Prior studies of the association between oral contraceptives (OCs) and gallbladder disease (GBD) have yielded conflicting results. To clarify this association, a retrospective (historical) cohort study was performed on a very large data base including 1980 and 1981 Medicaid billing data from the states of Michigan and Minnesota in which 138,943 users of OCs were compared with 341,478 nonusers. The crude relative risk (RR) and 95% confidence interval (CI) for symptomatic GBD resulting in medical care was 1.14 (CI 1.09 to 1.20), with a clear dose-response (P less than 0.001). Age markedly modified the effect of OCs on GBD. The RR (CI) decreased from 3.1 (2.7 to 3.6) in women 15 to 19 years old to 1.2 (0.9 to 1.5) in women 40 to 44 years old, providing an explanation for previously conflicting reports. The effects of a number of other risk factors on GBD, some which have been controversial, were also confirmed. Adjustment for these did not change the results. In conclusion, OCs are risk factors for GBD, although the risk is of sufficient magnitude to be of potential clinical importance only in young women.
PIP: To clarify the association between oral contraceptives (OCs) and gallbladder disease (GBD), a retrospective (historical) cohort study was performed with 1980 and 1981 Medicaid billing data from the states of Michigan and Minnesota in which 138,943 users of OCs were compared to 341,478 nonusers. There were 12,292 cases of GBD that required medical attention during the 2-year study, giving an overall prevalence rate of 25.6/1000 persons over the 2 years. Of the 138,943 OC users in this study, 3889 had GBD, giving a prevalence of 28.0/1000 persons in the 2-year study. Of the 341,478 nonusers, 8403 had GBD, resulting in a prevalence rate of 24.6/1000 persons in these 2 years. The overall prevalence rate in the unexposed subjects in Michigan was higher than that in Minnesota (28.5 vs. 12.3/1000 persons in the 2 year, respectively). This difference in prevalence by state may rest in part from differences in urbanization or to the known differences in racial distribution. Comparing Minnesota with Michigan, blacks are markedly underrepresented (5.9% versus 35.6%), Indians are overrepresented (3.9% versus 0.37%), and Orientals are overrepresented (5.7% versus 0.48%). Alternatively, this difference in prevalence by state may result from administrative dissimilarities between the 2 Medicaid programs, such as in differences in the number of diagnoses that can be provided per visit and the number of visits that can be included on each claim form. The results indicate that subsequent analyses need to be state specific or state adjusted. The crude relative risks confidence intervals for the effect of OCs on GBD were 1.14 overall, 1.08 for Michigan, and 1.39 for Minnesota. While the proportion of subjects using OCs decreased with advancing age, the prevalence of GBD increased steadily with age in both users and nonusers. Stratification by 5-year age intervals revealed age to be a strong modifier of the effect of OCs on GBD, with younger women at a higher risk of GBD from OCs than middle-aged women. The effects of a number of other risk factors on GBD also were confirmed. Adjustment for these failed to change the results. The relationship between OCs and GBD remained statistically significant even after age, state, and each confounding variable was controlled for logistic regression. In sum, OCs are risk factors for GBD, although the risk is of sufficient magnitude to be of potential clinical importance only in young women.