Reproductive Endocrine Considerations and Hormonal Therapy for Men with Epilepsy

Summary: Androgen deficiency is unusually common among men with epilepsy. It may contribute to reproductive and sexual dysfunction and possibly exacerbate seizure frequency. The most important androgen is testosterone. It exists in the serum in a free form or bound to albumin or sex hormone-binding globulin (SHBG). Free testosterone levels have correlated significantly with measures of potency and sexual interest. The possibility that measures of non-SHBG-bound testosterone may provide a more sensitive assessment of biologically and perhaps clinically significant androgen levels is raised for consideration. Androgen deficiency may result from increased catabolism and binding induced by antiepileptic drugs (AEDs). It is a feature of the reproductive endocrine disorders that are often associated with epilepsy: hypogonad-otropic hypogonadism, hypergonadotropic hypogonadism, and functional hyperprolactinemia. It may be a consequence of medication-induced elevations in serum estradiol. Estradiol exerts a potent inhibitory influence on luteinizing hormone secretion and may contribute to premature aging of the reproductive system, both at the level of the testes and the hypothalamus. Testosterone therapy may moderately benefit reproductive and sexual function. Despite its antiseizure effects in animal experiments, however, it has not been reported to improve seizures clinically. One possible explanation is that AEDs that induce enzyme synthesis may enhance the conversion of testosterone to estradiol by aromatase. This possibility is supported by the improved seizure control achieved with the adjunctive use of the aromatase inhibitor testolactone or the antiestrogen clomiphene.