Sex Steroids, Sleep, and Metabolic Dysfunction in Women
Sex Steroids, Sleep, and Metabolic Dysfunction in Women
Increased plasma triglyceride concentration is a common feature of the metabolic
 abnormalities associated with obesity and a major risk factor for cardiovascular disease.
 Obesity is a major risk factor for two conditions that appear to be increasing in prevalence
 in women: the polycystic ovary syndrome (PCOS) and sleep disordered breathing. PCOS affects
 5-8% of women. Sleep disordered breathing affects up to 10% of women. Obstructive sleep apnea
 (OSA) is the most common cause for sleep disordered breathing and particularly prevalent in
 obese women with PCOS (~50%). Both PCOS and OSA augment the increase in plasma triglyceride
 (TG) concentration associated with obesity, and the effects of PCOS and OSA on plasma TG
 concentration appear to be additive. The mechanisms responsible for the adverse effects on
 plasma TG metabolism are not known. The primary goal of this project, therefore, is to
 determine the mechanisms responsible for the increase in plasma TG concentration in obese
 women with PCOS and OSA. It is our general hypothesis that alterations in the hormonal milieu
 that are characteristic of these two conditions are, at least in part, responsible for the
 increase in plasma TG concentration in obese women with the conditions. Furthermore, we
 hypothesize that the hormonal aberrations characteristic of the two conditions are
 particularly harmful to obese, compared with lean, women.

 The effects of PCOS on skeletal muscle protein metabolism are also not known. However, sex
 hormones are thought to be important regulators of muscle protein turnover suggesting that
 muscle protein metabolism is likely to be affected by PCOS. We will examine this by
 determining the effect of individual sex hormones on muscle protein metabolism and
 hypothesize that testosterone administration will stimulate muscle protein metabolism while
 estrogen and progesterone administration will inhibit muscle protein metabolism.
Inclusion Criteria:

 -  Women aged 18-75 years and men 45-75 years

 -  Healthy lean, overweight and obese women (BMI 18-40 kg/m2) and obese men (BMI 30-40
 kg/m2)

 -  Obese women (BMI 30-40 kg/m2) with OSA or PCOS

 Exclusion Criteria:

 -  Pregnant, lactating, peri- or postmenopausal women will be excluded from the study
 because of potential confounding influences of these factors and potential ethical
 concerns (pregnant women)

 -  Women taking medications known to affect substrate metabolism and those with evidence
 of significant organ dysfunction (e.g. impaired glucose tolerance, diabetes mellitus,
 liver disease, hypo- or hyper-thyroidism) other than PCOS and OSA

 -  Severe hypertriglyceridemia (fasting plasma TG concentration >400 mg/dl)

 -  Subjects with OSA who have an apnea-hypopnea index (AHI) score >30 (the total number
 of obstructive events divided by the total hours of sleep) will be excluded and
 instructed to seek medical care