Although a subgroup of patients with catamenial epilepsy appears to benefit from progesterone therapy, the condition is more likely than noncatamenial epilepsy to be refractory and accompanied by brain lesions, according to results from two separate studies.
BALTIMORE—Progesterone appears to benefit a subgroup of patients with catamenial epilepsy, researchers reported at the 65th Annual Meeting of the American Epilepsy Society.
“Women who have intractable seizures that show greater than two- or threefold exacerbation perimenstrually may warrant a trial of natural progesterone supplement on the basis of our trial and our clinical experience,” Andrew G. Herzog, MD, Professor of Neurology at Harvard Medical School in Boston, told Neurology Reviews.
However, women with catamenial epilepsy are more likely than those with noncatamenial epilepsy to have refractory seizures and brain lesions, according to the results of a separate study.
“It is amazing how different this population is from the general epilepsy population,” said Mona Sazgar, MD, Director of the Comprehensive Epilepsy Program at the University of California, Irvine (UCI).
Greater Benefits for Worse Exacerbations
Dr. Herzog and colleagues randomized 294 women with partial epilepsy and intractable seizures to progesterone or placebo for three menstrual cycles, stratifying the patients by whether their seizures were catamenial. Next, the investigators compared proportions of 50% responders and changes in seizure frequency between the two treatment groups.
Although the researchers’ primary analysis found no significant differences between the treatment groups, their exploratory analyses found that progesterone benefited women who had high levels of perimenstrual seizure exacerbation at baseline. With increasing levels of perimenstrual exacerbation, the proportion of progesterone responders increased from 21% to 57%, compared with an increase of 19% to 20% among placebo responders. In addition, reductions in seizure frequency with progesterone progressed from 26% to 71%, while such reductions with placebo progressed from 25% to 26%, with increasing levels of perimenstrual exacerbation.
The FDA has not yet approved progesterone for regular use in women with catamenial epilepsy, Dr. Herzog noted. Before it can do so, a new trial needs to confirm the current trial’s findings while using progesterone’s effects on women with high levels of perimenstrual seizure exacerbation as its primary outcome. Dr. Herzog added that despite the hormone’s apparent benefits in this subgroup, other treatments—such as depot medroxyprogesterone or gonadotropin-releasing hormone analogues—are better suited to women with other types of catamenial epilepsy.
Catamenial Versus Noncatamenial Trends
Dr. Sazgar and Avriel Linane, DO, a Neurology Resident at UCI, retrospectively analyzed data on 217 women of reproductive age with epilepsy and found that catamenial epilepsy was associated with several distinct trends.
Among the cohort’s 26 patients with catamenial epilepsy, 73%—almost double the 37% rate seen among noncatamenial patients in the same age group—had refractory seizures. Fourteen of the 26 patients with catamenial epilepsy (54%) and 11 of the 17 patients with catamenial partial epilepsy (65%) had MRI lesions. In contrast, about 20% to 30% of the general population with partial epilepsy has MRI lesions, said Dr. Sazgar. Thirty-five percent of patients with catamenial epilepsy had primary generalized epilepsy, compared with 17% of the noncatamenial patients in the cohort. Dr. Sazgar also noted that of the eight patients with catamenial epilepsy who had children, six (75%) reported having an increase in seizures during their pregnancy.
“So what is it about this population?” Dr. Sazgar asked of the patients with catamenial epilepsy. “To find out, I think the next step is looking at the brain circuitry involved.”
She described tentative plans for a prospective study that investigates this circuitry by comparing brain images taken during periods of seizure exacerbation and periods of seizure control. The study may use such techniques as diffusion tensor imaging and sodium MRI to look for menstruation-related changes in patients’ hippocampi, amygdalae, and hypothalamic-pituitary-ovarian pathways, said Dr. Sazgar.
—Jack Baney