Metabolic Syndrome in PCOS: Precursors and Interventions

Study Overview
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Brief Summary
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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
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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.

Official Title
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Metabolic Syndrome in PCOS: Precursors and Interventions

Conditions
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Polycystic Ovary Syndrome, Metabolic Syndrome

Intervention / Treatment
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* Drug: flutamide
* Drug: ethinyl estradiol 35 mcg and drospirenone 3 mg
* Other: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>oral contraceptive (35 mg ethinyl estradiol) | Drug: ethinyl estradiol 35 mcg and drospirenone 3 mg<br>* one active pill per day for three weeks and then 1 sugar pill per day for one week<br>* Other names: Yasmin;|
| Experimental: 2<br>Flutamide 250 mg twice daily | Drug: flutamide<br>* 250 mg twice daily<br>* Other names: Eulexin;|
| Placebo Comparator: 3<br>Placebo | Other: placebo<br> <br> * Other names: sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 6 months | 
| 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) | 6 months | 
| 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) | 6 months | 
| 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) | 6 months | 
| 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) | 6 months | 
| 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) | 6 months | 
| 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) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polycystic Ovary Syndrome, Metabolic Syndrome, PCOS, overweight, infertility, Insulin Resistance, menstrual cycle