The effect of flutamide on basal and ACTH-stimulated plasma levels of adrenal androgens in patients with advanced prostate cancer

The effect of flutamide on basal and ACTH-stimulated plasma levels of adrenal androgens was investigated in 6 patients with untreated advanced prostate cancer, aged 52–75 yr. Flutamide was administered (250 mg three times daily) for 10 days; before and after treatment, a synthetic ACTH1 -24 stimulation test (250 µg im, with blood sampling immediately before and 60 min after the stimulus) was performed. Basal plasma 170H-pregnenolone (Δ5-170HP), 170H-progesterone (A4-170HP), androstenedione (A), dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) were unchanged by flutamide treatment. In contrast, basal plasma testosterone (T) concentrations significantly increased (p < 0.05). The response of Cortisol Δ 4-170HP, Δ 5-170HP, A and DHEA to ACTH, as well as the ACTH-stimulated Δ5-170HP/Δ4-170HP, Δ5-170HP/DHEA, Δ4-170HP/A and DHEA/A ratios, were unchanged by flutamide treatment. These findings indicate that: a) Short-term flutamide administration enhances testicular steroidogenesis, via augmented LH pulse frequency; b) Adrenal steroidogenesis seems to be not affected by the drug, since ACTH-stimulated plasma levels of adrenal androgens and precursors/products ratios were unchanged.