The report by Shepherd et al in this issue of the Archives1 is the latest step in an evolving story. For me, the story began in 1979, in the second year of my early studies with ketoconazole as a therapy for deep mycoses.2 A young male patient with coccidioidomycosis, on no other medications, developed gynecomastia. It was this observation and the development of gynecomastia in a second patient receiving ketoconazole therapy the next year that led to a collaboration with Allan Pont, MD, then chief of endocrinology at Santa Clara Valley Medical Center, San Jose, Calif, to investigate whether this occurrence might be explained by a ketoconazole-induced alteration of sex hormone synthesis or action. We initially found that random testosterone determinations in several patients showed a temporal relationship with the time of their daily ketoconazole dose. We thought the best way to substantiate this relationship would be
Stevens DA. Ketoconazole Metamorphosis: An Antimicrobial Becomes an Endocrine Drug. Arch Intern Med. 1985;145(5):813–815. doi:10.1001/archinte.1985.00360050057008
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