Role of Hormones in Susceptibility to Seizures in Women With Epilepsy

Objectives. This is an initial pilot study to acquire information upon which a more specific, statistically rigorous follow-on investigation will be based. The objectives of the overall project are: (1) to compare the absolute levels and rates of change in levels of gonadal and neuroactive steroids in women with complex partial seizures and catamenial epilepsy with those of women with non-catamenial epilepsy and women volunteers without epilepsy, and (2) to determine if fluctuations in the levels of gonadal hormones (estrone, estradiol, progesterone) and neuroactive steroids (allopregnanolone, pregnenolone and dehydroepiandrosterone) correlate with seizure occurrence and the frequency of interictal spikes/wave discharges in women with catamenial seizure exacerbations. Study Populations. Group A: adult women with complex partial seizures and catamenial exacerbations. Group B: adult women with complex partial seizures without catamenial seizure exacerbations. Group C: adult female volunteers without epilepsy. Design. Subjects will undergo baseline monitoring of seizures and menses for two months prior to entry. Upon enrollment into the study, blood (10 ml) will be drawn for determinations of estradiol, estrone, progesterone, allopregnanolone, dehydroepiandrosterone (DHEA) and pregnenolone in all study populations once daily at 08:30 hr on menstrual cycle days, 10, 14, 17, 19 and 21; and three times daily at 08:30, 13:30 and 18:00 starting 5 days before expected menses and continuing for a total of 8 days as well as on menstrual cycle day 6. During 8 days starting 5 days before expected menses interictal spike activity and seizures will also be monitored continuously with EEG. Comparisons of the rates of change of hormone levels and spike and seizure frequency will be made using the time derivatives of fluctuations in hormone levels or hormone level ratios. Comparisons of time series data will be made using nonlinear regression with an arbitrary (cubic spine) model. Outcome Parameters. The goal of this preliminary study is to obtain data regarding the fluctuation, during one menstrual cycle, of several hormones in epileptic and non-epileptic women of reproductive age. If the data show a relationship between (i) falling levels of plasma progesterone and allopregnanolone, (ii) increased levels of DHEA or pregnenolone or (iii) increased ratios of estrogen/progesterone, DHEA/progesterone, DHEA/allopregnanolone, pregnenolone/allopregnanolone and seizure manifestations and EEG documented interictal spike and seizure activity it would support the hypothesis that alterations in the levels of these steroid hormones are related to seizure exacerbations in women with catamenial epilepsy.