Journal of Clinical Endocrinology & Metabolism, Vol 63, 1121-1125, Copyright © 1986 by Endocrine Society

ARTICLES

Ketoconazole-induced stimulation of gonadotropin output in men: basis for a potential test of gonadotropin reserve

AR Glass

The antifungal drug ketoconazole is known to inhibit testosterone biosynthesis and decrease serum testosterone concentrations. To assess whether the ketoconazole-induced reduction in serum testosterone might stimulate LH and FSH output in a manner suitable as a test of pituitary gonadotropin reserve, we gave normal men ketoconazole every 8 h for 1 week in dosages of 300-1200 mg/day. Ketoconazole administration caused a dose-dependent reduction in serum testosterone which correlated inversely with serum ketoconazole (r = -0.82; P less than 0.001). This fall in serum testosterone stimulated increases in serum LH and FSH which were maximal at a ketoconazole dose of 900 mg/day [LH increase, 127 +/- 27% (+/- SEM); FSH increase, 63 +/- 15%]. Ketoconazole tended to blunt the LH and FSH responses to LHRH. Ketoconazole increased serum 17-hydroxyprogesterone, reflecting blockade of 17,20-desmolase by the drug, while having inconsistent effects on serum estradiol. I conclude that ketoconazole administration for 1 week to normal men stimulates LH and FSH output in a fashion that makes it potentially suitable, after additional verification in subjects with normal and abnormal pituitary- testicular function, as a test of pituitary gonadotropin reserve.

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