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  • Title: Ketoconazole-induced increase in estradiol-testosterone ratio. Probable explanation for gynecomastia.
    Author: Pont A, Goldman ES, Sugar AM, Siiteri PK, Stevens DA.
    Journal: Arch Intern Med; 1985 Aug; 145(8):1429-31. PubMed ID: 4040740.
    Abstract:
    Ketoconazole, an antifungal drug, causes gynecomastia in some patients. It also inhibits androgen and glucocorticoid synthesis. In four volunteer male subjects, 600-mg doses of ketoconazole depressed serum testosterone concentrations markedly, but serum estradiol to a much lesser degree. The bound and free percentages of both hormones were not significantly altered. The net result was a significant elevation of the estradiol-testosterone ratio, expressed as either total circulating hormone or free hormone. In five male patients receiving long-term high-dose ketoconazole therapy, the testosterone concentrations fell, but the effect on estradiol was variable. In these patients the estradiol-testosterone ratio was persistently increased. Since gynecomastia appears to be the result of an elevated estradiol-testosterone ratio, the selective hormonal effect demonstrated may explain the side effect of gynecomastia after ketoconazole therapy.
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