PCOS, Sleep Apnea and Metabolic Risk in Women
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.
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
Sex steroid levels
After treatment (6 weeks)
No
David A Ehrmann, MD
Principal Investigator
University of Chicago
United States: Food and Drug Administration
15872B
NCT00696111
December 2007
August 2012
Name | Location |
---|---|
University of Chicago Department of Medicine, Section of Endocrinology, Diabetes & Metabolism | Chicago, Illinois 60637 |