An understanding of the anatomy and physiology of normal penile erection is crucial to appropriate identification of likely etiologies and planning treatment strategies. Attainment of an erection results from multiple influences converging on the penile smooth muscle. An erection requires adequate blood flow to the paired corpora cavernosae surrounding the penile urethra and the corpus spongiosum at the glans penis (Fig. 24.1).

The central nervous system plays an important role in erectile function. The hypothalamus (medial preoptic area) is the integration point for the central control of erection. This area receives rich sensory impulses from a multitude of brain areas. Auditory stimuli, visual stimuli, and fantasy-initiated impulses project to this area and then travel down the spinal cord to peripheral nerves that innervate the penile vasculature initiating an erection. The penis is innervated by the sympathetic (T11-L2), parasympathetic (S2-S4), and somatic (S2-S4) nervous systems. Sympathetic input is antierectile, whereas parasympathetic and somatic inputs are proerectile. Both sympathetic and parasympathetic fibers reach the inferior hypogastric plexus in the pelvis, where the autonomic input to the penis is integrated and penile innervation via the cavernous nerves originates. The lesser cavernous nerves travel along the penis to supply the penile urethra and erectile tissue of the corpus spongiosum, while the greater cavernous nerves innervate the helicine arteries in the erectile tissue. The somatic component, the pudendal nerve, through the dorsal nerve branches is responsible for penile sensation and the contraction and relaxation of the extracorporeal striated muscles (bulbocavernous and ischiocavernous).

In response to sexual stimulation, parasympathetic neural activity predominates, resulting in increased blood flow into the cavernous sinuses and achievement of erection due to smooth muscle relaxation. The main neurotransmitter mediating smooth muscle relaxation is nitric oxide, which is released from the endothelium of the corpus cavernosa during nonadrenergic, noncholinergic neurotransmission. Nitric oxide, in turn, activates soluble guanylyl cyclase, which increases intracellular concentrations of cyclic guanosine monophosphate (cGMP). cGMP, in turn, results in the activation of cGMP-dependent protein kinase, which, in turn, phosphorylates specific proteins and ion channels. The consequence is a decrease in intracellular calcium concentration and relaxation of the smooth muscle. The rapid filling of the penile sinusoids results in expansion of the sinuses with resultant compression of the subtunical venular plexuses, resulting in near total occlusion of venous outflow. This results in trapping of blood within the corpus cavernosum raising the penis from a dependent position to an erect position. Resultant intracavernosal pressures may exceed 90 mm Hg during the full phase of penile erection. During the course of sexual intercourse or masturbation, the bulbocavernous reflex results in forcible compression of the base of the blood-filled corpora cavernosa, resulting in the penis becoming harder with intracavernous pressures exceeding several 100 mm Hg. During this maintenance phase of penile erection, both blood entering and blood leaving the penis temporarily seize.

This results from the sudden suppression of neurotransmitter release, breakdown of second messenger products, or discharge of sympathetic stimuli during ejaculation. Constriction of the trabecular smooth muscles reopens the venous channels resulting in expulsion of the trapped blood and return of a flaccid state. ED may result in abnormalities in one or several of these steps involved in the initiation or maintenance of an erection.

Neurologic. Damage to the CNS from cerebrovascular accidents and degenerative processes such as Alzheimer’s or Parkinson’s disease may all result in ED. Similarly, damage to the peripheral nervous system as may ensue from spinal cord injury, diabetic neuropathy, and vascular or prostate surgery are common causes of ED.

Endocrine. Testosterone deficiency causes both decreased libido and an inability to maintain an erection secondary to low levels of nitric oxide synthase. In addition, hyperprolactinemia, hyperthyroidism, and hypothyroidism can all cause ED. In these settings, normalizing hormonal levels often results in return of normal male sexual function.

Vasculogenic. Anatomic defects in the arterial and venous systems may cause ED. Arterial stenosis and vasodilator dysfunction secondary to atherosclerosis can prevent adequate blood flow to the penis for an erection and are the most common causes of ED. Arterial stenosis involving the aortoiliac blood vessels resulting in claudication in one or both legs, diminution in femoral pulses, and ED is referred to as Leriche’s syndrome. Venous dysfunction causing failure of veins to close during an erection may prevent the maintenance of an erection. Causes of abnormal venous drainage include Peyronie’s disease, aging, and diabetes mellitus.

Medications. Table 24.3 lists common medications that should be considered during the evaluation of ED.