Effects of flutamide and aminoglutethimide on plasma 5 alpha-reduced steroid glucuronide concentrations in castrated patients with cancer of the prostate.

Plasma levels of androstane-3 alpha, 17 beta-diol glucuronide (3 alpha-diol-G) and androsterone glucuronide (ADT-G) have been found to be effective markers of C-19 steroid metabolism in periphery in man. The present study has been performed in order to study in castrated patients the effect of antiandrogen administered alone or in combination with aminoglutethimide (AG) on the metabolism of adrenal C-19 steroid. Ten castrated patients with prostatic cancer received flutamide (FLU) alone for 2 months and, afterwards, the combined therapy of FLU and AG for 2 months. Antiandrogen treatment alone reduces the levels of dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone glucuronide (DHEA-G) and androstenedione (4-ene-dione) by 43, 34 and 38% (P less than or equal to 0.01) respectively while dehydroepiandrosterone (DHEA), androst-5-ene-3 beta,17 beta-diol (5-ene-diol) and androst-5-ene-3 beta,17 beta-diol-glucuronide (5-ene-diol-G) levels show a nonsignificant inhibition. In these patients, plasma 3 alpha-diol-G and ADT-G concentrations are nonsignificantly stimulated to 122 and 143%. Moreover, when patients were receiving the combined administration of FLU and AG, adrenal C-19 steroids were further inhibited while both 3 alpha-diol-G and ADT-G show a small but nonsignificant decrease. Our data indicate that the antiandrogen increases the formation and/or the metabolism of adrenal C-19 steroids into steroid glucuronides.