Trial Outcomes & Findings for Sex Steroids, Sleep, and Metabolic Dysfunction in Women (NCT NCT00805207)

Last Updated: 2018-08-01

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

61 participants

Primary outcome timeframe

Before and at the end of interventions

Results posted on

2018-08-01

Participant Flow

Participant milestones

Participant milestones
Measure	Progesterone - PCOS 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.	Progesterone - Postmenopausal Women 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.	Testosterone - Premenopausal Women 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.	Testosterone - Postmenopausal Women 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.	Continuous Positive Airway Pressure 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	Glucocorticoid Lean and obese healthy women, and obese men glucocorticoid: Dexamethasone 0.013 mg/kg fat-free mass daily, 21 days	Estrogen Postmenopausal women Estrogens: Estrogen treatment (100 ug Estradiol daily) administered 14 days followed by 14 days without treatment. Repeat this cycle 3 times.	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	Control - Baseline Testing Only Baseline testing only in pre- and postmenopausal women
Overall Study STARTED	1	9	12	6	3	12	6	6	6
Overall Study COMPLETED	1	7	11	6	2	9	6	6	6
Overall Study NOT COMPLETED	0	2	1	0	1	3	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Progesterone - Postmenopausal Women 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.	Testosterone - Premenopausal Women 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.	Continuous Positive Airway Pressure 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	Glucocorticoid Lean and obese healthy women, and obese men glucocorticoid: Dexamethasone 0.013 mg/kg fat-free mass daily, 21 days
Overall Study Protocol Violation	0	1	0	0
Overall Study Physician Decision	1	0	0	1
Overall Study Withdrawal by Subject	1	0	1	2

Baseline Characteristics

Sex Steroids, Sleep, and Metabolic Dysfunction in Women

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Testosterone - Premenopausal Women n=12 Participants 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 - Postmenopausal Women n=6 Participants 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.	Progesterone - PCOS n=1 Participants 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 - Postmenopausal Women n=9 Participants 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.	Continuous Positive Airway Pressure n=3 Participants 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	Glucocorticoid n=12 Participants 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.	Estrogen n=6 Participants 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.	Control n=6 Participants 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	Control - Baseline Testing Only n=6 Participants Healthy men and women Baseline testing only	Total n=61 Participants Total of all reporting groups
Age, Continuous	35 years STANDARD_DEVIATION 8 • n=93 Participants	57 years STANDARD_DEVIATION 6 • n=4 Participants	22 years STANDARD_DEVIATION 0 • n=27 Participants	63 years STANDARD_DEVIATION 7 • n=483 Participants	62 years STANDARD_DEVIATION 12 • n=36 Participants	38 years STANDARD_DEVIATION 13 • n=10 Participants	59 years STANDARD_DEVIATION 10 • n=115 Participants	64 years STANDARD_DEVIATION 6 • n=40 Participants	41 years STANDARD_DEVIATION 15 • n=8 Participants	49 years STANDARD_DEVIATION 16 • n=62 Participants
Sex: Female, Male Female	12 Participants n=93 Participants	6 Participants n=4 Participants	1 Participants n=27 Participants	9 Participants n=483 Participants	2 Participants n=36 Participants	9 Participants n=10 Participants	6 Participants n=115 Participants	6 Participants n=40 Participants	5 Participants n=8 Participants	56 Participants n=62 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants	3 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	1 Participants n=8 Participants	5 Participants n=62 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	0 Participants n=62 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	1 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	1 Participants n=62 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	0 Participants n=62 Participants
Race (NIH/OMB) Black or African American	7 Participants n=93 Participants	2 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants	2 Participants n=36 Participants	3 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	3 Participants n=8 Participants	19 Participants n=62 Participants
Race (NIH/OMB) White	5 Participants n=93 Participants	4 Participants n=4 Participants	1 Participants n=27 Participants	7 Participants n=483 Participants	1 Participants n=36 Participants	8 Participants n=10 Participants	6 Participants n=115 Participants	6 Participants n=40 Participants	3 Participants n=8 Participants	41 Participants n=62 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	0 Participants n=62 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	0 Participants n=62 Participants
Region of Enrollment United States	12 participants n=93 Participants	6 participants n=4 Participants	1 participants n=27 Participants	9 participants n=483 Participants	3 participants n=36 Participants	12 participants n=10 Participants	6 participants n=115 Participants	6 participants n=40 Participants	6 participants n=8 Participants	61 participants n=62 Participants

PRIMARY outcome

Timeframe: Before and at the end of interventions

Population: 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.

Outcome measures

Outcome measures
Measure	Testosterone - Premenopausal Women n=10 Participants 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 - Postmenopausal Women n=6 Participants 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.	Progesterone - PCOS n=1 Participants 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 - Postmenopausal Women n=6 Participants 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.	Continuous Positive Airway Pressure n=2 Participants 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	Glucocorticoid n=9 Participants 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.	Estrogen n=6 Participants 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.	Control n=6 Participants 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	Control - Baseline Testing Only n=6 Participants Healthy men and women Baseline testing only
Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate Before	3.13 umol/min/L plasma Standard Deviation 2.11	2.03 umol/min/L plasma Standard Deviation 0.35	4.66 umol/min/L plasma	3.36 umol/min/L plasma Standard Deviation 1.65	2.87 umol/min/L plasma Standard Deviation 0.03	3.80 umol/min/L plasma Standard Deviation 1.52	2.87 umol/min/L plasma Standard Deviation 0.86	2.47 umol/min/L plasma Standard Deviation 0.85	3.53 umol/min/L plasma Standard Deviation 2.88
Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate After	3.00 umol/min/L plasma Standard Deviation 1.58	2.11 umol/min/L plasma Standard Deviation 0.80	7.77 umol/min/L plasma	3.24 umol/min/L plasma Standard Deviation 1.55	3.94 umol/min/L plasma Standard Deviation 0.42	3.42 umol/min/L plasma Standard Deviation 2.01	2.94 umol/min/L plasma Standard Deviation 1.40	2.57 umol/min/L plasma Standard Deviation 1.26	—

SECONDARY outcome

Timeframe: Before and at the end of the interventions

Population: 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.

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

Outcome measures

Outcome measures
Measure	Testosterone - Premenopausal Women n=10 Participants 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 - Postmenopausal Women n=6 Participants 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.	Progesterone - PCOS n=1 Participants 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 - Postmenopausal Women n=6 Participants 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.	Continuous Positive Airway Pressure n=2 Participants 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	Glucocorticoid n=9 Participants 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.	Estrogen n=6 Participants 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.	Control n=6 Participants 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	Control - Baseline Testing Only n=6 Participants Healthy men and women Baseline testing only
Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration After	0.40 mmol/L Standard Deviation 0.50	0.18 mmol/L Standard Deviation 0.10	1.03 mmol/L	0.44 mmol/L Standard Deviation 0.36	0.64 mmol/L Standard Deviation 0.18	0.33 mmol/L Standard Deviation 0.22	0.35 mmol/L Standard Deviation 0.22	0.28 mmol/L Standard Deviation 0.16	—
Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration Before	0.31 mmol/L Standard Deviation 0.29	0.18 mmol/L Standard Deviation 0.09	0.75 mmol/L	0.42 mmol/L Standard Deviation 0.18	0.50 mmol/L Standard Deviation 0.06	0.35 mmol/L Standard Deviation 0.16	0.50 mmol/L Standard Deviation 0.28	0.30 mmol/L Standard Deviation 0.15	0.32 mmol/L Standard Deviation 0.17

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Testosterone - Premenopausal Women n=10 Participants 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 - Postmenopausal Women n=6 Participants 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.	Progesterone - PCOS n=1 Participants 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 - Postmenopausal Women n=6 Participants 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.	Continuous Positive Airway Pressure n=3 Participants 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	Glucocorticoid n=9 Participants 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.	Estrogen n=6 Participants 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.	Control n=6 Participants 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	Control - Baseline Testing Only n=6 Participants Healthy men and women Baseline testing only
VLDL-TG Plasma Clearance Rate (Means) Before	42.2 mL/min Standard Deviation 16.3	35.1 mL/min Standard Deviation 16.5	20.3 mL/min	21.2 mL/min Standard Deviation 7.5	19.1 mL/min Standard Deviation 2.7	33.8 mL/min Standard Deviation 11.3	17.4 mL/min Standard Deviation 6.7	22.6 mL/min Standard Deviation 9.0	33.1 mL/min Standard Deviation 13.1
VLDL-TG Plasma Clearance Rate (Means) After	58.1 mL/min Standard Deviation 51.6	34.5 mL/min Standard Deviation 15.8	24.6 mL/min	24.9 mL/min Standard Deviation 15.3	20.8 mL/min Standard Deviation 2.8	34.3 mL/min Standard Deviation 21.9	25.1 mL/min Standard Deviation 6.1	23.3 mL/min Standard Deviation 5.0	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Testosterone - Premenopausal Women n=10 Participants 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 - Postmenopausal Women n=6 Participants 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.	Progesterone - PCOS n=1 Participants 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 - Postmenopausal Women n=6 Participants 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.	Continuous Positive Airway Pressure n=3 Participants 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	Glucocorticoid n=9 Participants 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.	Estrogen n=6 Participants 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.	Control n=6 Participants 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	Control - Baseline Testing Only n=6 Participants Healthy men and women Baseline testing only
VLDL-TG Plasma Clearance Rate (Medians) After	43.6 mL/min Interval 19.4 to 63.5	32.7 mL/min Interval 24.4 to 48.1	20.3 mL/min	22.8 mL/min Interval 15.7 to 34.3	20.8 mL/min Interval 19.9 to 21.8	27.4 mL/min Interval 21.5 to 38.7	24.2 mL/min Interval 22.0 to 29.1	22.3 mL/min Interval 19.0 to 26.9	—
VLDL-TG Plasma Clearance Rate (Medians) Before	40.6 mL/min Interval 33.8 to 52.9	32.1 mL/min Interval 23.1 to 47.8	20.3 mL/min	20.8 mL/min Interval 15.4 to 25.4	19.1 mL/min Interval 18.1 to 20.1	35.8 mL/min Interval 29.6 to 40.5	14.4 mL/min Interval 12.7 to 20.5	19.6 mL/min Interval 16.6 to 26.8	33.4 mL/min Interval 22.8 to 43.7

SECONDARY outcome

Timeframe: Before and at the end of the intervention

Population: 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.

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.