Purpose: To review the association between combined oral contraceptives and cardiovascular disease, with emphasis on oral contraceptives containing low doses of estrogen (low-dose oral contraceptives).
Data sources: A systematic search of the MEDLINE database was done for all relevant articles published between 1967 (when low-dose oral contraceptives were introduced in the United States) and June 1997. Textbooks, meeting proceedings, and reference lists were also searched.
Study selection: All English-language human epidemiology studies of oral contraceptives that used cardiovascular disease as an end point were reviewed. Animal and metabolic studies were reviewed only if they were especially relevant to the mechanism of action of oral contraceptives.
Data extraction: Descriptive and analytic data from each study were collected.
Data synthesis: Data were organized by cardiovascular end point, study design, estrogen dose, and type of progestogen. Data on relative and absolute risk are presented to address current prescription guidelines.
Conclusions: The risk for cardiovascular disease is lower with current preparations of oral contraceptives, including those that contain the new progestogens, than with older oral contraceptives containing high doses of estrogen. Among users of low-dose oral contraceptives, cardiovascular diseases occur mainly in smokers and women with predisposing factors. Every effort should be made to encourage smoking cessation among potential users of oral contraceptives.
PIP: The cardiovascular risk associated with use of combined oral contraceptives (OCs) was assessed through a review of the English-language literature published from 1967 (when low-dose OCs were introduced in the US) and June 1997. Data were organized by cardiovascular end point (myocardial infarction, stroke, venous thrombosis and pulmonary embolism), study design, estrogen dose, and type of progestogen. As a result of the rarity of cardiovascular disease in young women, few such events are available for analysis, even in large cohorts of women. However, the review suggested that the overall risk for cardiovascular disease is substantially lower with current OC preparations containing 50 mcg of estrogen or less, including those that contain the new progestogens, than with older OCs containing high doses of estrogen. Preliminary case-control studies indicate that the risk of myocardial infarction is lower among users of OCs containing desogestrel and gestodene while that of venous thromboembolism may be elevated with these progestogens compared with levonorgestrel. Of concern is emerging evidence that the newer OCs have an attenuated acute prothrombotic reaction with cigarette smoking compared to older formulations. For stroke as well, OC users who smoke are substantially more susceptible than nonsmoking users. Every effort should be made to encourage smoking cessation among potential or current users of OCs.