Metabolic Profiling Identifies Infertile Men at Risk of Accelerated Aging: Implications for Systemic and Reproductive Health.

Authors

Edoardo Pozzi, Fausto Negri, Massimiliano Raffo, Luca Boeri, Eugenio Ventimiglia, Alessia d'Arma, Giada Amodio, Luca Pagliardini, Massimo Alfano, Francesco Montorsi, Silvia Gregori, Andrea Salonia

Published in

Andrology. Jun 12, 2026. Epub Jun 12, 2026.

Abstract

Male infertility is increasingly recognized as a systemic condition associated with impaired long-term health, yet clinically applicable frameworks linking reproductive dysfunction to comorbidity burden remain limited. Here, we investigated whether a composite immuno-metabolic signature could capture comorbidity burden and reduced reproductive capacity in men with primary male factor infertility (MFI).
In a cross-sectional cohort of 2953 men, metabolic and inflammatory variables were systematically screened for directional and independent associations with comorbidity burden, defined by the Charlson Comorbidity Index (CCI) ≥1, and impaired reproductive capacity, assessed by total motile sperm count (TMSC) <5 million. Three variables-LDL cholesterol, waist circumference, and C-reactive protein (CRP)-met selection criteria and were integrated into an unweighted standardized score.
Three variables met selection criteria: LDL cholesterol, waist circumference, and C-reactive protein. Higher immuno-metabolic scores were observed in men with comorbidity burden (0.20 ± 0.73 vs. -0.02 ± 0.62, p < 0.001) and in those with TMSC <5M (0.13 ± 0.64 vs. -0.07 ± 0.62, p < 0.001). Each unit increase in the score was independently associated with comorbidity burden (OR 1.50, 95% CI 1.23-1.82, p < 0.001) and TMSC <5M (OR 1.67, 95% CI 1.48-1.89, p < 0.001). Predicted probabilities rose across the score range from 2% to 40% for comorbidity and from 12% to 75% for reduced reproductive capacity.
These findings identify a biologically coherent immuno-metabolic signature linking spermatogenic impairment with systemic comorbidity in men with primary MFI and support a model in which male infertility reflects broader immuno-metabolic vulnerability. Prospective external validation is warranted before clinical implementation.

PMID:
42286945
Bibliographic data and abstract were imported from PubMed on 13 Jun 2026.

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