A large-scale Danish study has found that certain hormonal contraceptives significantly increase women's risk of serious cardiovascular events, including heart attacks and strokes. The research, published in The BMJ, adds to growing evidence about the varying cardiovascular safety profiles of different hormonal contraceptive methods.
The most commonly prescribed birth control formulation—combination pills containing estrogen plus progestin—was associated with double the relative risk of heart attack and ischemic stroke. However, researchers emphasized that the absolute risk remains very low, translating to one extra stroke for every 4,760 women using the pill for one year and one additional heart attack per 10,000 women annually.
Dr. Harman Yonis from Nordsjaellands Hospital in Denmark, who led the research team, stated: "Although absolute risks were low, clinicians should include the potential risk of arterial thrombosis [blood clots] in their assessment of the benefits and risks when prescribing hormonal contraceptive method."
Comprehensive Analysis of Contraceptive Methods
The study analyzed national prescription records for more than 2 million Danish women aged 15-49, tracked from 1996 through 2021. Researchers examined various contraceptive methods including combination pills, vaginal rings, skin patches, progestin-only pills, intrauterine devices (IUDs), implants, and injections.
After controlling for factors such as age, education level, and pre-existing conditions like hypertension and diabetes, the findings revealed a hierarchy of risk among different contraceptive methods:
- Vaginal rings and skin patches containing estrogen-progestin combinations posed the highest risk, increasing ischemic stroke risk by 2.4-fold and heart attack risk by 3.8-fold
- Dual-hormone skin patch contraceptives specifically increased ischemic stroke risk by 3.4-fold
- Progestin-only pills and implants showed slightly elevated cardiovascular risks, but less than combination methods
- Progestin-only IUDs were the only hormonal contraceptive option that showed no increased cardiovascular risk, even with extended use
Similar Concerns with Hormone Replacement Therapy
A parallel Swedish study published in The BMJ examined hormone replacement therapy (HRT) used for menopausal symptom relief, finding similar cardiovascular concerns with certain formulations.
The Swedish analysis of over 919,000 women aged 50-58 found that oral estrogen-progestin HRT increased heart disease risk by 21% and dangerous blood clot risk by 61%. Similarly, the synthetic hormone pill tibolone (not approved in the U.S.) increased heart disease risk by 46% and nearly doubled stroke and heart attack risk.
Therese Johansson, a doctoral student at Uppsala University who led the HRT research, noted that while tibolone use has decreased in Sweden, "in 2018, approximately 1000 women initiated tibolone, which is estimated to have caused one stroke or heart disease event."
Route of Administration Matters
The research highlights important differences based on how hormones are delivered. Topical HRT applications (patches, gels, or creams) showed no increased heart disease risk, though they still elevated blood clot risk.
Researchers theorize this difference may be due to how oral hormones are metabolized in the liver, where many blood coagulants are produced. Oral administration may trigger increased coagulant production, raising clot risk, while topical applications largely bypass liver metabolism.
Clinical Implications
With an estimated 250 million women worldwide using hormonal contraception, these findings have significant public health implications despite the low absolute risk for individuals.
"These studies provide valuable information for both clinicians and patients to make more informed decisions about contraception and menopausal hormone therapy," said Dr. Yonis. "The varying risk profiles between different formulations and delivery methods give us options to personalize treatment based on a woman's individual risk factors."
For women with existing cardiovascular risk factors, these findings suggest that progestin-only IUDs may be the safest hormonal contraceptive option, while those seeking HRT might benefit from topical rather than oral formulations.
Healthcare providers are encouraged to consider these findings when discussing contraceptive and HRT options with patients, weighing the small but significant cardiovascular risks against the benefits and considering each woman's individual risk profile.
