Thrombotic Stroke and Myocardial Infarction With Hormonal Contraception

Study Questions:

Are newer hormonal contraception therapies associated with risk for thrombotic stroke and myocardial infarction (MI)?


Data from an open historical cohort of Danish women (ages 15-49 years) were used for this analysis. Women were followed for a 15-year period between January 1995 and December 2009. Prescription data were obtained from the Register of Medicinal Products Statistics, and hormonal therapies were categorized by estrogen dose, progestin type, and route of administration. Information on clinical endpoints was obtained from the National Registry of Patients, which includes discharge diagnoses from hospitals in Denmark, and from the Register of Causes of Death. Events were restricted to first occurrence. Women were excluded if they had had a diagnosis of venous or arterial thrombosis outside of the study period (1977-1994).


A total of 1,626,158 women were included this study (14,251,063 person-years of observation). Over the follow-up period, 3,311 women experienced a first thrombotic stroke (21.4 per 100,000 person-years), and 1,725 experienced a first MI (10.1 per 100,000 person-years). The case fatality rate during the primary event or subsequent hospital stay was 1.0% for thrombotic stroke (34 of 3,311 women) and 10.8% for MI (186 of 1,725). Current use of oral contraceptives that included ethinyl estradiol at a dose of 30-40 μg was associated with risk for thrombotic stroke and MI, according to progestin type: norethindrone, relative risk [RR], 2.2 (95% confidence interval [CI], 1.5-3.2) and RR, 2.3 (95% CI,1.3-3.9); levonorgestrel, RR, 1.7 (95% CI,1.4-2.0) and RR, 2.0 (95% CI, 1.6-2.5); norgestimate, RR, 1.5 (95% CI, 1.2-1.9) and RR, 1.3 (95% CI, 0.9-1.9); desogestrel, RR, 2.2 (95% CI, 1.8-2.7) and RR, 2.1 (95% CI, 1.5-2.8); gestodene, RR, 1.8 (95% CI, 1.6-2.0) and RR, 1.9 (95% CI, 1.6-2.3); and drospirenone, RR, 1.6 (95% CI, 1.2-2.2) and RR, 1.7 (95% CI, 1.0-2.6), respectively, compared to nonusers. With ethinyl estradiol at a dose of 20 μg, the corresponding relative risks according to progestin type were as follows: desogestrel, 1.5 (95% CI, 1.3-1.9) and 1.6 (95% CI, 1.1-2.1); gestodene, 1.7 (95% CI, 1.4-2.1) and 1.2 (95% CI, 0.8-1.9); and drospirenone, 0.9 (95% CI, 0.2-3.5) and 0.0. For transdermal patches, the corresponding relative risks were 3.2 (95% CI, 0.8-12.6) and 0.0, and for a vaginal ring, 2.5 (95% CI, 1.4-4.4) and 2.1 (95% CI, 0.7-6.5).


The authors concluded that although the absolute risks of thrombotic stroke and MI associated with the use of hormonal contraception were low, the risk was increased by a factor of 0.9-1.7 with oral contraceptives that included ethinyl estradiol at a dose of 20 μg, and by a factor of 1.3-2.3 with those that included ethinyl estradiol at a dose of 30-40 μg, with relatively small differences in risk according to progestin type.


These data are very helpful for clinicians and their patients who wish to consider hormonal therapies, specifically weighing the risk for outcomes such as MI. Registry data used in this study allow for a comparison of risk in a real-world population of women. To attempt to provide this type of data from a randomized controlled trial would be a herculean task.

Keywords: Desogestrel, Progestins, Norpregnenes, Myocardial Infarction, Stroke, Contraceptives, Oral, Denmark, Norgestrel, HLA-C Antigens, Norethindrone, Ethinyl Estradiol, Length of Stay, Cause of Death, Contraceptive Devices, Female, Levonorgestrel, Thrombosis, Estrogens, Cardiovascular Diseases, Confidence Intervals

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