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Microvascular dysfunction and efficacy of PDE5 inhibitors in BPH–LUTS

Nature Reviews Urology volume 11, pages 231–241 (2014)Cite this article

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Abstract

Benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS) and erectile dysfunction commonly coexist, and both respond to phosphodiesterase (PDE) 5 inhibitors, suggesting a shared pathophysiological mechanism. We propose that both BPH–LUTS and erectile dysfunction are caused by microvascular dysfunction within the pelvic organs, and we present an overview of preclinical and clinical studies supporting the hypothesis that, within both the penis and the lower urinary tract, a combination of endothelial and neural dysfunction leads to a vicious cycle of hypoxia, vasoconstriction, altered smooth muscle contractility, and degeneration of autonomic neurons and ganglia. This hypothesis explains much of the preclinical and clinical research relating to these two conditions, and provides a rationale for further investigation into the effects of PDE5 inhibitors on the pathophysiology and symptoms of BPH–LUTS.

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Figure 1: Proposed microvascular dysfunction hypothesis linking BPH–LUTS and erectile dysfunction.
Figure 2: The role of NO, cGMP and PDE5 in the male genitourinary tract.

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Acknowledgements

The authors thank Dr Janet Douglas for editorial assistance with the preparation of this article.

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Authors and Affiliations

  1. Cranfield University, MK43 0AL, Bedfordshire, UK

    Selim Cellek

  2. School of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK

    Norman E. Cameron & Mary A. Cotter

  3. Department of Physiology and Pharmacology, University of Bristol, Medical Sciences Building, University Walk, Bristol, BS8 1TD, UK

    Christopher H. Fry

  4. Lilly UK, Lilly House, Priestley Road, Basingstoke, RG24 9NL, Hampshire, UK

    Dapo Ilo

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S.C. and C.F. declare that they are consultants for Eli Lilly and Company. S.C. declares that he is a shareholder and has a family member who is an employee of GlaxoSmithKline. C.F. declares that he has received honoraria for speaking from Pfizer, and research grant support from Boston Scientific and Takeda Pharmaceutical. D.I. declares that he is an employee and shareholder of Eli Lilly and Company. N.C. and M.C. declare no competing interests.

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Cellek, S., Cameron, N., Cotter, M. et al. Microvascular dysfunction and efficacy of PDE5 inhibitors in BPH–LUTS. Nat Rev Urol 11, 231–241 (2014). https://doi.org/10.1038/nrurol.2014.53

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