Evidence for a defect in insulin metabolism in hyperandrogenic women with polycystic ovarian syndrome.

It has been well established that the hypertestosteronemia of patients with polycystic ovarian syndrome (PCO) is associated with hyperinsulinemia and insulin resistance. We have recently noted a disparity between serum levels of insulin and C-peptide in certain hypertestosteronemic women with PCO and hypothesized a possible association between testosterone and insulin metabolism. Therefore, we have studied insulin clearance (baseline steady-state ratios of C-peptide to insulin) in 15 obese PCO women, 12 weight-matched controls (OC), and nine lean controls (LC), and examined the interactions of testosterone and insulin metabolism by examining the correlations between testosterone and insulin clearance and by studying the direct in vitro actions of testosterone on T-lymphocyte insulin binding and degradation. We found that the C-peptide to insulin ratio at baseline and T-lymphocyte insulin degradation of the PCO group were twofold below the LC and OC values. Basal C-peptide to insulin ratios and insulin-degradative activities were significantly and negatively interrelated (r = .56, P < .01), and both of these parameters were highly correlated (P < .01) with basal testosterone levels (r = .49 for basal C-peptide to insulin and r = -.61 for insulin degradation). In experiments where testosterone was added to cell cultures, insulin degradation was impaired in a biphasic fashion. We conclude that (1) elevated testosterone levels may contribute to impairments in insulin metabolism, and (2) the hyperinsulinemia of hyperandrogenic women may occur in part from defects in insulin clearance and peripheral tissue insulin degradation.