Study: Certain Hormonal Contraceptives Increase Risks of Ischemic Stroke, Myocardial Infarction

A Danish study published in the British Journal of Medicine found that the use of hormonal contraceptive methods was associated with an increased risk of ischemic stroke and myocardial infarction. Levonorgestrel-releasing intrauterine devices (IUDs)—Mirena (Bayer), Kyleena (Bayer), Liletta (Allergan), and Skyla (Bayer)—were not associated with these risks.¹

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Approximately 248 million women worldwide are estimated by the WHO to use hormonal contraception. Because currently marketed options have acceptable and similar efficacy in the prevention of unwanted pregnancies, safety is often a key consideration when health care professionals consider which option is most suitable for a patient.¹

To evaluate the association between contemporary hormonal contraceptive use and the risk of incident ischemic stroke and myocardial infarction, the investigators conducted a real-world, nationwide, prospective cohort study that enrolled all women aged 15 to 49 who resided in Denmark between 1996 and 2021. Women were enrolled through national registries and did not have a history of the following: arterial or venous thrombosis; use of antipsychotics; cancer; thrombophilia; liver disease; kidney disease; polycystic ovary syndrome; endometriosis; infertility treatment; hormone therapy use; oophorectomy; and hysterectomy.¹

Among 2,025,691 women who were followed up for 22,209,697 person-years, 4730 ischemic strokes and 2072 myocardial infarctions were observed. The findings showed that the respective standardized ischemic stroke and myocardial infarction rates per 100,000 person-years were 18 (95% CI: 18-19) and 8 (95% CI: 8-9) for no hormonal birth control use, 39 (95% CI: 36-42) and 18 (95% CI: 16-20) for combined oral contraception, 33 (95% CI: 25-44) and 13 (95% CI: 8-19) for progestin-only pills, and 23 (95% CI: 17-29) and 11 (95% CI: 7-16) for IUDs.¹

"Our findings may suggest a dose-related association between progestin-only products and arterial thrombotic risk, with the highest risk associated with implant use, then pills. IUDs, which cause the smallest increase in serum progestin level, were not associated with increased risk," study author Harman Yonis, MD, Nordsjaellands Hospital and University of Copenhagen in Denmark, said in a news release.²

Compared with no use, current use of combined oral contraception was associated with an adjusted rate ratio of about 2.0 (95% CI: 1.9-2.2) for ischemic stroke and 2.0 (95% CI: 1.7-2.2) for myocardial infarction. Progestin-only pills were lower and were associated with an adjusted rate ratio of 1.6 (95% CI 1.3-2.0) and 1.5 (95% CI: 1.1-2.1), respectively. Additionally, increased arterial thrombotic risks were also observed with the use of the combined vaginal ring (ischemic stroke: 2.4 [95% CI 1.5-3.7]; myocardial infarction: 3.8 [95% CI 2.0-7.3]), patch (ischemic stroke: 3.4 [95% CI 1.3-9.1]; no myocardial infarctions), and progestin-only implant (ischemic stroke: 2.1 [95% CI 1.2-3.8] and ≤3 myocardial infarctions), whereas no increased risk was observed with progestin-only IUDs (ischemic stroke: 1.1 [95% CI 1.0-1.3]; myocardial infarction: 1.1 [95% CI 0.9-1.3]).

Overall, the investigators determined that contemporary estrogen-progestin and progestin-only contraceptives were associated with an increased risk of ischemic stroke and myocardial infarction in certain cases, except for levonorgestrel-releasing IUDs, which were not associated with either. The absolute risk remains low, the authors noted, but health care professionals should be aware of these risks and inform their patients accordingly when helping them find a suitable hormonal contraceptive method.¹

“It is important to note that the absolute risk remains low. Nonetheless, these side effects are serious, and given that approximately 248 million women use hormonal contraceptives daily, the results carry important implications,” explained Therese Johansson, PhD, of KTH Royal Institute of Technology in Stockholm, Sweden, in the news release. “Policymakers should prioritize making safer alternatives, such as the levonorgestrel-releasing IUD for women with cardiovascular risk factors, both affordable and accessible, particularly in low-resource settings where cardiovascular risks are frequently underdiagnosed and untreated.”²

REFERENCES

1. Yonis H, LøLøkkegaard E, Kragholm K, et al. Stroke and myocardial infarction with contemporary hormonal contraception: real-world, nationwide, prospective cohort study. BMJ. 2025;388:e082801 doi:10.1136/bmj-2024-082801

2. MedPage Today. Hormonal Contraceptives Tied to Strokes, Heart Attacks in Real-World Data. News release. February 12, 2025. Accessed February 17, 2025. https://www.medpagetoday.com/obgyn/generalobgyn/114198?xid=nl_mpt_OB/GYN_update_2025-02-13&mh=b76ab89cefe06c0f6fdb962df1779b32&zdee=gAAAAABnlOuJ-qaiwyusB3p3P0TpVA_ZJQKOeJF-U0fWJxOLDy4ox6WGx9vMUy4C4o5vQJR4_9cF1UvdHsRfOROEajAC1puvrMsLRjNXZBuuc9J5QaiVfXw%3D&utm_source=Sailthru&utm_medium=email&utm_campaign=Automated%20Specialty%20Update%20OBGYN%202025-02-13&utm_term=NL_Spec_OBGYN_Update_Active