Cancer commonly leads to weight loss associated with increased glucose production and protein breakdown. Medical or surgical castration results in decreased muscle mass, increased fat mass, and weight gain. The aim of this study was to evaluate the changes in body composition, protein metabolism, hepatic glucose production, (HGP), and basal energy expenditure in 10 men with advanced stage C and D prostate cancer receiving a gonadotropin-releasing hormone (GnRH) agonist (Buserelin). Metabolic parameters and nutritional status were determined at 0, 2, 6, and 12 months of therapy. Baseline measurements of plasma leucine appearance (76.2 +/- 5.4 microM/kg/h) and HGP rates (80.1 +/- 2.9 mg/m2/min) were greater than previously reported for normal volunteers. GnRH agonist therapy in prostate cancer patients was associated with a significant reduction in serum testosterone, dihydrotestosterone (DHT), luteinizing hormone (LH), and cortisol, and significant increases in triiodothyronine (T3) and free triiodothyronine (free T3). Neither basal energy expenditure nor plasma leucine appearance rates were changed over time, but there were significant linear reductions in HGP rates (80.1 +/- 2.9 mg/m2/min, mean +/- SEM; 79.9 +/- 2.3, 73.7 +/- 3.4, 72.5 +/- 2.3; P less than .01; baseline, 2, 6, and 12 months, respectively, by repeated measures ANOVA). In all patients, significant increases in body weight, triceps skin fold, cholesterol, and fat mass were noted. Total body water content was not significantly increased after the 12-month period; therefore, the weight gain seen in these patients was water-free tissue, ie, fat mass.