Effects of Testosterone as a Gender-Affirming Hormone Therapy (GAHT-T) in the cardiovascular system: molecular mechanisms and potential biomarkers of cardiovascular risk

• Grant number: 23/12013-1
• Support Opportunities: Research Projects - Thematic Grants
• Start date: December 01, 2024
• End date: November 30, 2029
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Rita de Cassia Aleixo Tostes Passaglia
• Grantee: Rita de Cassia Aleixo Tostes Passaglia
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• City of the host institution: Ribeirão Preto
• Principal investigators: Alline Cristina de Campos ; Carlos Renato Tirapelli ; Michele Mazzaron de Castro
• Associated researchers: Carolina Sales Vieira ; Cristina Antoniali Silva ; Daniela Carlos Sartori ; Fausto Bruno dos Reis Almeida ; Fernando Morgan de Aguiar Correa ; Fernando Silva Carneiro ; Franciele Franco Scarante ; Ivaldo de Jesus Almeida Belém Filho ; Jeimison Duarte Santos ; Katiuchia Uzzun Sales ; Leonardo Resstel Barbosa Moraes ; Lucia Alves da Silva Lara ; Mauricio Serra Ribeiro ; Minna Moreira Dias Romano ; Sergio Henrique Pires Okano ; Vânia Luiza Deperon Bonato
• Associated scholarship(s): 25/13493-2 - Effects of THAG-T on behavioral and neuroplastic events induced by chronic stressor models., BP.PD; 25/03123-3 - Evaluation of autonomic cardiovascular responses evoked by restrain stress in an experimental model of testosterone hormone therapy, BP.IC; 23/02962-6 - The cGAS-STING pathway on vascular dysfunction induced by testosterone in a gender-affirming hormone therapy mouse model., BP.PD; 21/10014-5 - Involvement of oxytocinergic neurotransmission from the hypothalamic paraventricular nucleus on defensive responses and behavioral and cardiovascular changes in rats submitted to the intermittent social stress model, BP.PD

Abstract

Testosterone is the main pharmacological approach used by transmasculine individuals during gender-affirming hormone therapy (GAHT-T). Although presenting a safe profile, it can increase cardiovascular risk in this population. Of note, the literature lacks studies addressing the effects of testosterone, and related mechanisms, in the cardiovascular system of biological female organisms, especially in the context of GAHT-T. Thus, new studies are needed to elucidate the mechanisms and cardiovascular effects by GAHT-T, ultimately contributing to therapy optimization. Our proposal will evaluate the mechanisms whereby GAHT-T alters cardiovascular performance. It comprises 3 axes that address: axis 1) immune system-related mechanisms that alter cardiovascular function during GAHT-T; axis 2) central nervous system-mediated mechanisms that might impact cardiovascular function during GAHT-T; axis 3) the role of exosomes and its associated mechanisms contributing to cardiovascular damage during GAHT-T. The data will significantly advance the current knowledge on the impact of testosterone in cardiovascular biology, and the mechanisms whereby testosterone affects the blood vessels and the heart. In addition, it can uncover potential biomarkers for cardiovascular risk stratification in transmasculine individuals. Thus, our proposal may, ultimately, improve clinical practices for the transmasculine population, and the quality of life of those individuals. (AU)