Factors that mediate contraction in the penis include noradrenaline, endothelin-1, neuropeptide Y, prostanoids, angiotensin II, and others not yet identified. Factors that mediate relaxation include acetylcholine, nitric oxide (NO), vasoactive intestinal polypeptide, pituitary adenylyl cyclase–activating peptide, calcitonin gene–related peptide, adrenomedullin, adenosine triphosphate, and adenosine prostanoids.

The physical side effects of chemotherapy are usually temporary and resolve within one to two weeks after stopping the chemotherapy. However, chemotherapy agents, such as Ciplatin or Vincristine, may interfere with the nerves that control erection leading to possible impotence. Make sure you discuss potential side effects of cancer chemotherapy with your doctor or healthcare provider.
In 1983, Brindley injected the corpora of several SCI men with phentolamine (85). Two out of the three men had a sufficient erection produced. Since then multiple reports on the efficacy of intracavernosal therapy have been published using, phentolamine, papaverine, prostaglandin, vasoactive intestinal peptide (VIP), and these medications in combination (86-90). These medications have been found to be extremely effective for neurogenic ED due to their ability act locally and essentially bypassing neuronal pathways. Local therapies are usually considered second-line after PDE5i fail to elicit a desired response which can occur in about 25–30% of men with ED, in general (91). Furthermore, the locally delivered medications can be quite dangerous if not used appropriately as priapism and significant pain with injections can occur. These specific occurrences have been suggested as a reason for high discontinuation rates with intracavernosal therapy (92).
Multiple combinations of intracavernosal therapy exist and the effectiveness of them varies based on patient characteristics and varying dosing strength (Table 1). Combination therapy have been extremely effective in the SCI population, and have several advantages including a reduction in cost per dose and side effects base on the lowered dose of each component (101,102). Effectiveness of combination therapy in the spinal cord population is well established, but no specific dose recommendations can be made based on the data (103-106). The use of combination therapy on other forms of neurogenic ED have not been well studied, but there use can be trialed as second-line therapy, or for populations were the side effects of PDE5i may preclude use such as in MSA due to hypotension.
Sure, this condition might be common – but isn’t erectile dysfunction a problem that only middle and senior-aged men get? It is true that erectile problems are common in older men. It often happens due to lower levels of testosterone and reduced blood flow to the penis. But this study showed that a quarter of all men under the age of 40 experience erectile dysfunction of some kind!
Clearly, PDE5i have revolutionized the treatment of ED in general and the neurogenic ED population is no exception. They remain safe and effective in most men with neurogenic ED; however, care must be taken in prescribing PDE5i to men high spinal cord lesions, MSA or possibly PD. VEDs are minimally-invasive and can be as effective as other modalities at leading to erection. However, high discontinuation rates are associated with VED use related to pain, difficulty using the device or cold penis. Intracavernosal therapy has been a mainstay of treatment for neurogenic ED and remains extremely successful in the SCI population. Trial of intracavernosal therapy for other causes of neurogenic ED can be considered second-line therapy, but there is a relative paucity of data for clinical outcomes related to its use outside of SCI men. Surgical therapy via penile implantation remains another second line approach and may also be utilized to assist men with bladder management. Higher complication rates of infections, and perforation have been reported compared to neurologically intact men. Many other compounds are currently being evaluated for the treatment of neurogenic ED as well as gene and stem cell therapy, but still should be considered investigational until substantiated by randomized controlled trials.
Finally, there are NO-releasing polymers that are capable of delivering NO in a pharmacologically useful way. Such compounds include compounds that release NO upon being metabolised and compounds that release NO spontaneously in aqueous solution. Initial animal studies suggest that cavernosal injections of NO polymers can significantly improve erectile function.48
Clinical experience in switching medications to improve ED has been disappointing in that improvement does not often occur. Nonetheless, it is important to try to discontinue possible offending medications before proceeding to more invasive ED treatment options. Oral ED medications have changed the way clinicians discontinue medications in patients with ED and has improved the approach. For example, a patient may develop ED on a thiazide diuretic. The diuretic may be withdrawn, but a trial of oral ED therapy can be initiated during the observation period while the patient is waiting to see if any spontaneous improvement in ED occurs after drug withdrawal. Alternatively, if diuretic therapy is effective, well tolerated, and controlling blood pressure, oral ED therapy can be used on an ongoing basis to treat the side effect of ED.

Sexual stimulation causes the release of neurotransmitters from cavernosal nerve endings and relaxation factors from endothelial cells lining the sinusoids. NOS produces NO from L-arginine, and this, in turn, produces other muscle-relaxing chemicals, such as cGMP and cyclic adenosine monophosphate (cAMP), which work via calcium channel and protein kinase mechanisms (see the image below). This results in the relaxation of smooth muscle in the arteries and arterioles that supply the erectile tissue, producing a dramatic increase in penile blood flow.
Diabetes is a well-recognized risk factor for ED. A systematic review and meta-analysis found that the prevalence of ED was 37.5% in type 1 diabetes, 66.3% in type 2 diabetes, and 52.5% in diabetes overall—a rate approximately 3.5 times higher than that in controls. [39]  The etiology of ED in diabetic men probably involves both vascular and neurogenic mechanisms. Evidence indicates that establishing good glycemic control can minimize this risk.
Surgery: If neither drugs nor the vacuum pump works, your doctor may suggest surgery. With surgery, the doctor can place a device in your penis that will cause enough hardness for intercourse. In a few cases, infections may develop after the operation, and the doctor may have to remove the device. Another operation that may help you is rebuilding the blood vessels in the penis to increase blood flow into the penis or decrease blood flow out of the penis. These procedures can help you to get and maintain an erection.
Supplements are popular and often cheaper than prescription drugs for ED. However, supplements have not been tested to see how well they work or if they are a safe treatment for ED. Patients should know that many over-the-counter drugs have been found on drug testing to have ‘bootlegged' PDE 5 Inhibitors as their main ingredient. The amounts of Viagra, Cialis, Levitra or Stendra that may be in these supplements is not under quality control and may differ from pill to pill. The FDA has issued consumer warnings and alerts.
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