Oral contraceptives and cardiovascular disease: a critique of the epidemiologic studies

Observational study designs used to investigate the relationship of oral contraceptive use to the occurrence of venous thromboembolism, stroke, myocardial infarction, and cardiovascular death include case-control, cohort, and mortality statistics studies. This analysis catalogs the findings of each of these epidemiologic studies, its statistical significance, and its performance with regard to scientific methodologic standards. An association between current oral contraceptive use and incidence of venous thromboembolism without predisposition has been consistently observed in case-control and cohort studies. Associations are less consistent for various types of stroke and for myocardial infarction. Only the Royal College of General Practitioners study found a significantly elevated risk of cardiovascular death with oral contraceptive use. The majority of mortality statistics studies offer little support for a relationship between oral contraceptive use and cardiovascular events. Major systematic problems in the epidemiologic studies include potential for bias in the detection of cardiovascular events and differences in the prognostic susceptibility of compared groups. Bias in the ascertainment of drug exposure is an unresolved issue for most of the case-control studies. Because of possible biases arising from methodologic deficiencies in these epidemiologic studies, questions as to the validity of the observed associations between oral contraceptive use and cardiovascular events should remain.