Treatment of catamenial epilepsy is still up in the air.

Commentary Seizure clustering is a common occurrence in many types of epilepsy. As with any phenomenon distributed unevenly, the human mind strives to find explanations for periods of relative quiescence interspersed with periods of prominent activity. Women with epilepsy have consistently associated seizure clustering with the menstrual cycle, so much so that there is a name for the phenomenon of women who experience exacer-bation during this time: catamenial epilepsy. There has been a struggle to explicitly define catamenial epilepsy, since epilepsy occurs in so many different and complex patterns. Likely, women who have seizures in a monthly pattern will attribute it to the menstrual cycle whether or not there is a relationship. Notably, women are not alone in cycling of seizures: This phenomenon may be reported in men as well. In a questionnaire study of 141 men and women presenting to an epilepsy center, 29% reported seizure clustering, and gender was not a significant predictor of patients reporting clusters (1). Given the fact that clustering is very common, it is quite possible that at least some clustering is indeed related to cycling of hormones and, therefore, tied to the menstrual pattern. Several different catamenial patterns have been reported, including seizures that occur perimenstrually (between days-3 to 3 of the menstrual cycle, the so-called " C1 pattern "), those that occur in the periovulatory period (Days 10–13, the " C-2 pattern "), and those that occur in anovulatory cycles (Days 10–3, the " C3 pattern ") (2). Since there is an acknowledged likely association of seizure clusters to menses, there have been numerous attempts to intervene with various therapeutic maneuvers—including acetazolamide and intermittent benzodiazepine therapy— and potentially more targeted interventions that would address hormonal surges that have been implicated in catame-nial epilepsy. The most promising intervention appeared to be introduction of natural progesterone on Days 14 to 25 of the menstrual cycle. Yet, no intervention, including this one, had been subjected to a randomized controlled trial until the present study, which was a welcome attempt to finally OBJECTIVE: To assess progesterone treatment of intractable seizures in women with partial epilepsy. METHODS: This randomized, double-blind, placebo-controlled, phase III, multicenter, clinical trial compared the efficacy and safety of ad-junctive cyclic natural progesterone therapy versus placebo treatment of intractable seizures in 294 subjects randomized 2:1 to progesterone or placebo, stratified by catamenial and noncatamenial status. It compared treatments on proportions of ≥ 50% responders …