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 持续性环孕酮治疗降低女性癫痫患者难治性癫痫发作的频率 定位相关性癫痫 有相当多的科学证据表明，雌激素一般增加，而孕激素 降低神经元兴奋性和癫痫发作。初步的开放试验表明， 连续性天然孕酮补充剂可以减少癫痫发作频率超过50%， 女性的更年期症状加重，顽固性癫痫发作。相反，口服合成孕激素 显示出显著的功效。Progesterone并没有被广泛使用，因为它的好处还没有被发现。 最终证明。我们已经证明了孕酮试验的可行性和安全性，使用150 在调查的最初阶段。我们现在建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，癫痫发作和月经记录 基线癫痫发作频率，并确定癫痫发作是否显示月经性加重模式。 然后将受试者分为月经和非月经阶层。每一层都是随机的， 2：1的比例分为孕酮和安慰剂治疗组。3个月治疗期间癫痫发作频率 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%的患者 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%有月经失调。 癫痫发作加重。如果这组人对激素治疗反应良好，人们可以预料， 孕酮可使大约（1，000，000 ×.30 ×.35）100，000名月经期癫痫妇女受益 也许更多的妇女没有先验表现出对癫痫发作的激素敏感性。

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.