[Pathophysiology and therapy of benign prostatic hyperplasia].
Benign prostatic hyperplasia (BPH) and benign prostatic enlargement (BPE) are among the most frequent medical disorders of elderly men and cause a number of annoying symptoms of the lower urinary tract (LUTS), leading to reduced quality of life and severe complications, including acute urinary retention. Nodular overgrowth of the epithelium and in particular the fibromuscular tissue is observed in the transition zone and periurethral areas. In particular, functional and phenotypic transdifferentiation of fibroblasts into myofibroblasts is a hallmark of the tissue remodeling in the benign hyperplastic prostate. BPH/BPE have a complex pathophysiology with a multitude of endocrine and local factors involved. Two risk factors, namely aging and circulating androgens, contribute significantly to risk of BPH/BPE. One of the primary initiating mechanisms appears to be a consequence of age-related changes in systemic sex steroid hormone levels accompanied by alterations in local androgen metabolism. This results in the disruption of the delicate balance of interacting growth factor signaling pathways and stromal/epithelial interactions generating a growth promoting and tissue remodeling microenvironment that leads to an increase in prostate volume. Secondarily, altered cytokine and chemoattractant production by the remodeled stroma promotes local inflammation that may further contribute to disease progression via lymphocyte-derived inflammatory cytokines and reactive oxygen/nitrogen species. Local hypoxia as a result of increased oxygen demands of proliferating cells may induce low levels of reactive oxygen species promoting neovascularization and fibroblast-to-myofibroblast transdifferentiation. Medical therapies for LUTS due to BPH/BPE have changed little over the past 15 years with mainstay treatments being alpha-adrenoreceptor blockade and 5alpha-reductase inhibitors. We provide an in depth view of the mechanisms underlying BPH/BPE and relate new research findings to the clinical picture with the prospect of novel therapeutic targets, including selective hormone antagonists/agonists, anti-stromal therapy, vitamin-D analogues and approaches to redress the redox imbalance.
Sampson
Natalie
N
Institut für Biomedizinische Alternsforschung, Osterreichische Akademie der Wissenschaften, Innsbruck, Austria.
Madersbacher
Stephan
S
Berger
Peter
P
D058891:5-alpha Reductase Inhibitors; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D000728:Androgens / Q000097:blood; D001341:Autonomic Nervous System / Q000503:physiopathology; D002455:Cell Division / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D003238:Connective Tissue / Q000503:physiopathology; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D006801:Humans; D008297:Male; D009130:Muscle, Smooth / Q000503:physiopathology; D011467:Prostate / Q000503:physiopathology; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000150:complications / Q000503:physiopathology* / Q000628:therapy; D017382:Reactive Oxygen Species / Q000097:blood; D015398:Signal Transduction / Q000502:physiology; D001748:Urinary Bladder Neck Obstruction / Q000503:physiopathology / Q000628:therapy; D016055:Urinary Retention / Q000503:physiopathology / Q000628:therapy; D019459:Urothelium / Q000503:physiopathology
D058891:5-alpha Reductase Inhibitors; D000317:Adrenergic alpha-Antagonists; D000728:Androgens; D016207:Cytokines; D017382:Reactive Oxygen Species