Effects of lifelong testosterone exposure on health and disease: a Mendelian randomization study
- McMaster University, Canada
Abstract
Testosterone products are prescribed to males for a variety of possible health benefits, but causal effects are unclear. Evidence from randomized trials are difficult to obtain, particularly regarding effects on long-term or rare outcomes. Mendelian randomization analyses were performed to infer phenome-wide effects of free testosterone on 461 outcomes in 161,268 males from the UK Biobank study. Lifelong increased free testosterone had beneficial effects on increased bone mineral density, and decreased body fat; adverse effects on decreased HDL, and increased risks of prostate cancer, androgenic alopecia, spinal stenosis, and hypertension; and context-dependent effects on increased haematocrit and decreased C-reactive protein. No benefit was observed for type 2 diabetes, cardiovascular or cognitive outcomes. Mendelian randomization suggests benefits of long-term increased testosterone should be considered against adverse effects, notably increased prostate cancer and hypertension. Well-powered randomized trials are needed to conclusively address risks and benefits of testosterone treatment on these outcomes.
Data availability
Individual-level data cannot be provided, but it is available to all researchers by application to the UK Biobank. Summary-level GWAS data will be returned to the UK Biobank Access Team for use by other researchers. All MR results and genome-wide significant SNPs have been provided in Supplementary Tables 4 to 12.
Article and author information
Author details
Funding
Canadian Institutes of Health Research (Frederick Banting and Charles Best Canada Graduate Scholarships Doctoral Award)
- Michael Chong
Canadian Institutes of Health Research (Post-Doctoral Fellowship)
- Robert W Morton
McMaster University (E.J. Moran Campbell Internal Career Research Award)
- Marie Pigeyre
McMaster University (McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care)
- Hertzel C Gerstein
Cisco Systems (Professorship in Integrated Health Biosystems)
- Guillaume Paré
Canada Research Chairs (Canada Research Chair in Genetic and Molecular Epidemiology)
- Guillaume Paré
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: UK Biobank received ethical approval from the North West Multi-Centre Research Ethics Committee (REC reference: 11/NW/0382). This research was conducted using the UK Biobank under Application Number 15255.
Copyright
© 2020, Mohammadi-Shemirani et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Effects of lifelong testosterone exposure on health and disease: a Mendelian randomization study
eLife 9:e58914.
https://doi.org/10.7554/eLife.58914
