Sex Steroids, Sleep, and Metabolic Dysfunction in Women
Condition: Polycystic Ovary Syndrome (PCOS); Obstructive Sleep Apnea; Obesity
MeSH terms: Polycystic Ovary Syndrome; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
Study type: Interventional

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.
    


Intervention name(s): Progesterone; testosterone; glucocorticoid; continuous positive airway pressure; Estrogen; Control
Intervention type(s): Drug; Drug; Drug; Device; Drug; Other
Intervention description(s): Micronized progesterone, 100 mg/d vaginally. The intervention lasts 70 days in total and consisted of 14 days on treatment, 14 days off treatment, 14 days on treatment, 14 days off treatment and a final 14 days on treatment. Testing is performed before and at the end of the 70 day intervention.; Testosterone gel 1250 ug/d applied transdermally for a total of 21 days. Testing is performed before and at the end of the 21 day intervention.; Dexamethasone 0.013 mg/kg fat-free mass daily taken orally for a total of 21 days. Testing is performed before and at the end of the 21 day intervention.; Breathe through the mask of a continuous positive airway pressure device every night when sleep, for 6 weeks. Testing is performed before and at the end of the 6 week intervention.; Estrogen treatment (100 ug Estradiol daily) administered transdermally by using continuous delivery patches. The intervention lasted 70 days in total and consisted of 14 days on treatment, 14 days off treatment, 14 days on treatment, 14 days off treatment and a final 14 days on treatment.; No treatment with studies performed 31 to 72 days apart
Other intervention name(s): Endometrin; 1% AndroGel; Estradiol Patch, Mylan Pharmaceuticals Inc.
Intervention MeSH terms: Estradiol; Estrogens; Testosterone; Progesterone; Glucocorticoids
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: sleep apnea; obese; Very-low density lipoprotein (VLDL) metabolism; isotope tracer; women