Oral menopause hormone therapy linked to higher clot risk; patches and gels were not, Danish study finds

A large Danish study published in The BMJ on 23 September examined how different forms of menopausal hormone therapy (often called HRT) relate to blood clots, stroke and heart attack.

How it was done

Researchers used national health registries covering women aged 50–69 living in Denmark between 2003 and 2021. They identified 9,807 women with a first venous thromboembolism (a clot in a leg vein or the lungs), 18,460 with an ischaemic stroke and 11,974 with a heart attack, and compared each group with women of the same birth year who had no such event. Prescription records showed who was using hormone therapy, by which route, at what dose and for how long.

Main findings

• Current use of any oral hormone therapy was associated with a higher risk of venous clots, regardless of dose or duration.
• Higher risks of stroke and heart attack were seen only with high-dose oral estradiol (above 1 mg a day) taken for more than a year, rising with longer use.
• Transdermal therapy — patches, gels or sprays — showed no general increase in clot-related risk, whatever the regimen, dose or duration. The one exception, a higher heart-attack rate with a combined cyclic transdermal regimen, was based on sparse data.

In absolute terms

Oral estrogen (alone or with a progestin) was linked to roughly one extra venous clot for every 1,055 women treated for a year, one extra stroke per 1,642 and one extra heart attack per 3,846.

Caveats

The study is observational, so it cannot prove cause and effect. It lacked data on age at menopause, body-mass index and smoking, and the results may not apply to more ethnically diverse populations. Anyone using or considering hormone therapy should discuss the route and dose with a doctor rather than change treatment on their own.