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Use of Low-Dose Oral Contraceptives and Stroke in Young Women

Stephen M. Schwartz, PhD, MPH; David S. Siscovick, MD, MPH; W.T. Longstreth Jr., MD, MPH; Bruce M. Psaty, MD, PhD, MPH; R. Kevin Beverly, MS; T.E. Raghunathan, PhD; Danyu Lin, PhD; and Thomas D. Koepsell, MD, MPH
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From University of Washington, Seattle, Washington. Acknowledgments: The authors thank the hospital record administrators and physicians who assisted in identifying patients for this study; Fran Chard, Karen Graham, and Carol Handley-Dahl for abstracting medical records; Judy Kaiser, Marlene Bengeult, Carol Ostergard, Denise Horlander, and Barb Twaddell for recruiting and interviewing case-patients and controls; Sandy Tronsdal and Jill Ashman for coordinating these activities; and all of the women who participated in the study. Grant Support: By contract HD-1-3107 with the National Institute of Child Health and Human Development. Requests for Reprints: Stephen M. Schwartz, PhD, Cardiovascular Health Research Unit, 1730 Minor Avenue, Suite 1360, Seattle, WA 98101. Current Author Addresses: Drs. Schwartz, Siscovick, Psaty, Lin, and Koepsell: Cardiovascular Health Research Unit, 1730 Minor Avenue, Suite 1360, Seattle, WA 98101. Dr. Longstreth: Harborview Medical Center, Department of Neurology, Box 359775, Seattle, WA 98195. Dr. Raghunathan: Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI 48106-1248.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1997;127(8_Part_1):596-603. doi:10.7326/0003-4819-127-8_Part_1-199710150-00003
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Background: Low-dose oral contraceptives are widely used, but there are limited data on the cerebrovascular risks associated with these medications.

Objective: To determine whether use of low-dose oral contraceptives influences the risk for stroke.

Design: Population-based case–control study.

Setting: Women 18 to 44 years of age who resided in western Washington State between 1991 and 1995.

Participants: Patients with ischemic stroke (n = 60), hemorrhagic stroke (n = 102), and other types of stroke (n = 11) and controls identified through random-digit dialing (n = 485).

Measurements: Details about oral contraceptive use and other risk factors for stroke were obtained through in-person interviews.

Results: The estimated incidences of hemorrhagic stroke and ischemic stroke were 6.4 and 4.3 per 100 000 women-years, respectively. Compared with women who had never used oral contraceptives (after adjustment for risk factors for stroke), current users of low-dose oral contraceptives had estimated odds ratios of 0.93 (95% CI, 0.37 to 2.31) for hemorrhagic stroke and 0.89 (CI, 0.27 to 2.94) for ischemic stroke. Compared with past users of oral contraceptives, current users had odds ratios of 1.41 (CI, 0.67 to 2.96) for hemorrhagic stroke and 1.37 (CI, 0.49 to 3.81) for ischemic stroke. For past users compared with never users, the odds ratios were 0.59 (CI, 0.30 to 1.18) for hemorrhagic stroke and 0.57 (CI, 0.25 to 1.32) for ischemic stroke. The odds ratio for hemorrhagic stroke in current users of low-dose oral contraceptives containing norgestrel or levonorgestrel was elevated (3.23 [CI, 1.24 to 8.41]). Among patients with hemorrhagic stroke, the odds ratio for aneurysmal bleeding associated with current use of low-dose oral contraceptives containing norgestrel or levonorgestrel was 4.46 (CI, 1.58 to 12.53).

Conclusions: The overall risk for stroke and type of stroke was not increased among current users of low-dose oral contraceptives in the study population. Larger studies are needed to clarify both the relation of risk for stroke to past use of oral contraceptives and the possible association between current use of norgestrel-containing oral contraceptives and hemorrhagic stroke.


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Figure 1.
Odds ratios and 95% CIs for stroke in current users of low-dose oral contraceptives. Top.Bottom.

For total stroke by personal characteristics. According to progestin type, by type of stroke. * Compared with women who were not current users, adjusted for age (continuous), treated diabetes (yes, no), ethnicity (African American, other), and other risk factors for stroke listed. For example, odds ratios according to smoking are adjusted for age (continuous), treated diabetes (yes, no), ethnicity (African American, other), body mass index (BMI) (continuous), and treated hypertension (yes, no). † Compared with women who were not current users, adjusted for age (continuous), cigarette smoking (current, not current), ethnicity (African American, other), treated hypertension (yes, no), treated diabetes (yes, no), and body mass index (continuous). ‡ Compared with women who were not current users, adjusted for age (years), treated hypertension (yes, no), smoking (current, past, never), race (white non-Hispanic, African American, other), and average frequency of alcohol use in the year before the reference date (≥1 time per week, 1 to 3 times per month, < 1 time per month).

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