Mitochondrial dysfunction as a crucial mediator of ADT-induced cardiovascular risk

Abstract

We read with great interest the recent Review article by Tisseverasinghe et al.¹, which offers a comprehensive overview of cardiovascular risks associated with various prostate cancer therapies, including androgen deprivation therapy (ADT) (Assessing the effects of prostate cancer therapies on cardiovascular health. Nat. Rev. Urol. https://doi.org/10.1038/s41585-025-01002-0; 2025). We wish to highlight an additional perspective, according to which mitochondrial dysfunction is likely to be a central mechanism bridging ADT to the diverse cardiometabolic sequelae.

Accumulating evidence indicates that low testosterone levels induce oxidative stress and impair mitochondrial function². Mitochondria, the cell’s powerhouse, regulate ATP production, redox balance and apoptosis. Perturbations in these processes during testosterone suppression might explain the heightened risk of atherosclerosis, QT prolongation and heart failure in men receiving ADT^3,4. Indeed, cardiomyocytes are known to depend heavily on efficient mitochondrial ATP synthesis, and even subtle mitochondrial impairment can precipitate electrical instability (leading to arrhythmias) and structural remodelling (promoting cardiomyopathies)⁴.