Abstracts

Rationale: Since 1) anovulatory cycles have higher estradiol/progesterone (E/P) ratios during the luteal phase than ovulatory cycles and 2) reproductive steroids have neuroactive properties such that estradiol may promote and progesterone may lessen seizures, we conducted an exploratory investigation to determine if seizure frequency differed between anovulatory and ovulatory cycles in women with intractable focal onset seizures. If so, we determined whether the difference was related to the midluteal serum E/P ratios. Methods: 281 women, 13-48 years old, participated in the 3-month baseline phase of a prospective, multicenter investigation of adjunctive cyclic progesterone therapy for intractable focal onset seizures. The data come from the seizure-menses charts of 92 women who had both anovulatoy and ovulatory cycles during the baseline phase. Mid luteal progesterone levels ?5 ng/ml were used to designate cycles as ovulatory. Average daily seizure frequency (ADSF) for all seizures combined and each type of seizure considered separately (generalized tonic clonic seizures - GTCS, complex partial seizures - CPS, simple partial seizures - SPS) were compared between anovulatory and ovulatory cycles using paired t-tests. A relationship between the proportional differences in ADSF, i.e. anovulatory/ovulatory ADSF ratios, and the midluteal E/P levels, i.e. anovulatory/ovulatory E/P ratios, was determined using bivariate correlational testing. Results: ADSF was 29.5% greater for GTCS during anovulatory than during ovulatory cycles (anovulatory: .237 .488 v ovulatory: .183 .440; t = 2.324, p = .028) (Table 1). ADSF did not differ significantly for CPS or SPS or for all seizures combined. The likelihood of finding a significant difference, i.e. power of the comparison, was .1068 for CPS and .0506 for SPS. Rates of anovulatory cycles were similar for GTCS (26.0%), CPS (28.8%) and SPS (26.3%) (?2 = N.S.). Anovulatory/ovulatory GTCS ADSF ratios correlated significantly with anovulatory/ovulatory E/P ratios (Spearman rho = .663, p = .005). Conclusions: Seizure frequency is significantly greater for GTCS, but not CPS or SPS, during anovulatory cycles than during ovulatory cycles. Since the increase in generalized seizure frequency during anovulatory cycles correlates with the proportional difference in mid luteal serum E/P level ratios between anovulatory and ovulatory cycles, these finding support a possible role for reproductive steroids in influencing the rates of seizure occurrence. Although seizure frequency is related to anovulation for GTCS only, the three seizure types (GTCS, CPS and SPS) do not differ in anovulatory rates. Supported by NIH R01 NS39466