Evidence Matters

Is There an Increased Risk of Stroke and Heart Attack Associated with Modern Hormonal Contraceptive Use?

BACKGROUND AND PURPOSE:

Some studies have found a link between hormonal contraception and stroke and myocardial infarction
- However, there is also contradictory evidence, and research has mostly focused on the combined oral contraceptive pill
Yonis et al. (BMJ, 2025) evaluated the association between contemporary hormonal contraceptive use and the risk of incident ischemic stroke and myocardial infarction

METHODS:

Nationwide, prospective cohort study
- Nationwide prospective cohort study of all Danish women
Participants
- All women aged 15 to 49 living in Denmark between 1996 and 2021
- No history of
  - Arterial or venous thrombosis | Cancer (except non-melanoma skin cancer) | Thrombophilia | Liver disease | Kidney disease | Use of antipsychotics | Infertility treatment | Hormone therapy use | Oophorectomy | Hysterectomy | PCOS | Endometriosis
Exposures
- Hormonal contraceptive use and type
Study design
- Poisson regression used to estimate adjusted incidence rate ratios
Primary outcome
- First time diagnosis of ischemic stroke or myocardial infarction

RESULTS:

2,025,691 women | 22,209,697 person years of follow-up
- Ischemic stroke: 4730 | Myocardial infarction: 2072
Standardized ischemic stroke rate
- No hormonal contraceptive use: 18 (95% CI, 18 to 19) per 100,000 person years
- Combined pill: 39 (95% CI, 36 to 42) per 100,000 person years
- Progestin-only pill: 33 (95% CI, 25 to 44) per 100,000 person years
- IUD: 23 (95% CI, 17 to 29) per 100,000 person years
Standardized myocardial infarction rate
- No hormonal contraceptive use: 8 (95% CI, 8 to 9) per 100,000 person years
- Combined pill: 18 (95% CI, 16 to 20) per 100,000 person years
- Progestin-only pill: 13 (95% CI, 8 to 19) per 100,000 person years
- IUD: 11 (95% CI, 7 to 16) per 100,000 person years
Compared with no use, current use of combined oral contraception was associated with a higher rate of stroke and myocardial infarction
- Stroke: adjusted rate ratio (aRR) 2.0 (95% CI, 1.9 to 2.2)
  - Extra strokes per 100,000 person years: 21 (95% CI, 18 to 24)
- Myocardial infarction: aRR 2.0 (95% CI, 1.7 to 2.2)
  - Extra myocardial infarctions per 100,000 person years: 10 (95% CI, 7 to 12)
Compared with no use, current use of combined oral contraception was also associated with a higher rate of stroke and myocardial infarction
- Stroke: aRR 1.6 (95% CI, 1.3 to 2.0)
  - Extra strokes per 100,000 person years: 15 (95% CI, 6 to 24)
- Myocardial infarction: aRR 1.5 (95% CI, 1.1 to 2.1)
  - Extra myocardial infarctions per 100,000 person years: 4 (95% CI, –1 to 9)
Increased arterial thrombotic risk was also observed with use of the
- Combined vaginal ring
  - Stroke: aRR 2.4 (95% CI, 1.5 to 3.7)
  - Myocardial infarction: aRR 3.8 (95% CI, 2.0 to 7.3)
- Patch
  - Stroke: aRR 3.4 (95% CI, 1.3 to 9.1)
  - No myocardial infarctions
- Progestin-only implant
  - Stroke: aRR 2.1 (95% CI, 1.2 to 3.8)
  - ≤3 myocardial infarctions
There was no increased risk of arterial thrombosis with the progestin-only IUD
- Stroke: aRR 1.1 (95% CI, 1.0 to 1.3)
- Myocardial infarction: aRR 1.1 (95% CI, 0.9 to 1.3)

CONCLUSION:

Use of most modern contraceptive methods was associated with an increased rate of ischemic stroke and, in some cases, myocardial infarction
- Absolute risk remained small
The progestin-only IUD was not associated with increased rates of either stroke or myocardial infarction
Limitation of this study include observational design vs RCT and therefore possible residual confounding
The authors state in an opinion paper

Our findings underscore the critical need for continued research into the cardiovascular effects of hormonal contraception

Future studies should focus on identifying potential biological mechanisms underlying these risks, exploring how individual factors such as genetic predisposition, lifestyle, and comorbidities interact with contraceptive use