Reply to ‘Mitochondrial dysfunction as a crucial mediator of ADT-induced cardiovascular risk’

We appreciate the thoughtful comments from Yu-Hsiang Lin et al. regarding our Review article (Assessing the effects of prostate cancer therapies on cardiovascular health. Nat. Rev. Urol. https://doi.org/10.1038/s41585-025-01002-0; 2025)¹. In their Correspondence (Mitochondrial dysfunction as a crucial mediator of ADT-induced cardiovascular risk. Nat. Rev. Urol. https://doi.org/10.1038/s41585-025-01050-6; 2025)², the authors highlight the potential role of mitochondrial dysfunction as a unifying mechanism underlying the diverse systemic effects of androgen deprivation therapy (ADT), including cardiovascular, metabolic and neurocognitive complications.

We agree that mitochondrial dysfunction is indeed a possible understudied contributor to ADT-induced cardiotoxicity. As Lin et al. note, low testosterone levels have been linked to oxidative stress and impaired mitochondrial function, which could contribute to conditions such as atherosclerosis, arrhythmias and heart failure^3,4. These observations are further supported by preclinical and clinical evidence suggesting that ADT disrupts processes heavily reliant on mitochondrial integrity, including cellular energy metabolism, redox balance and apoptosis pathways^5,6. Beyond cardiovascular effects, we also agree that mitochondrial dysfunction might potentially have a role in the progression of castration-resistant prostate cancer and ADT-associated neurocognitive decline. The observed shift towards aerobic glycolysis, often referred to as the Warburg effect, in prostate cancer cells under ADT might suggest a possible role for mitochondrial regulation in both oncogenesis and treatment resistance⁷.