Taubøll Erik, Sveberg Line, Svalheim Sigrid
Department of Neurology, Oslo University Hospital - Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
Department of Neurology, Oslo University Hospital - Rikshospitalet, Oslo, Norway.
Seizure. 2015 May;28:3-11. doi: 10.1016/j.seizure.2015.02.012. Epub 2015 Feb 23.
There is a complex, bidirectional interdependence between sex steroid hormones and epilepsy; hormones affect seizures, while seizures affect hormones thereby disturbing reproductive endocrine function. Both female and male sex steroid hormones influence brain excitability. For the female sex steroid hormones, progesterone and its metabolites are anticonvulsant, while estrogens are mainly proconvulsant. The monthly fluctuations in hormone levels of estrogen and progesterone are the basis for catamenial epilepsy described elsewhere in this issue. Androgens are mainly anticonvulsant, but the effects are more varied, probably because of its metabolism to, among others, estradiol. The mechanisms for the effects of sex steroid hormones on brain excitability are related to both classical, intracellularly mediated effects, and non-classical membrane effects due to binding to membrane receptors. The latter are considered the most important in relation to epilepsy. The different sex steroids can also be further metabolized within the brain to different neurosteroids, which are even more potent with regard to their effect on excitability. Estrogens potentiate glutamate responses, primarily by potentiating NMDA receptor activity, but also by affecting GABA-ergic mechanisms and altering brain morphology by increasing dendritic spine density. Progesterone and its main metabolite 5α-pregnan-3α-ol-20-one (3α-5α-THP) act mainly to enhance postsynaptic GABA-ergic activity, while androgens enhance GABA-activated currents. Seizures and epileptic discharges also affect sex steroid hormones. There are close anatomical connections between the temporolimbic system and the hypothalamus controlling the endocrine system. Several studies have shown that epileptic activity, especially mediated through the amygdala, alters reproductive function, including reduced ovarian cyclicity in females and altered sex steroid hormone levels in both genders. Furthermore, there is an asymmetric activation of the hypothalamus with unilateral amygdala seizures. This may, again, be the basis for the occurrence of different reproductive endocrine disorders described for patients with left-sided or right-sided temporal lobe epilepsy.
性类固醇激素与癫痫之间存在复杂的双向相互依存关系；激素影响癫痫发作，而癫痫发作也会影响激素，进而扰乱生殖内分泌功能。雌性和雄性性类固醇激素都会影响大脑兴奋性。对于雌性性类固醇激素而言，孕酮及其代谢产物具有抗惊厥作用，而雌激素主要具有促惊厥作用。雌激素和孕酮的激素水平每月波动是本期其他地方所述月经性癫痫的基础。雄激素主要具有抗惊厥作用，但其作用更为多样，可能是因为它会代谢为雌二醇等物质。性类固醇激素影响大脑兴奋性的机制既与经典的细胞内介导效应有关，也与因与膜受体结合而产生的非经典膜效应有关。后者被认为与癫痫最为相关。不同的性类固醇还可在大脑内进一步代谢为不同的神经类固醇，它们对兴奋性的影响更强。雌激素主要通过增强NMDA受体活性来增强谷氨酸反应，但也会通过影响γ-氨基丁酸能机制以及增加树突棘密度来改变脑形态。孕酮及其主要代谢产物5α-孕烷-3α-醇-20-酮（3α-5α-四氢孕酮）主要作用是增强突触后γ-氨基丁酸能活性，而雄激素则增强γ-氨基丁酸激活的电流。癫痫发作和癫痫放电也会影响性类固醇激素。颞叶边缘系统与控制内分泌系统的下丘脑之间存在紧密的解剖学联系。多项研究表明，癫痫活动，尤其是通过杏仁核介导的癫痫活动，会改变生殖功能，包括女性卵巢周期性的降低以及两性性类固醇激素水平的改变。此外，单侧杏仁核癫痫发作会导致下丘脑不对称激活。这可能再次成为左侧或右侧颞叶癫痫患者出现不同生殖内分泌紊乱的基础。
