INSULIN SENSITIVITY AND ANTIANDROGENIC THERAPY IN WOMEN WITH POLYCYSTIC-OVARY-SYNDROME

Polycystic ovary (PCO) syndrome is strongly associated with insulin re sistance and the accompanying adverse metabolic profile. To distinguis h the mechanisms of this association, we determined the interactions o f PCO with obesity and the influence of ameliorating direct androgenic actions via short-term treatment with the antiandrogen flutamide. Ins ulin sensitivity was determined by the hyperinsulinemic euglycemic cla mp in groups of lean and obese PCO women and weight-matched controls. Compared with control values, insulin-mediated glucose utilization in PCO women was significantly lower in lean (1.96 +/- 0.17 v 1.24 +/- 0. 10, P < .01) and obese (1.23 +/- 0.18 v 1.03 +/- 0.09 mmol/m(2)/min, P < .01)subjects. ANOVA indicated that the effects of obesity and andro genicity are independent and additive. In both lean and obese PCO wome n, treatment with flutamide for 1 or 3 months markedly improved the cl inical and biochemical androgenic features, but did not significantly influence the overall insulin sensitivity. A large disparity between i ndividuals in the response to treatment correlated significantly with a simultaneous reduction in plasma levels of dehydroepiandrosterone su lfate (DHEA-S). Thus in women, PCO and obesity exert synergistic effec ts on insulin resistance. The decreased insulin sensitivity is mediate d via indirect androgenic actions or nonandrogenic mechanisms. In some individuals, a direct effect of androgens might have been masked by a decrease in DHEA-S levels. Copyright (c) 1995 by W.B. Saunders Compan y