Allopregnanolone levels and seizure frequency in progesterone-treated women with epilepsy

Abstract

Objective: To determine whether allopregnanolone (AP) may mediate seizure reduction in progesterone-treated women with epilepsy. Methods: The NIH Progesterone Trial compared the efficacy of adjunctive cyclic natural progesterone therapy vs placebo treatment of intractable seizures in 294 subjects, randomized 2:1 to progesterone or placebo, stratified by catamenial vs noncatamenial designation. Treatments were compared on proportions of 50% responders, and changes in seizure frequency from 3 baseline to 3 treatment cycles. Serum AP levels were measured by radioimmunoassay from 155 women with intractable focal-onset seizures who had baseline and treatment-phase midluteal serum samples drawn each cycle for hormone measurements. Results: There was no significant correlation between percentage changes in AP levels and seizure frequencies from baseline to treatment for either the catamenial or noncatamenial stratum. There was a significant correlation for the subset of subjects who showed a significantly greater responder rate in the post hoc analysis of the trial, i.e., subjects who had a 3-fold or greater increase in average daily seizure frequency perimenstrually compared with the midfollicular and midluteal phases (C1 ≥3: r = 20.442, p = 0.013, and specifically for C1 ≥3 progesterone-treated subjects [r = 20.452, p 5 0.035], but not other groups [C1 ≥3 placebo: r = -0.367; C1 <3 progesterone: r = 0.099; C1 <3 placebo: r = 0.131; p = not significant]). Conclusions: The findings support AP as a mediator of seizure reduction in progesterone-treated women who have a substantial level of perimenstrually exacerbated seizures. © 2014 American Academy of Neurology.