Serum Minerals and Male Age-related Hypogonadism: Multimodal Evidence Decoding Associations and Intervention Strategies
Authors' conclusion
Serum iron bidirectionally modulates testicular function through redox and metabolic networks. Our findings establish age as an effect modifier in mineral-endocrine interactions, emphasize personalized precision nutrition strategies, and uncover novel bilirubin-mediated regulatory pathways.
Study context
- Population
- Age-stratified males, NHANES 2013–2016
- Participants
- 687 age-stratified males
- Outcome
- Association of serum iron with TT
Methodological detailsweighted linear regression, restricted cubic splines, piecewise regression, univariable and multivariable Mendelian randomization, instrumental variable mediation analysis
- Weighted linear regression
- Restricted cubic splines
- Piecewise regression
- Univariable and multivariable Mendelian randomization
- Instrumental variable mediation analysis
Main finding
As reported in the abstract
Serum iron and TT in middle-aged males
- Positive association between serum iron and TT (β)
- 0.194-0.244, P = .016-.033
- J-shaped nonlinear relationship (nonlinear P)
- P = .044
- Inflection point (threshold effect analysis)
- 12.18 µmol/L
Observational data: associations, not effects.
Further findings
Phosphorus, copper, zinc, calcium and sex hormones in other age strata
- Associations attenuated upon multivariable adjustments
Causal effect of iron on TT (Mendelian randomization)
- Univariable MR supported causal effect
- P = 1.24 × 10-5
- Effect diminished in multivariable MR after adjustment for metabolic factors
Mediation by bilirubin degradation metabolite C16H18N2O5 (2)
- Negative mediator, mediation proportion
- −68.0%, P = .016
Original publication
Serum Minerals and Male Age-related Hypogonadism: Multimodal Evidence Decoding Associations and Intervention Strategies. J Clin Endocrinol Metab. Published 17 September 2025. doi:10.
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