Endocrine Abstracts

Introduction: Feminizing hormone therapy (HT) for male-assigned at birth (AMAB) includes estrogens, often in combination with anti-androgens. Several studies have reported an increased incidence of cardiovascular diseases and venous thromboembolism in AMAB receiving estrogens. Indeed, procoagulant changes induced by estrogen-based HT occur in transwomen as well as in cisgender individuals. Therefore, using estrogen in gender-affirming HT is relatively contraindicated in those with a history of thrombosis or thrombophilia. Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by increased erythropoiesis and is a relative contraindication to HT because of its high thrombotic risk.

Case Presentation: We describe a 36-year-old AMAB with PV and gender dysphoria. The patient had suffered clinically significant distress due to gender incongruence with a stable female gender identity since childhood. Indeed, in 2020, a diagnosis of gender dysphoria was made, and the patient expressed her firm will to begin a feminizing transition. However, in 2017, she was diagnosed with JAK2-positive PV and started treatment with low-dose aspirin and phlebotomy every month. Given her younger age and no history of thrombosis, her PV was considered at low risk for recurrent thrombosis. Nevertheless, the use of estrogen in her gender-affirming therapy was initially avoided due to the negative advice of her hematologist. Thus, to reduce her significant dysphoria, low-dose anti-androgen therapy with spironolactone 25 mg/day, preferred for less procoagulant effects, was started in June 2021 and titrated to 50 mg/day with clinical and psychological benefit. After one-year, lower testosterone levels were detected with concomitant improvement in hematocrit (43.5% vs 47.5% pre-treatment) and erythrocyte count (5.3/mm³ vs 6.2/mm³), allowing to extend the phlebotomy interval to 3 months.

Discussion & Conclusion: To date, there are no guidelines for gender-affirming HT in PV patients, and to our knowledge, no cases have been reported. Because of the lack of literature, we investigated the thrombosis risk of PV in other hyperestrogenic conditions, such as pregnancy. In patients with low-risk PV during pregnancy, antiplatelet therapy alone appears to be sufficient to prevent thrombotic complications. Therefore, even in our patient, low-dose aspirin helps to control the thrombotic risk. Moreover, anti-androgen therapy also had a beneficial effect by lowering the hematocrit, may be related to the decrease in testosterone levels, which normally increase erythropoietin and erythrocyte production. However, anti-androgen therapy alone could lead to hypogonadism with all its complications. Therefore, in our AMAB with PV we are currently considering combining anti-androgens with low-doses transdermal estrogens.