Abstracts

RATIONALE: We have observed that a group of women with epilepsy who had an early onset of menopause (last menses at 37-45 years) generally had more frequent seizures than women with epilepsy who had a later onset menopause (last menses at 50-56 years). Other investigators have also suggested that women with epilepsy have an increased risk of premature menopause (Klein et al., Epilepsia 2001). We sought to further explore the age of menopause and factors associated with early onset of menopause in women with epilepsy.
METHODS: Sixty-eight women with epilepsy who were naturally menopausal (at least 1 year since last menstrual period) were surveyed by interview and chart review for reproductive characteristics, epilepsy history, and other known factors which affect the onset of menopause. Subjects were obtained from four urban academic medical centers. Subjects were categorized into one of three broad seizure frequency groups; seizure frequency was estimated over the course of the subject[scquote]s epilepsy. Group 1 was [lt]20 seizures in lifetime, Group 2 was [gt]20 seizures in lifetime and [lt]1 seizure/month and Group 3 was [gt]1 seizure/month. Statistical analysis was performed using bivariate correlations (Pearson and Spearman), one-way ANOVA and univariate General Linear Model.
RESULTS: Fifteen women were in Group 1(mean age 55 years), 25 women were in Group 2 (mean age 54 years), and 28 women were in group 3 (mean age 52 years). The mean age of last menses was significantly different between groups (p=0.042); Group 1=49.9 years, Group 2=47.7 years and Group 3=46.7 years. The age of last menses did not change in the subsets of subjects having onset of epilepsy [lt]42 years (n=49) or onset of epilepsy[gt]42 years (n=14). The number of enzyme-inducing antiepileptic drugs (EIAEDs) ever used for 1 year or more significantly negatively correlated with age of last menses (more EIAEDs used correlated with lower age of last menses) and positively correlated with seizure frequency group. Age of onset of epilepsy also significantly negatively correlated with seizure group (earlier age onset correlated with higher seizure frequency group) and positively correlated with age of last menses. When factoring in these 2 confounders, the mean age of menopause in each seizure severity group did not change: Group 1=50 years, Group 2=47.5 years, Group 3=46.5 years.
Four subjects had premature ovarian failure (onset of menopause prior to age 42). Three were in the highest seizure frequency group and 1 was in the intermediate group.
No other factors had significant effects on age of last menses including cigarette use, # pack-years, race, # of children, age of last child, # total AEDs, or # years of any [dsquote]classic[dsquote] AED.
CONCLUSIONS: Seizure frequency may affect the age of menopause, causing it to decrease from a population norm of 50 years to as much as 3 years earlier. The use of EIAEDs may also contribute to this effect. These findings cannot clarify whether central nervous system factors or direct ovarian factors are most important in the relationship of epilepsy to menopause. Further evaluation is needed to rule out confounding effects.
[Supported by: NIH [ndash] National Institute of Neurological Diseases and Stroke, R01 NS38473]