Late-onset hypogonadism: Clinical evidence, biological aspects and evolutionary considerations

Area of Science:

• Evolutionary Medicine
• Endocrinology
• Gerontology

Background:

• Increasing life expectancy drives interest in interventions for age-related diseases like vascular calcification, cognitive decline, sarcopenia, osteoporosis, and sexual dysfunction.
• Testosterone replacement therapy (TRT) is explored for aging men, particularly those with late-onset hypogonadism (LOH), but its safety is not fully established.
• Age-related testosterone decline occurs across species, prompting questions about whether it's pathological or an adaptive response.

Purpose of the Study:

• To apply evolutionary medicine principles to testosterone biology and LOH for a novel perspective.
• To explore the adaptive significance of age-related testosterone changes.
• To discuss the cost-benefit considerations and potential risks of TRT in aging men.

Main Methods:

• Application of evolutionary medicine principles to testosterone and LOH.
• Review and discussion of data from animal models on testosterone trajectories.
• Analysis of cost-benefit considerations and potential caveats of TRT.

Main Results:

• Testosterone levels decrease with age in multiple species, but the implications are debated.
• Animal data illustrate the plasticity of testosterone levels across the lifespan.
• TRT can alleviate some LOH symptoms, but safety concerns persist.

Conclusions:

• Evolutionary medicine provides a valuable framework for understanding testosterone changes in aging.
• The adaptive role of age-related testosterone decline requires further investigation.
• Careful consideration of risks and benefits is crucial for TRT in aging men.