Sex Steroids, Sleep, and Metabolic Dysfunction in Women

Study Summary

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.

Primary Outcome

VLDL was isolated from plasma by ultracentrifugation with the tracer-to-tracee (TTR) of free glycerol in plasma and glycerol in VLDL-TG determined by gas chromatography-mass spectrometry. The fractional turnover rates of VLDL-TG was determined by fitting the glycerol TTR time courses in plasma and in VLDL-TG to a multicompartmental model. The hepatic (liver) secretion rates of VLDL-TG was calculated by multiplying the fractional turnover rates of VLDL-TG by the of VLDL-TG concentration.

Interventions

• DRUG Progesterone
• DRUG Estrogen
• DRUG testosterone
• DRUG glucocorticoid
• DEVICE continuous positive airway pressure