Obesity Clinical Trial
Official title:
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.
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