ABSTRACT: Several studies published in the past 10 years have evaluated the risk of venous thromboembolic complications with the use of newer hormonal contraceptives, but few have examined the risk of thrombotic stroke and myocardial infarction. Results of the few available studies have been conflicting.
The aim of the Danish historical cohort study was to assess the risks of thrombotic stroke and myocardial infarction among women who received various types of hormonal contraception. Over a 15-year period (1995–2009), data were obtained on use of hormonal contraception, clinical end points, and potential confounders from national registries for nonpregnant women, 15 to 49 years old, who had no history of cardiovascular disease or cancer. Data on contraceptives were stratified according to estrogen dose, progestin, and route of administration. The crude incidence rate and adjusted relative risk (RR) of thrombotic events were compared in users of contraceptives and nonusers.
The study cohort was composed of 1,626,158 women with 14,251,063 person-years of observation. Among this population, 3311 had a first thrombotic stroke (21.4 per 100,000 person-years), and 1725 had a first myocardial infarction (10.1 per 100,000 person-years). Relative risks for thrombotic stroke or myocardial infarction among current users of oral contraceptives at a dose of ethinyl estradiol of 30 to 40 μg, according to the type of progestin, compared with nonuse were as follows: norethindrone, 2.2 (95% confidence interval, 1.5–3.2) and 2.3 (1.3–3.9); levonorgestrel, 1.7 (1.4–2.0) and 2.0 (1.6–2.5); norgestimate, 1.5 (1.2-1.9) and 1.3 (0.9–1.9); desogestrel, 2.2 (1.8–2.7) and 2.1 (1.5–2.8); gestodene, 1.8 (1.6–2.0) and 1.9 (1.6–2.3); and drospirenone, 1.6 (1.2–2.2) and 1.7 (1.0–2.6), respectively. At a reduced dose of ethinyl estradiol (20 μg), the RRs for thrombotic stroke or myocardial infarction were as follows: desogestrel, 1.5 (1.3–1.9) and 1.6 (1.1–2.1); gestodene, 1.7 (1.4–2.1) and 1.2 (0.8–1.9); and drospirenone, 0.9 (0.2–3.5) and 0.0. The corresponding RRs among women who used contraceptive patches were 3.2 (0.8–12.6) and 0.0; RRs for use of a vaginal ring were 2.5 (1.4–4.4) and 2.1 (0.7–6.5).
These findings show that the absolute risks of thrombotic stroke and myocardial infarction associated with the use of hormonal contraception are low, but the risk increases by a factor of 0.9 to 1.7 with use of oral contraceptives including ethinyl estradiol at a low dose (20 μg) and by a factor of 1.3 to 2.3 with those including ethinyl estradiol at a higher dose (30–40 μg), with only small differences in risk according to progestin type.