Elsevier

The Lancet

Volume 381, Issue 9861, 12–18 January 2013, Pages 153-165
The Lancet

Seminar
Erectile dysfunction

https://doi.org/10.1016/S0140-6736(12)60520-0Get rights and content

Summary

Erectile dysfunction is a common clinical entity that affects mainly men older than 40 years. In addition to the classical causes of erectile dysfunction, such as diabetes mellitus and hypertension, several common lifestyle factors, such as obesity, limited or an absence of physical exercise, and lower urinary tract symptoms, have been linked to the development of erectile dysfunction. Substantial steps have been taken in the study of the association between erectile dysfunction and cardiovascular disease. Erectile dysfunction is a strong predictor for coronary artery disease, and cardiovascular assessment of a non-cardiac patient presenting with erectile dysfunction is now recommended. Substantial advances have occurred in the understanding of the pathophysiology of erectile dysfunction that ultimately led to the development of successful oral therapies, namely the phosphodiesterase type 5 inhibitors. However, oral phosphodiesterase type 5 inhibitors have limitations, and present research is thus investigating cutting-edge therapeutic strategies including gene and cell-based technologies with the aim of discovering a cure for erectile dysfunction.

Introduction

Inadequate penile erection, otherwise known as erectile dysfunction, is defined as the inability to attain or maintain a penile erection sufficient for successful vaginal intercourse.1 This clinical disorder was described in early historical records, with descriptions of poor penile erection in men found in ancient Egyptian scriptures that are more than 5000 years old.2, 3 1998 marked the milestone introduction of the first effective oral drug treatment, sildenafil citrate (Viagra, Pfizer, New York, NY, USA), for the treatment of erectile dysfunction.4 Sildenafil belongs to a group of well-characterised drugs that are called selective phosphodiesterase type 5 inhibitors (PDE5-Is).5, 6, 7, 8, 9 These drugs were all developed on the basis of a conceptual understanding of the fundamental role of nitric oxide (NO) smooth muscle relaxation in penile cavernous tissues.10, 11, 12 Recognition of the important part NO plays in signalling smooth muscle relaxation in penile tissue led to a dramatic expansion of research focused on sexual dysfunction in men.

Section snippets

Epidemiology

Erectile dysfunction is a common medical disorder that primarily affects men older than 40 years of age. A recent extensive analysis of published work on the prevalence of erectile dysfunction,13 reported by the International Consultation Committee for Sexual Medicine on Definitions/Epidemiology/Risk Factors for Sexual Dysfunction, showed that the prevalence of erectile dysfunction was 1–10% in men younger than 40 years. Prevalence of erectile dysfunction range from 2% to 9% in men between the

Physiology of penile erection

NO, released from the endothelium and the parasympathetic nerve terminals, is the primary neurotransmitter involved in penile erection, although other transmitters can also be involved.37 NO-dependent relaxation of the cavernosal smooth muscles leads to compression of the subtunical small veins, occluding local venous return and resulting in an erection (figure 1). Penile detumescence begins with activation of the adrenergic receptors on the cavernous arteries and trabecular smooth muscles,

Pathophysiology and cause

Normal sexual function has been described as a biopsychosocial process that involves the coordination of psychological, endocrine, vascular, and neurological systems.38 Erectile dysfunction is classified as psychogenic, organic (ie, neurogenic, hormonal, arterial, cavernosal, or drug induced), or mixed psychogenic and organic (panel 1). Erectile dysfunction is usually of a mixed psychogenic and organic nature.

Diagnosis

At present, the scientific consensus has been to adopt a goal-directed approach during the assessment of patients complaining of erectile dysfunction.68, 69, 70, 71 The main goals of assessment of erectile dysfunction are to establish whether the disorder is truly erectile dysfunction, to identify the cause of the disorder, and to ascertain risk factors and potentially life-threatening comorbid disorders associated with erectile dysfunction.

Treatment

Overall, oral PDE5-Is are the mainstay of treatment of erectile dysfunction. Other treatment modalities include lifestyle modification, injection therapies, testosterone therapy, penile devices, and psychotherapy (figure 4).68, 69, 70

Future perspectives

Although PDE5-Is are undoubtedly a huge step forward in the management of erectile dysfunction, they are far from flawless. Well-known shortcomings of PDE5-Is are their non-universal success rate, absence of spontaneity, and life-long drug commitment. At present, specific treatments that target more than just the inhibition of the PDE5 enzyme are being developed. For example, several guanylate cyclase activators have already undergone preclinical trials and promising results have been reported.

Conclusions

Substantial advances in our understanding of the physiology of erection and the pathophysiology of erectile dysfunction led to the development of the first successful group of oral treatments for erectile dysfunction—PDE5-Is. Erectile dysfunction is now recognised as an early predictor of CAD. Despite these advances, there is still a great need for more effective therapeutic drugs that can provide long-lasting improvement for erectile dysfunction. Future promising therapeutic strategies,

Search strategy and selection criteria

We searched PubMed for papers published in English between 1980 and March, 2012, with the terms “erectile dysfunction” and “impotence”, “diagnosis”, “treatment”, “epidemiology”, “physiology”, and “pathophysiology”. We also reviewed recent and past textbooks. We mainly focused on publications in the past 5 years; however, we did not ignore landmark relevant articles. Other relevant articles identified by review of the reference lists of selected articles were also included. We also reviewed

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