SCOR: Sex Steroids, Sleep, and Metabolic Dysfunction in Women

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT00805207
• Collaborator: (none)
• Enrollment: 61
• Location: 1
• Arms: 9
• Duration (Months): 66
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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	N/A

Study Design

• Study Type: Interventional
• 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: Sep 1, 2007
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

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 Names: 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 Names: 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 Names: Estradiol Patch, Mylan Pharmaceuticals Inc.
Other: 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 Names: 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 Names: 1% AndroGel

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• 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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT00805207
• Other Study ID Numbers: 07-0692; NIH P50 HD057796
• First Posted: Dec 9, 2008
• Last Update Posted: Aug 1, 2018
• Last Verified: Jul 1, 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: Polycystic Ovary Syndrome; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Estradiol; Estrogens; Testosterone; Progesterone; Glucocorticoids

Study Results

Participant Flow

Arm/Group Title	Progesterone - PCOS	Progesterone - Postmenopausal Women	Testosterone - Premenopausal Women	Testosterone - Postmenopausal Women	Continuous Positive Airway Pressure	Glucocorticoid	Estrogen	Control	Control - Baseline Testing Only
Arm/Group Description	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.	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	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.	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	Baseline testing only in pre- and postmenopausal women
Period Title: Overall Study
STARTED	1	9	12	6	3	12	6	6	6
COMPLETED	1	7	11	6	2	9	6	6	6
NOT COMPLETED	0	2	1	0	1	3	0	0	0

Baseline Characteristics

Arm/Group Title	Testosterone - Premenopausal Women	Testosterone - Postmenopausal Women	Progesterone - PCOS	Progesterone - Postmenopausal Women	Continuous Positive Airway Pressure	Glucocorticoid	Estrogen	Control	Control - Baseline Testing Only	Total
Arm/Group Description	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	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.	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.	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.	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	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.	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	Total of all reporting groups
Overall Participants	12	6	1	9	3	12	6	6	6	61
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35 (8)	57 (6)	22 (0)	63 (7)	62 (12)	38 (13)	59 (10)	64 (6)	41 (15)	49 (16)
Sex: Female, Male (Count of Participants)
Female	12 100%	6 100%	1 100%	9 100%	2 66.7%	9 75%	6 100%	6 100%	5 83.3%	56 91.8%
Male	0 0%	0 0%	0 0%	0 0%	1 33.3%	3 25%	0 0%	0 0%	1 16.7%	5 8.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	1 8.3%	0 0%	0 0%	0 0%	1 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	7 58.3%	2 33.3%	0 0%	2 22.2%	2 66.7%	3 25%	0 0%	0 0%	3 50%	19 31.1%
White	5 41.7%	4 66.7%	1 100%	7 77.8%	1 33.3%	8 66.7%	6 100%	6 100%	3 50%	41 67.2%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	12 100%	6 100%	1 100%	9 100%	3 100%	12 100%	6 100%	6 100%	6 100%	61 100%

Outcome Measures

1. Primary Outcome

Title	Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate
Description	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.
Time Frame	Before and at the end of interventions

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Testosterone - Premenopausal Women	Testosterone - Postmenopausal Women	Progesterone - PCOS	Progesterone - Postmenopausal Women	Continuous Positive Airway Pressure	Glucocorticoid	Estrogen	Control	Control - Baseline Testing Only
Arm/Group Description	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.	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.	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.	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.	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	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.	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
Measure Participants	10	6	1	6	2	9	6	6	6
Before	3.13 (2.11)	2.03 (0.35)	4.66	3.36 (1.65)	2.87 (0.03)	3.80 (1.52)	2.87 (0.86)	2.47 (0.85)	3.53 (2.88)
After	3.00 (1.58)	2.11 (0.80)	7.77	3.24 (1.55)	3.94 (0.42)	3.42 (2.01)	2.94 (1.40)	2.57 (1.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Testosterone - Premenopausal Women
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.85
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Glucocorticoid
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Testosterone - Postmenopausal Women, Progesterone - Postmenopausal Women, Estrogen, Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.88
	Comments	P-value is the main effect of treatment (i.e., Before vs. After) from ANOVA
	Method	ANOVA
	Comments	VLDL-TG secretion rates were skewed and log transformed prior to performing ANOVA

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Testosterone - Postmenopausal Women, Progesterone - Postmenopausal Women, Estrogen, Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments	P-value is the main effect of group (i.e., Testosterone, Progesterone, Estrogen and Control) from ANOVA
	Method	ANOVA
	Comments	VLDL-TG secretion rates were skewed and log transformed prior to performing ANOVA

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Testosterone - Postmenopausal Women, Progesterone - Postmenopausal Women, Estrogen, Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.98
	Comments	P value is the group by treatment interaction from the ANOVA
	Method	ANOVA
	Comments	VLDL-TG secretion rates were skewed and log transformed prior to performing ANOVA

2. Secondary Outcome

Title	Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration
Description	VLDL was isolated from plasma by ultracentrifugation with VLDL-TG concentration measured by using a colorimetric enzymatic kit (Sigma-Aldrich, St. Louis, MO).
Time Frame	Before and at the end of the interventions

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Testosterone - Premenopausal Women	Testosterone - Postmenopausal Women	Progesterone - PCOS	Progesterone - Postmenopausal Women	Continuous Positive Airway Pressure	Glucocorticoid	Estrogen	Control	Control - Baseline Testing Only
Arm/Group Description	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.	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.	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.	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.	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	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.	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
Measure Participants	10	6	1	6	2	9	6	6	6
Before	0.31 (0.29)	0.18 (0.09)	0.75	0.42 (0.18)	0.50 (0.06)	0.35 (0.16)	0.50 (0.28)	0.30 (0.15)	0.32 (0.17)
After	0.40 (0.50)	0.18 (0.10)	1.03	0.44 (0.36)	0.64 (0.18)	0.33 (0.22)	0.35 (0.22)	0.28 (0.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Testosterone - Premenopausal Women
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.31
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Glucocorticoid
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.82
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Estrogen, Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progesterone - Postmenopausal Women, Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.87
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Testosterone - Postmenopausal Women, Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.57
	Comments
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	VLDL-TG Plasma Clearance Rate (Means)
Description	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.
Time Frame	Before and at the end of the interventions

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Testosterone - Premenopausal Women	Testosterone - Postmenopausal Women	Progesterone - PCOS	Progesterone - Postmenopausal Women	Continuous Positive Airway Pressure	Glucocorticoid	Estrogen	Control	Control - Baseline Testing Only
Arm/Group Description	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.	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.	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.	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.	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	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.	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 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
Measure Participants	10	6	1	6	3	9	6	6	6
Before	42.2 (16.3)	35.1 (16.5)	20.3	21.2 (7.5)	19.1 (2.7)	33.8 (11.3)	17.4 (6.7)	22.6 (9.0)	33.1 (13.1)
After	58.1 (51.6)	34.5 (15.8)	24.6	24.9 (15.3)	20.8 (2.8)	34.3 (21.9)	25.1 (6.1)	23.3 (5.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Glucocorticoid
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.94
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Estrogen, Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Progesterone - Postmenopausal Women, Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.53
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Testosterone - Postmenopausal Women, Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments
	Method	ANCOVA
	Comments

4. Secondary Outcome

Title	VLDL-TG Plasma Clearance Rate (Medians)
Description	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.
Time Frame	Before and at the end of the interventions

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Testosterone - Premenopausal Women	Testosterone - Postmenopausal Women	Progesterone - PCOS	Progesterone - Postmenopausal Women	Continuous Positive Airway Pressure	Glucocorticoid	Estrogen	Control	Control - Baseline Testing Only
Arm/Group Description	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.	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.	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.	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.	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	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.	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 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
Measure Participants	10	6	1	6	3	9	6	6	6
Before	40.6	32.1	20.3	20.8	19.1	35.8	14.4	19.6	33.4
After	43.6	32.7	20.3	22.8	20.8	27.4	24.2	22.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Testosterone - Premenopausal Women
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.80
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Basal, Postabsorptive Fractional Synthesis Rates of Muscle Protein Synthesis
Description	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.
Time Frame	Before and at the end of the intervention

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Testosterone - Premenopausal Women	Testosterone - Postmenopausal Women	Progesterone - PCOS	Progesterone - Postmenopausal Women	Continuous Positive Airway Pressure	Glucocorticoid	Estrogen	Control	Control - Baseline Testing Only
Arm/Group Description	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.	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.	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.	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.	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	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.	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
Measure Participants	10	6	1	6	0	3	6	6	0
Before	0.064 (0.023)	0.056 (0.007)	0.049	0.054 (0.12)	0.059 (0.007)	0.063 (0.016)	0.064 (0.012)
After	0.092 (0.024)	0.079 (0.030)	0.083	0.085 (0.018)	0.061 (0.037)	0.063 (0.026)	0.067 (0.011)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Testosterone - Premenopausal Women
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Testosterone - Postmenopausal Women, Progesterone - Postmenopausal Women, Estrogen, Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments	P-value is the main effect of treatment (i.e., Before vs. After) from ANOVA
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Testosterone - Postmenopausal Women, Progesterone - Postmenopausal Women, Estrogen, Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.96
	Comments	P-value is the main effect of group (i.e., Testosterone, Progesterone, Estrogen and Control) from ANOVA
	Method	ANOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Testosterone - Postmenopausal Women, Progesterone - Postmenopausal Women, Estrogen, Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments	P value is the group by treatment interaction from the ANOVA
	Method	ANOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Testosterone - Postmenopausal Women
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	Tukey test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Progesterone - Postmenopausal Women
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	Tukey test
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Estrogen
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.10
	Comments
	Method	Tukey test
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.10
	Comments
	Method	Tukey test
	Comments

Adverse Events

Time Frame	Adverse events were monitored over the following periods; Estrogen = 70 days (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.); Testosterone = 21 days; continuous positive airway pressure = 6 weeks; Dexamethasone = 21 days; Progesterone = 70 days (consisted of 14 days on, 14 days off, 14 days on, 14 days off and a final 14 days on treatment); Control (no treatment) = 31 to 72 days between testing visits.
Arm/Group Title	Testosterone - Premenopausal Women		Testosterone - Postmenopausal Women		Progesterone - PCOS		Progesterone - Postmenopausal Women		Continuous Positive Airway Pressure		Glucocorticoid		Estrogen		Control		Control - Baseline Testing Only
Arm/Group Description	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.		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.		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.		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.		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.		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.		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
All Cause Mortality
	Testosterone - Premenopausal Women		Testosterone - Postmenopausal Women		Progesterone - PCOS		Progesterone - Postmenopausal Women		Continuous Positive Airway Pressure		Glucocorticoid		Estrogen		Control		Control - Baseline Testing Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/6 (0%)		0/1 (0%)		0/9 (0%)		0/3 (0%)		0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Serious Adverse Events
	Testosterone - Premenopausal Women		Testosterone - Postmenopausal Women		Progesterone - PCOS		Progesterone - Postmenopausal Women		Continuous Positive Airway Pressure		Glucocorticoid		Estrogen		Control		Control - Baseline Testing Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/6 (0%)		0/1 (0%)		0/9 (0%)		0/3 (0%)		0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Testosterone - Premenopausal Women		Testosterone - Postmenopausal Women		Progesterone - PCOS		Progesterone - Postmenopausal Women		Continuous Positive Airway Pressure		Glucocorticoid		Estrogen		Control		Control - Baseline Testing Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/6 (0%)		0/3 (0%)		3/9 (33.3%)		0/3 (0%)		0/12 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Gastrointestinal disorders
Vomiting	0/12 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/3 (0%)	0	0/12 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Diarrhea	0/12 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/3 (0%)	0	0/12 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Musculoskeletal and connective tissue disorders
Shaking	0/12 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/3 (0%)	0	0/12 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Broken ankle	0/12 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/3 (0%)	0	0/12 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Reproductive system and breast disorders
Vaginal discharge	0/12 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/3 (0%)	0	0/12 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0
Skin and subcutaneous tissue disorders
Acne	0/12 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/9 (0%)	0	0/3 (0%)	0	0/12 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0
Itchiness	0/12 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1	0/3 (0%)	0	0/12 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.