Epilepsy, sex hormones and antiepileptic drugs in female patients

Women with epilepsy have a higher incidence of reproductive endocrine disorders than the general female population. These alterations include polycystic ovary syndrome, hyperandrogenemia, infertility, hypothalamic amenorrhea and hyperprolactinemia. Reproductive dysfunction is attributed both to epilepsy itself and to antiepileptic drugs (AEDs). Focal epileptic discharges from the temporal lobe may have a direct influence on the function of the hypothalamic pituitary axis, thus altering the release of sex steroid hormones, including the production of luteinizing hormone, follicle-stimulating hormone, gonadotropin-releasing hormone and prolactin. AEDs may modulate hormone release from the hypothalamic pituitary gonadal axis and they may alter the metabolism of sex hormones and their binding proteins. Hepatic enzyme-inducing AEDs, such as carbamazepine and phenytoin, may be most clearly linked to altered metabolism of sex steroid hormones, but valproic acid, an enzyme inhibitor, has also been associated with a frequent occurrence of polycystic ovary syndrome and hyperandrogenism in women with epilepsy. Therefore, treatment of epilepsy and selection of AEDs are important for reproductive health in female patients. The aim of the present review is to critically evaluate the recently published data concerning the interactions between sex hormones, epilepsy and AEDs.