Polycystic Ovary Syndrome (PCOS) and Sleep Apnea
Polycystic ovary syndrome (PCOS) affects 5-10% of women in the United States. Its onset is usually at the time of puberty with manifestations of menstrual irregularity, hirsutism, and obesity. Women with PCOS suffer at an early stage of adulthood from all of the components of the metabolic syndrome, a syndrome that typically has its peak in mid-life in other subject populations. Women with PCOS are more insulin resistant than weight-matched control women and have exceptionally high rates of early-onset impaired glucose tolerance and type 2 diabetes, as well as a substantially elevated risk for hypertension, dyslipidemia, coronary, and other vascular diseases. While recent evidence indicates that the prevalence of sleep-disordered breathing (SDB) is 30-40 fold higher in PCOS than in weight-matched control women, the possible role of SDB in causing the increased metabolic and cardiovascular risks of PCOS has not been evaluated. The overall objective of the proposed study is to analyze the direction of causality between sleep disturbances and markers of the metabolic syndrome in PCOS.
Polycystic Ovary Syndrome
Obstructive Sleep Apnea
Device: continuous positive airway pressure (CPAP)
Drug: depot leuprolide plus estrogen/progestin replacement
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
|Official Title:||Sleep, Metabolic, and Cardiovascular Dysfunction in Polycystic Ovary Syndrome|
- oral glucose tolerance [ Time Frame: up to 2 hrs. ] [ Designated as safety issue: No ]
- intravenous glucose tolerance [ Time Frame: up to 24 hrs. ] [ Designated as safety issue: Yes ]
- testosterone levels [ Time Frame: up to 24 hrs. ] [ Designated as safety issue: No ]
- luteinizing hormone levels [ Time Frame: 15 minutes over a period of 24 hours (except meals) ] [ Designated as safety issue: No ]
- sleep apnea events [ Time Frame: 20 minutes, 5 times @ 2-hr. intervals, over the course of a day ] [ Designated as safety issue: No ]
- left ventricular function [ Time Frame: up to half of an hour ] [ Designated as safety issue: No ]
- blood pressure [ Time Frame: up to 24 hours ] [ Designated as safety issue: No ]
- leptin levels [ Time Frame: 15 minutes over a period of 24 hours ] [ Designated as safety issue: No ]
- ghrelin levels [ Time Frame: 10 minutes over a period of 24 hours ] [ Designated as safety issue: No ]
- cortisol levels [ Time Frame: 10 minutes, over a period of 24 hours ] [ Designated as safety issue: No ]
- visceral adiposity [ Time Frame: up to half of an hour ] [ Designated as safety issue: No ]
- brachial artery reactivity [ Time Frame: up to half of an hour ] [ Designated as safety issue: No ]
|Study Start Date:||September 2003|
|Study Completion Date:||June 2008|
|Primary Completion Date:||June 2008 (Final data collection date for primary outcome measure)|
Device: continuous positive airway pressure (CPAP)
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 estrogen/progestin 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 estrogen/progestin) 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 baseline sleep.
|United States, Illinois|
|University of Chicago|
|Chicago, Illinois, United States, 60637|
|Principal Investigator:||David A Ehrmann, M.D.||University of Chicago|
|Study Director:||Esra Tasali, M.D.||University of Chicago|
|Study Director:||Eve Van Cauter, Ph.D.||University of Chicago|