Abstract

Benign prostatic hyperplasia (BPH) is a highly prevalent condition in aging men, historically attributed to 
androgenic stimulation and age-related tissue remodeling. Emerging evidence, however, suggests that metabolic 
dysfunction and systemic inflammation-particularly those associated with type 2 diabetes (T2DM), obesity, and 
metabolic syndrome-play influential roles in modifying prostate biology, driving stromal–epithelial proliferation, 
and promoting lower urinary tract symptoms (LUTS). This review synthesizes current knowledge on 
immune-metabolic dysregulation in BPH, focusing on how hyperglycemia, insulin resistance, chronic low-grade 
inflammation, oxidative stress, and adipokine imbalance modulate immune activation and prostate tissue 
remodeling. We examine mechanistic pathways linking diabetes to prostate enlargement, including altered 
insulin/IGF-1 signaling, inflammatory macrophage and T-cell infiltration, mitochondrial dysfunction, and redox 
imbalance. Particular attention is given to how metabolic disease reshapes immune phenotypes, such as promoting 
Th17 responses, senescence-associated secretory phenotypes (SASP), and pro-fibrotic myofibroblast activation, 
driving progression from benign hyperplasia to symptomatic obstruction. Finally, we discuss therapeutic 
implications, highlighting opportunities for metabolic therapies, anti-inflammatory interventions, antioxidant 
strategies, and microbiome-targeted approaches to modify disease trajectory. Understanding immune–metabolic 
crosstalk in BPH opens important avenues for precision medicine, especially in populations experiencing rising 
diabetes prevalence and associated inflammatory burden.