Thrombosis Risk with Estrogen Therapy

Estrogen therapy as part of feminizing hormone therapy increases the risk of venous thromboembolism (VTE): blood clots in the veins of the legs (deep vein thrombosis) or in the lungs (pulmonary embolism). This risk depends on the route of administration, dosage and patient characteristics.

Research evidence

The cohort study by Getahun and colleagues (2018), published in Annals of Internal Medicine, found a higher incidence of venous thromboembolism among trans women receiving estrogen therapy compared with controls. The European ENIGI cohorts and the longer-term study by Wierckx and colleagues (2012) also reported a higher incidence of thrombosis among trans women. An overview of cardiovascular risks, including thrombosis, is available at transkompas.nl.

Oral versus transdermal

The Endocrine Society Clinical Practice Guideline (2017) states that oral ethinylestradiol has a stronger effect on liver clotting factors than other estrogen preparations and is associated with a higher risk of VTE. Transdermal estradiol (patch or gel) is associated with a lower risk and is recommended for patients at increased risk.

Risk factors

• Age over forty
• Smoking
• Overweight and obesity
• Inherited clotting disorders (such as factor V Leiden)
• Prolonged immobilization or surgery
• Previous thrombosis or pulmonary embolism

Recommendations in clinical practice

International guidelines recommend a risk assessment before starting estrogen therapy, taking family history, lifestyle and coexisting conditions into account. For patients at increased risk, transdermal administration is preferred. Smoking is strongly discouraged, and estrogen use is often temporarily discontinued around surgical procedures. The broader picture is covered in cardiovascular disease during transition and side effects of hormone therapy; progesterone may also increase the risk of clotting.