Trial Backs Progesterone for Subset of Women With Epilepsy

Allison Shelley

December 05, 2011

December 5, 2011 (Baltimore, Maryland) — Long-awaited results from a phase 3 National Institutes of Health trial suggest that progesterone can help curb catamenial seizures in some women.

"Progesterone can provide a clinically important benefit for a substantial portion of women with catamenial seizures," Andrew Herzog, MD, from Harvard University School of Medicine, Boston, Massachusetts, said in a news release. "The level of perimenstrual seizure exacerbation is a significant predictor of women most likely to benefit from this hormonal therapy."

"Historic Finding"

This is an historic finding, session coordinator Doodipala Samba Reddy, PhD, from the Texas A&M Health Science Center, College Station, said here at the American Epilepsy Society (AES) 65th Annual Meeting. "While progesterone is not indicated for all women across the board," he pointed out, "it may make sense for some."

An estimated 30% of women have persistent seizures despite receiving antiepileptic drug treatment. Seizures may increase either at the time of menstruation or at ovulation. The increase is attributed to fluctuations of estrogen and progesterone, an epilepsy subset called catamenial seizures. If hormones can influence seizures, researchers say, they may also play a role in treatment.

Progesterone is not widely prescribed because its benefits have yet to be conclusively demonstrated. This highly anticipated trial was positioned to inform treatment decisions. Investigators had hoped to see stronger numbers, but the progesterone study group was left with a mild response and more questions for future study.

Lukewarm Response

The randomized, double-blind, placebo-controlled multicenter trial compared the short-term efficacy and safety of adjunctive cyclic progesterone therapy with that of placebo.

The study included 462 women with partial epilepsy and intractable seizures. Patients were randomly assigned in a ratio of 2:1 to receive either progesterone treatment or placebo, stratified by catamenial and noncatamenial phase.

The researchers found that there was no significant difference in the number of responders for all seizures.

Table 1. Response for All Seizures

Phase Progesterone (%) Placebo (%) P Value
Catamenial 23 20 .718
Noncatamenial 20 19 .887

Prespecified exploratory analysis showed that the level of perimenstrual seizure exacerbation was a significant predictor of responders for progesterone (P = .001), but not placebo.

Table 2. Response With Increasing Perimenstrual Activity

Outcome Progesterone (%) Placebo (%)
Number of responders 21 - 57 19 - 20
Reduction in seizure frequency 26 - 71 25 - 26

Asked by Medscape Medical News to comment on the findings, Mona Sazgar, MD, from the University of California, Irvine, School of Medicine said she too was hoping to see a strong response across the board and was disappointed that this did not happen. "But it is still encouraging there was a benefit in a subgroup of patients."

Dr. Sazgar also presented study results at the meeting. She showed that nearly three quarters of the 567 women with catamenial seizures in her analysis had medically refractory epilepsy, which was a rate twice that of female patients without catamenial seizures.

More of these patients also had primary generalized epilepsy, were more likely to have lesions, and tended to experience more seizures during their pregnancies.

"There is definitely something going on with these patients," Dr. Sazgar said. "It's fascinating to observe and very, very difficult to treat."

She pointed to the risks of hormonal therapies, which include blood clots, depression, and potential long-term cerebrovascular consequences, but she admitted that the immediate dangers surrounding uncontrolled seizures often take precedence. "We consider the lowest possible dose when weighing the risks and benefits," she said.

This study was funded by the National Institutes of Health. Dr. Herzog, Dr. Reddy, and Dr. Sazgar have disclosed no relevant financial relationships.

American Epilepsy Society 65th Annual Meeting: Abstract 3.191. Presented December 3, 2011.

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