Musculoskeletal and metabolic effects of androgen deprivation therapy in men with prostate cancer

The aim of this review is to summarize contemporary evidence on the impact of androgen deficiency and androgen deprivation therapy (ADT) for prostate cancer on muscle-bone and cardiometabolic health in men. The key physiological mechanisms by which testosterone, including its aromatisation to estradiol, regulates bone remodelling, muscle-bone crosstalk, and the maintenance of skeletal integrity are outlined. We also discuss studies demonstrating the relationships between low testosterone and estradiol concentrations, elevated sex hormone-binding globulin (SHBG) levels, reduced bone mineral density (BMD), and an increased risk of osteoporotic fractures in men. The effects of testosterone replacement therapy (TRT) on BMD and muscle mass are reviewed, with emphasis on the fact that, despite consistent improvements in skeletal parameters, current data do not allow firm conclusions to be drawn regarding fracture risk reduction. Particular attention is paid to the metabolic and inflammatory sequelae of ADT—including dyslipidaemia, insulin resistance, chronic low-grade inflammation and increased cardiovascular risk—and their links with sarcopenia and osteosarcopenia. Finally, we discuss clinical strategies for early identification and risk stratification, including DXA screening, assessment of muscle strength and cardiometabolic profile, and a multidisciplinary approach that combines antiresorptive therapy, lifestyle optimization, and structured exercise programmes to mitigate the adverse effects of ADT. The need for an individualised approach in men with hypogonadism, especially those receiving ADT, is highlighted, as is the need for future studies evaluating combined pharmacological and non-pharmacological preventive strategies, including novel osteoanabolic agents and targeted therapies for sarcopenia.