Abstracts

Previous reports have suggested that hormone replacement therapy (HRT) could increase seizure activity in women with epilepsy. We sought to determine whether adding HRT to the medication regimen of menopausal women with epilepsy was associated with seizure increase. This is a randomized, double-blinded, placebo-controlled trial of the effect of HRT on seizure frequency in menopausal women with epilepsy taking stable doses of antiepileptic drugs (AEDs) and within 10 years of their last menses. After a three month prospective baseline, subjects were randomized to placebo, Prempro (0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate) daily, or double-dose Prempro daily for a three month treatment period. Baseline characteristics between treatment arms were compared using univariate ANOVA. The proportion of subjects with increased seizure frequency in the treatment arm was compared with those whose seizures decreased or stayed the same relative to baseline (Chi-square). Bivariate correlations (Spearman[rsquo]s rank) were also used. Significance level set at 0.05. Twenty-one subjects were randomized after completing baseline. The subjects[rsquo] age ranged from 54-62 years (mean=53 years, SD= +/-5), number of AEDs used ranged from 1-3 (mean=1.6, SD=+/-0.8). Seven subjects had no seizures during baseline. No differences between treatment arms were present at baseline for age, number of AEDs used, and seizure frequency.
Four out of seven subjects had a worsening seizure frequency of their most severe seizure type on double-dose Prempro, compared to 3/8 on single dose Prempro and 0/6 on placebo. The association of increased seizure frequency with increasing Prempro dose was significant (p=0.032, r=0.470). The association of increased complex partial seizure frequency with increased Prempro dose was also significant (p=0.048, r=0.436). Chi-square analyses of seizure frequency vs. treatment arm revealed no significant results, however increased frequency of the subject[rsquo]s most severe seizure type was associated with increasing Prempro dose at a level that approached significance (p=0.089).
Four subjects in the double-dose Prempro arm discontinued before completion of the treatment period; 2 due to HRT-related adverse effects, 1 due to seizure increase (met exit criteria) and one due to the WHI study results. One subject in the single-dose Prempro arm discontinued early, due to HRT-related effects; only one subject in the placebo arm discontinued early, due to the WHI study results. Prempro is associated with a dose-related increases in seizure frequency in menopausal women with epilepsy. (Supported by RO1-NS38473)