Women with the polycystic ovary syndrome (PCO) have significant insulin resistance and are at risk to develop noninsulin-dependent diabetes mellitus. It remains controversial, however, whether hyperandrogenism directly decreases insulin action. Hence, we performed 2-h euglycemic glucose (approximately 772 pmol/L steady state insulin levels) clamps in nine PCO women with insulin resistance basally and after the 12th week of therapy with a superagonist GnRH analog (40 micrograms every 8 h, sc). Diet, activity, and weight were kept constant. Despite significant decreases in plasma testosterone and androstenedione levels (both P less than 0.05), there was no significant change in insulin-mediated glucose disposal, plasma insulin levels, or hepatic glucose production. The sample size was adequate to detect a clinically significant change in insulin-stimulated glucose disposal (i.e. approximately 3.3 mumol/kg.min; P less than or equal to 0.05). We conclude that suppressing androgen levels into the normal range did not result in significant changes in insulin resistance in PCO. Thus, controlling hyperandrogenemia is not a clinically effective modality to improve insulin action and thereby decrease the risk of noninsulin-dependent diabetes in PCO.