Editing Hormonal Therapy (section)

===== Ketoconazole (historical) =====
* Orally active, '''broad-spectrum antifungal agent'''
* '''Non-specific inhibitor of several cytochrome P450–dependent pathways, resulting in loss of adrenal steroid synthesis and testosterone synthesis by Leydig cells'''
* '''Effects are rapid''', '''with testosterone levels dropping to the castrate level with 4 hours of administration''' in some cases. The effects are also immediately reversible, indicating '''dosing must be continuous (every 8 hours) to maintain low testosterone levels.'''
* Previously used as the first or second agent in so-called secondary hormonal manipulation for CRPC
* Adverse events include gynecomastia (caused by alterations in testosterone/estradiol ratios), lethargy, weakness, hepatic dysfunction, visual disturbance, and nausea.
* Because of the adrenal suppression, usually given with hydrocortisone (20 mg BID).