Molecular medicine reportsOct 24, 2026

How Aging and Obesity Affect the Male Reproductive System and Ways to Manage Them

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 25, 2026

Abstract

Aging, obesity, and testosterone deficiency synergistically drive the pathological progression of late-onset hypogonadism (LOH).

Late-onset hypogonadism is primarily caused by a gradual reduction in serum testosterone levels associated with aging.
Age-dependent changes in testicular cells, including Sertoli cells and spermatogonial stem cells, contribute to testicular functional decline.
An imbalance in the testicular immune microenvironment is linked to the deterioration of reproductive health in aging males.
Obesity may trigger insulin resistance and chronic inflammation, which directly inhibit testosterone production and accelerate testicular aging.
Low testosterone levels could promote further obesity and metabolic disorders, creating a vicious cycle of health deterioration.
Various therapeutic strategies for testicular dysfunction are categorized based on genetic, developmental, and metabolic causes.

Simplified

With the intensification of the aging of the global population, reproductive health problems among middle‑aged and elderly males have emerged as a prominent public health issue. Late‑onset hypogonadism (LOH), primarily induced by an age‑related gradual reduction in serum testosterone, has garnered widespread clinical attention. The present review systematically elaborates the molecular and cellular mechanisms underlying testicular aging. Specifically, age‑dependent alterations in Sertoli cells, interstitial cells and spermatogonial stem cells, as well as an imbalance in the testicular immune microenvironment, constitute the inherent pathological basis of testicular functional deterioration. A vicious cycle exists between obesity and testosterone deficiency: Obesity‑triggered insulin resistance, chronic low‑grade inflammation and oxidative stress directly inhibit testosterone synthesis and accelerate testicular aging; in turn, low testosterone levels promote visceral fat accumulation and insulin resistance, exacerbating obesity and metabolic disorders. Aging, obesity and testosterone deficiency synergistically drive the pathological progression of LOH. In terms of clinical intervention, the present review classifies the therapeutic strategies for testicular dysfunction induced by genetic, developmental and metabolic disorders based on etiological characteristics. The review also summarizes innovative therapeutic approaches targeting the testicular microenvironment and cellular senescence pathways, as well as frontier research hotspots, including natural product interventions and regenerative medicine. By integrating the interactive mechanisms of testicular aging and obesity and summarizing relevant multidimensional intervention strategies, this review provides a systematic theoretical basis for further exploring the pathogenesis and improving the clinical prevention and treatment system of LOH.

How Aging and Obesity Affect the Male Reproductive System and Ways to Manage Them

Abstract

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