The aim of this work was to examine the effect of an insulin infusion on SHBG levels as well as the relationship between SHBG levels and insulin sensitivity. Acute insulin infusion was used with the insulin-glucose clamp technique. The subjects were 14 consecutive well-characterized hyperandrogenic non-diabetic obese women without biological and echographic symptoms of polycystic ovary syndrome. Adiposity and fat distribution were assessed respectively by the body mass index (BMI: 38.7 +/- 1.6 kg/m2) and by the waist hip ratio (WHR: 0.91 +/- 0.01). Hyperandrogenism was evidenced by hirsutism and serum testosterone greater than 2.8 nM. Circulating SHBG levels were determined in the fasting state by RIA. Insulin sensitivity was assessed using the euglycemic hyperinsulinemic glucose clamp technique with three incremental doses of insulin. Seven non-obese non-hyperandrogenic subjects (BMI: 21.0 +/- 0.6 kg/m2) served as controls for the study of the insulin resistance state. Because of supraphysiological insulin infusion rates (40, 100, and 350 mU/min.m2, each dose for 2 h), insulin sensitivity was mainly studied at peripheral level. We calculated the Km, i.e. the ED50 of the dose-response curve, the glucose disposal rate, and the maximal glucose disposal rate per U insulin (M/I). The hyperandrogenic obese subjects exhibited marked insulin resistance. SHBG levels, although already in the lower half of normal in the basal state, decreased from 34.8 +/- 3.4 nmol/l to 29.7 +/- 3.3 nmol/l (P = 0.001; normal values are 18-83 nmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)