Hormonal contraceptives linked to increased stroke and heart attack risk

Hormonal contraceptives linked to increased stroke and heart attack risk | Image Credit: © utah51 - © utah51 - stock.adobe.com.

The risks of stroke and heart attack are increased by certain hormonal contraceptives, according to a recent study published in The BMJ.¹

The study found increased risks from multiple forms of hormonal contraceptives, but the most significant risks were from oestrogen products. Researchers noted that the absolute risks remain low overall.

Hormonal contraceptive use has been reported in over 250 million women worldwide, but investigators noted inconsistent findings about the link of these contraceptives with ischemic stroke and heart attack risks. “There is also a lack of evidence on the effects of different hormone combinations,” investigators said.

The study was conducted to fill this research gap. Participants included Danish women aged 15 to 49 years between 1996 and 2001. These women had no medical history of any arterial or venous thrombosis, liver disease, cancer, kidney disease, thrombophilia, antipsychotic use, hysterectomy, oophorectomy, endometriosis, or polycystic ovary syndrome.²

Follow-up lasted until death, emigration, exclusion conditions, or July 1, 2021. Data about participants’ sex, date of birth, and vital status was obtained from the Civil Registration System, while redeemed prescription data was obtained from the National Registry of Medicinal Product Statistics.

Additional data collected included discharge diagnoses and surgical procedures from the National Registry of Patients, live births and death births from the Danish National Birth Registry, induced abortions from the Registry of Legally Induced Abortions, and education status from Statistics Denmark.

Women with a filled prescription for any hormonal contraceptive were considered current users. The date of redemption, type, and quantity of the contraceptive were reported for these patients.

The number of daily doses purchased was reported to determine the duration of use for oral, ring, patch, and injection contraceptives. Time of no use was defined as gaps in contraception use longer than 28 days.

International Classification of Diseases, Tenth Revision codes were used to identify cases of ischemic stroke. Covariates included calendar time, age, surgery, pregnancy, education level, oral tranexamic acid use, and comorbidities.

There were 2,025,691 women with 22,209,697 person years of follow-up time included in the final analysis. During the follow-up period, 4730 incident ischemic strokes and 2072 incident myocardial infractions were reported, with death within 30 days occurring in 2% and 8.9% of women developing these conditions, respectively.

In patients using combined oral contraceptives, the ischemic stroke rate was 39 per 100,000 person years. For myocardial infractions, this rate was 18 per 100,000 person years.

The adjusted incidence rate ratio for ischemic stroke and myocardial infraction were both 2 for using oral contraceptives with oestrogen and progestin vs no hormonal contraception. This indicated 21 and 10 additional ischemic strokes and myocardial infractions per 100,000 person years, respectively.

When using combined oral contraceptives with 20 µg of ethinyl oestradiol, an adjusted incidence rate ratio of 1.9 was reported for ischemic stroke, vs 2 for tablets with 30 to 40 µg. For myocardial infractions, these rate ratios were 1.6 vs 2.1, respectively.

An adjusted risk ratio of 2.4 for ischemic stroke and 3.8 for myocardial infraction was reported when using the combined vaginal ring vs no hormonal contraception. These corresponded to incidence rate differences of 28 and 41 per 100,000 person years, respectively.

For the hormonal patch, the adjusted risk ratio was 3.4 for ischemic stroke. However, no cases of myocardial infraction were observed for combined hormonal patch use. Rates of 33 and 13 per 100,000 person years for ischemic stroke and myocardial infraction, respectively, were reported when using progestin-only oral contraceptives.

These results indicated increased ischemic stroke and myocardial infraction rates from the use of certain hormonal contraceptives. Investigators concluded health care providers “should consider these risks when assessing the benefit-risk profile of hormonal contraceptives.”

References

1. New study adds to evidence of stroke and heart attack risk with some hormonal contraceptives. BMJ Group. February 12, 2025. Accessed February 13, 2025. https://www.eurekalert.org/news-releases/1073300
2. 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. doi:10.1136/bmj-2024-082801