Translational Pharmacology in Aging Men with Benign Prostatic Hyperplasia: Molecular and Clinical Approaches to Alpha1-Adrenoceptors

Yoshiyuki      Kojima; Yasue      Kubota; Shoichi      Sasaki; Yutaro      Hayashi; Kenjiro      Kohri

Abstract

Benign prostatic hyperplasia (BPH) occurs in over 50% of men over 60 years of age, most of whom have lower urinary tract symptoms (LUTS). The incidence of BPH appears to be increasing due to the increased longevity of men. LUTS associated with BPH (LUTS/BPH) greatly affects the patient ’ s quality of life. Physicians should be aware of other issues associated with advancing age, such as cardiovascular diseases, sexual dysfunction and cataract, that may complicate the treatment of aging men with LUTS/BPH; therefore, management of LUTS/BPH requires careful selection of the most appropriate treatment for each patient. Alpha1-adrenoceptor (α1-AR) stimulation plays an important role in the regulation of prostate smooth muscle contraction. Recent remarkable advances in molecular biology offer the possibility of new findings about the role of α1-AR subtypes and new therapeutic options for BPH; however, even though α1-AR antagonists are used as the first-line medical treatment for patients affected by LUTS/BPH, responses to α1-AR antagonists differ among patients. The risks of unexpected adverse events, acute urinary retention and the need for invasive therapy also differ among patients. Translational pharmacology is the collaboration between researchers and clinicians to discover more effective medical therapies and to identify new drugs for various diseases. This review summarizes the recent molecular and physiological findings of α1-AR subtypes and discusses potential new strategies for BPH medical treatment. In the future, the promise of genetic-based prescriptions and therapeutic plans as a useful strategy to improve clinical outcomes of BPH medical therapy may become credible and warrants further investigation.

Keywords: Benign prostatic hyperplasia, lower urinary tract symptom, aging men, alpha1-adrenoceptors, alpha1-adrenoceptor antagonists, knockout mice, translational pharmacology, pharmacogenomics