Ganzhe Xu,1 Guoyu Dai,2 Zhongli Huang,3 Qiunong Guan,2 Caigan Du,2 Xiaoming Xu4 

1Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2Department of Biomedical Engineering, Guoke Ningbo Life Science and Health Industry Research Institute, Ningbo, Zhejiang, People’s Republic of China; 3Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Urology, Ningbo No. 2 Hospital, Ningbo, Zhejiang, People’s Republic of China

Correspondence: Caigan Du, Department of Biomedical Engineering, Guoke Ningbo Life Science and Health Industry Research Institute, Ningbo, Zhejiang, People’s Republic of China, Email ducaigan@ucas.ac.cn Xiaoming Xu, Department of Urology, Ningbo No. 2 hospital, Ningbo, Zhejiang, People’s Republic of China, Email xiaomingxu6@sohu.com

Abstract: Benign prostatic hyperplasia (BPH) mainly causes lower urinary tract symptoms in ageing men, but its exact etiology and pathogenesis have not been established. The objective of this review was to design an update on the advances of human BPH research. We undertook a literature search for identifying studies of the roles of sex hormones (androgens and estrogens) in the onset and development of human BPH using the Pubmed database. In literature, many studies have indicated that ageing and obesity are the factors for preceding the onset of BPH. No evidence for the role of testosterone (T) or dihydrotestosterone (DHT) is found in BPH initiation. Since BPH exclusively occurs in the transitional zone (TZ) surrounding the urethra, it is postulated that years of exposure to uncharacterized urinary toxins could disrupt the homeostasis of the stroma and/or epithelium of this prostatic zone that are typically occurring in ageing men. After cellular damage and subsequent inflammation generated, the intraprostatic DHT produced mainly from T by 5α-reductase promotes BPH development. Further, estrogens could take part in the nodular proliferation of stromal cells in some BPH patients. The confounding of BPH may attenuate the development of prostate tumor in the TZ. In conclusion, evidence in literature suggests that androgens are not etiological factors for BPH, and intraprostatic DHT along with chronic inflammation are mainly responsible for nodular proliferation of stromal and/or epithelial cells in prostatic TZ. The urinary factors for the etiology of BPH and BPH as a prediction of PCa progression still need further investigation.

Keywords: benign prostatic hyperplasia, tissue homeostasis, etiology, nodular proliferation, stroma, epithelium, androgens, steroid sex hormones