; cardiovascular function; clinical research; estrogens; female; hormone regulation /control mechanism; hormone therapy; human middle age (35-64); human subject; insulin; metabolic syndrome; metabolism; patient oriented research; polycystic ovary syndrome; sleep apnea; sleep disorders; young adult human (21-34)

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，可被视为雄激素过多症与年轻女性代谢综合征典型特征的结合。 PCOS 提供了一个独特的机会，可以在衰老的内在影响尚未显现的人群中剖析代谢和心血管风险与睡眠呼吸障碍 (SDB) 之间的关系。由于在没有 PCOS 的男性和女性中也观察到阻塞性睡眠呼吸暂停、胰岛素抵抗和睾酮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。本申请的具体目的是： 具体目的1：检验睡眠障碍是由PCOS特征的高雄激素血症和高胰岛素血症引起的假设。在对睡眠、激素、代谢和心血管参数进行详细的基线评估后，患有 PCOS 的女性将被随机分配到为期 8 周的治疗阶段，使用吡格列酮或长效亮丙瑞林加雌孕激素替代品或安慰剂。吡格列酮会降低多囊卵巢综合症患者的胰岛素水平，从而降低雄激素水平。我们将比较单独降低雄激素（长效亮丙瑞林加雌孕激素）与胰岛素加吡格列酮降低雄激素的效果。主要比较是安慰剂和吡格列酮之间睡眠参数相对于基线的变化；安慰剂和亮丙瑞林/雌激素/孕激素；吡格列酮和亮丙瑞林/雌激素/孕激素。具体目标 2：检验睡眠障碍导致多囊卵巢综合征女性荷尔蒙、代谢和心血管发生变化的假设。患有 SDB 的 PCOS 女性和患有 SDB 的匹配对照女性将在基线时和 CPAP 治疗 8 周后进行评估。主要比较 PCOS 女性的基线参数和治疗后参数。第二个比较是 PCOS 和对照女性治疗后相对于基线的变化，以检验这样的假设：对于 SDB 改善相同程度的情况，PCOS 患者代谢和心血管指标的变化幅度将大于对照。具体目标 3：检验以下假设：在正常年轻女性中，对睡眠进行实验性操作（重现 PCOS 女性睡眠障碍的特征）将导致代谢综合征典型的代谢、激素和心血管变化。将使用随机交叉设计对一组健康的年轻女性进行两次研究。在一项研究中，快速眼动睡眠将被连续 3 个晚上的实验诱发的微唤醒打断，而非快速眼动睡眠将不受干扰。另一方面，慢波活动将被抑制，而不会唤醒受试者，并且快速眼动睡眠将不受干扰。每项研究之前都会有 2 晚的基础睡眠。