Longitudinal thrombo-inflammatory profiling of individuals undergoing gender-affirming hormone therapy (Hyper-gender study)
Transgender people who wish a physical appearance closer to their gender identity can get access to gender-affirming hormone therapy, which for transgender women include estrogens in combination with androgen-lowering medications and for transgender men include testosterone. Among the pathways most influenced by the cross-sex hormone therapy are the coagulation profile and the inflammatory status, which may cooperate to increase the cardiovascular risk also in young people. Particularly, transgender men appear to carry an increased risk of venous thromboembolism related to an estrogen-driven hypercoagulable state, while transgender women are at increased risk of cardiovascular events due to testosterone-associated dyslipidemia. However, the mechanisms underpinning these harmful relationships are not known. Combining the expertise of three leading Centers in Italy on transgender medicine, coagulation and cardiovascular diseases, as well as iron metabolism disorders, hence taking advantage of a multidisciplinary approach, the project aims at elucidating the overall prothrombotic mechanisms occurring during a 2-year course of gender-affirming hormone therapy with different hormonal strategies. The role of chronic inflammation and iron state changes associated with the use of these hormone protocols together with development of non-alcoholic fatty liver disease (NAFLD) will be also evaluated. A cohort of at least 100 transgender subjects, both Assigned Females at Birth (AFAB) and Assigned Males at Birth (AMAB), starting gender-affirming hormone therapy will be recruited at baseline and parameters longitudinally assessed 3-, 6-, 12- and 24 months after the initiation of GAHT. The combined longitudinal changes in coagulation, inflammatory and lipid profile will be correlated with the occurrence of endothelial dysfunction. Alterations of iron pathways and related readouts will be associated with coagulation and inflammatory perturbations in order to ascertain the possible pro-thrombotic additional effect. In this complex scenario, hepatic dysfunction exemplified by fatty liver disease (NAFLD/NASH) may play a relevant role, since it is often accompanied by a procoagulant and proinflammatory status, as well as by erythrocytosis. Thus, we will focus on liver function and stiffness (readout of fibrosis) modifications and liver local inflammation and repair linked to cross-sex hormone therapy. The results of this proposal will provide a clear description of the complete pathophysiologic modifications associated with long-term use of cross-sex hormones, covering a knowledge gap in the subject of transgender medicine and hormones-related effects on cardiovascular diseases. Data generated have the potential to decipher novel pathophysiological mechanisms useful for possible pharmacological and non-pharmacological preventive interventions specifically in the transgender population, but also in other acquired thrombo-inflammatory conditions.
Data di avvio 30 Novembre 2023
Data di completamento 30 Novembre 2025
Total cost €34810
Progetto P2022RWMFC finanziato all’interno del Bando PRIN 2022 PNRR di cui al Decreto Direttoriale n. 1409 del 14/9/2022 nell’ambito del Piano Nazionale di Ripresa e Resilienza, Missione 4 – Componente 2. Dalla Ricerca all’Impresa - Investimento 1.1 Fondo per il Programma Nazionale della Ricerca (PNR) e Progetti di Ricerca di Rilevante Interesse Nazionale (PRIN), finanziato dall’Unione europea – NextGenerationEU – CUP B53D23031770001
Ultimo aggiornamento
04.06.2024