Estrogens and epilepsy: why are we so excited?

Estrogens are essential for normal brain function throughout life. The source of estrogens is not only from the periphery, but local production has also been demonstrated in the CNS. Actions of estrogens involve a variety of effects, which include modulation of gene expression, regulation of neurotransmitter release, or direct inter-actions with neurotransmitter receptors. By these effects, estrogens affect neuronal excitability and thus may play an important role in seizure disorders. Although the original clinical as well as animal studies suggest that estrogens have exclusively proconvulsant properties, it has now become clear that estrogens also produce anticonvulsant effects. These opposite effects of estrogens on seizures may depend on treatment duration, latency prior to seizure testing, mode of administration, estrogen dose and hormonal status, estrogenic species, the region/neurotransmitter system involved, seizure type/model used, and sex. Animal data also suggest that estrogens, specifically beta-estradiol, have neuroprotective effects on seizure-induced hippocampal damage. Further studies are necessary to understand the role of estrogens in seizure disorders. Such under-standing is important, especially for women with epilepsy, to make qualified decisions regarding administration of contraceptives and hormonal replacement therapy as well as for the design of new therapeutic strategies for better seizure control and prevention of seizure-induced neuronal damage.