Erectile Dysfunction, Metabolic Syndrome, and Cardiovascular Risks

Facts and Controversies

Edward Sanchez; Alexander W. Pastuszak; Mohit Khera


Transl Androl Urol. 2017;6(1):28-36. 

In This Article

A Common Pathophysiology for ED and CVD

To better understand the link between ED and CVD, an understanding of the physiology of erection is useful. Erection results from coordinated communication of hormonal, neural, and vascular systems as well as psychological inputs. Sensory input from receptors in the skin, glans, urethra, and corporat cavernosa travel via the dorsal nerve of the penis, and later the pudendal nerve, to S2–S4 nerve roots. Interaction with the thalamus and sensory cortex leads to parasympathetic activation and release of nitric oxide (NO) from the cavernous nerves and endothelial cells. NO activates guanylyl cyclase, which catalyzes the formation of cyclic guanosine monophosphate (cGMP). Protein kinase G is activated by cGMP and leads to phosphorylation of potassium and calcium channels, cellular hyperpolarization, reduced intracellular calcium, and smooth muscle relaxation. This smooth muscle relaxation, along with decreased peripheral arteriolar resistance promotes blood inflow into the corporal tissues. In addition, adenosine, prostaglandins, and calcitonin gene-related peptides may activate cyclic adenosine monophosphate (cAMP), a similar mediator of smooth muscle relaxation.[20] cGMP and cAMP are later degraded by phosphodiesterase type 5 (PDE5) and PDE4, respectively.[21]

The discovery of NO as a signaling molecule and its part in the cascade that ultimately leads to an erection led to further exploration of the role of endothelial dysfunction in ED. Endothelial integrity is crucial to this process, and endothelial dysfunction is thought to be a common denominator between ED and CVD.[22] Initial impairments to the endothelium-dependent vasodilation in penile tissues may lead to late structural changes, penile artery atherosclerosis, and flow-limiting stenosis similar to that seen in CAD.[23]