The Collection and Interpretation of Epidemiological Data About the Cardiovascular Risks Associated With the Use of Steroid Contraceptives

A variety of epidemiological approaches have been used to assess the safety of steroid contraceptives. Each study design has its own strengths and weaknesses, especially with respect to susceptibility to bias and confounding. Randomized controlled trials provide the strongest evidence of a cause and effect relationship, but the low incidence of cardiovascular disease in women of reproductive age precludes the use of this study design to examine these clinical endpoints. Consequently, observational cohort and case-control studies have provided the most useful clinical information about the main cardiovascular effects of steroid contraceptives. Data from epidemiological research need to be interpreted carefully taking into consideration which of the potential biases or sources of confounding are likely to have affected a particular study, and what effect these may have on any inferences from the study. Additional factors that need to be considered before deciding whether a causal relationship exists include evidence that the exposure preceded the disease, the strength of association, consistency of findings with other studies, presence of dose gradients, and agreement with animal or laboratory research. Even if a causal link is thought to be plausible, the public health implications may be minimal; absolute (attributable) risks are required in order to assess these. An understanding of these epidemiological issues will enable clinicians to advise their clients whether steroid contraceptives alter the risk of cardiovascular disease and, if so, the clinical significance of such changes.