EFFECTS OF LONG-TERM ANTIEPILEPTIC THERAPY ON THE CATABOLISM OF TESTOSTERONE

The serum levels of testosterone, sex hormone binding globulin, and free testosterone index were measured in 51 epileptic men (age 18-45) in order to assess the possible effects of antiepileptic drugs on sexual dysfunction. An analytical gas chromatography-mass spectrometry method was developed to assess the urinary excretion of testosterone, epitestosterone, androsterone, etiocholanolone, 11-OH androsterone and 11-OH etiocholanolone and to evaluate if the catabolism of testosterone had been increased. Twenty normal healthy males of similar age, 18-45 years, served as control group. Patients receiving polytherapy (n=34) or monotherapy with carbamazepine (n=8) or phenytoin (n=9) showed higher levels of sex hormone binding globulin and testosterone, and lower levels of free testosterone than did the controls (P<0.03). Urinary excretion of the metabolites androsterone and 11-OK androsterone was significantly reduced (P<0.02) in the polytherapy group, while the monotherapy group showed only significant differences (P<0.02) in the elimination of 11-OH androsterone. Our results suggest that an induction of the hepatic synthesis of sex hormone binding globulin may be the mechanism by which the antiepileptic drugs lower the levels of free testosterone in serum. However, the reduced excretion of androsterone and the normal levels of etiocholanolone show that the antiepileptic drugs do not produce an increase in the main catabolism pathway of testosterone.