Sex differences in the anticonvulsant activity of neurosteroids

Epilepsy is one of the leading causes of chronic neurological morbidity worldwide. Acquired epilepsy may result from a number of conditions, such as brain injury, anoxia, tumors, stroke, neurotoxicity, and prolonged seizures. Sex differences have been observed in many seizure types; however, some sex-specific seizure disorders are much more prevalent in women. Despite some inconsistencies, substantial data indicates that sensitivity to seizure stimuli differs between the sexes. Men generally exhibit greater seizure susceptibility than women, whereas many women with epilepsy experience a cyclical occurrence of seizures that tends to center around the menstrual period, which has been termed catamenial epilepsy. Some epilepsy syndromes show gender differences with female predominance or male predominance. Steroid hormones, endogenous neurosteroids, and sexually dimorphic neural networks appear to play a key role in sex differences in seizure susceptibility. Neurosteroids, such as allopregnanolone, reflect sex differences in their anticonvulsant activity. This Review provides a brief overview of the evidence for sex differences in epilepsy and how sex differences influence the use of neurosteroids in epilepsy and epileptogenesis. © 2016 Wiley Periodicals, Inc.