The mechanisms linking hormonal and autonomic regulation with prostate cancer risk and outcomes remain unclear. Testosterone influences prostate tissue growth, metabolism, and inflammation, yet its role in prostate cancer development and progression is still debated. Heart rate variability (HRV), a measure of autonomic nervous system activity, reflects stress, inflammation, and cardiovascular health, but its relevance to prostate cancer has not been systematically explored.
Using UK Biobank data, this project will investigate the associations of circulating testosterone and HRV with prostate cancer incidence, mortality and survival amongst men. We will assess whether testosterone and HRV act as mediators or independent predictors of cancer risk and progression. Anthropometric, lifestyle, and metabolic factors-for example, adiposity, diet, physical activity, alcohol, smoking, and metabolic biomarkers-will be examined as exposures influencing these biological pathways.
We will conduct prospective analyses using Cox regression to estimate associations with cancer risk and survival, and casual mediation models to quantify indirect effects via testosterone and HRV. Where data allow, tumour characteristics and subtypes will be explored. This research aims to clarify hormonal and autonomic mechanisms underlying prostate cancer development and prognosis, improving understanding of how modifiable lifestyle and metabolic factors influence men’s cancer risk. The findings may help identify novel biological targets and support prevention and early detection strategies, aligning with UK biobank’s mission to advance population health for the public good.