The
epilepsies are common
neurologic disorders characterized by spontaneous recurrent
seizures. Boys, girls, men, and women of all ages are affected by
epilepsy and, in many cases, by associated comorbidities as well. The primary courses of treatment are pharmacological, dietary, and/or surgical, depending on several factors, including the areas of the brain affected and the severity of the
epilepsy. There is a growing appreciation that sex differences in underlying brain function and in the neurobiology of
epilepsy are important factors that should be accounted for in the design and development of new
therapies. In this review, we discuss the current knowledge on sex differences in
epilepsy and associated comorbidities, with emphasis on those aspects most informative for the development of new
pharmacotherapies. Particular focus is placed on sex differences in the prevalence and presentation of various focal and
generalized epilepsies; psychiatric, cognitive, and physiologic comorbidities; catamenial
epilepsy in women; sex differences in brain development; the neural actions of sex and stress
hormones and their metabolites; and cellular mechanisms, including
brain-derived neurotrophic factor signaling and neuronal-glial interactions. Further attention placed on potential sex differences in
epilepsies, comorbidities, and drug effects will enhance therapeutic options and efficacy for all patients with
epilepsy. SIGNIFICANCE STATEMENT:
Epilepsy is a common
neurological disorder that often presents together with various comorbidities. The features of
epilepsy and seizure activity as well as comorbid afflictions can vary between men and women. In this review, we discuss sex differences in types of
epilepsies, associated comorbidities, pathophysiological mechanisms, and
antiepileptic drug efficacy in both clinical patient populations and preclinical animal models.