Cardiovascular Risk with Gender‑Affirming Hormone Therapy

Abstract

Gender incongruence refers to a persistent mismatch between an individual’s experienced gender and the sex assigned at birth. While modern terminology is recent, descriptions of gender variance date back to antiquity, including writings attributed to Hippocrates.

By the 7^th century, Paul of Aegina, in his Medical Compendium, described surgical procedures aimed at modifying sex characteristics. While these early interventions were not grounded in a modern understanding of gender identity, they reflect attempts to address distress related to discordance between physical characteristics and lived experience. For much of history, surgical intervention—most commonly orchiectomy—remained the primary medical approach.

A more structured medical understanding began to emerge in the early 20^th century, including the establishment of early centres dedicated to the study and care of gender‑diverse individuals.

In modern practice, access to gender‑affirming hormone therapy (GAHT) and surgical interventions has improved. However, there remains a relative paucity of high-quality clinical research to guide management. Randomized controlled trials are lacking, and current recommendations are largely based on retrospective observational studies and extrapolation from cisgender populations. This limited evidence base makes it challenging to balance treatment goals with risk mitigation—particularly with respect to cardiovascular disease. This brief review aims to summarize the current evidence and provide a practical framework for clinicians.