Estrogens and Epilepsy: Why Are We So Excited?

Abstract

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.

Animal models of absence epilepsies: What do they model and do sex and sex hormones matter?

“…The possibility that progesterone is the cause for the enhancement of SWDs was however not considered. A proepileptic effect of estrogens is classically assumed (Velísková, 2007), although estrogens have also antiepileptic effects as was established on clonic seizures in a KA induced SE model (Velísková et al, 2000). In contrast to all this, β-estradiol had either no effects in a typical absence model or anti-absence effects (in the atypical absence model, see Ovarian cycle and acute pharmacological studies in typical and atypical absence models section).…”

The role of neurosteroids in the pathophysiology and treatment of catamenial epilepsy

“…Estradiol has been widely investigated in animal epilepsy models. However, the effect of estrogens on seizure susceptibility is highly variable and depends on factors such as treatment duration, dosage, hormonal status and the seizure model (Veliskova, 2007). …”

Tamoxifen Mimics the Effects of Endogenous Ovarian Hormones on Repeated Seizures Induced by Pentylenetetrazole in Rats

“…Thus, it is suggested that this hormone affects the structures and functions of hippocampal neurons [3, 4]. This female sexual hormone acts via various mechanisms such as modulation of gene expression, regulation of neurotransmitter release, or direct interactions with neurotransmitter receptors [5]. Thus, estrogen can affect neuronal excitability and seizure susceptibility [6].…”

“…Furthermore, it has been shown that estrogen has neuroprotective effects against seizure-induced neuronal damage [10, 12, 13]. It is suggested that the different effects of estrogens on seizures may depend on various factors such as duration of the treatment, the priority of latency to seizure testing, the mode of administration, the applied dose of estrogen and hormonal status, the region of nervous system or the neurotransmitter system involved, the different seizure inducing models applied, and the sex of the samples [5]. …”