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Sleep, Metabolic, and Cardiovascular Dysfunction in Polycystic Ovary Syndrome

Phase 4
18 Years
40 Years
Not Enrolling
Polycystic Ovary Syndrome, Obstructive Sleep Apnea

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Trial Information

Sleep, Metabolic, and Cardiovascular Dysfunction in Polycystic Ovary Syndrome

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.

Inclusion Criteria:

- PCOS subjects will be recruited from the Endocrinology Clinics of the University of
Chicago. All will be at least 2 years postmenarche and less than 40 years of age. A
diagnosis of PCOS will require:

- the presence of oligo/amenorrhea;

- hyperandrogenemia, defined by a supranormal plasma free testosterone level (> 10

- hyperandrogenism, as evidenced by infertility, hirsutism, acne, or androgenetic
alopecia; and

- exclusion of nonclassic 21-hydroxylase deficiency congenital adrenal
hyperplasia, Cushing's syndrome, hypothyroidism, or significant elevations in
serum prolactin. Thus, all subjects will meet the National Institutes of Health
(NIH) consensus criteria for PCOS.

- Control subjects will be matched, as closely as possible, for age, ethnicity, body
mass index (BMI), and body fat distribution (as assessed by single cut abdominal
computed tomography [CT] scan and dual energy x-ray absorptiometry [DEXA] scan).

- Normal lean (BMI <25 kg/m2) women will be between 18 and 40 years of age, in good
health, with normal menstrual cycles, no sleep complaints, no history of endocrine
disorder. All studies will be initiated in the early follicular phase (days 2-4).

- For at least 2 months before the study, all subjects (PCOS and control) must not take
steroid preparations (including oral contraceptives), medications known to alter
insulin secretion and/or action, or medications known to influence sleep.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Outcome Measure:

oral glucose tolerance

Outcome Time Frame:

up to 2 hrs.

Safety Issue:


Principal Investigator

David A Ehrmann, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago


United States: Institutional Review Board

Study ID:




Start Date:

September 2003

Completion Date:

June 2008

Related Keywords:

  • Polycystic Ovary Syndrome
  • Obstructive Sleep Apnea
  • polycystic ovary syndrome
  • metabolic syndrome
  • obstructive sleep apnea
  • impaired glucose tolerance
  • insulin resistance
  • Apnea
  • Polycystic Ovary Syndrome
  • Sleep Apnea Syndromes
  • Sleep Apnea, Obstructive



University of Chicago Chicago, Illinois  60637