 This has been determined to be due to uptake of circulating weak adrenal androgens like dehydroepiandrosterone (DHEA) and androstenedione (A4) by the prostate and their "de novo" transformation into testosterone and .As such, a considerable amount of androgen signaling continues within the prostate gland even with castration.In the past, surgical adrenalectomy and early androgen biosynthesis inhibitors like ketoconazole and aminoglutethimide were successfully employed in the treatment of castration-resistant prostate cancer.