Reduced fertility and neuroendocrine dysfunction in women with epilepsy

A reduction of fertility in women with epilepsy has been reported since 1950 and is confirmed in recent epidemiological studies. This phenomenon has usually been attributed to the increase of medical and socioeconomic problems in these patients or to hyposexuality, which has been consistently observed in epileptic subjects. Recently, a higher occurrence of reproductive endocrine diseases has been reported in epileptic women and proposed as an important cause of reduced fertility. In particular, polycystic ovary syndrome and hypothalamic ovarian failure have been reported in epileptic women with increased frequency compared to the general population. Moreover, an abnormal pattern of luteinizing hormone (LH) pulsatility has been observed in normally cycling, drug-free epileptic women. We suggest that epilepsy may interfere with the functional activity of the gonadotropin releasing hormone (GnRH) pulse generator. It is possible that paroxysmal discharges spreading within the hypothalamus might affect the regularity of the GnRH pulse generator; alternatively, a neurotransmitter dysfunction might at the same time be responsible both for the lowering of the seizure threshold and for the dysfunction of GnRH secretion. The consequent alteration of LH pulsatility might in the long run, under the effect of additional factors, give rise to a clinical reproductive endocrine disorder.