Erectile Dysfunction

Erectile Dysfunction

Asif Muneer, David J Ralph, Nigel Borley
European Endocrine Disease 2007 - Issue I
Published: October 2008
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Erectile dysfunction is a common male sexual function disorder and is defined as the inability to achieve and maintain an erection satisfactory for sexual intercourse. The Male Massachusetts Aging Study (MMAS) provides data from a large cohort of men (n=1,290, age 40–70 years) and estimates that 150 million men worldwide experience some degree of erectile dysfunction.1 When these data are extrapolated from worldwide demographics, it is estimated that by 2025 this figure is likely to double. The last two decades have seen significant advances in the understanding of the physiological basis of penile erection. Central to this was the discovery that smooth muscle relaxation was mediated by an endothelial-derived relaxing factor (EDRF), which was later characterized as nitric oxide (NO).2 Combined with the development of oral phosphodiesterase type 5 (PDE-5) inhibitors, which were approved by the US Food and Drug Administration (FDA) in 1998, pharmacotherapeutic options are readily available to patients with erectile dysfunction. The availability of these drugs has also resulted in more men seeking treatment for their condition.

Physiology of Normal Penile Erection
Penile erection is a complex hemodynamic event that involves a combination of local, humoral, and neural factors. A key step in the signaling pathway is the release of NO from nitrergic nerves via neuronal nitric oxide synthase (nNOS), combined with the release of endothelial NO via endothelial nitric oxide synthase (eNOS) following penile engorgement and shear stress. The NO-mediated catalysis of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP) via interaction with the hemoprotein-soluble guanylate cyclase (sGC) is a key step in the pathway. Peripherally, this culminates in the relaxation of the corpus cavernosum smooth muscle and penile vasculature, resulting in increased bloodflow into the trabecular network and sinusoidal spaces. Subsequent compression of the subtunical venules reduces the venous outflow from the corpus cavernosum and maintains tumescence (see Figure 1).

Figure 1: Mechanism of Penile Erection Illustrating the Effects of Subtunical Venule Compression
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