Oral contraceptives and cardiovascular outcomes: cause or bias?

The 1995-1996 "pill" scare, which suggested that third-generation oral cont raceptives (OCs) were associated with a greater risk of venous thromboembol ism (VTE) than second-generation OCs, had serious social and public health consequences, as women discontinued OCs, resulting in unwanted pregnancies and unnecessary abortions. This article uses the Bradford Hill criteria, fo r diagnosing causality from an observed association, to interpret evidence from recent studies as to whether there is any difference in the risk of VT E between third- and second-generation OCs. Bias and the influence of confo unders have also been examined in relation to the difference in the risk of VTE between third- and second-generation OCs reported in the 1995-1996 stu dies. It is clear from the results of this analysis that none of the Bradfo rd Hill criteria are fulfilled. Thus, a causal relationship cannot be infer red from the alleged association of third-generation OCs with VTE. Indeed, it would appear that the unavoidable bias in observational research is a mo re likely explanation for the apparent difference in the risk of VTE betwee n third- and second-generation OCs in the 1995-1996 studies. Recent studies , which employed more appropriate controls for these biases showed no diffe rence in the risk of VTE between third- and second-generation OCs. A Danish study (1994-1996) demonstrated a lower risk of thrombotic morbidity and mo rtality with third-generation OCs compared with second-generation OCs. In a ddition, the Transnational study has shown that third-generation OCs have a significantly lower relative risk (0.3 [0.1-0.9]) for acute myocardial inf arction (MI) compared with second-generation products. In conclusion, there is no convincing evidence for a difference in the risk of stroke or VTE be tween third- and second-generation OCs. Moreover, third-generation OCs may be associated with a lower risk of MI than second-generation OCs. (C) 2000 Elsevier Science Inc. All rights reserved.