Management of Recurrent Deep Vein Thrombosis in a Transgender Woman

Background: Transgender people using hormone treatment require lifelong medical care. Although cross-sex hormone treatment (CSHT) is usually considered safe, serious adverse events may occur. Here we report a case of deep vein thrombosis associated with estradiol treatment in an otherwise healthy young transgender woman. Case Presentation: A 21-year-old transgender woman using CSHT applied to our outpatient clinic with the complaint of painful swelling in her left leg. She was diagnosed with deep vein thrombosis (DVT) in the same leg one year earlier when she was admitted to the emergency room of another hospital with similar symptoms, and was given warfarin treatment for 3 months which has improved the symptoms. Three months after cessation of warfarin, symptoms re-occurred, but she was only able to apply to our clinic after another 3 months due to COVID-19 pandemic. Physical examination was unremarkable except asymmetrical swelling in the left leg. She has been receiving oral estradiol 6 mg/day and spironolactone 200 mg/day for 2 years. She denied taking estradiol in higher doses than recommended. She did not have any predisposing factors for DVT including obesity, immobilization and smoking. She had no prior history of venous thromboembolic events (VTE). Family history was also negative for thrombophilia except her uncle was diagnosed with ischemic cerebrovascular event at the age of 60. Lower extremity venous doppler ultrasonography revealed a thrombus in the left popliteal vein that caused total obstruction of blood flow to the distal. Plasma levels of d-dimer and fibrinogen were 0.35 mg/L and 262 mg/dL, respectively. Serum levels of sex hormones were estradiol: 204 pg/mL, total testosterone: 22.4 ng/dL, FSH: 0.22 mIU/mL, LH: 1.5 mIU/mL. Thrombophilia panel revealed a homozygous mutation in MTHFR (1296), and heterozygous mutations in both Factor V Leiden and plasma activator inhibitor (4G/5G). She was given enoxaparin in addition to warfarin until INR was elevated up to desired levels. Oral estradiol treatment was switched to transdermal route. Life-long anticoagulant treatment was suggested since the thrombotic event was triggered by estradiol treatment which will be continued. Conclusions: Limited data are available on incidence and management of VTE associated with estradiol treatment in male-to-female individuals. As in general population, routine screening for thrombophilia is not recommended in transgender women prior to the initiation of CSHT if no personal or family history of VTE is present. Even in the absence of predisposing factors, life-long anticoagulant therapy may be considered since the VTE-provoking estradiol treatment will be continued. Switching the route of estradiol treatment from oral to transdermal may be beneficial.