A scoping review of the role of heritability and environmental exposures in the development and severity of benign prostatic hyperplasia.

BACKGROUND

Benign prostatic hyperplasia (BPH) is a common condition among aging men, significantly affecting quality of life and contributing to a substantial healthcare burden. The pathogenesis of BPH is strongly influenced by genetic factors, with heritability estimates showing a wide range from 20% to 83%. Emerging evidence also highlights the critical role of environmental exposures, including endocrine-disrupting chemicals (EDCs), in BPH risk, progression, and therapeutic response. This review synthesizes current knowledge on genetic and environmental determinants of BPH pathogenesis, severity, and management.

METHODS

A scoping review of the literature was conducted using the databases PubMed, Scopus, and Web of Science. Relevant studies on genetic predisposition, environmental exposures, and their contributions to BPH were analyzed. Data from epidemiological studies, genome-wide association studies (GWAS), familial aggregation analyses, and research on environmental exposures were integrated to provide an understanding of these factors and BPH pathogenesis.

RESULTS

Familial clustering indicates a significantly elevated risk, particularly among first-degree male relatives. Key genetic determinants include androgen receptor () gene CAG repeat polymorphisms, where shorter repeats are linked to increased AR activity and prostate enlargement. Estrogen pathway genes, such as and , and variants in dihydrotestosterone (DHT) synthesis genes, notably , influence disease progression and risk. GWAS have identified additional loci, such as and , associated with prostate volume and aggressive BPH phenotypes. Polygenic risk scores offer promising applications in identifying individuals at high risk for severe BPH. Environmental exposures, particularly to EDCs such as bisphenol A (BPA), bisphenol S (BPS), and bisphenol AF (BPAF), were found to disrupt hormonal regulation, contributing to prostatic hyperplasia. Air pollution, primarily particulate matter, exacerbates prostate inflammation and hyperplasia, with regional differences in BPH symptom severity correlating with air quality. Lifestyle factors, including high-fat diets and sedentary behaviors, further modulate disease severity.

CONCLUSIONS

The development and progression of BPH are shaped by a complex interplay of genetic and environmental factors. EDCs contribute significantly to prostatic hyperplasia, while heritable factors influence disease onset, severity, and response to treatment. Integrating genetic risk profiling and environmental exposure assessments into clinical practice holds the potential to enhance BPH management and personalized therapeutic strategies.