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Hormone Replacement Therapy and Associated Risk of Stroke in Postmenopausal Women
Rozenn N. Lemaitre, PhD, MPH;
Susan R. Heckbert, MD, PhD;
Bruce M. Psaty, MD, PhD;
Nicholas L. Smith, PhD;
Robert C. Kaplan, PhD;
W. T. Longstreth, Jr, MD, MPH
Arch Intern Med. 2002;162:1954-1960.
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 [0.69-1.37]) 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 [0.43-1.28]) 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.
From the Departments of Medicine (Drs Lemaitre, Psaty, and Smith) and
Epidemiology (Drs Heckbert, Psaty, Smith, and Longstreth), Cardiovascular
Health Research Unit, and the Department of Neurology (Dr Longstreth), University
of Washington, Seattle; and the Department of Epidemiology and Social Medicine,
Albert Einstein College of Medicine, New York, NY (Dr Kaplan).
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