ANTIANDROGENIC EFFECT OF SPIRONOLACTONE

I. STUDIES ON SPIRONOLACTONE-INDUCED ALTERATIONS IN THE PLASMA HORMONAL PATTERNS

Abstract

Spironolactone, an aldosterone antagonist has an antiandrogenic effect by potentially inhibiting some enzymatic steps in androgen synthesis in testes and adrenals. In order to clarify the site and mode of the antiandrogenic action of spironolactone in vivo, spironolactone-induced alterations in the hormonal patterns were studied in normal mature male dogs and men with prostatic carcinoma. Decrease in the level of plasma testosterone and increase in the level of plasma progesterone were noted by the administration of spironolactone for a period of 20 days in the animal study as well as in the clinical study. No significant changes were noted in the plasma level of cortisol and 17 β-estradiol as well as LH and FSH. The plasma level of LH, however, increased significantly in one patient whose duration of the drug was extended up to 30 days. Spironolactone did not inhibit the secretion of gonadotropins, however, it was considered that increased level of plasma progesterone would counteract the stimuli of gonadotropin release caused by the low level of testosterone. From these observations, it would be concluded that spironolactone acts directly on the enzyme system contributing to the conversion of progesterone to testosterone, and this agent would be used as antiandrogenic drug for the treatment of patients with cancer of the prostate.