Effect of the nonsteroidal antiandrogen nilutamide on adrenal androgen secretion

The nonsteroidal androgen-receptor antagonist nilutamide has previously been shown to inhibit adrenal androgen steroidogenesis in patients with prostatic carcinoma treated in combination with an LHRH agonist. In order to understand better the mechanisms subserving this observation, we have studied the effects of nilutamide alone on the serum concentrations of androstenedione (A), dehydroepiandrosterone (DHEA), and DHEA-sulphate (DHEA-S) in 12 patients with prostatic cancer and compared them with those achieved in 21 patients treated with the agonist D-Trp-6-LHRH. In addition, the adrenocorticotropic hormone (ACTH)-stimulated adrenal response and the thyrotropin releasing hormone (TRH)-stimulated prolactin (PRL) response observed in the patients treated with nilutamide were compared with a control group of healthy age-matched controls. No significant variation in the basal concentrations of adrenal androgens occurred either within or between both treatment groups. In response to ACTH, a decreased 17-alpha hydroxyprogesterone (17-OHP) accumulation and an augmented A/17-OHP ratio were observed in the antiandrogen group (P < 0.05 for both), suggesting the partial removal of the 17,20 lyase block which was distinctive of the untreated controls, while no significant difference was found for other steroids. Basal PRL levels were not affected by the antiandrogen, but the response to TRH was increased. We conclude that no significant inhibition of adrenal androgen secretion occurs after nilutamide or LHRH agonist treatment. Rather, administration of the antiandrogen alone may partially remove the physiological decrease in adrenal androgen secretion observed in the elderly.