Abstracts

RATIONALE: Estrogen hormone replacement therapy is widely used in menopause to prevent the consequences of chronic low estrogen state, such as osteoporosis and increased risk of cardiovascular ischaemic disease. Estrogens potentiate excitatory cellular function in limbic structures, induce seizures and lower seizure threshold in animal models of seizures and facilitate interictal epileptiform discharges and seizures in epileptic women (1). A questionnaire survey suggested that hormone replacement therapy may exacerbate seizures during perimenopause or menopause (2). One case of premarin-related seizures in menopause has previously been reported (3). Here, I report two cases of estrogen-related seizures in menopause.
METHODS: The subjects were two women referred for evaluation of possible seizures. The evaluation included standard clinical, EEG and neuroimaging assessment and reproductive endocrine histories.
RESULTS: Case 1: A woman without seizure risk factors had four partial seizures with secondary generalization during two years of treatment with an oral contraceptive at the age of 28-30. Seizures ceased after discontinuation of the contraceptive. She was well until the age of 53 when, one year of her last period, she was treated with premarin for hot flushes and sweating. Four weeks later, she had a seizure. Examination and EEG were normal. MRI scan of the brain showed several 1-3 mm foci of high T2 signal intensity suggestive of small vessell ischaemic changes, including one in the left hippocampal region. Premarin was stopped. One more seizure occurrred one year later. Gabapentin 300 mg b.i.d. was started. no further seizures have occurred during a 4 year follow up.
Case 2. A 32 year old woman had a history of episodes of dizziness, intense fear, anxiety and altered awareness which began one year after menarche. The episodes occurred mainly during the week prior to menstruation. They stoped during pregnancy at the age of 28. At the age of 32, she developed irregular menses and menorrhagia, for which she undewent hysterectomy and bilateral oophorectomy. Estrogen replacement therapy was started after hysterectomy. One month later, the spells recurred. Two weeks later, she had a major clonic seizure. Neurological examination and CT examination of the brain were normal. EEG showed independent bitemporal spikes, left greater than right. Phenytoin was started. Seizures persisted. They stopped shortly after discontinuation of estrogen replacement therapy.
CONCLUSIONS: Unopposed estrogen therapy in menopause may activate seizures in women with hormonally sensitive partial seizures, even if the seizures have been quiescent for many years. This finding should be considered before instituting estrogen replacement therapy in menopausal women with a history of epilepsy.