Role of Metabolic Syndrome Components in the Molecular and Biochemical Pathogenesis of Benign Prostatic Hyperplasia: A Systematic Review and Meta-Analysis

Abstract

Background: Benign prostatic hyperplasia (BPH) is increasingly recognized as a disorder in which ageing and androgen-dependent growth interact with systemic metabolic dysfunction. Metabolic syndrome (MetS), characterized by central obesity, insulin resistance/hyperglycaemia, dyslipidaemia and elevated blood pressure, may influence prostate growth through endocrine, inflammatory, vascular and redox pathways. Objective: To quantify the association between MetS and major clinical BPH phenotypes and to integrate current evidence on the molecular and biochemical mechanisms through which individual MetS components may promote prostatic enlargement, fibrosis and lower urinary tract dysfunction. Methods: Ten observational studies involving 3,947 men with BPH met the criteria for quantitative synthesis. Random-effects DerSimonian-Laird models were used to pool MetS prevalence, mean difference (MD) in prostate volume and standardized mean difference (Hedges g) in International Prostate Symptom Score (IPSS). Mechanistic evidence was updated through 7 August 2026 using PubMed/MEDLINE and citation chaining, with emphasis on insulin/IGF-1 signalling, adipokines, inflammation, oxidative stress, dyslipidaemia, sex-steroid biology, vascular dysfunction and fibrosis. Results: The pooled prevalence of MetS among men with BPH was 43.49% (95% CI 36.41-50.85; I²=94.7%). Men with MetS had significantly larger prostates than those without MetS (MD 10.17 mL, 95% CI 5.47-14.87; I²=88.4%). The pooled difference in IPSS was not statistically significant (Hedges g 0.37, 95% CI -0.23 to 0.96; I²=98.1%). Recent prospective evidence from 163,975 UK Biobank participants associated MetS with incident BPH (HR 1.07, 95% CI 1.03-1.10), while Mendelian-randomization evidence implicated waist circumference and particularly diastolic blood pressure. Mechanistic studies support convergent roles for hyperinsulinaemia/IGF-1, adipokine imbalance, TNF-α and IL-6 signalling, Toll-like receptor-mediated inflammation, oxidative lipid mediators, altered androgen-oestrogen balance, microvascular dysfunction and periurethral fibrosis. Conclusion: MetS is more consistently associated with structural prostatic enlargement than with symptom severity. Central adiposity, insulin resistance, dyslipidaemic inflammation and vascular dysfunction appear to converge on proliferative, inflammatory and fibrotic pathways in the prostate. BPH should therefore be considered, in a clinically important subset of men, a metabolically influenced inflammatory-remodelling disorder. Prospective trials are required to establish whether improving metabolic health can modify prostate growth or BPH progression.

Keywords: benign prostatic hyperplasia; metabolic syndrome; obesity; insulin resistance; diabetes; dyslipidaemia; hypertension; adipokines; inflammation; oxidative stress; IGF-1; prostate volume; fibrosis.