Insulin Resistance, Polycystic Ovary Syndrome, and Bone Research Study

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

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).

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.

Overweight adolescent females without PCOS to use as comparison of normal developmental changes. *No participants were enrolled in this Arm.

Lean healthy girls without PCOS to serve as controls for the cardiovascular markers. *No participants were enrolled in this Arm.

Glucose tolerance status was classified according to the ADA (American Diabetes Association) criteria.

Total testosterone was measured by HPLC(high-performance liquid chromatography)-tandem mass spectroscopy.

DHEAS (dehydroepiandrosterone sulfate) was measured by radioimmunoassay in dilute serum after hydrolysis.

HDL (high-density lipoprotein) was measured using the standards of the Centers for Disease Control and Prevention.

LDL (low-density lipoprotein) was measured using the standards of the Centers for Disease Control and Prevention.

Non-HDL cholesterol was measured using the standards of the Centers for Disease Control and Prevention.

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)

Tfayli H, Ulnach JW, Lee S, Sutton-Tyrrell K, Arslanian S. Drospirenone/ethinyl estradiol versus rosiglitazone treatment in overweight adolescents with polycystic ovary syndrome: comparison of metabolic, hormonal, and cardiovascular risk factors. J Clin Endocrinol Metab. 2011 May;96(5):1311-9. doi: 10.1210/jc.2010-2547. Epub 2011 Feb 16.