Abstracts

Rationale: There is controversy regarding the effects of hormonal contraception (HC) on seizures. While reviews have suggested that there is no evidence that HC exacerbates seizures, class 1 evidence is sparse and underpowered (Espir M. BMJ 1969;1:294-5) and drug inserts still include a warning about possible seizure exacerbation as do some published data. There is also a consideration as to whether hormonally sensitive seizures, as suggested by a designation of catamenial epilepsy, might influence the response. The purpose of this investigation was to determine 1) what proportion of women report an increase in seizures with past HC use, and 2) whether women with catamenial epilepsy differ from those without catamenial epilepsy in the response of their seizures to HC. Methods: The subjects were the first 141 women with localization-related epilepsy and a past history of HC use, 13-45 years of age, who enrolled in a multicenter investigation of progesterone therapy for the treatment of intractable seizures. At enrollment, the women were surveyed as to whether they experienced seizure worsening with past HC use. The women prospectively recorded seizures and menses during 3 baseline cycles after which they were classified as having catamenial or noncatamenial patterns of seizure exacerbation using established criteria (Herzog AG et al Epilepsia 1997; 38:1082-1088). Outcomes included 1) the proportion of women who reported seizure worsening with past HC and 2) the proportion of women with catamenial and noncatamenial designations who had experienced seizure worsening with HC. Results: The results show that 31 of the 141 (22.7%) women reported seizure exacerbation in relation to past HC. The proportions of women who reported seizure exacerbation with HC were not different between the catamenial(C) and noncatamenial(NC) groups (C: 21.5% vs NC: 23.7%; Χ2 = 0.92; p = N.S.; power: 75% to detect a doubling of seizure frequency with α = .05). By way of context, 22.7% approximates the 26.3% of the women who showed a notable random ≥100% increase in seizures between month 1 & 2 of the baseline phase without HC exposure and is not significantly different from the 35% (7 of 20) of women with worsening of seizures on placebo tablets in the Espir trial (Χ2 = 1.00; p = N.S.). The 22.7% is significantly less (Χ2 = 4.81; p = 0.05) than the 45% (9 of 20) of women who had documented increases in seizures on HC in the Espir trial in which no significant difference was found between HC and placebo. This significant difference, however, may relate to differences in methodology, recollection vs charting, and to the higher hormonal content of the contraceptive Norinyl in the Espir trial. Conclusions: The findings suggest that while seizure worsening may occur in relation to HC, the proportion of affected women may not differ significantly from random change or placebo use. Moreover, there is no significant difference in the proportions of women with seizure worsening between the catamenial and noncatamenial groups. Further study is needed to determine more definitively the effects of HC on seizures and whether there are differential effects of various forms and dosages of HC.