Hormonal contraceptives with ethinyl estradiol were associated with increased thrombotic stroke and MI

Abstract

QUESTION Are hormonal contraceptives associated with increased risk for thrombotic stroke or myocardial infarction (MI)? METHODS DESIGN Population-based cohort study with linkage of 4 national registries between 1995 and 2009. SETTING Denmark. PARTICIPANTS 1 626 158 women 15 to 49 years of age. Exclusion criteria included past venous or arterial thrombotic event; past gynecologic breast lung abdominal or hematologic cancer; or past hysterectomy sterilization bilateral oophorectomy or 2 unilateral oophorectomies. Data were censored during pregnancies. RISK FACTORS Filled prescriptions for hormonal contraceptives. Analyses were adjusted for age; education (level and duration); calendar year; and use of medications for hypertension heart disease diabetes and hyperlipidemia. OUTCOMES Thrombotic stroke and MI identified through diagnostic codes in the National Registry of Patients and the Register of Causes of Death. MAIN RESULTS 3311 (0.2%) women had a thrombotic stroke and 1725 (0.1%) had an MI during 14 251 063 woman-years of follow-up. Thrombotic stroke. Incidence in nonusers was 24 per 100 000 woman-years (2260 events). Levonorgestrel intrauterine devices (IUDs) were associated with reduced risk (adjusted relative risk [aRR] 0.73 95% CI 0.54 to 0.98); progestin-only pills or implants were not associated with increased risk (aRR range 0.44 to 1.4). Two of three 20-microg ethinyl estradiol formulations six of seven 30- to 40-microg formulations and one of two 50-microg formulations were associated with increased risk (aRR range 1.5 to 2.3) (Table). The vaginal ring was associated with increased risk (aRR 2.5 CI 1.4 to 4.4). MI. Incidence in nonusers was 13 per 100 000 woman-years (1228 events). Progestin-only interventions were not associated with increased risk (aRR range 0 to 2.1). One 20-microg ethinyl estradiol formulation five 30- to 40-microg formulations and both 50-microg formulations were associated with increased risk (aRR range 1.6 to 4.3) (Table). The vaginal ring was not associated with increased risk. Data were insufficient to evaluate hormonal contraceptives given in a patch. CONCLUSION Oral hormonal contraceptives containing ethinyl estradiol were associated with increased risk for thrombotic stroke and myocardial infarction.Association between prescription for hormonal contraceptives and thrombotic stroke or MI*OutcomesHormonal contraceptivesRRdagger (95% CI)Thrombotic strokeEthinyl estradiol 20 microg plus progestindouble dagger1.6 (1.4 to 1.9)Ethinyl estradiol 30 to 40 microg plus progestin section sign1.8 (1.6 to 1.9)Ethinyl estradiol 50 microg plus progestin||2.0 (1.5 to 2.7)MIEthinyl estradiol 20 microg plus progestindouble dagger1.4 (1.1 to 1.8)Ethinyl estradiol 30 to 40 microg plus progestin section sign1.9 (1.7 to 2.1)Ethinyl estradiol 50 microg plus progestin||3.7 (2.8 to 5.0)*MI = myocardial infarction; RR = risk ratio; CI defined in Glossary.daggerAdjusted for progestin type age and calendar year. Risk > 1.0 indicates increased risk associated with hormonal contraceptive use. P = 0.24 for dose trend in thrombotic stroke; P < 0.001 for dose trend in MI.double daggerProgestin = desogestrel gestodene or drospirenone. section signProgestin = norethindrone levonorgestrel norgestimate desogestrel gestodene drospirenone or cyproterone acetate.||Progestin = norethindrone or levonorgestrel.