Abstract
A single oral dose of 400 mg ketoconazole, a broad-spectrum antifungal drug, administered orally to 5 young men induced a drop in serum and saliva testosterone into the range of hypogonadism, while LH, FSH and prolactin levels remained unchanged. In vitro studies with mouse Leydig cells demonstrated a direct reversible inhibition of testosterone biosynthesis by ketoconazole. Comparative studies with chemically related compounds showed similar effects on testosterone production of mouse Leydig cells by isoconazole, miconazole, econazole and clotrimazole, while metronidazole and levamisole were without influence on testosterone biosynthesis. Since all tested imidazoles which suppress testosterone production have as a common feature a phenylated side chain of the imidazole molecule, this indicates a structure/activity relationship for the effects observed.
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