September 23, 2026

expert reaction to oral menopause hormone therapy linked to increased risk of blood clots, and cardiovascular disease at higher doses

Scientists comment on a study, published in The BMJ, that investigates a link between oral menopause hormone therapy and increased risk of blood clots and cardiovascular disease at higher doses. 

Prof Robert F. Storey, Professor of Cardiology, University of Sheffield, said:

“This is a high-quality ‘case-control’ study of women living in Denmark, comparing those who had suffered from venous thromboembolism (mostly related to leg vein clots), strokes or heart attacks (a large proportion of which are caused by blood clots) with others in the same age range who had not suffered from any of these conditions. The authors conclude that oral oestrogen replacement therapy, even for a short duration, is associated with increased risk of venous thromboembolism whereas only high-dose oral oestrogen replacement therapy given for more than 1 to 5 years was associated with increased risk of stroke or heart attack. On the other hand, oestrogen replacement patches applied to the skin were not associated with increased risk. 

The conclusions of the authors are well supported by their data. It is well recognised that oral oestrogen replacement increases the risk of leg vein clots, which can cause life-threatening lung blood clots. Taking oral oestrogen replacement leads to a spike in the level that stimulates the liver to increase production of factors that stimulate blood clot formation. Similarly, it is well described that oestrogen replacement patches don’t carry the same risk since they don’t stimulate the liver in the same way, so the study results confirm this in a convincing way. The increased risk of stroke and heart attack associated with high dose oral oestrogen replacement reported in this study raises concerns about this treatment, even though it remains uncertain whether this treatment is directly responsible since these observational studies cannot exclude other explanations that are not apparent from the data. For example, if it is more likely for people to continue oestrogen replacement for longer if they have symptoms of unrecognised heart disease then this could bias the findings. However, it does emphasise the importance of ensuring that risk factors for cardiovascular disease are well controlled in women receiving oral oestrogen replacement therapy, including satisfactory control of cholesterol and blood pressure. The study emphasises the superior safety of patches over oral treatment and, in view of their higher cost, further cost-effectiveness analyses are warranted to guide who these should be prioritised for but evidently, they should be a priority in anyone who has an increased risk of leg vein clots, stroke or heart attack.”

 ‘Contemporary menopausal hormone therapy and thrombotic disease: nationwide nested case-control study’ by Julie Berggreen et al. was published in The BMJ at 23:30 UK time on Wednesday 23^rd September.

DOI: 10.1136/bmj-2026-100688

Declared interests

Prof Robert F. Storey: “I don’t have any conflicts of interest related to oestrogen replacement therapy.”