Metabolic Syndrome, Polycystic Ovary Syndrome
Conditions
Keywords
Polycystic Ovary Syndrome, Metabolic Syndrome, PCOS, overweight, infertility, Insulin Resistance, menstrual cycle
Brief summary
The purpose of this study is to investigate the metabolic effects of anti-androgens and oral contraceptive pills (OCPs), compared with placebo, in the treatment of women with PCOS. We hypothesized that controlling elevated androgen levels with either anti-androgens or OCPs would produce improvement in metabolic markers in PCOS women and would reduce their long term metabolic risk.
Detailed description
Polycystic ovary syndrome (PCOS) is one of the most common conditions of young women, and it is frequently associated with insulin resistance or metabolic syndrome (MBS). In addition, affected women have significantly elevated mean low-density lipoprotein (LDL) levels and an increased prevalence of at risk LDL levels, independent of obesity. We are directly testing the role of androgens in the metabolic abnormalities in PCOS by examining the impact of direct androgen receptor blockade by anti-androgen medications and indirect suppression of androgen production through suppression of leutinizing hormone (LH) with oral contraceptive pills (OCPs), compared with placebo, on visceral adiposity, circulating LDL levels, insulin secretion and sensitivity as measured by frequently-sampled IV glucose tolerance tests (FSIGT) and oral glucose tolerance tests (OGTT), resting energy expenditure, and maximal aerobic capacity measurement. Note: Originally there were 2 additional study arm, Metformin only and Metformin + Flutamide. These study arms were ultimately eliminated and were not included in analysis of baseline characteristics or endpoints.
Interventions
DRUGflutamide
250 mg twice daily
DRUGethinyl estradiol 35 mcg and drospirenone 3 mg
one active pill per day for three weeks and then 1 sugar pill per day for one week
OTHERplacebo
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* 6 periods or fewer per year * Overweight * All ethnicities
Exclusion criteria
* Diabetes * Heart Disease * Chronic illness * Regular Smokers * Current use of Birth Control Pills, Patch, Ring, Depo
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Low-density Lipoprotein (LDL) Levels Over the Study Period | 6 months | Change in low-density lipoprotein (LDL) levels over the study period (LDL level at study endpoint - baseline LDL level) |
| Change in High-density Lipoprotein (HDL) Levels During Study Period | 6 months | Change in high-density lipoprotein (HDL) levels during study period (HDL level at study endpoint - baseline HDL) |
| Change in Visceral Adipose Tissue (VAT) Volume as Measured by MRI | 6 months | Change in visceral adipose tissue (VAT) volume as measured by MRI (VAT at study endpoint - baseline VAT) |
| Change in Fat Percentage as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan Over the Study Period | 6 months | Change in fat percentage as measured by DEXA scan over the study period (Fat percentage at study endpoint - baseline fat percentage) |
| Change in Disposition Index | 6 months | Change in disposition index (DI, insulin secretion corrected for insulin secretion) as measured by frequently-sampled IV glucose tolerance test (DI at study endpoint - baseline DI) |
| Change in Resting Energy Expenditure (REE) Over the Study Period | 6 months | Change in resting energy expenditure (REE) over the study period (REE at study endpoint - baseline REE) |
| Change in Maximal Aerobic Exercise Capacity (VO2 Max) Over the Study Period | 6 months | Change in maximal aerobic exercise capacity (VO2 max) over the study period (VO2 max at study endpoint - baseline VO2 max) |
Countries
United States
Participant flow
Pre-assignment details
97 total subjects enrolled. Prior to randomization, 16 subjects were excluded or dropped out, leaving 81 active subjects. Early in the study, 2 of the 5 study arms were discontinued: participants receiving Metformin only (8 subjects) and those receiving Metformin + Flutamide (6 subjects) - leaving 67 subjects whose data were analyzed
Participants by arm
| Arm | Count |
|---|---|
| Oral Contraceptive - 1 Oral contraceptive (containing 35mcg of ethinyl estradiol and 3mg of drospirenone) | 21 |
| Flutamide - 2 Flutamide
Flutamide: 250 mg twice daily | 24 |
| Placebo - 3 Placebo | 22 |
| Total | 67 |
Baseline characteristics
| Characteristic | Oral Contraceptive - 1 | Flutamide - 2 | Placebo - 3 | Total |
|---|---|---|---|---|
| Age, Continuous | 28 years STANDARD_DEVIATION 4 | 28 years STANDARD_DEVIATION 4 | 28 years STANDARD_DEVIATION 5 | 28 years STANDARD_DEVIATION 4 |
| Body mass index (kg/m^2) | 37.1 kg/m^2 STANDARD_DEVIATION 5.5 | 40.1 kg/m^2 STANDARD_DEVIATION 5.6 | 40.0 kg/m^2 STANDARD_DEVIATION 6.7 | 39.3 kg/m^2 STANDARD_DEVIATION 6 |
| Sex: Female, Male Female | 21 Participants | 24 Participants | 22 Participants | 67 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 21 | 4 / 24 | 0 / 22 |
| serious Total, serious adverse events | 0 / 21 | 0 / 24 | 0 / 22 |
Outcome results
Primary
Change in Disposition Index
Change in disposition index (DI, insulin secretion corrected for insulin secretion) as measured by frequently-sampled IV glucose tolerance test (DI at study endpoint - baseline DI)
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Contraceptive - 1 | Change in Disposition Index | 1653 min^-1 | Standard Deviation 6008 |
| Flutamide - 2 | Change in Disposition Index | 194 min^-1 | Standard Deviation 1424 |
| Placebo - 3 | Change in Disposition Index | -184 min^-1 | Standard Deviation 825 |
Primary
Change in Fat Percentage as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan Over the Study Period
Change in fat percentage as measured by DEXA scan over the study period (Fat percentage at study endpoint - baseline fat percentage)
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Contraceptive - 1 | Change in Fat Percentage as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan Over the Study Period | 0.4 percentage of body mass | Standard Deviation 1.5 |
| Flutamide - 2 | Change in Fat Percentage as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan Over the Study Period | -1.9 percentage of body mass | Standard Deviation 3.9 |
| Placebo - 3 | Change in Fat Percentage as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan Over the Study Period | -1.9 percentage of body mass | Standard Deviation 2.3 |
Primary
Change in High-density Lipoprotein (HDL) Levels During Study Period
Change in high-density lipoprotein (HDL) levels during study period (HDL level at study endpoint - baseline HDL)
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Contraceptive - 1 | Change in High-density Lipoprotein (HDL) Levels During Study Period | 6 mg/dL | Standard Deviation 4 |
| Flutamide - 2 | Change in High-density Lipoprotein (HDL) Levels During Study Period | -5 mg/dL | Standard Deviation 7 |
| Placebo - 3 | Change in High-density Lipoprotein (HDL) Levels During Study Period | -2 mg/dL | Standard Deviation 5 |
Primary
Change in Low-density Lipoprotein (LDL) Levels Over the Study Period
Change in low-density lipoprotein (LDL) levels over the study period (LDL level at study endpoint - baseline LDL level)
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Contraceptive - 1 | Change in Low-density Lipoprotein (LDL) Levels Over the Study Period | -6 mg/dL | Standard Deviation 17 |
| Flutamide - 2 | Change in Low-density Lipoprotein (LDL) Levels Over the Study Period | -9 mg/dL | Standard Deviation 14 |
| Placebo - 3 | Change in Low-density Lipoprotein (LDL) Levels Over the Study Period | -7 mg/dL | Standard Deviation 17 |
Primary
Change in Maximal Aerobic Exercise Capacity (VO2 Max) Over the Study Period
Change in maximal aerobic exercise capacity (VO2 max) over the study period (VO2 max at study endpoint - baseline VO2 max)
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Contraceptive - 1 | Change in Maximal Aerobic Exercise Capacity (VO2 Max) Over the Study Period | -0.5 L/min | Standard Deviation 6.5 |
| Flutamide - 2 | Change in Maximal Aerobic Exercise Capacity (VO2 Max) Over the Study Period | -1.6 L/min | Standard Deviation 4.4 |
| Placebo - 3 | Change in Maximal Aerobic Exercise Capacity (VO2 Max) Over the Study Period | 1.1 L/min | Standard Deviation 4.9 |
Primary
Change in Resting Energy Expenditure (REE) Over the Study Period
Change in resting energy expenditure (REE) over the study period (REE at study endpoint - baseline REE)
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Contraceptive - 1 | Change in Resting Energy Expenditure (REE) Over the Study Period | 7 Kcal/day | Standard Deviation 209 |
| Flutamide - 2 | Change in Resting Energy Expenditure (REE) Over the Study Period | -79 Kcal/day | Standard Deviation 239 |
| Placebo - 3 | Change in Resting Energy Expenditure (REE) Over the Study Period | -88 Kcal/day | Standard Deviation 203 |
Primary
Change in Visceral Adipose Tissue (VAT) Volume as Measured by MRI
Change in visceral adipose tissue (VAT) volume as measured by MRI (VAT at study endpoint - baseline VAT)
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Contraceptive - 1 | Change in Visceral Adipose Tissue (VAT) Volume as Measured by MRI | -0.1 L | Standard Deviation 0.3 |
| Flutamide - 2 | Change in Visceral Adipose Tissue (VAT) Volume as Measured by MRI | -0.1 L | Standard Deviation 0.6 |
| Placebo - 3 | Change in Visceral Adipose Tissue (VAT) Volume as Measured by MRI | 0.1 L | Standard Deviation 0.6 |