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Thrombosis risk with estrogen therapy

Estrogen therapy in feminising hormone treatment increases the risk of venous thromboembolism (VTE): blood clots in leg veins (deep venous thrombosis) or in the lungs (pulmonary embolism). This risk depends on the form of administration, dose and patient characteristics.

Evidence from research

The cohort study by Getahun and colleagues (2018), published in Annals of Internal Medicine, found in trans women on estrogen therapy an increased incidence of venous thromboembolism compared to controls. The European ENIGI cohorts and the long-term study by Wierckx and colleagues (2012) also report an increased thrombosis incidence in trans women.

Oral versus transdermal

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

Risk factors

• Age above forty years
• Smoking
• Overweight and obesity
• Hereditary clotting disorders (such as factor V Leiden)
• Prolonged immobilisation or surgical procedures
• Previous thrombosis or pulmonary embolism

Advice in clinical practice

International guidelines recommend a risk assessment before starting estrogen therapy, with attention to family history, lifestyle and comorbidities. With elevated risk, transdermal administration is preferred. Smoking is strongly discouraged, and around surgical procedures estrogen use is often temporarily stopped.