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A research team led by scholars at the School of Public Health, LKS Faculty of Medicine at The University of Hong Kong (HKUMed) evaluated the impact of testosterone in risk of blood clots, heart failure, and heart attacks using Mendelian randomisation in a large cohort study (UK Biobank). The team concluded that having a genetic predisposition to high testosterone levels could play a role in the development of major heart problems in men, such as blood clots and heart failure¹. The findings may also have implications for men who take testosterone supplements to boost energy levels and sex drive.

Background

Some evidence suggests that genetically predicted (“endogenous”) testosterone is positively associated with heart disease and stroke, especially in men². It is not clear whether testosterone has a causal role in the development of heart disease, but this is an important question for public health and regulators.

An international research team, led by Dr Mary Schooling at HKUMed, set out to assess the effect of endogenous testosterone on major blood clots, heart failure, and heart attacks using a technique called Mendelian randomisation. This approach may circumvent some of the limitations present in traditional observational studies.

Research method and findings

Using Mendelian randomisation, the researchers analysed genetic variants that predict testosterone levels and their associations with blood clots (thromboembolism), heart failure and heart attack (myocardial infarction) in almost 400,000 men and women from a large genome study and the UK Biobank database. Participants were aged 40 to 75 years and most were of British or European ancestry. Heart conditions were identified from self-reports, hospital and death records, and results were validated using data from another large genome study.

Analysing genetic information in this way avoids some of the problems that afflict traditional observational studies, making the results less prone to unmeasured (confounding) factors, and therefore more likely to be reliable. An association that is observed using Mendelian randomisation therefore strengthens the inference of a causal relationship.

The researchers found in the UK Biobank that in men, endogenous testosterone was associated with a higher risk of blood clots and heart failure, but not heart attack. In another large genetic study from the CARDIoGRAMplusC4D consortium, endogenous testosterone was also found to be associated with a higher risk of heart attack. Associations were less obvious in women.

The researchers point to some study limitations. For example, UK Biobank participants tend to be more highly educated and have healthier lifestyles compared with the general population, which may have affected the results. Nevertheless, they say these findings extend and complement previous findings, and suggest that endogenous testosterone “is detrimental for thromboembolism, heart failure, and myocardial infarction, especially in men.” Further evidence is needed to clarify whether these findings are relevant to the higher rates of these diseases in men than in women, and suggest it might be worth considering whether existing treatments that lower testosterone could help protect against these conditions.

1. Luo S, Au Yeung SL, Zhao JV, Burgess S, Schooling CM. Association of genetically predicted testosterone with thromboembolism, heart failure, and myocardial infarction: mendelian randomisation study in UK Biobank. BMJ, 2019 [in press]
2. Schooling CM, Luo S, Au Yeung SL, Thomson DJ, Karthikeyan S, Bolton TR, Mason AM, Ingelsson E, Burgess S. Genetic predictors of testosterone and their associations with cardiovascular disease and risk factors: A Mendelian randomisation investigation. International Journal of Cardiology, 2018. 267: 171-176

About the research team

The research was conducted by: Dr C Mary Schooling, Associate Professor and Cluster Leader (Non-communicable Diseases in Global Health) of the School of Public Health, HKUMed; Ms Shan Luo, PhD candidate, Dr Ryan Au Yeung, Assistant Professor, and Dr Jie Zhao, Research Assistant Professor, School of Public Health, HKUMed; and Dr Stephen Burgess, Sir Henry Welcome Post-Doctoral Fellow, Department of Public Health and Primary Care, University of Cambridge. This project was supported by the Small Project Funding (#201409176231) of The University of Hong Kong.

About the School of Public Health, HKUMed

The School of Public Health, LKS Faculty of Medicine of The University of Hong Kong has a long and distinguished history in public health education and high impact research. With world leading research in infectious diseases as well as on non-communicable diseases of both local and global importance, the School has made significant contributions through its research and advocacy to improve the health of populations and individuals, both locally and globally. The School is a leading research and teaching hub in public health on influenza and other emerging viruses, control of non-communicable and infectious diseases, tobacco control, air pollution, psycho-oncology, behavioural sciences, exercise science, life-course epidemiology, and health economics, health services planning and management. This work has informed international (e.g. the US Food and Drug Administration, Health Canada, the World Health Organization), national and local public health policies.

Media enquiries

Please contact LKS Faculty of Medicine of The University of Hong Kong by email (medkefa@hku.hk).

Please visit the website at http://www.med.hku.hk/news/ for press photo and presentation slides.