Ketoconazole-induced increase in estradiol-testosterone ratio. Probable explanation for gynecomastia.
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.
D004958:Estradiol / Q000097:blood / Q000378:metabolism*; D006177:Gynecomastia / Q000139:chemically induced*; D006801:Humans; D007654:Ketoconazole / Q000009:adverse effects* / Q000097:blood; D007700:Kinetics; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000097:blood; D013739:Testosterone / Q000097:blood / Q000378:metabolism*; D013997:Time Factors
D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D007654:Ketoconazole