Stroke and myocardial infarction with contemporary hormonal contraception: real-world, nationwide, prospective cohort study
BMJ 2025; 388 doi: https://doi.org/10.1136/bmj-2024-082801 (Published 12 February 2025) Cite this as: BMJ 2025;388:e082801Linked Editorial
Arterial thrombosis in users of contemporary hormonal contraception
Linked Opinion
Research on hormonal contraceptives is needed to monitor their evolving safety profile
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Dear Editor,
Yonis et al. 2025 [https://doi.org/10.1136/bmj-2024-082801] explore the association between various hormonal contraceptives and the risk of ischaemic stroke and myocardial infarction among Danish women aged 15-49 [1]. Despite shedding light on various findings, the following aspects warrant scrutiny.
First and foremost, the incongruency between absolute and relative risks remains striking. The study shows increased relative risks of ischaemic stroke and MI associated with particular hormonal contraceptives, especially those obtaining estrogen [1]. However, the absolute risk increase is dismal, owing to the low baseline incidence of these occurrences in the population of interest. Unarguably, relative risk emphases in the absence of proper context often culminate in misinterpretation of the real danger posed by these contraceptives [2].
Also, the absence of individualized risk assessment remains a critical concern. The study reveals population-level associations but fails to explore individualized risk assessments. Patient factors such as family history of thrombosis and past medical histories play a critical role in determining the safest contraceptive method for every woman [3]. Moreover, EBP demands the tailoring of contraceptive choices to individual risk profiles.
In conclusion, Yonis et al.’s study sheds light on the relationship between contemporary hormonal contraceptives and arterial thrombosis risk. More importantly, clinicians should interpret these outcomes with caution. Moreover, further research should be carried out to confirm these associations and guide safe contraceptive use.
References
[1] 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 Feb 12;e082801.
[2] Jiroutek MR, Turner JR. Relative vs absolute risk and odds: Understanding the difference. The Journal of Clinical Hypertension. 2019 Apr 25;21(6):859–61.
[3] Bezemer ID, van der Meer FJM, Eikenboom JCJ, Rosendaal FR, Doggen CJM. The Value of Family History as a Risk Indicator for Venous Thrombosis. Archives of Internal Medicine [Internet]. 2009 Mar 23;169(6):610. Available from: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/414874
[4] Brant A, Shin R, Pelin Batur. Contraception: Evidence-Based Practice Guidelines and Recommendations. Springer eBooks. 2022 Jan 1;553–71.
Competing interests: No competing interests
Dear Editor,
I read with great interest the recent nationwide study investigating the association between hormonal contraceptive use and arterial thrombosis in Danish women. Although the study provides useful epidemiological information, there are several issues that deserve discussion.
First, while the relative risks for ischaemic stroke and myocardial infarction are increased with some contraceptive methods, the absolute risk differences are small. 1. Presenting relative risks, uncontextualized, may exaggerate clinical significance — for example, the similar but much lower absolute risk of an event may get lost in translation, with concern disproportionately flaring among clinicians and patients alike.
Second, as an observational study using registry data, the results are always prone to residual confounding. Important covariates like smoking, obesity, and socioeconomic variables were not adequately considered. Unmeasured confounders could, at least in part, account for the relationships seen.
Third, there are other issues which include, but may not be limited to the potential misclassification bias introduced by the 25 years of data. The changing diagnostic criteria and practices for recording these for such an extended period may have continued to affect the accuracy of all exposure and outcome data.
So in conclusion, this research provides an important insight, but its limitations augur extreme caution when coming up to its implications. Hormonal contraceptives are beneficial, but the risks are plausible and need to be understood scientifically. Further studies based on granular data and rigorous control for confounding factors are recommended to make an informed clinical decision.
Yours sincerely,
Dr. Abdul Malik Soomro, Resident Doctor
Competing interests: No competing interests
Re: Stroke and myocardial infarction with contemporary hormonal contraception: real-world, nationwide, prospective cohort study
Dear Editor，
The recent nationwide cohort study by Yonis et al. (BMJ 2024;384:e082801) provides valuable insights into the association between contemporary hormonal contraceptives and arterial thrombotic events. While the study’s large sample size and prospective design are commendable, several methodological and contextual limitations warrant discussion.
Despite adjusting for comorbidities, unmeasured confounders (e.g., smoking, BMI) were only partially addressed in subanalyses. Smoking data, limited to parous women, may not reflect the broader cohort. Reliance on prescription records (vs. actual use) may overestimate exposure, especially for long-acting methods (e.g., intrauterine devices), where early discontinuation is common. For less common contraceptives (patch, injection), the low number of thrombotic events (e.g., 0 myocardial infarctions with patch use) limits confidence in risk estimates. The homogeneous Danish population may not reflect risks in ethnically diverse cohorts, where genetic and lifestyle factors differ. The study designed censored individuals during pregnancy or surgery, potentially excluding high-risk periods for thrombosis, which could underestimate baseline risks.
Future studies should confirm findings using randomized designs or international cohorts to address confounding and generalizability and present absolute risks alongside relative risks to guide shared decision-making. Furthermore, they could investigate cumulative risks beyond four years of use, as the study found no duration-dependent effects—a finding inconsistent with UK Biobank data (Johansson et al., Stroke 2022).
In summary, while this study advances understanding of hormonal contraception safety, clinicians should interpret results cautiously, considering both its strengths and inherent observational limitations.
Reference
Johansson T, Fowler P, Ek WE, Skalkidou A, Karlsson T, Johansson Å. Oral Contraceptives, Hormone Replacement Therapy, and Stroke Risk. Stroke. 2022;53(10):3107-3115.
Yonis H, Løkkegaard E, Kragholm K, et al. Stroke and myocardial infarction with contemporary hormonal contraception: real-world, nationwide, prospective cohort study. BMJ. 2025;388:e082801.
Competing interests: No competing interests