Approved research

Sex hormones as predictors of key health outcomes in men from the UK Biobank

Lay summary

As men grow older, testosterone production and the level of testosterone in the blood declines. However, this varies between men, such that men of the same age might have different testosterone levels. An increasing number of research studies have reported findings suggesting that men with low levels of testosterone have an increased the risk of poor health outcomes in future. However, results have differed among studies. The purpose of this research to clarify the role of testosterone and other sex hormones on health outcomes in men. The UK Biobank is an important resource for health research which contains information from more than 500,000 individuals. In this project, researchers will analyse anonymised data (no identifying information) from adult male participants, including age, health status, ethnicity, smoking and alcohol consumption at enrolment; the level of testosterone and other sex hormones already measured from blood samples; as well as additional data that have been subsequently collected from medical records and the national death registry. A series of analyses will be done to determine whether a low or a high level of testosterone measured at enrolment is more or less likely to predict subsequent illness or death in men. Since the UK Biobank information is collected from a relative large sample of the population, this provides a valuable opportunity to explore these questions. That it is a large sample means that results are likely to be broadly representative of what is happening in the population, and therefore suitable for drawing conclusions on public health. A relatively large dataset means that more precise and reliable estimates can be obtained, compared to other smaller-scale studies that have been published to date. Findings from this study will help to resolve conflicting reports about whether testosterone is a biomarker for ill health in men or whether it contributes to the incidence of disease. Additionally, when these findings are interpreted together with separate analyses that combine data from many individual smaller-scale studies, stronger conclusions can be made about the importance of sex hormone levels in men for their future health, and results from this large UK cohort study will be placed into a global context.

Scope extension:

This study aims to investigate the role of circulating sex hormones to influence health outcomes in men from a large cohort in the United Kingdom. Our primary aim is to define the associations of plasma testosterone concentrations with incidence of cardiovascular events, cancer, cognitive decline, dementia and mortality risk, and to identify factors predicting testosterone concentrations in men from the UK Biobank population. Results from this investigation will be compared and contrasted with results from an Individual Participant Data (IPD) meta-analysis involving nine prospective cohort studies (from Australia, Europe and the United States) which will examine associations of sex hormones with these outcomes in men. Together, these insights will clarify the influence of sex hormone exposures on several important health outcomes in men, and thus addressing the varying and conflicting results published on this topic. The analysis of data from the UK Biobank, and from the IPD meta-analysis will complement each other in addressing these aims, and will place results from this large UK cohort into a global context.

We propose to extend the scope of this research by investigating the associations of sex hormone variables (testosterone and SHBG) with the additional health outcome of biological ageing, as indicated by leucocyte telomere lengths (LTL). The aim is to clarify associations with LTL using data from the University of Leicester and UK Biobank, as this is a large cohort study and offers the prospect for estimating effects with increased precision.