Aging, obesity and testosterone deficiency synergistically drive late-onset hypogonadism through a vicious cycle, and the review organizes etiology-based and emerging interventions (testicular microenvironment and senescence-targeting, natural products, regenerative medicine) as a theoretical basis for improved prevention and treatment.
Late-onset hypogonadism (LOH) is primarily induced by an age-related gradual reduction in serum testosterone and is a prominent public health issue among middle-aged and elderly males.
Testicular aging involves age-dependent alterations in Sertoli cells, interstitial cells and spermatogonial stem cells, together with an imbalance in the testicular immune microenvironment.
Obesity directly inhibits testosterone synthesis and accelerates testicular aging through insulin resistance, chronic low-grade inflammation and oxidative stress.
Low testosterone in turn promotes visceral fat accumulation and insulin resistance, creating a vicious cycle between obesity and testosterone deficiency.
The review classifies therapeutic strategies for testicular dysfunction caused by genetic, developmental and metabolic disorders according to etiological characteristics.
Innovative therapeutic approaches target the testicular microenvironment and cellular senescence pathways, with frontier research in natural product interventions and regenerative medicine.
By integrating mechanisms of testicular aging and obesity with multidimensional intervention strategies, the review aims to provide a theoretical basis for understanding LOH pathogenesis and improving its prevention and treatment system.
This review article brings together existing research on why testosterone falls as men age and how excess body fat makes the problem worse. Late-onset hypogonadism is a condition in which testosterone declines gradually with age. The review describes how aging changes several cell types in the testis and disrupts the immune environment there, which weakens testicular function. The authors describe a vicious cycle. Obesity brings insulin resistance, chronic low-grade inflammation and oxidative stress, which can suppress testosterone production and speed up testicular aging. Low testosterone, in turn, tends to promote belly (visceral) fat and insulin resistance, which worsens obesity and metabolic problems. Aging, obesity and low testosterone therefore appear to reinforce one another. The review also sorts treatment approaches by their cause, whether genetic, developmental or metabolic. It also covers newer ideas such as therapies aimed at the testicular environment and cellular aging, natural products, and regenerative medicine. As a review, it does not present new trial results. It offers a framework that may guide future research and clinical care for older men with low testosterone and obesity.
Luo D, Zhang L, Qi X, Guan Q, Xu F, Lu P, et al.. (2026). Mechanisms of the interaction between aging of the male reproductive system and obesity, and clinical management strategies (Review).. Molecular medicine reports. https://doi.org/10.3892/mmr.2026.14051