ORIGINAL RESEARCH—PATHOPHYSIOLOGY
Pathophysiology of Erectile Dysfunction

https://doi.org/10.1111/j.1743-6109.2005.20103.xGet rights and content

Summary of Committee. For the complete report please refer to Sexual Medicine: Sexual Dysfunctions in Men and Women, edited by T.F. Lue, R. Basson, R. Rosen, F. Giuliano, S. Khoury, F. Montorsi, Health Publications, Paris 2004.

ABSTRACT

Introduction.  Multiple regulatory systems are involved in normal erectile function. Disruption of psychological, neurological, hormonal, vascular, and cavernosal factors, individually, or in combination, can induced erectile dysfunction (ED). The contribution of neurogenic, vascular, and cavernosal factors was thoroughly reviewed by our committee, while psychological and hormonal factors contributing to ED were evaluated by other committees.

Aim.  To provide state of the art knowledge on the physiology of ED.

Methods.  An international consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state‐of‐the‐art knowledge in the respective sexual medicine topic represent the opinion of experts from five different continents developed in a process over a 2‐year period. Concerning the pathophysiology of ED committee, there were seven experts from five different countries.

Main Outcome Measure.  Expert opinion was based on the grading of evidence‐based medical literature, widespread internal committee discussion, public presentation, and debate.

Results.  The epidemiology and classification of neurogenic ED was reviewed. The evidence for the association between vascular ED and atherosclerosis/hypercholesterolemia, hypertension and diabetes was evaluated. In addition, the pathophysiological mechanisms implicated in vascular ED were defined, including: arterial remodeling, increased vasoconstriction, impaired neurogenic vasodilatation, and impaired endothelium‐dependent vasodilatation. The possible mechanisms underlying the association between chronic renal failure and ED were also evaluated as well as the evidence supporting the association of ED with various classes of medications.

Conclusions.  A better understanding of how diseases interfere with the physiological mechanisms that regulate penile erection has been achieved over the last few years, which helps establish a strategy for the prevention and treatment of ED.

Section snippets

Neurogenic Erectile Dysfunction

Events that disrupt central neural networks or the peripheral nerves involved in sexual function can cause ED. This form of ED has been termed “neurogenic impotence.” It has been estimated that 10–19% of ED is of neurogenic origin [1, 2].

The etiologies of neurogenic ED can be classified as:

  • Peripheral (peripheral ED)

  • Spinal (sacral‐peripheral ED, suprasacral‐central ED)

  • Supraspinal (suprasacral ED)

Peripheral ED can be secondary to the disruption of sensory nerves that bring local information to

Vascular Erectile Dysfunction

Erectile dysfunction and cardiovascular disease share the same risk factors such as hypertension, diabetes mellitus, hypercholesterolemia, and smoking [20, 21]. This led to the suggestion that ED is another manifestation of vascular disease [22, 23].

Diabetes

There is good epidemiological evidence of a causal link between diabetes and ED [70]. The prevalence of ED is three times higher in diabetic men (28% vs. 9.6%) [21], occurs at an earlier age, and increases with disease duration, being approximately 15% at age 30 rising to 55% at 60 years [71, 72].

Diabetes mellitus may cause ED through a number of pathophysiological changes affecting psychological function, central nervous system (CNS) function, androgen secretion, peripheral nerve activity,

Primary Erectile Dysfunction

Physical causes of primary ED are likely to relate to maldevelopment of the corpora or their blood and nerve supply. In addition, vascular or neurological damage may occur during fetal life or childhood. Primary psychological dysfunction can also occur and is usually related to anxiety about sexual performance stemming from adverse childhood events or traumatic early sexual experience. Endocrine abnormalities, particularly low testosterone levels, may also be implicated in primary ED although

Chronic Renal Failure and Erectile Dysfunction

Men suffering chronic renal failure (CRF) requiring renal replacement therapy have a high prevalence of sexual dysfunction (20–50%) [96]. A recent well‐performed cross‐sectional study demonstrated a prevalence of severe self‐reported ED among men on hemodialysis of 45%[97]. The risk was increased by older age, diabetes, and nonuse of ACE inhibitors. Many of the pathophysiological effects of persistent uremia can potentially contribute to the development of ED including disturbance of the

Drugs Causing Erectile Dysfunction

In order to confidently establish a causative relationship, three conditions should be satisfied. There should be a higher prevalence of ED among men taking the drug calculated from data with placebo control and stratification for known risk factors of ED. A greater prevalence of ED should also be found for the target drug compared to another drug with an equivalent therapeutic effect using data from a randomized controlled trial, again with allowance for confounding variables. Finally, a

References (150)

  • A. Nehra et al.

    Cavernosal expandability is an erectile tissue mechanical property which predicts trabecular histology in an animal model of vasculogenic erectile dysfunction

    J Urol

    (1998)
  • K.M. Azadzoi et al.

    Relative roles of cyclooxygenase and nitric oxide synthase pathways in ischemia‐induced increased contraction of cavernosal smooth muscle

    J Urol

    (1999)
  • K.M. Azadzoi et al.

    Mechanisms of ischemia‐induced cavernosal smooth muscle relaxation impairment in a rabbit model of vasculogenic erectile dysfunction

    J Urol

    (1998)
  • K.M. Azadzoi et al.

    Hypercholesterolemia impairs endothelium‐dependent relaxation of rabbit corpus cavernosum smooth muscle

    J Urol

    (1991)
  • J.H. Kim et al.

    Experimental hypercholesterolemia in rabbits induces cavernosal atherosclerosis with endothelial and smooth‐muscle cell dysfunction

    J Urol

    (1994)
  • M. Burchardt et al.

    Hypertension is associated with severe erectile dysfunction

    J Urol

    (2000)
  • C.B. Johannes et al.

    Incidence of erectile dysfunction in men 40–69 years old: Longitudinal results from the Massachusetts male aging study

    J Urol

    (2000)
  • J.M. Kaufman et al.

    Impotence and chronic renal failure: A study of the hemodynamic pathophysiology

    J Urol

    (1994)
  • T.M. Hale et al.

    Recovery of erectile function after brief aggressive antihypertensive therapy

    J Urol

    (2002)
  • J.T. Daley et al.

    Prostanoid production in rabbit corpus cavernosum: I. Regulation by oxygen tension

    J Urol

    (1996)
  • R.B. Moreland et al.

    PGE1 suppresses the induction of collagen synthesis by transforming growth factor‐β1 in human corpus cavernosum smooth muscle

    J Urol

    (1995)
  • A. Nehra et al.

    Transforming growth factor‐beta1 (TGF‐beta1) is sufficient to induce fibrosis of rabbit corpus cavernosum in vivo

    J Urol

    (1999)
  • J.E. Toblli et al.

    Morphological changes in cavernous tissue in spontaneously hypertensive rats

    Am J Hypertens

    (2000)
  • T.M. Hale et al.

    Antihypertensive drugs induce structural remodeling of the penile vasculature

    J Urol

    (2001)
  • Y.C. Tong et al.

    The norepinephrine tissue concentration and neuropeptide Y immunoreactivity in genitourinary organs of the spontaneously hypertensive rat

    J Auton Nerv Syst

    (1996)
  • U. Simonsen et al.

    Effect of sildenafil on non adrenergic non‐cholinergic neurotransmission in bovine penile small arteries

    Eur J Pharmacol

    (2001)
  • T. Heitzer et al.

    Increased NAD(P)H oxidase‐mediated superoxide production in renovascular hypertension: Evidence for an involvement of protein kinase C

    Kidney Int

    (1999)
  • T.J. Bivalacqua et al.

    Increased expression of arginase II in human diabetic corpus cavernosum: In diabetic‐associated erectile dysfunction

    Biochem Biophys Res Commun

    (2001)
  • J. Angulo et al.

    Diabetes impairs endothelium‐dependent relaxation of human penile vascular tissues mediated by NO and EDHF

    Biochem Biophys Res Commun

    (2003)
  • C.J. Mullarkey et al.

    Free radical generation by early glycation products: A mechanism for accelerated atherogenesis in diabetes

    Biochem Biophys Res Commun

    (1990)
  • A.D. Seftel et al.

    Advanced glycation end products in human penis: Elevation in diabetic tissue, site of deposition and possible effect through iNOS or eNOS

    Urology

    (1997)
  • M.F. Usta et al.

    The protective effect of aminoguanidine on erectile function in streptozotocin diabetic rats

    J Urol

    (2003)
  • C. Gocmen et al.

    Effects of vitamin E and sodium selenate on neurogenic and endothelial relaxation of corpus cavernosum in the diabetic mouse

    Eur J Pharmacol

    (2000)
  • C.R. Woodhouse

    Sexual function in boys born with exstrophy, myelomeningocele, and micropenis

    Urology

    (1998)
  • C. Teloken et al.

    Congenital abnormality of corpora cavernosa and erectile dysfunction: A case report

    J Urol

    (1993)
  • D.K. Montague et al.

    Primary erectile dysfunction in a man with congenital isolation of the corpora cavernosa

    Urology

    (1995)
  • T.F. Lue

    Surgery for crural venous leakage

    Urology

    (1999)
  • C.C. Carson et al.

    The epidemiology, anatomy, physiology, and treatment of erectile dysfunction in chronic renal failure patients

    Adv Ren Replace Ther

    (1999)
  • S.E. Rosas et al.

    Prevalence and determinants of erectile dysfunction in haemodialysis patients

    Kidney Int

    (2001)
  • J.H. Abicht

    Testing the autonomic system

  • S. Aboseif et al.

    The effect of cryosurgical ablation of the prostate on erectile function

    Br J Urol

    (1997)
  • A.T. Chuang et al.

    Neurophysiology of penile erection

  • D.B. Caetano et al.

    Disturbances of sexual potency in patients with basilar impression and Arnold‐Chiari malformation

    J Neurol Neurosurg Psychiatry

    (1975)
  • G.J. Christ et al.

    The application of gene therapy to the treatment of erectile dysfunction

    Int J Impot Res

    (1998)
  • O. Adsan et al.

    The value of cavernous body biopsy in evaluating of impotent men

    Arch Ital Urol Androl

    (1997)
  • S.T. Ali et al.

    HIV‐1 associated neuropathies in males; impotence and penile electrodiagnosis

    Acta Neurol Belg

    (1994)
  • R.D. Amelar et al.

    Impotence in the low‐back syndrome

    JAMA

    (1971)
  • M.V. Autieri et al.

    Identification of a down‐regulated mRNA transcript in corpus cavernosum from diabetic patients with erectile dysfunction

    Int J Impot Res

    (1996)
  • C.D. Betts et al.

    Erectile dysfunction in multiple sclerosis. Associated neurological and neurophysiological deficits, and treatment of the condition

    Brain

    (1994)
  • E. Bors et al.

    Neurological urology.

    (1971)
  • Cited by (0)

    View full text