In vivo effects of terbinafine and ketoconazole on testosterone plasma levels in healthy males.

Ten healthy male volunteers received daily 200 mg of ketoconazole or 500 mg of terbinafine (SF 86-327) for a period of 8 days according to a crossover double-blind design. Between the periods of treatment there was an interval of 3 weeks. Before and during the treatments, on 3 days in all, blood levels of testosterone were determined in the morning at 08.00 and 12.00 h. On the following day in each case, after taking a basal blood sample, 5,000 IU of hCG were injected intravenously and 2 h later a further blood sample for plasma testosterone determination was taken (short-term hCG stimulation test). Prior to treatment, the mean plasma testosterone levels at 12.00 h were slightly below the level at 08.00 h (6.5 +/- 3.5 against 7.2 +/- 3.1 ng/ml). The difference increased and was statistically significant with ketoconazole treatment (4.2 +/- 3.2 against 7.7 +/- 3.0 ng/ml), but did not alter during administration of terbinafine (7.8 +/- 4.4 against 6.8 +/- 3.0 ng/ml). The administration of testosterone levels by hCG stimulated 25.6% prior to treatment. The stimulation was suppressed to zero by ketoconazole but clearly intensified (41.7%) by terbinafine treatment. The results demonstrate once more the well-known effect of ketoconazole on testosterone production and confirm that terbinafine obviously does not have this effect.