Adipose as a Driver, Not a Bystander: A Modern Synthesis of Obesity-Related Erectile Dysfunction

Obesity and erectile dysfunction (ED) are increasingly co-prevalent, yet adipose tissue is often viewed as a secondary contributor rather than a primary driver of erectile impairment.

To evaluate an adipose-centric framework in which depot-specific adipose dysfunction regulates vascular, neuroendocrine, and smooth muscle processes essential for erection.

A narrative synthesis of mechanistic, preclinical, and clinical studies was conducted, focusing on inflammation, cellular senescence, extracellular vesicle signaling, ferroptosis, mitochondrial dysfunction, and glycocalyx injury across visceral, perivascular, and periprostatic adipose depots.

Dysfunctional adipose tissue remodels systemic and local microenvironments through adipokines, cytokines, extracellular vesicle cargo, and oxidized lipid mediators. These processes reduce nitric oxide bioavailability, increase vascular stiffness, disrupt neuroendocrine signaling, and promote cavernosal fibrosis. Perivascular adipose tissue exerts localized effects on penile hemodynamics. Clinical and genetic evidence supports a causal link between central adiposity and ED, while weight loss and adipose-targeted interventions improve erectile outcomes.

Adipose tissue functions as an upstream regulator of ED pathogenesis. Targeting adipose dysfunction through lifestyle, pharmacological, and emerging strategies such as senolytics and extracellular vesicle modulation may modify disease progression rather than provide symptomatic relief.