Sex Steroids, Sleep, and Metabolic Dysfunction in Women (SCOR)
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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 |
- 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 ]
- 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 |
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| United States, Missouri | |
| Washington University School of Medicine | |
| St. Louis, Missouri, United States, 63110 | |
| Principal Investigator: | Bettina Mittendorfer, PhD | Washington University School of Medicine |
More Information
No publications provided
| 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:
|
Apnea Obesity Polycystic Ovary Syndrome Sleep Apnea Syndromes Sleep Apnea, Obstructive Respiration Disorders Respiratory Tract Diseases Signs and Symptoms, Respiratory Signs and Symptoms Overnutrition Nutrition Disorders Overweight Body Weight Ovarian Cysts Cysts |
Neoplasms Ovarian Diseases Adnexal Diseases Genital Diseases, Female Gonadal Disorders Endocrine System Diseases Sleep Disorders, Intrinsic Dyssomnias Sleep Disorders Nervous System Diseases Testosterone Testosterone enanthate Testosterone undecanoate Testosterone 17 beta-cypionate Methyltestosterone |
ClinicalTrials.gov processed this record on May 23, 2013