Neurosteroids are involved in the pathophysiology of many neuroendocrine disorders in women. This review describes recent advancements in pharmacology of neurosteroids and emphasizes the benefits of neurosteroid replacement therapy for the management of neuroendocrine disorders such as catamenial epilepsy (CE), postpartum depression (PPD) and premenstrual brain conditions. Neurosteroids are endogenous modulators of neuronal excitability. A variety of neurosteroids are present in the brain including allopregnanolone (AP), allotetrahydro-deoxycorticosterone and androstanediol. Neurosteroids interact with synaptic and extrasynaptic GABA_A receptors in the brain. AP and related neurosteroids, which are positive allosteric modulators of GABA_A receptors, are powerful anticonvulsants, anxiolytic, antistress and neuroprotectant agents. In CE, seizures are most often clustered around a specific menstrual period in women. Neurosteroid withdrawal-linked plasticity in extrasynaptic receptors has been shown to play a key role in catamenial seizures, anxiety and other mood disorders. Based on our extensive research spanning two decades, we have proposed and championed neurosteroid replacement therapy as a rational strategy for treating disorders marked by neurosteroid-deficiency, such as CE and other related ovarian or menstrual disorders. In 2019, AP (renamed as brexanolone) was approved for treating PPD. A variety of synthetic neurosteroids are in clinical trials for epilepsy, depression and other brain disorders. Recent advancements in our understanding of neurosteroids have entered a new era of drug discovery and one that offers a high therapeutic potential for treating complex brain disorders.

中文翻译：

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神经类固醇替代疗法治疗女性经期癫痫、产后抑郁症和神经内分泌疾病

神经类固醇与女性许多神经内分泌疾病的病理生理学有关。这篇综述描述了神经类固醇药理学的最新进展，并强调了神经类固醇替代疗法对治疗神经内分泌疾病如月经性癫痫 (CE)、产后抑郁症 (PPD) 和经前脑部疾病的益处。神经类固醇是神经元兴奋性的内源性调节剂。大脑中存在多种神经类固醇，包括别孕酮 (AP)、别四氢脱氧皮质酮和雄甾烷二醇。神经类固醇与大脑中的突触和突触外 GABA _{A受体相互作用。AP 和相关的神经类固醇，它们是 GABA A}的正变构调节剂受体是强大的抗惊厥剂、抗焦虑剂、抗应激剂和神经保护剂。在 CE 中，癫痫发作通常集中在女性的特定月经期。神经类固醇戒断相关的突触外受体可塑性已被证明在月经期癫痫发作、焦虑和其他情绪障碍中起关键作用。基于我们跨越二十年的广泛研究，我们提出并支持神经类固醇替代疗法作为治疗以神经类固醇缺乏为特征的疾病的合理策略，例如 CE 和其他相关的卵巢或月经疾病。2019年，AP（更名为brexanolone）获批用于治疗PPD。多种合成神经类固醇正在用于治疗癫痫、抑郁症和其他脑部疾病的临床试验中。