Abstracts

Rationale: Estrogen has been shown to be proconvulsant in many animal seizure models, however clinical examples of this effect are infrequent. We present the case of a man with epilepsy who experienced seizure exacerbation while undergoing gender transformation using estrogen therapy. Methods: We reviewed the seizure course of a man undergoing initial gender transformation with reproductive hormone modulation. Results: The patient is a 20 year-old right-handed adopted man with a history of seizures since age 10 thought to be typical absence seizures. He has no known risk factors for epilepsy. At age 10, he was treated with valproate and did well with no side effects and had only one seizure per year. He presented with increased seizure frequency over the previous five months which now included convulsive seizures, and had undergone antiepileptic drug trials of carbamazepine, oxcarbazepine, topiramate and zonisamide without achieving seizure control. Concomitant with seizure exacerbation, he had started estradiol 8 mg per day and spirinolactone 100 mg per day (antiandrogen) as pre-operative transgender treatment. The usual maximum dose of estradiol for gender transformation is 4 mg per day. Brain MRI was normal, interictal EEG showed right frontal spikes and neuropsychological testing showed normal intellect. Under our care, the patient was changed back to valproate with therapeutic levels, however, seizure frequency increased with daily convulsive seizures, at times occurring in clusters. The patient underwent video-EEG monitoring which showed nocturnal seizures with right hemisphere onset and frontal lobe semiology. Interictal findings were right frontal and right anterior temporal spikes. Rufinamide was started as adjunctive therapy with no significant improvement in seizure frequency. In order to improve seizure frequency, the patient saw an endocrinologist for the transgender community who discontinued the estradiol due to the very high dose; stable doses of rufinamide 1200 mg per day and valproate 1000 mg per day were maintained. The patient’s seizure frequency decreased to zero over the course of 3 weeks. Conclusions: The clinical course suggests that seizure frequency was exacerbated by high dose estrogen therapy in this young man with frontal lobe epilepsy. This case demonstrates a sustained and severe proconvulsant effect of estrogen in a vulnerable substrate and the time course of seizure improvement is consistent with slow release of estrogen stored in adipose tissue.