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Pathophysiologie und Therapie der benignen Prostata-Hyperplasie

Pathophysiology and therapy of benign prostatic hyperplasia

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Summary

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 α-adrenoreceptor blockade and 5α-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.

Zusammenfassung

Die Benigne Prostata Hyperplasie/Vergrößerung (BPH/BPE) ist der häufigste gutartige Tumor des alternden Mannes. Dieser gilt als eine Ursache einer Reihe von Symptomen des unteren Urogenitaltraktes (LUTS, Lower Urinary Tract Symptoms). Die BPH/BPE führt zu Einschränkungen der Lebensqualität sowie zu medizinischen Komplikationen bis hin zur akuten Harnverhaltung. Noduläres Wachstum, vorwiegend des fibromuskulären Gewebes der Transitionszone und der periurethralen Anteile, sowie funktionelle Änderungen der Zellen sind charakteristisch für die beobachtete Gewebsreorganisation in der BPH/BPE. Die Pathophysiologie der BPH/BPE ist komplex und es ist hierbei eine Anzahl endokriner und lokaler Faktoren involviert. Zwei Risikofaktoren sind essentiell für die Entwicklung der BPH/BPE, Altern und Androgene. Einen bedeutenden Einfluss auf die Entstehung scheinen die ab dem 35. Lebensjahr einsetzenden Veränderungen der Sexualsteroidhormon-Serumspiegel und -ratios zu haben. Diese laufen parallel zu Veränderungen im lokalen Sexualsteroidhormon-Stoffwechsel und zu Störungen in Wachstumsfaktor Signaltransduktionswegen in Stroma und Epithel. Das veränderte Stroma fördert über eine veränderte Zytokinproduktion lokale inflammatorische Prozesse, die das Fortschreiten der Erkrankung über inflammatorische Zytokine lymphozytären Ursprungs begünstigen. Lokale Hypoxie, ausgelöst durch zelluläre Proliferation, führt zur Produktion von Sauerstoffradikalen, welche eine Neovaskularisierung und die charaktreristische Transdifferenzierung von Fibroblasten zu glatten Muskelzellen bzw. Myofibroblasten auslösen. Die medikamentösen Standardtherapien von LUTS auf Grund von BPH/BPE haben sich seit 15 Jahren wenig geändert. Es sind dies die Blockade α-adrenerger Rezeptoren und die Hemmung des DHT-konvertierenden Enzyms 5α-Reduktase. In unserer Arbeit fassen wir die vermutlichen molekularen Mechanismen zur Entstehung der BPH/BPE zusammen und zeigen neue Wege zur therapeutischen Intervention auf. Zukünftige Ansätze beinhalten möglicherweise selektive Hormon Antagonisten/Agonisten, anti-stromal Therapie, Vitamin-D Analoga und Substanzen zur Wiederherstellung des Redox Gleichgewichts.

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Authors and Affiliations

  1. Institut für Biomedizinische Alternsforschung, Österreichische Akademie der Wissenschaften, Innsbruck, Austria

    Natalie Sampson & Peter Berger

  2. Abteilung für Urologie und Andrologie, Donauspital, Wien, Austria

    Stephan Madersbacher

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  1. Natalie Sampson
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  2. Stephan Madersbacher
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  3. Peter Berger
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Correspondence to Peter Berger.

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Sampson, N., Madersbacher, S. & Berger, P. Pathophysiologie und Therapie der benignen Prostata-Hyperplasie. Wien Klin Wochenschr 120, 390–401 (2008). https://doi.org/10.1007/s00508-008-0986-5

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  • DOI: https://doi.org/10.1007/s00508-008-0986-5

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