Higher Stroke Risk Tied to Early Menopause


SAN DIEGO — Women who reach menopause before the age of 42 years are twice as likely to suffer a stroke in later life as women who reach menopause after age 42, according to a new analysis of data from the Framingham Heart Study presented at the International Stroke Conference.

The study involved prospectively collected data from 1,430 women who were followed for an average of 22 years, said Lynda Lisabeth, Ph.D., of the University of Michigan, Ann Arbor. All participants were stroke-free at 60 years of age, experienced natural menopause, and had never taken estrogen before menopause. The use of self-reported data on the age of menopause was a limitation of the study, Dr. Lisabeth acknowledged.

In all, the women had 234 ischemic strokes at an average age of 80 years. The unadjusted rate of strokes was 23% among women who reached menopause before the age of 42 years, 16% among women who reached menopause between the ages of 42 and 54 years, and 11% among women who reached menopause at age 55 years or older.

After adjustment for age, systolic blood pressure, atrial fibrillation, diabetes, current smoking, cardiovascular disease, and estrogen use after menopause, the investigators determined that the age of menopause was an independent predictor of ischemic stroke.

Compared with women who reached menopause before age 42 years, women who reached menopause between ages 42 and 54 years were half as likely to experience a stroke, and those who reached menopause at age 55 or older were 69% less likely to experience a stroke.

In other words, women who reached menopause before age 42 years were 2.03-fold more likely to have a stroke than the other women. This difference was statistically significant.

The study showed that 4%–5% of strokes in women can be attributed to menopause before age 42, Dr. Lisabeth said.

About 1%–2% of women reach menopause at or before age 40 years, which is referred to as “premature ovarian failure.” The etiology of this condition remains unknown, but investigators are certain that it's different than natural menopause. About 3%–10% of women experience “early” menopause, defined as natural menopause before age 45 years.

Several possible mechanisms could account for the increased rate of stroke, Dr. Lisabeth said. Estrogen may play a role, since estrogen deficiency is thought to promote cardiovascular disease through functional or structural changes in arteries. Androgens and sex hormone-binding globulin are also risk factors for cardiovascular disease.

Additional studies with measures of endogenous hormones would be needed to unravel the relationship between the hormonal changes of menopause and ischemic stroke, she said.

The study was supported by the National Heart, Lung, and Blood Institute and the National Institute of Neurological Disorders and Stroke. Dr. Lisabeth said that she had no conflicts of interest.

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