In a study of Danish women, oral contraceptive pills containing estrogen and progestin were associated with increased risks of stroke and myocardial infarction (MI). Variations in risk according to estrogen dose and progestin type were modest.
The risk of thromboembolic complications with the use of hormonal contraception is an important issue scientifically and is relevant for counseling women about contraceptive options. Several studies have assessed the risk of venous thromboembolism associated with the use of newer hormonal contraceptive products, but few studies have examined thrombotic stroke and myocardial infarction, and the results of available studies have been conflicting.
• How did the risk of arterial thrombosis among previous users of hormonal contraception compare to the risk among women who had never used it?
The risk among previous users was similar to the risk among women who had never used hormonal contraception. The rate ratio for thrombotic stroke among previous users, as compared with women who had never used hormonal contraception, was 1.04 (95% CI, 0.95 to 1.15), and for myocardial infarction, 0.99 (95% CI, 0.86 to 1.13).
• In this study, did the relative risk of an arterial thrombotic event in women taking an intermediate-dose estrogen oral contraceptive differ depending on the type of progestin that was prescribed?
The estimated relative risks of thrombotic stroke and myocardial infarction among users of combined oral contraceptive pills (OCPs) that included ethinyl estradiol at a dose of 30 to 40 micrograms did not differ significantly according to the type of progestin, ranging from 1.40 to 2.20 for stroke and from 1.33 to 2.28 for myocardial infarction. For both end points, the risk estimates were lowest with contraceptive pills that included norgestimate or cyproterone acetate and were highest with those that included norethindrone or desogestrel.
Morning Report Questions
Q: How did low dose estrogen containing OCPs differ from intermediate dose pills with respect to risk of stroke or myocardial infarction?
A: In this study, women who used oral contraceptives with ethinyl estradiol at a dose of 30 to 40 micrograms had a risk of arterial thrombosis that was 1.3 to 2.3 times as high as the risk among nonusers, and women who used pills with ethinyl estradiol at a dose of 20 micrograms had a risk that was 0.9 to 1.7 times as high, with only small differences according to progestin type. The absolute risk, however, is still small. The authors estimate that among 10,000 women who use desogestrel with ethinyl estradiol at a dose of 20 micrograms for 1 year, 2 will have arterial thrombosis and that 6.8 women taking the same product will have venous thrombosis.
Q: How did progestin containing IUDs and implants as well as the patch and vaginal ring compare to oral contraceptives?
A: None of the progestin-only products, including the levonorgestrel-releasing IUD and the subcutaneous implants, significantly increased the risk of thrombotic stroke or myocardial infarction. In contrast, the relative risk of thrombotic stroke was 3.15 (95% CI, 0.79 to 12.6) among women who used contraceptive patches and 2.49 (95% CI, 1.41 to 4.41) among those who used a vaginal ring. Numbers of myocardial infarctions were too low to provide reliable estimates. The authors conclude that until further evidence emerges, one should expect a higher risk of thrombotic stroke with parenteral administration than with oral administration (estrogen combined with progestin).