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Seizure frequency is associated with age at menopause in women with epilepsy

From the Comprehensive Epilepsy Center (Dr. Harden and B.G. Nikolov), Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY; Department of Neurology (Dr. Koppel), New York Medical College, Metropolitan Hospital Center, New York; Harvard Neuroendocrine Unit (Dr. Herzog), Beth Israel Deaconess Medical Center, Boston, MA; and G.H. Sergievsky Center (Dr. Hauser), Department of Neurology and Department of Epidemiology, College of Physicians and Surgeons of Columbia University, New York, NY.

Address correspondence and reprint requests to Dr. Cynthia L. Harden, Comprehensive Epilepsy Center, Weill Medical College of Cornell University, 525 East 68th Street, Room K-615, New York, NY 10021; e-mail: clharden{at}med.cornell.edu

Objective: To determine whether the age at menopause in women with epilepsy is associated with seizure frequency.

Methods: Women with epilepsy ages 45 and older from urban epilepsy centers were surveyed by interview and chart review for reproductive and general health characteristics, as well as seizure history, including frequency and treatment. Women who were not menopausal (1 year since last menses) were excluded. Subjects were divided into low, high, and intermediate seizure frequency groups. Statistical analyses included a one-way analysis of variance along with post hoc analysis (Bonferroni approach) to calculate pairwise comparisons.

Results: Sixty-eight subjects had a mean age at last menses (menopause) of 47.8 years (SD ± 4.1, range 37 to 59 years). The age at menopause was 49.9 years in the low seizure frequency group (n = 15), 47.7 years in the intermediate seizure frequency group (n = 25), and 46.7 in the high seizure frequency group (n = 28). The difference in age at menopause in the three groups spanned approximately 3 years (p = 0.042). There was a negative correlation between the age at menopause and seizure group based on estimated lifetime seizures (p = 0.014, r = -0.310). No confounding influences such as history of cigarette smoking, number of pregnancies, or use of enzyme-inducing antiepileptic drugs were present.

Conclusions: Seizure frequency or lifetime number of seizures is associated with the timing of cessation of reproductive cycling. Seizures may disrupt hypothalamic and pituitary function or alter neurally mediated trophic effects on the ovary.

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