Impact of insulin and body mass index on metabolic and endocrine variables in polycystic ovary syndrome.

To assess the differential impact of the insulin secretory pattern and obesity on the endocrinometabolic features of the polycystic ovary syndrome (PCOS), we studied 110 PCOS women. Patients underwent a gonadotropin-releasing hormone (GnRH) test, an oral glucose tolerance test (OGTT), and basal evaluation of hormonal and biochemical parameters. Basal androgens and lipids, basal and stimulated gonadotropins, insulin, and glucose levels were measured. Patients were classified into four groups according to the body mass index (BMI) and insulin secretion: normoinsulinemic-lean ([NL] n = 24), normoinsulinemic obese ([NO] n = 24), hyperinsulinemic lean ([HL] n = 17), hyperinsulinemic obese ([HO] n = 45). HL patients showed a higher luteinizing hormone (LH) area under curve (AUC) after GnRH stimulus compared with NL patients (HL v NL, 4,285 +/- 348 v 3,377 +/- 314 IU/L x 120 min, P < .05), whereas we failed to find a statistically significant difference in a similar comparison among obese subjects (HO v NO, 3,606 +/- 302 v 3,129 +/- 602 IU/L x 120 min). A trend toward increased plasma testosterone and decreased sex hormone-binding globulin (SHBG) was found in relation to hyperinsulinemia and obesity, thus resulting in a higher free androgen index (FAI) in groups HL and NO versus NL (HL, 5.54 +/- 0.51; NO, 5.64 +/- 0.49; NL, 4.13 +/- 0.33; P < .05 and P < .01, respectively). The presence of both exaggerated insulin secretion and obesity resulted in a synergistic additive effect on the FAI in the HO group (6.81 +/- 0.34). Concerning the lipoprotein lipid profile, the NL group showed lower plasma triglyceride levels compared with the other three groups, whereas no significant differences were found for nonesterified fatty acid (NEFA) concentrations. Higher low-density lipoprotein cholesterol (LDL-C) and very-low-density lipoprotein cholesterol (VLDL-C) and lower high-density lipoprotein cholesterol (HDL-C) levels were found in the obese groups compared with the lean counterparts, whereas the same parameters did not significantly differ in a comparison between normoinsulinemic and hyperinsulinemic groups. In conclusion, our data suggest an important role of hyperinsulinemia in the LH response to a GnRH stimulus and an independent and synergistic additive effect of obesity and hyperinsulinemia on the FAI in PCOS.