Age-related testosterone decline: mechanisms and intervention strategies

Contemporary societies exhibit delayed reproductive age and increased life expectancy. While the male reproductive system demonstrates relatively delayed aging compared to that of females, increasing age substantially impacts its function. A characteristic manifestation is age-induced testosterone decline. Testosterone, a crucial male sex hormone, plays pivotal roles in spermatogenesis and sexual function, and contributes significantly to metabolism, psychology, and cardiovascular health. Aging exerts profound effects on the hypothalamic-pituitary–gonadal axis and Leydig cells, precipitating testosterone reduction, which adversely affects male health. Exogenous testosterone supplementation can partially ameliorate age-related testosterone deficiency; however, its long-term safety remains contentious. Preserving endogenous testosterone production capacity during the aging process warrants further investigation as a potential intervention strategy.

Conclusion and future directions

In conclusion, aging affects testosterone synthesis through various pathways, including alterations in the HPG axis, testicular microenvironment, LC number and function, consequently impacting male reproductive function and quality of life. Understanding the mechanisms underlying age-related testosterone decline is fundamental for developing relevant diagnostic and therapeutic strategies, necessitating further research to elucidate its exact mechanisms. While existing treatment strategies can improve testosterone levels to some extent, safely and effectively enhancing endogenous testosterone levels remains a focus of future research. Stem cell transplantation and biologics targeting specific steps in testosterone production hold promise as therapeutic approaches, but further animal and clinical studies are needed to support their clinical application.

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