One of the questions that worries people starting gender-affirming hormone therapy most is that of cardiovascular risk. In transgender women it has long been known that oestrogen can raise the likelihood of thrombosis —the formation of blood clots—, but the exact mechanisms were not fully understood. A large European study now provides a key piece: it not only confirms that risk, it also shows how the blood changes in opposite directions depending on which hormone is taken. The results were published in Research and Practice in Thrombosis and Haemostasis, the journal of the International Society on Thrombosis and Haemostasis.
More than 570 people followed for a year
The work is part of the European ENIGI network, the world’s largest prospective cohort devoted to studying gender-affirming hormone therapy. Researchers in Amsterdam, Ghent and Odense followed 251 transgender women and 320 transgender men for twelve months, all of them over 17 years of age.
Before starting treatment and one year later, they analysed in the laboratory the characteristics of the fibrin clot —the protein mesh that forms when blood coagulates—. They measured three things: how fast the clot forms, how easily it dissolves afterwards and what structure it has. This is the technique known as turbidimetry.
Oestrogen speeds up clot formation
In transgender women, feminising therapy made the clot form faster and dissolve less well. In other words, the blood as a whole became more prone to clotting, something medicine calls a prothrombotic effect. All the changes were statistically very clear.
The most striking thing is that the effect depended on the route of administration. Oral oestradiol produced the biggest changes in coagulation. Those who took it transdermally (patches or gel) showed a smaller effect, something earlier studies had already suggested and which has to do with the so-called “first hepatic pass”: on passing through the liver, oral oestrogen stimulates the production of clotting proteins.
Testosterone does just the opposite
In transgender men the result was the opposite. Twelve months of testosterone made the clot form more slowly and dissolve better. The blood tended towards an antithrombotic effect, that is, more fluid and less likely to form thrombi.
Curiously, when the two groups were compared at the end of the year, the coagulation differences between transgender women and men were no longer statistically significant. The key lay not in the sex assigned at birth, but in the hormone itself and in the way it is administered.
What it means for clinical practice
These results help explain why the risk of thrombosis in feminising therapy is higher, above all in the first months and with oral oestradiol. They are not a reason to give up treatment, which has very positive effects on mental health and identity, but they are a reason to individualise it.
For transgender women with additional risk factors —obesity, smoking, a history of thrombosis or certain clotting disorders—, choosing a transdermal route instead of the oral one can be a relevant decision. The choice of route and dose should always be made with a medical team familiar with each person’s history.
A large study, with nuances
This is one of the largest samples ever assembled to study the effect of hormone therapy on coagulation, with a prospective one-year follow-up. The authors note that fibre density did not change, which indicates that the hormone acts above all on the formation and dissolution of the clot, not on its structure.
Open questions remain, such as the longer-term effect or the influence of antiandrogens. But the central message is clear and useful: gender-affirming hormone therapy changes the blood, and it does so in opposite directions depending on the hormone, with an important practical nuance for the health of transgender people.
Source: Feminizing and masculinizing gender-affirming hormone therapy affects fibrin clot characteristics in opposite directions. Bøgehave M, Glintborg D, Christensen LL, T’Sjoen G, den Heijer M, Andersen MS, Bladbjerg EM. Research and Practice in Thrombosis and Haemostasis 2026;10(4):106648. DOI: 10.1016/j.rpth.2026.106648.
Read the publication: Research and Practice in Thrombosis and Haemostasis.
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