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From the Neurovascular Service (Drs. Johnston and Gress), Department of Neurology, University of California, San Francisco, and the Division of Public Health Biology and Epidemiology (Dr. Colford), School of Public Health, University of California, Berkeley, CA.
Address correspondence and reprint requests to Dr. S. Claiborne Johnston, Department of Neurology, Box 0114, University of California, San Francisco, 505 Parnassus Street, San Francisco, CA 94143-0114.
Objective: The objective of this study is to estimate the risk of subarachnoid hemorrhage produced by oral contraceptive use.
Methods: Studies published since 1960 were identified using MEDLINE, Cumulated Index Medicus, Dissertation Abstracts On-line, and bibliographies of pertinent articles. Two independent reviewers screened published cohort and case-control studies that evaluated the risk of subarachnoid hemorrhage associated with oral contraceptives. Eleven of 21 pertinent studies met predefined quality criteria for inclusion in the meta-analysis. Relative risk(RR) estimations evaluating subarachnoid hemorrhage risk in oral contraceptive users compared with nonusers were extracted from each study by two independent reviewers. Study heterogeneity was assessed by design type, outcome measure(mortality versus incidence), exposure measure (current versus ever use), prevailing estrogen dose used, and control for smoking and hypertension.
Results: The overall summary RR of subarachnoid hemorrhage due to oral contraceptive use was 1.42 (95% CI, 1.12 to 1.80; p = 0.004). When the two study results failing to control for smoking were excluded from the analysis, a slightly greater effect was seen, with an RR of 1.55 (95% CI, 1.26 to 1.91;p < 0.0001). In the six studies controlling for smoking and hypertension the RR was 1.49 (95% CI, 1.20 to 1.85;p = 0.0003). High-estrogen oral contraceptives appeared to impart a greater risk than low-dose preparations in studies controlling for smoking, but the difference was not significant (high-dose RR, 1.94; 95% CI, 1.06 to 3.56; low-dose RR, 1.51; 95% CI, 1.18 to 1.92).
Conclusions: This meta-analysis of observational studies suggests that oral contraceptive use produces a small increase in the risk of subarachnoid hemorrhage.
Received December 24, 1997. Accepted in final form April 3, 1998.
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