Clinical trial NCT00805207: Sex Steroids, Sleep, and Metabolic Dysfunction in Women
Official title: Sex Steroids, Sleep, and Metabolic Dysfunction in Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Polycystic Ovary Syndrome (PCOS)
Obstructive Sleep Apnea
Obesity
Keywords: sleep apnea
obese
Very-low density lipoprotein (VLDL) metabolism
isotope tracer
women
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2008-12-09
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate
timeFrame: Before and at the end of interventions
Secondary outcomes:
measure: Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration
timeFrame: Before and at the end of the interventions
measure: VLDL-TG Plasma Clearance Rate (Means)
timeFrame: Before and at the end of the interventions
measure: VLDL-TG Plasma Clearance Rate (Medians)
timeFrame: Before and at the end of the interventions
measure: Basal, Postabsorptive Fractional Synthesis Rates of Muscle Protein Synthesis
timeFrame: Before and at the end of the intervention
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Bettina Mittendorfer, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang X, Magkos F, Patterson BW, Reeds DN, Kampelman J, Mittendorfer B. Low-dose dexamethasone administration for 3 weeks favorably affects plasma HDL concentration and composition but does not affect very low-density lipoprotein kinetics. Eur J Endocrinol. 2012 Aug;167(2):217-23. doi: 10.1530/EJE-12-0180. Epub 2012 May 22.
citation: Wang X, Smith GI, Patterson BW, Reeds DN, Kampelman J, Magkos F, Mittendorfer B. Testosterone increases the muscle protein synthesis rate but does not affect very-low-density lipoprotein metabolism in obese premenopausal women. Am J Physiol Endocrinol Metab. 2012 Mar 15;302(6):E740-6. doi: 10.1152/ajpendo.00533.2011. Epub 2012 Jan 17.
citation: Smith GI, Reeds DN, Okunade AL, Patterson BW, Mittendorfer B. Systemic delivery of estradiol, but not testosterone or progesterone, alters very low density lipoprotein-triglyceride kinetics in postmenopausal women. J Clin Endocrinol Metab. 2014 Jul;99(7):E1306-10. doi: 10.1210/jc.2013-4470. Epub 2014 Apr 2.
citation: Smith GI, Yoshino J, Reeds DN, Bradley D, Burrows RE, Heisey HD, Moseley AC, Mittendorfer B. Testosterone and progesterone, but not estradiol, stimulate muscle protein synthesis in postmenopausal women. J Clin Endocrinol Metab. 2014 Jan;99(1):256-65. doi: 10.1210/jc.2013-2835. Epub 2013 Dec 20.