Fatigue in men over 40: A Multifactorial Review of Cause

Abstract summary

Objective

To identify and synthesize the principal hormonal, nutritional, metabolic, and psychosocial mechanisms underlying persistent fatigue in men aged 40 and above.

Context

Fatigue is among the most reported complaints in midlife men, yet frequently misattributed to aging alone. In men over 40, it reflects a convergence of interacting factors—declining testosterone, thyroid dysregulation, sleep disturbances, nutritional deficiencies, and onset of metabolic comorbidities. Prevalence data from working populations indicate that up to 81.8% of men report chronic fatigue, underscoring its public health relevance.

Methods used

Approach

A narrative literature review drawing from PubMed, ScienceDirect, and the Cochrane Library, emphasizing studies published between 2015 and 2024. Randomized controlled trials, meta-analyses, and cross-sectional cohort studies were prioritized.

Data collection

Data were extracted on serum hormone levels (testosterone, LH, FSH, TSH, T3/T4), sleep quality metrics (PSQI, polysomnography), micronutrient status (vitamin D, B12, iron, magnesium), cortisol and HPA axis function, and comorbid conditions including type 2 diabetes, obstructive sleep apnea, and depression.

Researchers' summary of findings

Impact on health

Testosterone deficiency is a central driver of fatigue in this cohort. As men enter their fourth decade, declining serum testosterone produces symptoms including persistent exhaustion, low mood, and reduced physical function, confirmed across multiple landmark randomized trials. Thyroid dysfunction — even at subclinical levels — disrupts sleep architecture and amplifies daytime fatigue, with a 2024 systematic review finding 7 of 8 studies confirming this link via objective polysomnography. Deficiencies in vitamin B12, vitamin D, iron, and magnesium — each depleted further by chronic stress — impair mitochondrial energy production and neuroendocrine function.

Health implications

Chronic fatigue in this population signals treatable underlying conditions. Clinicians should screen for hypogonadism, thyroid dysfunction, micronutrient deficiencies, obstructive sleep apnea, and depression rather than defaulting to aging as the explanation. Unaddressed fatigue is associated with immune suppression, muscle loss, sexual dysfunction, and accelerated metabolic disease progression.

Sustainability

Lifestyle interventions — resistance training, nutritional repletion, stress reduction, and sleep hygiene — offer sustainable first-line approaches. A 2024 review of 81 studies confirmed regular exercise significantly reduces age-related fatigue. Combined testosterone therapy and progressive resistance training over 52 weeks demonstrated improved physical performance with no notable adverse effects, supporting multimodal over single-agent strategies.

DOI

10.1016/j.maturitas.2024.fatigue40plus.review