Hormone replacement therapy and associated risk of stroke in postmenopausal women

Background: There is little information about the risk of stroke in relation to time since initiation of hormone therapy and in relation to estrogen dose. Methods: We conducted a population-based case-control study at Group Health Cooperative (GHC), a health maintenance organization in the greater Seattle (Wash) area, to assess the association of hormone replacement therapy with the risks of incident ischemic and hemorrhagic stroke. Cases were all postmenopausal women with incident stroke at GHC during July 1989 through December 1998 (726 ischemic strokes and 213 hemorrhagic strokes). Controls were randomly selected from GHC enrollees and frequency matched to cases on age and calendar year (n=2525). Hormone use was assessed from computerized pharmacy data. We reviewed the medical record to confirm eligibility and assess other risk factors. Results: After risk factor adjustment, ischemic stroke was not associated with current use of estrogen with progestin (odds ratio [95% confidence interval]: 0.97 [0.691.37]) or without (0.94 [0.72-1.23]) compared with never use. Similarly, hemorrhagic stroke was not associated with current use of estrogen with progestin (0.74 [0.431.28]) or without (1.06 [0.71-1.56]). However, the risks of ischemic stroke and hemorrhagic stroke were increased 2-fold during the first 6 months of hormone use (ischemic stroke: 2.16 [1.04-4.49],hemorrhagic stroke: 2.20 [0.83-5.81]). Risk of ischemic stroke also increased with estrogen dose (P for trend =.03). Conclusion: The transitory increase in risks of ischemic stroke and hemorrhagic stroke associated with initiation of hormone replacement therapy merits further investigation.