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Pathophysiology of Erectile Dysfunction Following Radical Prostatectomy

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Book cover Sexual Function in the Prostate Cancer Patient

Part of the book series: Current Clinical Urology ((CCU))

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Abstract

Prostate cancer is the most common solid tumor in adult men, with an estimated 230,000 new cases diagnosed in the USA in 2006. There is a greater concern for quality of life after prostate cancer treatment due to the younger age of diagnosis and increased survival rate. One goal of radical prostatectomy surgery is to limit any further impairment of erectile function. We examine the current understanding of the pathophysiology of ED following radical prostatectomy.

During erection, parasympathetic tone dominates and a number of molecular pathways mediate a decrease in intracellular Ca, corporal smooth muscle relaxation, increased penile arterial inflow, and tumescence. Nitric oxide (NO) is generally agreed upon as the principle neurotransmitter involved in initiating and maintaining penile smooth muscle relaxation, and thus erection. It is clear that the extent to which the cavernous nerves are salvaged or damaged during radical prostatectomy is directly proportional to a patient’s degree of postoperative ED. An emerging concept in the field of erectile dysfunction is penile homeostasis. In order for an erection to occur, the complex and unique sinusoidal morphology of the corpora cavernosa must be maintained. New light has been shed on this process with the identification and investigation of the morphogenic protein Sonic hedgehog (SHH), along with its downstream targets Patched 1 (PTCH1), Hox, bone morphogenetic proteins (BMPs), vascular endothelial growth factor (VEGF), and NOS.

It is believed that chronic hypoxia and denervation of erectile tissue following radical prostatectomy result in permanent ED via apoptosis of smooth muscle cells, deposition of collagen (scar), and penile fibrosis. Hypoxia also causes an increase in release of potent vasoconstrictor molecules such as endothelin-1, a pro-fibrotic peptide, with synthesis.

Active investigation continues in the fields of penile homeostasis, the pathophysiology of ED, control of inflammation and fibrosis, prevention or limitation of smooth muscle apoptosis, and neural regenerative strategies influenced by TGF-B1.

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Acknowledgements

The authors would like to thank Yi Tang from Children’s Memorial Hospital, Chicago for the electron microscopic analysis of normal penile tissue.

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Authors and Affiliations

  1. Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Joshua Modder

  2. Assistant Professor of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Carol A. Podlasek

  3. FACS, Professor of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Kevin T. McVary

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  1. Joshua Modder
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  2. Carol A. Podlasek
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  3. Kevin T. McVary
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    © 2009 Humana Press, a part of Springer Science+Business Media, LLC

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    Modder, J., Podlasek, C.A., McVary, K.T. (2009). Pathophysiology of Erectile Dysfunction Following Radical Prostatectomy. In: Mulhall, J. (eds) Sexual Function in the Prostate Cancer Patient. Current Clinical Urology. Humana Press. https://doi.org/10.1007/978-1-60327-555-2_3

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