Oral contraceptives and the risk of subarachnoid hemorrhage: a meta-analysis

Abstract

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.

PIP: Both case-control and cohort studies have evaluated the risk of subarachnoid hemorrhage (SAH) among oral contraceptive (OC) users and identified relative risks as low as 0.5 and as high as 6.5. To determine whether OC use is indeed a risk factor for SAH after accounting for the variability in study designs and results, a meta-analysis was conducted of the 11 salient independent studies included in the research literature. The summary estimate of effect for all studies was a relative risk (RR) of 1.42 (95% confidence interval (CI), 1.12-1.80). There was a trend toward smaller RRs in the most recent studies, presumably as a result of decreases in the estrogen dose of modern OCs. In the 6 studies that controlled for both smoking and hypertension, the summary RR was 1.49 (95% CI, 1.20-1.85). Only 2 of the 11 studies found a protective effect of current OC use on SAH risk, and it was nonsignificant. Taken together, these studies support a weak positive association between OC use and SAH risk. In the US, an additional 430 patients each year with OC-related SAH would be expected. For most women, the SAH risk is inconsequential in evaluating the decision about OC use. However, for women at high risk of SAH due to unruptured aneurysms, a strong positive family history, smoking, or hypertension, it may be advisable to consider alternative contraceptive methods until more data are available.