Objectives: The study was intended to evaluate the effects of oral contraceptives and smoking on the risks of arterial and venous thromboembolic diseases among young women.
Study design: The study included a survey of data from published epidemiologic studies and evaluation of registry records of all Danish women discharged from the hospital from 1980 through 1993 after a first thromboembolic event. Questionnaires returned by survivors of such events and by control women during the period from 1994 through 1995 were analyzed.
Results: In the 1980-1993 data the absolute risk of thrombotic diseases was seen to increase rapidly with age-exponentially for acute myocardial infarction or cerebral thromboembolic attack, linearly for venous thromboembolism-with risks of arterial diseases exceeding those of venous diseases. In the 1994-1995 data the relative risk of thrombotic diseases was seen to increase among users of oral contraceptives irrespective of age. Risk of venous thromboembolism (but not of acute myocardial infarction or cerebral thromboembolic attack) declined as duration of current oral contraceptive use lengthened, risk of acute myocardial infarction or cerebral thromboembolic attack was significantly decreased as ethinyl estradiol doses were reduced, and the relative risk (compared with nonusers of oral contraceptives) for arterial thromboembolic disease among users of desogestrel or gestodene (in conjunction with midrange or low doses of ethinyl estradiol) was lower than the relative risk among users of second-generation progestogens (in conjunction with midrange doses of ethinyl estradiol). The combination of smoking with oral contraceptive use may have a synergistic effect on risks of acute myocardial infarction and cerebral thromboembolic attack (but not of venous thromboembolism), particularly among users of high-dose (50 micrograms) ethinyl estradiol preparations.
Conclusion: Among the formulations currently marketed in Denmark, where only the progestins desogestrel and gestodene are available with low-dose (20 micrograms) ethinyl estradiol (and only desogestrel was available in that form at the time of our studies), we prefer these third-generation oral contraceptives for smokers. We might also consider such oral contraceptives for women >35 years old as long as they had no other risk factors for thrombotic arterial diseases.
PIP: This study assesses the effects of cigarette smoking and oral contraceptive (OC) use on the risks of arterial and venous thromboembolic diseases among women in their reproductive years. A survey of published epidemiologic studies is included together with an evaluation of registry records of Danish women discharged from hospitals from 1980 through 1993 after a first thromboembolic event. Analysis was made of questionnaires sent to survivors of such an event and to control women during the period from 1994 through 1995. The study also includes an evaluation of thrombotic disease prevalence, determination of OC influence on the risk of the disease, and comparison of disease prevalence among smoking and nonsmoking users of OC. Results showed that the risk of acute myocardial infarction among OC users was significantly higher than among non-OC users. OC use had less of an effect on acute myocardial infarction risk than on the risk of cerebral thromboembolic attack. The risk of venous thromboembolism among users of OC was influenced by the duration of OC use; the shorter the use, the higher the risk, while smoking had little effect. Epidemiologic studies suggest that arterial disease risk in young (men/women) decreases within 5-10 years of smoking cessation. Smoking, with a low dose of OC, acted as an independent risk factor for myocardial infarction and cerebral attack. The absolute risk for older nonusers and nonsmokers was higher by 10-fold than the risk for younger counterparts. Thus, among the formulations available in Denmark, preference is given to third-generation OCs for young female smokers and for smoking women over age 35, provided they have no other risk factor for thrombotic arterial disease.