Symptoms and General Pathology

All Conditions

Nutritional and Metabolic Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Nervous System Diseases

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Behaviors and Mental Disorders

Syndrome

Obesity

Apnea

Sleep Apnea Syndromes

Sleep Apnea, Obstructive

Polycystic Ovary Syndrome

Respiration Disorders

Respiratory Tract Diseases

Parasomnias

Sleep Disorders, Intrinsic

Dyssomnias

Sleep Wake Disorders

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

All Drugs and Chemicals

Anti-Inflammatory Agents

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Antiemetics

Gastrointestinal Agents

Reproductive Control Agents

Estradiol

Dexamethasone

Methyltestosterone

Estrogens

Glucocorticoids

Dexamethasone acetate

Estradiol 17 beta-cypionate

Estradiol 3-benzoate

Polyestradiol phosphate

Testosterone

Testosterone undecanoate

Testosterone enanthate

Testosterone 17 beta-cypionate

Progesterone

Hormones

Hormone Antagonists

Androgens

Progestins

Women with obesity and polycystic ovary syndrome

Women and men with obesity and obstructive sleep apnea

Lean and obese healthy women, and obese men

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

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.

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.

testosterone

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.

glucocorticoid

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.

continuous positive airway pressure

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.

Estrogen

No treatment with studies performed 31 to 72 days apart

Control

Bettina Mittendorfer, PhD

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.

Sex Steroids, Sleep, and Metabolic Dysfunction in Women

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.

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

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.

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.

Washington University School of Medicine

Healthy, premenopausal women.

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.

Testosterone - Premenopausal Women

Postmenopausal women

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.

Testosterone - Postmenopausal Women

Women with obesity and polycystic ovary syndrome

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.

Progesterone - PCOS

Postmenopausal women

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.

Progesterone - Postmenopausal Women

Obese women and men with obstructive sleep apnea

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.

Continuous Positive Airway Pressure

Lean and obese healthy women, and obese men

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.

Glucocorticoid

Postmenopausal women

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.

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

Healthy men and women

Baseline testing only

Control - Baseline Testing Only

Healthy, premenopausal women

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

Women and men with obesity and obstructive sleep apnea

continuous positive airway pressure: Breathe through the mask of a continuous positive airway pressure device every night when sleep, for 6 weeks

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Gordon Smith, PhD

Before

After

Women and men with obesity and obstructive sleep apnea

Continuous positive airway pressure: Breathe through the mask of a continuous positive airway pressure device every night when sleep, for 6 weeks

Not included in final analysis:

Withdrawn/withdrew= Testosterone premenopausal women x 1; Progesterone postmenopausal women x 2; Glucocorticoid x 3.

VLDL-TG fractional turnover rate was 3 Standard Deviations from the mean = Testosterone - premenopausal women x 1.

Undetectable VLDL-TG concentration = Progesterone - Postmenopausal women x 1.

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

Not included in final analysis:

Withdrawn/withdrew = Testosterone premenopausal women x 1; Progesterone postmenopausal women x 2; Glucocorticoid x 3.

VLDL-TG fractional turnover rate was 3 Standard Deviations from the mean = Testosterone - premenopausal women x 1.

Undetectable VLDL-TG concentration = Progesterone - Postmenopausal women x 1.

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

Healthy premenopausal women.

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.

Obese women and men with obstructive sleep apnea

continuous positive airway pressure: Breathe through the mask of a continuous positive airway pressure device every night when sleep, for 6 weeks

Postmenopausal women

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

VLDL-TG Plasma Clearance Rate (Means)

VLDL-TG Plasma Clearance Rate (Medians)

Not included in final analysis:

Withdrawn/withdrew = Testosterone premenopausal women x 1; Progesterone postmenopausal women x 2; Glucocorticoid x 3.

Muscle not obtained = Testosterone - premenopausal women x 1; Progesterone postmenopausal women x 1; CPAP x 3; Glucocorticoid x 6; Control - baseline testing only x 6.

Basal, Postabsorptive Fractional Synthesis Rates of Muscle Protein Synthesis

Women with obesity and polycystic ovary syndrome

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.

Postmenopausal women

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.

Healthy premenopausal women

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.

Postmenopausal women

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.

Lean and obese healthy women, and obese men

glucocorticoid: Dexamethasone 0.013 mg/kg fat-free mass daily, 21 days

Postmenopausal women

Estrogens: Estrogen treatment (100 ug Estradiol daily) administered 14 days followed by 14 days without treatment. Repeat this cycle 3 times.

Baseline testing only in pre- and postmenopausal women

Spots Global Cancer Trial Database for isotope tracer