Effects of Testosterone Hormone Therapy on Cardiovascular Parameters and Autonomic Modulation in Transmasculine Individuals: Impact of Time of Use and Factors Associated with Autonomic and Cardiovascular Response

• Grant number: 25/08478-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2026
• End date: December 31, 2028
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Rita de Cassia Aleixo Tostes Passaglia
• Grantee: Andrey Alves Porto
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 23/12013-1 - Effects of Testosterone as a Gender-Affirming Hormone Therapy (GAHT-T) in the cardiovascular system: molecular mechanisms and potential biomarkers of cardiovascular risk, AP.TEM

Abstract

Testosterone hormone therapy (THAG-T) is a crucial intervention for transmasculine individuals seeking to align their physical characteristics with their gender identity. Despite its effectiveness, the risks associated with THAG-T, particularly regarding cardiovascular health, are not yet fully understood. Observational data suggest that testosterone may increase arterial stiffness and reduce vasodilation, raising long-term cardiovascular risk. This project aims to investigate the effects of THAG-T on cardiovascular hemodynamic and autonomic parameters, considering the time of use, in addition to identifying biomarkers of cardiovascular risk, contributing to more effective and personalized clinical protocols. Methods: The project will be divided into two studies: 1) Prospective Cohort Study: The population will be composed of transmasculine individuals who will initiate THAG-T. The design will adopt the within-subject approach, with evaluations performed in five phases, the first before the start of THAG-T and the other four every six months for 24 months. Five visits to the laboratory will be made, with collections of biological material for serum lipid, glucose and creatinine dosage, considered markers of cardiovascular risk; cardiorespiratory functional evaluation; analysis of arterial stiffness; recording of cardiovascular parameters such as blood pressure (BP) and heart rate (HR) for analysis of baroreflex sensitivity (BRS) and autonomic modulation of HR (HRV) and BP (BPV) variability. 2) Cross-Sectional Study with Retrospective Elements: Participants will include transmasculine individuals using THAG-T for at least 12 months. The design will allow for comparisons between groups, including healthy cisgender men and women. Existing data will be used to explore associations between testosterone exposure and cardiovascular/autonomic outcomes. Statistical analysis will include stratifications by duration of testosterone use, age range, and adrenergic receptor gene polymorphisms to identify patterns and relationships among clinical, autonomic and laboratory data. (AU)