Role of genetics in the age-related testosterone decline in men: a UK Biobank study
Authors' conclusion
Non-genetic factors are strongly associated with age-related BAT decline, whereas genetic predisposition may have a limited role. However, this does not rule out a potential genetic contribution. Our findings offer insight into the relationship between comorbidities and hormonal changes, supporting further research into their roles in T decline and related health risks in aging men.
Study context
- Population
- Men in UK Biobank with consecutive T, bioavailable testosterone (BAT) and sex hormone-binding globulin (SHBG) measurements; mean age 58.2 years, mean follow-up 4.3 years
- Participants
- 6,354 men
- Outcome
- Genetic contribution (PGS for BAT) to age-related T/BAT decline and its association with comorbidities
- Follow-up
- Mean 4.3 years
Methodological detailsUK Biobank, polygenic score, genome-wide analysis
- UK Biobank
- Polygenic score
- Genome-wide analysis
Main finding
As reported in the abstract
Age-related BAT decline
- BAT decline associated with prevalence of cancers
- P = .007
- BAT decline associated with prevalence of cardiovascular disease (CVD)
- .012
Observational data: associations, not effects.
Further findings
Baseline BAT, T and SHBG vs their relative changes at follow-up
- Baseline levels each negatively associated with respective relative changes
- all P < .001
Polygenic score (PGS) for BAT and baseline BAT
- PGS strongly associated with baseline levels
- P = 2.2 × 10-16, R²=0.16
- PGS developed in 183 909 UK Biobank participants
Original publication
Role of genetics in the age-related testosterone decline in men: a UK Biobank study. Eur J Endocrinol. Published 17 July 2025. doi:10.
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