Mitochondrial Fitness and Endurance May Help Men With Prostate Cancer Tolerate Androgen Deprivation Therapy Better

A study published in Nature Communications, “Muscle mitochondria, function, mass, and quality of life in prostate cancer during androgen deprivation therapy,” looked at how muscle health affects men with advanced prostate cancer during androgen deprivation therapy. The researchers followed 60 patients over six months and assessed body composition, strength, endurance, quality of life, and skeletal muscle mitochondrial function. Their results suggest that patients with better baseline endurance and healthier mitochondria cope better with treatment-related decline.

The study included 60 men, with 59 seen at baseline, 57 at 3 months, and 55 at 6 months. Most had advanced disease features: 32.2% had lymph node or distant metastases, 81.3% had grade group 3 or higher tumors, 61% also received radiotherapy. Most patients (93.2%) were treated with a GnRH agonist, while a small minority received another form of ADT. No significant tumor progression was seen during the 6-month follow-up.

At the start of study, right before starting androgen deprivation therapy (ADT), men with higher VO2 peak and stronger mitochondrial function tended to report better well-being and lower symptom burden. In contrast, muscle mass alone was not a reliable marker of how patients felt or functioned, and higher lean mass was sometimes linked to worse patient-reported outcomes. This is an important point because it shows that muscle quantity and muscle quality are not the same thing.

Over the course of treatment, the group as a whole experienced expected side effects. Lean mass decreased, fat mass increased, aerobic fitness declined, and several quality-of-life measures worsened. The study also found that higher baseline VO2 peak and mitochondrial respiration predicted smaller declines in muscle mass, physical performance, and quality of life. This means that the men who entered treatment in better metabolic shape were more resilient.

The investigators used several methods to get a detailed picture of the problem. They assessed body composition with DEXA scans, physical function with tests such as handgrip strength, stair climb power, and the six-minute walk test, and patient experience with validated quality-of-life questionnaires. They also performed muscle biopsies to study mitochondrial respiration and protein changes inside the muscle, which showed reduced mitochondrial-related pathways and increased inflammatory and remodeling signals after six months of therapy. In practical terms, this suggests that androgen deprivation therapy may make muscle less efficient at producing energy and more prone to stress-related changes.

Taken together, the study supports the idea that endurance training may be especially valuable for men receiving androgen deprivation therapy. Resistance training still matters for preserving strength and lean mass, but aerobic exercise appears particularly relevant for supporting mitochondrial health and stamina.

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