Metabolic Study of Women With Polycystic Ovary Syndrome and Sleep Apnea

Not Applicable

Completed

Conditions: Polycystic Ovary Syndrome
Obstructive Sleep Apnea

Interventions: Drug: Depot Lupron followed by estrogen plus placebo

Registration Number: NCT00696111

Lead Sponsor: University of Chicago

Brief Summary: The purpose of this study is to look at the metabolic (use of energy) and hormonal features of sleep problems in women with polycystic ovary syndrome (PCOS).

Detailed Description: The prevalence of obesity and chronic sleep loss are at record levels among Americans and evidence continues to emerge to support a causal link between the two conditions. Metabolic abnormalities related to sleep disruption are particularly evident in individuals with obstructive sleep apnea (OSA), a disorder traditionally associated with male gender. While more prevalent in men, OSA is underrecognized in women in part because its clinical and polysomnographic features differ from those of men. Women with polycystic ovary syndrome (PCOS) are particularly susceptible to OSA with at least a 5-fold higher risk for its development compared to obese women without PCOS. This study will enroll obese women with PCOS, with and without OSA. Those with OSA will be randomized to receive CPAP or to receive depot leuprolide to suppress ovarian steroid output over 12 weeks, reassessed at 6 weeks, and then randomized (double-blind, placebo controlled) to 6 weeks of either micronized estrogen + placebo or micronized progestin + placebo. The independent effects of androgen, estrogen, and progesterone on OSA and metabolic function will be assessed. In addition, primary human adipocytes will be prepared from fat biopsies obtained from subjects. Insulin sensitivity will be determined by phospho-specific immunoblotting in conjunction with glucose uptake and anti-lipolysis assays. In parallel, adipocytes from these subjects will be cultured for 1-5 days prior to metabolic assays to ascertain if removal of from circulating factors will improve insulin signaling, or if insulin resistance persists in vitro. Finally, there will be an interface with the Metabolomics Laboratory at Duke University (C. Newgard, Lab Director), and metabolomics assessment will be done on blood and urine samples.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 18

Inclusion Criteria

Clinical diagnosis of PCOS
Obese (BMI of at least 30 kg/m2)

Exclusion Criteria

Diagnosis of nonclassic 21-hydroxylase deficiency, Cushing syndrome, hypothyroidism, or significant elevations in prolactin
Taking steroid preparations (including oral contraceptives), medications known to alter insulin secretion and/or action, or medications known to influence sleep during the 2 months prior to starting the study
Positive pregnancy test
Diagnosis of diabetes mellitus
Hypertension (systolic > 140 mmHg and/or diastolic > 90 mmhg) not well-controlled on stable medication with either ACE inhibitors or diuretics
Habitual alcohol use
Excessive caffeine intake of more than 300 mg/day
Known peanut allergies, or allergies to medications used in the study
Hemoglobin < 11g/dL and/or hematocrit < 33%
Systemic illnesses, including heart, renal, liver, or malignant disease

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Depot Lupron and estrogen plus placebo	Depot Lupron followed by estrogen plus placebo	Randomized to receive depot Lupron for 6 weeks. Then randomized again to receive estrogen plus placebo for another 6 weeks.

Primary Outcome Measures

Name	Time	Method
Estrogen Levels	Baseline	Estrogen levels measured every 20 minutes for 24 hours and the the average of those values are presented. The units of measurement are picograms per milliter (pg/ml).
Sleep Efficiency Measured at Baseline	Baseline	Sleep efficiency recorded with polysomnography minimum value = 0%, maximum value = 100%, higher values are a better outcome.
Total Testosterone	Baseline	Total Testosterone levels measured every 20 minutes for 24 hours and the average of those values are presented. The units of measurement are picograms per milliter (pg/ml).

Secondary Outcome Measures

Name	Time	Method
Intravenous Glucose Tolerance Test	Baseline	Acute Insulin Response measured by the intravenous glucose tolerance test measured during baseline. The unit of measurement is mg/dl.