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Peer-reviewedCC BY 4.0Journal of Endocrinological Investigation

Late-onset and functional hypogonadism in aging men: an integrated perspective on hormonal, sleep, and metabolic dimensions

  • Monica Levy Andersen1,2
  • J. M. Sanches1,3
  • T. A. Alvarenga2
  • M. Toricelli2
  • M. B. Vasco4
  • S. Tufik1,2
4 affiliations
  1. 1Departamento de Psicobiologia, Universidade Federal de São Paulo (UNIFESP) Rua Napoleão de Barros, 925 Vila Clementino, São Paulo, SP 04024-002 Brazil
  2. 2Instituto do Sono, Associação Fundo de Incentivo à Pesquisa, São Paulo, Brazil
  3. 3Centro de Ciências Naturais e Humanas, Universidade Federal do ABC (UFABC), São Paulo, Brazil
  4. 4Disciplina de Urologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
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Abstract

Background and objective: Male reproductive aging is characterized by gradual hormonal and metabolic deterioration, often described as late-onset hypogonadism (LOH) or "andropause". However, these terms remain controversial and insufficient to capture the multifaceted nature of this process. This narrative review provides an integrated perspective on the interconnected hormonal, metabolic, sleep-related, and sexual consequences of male aging, with particular attention to the distinction between LOH and functional hypogonadism.

Methods: We synthesized current literature on hormonal decline, sleep disturbances, and metabolic dysfunction in aging men, with a focus on physiological mechanisms, clinical manifestations, and integrative management strategies.

Key findings and limitations: Progressive testosterone decline interacts with circadian disruption, sleep disorders, and metabolic imbalance in a bidirectional and clinically relevant manner. Unlike the abrupt hormonal changes in women, male decline is subtle, frequently underdiagnosed, and associated with reduced libido, fatigue, muscle loss, mood disturbances, and visceral adiposity. Sleep disturbances, including insomnia, sleep fragmentation, and obstructive sleep apnea, act both as consequences and amplifiers of endocrine and metabolic dysfunction. Current diagnostic criteria for LOH remain debated, limiting clinical recognition and delaying interventions. The distinction between LOH and functional hypogonadism is clinically meaningful, as the latter may be partially reversible through weight reduction, metabolic optimization, physical activity, and sleep-focused interventions. This review is narrative in nature, which may restrict systematic generalization of findings.

Conclusions and clinical implications: An integrated perspective on male reproductive aging that incorporates hormonal, metabolic, and sleep-related dimensions supports earlier diagnosis and personalized therapeutic strategies, with implications for improving men’s health, quality of life, and longevity.

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Cite

BibTeXRIS
BibTeX
@article{andersen2026lateonset,
  title = {{Late-onset and functional hypogonadism in aging men: an integrated perspective on hormonal, sleep, and metabolic dimensions}},
  author = {Monica Levy Andersen and J. M. Sanches and T. A. Alvarenga and M. Toricelli and M. B. Vasco and S. Tufik},
  journal = {Journal of Endocrinological Investigation},
  year = {2026},
  month = jul,
  doi = {10.1007/s40618-026-02981-6},
  url = {https://doi.org/10.1007/s40618-026-02981-6},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Late-onset and functional hypogonadism in aging men: an integrated perspective on hormonal, sleep, and metabolic dimensions
AU  - Monica Levy Andersen
AU  - J. M. Sanches
AU  - T. A. Alvarenga
AU  - M. Toricelli
AU  - M. B. Vasco
AU  - S. Tufik
PY  - 2026
DA  - 2026/07/20
JO  - Journal of Endocrinological Investigation
DO  - 10.1007/s40618-026-02981-6
UR  - https://doi.org/10.1007/s40618-026-02981-6
AB  - Background and objective: Male reproductive aging is characterized by gradual hormonal and metabolic deterioration, often described as late-onset hypogonadism (LOH) or "andropause". However, these terms remain controversial and insufficient to capture the multifaceted nature of this process. This narrative review provides an integrated perspective on the interconnected hormonal, metabolic, sleep-related, and sexual consequences of male aging, with particular attention to the distinction between LOH and functional hypogonadism.  Methods: We synthesized current literature on hormonal decline, sleep disturbances, and metabolic dysfunction in aging men, with a focus on physiological mechanisms, clinical manifestations, and integrative management strategies.  Key findings and limitations: Progressive testosterone decline interacts with circadian disruption, sleep disorders, and metabolic imbalance in a bidirectional and clinically relevant manner. Unlike the abrupt hormonal changes in women, male decline is subtle, frequently underdiagnosed, and associated with reduced libido, fatigue, muscle loss, mood disturbances, and visceral adiposity. Sleep disturbances, including insomnia, sleep fragmentation, and obstructive sleep apnea, act both as consequences and amplifiers of endocrine and metabolic dysfunction. Current diagnostic criteria for LOH remain debated, limiting clinical recognition and delaying interventions. The distinction between LOH and functional hypogonadism is clinically meaningful, as the latter may be partially reversible through weight reduction, metabolic optimization, physical activity, and sleep-focused interventions. This review is narrative in nature, which may restrict systematic generalization of findings.  Conclusions and clinical implications: An integrated perspective on male reproductive aging that incorporates hormonal, metabolic, and sleep-related dimensions supports earlier diagnosis and personalized therapeutic strategies, with implications for improving men’s health, quality of life, and longevity.
SN  - 0391-4097
SN  - 1720-8386
ER  -