Abstract
Hormones have an extremely large impact on seizures and epilepsy. Stress and stress hormones are known to reinforce seizure expression, and gonadal hormones affect the number of seizures and even the seizure type. Moreover, hormonal concentrations change drastically over an individual's lifetime, especially in women. The prevailing view on steroid hormones is that estrogen and corticosteroid hormones are proconvulsant, whereas progesterone is anticonvulsant, but recent studies in various absence models show that this is not the case in absence epilepsy. Progesterone facilitates the occurrence of absences, most likely through its conversion to the neurosteroid allopregnanolone and the non-genomic action of this neurosteroid on classical GABAA receptors. On the other hand, during pregnancy, when progesterone is enhanced, spike-wave discharges, typical for absence seizures, are diminished, suggesting an opposite relation between absence seizures and progesterone. How progesterone affects absence seizures differently during pregnancy, and during the various phases of the ovarian cycle is a challenging question. Most likely local neuroplastic changes of delta subunit containing GABAA receptors are interesting candidates to be involved in how and in which way progesterone exerts its effects on absence seizures and how this may be different across puberty, various phases of the ovulation cycle, pregnancy, and menopause. Estradiol fails to have an effect on absence seizures, while testosterone probably exerts its effects via its metabolites 5alpha-dihydrotestosterone and later to the GABAA receptor agonist 3alpha-androstanediol. Stressors also modulate absence seizures, it is tentatively proposed that this may occur also via modulation of GABAA receptors.
