UroToday.com - The etiology of multiple sclerosis (MS)-emergent erectile dysfunction (ED) is still matter of debate, since both organic and psychological factors have been implicated. There is an association between sexual dysfunction (SD) and destructive lesions in the pons, in MS patients. Central and peripheral nerves systems play a key role in the erectile process. The innervation of the penis is both autonomic (sympathetic and parasympathetic) and somatic (sensory and motor). Pudendal nerves have a central role in erection. Tactile stimulation of the penile shaft activates parasympathetic fibers, which travel in the pudendal nerve and function through the spinal reflex arc from S2 to S4. Neural signals originating in the brain are transmitted to a thoracolumbar erection center and trigger the psychogenic erection associated with either fantasy or viewing erotic material. In addition, the ischiocavernosus and bulbospongiosus striated muscles, which located at the penile crus, are innervated by the motor pudendal nerve. Contraction of these muscles has a definite, contributory role in penile erection. Therefore, erection is a neurovascular event, and any disease or dysfunction affecting the brain, spinal cord, or cavernous and pudendal nerves can induce ED. With respect to placebo, sildenafil produced a 16% greater success rate for vaginal penetration, and a 15% greater rate for successful intercourse. For satisfaction with erection hardness, and satisfaction with the sexual experience, sildenafil did not produce two-fold greater rates. For all efficacy variables, sildenafil had similar or slightly greater scores compared with placebo.

Although some clinical trials have demonstrated an overall success rate of greater than 70%, certain patients will be refractory to treatment with sildenafil. Sildenafil acts a potentiator of local mediators to maintain smooth muscle relaxation and thus cannot act in the absence of intact penile innervation. In this study, most of the participants had abnormal pudendal nerve cortical somatosensory evoked potentials (PEPs). The incidence of ED after non-nerve sparing radical retropubic prostatectomy is up to 97%. This is due to cavernosal nerve damage. A poor response to sildenafil in postoperative patients with unilateral or non-nerve-sparing radical retropubic prostatectomy has been demonstrated. Direct-acting medications might be expected to be efficacious in nonresponders who have nerve injury or nerve damage. Fifty percent of the post prostatectomy patients who had failed with sildenafil, reported improved EF with intraurethral alprostadil.

Sexual dysfunction is a frequent disorder associated to MS, which contributes to the worsening of quality of life of these patients. During the course of MS, prevalence of SD becomes increasingly more common, affecting, after 10 years of disease duration, 40-70% of patients.

Interactions between neural structures are essential to all phases of human sexual response and functioning. Neurophysiological studies give invaluable information on the involvement of the parts of the nervous system that are essential in the control of sexual function. The pudendal nerve and its terminal branch (dorsal nerve of the penis) provide somatosensory innervation to the genitalia in men. Sensory pathways, which are important in reflexogenic erections, transmit information to the CNS via the dorsal penile nerve and the pudendal nerve. Therefore, a neurophysiological test that assesses the pudendal nerve function such as the PEPs, has great value in an objective evaluation of SD.

We did not recommend second or third type PDE-5 inhibitors for sildenafil non-responders. All three FDA approved PDE-5 inhibitors are targeting the same site of action. Studies from the industry tend to favor preference for their own drug, whereas independent studies tend to show no major difference in preference. Multiple well-designed studies have shown that, all three available PDE-5 inhibitors, have a very similar efficacy and safety profile. In our experiences, well-educated sildenafil non-responders, seldom respond to other type of PDE-5 inhibitors.

Written by M.R Safarinejad, MD as part of Beyond the Abstract on UroToday.com

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