Obesity, Obstructive Sleep Apnea, Polycystic Ovary Syndrome (PCOS)
Conditions
Keywords
sleep apnea, obese, Very-low density lipoprotein (VLDL) metabolism, isotope tracer, women
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.
Interventions
DRUGProgesterone
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.
DRUGtestosterone
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.
DRUGglucocorticoid
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.
DEVICEcontinuous 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.
DRUGEstrogen
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.
OTHERControl
No treatment with studies performed 31 to 72 days apart
Sponsors
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Testosterone - Premenopausal Women 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 | 12 |
| Testosterone - Postmenopausal 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. | 6 |
| Progesterone - PCOS 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. | 1 |
| Progesterone - Postmenopausal Women 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. | 9 |
| Continuous Positive Airway Pressure 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 | 3 |
| Glucocorticoid 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. | 12 |
| Estrogen 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. | 6 |
| 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 | 6 |
| Control - Baseline Testing Only Healthy men and women
Baseline testing only | 6 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 1 | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Testosterone - Premenopausal Women | Total | Control - Baseline Testing Only | Control | Estrogen | Glucocorticoid | Continuous Positive Airway Pressure | Progesterone - Postmenopausal Women | Progesterone - PCOS | Testosterone - Postmenopausal Women |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 35 years STANDARD_DEVIATION 8 | 49 years STANDARD_DEVIATION 16 | 41 years STANDARD_DEVIATION 15 | 64 years STANDARD_DEVIATION 6 | 59 years STANDARD_DEVIATION 10 | 38 years STANDARD_DEVIATION 13 | 62 years STANDARD_DEVIATION 12 | 63 years STANDARD_DEVIATION 7 | 22 years STANDARD_DEVIATION 0 | 57 years STANDARD_DEVIATION 6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 19 Participants | 3 Participants | 0 Participants | 0 Participants | 3 Participants | 2 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 41 Participants | 3 Participants | 6 Participants | 6 Participants | 8 Participants | 1 Participants | 7 Participants | 1 Participants | 4 Participants |
| Region of Enrollment United States | 12 participants | 61 participants | 6 participants | 6 participants | 6 participants | 12 participants | 3 participants | 9 participants | 1 participants | 6 participants |
| Sex: Female, Male Female | 12 Participants | 56 Participants | 5 Participants | 6 Participants | 6 Participants | 9 Participants | 2 Participants | 9 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 0 Participants | 5 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 6 | 0 / 1 | 0 / 9 | 0 / 3 | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 12 | 0 / 6 | 0 / 3 | 3 / 9 | 0 / 3 | 0 / 12 | 1 / 6 | 0 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 12 | 0 / 6 | 0 / 1 | 0 / 9 | 0 / 3 | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone - Premenopausal Women | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate | Before | 3.13 umol/min/L plasma | Standard Deviation 2.11 |
| Testosterone - Premenopausal Women | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate | After | 3.00 umol/min/L plasma | Standard Deviation 1.58 |
| Testosterone - Postmenopausal Women | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate | Before | 2.03 umol/min/L plasma | Standard Deviation 0.35 |
| Testosterone - Postmenopausal Women | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate | After | 2.11 umol/min/L plasma | Standard Deviation 0.8 |
| Progesterone - PCOS | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate | After | 7.77 umol/min/L plasma | — |
| Progesterone - PCOS | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate | Before | 4.66 umol/min/L plasma | — |
| Progesterone - Postmenopausal Women | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate | After | 3.24 umol/min/L plasma | Standard Deviation 1.55 |
| Progesterone - Postmenopausal Women | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate | Before | 3.36 umol/min/L plasma | Standard Deviation 1.65 |
| Continuous Positive Airway Pressure | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate | After | 3.94 umol/min/L plasma | Standard Deviation 0.42 |
| Continuous Positive Airway Pressure | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate | Before | 2.87 umol/min/L plasma | Standard Deviation 0.03 |
| Glucocorticoid | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate | Before | 3.80 umol/min/L plasma | Standard Deviation 1.52 |
| Glucocorticoid | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate | After | 3.42 umol/min/L plasma | Standard Deviation 2.01 |
| Estrogen | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate | Before | 2.87 umol/min/L plasma | Standard Deviation 0.86 |
| Estrogen | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate | After | 2.94 umol/min/L plasma | Standard Deviation 1.4 |
| Control | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate | After | 2.57 umol/min/L plasma | Standard Deviation 1.26 |
| Control | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate | Before | 2.47 umol/min/L plasma | Standard Deviation 0.85 |
| Control - Baseline Testing Only | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Secretion Rate | Before | 3.53 umol/min/L plasma | Standard Deviation 2.88 |
p-value: 0.85t-test, 2 sided
p-value: 0.7t-test, 2 sided
p-value: 0.88ANOVA
p-value: 0.26ANOVA
p-value: 0.98ANOVA
Secondary
Basal, Postabsorptive Fractional Synthesis Rates of Muscle Protein Synthesis
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone - Premenopausal Women | Basal, Postabsorptive Fractional Synthesis Rates of Muscle Protein Synthesis | Before | 0.064 %/h | Standard Deviation 0.023 |
| Testosterone - Premenopausal Women | Basal, Postabsorptive Fractional Synthesis Rates of Muscle Protein Synthesis | After | 0.092 %/h | Standard Deviation 0.024 |
| Testosterone - Postmenopausal Women | Basal, Postabsorptive Fractional Synthesis Rates of Muscle Protein Synthesis | Before | 0.056 %/h | Standard Deviation 0.007 |
| Testosterone - Postmenopausal Women | Basal, Postabsorptive Fractional Synthesis Rates of Muscle Protein Synthesis | After | 0.079 %/h | Standard Deviation 0.03 |
| Progesterone - PCOS | Basal, Postabsorptive Fractional Synthesis Rates of Muscle Protein Synthesis | Before | 0.049 %/h | — |
| Progesterone - PCOS | Basal, Postabsorptive Fractional Synthesis Rates of Muscle Protein Synthesis | After | 0.083 %/h | — |
| Progesterone - Postmenopausal Women | Basal, Postabsorptive Fractional Synthesis Rates of Muscle Protein Synthesis | Before | 0.054 %/h | Standard Deviation 0.12 |
| Progesterone - Postmenopausal Women | Basal, Postabsorptive Fractional Synthesis Rates of Muscle Protein Synthesis | After | 0.085 %/h | Standard Deviation 0.018 |
| Glucocorticoid | Basal, Postabsorptive Fractional Synthesis Rates of Muscle Protein Synthesis | Before | 0.059 %/h | Standard Deviation 0.007 |
| Glucocorticoid | Basal, Postabsorptive Fractional Synthesis Rates of Muscle Protein Synthesis | After | 0.061 %/h | Standard Deviation 0.037 |
| Estrogen | Basal, Postabsorptive Fractional Synthesis Rates of Muscle Protein Synthesis | Before | 0.063 %/h | Standard Deviation 0.016 |
| Estrogen | Basal, Postabsorptive Fractional Synthesis Rates of Muscle Protein Synthesis | After | 0.063 %/h | Standard Deviation 0.026 |
| Control | Basal, Postabsorptive Fractional Synthesis Rates of Muscle Protein Synthesis | Before | 0.064 %/h | Standard Deviation 0.012 |
| Control | Basal, Postabsorptive Fractional Synthesis Rates of Muscle Protein Synthesis | After | 0.067 %/h | Standard Deviation 0.011 |
p-value: <0.001t-test, 2 sided
p-value: <0.01ANOVA
p-value: 0.96ANOVA
p-value: <0.05ANOVA
p-value: <0.01Tukey test
p-value: <0.01Tukey test
p-value: >0.1Tukey test
p-value: >0.1Tukey test
Secondary
Very-Low Density Lipoprotein-Triglyceride (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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone - Premenopausal Women | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration | After | 0.40 mmol/L | Standard Deviation 0.5 |
| Testosterone - Premenopausal Women | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration | Before | 0.31 mmol/L | Standard Deviation 0.29 |
| Testosterone - Postmenopausal Women | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration | After | 0.18 mmol/L | Standard Deviation 0.1 |
| Testosterone - Postmenopausal Women | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration | Before | 0.18 mmol/L | Standard Deviation 0.09 |
| Progesterone - PCOS | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration | Before | 0.75 mmol/L | — |
| Progesterone - PCOS | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration | After | 1.03 mmol/L | — |
| Progesterone - Postmenopausal Women | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration | After | 0.44 mmol/L | Standard Deviation 0.36 |
| Progesterone - Postmenopausal Women | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration | Before | 0.42 mmol/L | Standard Deviation 0.18 |
| Continuous Positive Airway Pressure | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration | After | 0.64 mmol/L | Standard Deviation 0.18 |
| Continuous Positive Airway Pressure | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration | Before | 0.50 mmol/L | Standard Deviation 0.06 |
| Glucocorticoid | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration | Before | 0.35 mmol/L | Standard Deviation 0.16 |
| Glucocorticoid | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration | After | 0.33 mmol/L | Standard Deviation 0.22 |
| Estrogen | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration | Before | 0.50 mmol/L | Standard Deviation 0.28 |
| Estrogen | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration | After | 0.35 mmol/L | Standard Deviation 0.22 |
| Control | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration | After | 0.28 mmol/L | Standard Deviation 0.16 |
| Control | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration | Before | 0.30 mmol/L | Standard Deviation 0.15 |
| Control - Baseline Testing Only | Very-Low Density Lipoprotein-Triglyceride (VLDL-TG) Concentration | Before | 0.32 mmol/L | Standard Deviation 0.17 |
p-value: 0.31t-test, 2 sided
p-value: 0.82t-test, 2 sided
p-value: <0.05ANCOVA
p-value: 0.87ANCOVA
p-value: 0.57ANCOVA
Secondary
VLDL-TG Plasma Clearance Rate (Means)
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone - Premenopausal Women | VLDL-TG Plasma Clearance Rate (Means) | Before | 42.2 mL/min | Standard Deviation 16.3 |
| Testosterone - Premenopausal Women | VLDL-TG Plasma Clearance Rate (Means) | After | 58.1 mL/min | Standard Deviation 51.6 |
| Testosterone - Postmenopausal Women | VLDL-TG Plasma Clearance Rate (Means) | Before | 35.1 mL/min | Standard Deviation 16.5 |
| Testosterone - Postmenopausal Women | VLDL-TG Plasma Clearance Rate (Means) | After | 34.5 mL/min | Standard Deviation 15.8 |
| Progesterone - PCOS | VLDL-TG Plasma Clearance Rate (Means) | After | 24.6 mL/min | — |
| Progesterone - PCOS | VLDL-TG Plasma Clearance Rate (Means) | Before | 20.3 mL/min | — |
| Progesterone - Postmenopausal Women | VLDL-TG Plasma Clearance Rate (Means) | After | 24.9 mL/min | Standard Deviation 15.3 |
| Progesterone - Postmenopausal Women | VLDL-TG Plasma Clearance Rate (Means) | Before | 21.2 mL/min | Standard Deviation 7.5 |
| Continuous Positive Airway Pressure | VLDL-TG Plasma Clearance Rate (Means) | After | 20.8 mL/min | Standard Deviation 2.8 |
| Continuous Positive Airway Pressure | VLDL-TG Plasma Clearance Rate (Means) | Before | 19.1 mL/min | Standard Deviation 2.7 |
| Glucocorticoid | VLDL-TG Plasma Clearance Rate (Means) | Before | 33.8 mL/min | Standard Deviation 11.3 |
| Glucocorticoid | VLDL-TG Plasma Clearance Rate (Means) | After | 34.3 mL/min | Standard Deviation 21.9 |
| Estrogen | VLDL-TG Plasma Clearance Rate (Means) | Before | 17.4 mL/min | Standard Deviation 6.7 |
| Estrogen | VLDL-TG Plasma Clearance Rate (Means) | After | 25.1 mL/min | Standard Deviation 6.1 |
| Control | VLDL-TG Plasma Clearance Rate (Means) | After | 23.3 mL/min | Standard Deviation 5 |
| Control | VLDL-TG Plasma Clearance Rate (Means) | Before | 22.6 mL/min | Standard Deviation 9 |
| Control - Baseline Testing Only | VLDL-TG Plasma Clearance Rate (Means) | Before | 33.1 mL/min | Standard Deviation 13.1 |
p-value: 0.94t-test, 2 sided
p-value: <0.05ANCOVA
p-value: 0.53ANCOVA
p-value: 0.23ANCOVA
Secondary
VLDL-TG Plasma Clearance Rate (Medians)
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
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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Testosterone - Premenopausal Women | VLDL-TG Plasma Clearance Rate (Medians) | After | 43.6 mL/min |
| Testosterone - Premenopausal Women | VLDL-TG Plasma Clearance Rate (Medians) | Before | 40.6 mL/min |
| Testosterone - Postmenopausal Women | VLDL-TG Plasma Clearance Rate (Medians) | After | 32.7 mL/min |
| Testosterone - Postmenopausal Women | VLDL-TG Plasma Clearance Rate (Medians) | Before | 32.1 mL/min |
| Progesterone - PCOS | VLDL-TG Plasma Clearance Rate (Medians) | Before | 20.3 mL/min |
| Progesterone - PCOS | VLDL-TG Plasma Clearance Rate (Medians) | After | 20.3 mL/min |
| Progesterone - Postmenopausal Women | VLDL-TG Plasma Clearance Rate (Medians) | Before | 20.8 mL/min |
| Progesterone - Postmenopausal Women | VLDL-TG Plasma Clearance Rate (Medians) | After | 22.8 mL/min |
| Continuous Positive Airway Pressure | VLDL-TG Plasma Clearance Rate (Medians) | Before | 19.1 mL/min |
| Continuous Positive Airway Pressure | VLDL-TG Plasma Clearance Rate (Medians) | After | 20.8 mL/min |
| Glucocorticoid | VLDL-TG Plasma Clearance Rate (Medians) | After | 27.4 mL/min |
| Glucocorticoid | VLDL-TG Plasma Clearance Rate (Medians) | Before | 35.8 mL/min |
| Estrogen | VLDL-TG Plasma Clearance Rate (Medians) | After | 24.2 mL/min |
| Estrogen | VLDL-TG Plasma Clearance Rate (Medians) | Before | 14.4 mL/min |
| Control | VLDL-TG Plasma Clearance Rate (Medians) | Before | 19.6 mL/min |
| Control | VLDL-TG Plasma Clearance Rate (Medians) | After | 22.3 mL/min |
| Control - Baseline Testing Only | VLDL-TG Plasma Clearance Rate (Medians) | Before | 33.4 mL/min |
p-value: 0.8Wilcoxon (Mann-Whitney)