Insulin Resistance, Polycystic Ovary Syndrome, and Bone Research Study

Phase 4

Completed

Conditions: Polycystic Ovary Syndrome

Interventions: Drug: drospirenone/ethinyl estradiol
Drug: rosiglitazone

Registration Number: NCT00640224

Lead Sponsor: Silva Arslanian

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 65

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Drospirenone/ethinyl estradiol	drospirenone/ethinyl estradiol	Treatment naive overweight adolescent females with PCOS treated with Drospirenone/ethinyl estradiol
Rosiglitazone	rosiglitazone	Treatment naive overweight adolescent females with PCOS treated with Rosiglitazone

Primary Outcome Measures

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

Secondary Outcome Measures

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