Some hormonal contraceptives are associated with a small but significant increased risk of stroke and heart attack, 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 team 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an association between hormonal contraception and heart attacks and strokes has been reported before the studies are outdated and have produced inconsistent results, they noted.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, used psychiatric medication, 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 heart attack, which translates to one extra stroke for every 4,760 women using the combined pill for one year, and one extra heart attack 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 heart attack 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 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 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.

‘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 first published by our sister title Pulse