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Risk of Stroke in Women Exposed to Low-Dose Oral Contraceptives
A Critical Evaluation of the Evidence
Wee-Shian Chan, MD, FRCPC, MSc;
Joel Ray, MD, FRCPC, MSc;
Eugene K. Wai, MD;
Shiphira Ginsburg, MD, MEd, FRCPC;
Mary E. Hannah, MDCM, MSc;
Paul N. Corey, PhD;
Jeffrey S. Ginsberg, MD, FRCPC
Arch Intern Med. 2004;164:741-747.
Background Use of the oral contraceptive pill (OCP) has been reported to be associated with stroke. With current OCPs containing less than 50 µg of ethinyl estradiol, and many earlier studies reporting the association between OCPs and stroke, subjected to biases, we determined whether such an association exists and, if so, the magnitude of the risk.
Methods Two independent searches were conducted to obtain relevant articles from MEDLINE, EMBASE, and Science Citation (1970 to June 2000). Eligible articles published in English describing OCP use and stroke outcomes were retrieved, and relevant data were abstracted. Pooling of results from these studies was performed using odds ratios (ORs) provided, and heterogeneity was calculated using  2 analysis.
Results From 779 potential articles, 36 eligible studies describing 20 distinct populations were retrieved (4 cohort and 16 case-control studies). The pooled OR from the cohort studies demonstrated no increased stroke risk with OCP use (0.95; 95% confidence interval [CI], 0.51-1.78; P = .01); the pooled OR from the case-control studies showed a significant association (2.13; 95% CI, 1.59-2.86; P<.001). The risk of stroke with OCP use, however, was significant only with thrombotic stroke (2.74; 95% CI, 2.24-3.35; P = .009) and not with hemorrhagic stroke or stroke death. There was statistically significant heterogeneity among these studies, and potential biases and confounders were not adequately addressed.
Conclusions These results cast doubt on a true association between low-dose OCPs and stroke because of the low absolute magnitude of the ORs, the severe methodological limitations, and the ORs of less than 1.0 in the cohort studies. The association is tenuous at best and perhaps nonexistent.
From the Departments of Medicine (Drs Chan, Ray, and Ginsburg) and Public Health Sciences (Drs Wai and Corey) and the Department of Obstetrics and Gynecology, Sunnybrook and Women's College Health Sciences Centre (Dr Hannah), University of Toronto, Toronto, Ontario; University of Toronto Maternal Infant and Reproductive Health Research Unit at the Centre for Research in Women's Health (Dr Hannah); and the Department of Medicine, McMaster University, Hamilton, Ontario (Dr Ginsberg). The authors have no relevant financial interest in this article.
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