Insulin Resistance, Polycystic Ovary Syndrome, and Bone Research Study

Study Overview
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Brief Summary
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The purpose is to investigate the effects of 2 different treatments (drospirenone/ethinyl estradiol versus rosiglitazone) on insulin sensitivity and androgen levels, inflammatory markers, vascular markers and bone development in overweight adolescent females with polycystic ovary syndrome (PCOS).

Detailed Description
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The purpose of this study is to: 1) to compare effects of treatment with drospirenone/ethinyl estradiol (Yasmin)versus rosiglitazone (Avandia) on hyperandrogenism, insulin resistance/hyperinsulinemia, adrenal hyperresponsiveness, body composition, chronic inflammation, bone mass and turnover. OCPs are the first-line therapy for PCOS, however, they do not address the insulin resistance or the inflammation. Insulin sensitizers have been used successfully to treat PCOS but thiazolidinediones such as rosiglitazone have not been used in adolescents. Therefore we will investigate the effects of treatment with drospirenone/ethinyl estradiol versus rosiglitazone in overweight adolescents with PCOS. We will obtain comprehensive evaluations before and 6 months after randomization, to the respective treatment arms to determine the differences between the 2 treatment modalities.

Official Title
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Obesity, Insulin Resistance, and Bone Metabolism in Adolescents With PCOS: Effects of Insulin Sensitizers Versus Oral Contraceptives

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: rosiglitazone
* Drug: drospirenone/ethinyl estradiol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 10 - 20 years Pubertal level of Tanner stage III-V and menarchal BMI percentile for age and sex greater than or equal to 85%ile Exclusion Criteria: Oral medications for PCOS, or that have impact on bone (i.e. anti-epileptics) Presence of other diseases, systemic or psychiatric, or chronic medications which could interfere with endocrine function Established diagnosis of diabetes Prior bone surgery, prior osteoporotic fracture, or fracture in the past 12 months Prior thromboembolic event, such as a deep venous thrombosis or pulmonary embolism (PCOS subjects only) Vitamin D deficiency (<10ng/mL) Hyperkalemia (K>5.0 meq/L) Positive pregnancy test (serum)

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 20 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rosiglitazone<br>Treatment naive overweight adolescent females with PCOS treated with Rosiglitazone | Drug: rosiglitazone<br>* 4 mg daily for 6 months<br>* Other names: Avandia;|
| Active Comparator: Drospirenone/ethinyl estradiol<br>Treatment naive overweight adolescent females with PCOS treated with Drospirenone/ethinyl estradiol | Drug: drospirenone/ethinyl estradiol<br>* 1 tab (3mg/30mcg) daily for 6 months<br>* Other names: Yasmin;|
| No Intervention: Overweight/Obese without PCOS<br>Overweight adolescent females without PCOS to use as comparison of normal developmental changes. *No participants were enrolled in this Arm. | |
| No Intervention: Lean without PCOS<br>Lean healthy girls without PCOS to serve as controls for the cardiovascular markers. *No participants were enrolled in this Arm. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peripheral Insulin Sensitivity at Baseline and 6 Months. | Peripheral insulin sensitivity was evaluated during the hyperinsulinemic-euglycemic clamp. | Baseline and 6 months | 
| Hepatic Insulin Sensitivity at Baseline and 6 Months. | Hepatic insulin sensitivity was evaluated prior to the hyperinsulinemic-euglycemic clamp. | Baseline and 6 months | 
| Glucose Tolerance Status at Baseline and 6 Months. | Glucose tolerance status was classified according to the ADA (American Diabetes Association) criteria. | Baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Fat Mass at Baseline and 6 Months | DXA (dual-energy x-ray absorptiometry) scans were done to measure total fat mass. | Baseline and 6 months | 
| Total Testosterone at Baseline and 6 Months | Total testosterone was measured by HPLC(high-performance liquid chromatography)-tandem mass spectroscopy. | Baseline and 6 months | 
| Percent Body Fat at Baseline and 6 Months | DXA scans were done to measure the percentage of body fat. | Baseline and 6 months | 
| Free Testosterone at Baseline and 6 Months | Free testosterone was measured by equilibrium dialysis. | Baseline and 6 months | 
| SHBG at Baseline and 6 Months | SHBG (sex hormone-binding globulin) was measured by immunoradiometric assay. | Baseline and 6 months | 
| DHEAS at Baseline and 6 Months | DHEAS (dehydroepiandrosterone sulfate) was measured by radioimmunoassay in dilute serum after hydrolysis. | Baseline and 6 months | 
| Delta Androstenedione at Baseline and 6 Months | Delta Androstenedione was measured by HPLC-tandem mass spectroscopy. | Baseline and 6 months | 
| Delta DHEA at Baseline and 6 Months | Delta DHEA was measured by HPLC-tandem mass spectroscopy. | Baseline and 6 months | 
| Delta 17-OHProg at Baseline and 6 Months | Delta 17-OHProg (17-hydroxyprogesterone) was measured by HPLC-tandem mass spectroscopy. | Baseline and 6 months | 
| Delta 17-OHPreg at Baseline and 6 Months | Delta 17-OHPreg (17-hydroxypregnenolone) was measured by HPLC-tandem mass spectroscopy. | Baseline and 6 months | 
| Cholesterol at Baseline and 6 Months | Cholesterol was measured using the standards of the Centers for Disease Control and Prevention. | Baseline and 6 months | 
| HDL at Baseline and 6 Months | HDL (high-density lipoprotein) was measured using the standards of the Centers for Disease Control and Prevention. | Baseline and 6 months | 
| LDL at Baseline and 6 Months | LDL (low-density lipoprotein) was measured using the standards of the Centers for Disease Control and Prevention. | Baseline and 6 months | 
| Triglycerides at Baseline and 6 Months | Triglycerides were measured using the standards of the Centers for Disease Control and Prevention. | Baseline and 6 months | 
| Non-HDL Cholesterol at Baseline and 6 Months | Non-HDL cholesterol was measured using the standards of the Centers for Disease Control and Prevention. | Baseline and 6 months | 
| Adiponectin at Baseline and 6 Months | Adiponectin was measured by radioimmunoassay. | Baseline and 6 months | 
| Leptin at Baseline and 6 Months | Leptin was measured by radioimmunoassay. | Baseline and 6 months | 
| Hs-CRP at Baseline and 6 Months | hs-CRP(high-sensitivity C-reactive protein) was measured by COAG-Nephelometry. | Baseline and 6 months | 
| Morning Blood Pressure at Baseline and 6 Months | Morning blood pressure was measured with an automated sphygmomanometer. | Baseline and 6 months | 
| Night Blood Pressure at Baseline and 6 Months | Night blood pressure was measured with an automated sphygmomanometer. | Baseline and 6 months |