The Etiology and Pathogenesis of Benign Prostatic Hyperplasia: The Roles of Sex Hormones and Anatomy

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: androgens; benign prostatic hyperplasia; epithelium; etiology; nodular proliferation; steroid sex hormones; stroma; tissue homeostasis.

Figure 1

The phase diagram of BPH development (etiology and pathogenesis) with age. At a young age, the functional organization of prostatic tissues including transitional zone (TZ), central zone (CZ), peripheral zone (PZ), urethra, and ejaculatory duct is well maintained by tissue homeostasis. At a middle age, after years of exposure to the waste chemicals from the urine, the tissue homeostasis of TZ is disrupted by accumulation of urinary wastes within the TZ and leukocyte infiltration (the onset of BPH) (hypothesis). From the middle to old age, after irreversible disruption of tissue homeostasis, inflammatory mediators induce cell death and fibrosis, while locally synthesized DHT and growth factors stimulate cell proliferation – to form epithelial hyperplasia (EH) and stromal hyperplasia (SH), which may represent different subtypes of TZ enlargement and lead to urethra obstruction.