Association of contemporary hormonal contraception and the risk of arterial thrombosis

Abstract Background While contemporary hormonal contraception is effective in preventing unwanted pregnancies, its potential link to an increased risk of stroke and myocardial infarction raises safety concerns. Purpose This study aimed to investigate the association between the use of contemporary hormonal contraception and the occurrence of ischemic stroke and myocardial infarction. Methods A nationwide prospective cohort study was conducted, comprising of all Danish women aged 15-49 years without a history of arterial and venous thrombosis, thrombophilia, and cancer from 1996 to 2021. Data on hormonal contraception use, stroke and myocardial infarction diagnoses, and potential confounders were collected from nationwide registers. A Poisson regression analysis was performed adjusting for age, education level, calendar year, hypertension, statin use, diabetes, and atrial fibrillation. Results The study followed 2,205,794 women over 23,700,659 person-years. Weighted median age was 33 (interquartile range (IQR): 24-41) for non-users and 25 (20-34) for users. A total of 5,346 ischemic strokes (22.6 per 100,000 person-years) and 2,351 myocardial infarctions (9.9 per 100,000 person-years) occurred during the study period. When compared to no use, oral contraceptives containing ethinyl estradiol at a dose of 30 to 40 μg was associated with the following adjusted incidence rate ratios (and 95% confidence intervals) for ischemic stroke and myocardial infarction, according to progestin type: levonorgestrel, 1.9 (1.7 to 2.2) and 2.0 (1.7 to 2.4); norgestimate, 1.9 (1.5 to 2.3) and 1.9 (1.4 to 2.6); desogestrel, 2.4 (2.0 to 2.9) and 2.2 (1.6 to 3.0); gestodene, 1.9 (1.7 to 2.2) and 1.9 (1.5 to 2.2); drospirenone, 2.0 (1.6 to 2.5) and 1.8 (1.1 to 2.8); cyproterone acetate, 1.7 (1.2 to 2.3) and 2.1 (1.3 to 3.4), respectively. At a dose of 20 μg of ethinyl estradiol, the incidence rate ratios for ischemic stroke and myocardial infarction varied based on the type of progestin as follows: desogestrel, 1.9 (1.6 to 2.2) and 1.4 (1.0 to 1.9); gestodene, 1.7 (1.4 to 2.0) and 1.7 (1.2 to 2.4); drospirenone, 1.4 (0.7 to 2.6) and 1.1 (0.3 to 4.4); For transdermal patch, the incidence rate ratio was 3.4 (1.4 to 8.2) and 0.0 (0.0 to 0.0); for vaginal ring, 2.2 (1.4 to 3.3) and 3.2 (1.7 to 6.3); for intrauterine device, 1.1 (0.9 to 1.2) and 1.1 (0.9 to 1.3); for implant, 2.0 (1.2 to 3.5) and 1.3 (0.4 to 3.9); for injection, 1.9 (0.9 to 3.8) and 0.6 (0.1 to 4.0). Conclusion Use of contemporary hormonal contraception appeared to be associated with ischemic stroke and myocardial infarction when compared to non-users. The incidence rate ratios varied across type of hormonal contraception, estrogen dose, progestin type and route of administration. The findings underscore the importance of informed decision-making when considering contraceptive options, with implications for public health and individual health choices.FlowchartAdjusted incidence rate ratios