Effects of Long‐Term Antiepileptic Therapy on the Catabolism of Testosterone

Abstract

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-OH 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.

Effects of valproate and carbamazepine monotherapy on neuroactive steroids, their precursors and metabolites in adult men with epilepsy

“…Similarly, the data in the literature indicates that VPA therapy appears to have no effect on SHBG levels [38,42,44,46,47,51]. Concerning CBZ therapy, in a number of studies CBZ enhanced serum SHBG [34,44,46,48,49,51,57,62] but the effect on serum SHBG was reversible [51]. On the other hand, there are several studies in which the effect of CBZ on SHBG did not reach significance [42,43].…”

“…Brunet et al evaluated the effects of long-term antiepileptic therapy on the catabolism of testosterone and followed urinary excretion of androsterone, etiocholanolone and their 11␤-hydroxy-metabolites [34]. However, although anticonvulsant properties were demonstrated for unconjugated androsterone and etiocholanolone [21], there are no studies available evaluating serum free or conjugated 3␣/␤-hydroxy-5␣/␤-androstane-17-ones in MWE.…”

“…The only exception is the study of Brunet et al who evaluated the effects of long-term antiepileptic therapy on the catabolism of testosterone and followed urinary excretion of androsterone, etiocholanolone and their 11␤-hydroxy-metabolites [34].…”

A New Look at the 5?-Reductase Inhibitor Finasteride

“…As these testosterone metabolites are produced via further reduction by 17â-hydroxysteroid dehydrogenase (after sequential actions by 5á-reductase and 3á-hydroxysteroid dehydrogenase), one can surmise that finasteride would decrease levels of androsterone and etiocholanolone. Notably, androsterone and etiocholanolone are the major excreted metabolites of testosterone (15,126), and long term antiepileptic drug therapy was found to decrease urinary excretion of both metabolites (e.g., 15). Thus, it was suggested that a reduction in GABAergic testosterone metabolites in men with epilepsy could contribute to increased seizure susceptibility (76).…”

Visceral and Subcutaneous Adipose Tissue Assessed by Magnetic Resonance Imaging in Relation to Circulating Androgens, Sex Hormone-Binding Globulin, and Luteinizing Hormone in Young Men

“…Reference intervals may lack statistical power and can be biased due to: 1) unintentional inclusion of hypogonadal subjects, which can be limited by testicular examination and a medical history focusing on testicular, pituitary, and chronic diseases (14), medication (15)(16)(17)(18)(19), excessive alcohol intake (20), and anabolic steroid abuse; 2) failure to recruit a population-based sample not mirroring the general population; 3) inappropriate timing of blood sampling; and 4) use of inaccurate testosterone assays. Commercially available direct immunoassays for assessment of total testosterone are widely used, but these assays suffer from a lack of accuracy (21)(22)(23)(24).…”