Some hormonal contraceptives are associated with a small but significant increased risk of stroke and myocardial infarction, according to a large and detailed study from Denmark.
The analysis was based on national prescription records for more than two million Danish women between 1996 and 2021.
It showed that ‘contemporary’ oestrogen-progestin and progestin-only contraceptives were associated with an increased risk of arterial thrombotic events.
Reporting in the BMJ, the researchers said the highest risks were seen with oestrogen containing products, in particular the vaginal ring and skin patch.
But no increased risk was found for the levonorgestrel-releasing intrauterine device.
While an association between hormonal contraception and myocardial infarction and strokes has been reported before, these studies are outdated and have produced inconsistent results, they researchers noted.
There had also been a lack of detail on the different types of contraception, route of administration and duration of use, they added.
They stressed that the risk they found remains low but, given widespread use, clinicians need to be aware of the potential risks when prescribing, they added.
Women were excluded from the analysis if they had a history of blood clots, cancer, liver disease, kidney disease, polycystic ovary syndrome, endometriosis or infertility treatment; if they used psychiatric medication or hormone therapy; or had undergone a hysterectomy.
Researchers also took into account confounding factors such as age, education level and existing conditions such as hypertension and diabetes.
The combined pill – the most common type prescribed – was associated with double the risk of ischaemic stroke and myocardial infarction, which translates to one extra stroke for every 4,760 women using the combined pill for one year, and one extra myocardial infarction for every 10,000 women per year of use.
Progestin-only contraceptives, including pills and implants, carried a slightly elevated risk, though lower than the combined pills, they reported.
By contrast, the vaginal ring increased ischaemic stroke risk 2.4-fold and myocardial infarction risk 3.8-fold, while the patch increased ischaemic stroke risk 3.4-fold.
But they also found that duration of use of hormonal contraceptive did not seem to influence the risk.
‘Although absolute risks were low, clinicians should include the potential risk of arterial thrombosis in their assessment of the benefits and risks when prescribing hormonal contraceptive method,’ they authors concluded.
A linked editorial noted that it was important women were able to make an informed choice but that clinicians needed up-to-date evidence and training.
Professor Angela Clerk, professor of biomedical science at the University of Reading, said the study appeared to be ‘comprehensive and rigorous’ but added there should be some caution in extrapolating to other populations with different ethnicities.
‘Genetic background and cultural variation could affect cardiovascular risk, and some ethnicities not fully covered by the Danish population could have greater vulnerability,’ she said.
‘This is clearly an important study but, while the focus is on the potential negative effects of contraception on cardiovascular risk, it is also clear that any increase in risk is actually very small.’
It highlighted the overall safety of the drugs, particularly when balanced against the negative effects of unwanted pregnancies resulting from a lack of contraception, she noted.
Dr Sonya Babu-Narayan, consultant cardiologist and clinical director at the British Heart Foundation, said: ‘The researchers made use of a wealth of long-term electronic healthcare information from over two million people in Denmark – this scale and breadth makes the findings more reliable and complete than previous studies and enables study of even rare complications like these.
‘However, 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.
‘This latest study supports the current practice of recommending the option of a progestin intrauterine device – the hormonal coil – for those already living with high cardiovascular risk, as this wasn’t linked to more heart attacks and strokes.‘
Dr Channa Jayasena, consultant in reproductive endocrinology, Imperial College London, said it was well known that the pill increases blood clot risk.
‘The absolute risk of having a stroke or heart attack on the pill is still very low,’ he said. ‘Women should take away the importance of smoking cessation, healthy eating, and exercise to minimise the (small) increased risk of stroke or heart attack associated with being on the pill.
‘Women who have high risks of stroke or heart attack that cannot be reduced should strongly consider a hormonal coil, because of its lack of associated increased stroke or heart attack risk.’
A version of this article was originally published by our sister publication Pulse.
