Progesterone Therapy for Women with Epilepsy

这项随机、安慰剂对照、双盲、多中心临床试验将评估 环孕酮辅助治疗降低女性难治性癫痫发作的频率 定位相关癫痫。 有相当多的科学证据表明，雌激素通常会增加，而黄体酮 减少神经元兴奋性和癫痫发作。初步开放试验表明，循环给药 补充天然黄体酮可使大多数患者的癫痫发作频率降低50%以上 患有月经性发作的妇女加剧了顽固性癫痫发作。相比之下，口服合成孕激素则没有。 显示出显著的疗效。黄体酮没有被广泛地开出，因为它的好处还没有被 确凿的证明。我们已经证明了黄体酮试验的可行性和安全性，使用150 调查的初始阶段的受试者。我们现在提议继续完成这项工作。 对640名受试者进行了最终调查。在基线阶段，癫痫发作和月经表记录 基线癫痫发作频率，并确定癫痫发作是否表现出月经性加重模式。 然后将受试者分为月经期和非月经期。每一层都被随机排列在一个 黄体酮治疗组和安慰剂治疗组的比例为2：1。治疗3个月内癫痫发作频率 与基线相比，同时监测抗癫痫药物和激素水平。 这项临床试验对女性癫痫患者具有相当大的潜在意义。约30%的人 尽管使用了抗癫痫药物，但仍持续癫痫发作。据估计，这些妇女中有35%有月经期 癫痫加重。如果这组人对荷尔蒙治疗反应良好，人们会预料到 黄体酮可使大约(1,000,000 x.30 x.35)100,000名患有月经性癫痫的妇女受益 也许更多没有先天经验的女性表现出对癫痫发作的荷尔蒙敏感性。

This randomized, placebo-controlled, double-blind, multicenter clinical trial will assess the efficacy of adjunctive cyclic progesterone therapy in lessening the frequency of intractable seizures in women with localization-related epilepsy. There is considerable scientific evidence to suggest that estrogen generally increases while progesterone decreases neuronal excitability and seizures. Preliminary open trials suggest that the cyclic administration of adjunctive natural progesterone supplement may lessen seizure frequency by over 50% in the majority of women with catamenially exacerbated intractable seizures. Oral synthetic progestins, in contrast, have not shown significant efficacy. Progesterone is not widely prescribed because its benefits have yet to be conclusively demonstrated. We have shown the feasibility and safety of a progesterone trial, using 150 subjects in the initial phase of this investigation. We now propose proceding with the completion of this definitive investigation of 640 subjects. During the baseline phase, seizure and menstrual charts document baseline seizure frequency and determine if seizure occurrence shows a catamenial pattern of exacerbation. The subjects are then divided into catamenial and non-catamenial strata. Each stratum is randomized in a 2:1 ratio into progesterone and placebo treatment groups. Seizure frequency during 3 months of treatment is compared to baseline, while monitoring antiepileptic drug and hormone levels. This clinical trial has considerable potential significance for women with epilepsy. Approximately 30% have persistent seizures despite antiepileptic drug use. It is estimated that 35% of these women have catamenial seizure exacerbation. If this group responds favorably to hormonal therapy, one would expect that progesterone may benefit approximately (1,000,000 x .30 x .35) 100,000 women with catamenial epilepsy and perhaps many more women with no a priori demonstrated hormonal sensitivity to seizure occurrence.