Stimulation of erythropoiesis by the non-steroidal anti-androgen nilutamide in men with prostate cancer: evidence for an agonistic effect?

The effects of steroid hormones are pleiotropic. Similarly, non-steroidal oestrogen receptor antagonists such as tamoxifen exert partial agonistic effects with a species- and tissue-specific pattern. Conversely, little is known of the biological effects of non-steroidal anti-androgens, whose role has been investigated in the palliative treatment of prostate cancer. We studied the effects of the non-steroidal anti-androgen nilutamide on parameters of red blood cells, an androgen-dependent cell compartment, in 24 men with prostate cancer and compared the results with those obtained in 38 historical control patients treated with D-tryptophan-6-LHRH. Administration of the anti-androgen induced a limited rise in testosterone concentrations (from 14.1 +/- 1.8 up to a maximum of 19.6 +/- 2.3 nmol l-1) and a significant increase with time in haemoglobin and haematocrit (y = 12.6 g dl-1 + 0.15 months and y = 37.3% + 0.46 months respectively, P = 0.008 for both), while no change occurred in red blood cell count (y = 4.19 x 10(6) mm-3 + 0.02 months, P = 0.2). Conversely, no variation in erythroid parameters was observed in the patients treated with the LHRH analogue (haemoglobin = 12.7 + 0.02 months, P = 0.59; haematocrit = 38.1 + 0.02 months, P = 0.9; red blood cells = 4.34 x 10(6) mm-3 + 0.15 months, P = 0.4). The difference between the linear regression slopes of haemoglobin in the two treatment groups was significant (F-ratio = 3.39, P = 0.03). While the stimulation of erythropoiesis induced by the anti-androgen might be due to incomplete neutralisation of endogenous androgens at the bone marrow level, a cell-specific agonistic effect of the drug cannot be excluded, thus calling into question the designation of pure antagonists which has been attributed to this class of compounds. Ongoing randomised trials should address this issue.