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Risk of ischemic stroke and lifetime estrogen exposure

From the University Hospital Ramon y Cajal (M.A.d.L.), Madrid, Spain; University Hospital Clinico San Carlos (J.A.E., C.F.), Madrid, Spain; Clínica Universitaria de Navarra (E.M-V.), Pamplona, Spain; University Hospital Clínico de Zaragoza (S.S.), Spain; Hospital Sta. Maria del Rosell (A.M.), Cartagena, Spain; University Hospital Virgen del Rocío (E.M.), Sevilla, Spain; Hospital Arnau de Vilanova (A.P.), Valencia, Spain; Hospital Universitari Vall d'Hebrón (J.A-S.), Barcelona, Spain; and Hospital San Pedro de Alcántara (I.C.), Cáceres, Spain.

Address correspondence and reprint requests to Dr. María Alonso de Leciñana, Department of Neurology, University Hospital Ramon y Cajal, Ctra de Colmenar Km 9,100, 28034 Madrid, Spain; e-mail: mariaalonsoleci{at}telefonica.net

Background: Estrogen loss has been related to higher incidence of stroke in postmenopausal women, but randomized trials have demonstrated an increased risk of stroke in women receiving hormone replacement therapy (HRT).

Objective: To assess the relationship between exposure to endogenous ovarian hormones and the risk of noncardioembolic ischemic stroke.

Methods: We conducted a multicenter, age-matched, case-control study in postmenopausal women (case: nonembolic ischemic stroke; control: no stroke) comparing duration of ovarian activity or lifetime estrogen exposure, which was defined as age at menarche to age at menopause. Embolic cardiopathy and unreliable gynecologic data were exclusion criteria. Cardiovascular disease risk factors were recorded. The relationships of the principal variables to the risk of stroke were assessed using a conditional logistic regression analysis.

Results: There were 430 cases and 905 controls in the study. In the multivariate analysis, hypertension (odds ratio [OR]: 2.73; 95% CI: 2.09 to 3.58; p < 0.0001), diabetes (OR: 3.38; 95% CI: 2.53 to 4.52; p < 0.0001), hyperlipidemia (OR: 1.31; 95% CI: 1.01 to 1.7; p = 0.045), lifespan of ovarian activity <34 years (OR: 1.51; 95% CI: 1.13 to 2.03; p = 0.005), and menarche at <13 years of age (OR 1.49; 95% CI: 1.15 to 1.92; p = 0.002) were independently related to an increased risk of stroke. Obesity (OR: 0.73; 95% CI: 0.56 to 0.95; p = 0.021) was related to a lower risk of stroke.

Conclusions: Longer lifetime exposure to ovarian estrogens may protect against noncardioembolic ischemic stroke. However, a very early age of exposure onset could be disadvantageous.

This study received an educational grant from Bristol Myers Squibb. Apart from logistic support, the funding source had no control over the study design, data collection and analysis, or manuscript preparation and decision to publish.

Disclosure: The authors report no conflicts of interest.

Received January 30, 2006. Accepted in final form September 20, 2006.

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