Allopregnanolone Level and Seizure Frequency in Progesterone Treated Women with Epilepsy

In the June 18, 2014, articles ahead of press in the journal Neurology, Drs. Herzog and others representing the progesterone trial study group present data about the relationship of pregnenolone levels and seizure frequency in women treated with progesterone. 

• The NIH progesterone trial compared the effectiveness of adjunctive cyclic natural progesterone therapy versus placebo treatment of intractable seizures in 294 patients randomized to progesterone or placebo, stratified by either having catamenial or non-catamenial epilepsy. 
• Treatments were compared on proportions of 50% responders. Serum AP levels were measured by radioimmunoassay from 155 women with intractable focal onset seizures.
• The authors found no significant correlation between percent of changes in Allopregnanolone levels and seizure frequencies from baseline to treatment for either group. There was a significant correlation for the subset of patients who showed a significantly greater responder rate in the post-hoc analysis of the trial. 
• These were people who had three-fold or greater increase in average daily seizure frequency peri-menstrually compared with the mid-follicular and mid-luteal phases and significantly for C1 > 3 progesterone treated subjects but not other groups. 

The findings support Allopregnanolone is a mediator, a seizure reduction in progesterone treated women who have a substantial level of peri-menstrually exacerbated seizures.