November 1982

Ketoconazole Blocks Testosterone Synthesis

Author Affiliations

From the Santa Clara Valley Medical Center and the Institute for Medical Research (Drs Pont, Williams, and Stevens), San Jose, Calif; the Endocrine and Metabolic Center (Dr Reitz and Ms Bochra), Oakland, Calif; the Geriatric Research and Educational Center (Drs Azhar and Smith) and the Department of Medicine, Stanford University (Drs Pont, Williams, Azhar, and Stevens), Stanford, Calif.

Arch Intern Med. 1982;142(12):2137-2140. doi:10.1001/archinte.1982.00340250097015

• Ketoconazole, a new oral drug used to treat systemic and superficial mycoses, inhibits sterol synthesis in fungi. The development of gynecomastia in two patients prompted us to investigate the effect of the drug on testosterone production. After a 200-, 400-, or 600-mg dose, volunteer male testosterone serum concentrations fell markedly, but returned toward baseline eight to 24 hours later as ketoconazole serum concentrations waned. A marked but transient drop in testosterone levels occurred in patients receiving long-term therapy, and continuous testosterone depression was noted in one. A block of synthesis was demonstrated in vitro. Ketoconazole at concentrations achievable in serum with currently used doses blocked basal and gonadotropin-stimulated testosterone production by rat Leydig cells. The diminution of testosterone synthesis could be significant as further therapeutic trials may use larger doses or more than once-daily administration. The paucity of reports of endocrinologic toxicity may relate to the "escape" from the block demonstrated in vivo.

(Arch Intern Med 1982;142:2137-2140)