Seizure exacerbation associated with inhibition of progesterone metabolism

The reduced progesterone metabolite tetrahydroprogesterone is a potent positive modulator of GABA(A) chloride conductance that exerts powerful neuroinhibitiory and antiseizure effects in animal models. Cyclic natural progesterone use may lessen seizure frequency in women with catamenial seizure exacerbation. We report a case in which efficacy was eliminated during concomitant treatment with a reductase inhibitor. The observation suggests that a reduced metabolite, rather than progesterone itself, was responsible for improved seizure control.