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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00805207
First received: December 5, 2008
Last updated: April 11, 2013
Last verified: April 2013
  Purpose

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 and sleep disordered breathing. PCOS affects 5-8% of women. Sleep disordered breathing affects up to 10% of women. Obstructive sleep apnea 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 TG concentration associated with obesity, and the effects of polycystic ovary syndrome and obstructive sleep apnea 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 triglyceride concentration in obese women with polycystic ovary syndrome and obstructive sleep apnea. 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 Intervention
Polycystic Ovary Syndrome
Obstructive Sleep Apnea
Obesity
Drug: Progesterone
Drug: testosterone
Drug: glucocorticoid
Device: continuous positive airway pressure
Drug: Estrogens

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Sex Steroids, Sleep, and Metabolic Dysfunction in Women

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • VLDL-TG secretion and plasma clearance rates, total plasma TG and VLDL-TG concentrations [ Time Frame: Before and at the end of interventions ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • VLDL-apoB-100 kinetics and plasma TG, VLDL-TG, VLDL-apoC-II, VLDL-apoC-III, and VLDL-apoE concentrations [ Time Frame: Before and at the end of the interventions ] [ Designated as safety issue: No ]
  • Basal, postabsorptive rates of muscle protein synthesis [ Time Frame: Before and at the end of the intervention ] [ Designated as safety issue: No ]

Enrollment: 61
Study Start Date: September 2007
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Progesterone
Obese women with polycystic ovary syndrome or postmenopausal women
Drug: Progesterone
Micronized progesterone, 100 mg/d vaginally, 14 days followed by 14 days of placebo. Repeat this cycle 3 times.
Active Comparator: PCOS control
Lean and obese healthy women
Drug: testosterone
Testosterone gel 1250 ug/d, 21 days
Experimental: OSA
Obese women and men with 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
Active Comparator: OSA control
Lean and obese healthy women, and obese men
Drug: glucocorticoid
Dexamethasone 0.013 mg/kg fat-free mass daily, 21 days
Experimental: estrogen
Postmenopausal women
Drug: Estrogens
Estrogen treatment (100 ug Estradiol daily) administered 14 days followed by 14 days without treatment. Repeat this cycle 3 times.
No Intervention: control
Postmenopausal women

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00805207

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

No publications provided by Washington University School of Medicine

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00805207     History of Changes
Other Study ID Numbers: 07-0692, NIH P50 HD057796
Study First Received: December 5, 2008
Last Updated: April 11, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
PCOS
sleep apnea
obese
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 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
Progesterone
Estrogens
Glucocorticoids
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014