Ketoconazole-induced stimulation of gonadotropin output in men: basis for a potential test of gonadotropin reserve.
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.
D019326:17-alpha-Hydroxyprogesterone; D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000097:blood; D006065:Gonadotropins, Pituitary / Q000097:blood / Q000378:metabolism*; D006801:Humans; D006908:Hydroxyprogesterones / Q000097:blood; D007654:Ketoconazole / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D013739:Testosterone / Q000097:blood
D006065:Gonadotropins, Pituitary; D006908:Hydroxyprogesterones; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D019326:17-alpha-Hydroxyprogesterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D007654:Ketoconazole