To evaluate the association between contemporary hormonal contraceptive use and the risk of incident ischaemic stroke and myocardial infarction.
Design
Real-world, nationwide, prospective cohort study.
Setting
Denmark, by use of national registries.
Participants
All women aged 15-49 years residing in Denmark between 1996 and 2021, with no history of arterial or venous thrombosis, antipsychotics use, cancer, thrombophilia, liver disease, kidney disease, polycystic ovary syndrome, endometriosis, infertility treatment, hormone therapy use, oophorectomy, and hysterectomy.
Main Outcome Measures
First time diagnosis of ischaemic stroke or myocardial infarction at discharge.
Results
Among 2 025 691 women followed up for 22 209 697 person years, 4730 ischaemic strokes and 2072 myocardial infarctions occurred. Standardised ischaemic stroke rate per 100 000 person years were 18 (95% confidence interval 18 to 19) for no use, 39 (36 to 42) for combined oral contraception, 33 (25 to 44) for progestin-only pills, and 23 (17 to 29) for intrauterine device. Standardised myocardial infarction rate per 100 000 person years were 8 (8 to 9) for no use, 18 (16 to 20) for combined oral contraception, 13 (8 to 19) for progestin-only pills, and 11 (7 to 16) for intrauterine device. Compared with no use, current use of combined oral contraception was associated with an adjusted rate ratio of 2.0 (1.9 to 2.2) for ischaemic stroke and 2.0 (1.7 to 2.2) for myocardial infarction. These corresponded to standardised rate differences of 21 (18 to 24) extra ischaemic strokes and 10 (7 to 12) extra myocardial infarctions per 100 000 person years. Compared with no use, current use of progestin-only pills was associated with an adjusted rate ratio of 1.6 (95% CI 1.3 to 2.0) for ischaemic stroke and 1.5 (1.1 to 2.1) for myocardial infarction, equating to 15 (6 to 24) extra ischaemic strokes and four (-1 to 9) extra myocardial infarctions per 100 000 person years. Increased arterial thrombotic risk was also observed with use of the combined vaginal ring (adjusted incidence rate ratio of 2.4 (1.5 to 3.7) for ischaemic stroke and 3.8 (2.0 to 7.3) for myocardial infarction), patch (3.4 (1.3 to 9.1) and no myocardial infarctions), and progestin-only implant (2.1 (1.2 to 3.8) and ≤3 myocardial infarctions), whereas no increased risk was observed with progestin-only intrauterine device (1.1 (1.0 to 1.3) for ischaemic stroke and 1.1 (0.9 to 1.3) for myocardial infarction).
Conclusions
Use of contemporary oestrogen-progestin and progestin-only contraceptives was associated with an increased risk of ischaemic stroke and, in some cases, myocardial infarction except for the levonorgestrel-releasing intrauterine device, which was not associated with either. Although absolute risks were low, clinicians should include the potential risk of arterial thrombosis in their assessment of the benefits and risks when prescribing a hormonal contraceptive method.
PMID 39938934 39938934 DOI 10.1136/bmj-2024-082801 10.1136/bmj-2024-082801 Yonis et al. 2025, Yonis 2025
Cite this article
Yonis, H., Løkkegaard, E., Kragholm, K., Granger, C. B., Møller, A. L., Mørch, L. S., Torp-Pedersen, C., & Meaidi, A. (2025). Stroke and myocardial infarction with contemporary hormonal contraception: real-world, nationwide, prospective cohort study. BMJ (Clinical research ed.), 388, e082801. https://doi.org/10.1136/bmj-2024-082801
Yonis H, Løkkegaard E, Kragholm K, Granger CB, Møller AL, Mørch LS, 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
Yonis, H., et al. "Stroke and myocardial infarction with contemporary hormonal contraception: real-world, nationwide, prospective cohort study." BMJ (Clinical research ed.), vol. 388, 2025, pp. e082801.
Keywords
Progestins, Contraceptives, Oral, Combined
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