Oral contraceptives that contained more than 50 mg of estrogen were withdrawn from the market in the United States in 1989. The newer oral contraceptives have one fourth of the estrogen and one tenth of the progestogen of the original combination agents. The newer progestogens (desogestrel, gestodene and norgestimate) have fewer androgenic metabolic effects, do not adversely affect lipid levels and may be associated with a lower risk for cardiovascular disease. Chasan-Taber and Stampfer reviewed the epidemiologic studies of oral contraceptives and cardiovascular disease performed between 1967 and mid-1997, paying special attention to preparations that contain less than 50 mg of estrogen.
Case-control and cohort studies suggest that much of the excess risk for myocardial infarction in current users of oral contraceptives is attributable to cigarette smoking. Two separate studies showed that the relative risk of myocardial infarction was 39 and 30 in women who smoked 25 or more cigarettes daily and used oral contraceptives. This risk was four to eight times greater than the risk associated with smoking alone. Studies suggest that current users of oral contraceptives who are younger than 40 years and do not smoke have little or no increased risk for myocardial infarction. Data on the oral contraceptives that contain the newest progestogens are incomplete but suggest a lower relative risk for myocardial infarction than that associated with the earlier preparations. The data are sparse, however, and are based on fewer than 10 exposed cases. Data from epidemiologic studies consistently show that past use of oral contraceptives is not associated with an increased risk of myocardial infarction.
The authors note that previous studies of stroke (hemorrhagic and ischemic) in women using oral contraceptives often combined users of high- and low-dose formulations, which inflated the overall relative risks. Several studies suggest a positive interaction between oral contraceptive use, smoking and the risk of stroke. No studies suggest an increased risk for stroke among past users of oral contraceptives, with the exception of smokers. The studies in current users are inconsistent but probably demonstrate no increased risk for hemorrhagic stroke among women who use low-dose contraceptives and do not have risk factors. Studies of low-dose oral contraceptives indicate that these agents produce little increase in the risk for ischemic stroke, but the authors note that a two- to threefold increase in risk cannot be excluded.
Recent studies point to a potentially increased risk of thromboembolic disease with the newer progestogens. However, confounding variables and bias may account for some of the differences in the incidence of venous thromboembolism. Women who are carriers for the factor V Leiden mutation have been shown to have a sevenfold increase in thrombosis as compared with noncarriers. This observation suggests that the newest progestogens may be associated with a prothrombotic state similar to that induced by factor V Leiden.
The authors conclude that current use of oral contraceptives by women who do not smoke does not seem to increase the risk for myocardial infarction. The information about stroke risk is less definitive. There may be a small to moderate increase in the risk for ischemic stroke. The risk for thromboembolic disease may be modestly higher among users of preparations containing the newest progestogens than among users of other oral contraceptives. Clearly, the current preparations, including those with the newer progestogens, are associated with a lower risk for cardiovascular disease relative to the risk associated with the older, high-dose estrogen contraceptives and the risk associated with full-term pregnancy. Since cardiovascular disease among oral contraceptive users occurs mainly in those who smoke, smoking cessation should be strongly encouraged in women who use oral contraceptives.