In-vitro studies of adipose tissue have shown that patients with polycystic ovarian syndrome (PCOS) have marked insulin resistance, the abnormalities being more pronounced during amenorrhoea compared to following an ovulatory cycle. If the insulin resistance in PCOS is a reflection of anovulation then patients with hypogonadotrophic hypogonadism (HH) should also have a reduction in insulin sensitivity. This study was designed to investigate insulin sensitivity in patients with HH. Seven patients with HH were studied and compared with eight age and body mass index matched female controls. Adipocyte insulin receptor binding was measured and adipocyte insulin action was assessed by measuring initial rates of 3-O-methylglucose uptake and inhibition of lipolysis. The specific insulin receptor binding per 10 cm(2) cell surface was 0.95 +/- 0. 25% in HH and 1.85 +/- 0.14% in control patients (P < 0.01). Maximum rates of glucose uptake were also impaired in HH compared with controls (3-O-methylglucose transport 0.81 +/- 0.22 versus 1.83 +/- 0.2 pmol/10 cm(2)/5 s)(P < 0.01). Hence, patients with HH have impaired insulin sensitivity to a degree similar to that seen in PCOS, suggesting a direct effect of anovulation on insulin sensitivity.