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Completed

NCT Number: NCT00805207

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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Key information

Conditions

Polycystic Ovary Syndrome (PCOS) Adnexal Diseases Apnea Body Weight Cysts Dyssomnias Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Gonadal Disorders Neoplasms Nervous System Diseases Nutrition Disorders Nutritional and Metabolic Diseases Obesity Obstructive Sleep Apnea Ovarian Cysts Ovarian Diseases Overnutrition Overweight Pathological Conditions, Signs and Symptoms Polycystic Ovary Syndrome Respiration Disorders Respiratory Tract Diseases Signs and Symptoms Sleep Apnea Syndromes Sleep Apnea, Obstructive Sleep Disorders, Intrinsic Sleep Wake Disorders Urogenital Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Progesterone

Drug

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.

Other names: Endometrin

Testosterone

Drug

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.

Other names: 1% AndroGel

glucocorticoid

Drug

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.

Continuous Positive Airway Pressure

Device

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

Drug

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.

Other names: Estradiol Patch, Mylan Pharmaceuticals Inc.

Control

Other

No treatment with studies performed 31 to 72 days apart

Primary outcomes

  1. Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate

    Time frame: Before and at the end of interventions

    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.

Secondary outcomes

  1. Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration

    Time frame: Before and at the end of the interventions

    VLDL was isolated from plasma by ultracentrifugation with VLDL-TG concentration measured by using a colorimetric enzymatic kit (Sigma-Aldrich, St. Louis, MO).

  2. VLDL-TG Plasma Clearance Rate (Means)

    Time frame: Before and at the end of the interventions

    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 plasma clearance rate of VLDL-TG was calculated by dividing the VLDL-TG secretion rate by the VLDL-TG concentration.

  3. VLDL-TG Plasma Clearance Rate (Medians)

    Time frame: Before and at the end of the interventions

    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 plasma clearance rate of VLDL-TG was calculated by dividing the VLDL-TG secretion rate by the VLDL-TG concentration.

  4. Basal, Postabsorptive Fractional Synthesis Rates of Muscle Protein Synthesis

    Time frame: Before and at the end of the intervention

    The fractional synthesis rate (FSR) of muscle protein synthesis was determined by assessing the incorporation of [5,5,5-2H3]leucine into muscle proteins. [5,5,5-2H3]leucine was infused for 5 hours with muscle biopsies obtained from the vastus lateralis muscle in the thigh 2 and 5 hours. The leucine tracer-to-tracee ratio (TTR) in muscle protein and the muscle free leucine pool was determined by gas chromatography-mass spectrometry (GCMS) and the FSR of muscle proteins calculated using a standard precursor-product model.

    The FSR was calculated as %/h, which reflects the percent of all proteins in the muscle that were synthesized (made) per hour.

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Registry information

Acronym: SCOR

Important dates

Study start
2007
Primary completion
2013
Study completion
2013
First posted
Dec 9, 2008
Registry last updated
Aug 1, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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