Oral contraceptives and cardiovascular disease: emerging evidence on potential associations with angina, myocardial infarction and stroke

Associations between combined estrogen/progestin oral contraceptives (OCs) and cardiovascular disease (CVD) have long been the focus of considerable concern. Initial, epidemiologic studies demonstrated increased risks of potential complications including deep venous thrombosis/pulmonary embolism, myocardial infarction and stroke. While the studies regarding venous thromboembolism consistently demonstrate at least some degree of risk associated with OC use, recent studies of both current and past OC users indicate that the association with arterial disease is dynamic, changing rapidly as OC formulations and OC-user populations change. As physicians increase selection, screening and monitoring of OC users, a healthier OC-user population is developing. Thus, many newer studies are demonstrating rates of angina and myocardial infarction that are either lower or the same as that of non-users, unless pre-existing risk factors are present leading to potential increases in risk of CVD. The evidence with regards to strokes is more complicated and controversial. While further study is necessary, current evidence suggests that OC use provides significant contraceptive benefits with minimal potential adverse effects in healthy users. The potential for CVD reduction in selected OC users merits the highest priority for further investigation. Arterial cardiovascular disease (CVD), herein defined as angina, myocardial infarction (MI), cerebrovascular accident and peripheral arterial disease, causes a distressing degree of morbidity and mortality in modern society. It is responsible for millions of deaths each year. In Europe, approximately four million deaths per year are attributed to CVD, accounting for almost half of all yearly deaths [101] . In the USA, nearly one million people died of cardiovascular-related diseases in 2002, resulting in 1 out of every 2.6 deaths being attributed to CVD [102]. Amongst women, CVD is the most common cause of death in developed nations. CVD-related morbidity and mortality are pre-eminent concerns in both basic science and clinical branches of medicine and represent a central focus of many public health programs. The significance of CVD bears considerable import in all aspects of women’s health, leading to heightened focus on any potential contributing factors. Common risk factors for adverse cardiovascular outcomes include obesity, hypercholesterolemia, smoking, diabetes and hypertension. With the exception of smoking, the prevalence of these risk factors is much higher in women over 35 years of age. Thus, the majority of cardiovascular morbidity and mortality occurs in peri-menopausal and postmenopausal women, whose age and long-term exposure to risk factors substantially increase incidence rates. Amongst premenopausal women, one factor that has been the source of significant scrutiny and controversy is the combined estrogen/progestin oral contraceptive pill (OC) – the focus of this review. Made widely available in the early 1960s, their immediate popularity spurred considerable concerns based on early studies that demonstrated an increased CVD risk in users of high-dose (> 50 ug ethinyl estradiol, and either norethynodrel, norethisterone or norethindrone) containing pills [1,2]. Cited concerns included increased risks of MI, fatal MI and stroke. As a result, OC formulations with lower doses of estradiol and newer progestins were marketed. Subsequently, many epidemiological studies have presented either conflicting results, or have demonstrated increased risks only in users of early generation OCs and/or those with risk factors at the time of prescription. The purpose of this article is to review the body of evidence in regards to the association of OCs and arterial CVD, with a specific focus on emerging evidence on differential risks for healthy versus atrisk OC users.