Mechanism of Inhibition of Human Testicular Steroidogenesis by Oral Ketoconazole

To determine the antisteroidogenic effect of ketoconazole (KTZ) in the human testis, we measured the plasma Δ5-pregnenolone, Δ5-17α-hydroxypregnenolone, dehydroepiandrosterone (DHEA), progesterone, 17α-hydroxyprogesterone, androstenedione (A), and testosterone (T) concentrations in three men with previously untreated metastatic prostate cancer at various time intervals for 24 h before and 48 h after the administration of 200 mg oral KTZ every 8 h. The adrenal glands of these three patients were suppressed (as measured by the plasma cortisol levels) by the administration of 1.0 mg dexamethasone daily for 7 days before and during the study. After six doses of KTZ, bilateral orchiectomy was performed, and the intratesticular concentration of the aforementioned seven steroids and the intratesticular activities of the 17α-hydroxylase, 17,20-desmolase, and 17β-hydroxysteroid dehydrogehase enzymes in the Δ4-steroidogenic pathway were determined. These seven intratesticular steroids and three intratesticular enzy...