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Evidence Against Using Hormone Therapy to Prevent Stroke

This small study supports previous findings suggesting that hormone therapy should not be used specifically to reduce a woman's risk for stroke.

In two recent clinical trials testing the efficacy of menopausal hormone therapy (HT) in preventing cardiovascular disease, researchers observed an increased incidence of events in the first 6 to 12 months of HT (WEST, N Engl J Med 2001; 345:1243, and HERS, JAMA 1998; 280:605). To explore the association between HT initiation and stroke risk in a population-based cohort, Lemaitre and colleagues conducted a case-control study at one Seattle HMO. Cases were postmenopausal women with ischemic (n=726) or hemorrhagic (n=213) stroke who had focal neurologic symptoms for at least 24 hours or radiographic evidence of infarction. Hemorrhages included subarachnoid, intraventricular, and intraparenchymal bleeds. Controls (n=2525) were postmenopausal women randomly selected from the HMO population and age- and year-matched to cases. Exposure was defined as current, ever, or never estrogen use, with or without a progestin. The study was powered to demonstrate a 25% lower risk for ischemic stroke and a 40% lower risk for hemorrhagic stroke associated with HT use. Pharmacy records were used to determine the time elapsed between HT initiation and stroke; however, an insufficient number of low-dose estrogen users prevented an adequately powered analysis of this category of HT.

Cases had a greater burden of vascular risk factors, particularly hypertension and coronary artery disease, than did controls. Ischemic, but not hemorrhagic, stroke cases were less likely than controls to be current or past HT users. After vascular risk factors were controlled for, there was no statistically significant relation between estrogen use (current or ever) and ischemic or hemorrhagic stroke. HT use of less than 6 months' duration was associated with a nonsignificantly increased risk for ischemic (odds ratio, 1.86) and hemorrhagic (OR, 1.70) stroke. Higher estrogen dose (>0.625 mg) was associated with higher risk for ischemic stroke. Dose did not affect hemorrhagic stroke risk. Longer duration of therapy did not increase risk for stroke.

Comment: This study supports earlier findings of an apparent increased risk for stroke in the first 6 months after HT initiation. The mechanism of this association remains unexplained but has important implications for selecting patients to begin HT. On the basis of the WEST results, there is no indication for beginning HT specifically to prevent recurrent stroke. The current study was limited by the number of cases; a relatively small association between HT use and stroke may have been missed.

— Karen Furie, MD

Dr. Furie is Assistant in Neurology, Massachusetts General Hospital, Boston.

Published in Journal Watch Neurology December 6, 2002

Citation(s):

Lemaitre RN et al. Hormone replacement therapy and associated risk of stroke in postmenopausal women. Arch Intern Med 2002 Sep 23; 162:1954-60.

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