Thrombophilia and hormonal therapy in transgender persons: A literature review and case series

Abstract

Background: Venous thromboembolism (VTE) is a rare side effect of hormonal therapy in transgender persons. Prothrombotic genetic variants can increase this risk. For this reason, previous VTE and/or genetic thrombophilia may be considered by some as contraindications to hormonal treatment. Aim: To formulate directions for clinical practice about the indications for thrombophilia screening and when to consider combination therapy of therapeutic anticoagulation and hormonal treatment as a safe alternative to withholding hormonal treatment. Methods: We conducted a literature search and describe a case series. All adult patients with gender dysphoria and a known prothrombotic genetic variant or history of VTE were invited by letter to participate in this study. Results: In our center, thrombophilia screening before start of hormonal treatment was restricted to those with a personal or family history of VTE. Sixteen individuals with a history of VTE and/or an underlying prothrombogenic condition were described. The time of follow up varied from 4 months to 20 years. Seven trans women had a positive thrombophilia screening (2 Factor V Leiden (FVL), 1 FVL + anticardiolipin antibodies, 1 FVL + high Factor VIII coagulant activity, 1 protein C deficiency, 1 prothrombin mutation, 1 positive lupus anticoagulant). Three trans women experienced an unprovoked VTE after start of hormonal therapy of which one lead to a positive thrombophilia screening. One VTE event in a trans woman was assumed to be provoked by surgery. Five trans men were identified with a prothrombogenic mutation (3 FVL, 1 protein C deficiency, 1 prothrombin mutation). One trans man, with a negative thrombophilia screen, experienced multiple provoked VTE events before start of hormonal therapy. Conclusion: Based on our literature review and case series we offer guidance when confronted with patients with previous VTE and/or genetic thrombophilia requesting hormonal interventions.

Venous Thromboembolism and Estrogen-Containing Gender-Affirming Hormone Therapy

“…A small proportion of this cohort (7.2%) had a thrombophilia, most of which were the lower risk heterozygous factor V Leiden mutation with only one protein S deficiency. A 2022 case series 55 included 7 transgender people with an underlying thrombophilia who received estrogen therapy, three of whom experienced a VTE over a 20-year study period (one case of VTE was provoked by surgery, the other two were considered unprovoked). The finding that underlying thrombophilia increases the risk of VTE is consistent with larger studies of cisgender women taking exogenous estrogen but it appears the risk is still lower in the transgender population.…”