Background
Androgen deprivation therapy (ADT) is an effective treatment for prostate cancer but has many adverse effects consequent to severe hypogonadism. Muscle mass declines with ADT, however changes at a histological level have not been studied in humans. In testosterone replacement, an increase in cross-sectional area of all fibre types is seen; therefore we hypothesised that in men undergoing ADT the opposite would occur.
Aim
To assess histological changes in skeletal muscle in men initiating ADT for prostate cancer.
Methods
This prospective cohort study involved obtaining percutaneous thigh muscle biopsies (vastus lateralis) from 9 men with localised prostate cancer. The samples were taken immediately before and 1 month (mean 30.3±4.1 days) after commencing ADT and immediately processed. Direct histology was performed to measure fibre size (H&E stains), fibre type distribution (ATPase and NADH stains) and mitochondrial activity (COX/SDH stains). Slides were also reviewed for lipid and glycogen content.
Results
Mean total testosterone decreased from 16.5 nmol/L at baseline to 0.4nmol/L 1 month post-ADT (p=0.008). There was no significant change in mean fibre size (pre-ADT 61.5±19.1μm, post-ADT 56.8±7.8μm, p=0.95) or fibre type distribution (ratio pre-ADT 1.36, ratio post-ADT 1.15, p=0.43) over time. The variability coefficient for fibre size increased post-ADT (p=0.04), indicating an increased range of fibre sizes in post-ADT muscle compared to pre-ADT. No mitochondrial abnormalities or changes in intramuscular fat or glycogen content were noted.
Conclusions
No consistent histological changes were identified 1 month post-ADT. Increased fibre size variability post-ADT may be a consequence of testosterone fluctuations related to a transient rise in testosterone levels after ADT followed by the rapid fall to castrate levels. Further longitudinal studies are required to assess changes in muscle morphology and their functional consequences following prolonged exposure to hypogonadism.