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

Nature Reviews Urology volume 22, pages 562–563 (2025)Cite this article

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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 ADT3,4. 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.

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Fig. 1: The central role of mitochondrial dysfunction in ADT-induced systemic effects.

References

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Authors and Affiliations

  1. Department of Urology, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan

    Yu-Hsiang Lin, Kuo-Jen Lin & Horng-Heng Juang

  2. School of Medicine, Chang Gung University, Taoyuan, Taiwan

    Yu-Hsiang Lin, Kuo-Jen Lin & Horng-Heng Juang

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Correspondence to Yu-Hsiang Lin.

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Lin, YH., Lin, KJ. & Juang, HH. Mitochondrial dysfunction as a crucial mediator of ADT-induced cardiovascular risk. Nat Rev Urol 22, 562–563 (2025). https://doi.org/10.1038/s41585-025-01050-6

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