Suppression of plasma androgens by the antiandrogen flutamide in prostatic cancer patients treated with Zoladex, a GnRH analogue

Abstract

Chronic treatment with the GnRH (gonadotrophin hormone releasing hormone) agonist Zoladex causes suppression of testicular androgens. Use of antiandrogens has been advocated to block the effects of the initial surge of androgens, and to block any presumed effects of adrenal androgens. We have measured plasma concentrations of androgens and possible precursors before and during treatment in the following prostate cancer patients: 10 who received Zoladex alone (Z), nine who received Zoladex + the anti-androgen flutamide (Z + F) and five who were orchidectomized (O). Testosterone fell in the Z + F group to 0.84 +/- 0.21 nmol/l (mean +/- SD) significantly lower (Wilcoxon P less than 0.05) than after Z (1.58 +/- 1.84 nmol/l) alone. Progesterone and 17 alpha-hydryxyprogesterone did not change significantly in any group. Androstenedione and dehydroepiandrosterone sulphate (DHAS) showed significant falls in Z + F (from 3.44 +/- 0.34 to 1.92 +/- 0.18 mumol/l and from 3.88 +/- 0.64 to 1.92 +/- 0.36 mumol/l respectively) but not in other groups. These results are consistent with our demonstration of an inhibitory effect of flutamide, hydroxyflutamide and other antiandrogens on human adrenal microsomal 17 alpha-hydroxylase and 17,20-lyase activities in vitro.