Female Hormone Replacement Therapy May Increase Seizure Frequency

Harden

“Until recently, hormone replacement therapy (HRT) was widely used in menopausal women with epilepsy to alleviate their menopausal symptoms such as hot flashes and vaginal dryness. Now, due to the Women’s Health Initiative findings published in July 2002, showing an increased risk of breast cancer due to HRT, the use of HRT has been drastically curtailed. However, our study shows that even short-term use of HRT, which doctors still prescribe, poses a risk to women with epilepsy”, said Cynthia Harden,M.D., Department of Neurology, Weill Cornell Medical Center in New York City, today at the 58th AES conference in New Orleans.


Study Design

According to Harden, “Previous reports have suggested that HRT could increase seizure activity in women with epilepsy although most women with epilepsy seemed to have used HRT safely. We sought to determine whether adding HRT to the medication regimen of menopausal women with epilepsy was associated with seizure increase.”

Therefore, Harden et al. conducted a randomized, double-blind, placebo controlled trial of the effect of 2 different doses of HRT on seizure frequency in 21 menopausal women with epilepsy taking stable doses of antiepileptic drugs (AEDs) and within 10 years of their last menses. After a three-month prospective baseline, subjects were randomized to receive either placebo, a standard dose of Prempro (0.625 mg daily), or double-dose Prempro daily for a three-month treatment period.

Results

Harden and her colleagues found that Prempro was associated with a dose-related increase in seizure frequency in the menopausal women with epilepsy enrolled in their study. However, the results showed there was no increase in severity of seizures. When asked why they chose Prempro as the drug to be studied Harden responded, “Prempro is the most commonly used HRT, at least at the time of the study, and we wanted to make the study as practical as possible and wanted the results to have the most applicability.” Harden also points out that it is not standard practice for menopausal women to take a double dose of Prempro. Furthermore, she stated that the purpose of this particular aspect of the study design was to advance the dose-rated hypothesis and was not representative of true clinical practice.

Implications of the Study

Based on the findings Harden believes it is important for menopausal women with epilepsy to consult their primary care physician in determining the best course of treatment for their menopausal symptoms. After balancing the risks and benefits, if it is decided to use short-term HRT, Harden recommends that a regimen other than Prempro be used for women with epilepsy. Instead of using a multi-estrogen based therapy coupled with a synthetic progestin, like Prempro, Dr. Harden suggests trying a single estrogen treatment such as the estradiol patch coupled with a natural progesterone for short-term symptom relief. Harden said, “Menopausal women with epilepsy may experience sleep difficulties due to hot flashes which can in turn increase the frequency of their seizures. Treatment of these symptoms, therefore, is clinically important and they could be alleviated, using short-term HRT, although this decision must be carefully considered.”

The abstract of this study is published in Epilepsia 2004, Vol. 45, Supplement 7, p.230-231.

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