2010 by Taylor and Francis Group, LLC. The term catamenial epilepsy is used to describe the cyclical occurrence of seizure exacerbations during particular phases of the menstrual cycle in women with preexisting epilepsy (Newmark and Penry, 1980). The types of epilepsies and seizures that are susceptible to catamenial fluctuations have not been defined in detail. However, it seems that seizures in both partial epilepsies (such as mesial temporal lobe epilepsy) and certain primary generalized epilepsies (such as juvenile myoclonic epilepsy) can exhibit catamenial exacerbations (Agathonikou et al., 1997; Herzog et al., 1997; Panayiotopoulos et al., 1994). It has been recognized that the menstrual cycle can influence seizure susceptibility since antiquity. Today, because women with epilepsy severe enough to exhibit cyclical changes in seizure frequency are invariably treated with antiepileptic medications, catamenial epilepsy is now a specific form of intractable (pharmacoresistant) epilepsy. With drug treatment, some of these women experience a resolution of seizures except at certain times during the menstrual cycle; others do not respond to medications. In either case, the subjects have intractable seizures. The former situation is an example of state-dependent pharmacoresistance and may provide insight into mechanisms of drug intractability. Catamenial seizure exacerbations affect as few as 10% or as many as 70% of women with epilepsy who are of reproductive age (Bazan et al., 2005; Duncan et al., 1993; Herzog et al., 2004; Tauboll et al., 1991). The large variation in prevalence is mainly due to definitional differences. Herzog et al. (1997) proposed a research definition that requires a twofold increase in average daily seizure frequency during a phase of exacerbation relative to the other phases. By this criterion, catamenial conditions are met by as many as one third of women with intractable partial epilepsy (Herzog et al., 2004). Herzog et al. (1997) defined three forms of catamenial epilepsy: (1) perimenstrual (C1, days -3 to 3), (2) periovulatory (C2, days 10 to -13) in normal cycles, and (3) luteal (C3, days 10 to 3) in inadequate luteal phase cycles, where day 1 is the first day of menstrual flow and ovulation is presumed to occur 14 days before the subsequent onset of menses (day -14). The most common form is perimenstrual. In this article, treatment approaches for catamenial epilepsy are described and a rationale is provided for an investigational approach for the perimenstrual form involving exogenous administration of neurosteroids or neurosteroid analogs, referred to as neurosteroid replacement therapy.
