The antimycotic drug terbinafine in contrast to ketoconazole lacks acute effects on the pituitary-testicular function of healthy men: a placebo-controlled double-blind trial

Abstract

Abstract. Among the side-effects of the antimycotic drug ketoconazole, inhibition of testosterone biosynthesis is highly pronounced. The decrease in testosterone may cause impotence and gynecomastia, and this side-effect has been exploited in drug tests for the treatment of androgen-dependent tumours. Terbinafine, an allylamine derivate, from a new group of antifungal substances, did not show similar inhibiting effects on steroid synthesis in vitro and in vivo in animal experiments. In a double-blind, placebo-controlled study the influence of terbinafine and ketoconazole on the pituitary-testicular axis in normal young men were compared. Serial blood sampling for 12 h was followed by the ingestion of the placebo, ketoconazole (200 mg) or terbinafine (500 mg) on three different occassions in random order. Ketoconazole administration caused a steep decrease of serum testosterone reaching a nadir after 4–5 h. Simultaneously an increase in 17-hydroxyprogesterone occurred with peak values after 5 h. During 12 h after the administration of ketoconazole no changes in LH pulse frequency and amplitude were found, although testosterone serum levels were in the subnormal range for about 8–9 h. Terbinafine showed no effects on testosterone and 17-hydroxyprogesterone levels or on LH pulse frequency and amplitude. Estradiol, prolactin and FSH remained unchanged after ketoconazole and terbinafine ingestion compared with placebo treatment. The study confirms the acute effect of ketoconazole on serum testosterone and 17-hydroxyprogesterone, whereas terbinafine shows no acute influence on the pituitary-gonadal axis.