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Sex Steroids, Sleep, and Metabolic Dysfunction in Women (SCOR)

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ClinicalTrials.gov Identifier: NCT00805207
Recruitment Status : Completed
First Posted : December 9, 2008
Results First Posted : August 1, 2018
Last Update Posted : August 1, 2018
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

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.


Condition or disease Intervention/treatment Phase
Polycystic Ovary Syndrome (PCOS) Obstructive Sleep Apnea Obesity Drug: Progesterone Drug: testosterone Drug: glucocorticoid Device: continuous positive airway pressure Drug: Estrogen Other: Control Not Applicable

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Sex Steroids, Sleep, and Metabolic Dysfunction in Women
Study Start Date : September 2007
Actual Primary Completion Date : March 2013
Actual Study Completion Date : March 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Progesterone - PCOS
Women with obesity and polycystic ovary syndrome
Drug: Progesterone
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 Name: Endometrin

Experimental: Testosterone - premenopausal women
Healthy premenopausal women.
Drug: testosterone
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 Name: 1% AndroGel

Experimental: Continuous positive airway pressure
Women and men with obesity and obstructive sleep apnea
Device: continuous positive airway pressure
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.

Experimental: Glucocorticoid
Lean and obese healthy women, and obese men
Drug: glucocorticoid
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.

Experimental: Estrogen
Postmenopausal women
Drug: Estrogen
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 Name: Estradiol Patch, Mylan Pharmaceuticals Inc.

control
Postmenopausal women - tested before and after no treatment. Duration between before and after testing ranged from 31 to 78 days with an average of 46 days between visits
Other: Control
No treatment with studies performed 31 to 72 days apart

No Intervention: control - baseline testing only
Healthy men and women
Experimental: Progesterone - Postmenopausal women
Postmenopausal women
Drug: Progesterone
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 Name: Endometrin

Experimental: Testosterone - Postmenopausal women
Postmenopausal women
Drug: testosterone
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 Name: 1% AndroGel




Primary Outcome Measures :
  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 Outcome Measures :
  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.




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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00805207


Locations
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Bettina Mittendorfer, PhD Washington University School of Medicine

Publications of Results:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00805207     History of Changes
Other Study ID Numbers: 07-0692
NIH P50 HD057796
First Posted: December 9, 2008    Key Record Dates
Results First Posted: August 1, 2018
Last Update Posted: August 1, 2018
Last Verified: July 2018

Keywords provided by Washington University School of Medicine:
sleep apnea
obese
Very-low density lipoprotein (VLDL) metabolism
isotope tracer
women

Additional relevant MeSH terms:
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Polycystic Ovary Syndrome
Apnea
Respiration Disorders
Respiratory Tract Diseases
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Estradiol
Progesterone
Estrogens
Glucocorticoids
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists