| Title: | Role of genetics in the age-related testosterone decline in men: a UK Biobank study |
| Journal: | European Journal of Endocrinology |
| Published: | 17 Jul 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40673695/ |
| DOI: | https://doi.org/10.1093/ejendo/lvaf143 |
| URL: | https://pubmed.ncbi.nlm.nih.gov/40673695 |
Publication 16153
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Abstract
OBJECTIVE: Age-related decline in circulating testosterone (T) levels in men varies significantly and is often linked to comorbidities such as Type 2 diabetes and cardiovascular disease (CVD). While the genetic basis of T levels is well studied, the role of genetics in age-related T decline remains unclear. This study aims to investigate the genetic contribution to age-related T decline in men and its association with comorbidities.</p>
DESIGN: A longitudinal, population-based study in 6354 men including consecutive T, bioavailable testosterone (BAT), and sex hormone-binding globulin (SHBG) measurements.</p>
METHODS: We assessed the association of longitudinal serum biomarker changes with changes in disease prevalences and a polygenic score (PGS) for BAT developed in 183 909 UK Biobank participants.</p>
RESULTS: In the follow-up cohort (mean age: 58.2 years; mean follow-up: 4.3 years), baseline levels of BAT, T, and SHBG were each negatively associated with their respective relative changes at follow-up (all P < .001). A PGS for BAT, strongly associated with baseline levels (P = 2.2 × 10-16, R²=0.16), was not associated with BAT decline over time. Genome-wide analysis of BAT change identified no significant genetic loci. Instead, the BAT decline was associated with prevalence of several comorbidities including cancers and CVD (P = .007 and .012, respectively).</p>
CONCLUSIONS: 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.</p>
14 Keywords
- Aged
- Aging
- Biological Specimen Banks
- Biomarkers
- Cardiovascular Diseases
- Genome-Wide Association Study
- Humans
- Longitudinal Studies
- Male
- Middle Aged
- Sex Hormone-Binding Globulin
- Testosterone
- UK Biobank
- United Kingdom
6 Authors
- Lynn Ogoniak
- Sarah Sandmann
- Julian Varghese
- Michael J Ziller
- Nina Neuhaus
- Alexander Siegfried Busch
1 Application
| Application ID | Title |
|---|---|
| 100261 | Uncovering the genetic basis of reproductive health and its links to general health |
Enabling scientific discoveries that improve human health