EFFECT OF THE NONSTEROIDAL ANTIANDROGEN NILUTAMIDE ON ADRENAL ANDROGEN SECRETION

The nonsteroidal androgen-receptor antagonist nilutamide has previousl y been shown to inhibit adrenal androgen steroidogenesis in patients w ith prostatic carcinoma treated in combination with an LHRH agonist. I n order to understand better the mechanisms subserving this observatio n, we have studied the effects of nilutamide alone on the serum concen trations of androstenedione (A), dehydroepiandrosterone (DHEA), and DH EA-sulphate (DHEA-S) in 12 patients with prostatic cancer and compared them with those achieved in 21 patients treated with the agonist D-Tr p-6-LHRH. In addition, the adrenocorticotropic hormone (ACTH)-stimulat ed adrenal response and the thyrotropin releasing hormone (TRH)-stimul ated prolactin (PRL) response observed in the patients treated with ni lutamide were compared with a control group of healthy age-matched con trols. 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) a ccumulation and an augmented A/17-OHP ratio were observed in the antia ndrogen group (P < 0.05 for both), suggesting the partial removal of t he 17,20 lyase block which was distinctive of the untreated controls, while no significant difference was found for other steroids. Basal PR L levels were not affected by the antiandrogen, but the response to TR H 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 physiologic decrease in adrenal androgen secretion observed in th e elderly. (C) 1994 Wiley-Liss, Inc.