The erectile–endothelial dysfunction nexus: new opportunities for cardiovascular risk prevention


Erectile and endothelial dysfunction are common in individuals with multiple cardiovascular risk factors and are longitudinal predictors of cardiovascular events. The pathogenesis of both endothelial and erectile dysfunction is intimately linked through increased expression and activation of endothelial nitric oxide synthase, and the subsequent physiological actions of nitric oxide. Endothelial production of nitric oxide by endothelial nitric oxide synthase in the corpus cavernosum is involved in the maintenance of penile erection. Erectile dysfunction can be detected clinically using systematic questioning and could potentially be employed as an independent predictor of cardiovascular risk to target treatment of cardiovascular risk factors. Both erectile and endothelial dysfunction respond to lifestyle modifications, particularly in individuals with the metabolic syndrome. Drugs that improve endothelial dysfunction can also improve erectile dysfunction, but responses are not always concordant. Phosphodiesterase type 5 inhibitors, however, are powerful agents that commonly improve erectile and endothelial dysfunction, with potential cardiac applications. The recent Princeton consensus requires more extensive implementation and evaluation in clinical practice. The judicious diagnosis of erectile dysfunction, nevertheless, provides a unique opportunity for the prevention of cardiovascular disease.

Key Points

  • Endothelial and erectile dysfunction are intimately associated; both disorders arise from disturbance in the release and action of nitric oxide from endothelial cells

  • Erectile and endothelial dysfunction can be readily detected clinically and are associated with a wide spectrum of cardiovascular risk factors, and are also independently predictive of cardiovascular events

  • Both conditions can be improved by lifestyle modifications and by several pharmacological agents

  • Phosphodiesterase type 5 inhibitors improve both endothelial and erectile dysfunction by potentiating the action of nitric oxide from endothelial cells

  • The Princeton consensus offers practical guidelines for assessing cardiovascular risk in patients with erectile dysfunction and managing erectile dysfunction in patients with established coronary artery disease

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Figure 1: The physiology of penile erection—peripheral mechanisms
Figure 2: The roles of two forms of nitric oxide synthase in cavernosal smooth muscle relaxation and the initiation and maintenance of penile erection
Figure 3: The prevalence of erectile dysfunction, estimated by the IIEF-5 score, and serum high-sensitivity CRP levels in relation to components of the metabolic syndrome, as defined by the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults
Figure 4: The 'artery size' hypothesis
Figure 5: Mechanism of action of phosphodiesterase type 5 inhibitors in inducing smooth-muscle relaxation in cavernosal arteries and in the peripheral circulation


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Correspondence to Gerald F Watts.

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Watts, G., Chew, K. & Stuckey, B. The erectile–endothelial dysfunction nexus: new opportunities for cardiovascular risk prevention. Nat Rev Cardiol 4, 263–273 (2007).

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