Hormonal Contraception Carries Slightly Elevated but Low Overall Cardiovascular Risk

Hormonal contraception is a cornerstone of reproductive healthcare, used by millions of women around the globe.

New research, conducted in Denmark, examined how different types of hormonal contraceptives influence the risk of arterial thrombosis. Published in the BMJ, the study found that most hormonal contraceptives were associated with an increased risk, although the absolute risks remained low.

The history of hormonal contraception

Hormonal contraception is one of the most widely used medical interventions worldwide, with the number of women using a modern contraceptive method increasing from 663 million to 851 million between 2000 and 2020. From the introduction of the first combined oral contraceptive pill in the 1960s to the development of newer formulations and delivery methods, these contraceptives have played a vital role in reproductive health. Beyond pregnancy prevention, they are commonly prescribed to manage conditions such as endometriosis, polycystic ovary syndrome and heavy menstrual bleeding, improving the quality of life for millions of women.

Over the decades, the range of available hormonal contraceptive methods has expanded beyond the traditional pill to include patches, vaginal rings, intrauterine systems, subcutaneous implants and injectable progestins.

"Despite their longstanding presence on the market, hormonal contraceptives continue to evolve with new formulations featuring lower doses and diverse active ingredients. These innovations, although designed to improve tolerability and usability, necessitate continual evaluation," said lead authors Dr. Amani Meaidi, a postdoctoral researcher, and Dr. Harman Yonis, a medical doctor and PhD student, from Copenhagen University Hospital.

Since the early years of hormonal contraception, concerns about an increased risk of blood clots have persisted. Most research has focused on venous thromboembolism – a condition that causes blood clots to form in veins – however, far less attention has been given to the risk of arterial thromboses. These events include ischemic stroke and myocardial infarction (heart attack).

“Although previous research has provided valuable insights, it is largely based on combined oral products and older formulations. This leaves gaps in knowledge regarding the risks associated with newer products, including insufficient information on the effects of mode of administration, estrogen type, progestin type and duration of use,” said Meaidi and Yonis.

“Sex hormones influence a wide array of tissues and physiological processes beyond reproduction, and it is essential to understand the intended and unintended effects of these medications. Ongoing research is critical to identifying potential risks, ensuring that the benefits of hormonal contraception continue to outweigh any associated harms,” they added.

Linking hormonal contraception to arterial thrombosis risk

The study used Denmark’s national health registers, which provided comprehensive prescription and medical records for over 2 million women aged 15 to 49. The researchers tracked hormonal contraceptive use and recorded instances of ischemic stroke and myocardial infarction over a follow-up period of 22 million person-years. Meaidi, Yonis and the team linked prescription data with hospital records to evaluate the risks associated with different contraceptive formulations, adjusting for factors such as hypertension, diabetes, smoking and family history of cardiovascular disease.

They found that most hormonal contraceptives were associated with an increased risk of arterial thrombosis, however, the level of risk varied depending on the type of hormonal contraceptive used.

Combined hormonal contraceptives, which contain both estrogen and progestin, were linked to the highest risk. The combined oral pill was associated with a 2-fold increase in both ischemic stroke and myocardial infarction, whereas the vaginal ring increased the risk of ischemic stroke 2.4-fold and myocardial infarction 3.8-fold. The contraceptive patch also increased stroke risk 3.4-fold.

Progestin-only contraceptives also carried an increased risk, though lower than the combined methods. The levonorgestrel intrauterine system was the only method not associated with an increased risk of arterial thrombosis.

Relative vs. absolute risk in hormonal contraceptive use

While the study found an increased relative risk with most hormonal contraceptives, it is important to interpret these findings in the context of absolute risk. The risk of arterial thrombosis in young women is inherently low, meaning that even a doubling of risk translates to only a small increase in cases.

Among women using the combined pill, the increase in absolute risk equates to ~1 additional ischemic stroke for every 4,760 users per year, and 1 additional myocardial infarction per 10,000 users per year.

“Although the absolute increased risks of stroke and myocardial infarction with hormonal contraception use were low, reflecting the rarity of these conditions in young women, the findings are of substantial public interest. Hormonal contraception is widely used worldwide, and even a small increase in the risk of serious adverse events can have meaningful implications at a population level,” said Meaidi and Yonis.

Understanding contraceptive safety and individualized choices

The findings underscore the need for individualized contraceptive choices to ensure the safest options for each patient. Healthcare providers should be equipped with up-to-date information to guide patients in making informed decisions about their contraceptive options.

"The key takeaway is that not all hormonal contraceptives carry the same risk of stroke and myocardial infarction, and individualized prescribing – considering factors such as dose, active ingredients and patient-specific risk factors – may enhance safety in contraceptive choices," said Meaidi and Yonis. 

Dr. Sonya Babu-Narayan, clinical director at the British Heart Foundation and consultant cardiologist, commented on the study, reassuring women that the additional risk remains low: “You shouldn’t be overly alarmed by these findings if you are using or considering starting hormonal contraception.  The additional risk of heart attack and stroke is very low for the vast majority.”

“The study is observational so it can’t prove cause and effect, and there may be other factors at play driving the links seen that aren’t sufficiently accounted for,” she added.

Dr. Becky Mawson, NIHR Clinical Lecturer in Primary Care at the University of Sheffield, also warned against overreaction:

“The risk of stroke and heart attack in pregnancy and postnatal period is significantly higher than the risks reported in this study for contraceptives.  For those using contraceptives for treatment of health conditions, the slightly increased risk needs to be balanced with the benefit in quality of life for those suffering debilitating gynaecological and hormonal conditions.”

“While it remains true as it has done for years that we need to find better, risk-free alternatives to prevent pregnancy, in my view this study hasn’t changed that and should not cause alarm but does add to growing knowledge in this area,” said Mawson.

“We urge the medical and scientific communities to maintain a strong focus on this field. Hormonal contraception may be an old drug category, but its story is still unfolding. Continuous research ensures that we remain attuned to its evolving safety profile, safeguarding the health of millions of women worldwide,” Meaidi and Yonis concluded.

Reference: Yonis H, Løkkegaard E, Kragholm K, et al. Stroke and myocardial infarction with contemporary hormonal contraception: real-world, nationwide, prospective cohort study. BMJ.  2025:e082801. doi: 10.1136/bmj-2024-082801

This article is a rework of a press release issued by the BMJ. Material has been edited for length and content.