Oral contraceptives and the risk of gallbladder disease: A meta-analysis

Objectives. This study was designed to assess the risk of gallbladder disease due to oral contraceptive use by conducting a thorough literature review. Methods. Controlled epidemiologic studies published through March 1992 were systematically searched and evaluated. Of 25 studies (27 publications), 9 could stand the test of critical appraisal with respect to validity. Restriction to these studies was judged to circumvent publication bias at the same time. Results. Oral contraceptive use is associated with a slightly and transiently increased rate of gallbladder disease. The results of six selected studies in which asymptomatic women were screened for gallstones were strikingly similar. Pooling of these results yielded an odds ratio, for ever vs never oral contraceptive use, of 1.36. A dose-effect relationship was indicated, suggesting that modern low-dose oral contraceptives are safer than older formulas, but an effect cannot be excluded. Conclusions. Considering the large efforts already devoted to this exposure-disease relationship, the probably weak effect, and the rapidly changing formulas of oral contraceptives, the authors suggest that the safety of new oral contraceptives be evaluated by studying bile saturation and biliary function rather than by waiting for gallbladder disease to develop.