Several pre-treatment factors have been described that may indicate success with PDE5i therapy. The presence of an upper motor neuron lesion up to T12 suggests a successful response, as well as requirement for a lower dosage of medication (62,68-71). Additionally, the presence of residual erections after injury or an incomplete SCI (ASI-A vs. ASIB-D) also improve the chance of PDE5i treatment success (59,67,68,71).
Lifestyle choices that impair blood circulation can contribute to ED. Smoking, excessive drinking, and drug abuse may damage the blood vessels and reduce blood flow to the penis. Smoking makes men with atherosclerosis particularly vulnerable to ED. Being overweight and getting too little exercise also contribute to ED. Studies indicate that men who exercise regularly have a lower risk of ED.
Diabetes is an example of an endocrine disease that can cause a person to experience impotence. Diabetes affects the body’s ability to utilize the hormone insulin. One of the side effects associated with chronic diabetes is nerve damage. This affects penis sensations. Other complications associated with diabetes are impaired blood flow and hormone levels. Both of these factors can contribute to impotence.
On the horizon is gene therapy that would deliver genes that produce products or proteins that may not be functioning properly in the penile tissue of men with ED. Replacement of these proteins may result in improvement in erectile function. Experimental animal models have demonstrated improvement in erectile function with gene therapy. Human studies may also demonstrate success with this therapy. Gene therapy may take a long time for regulatory approval and public acceptance.
Malleable implants usually consist of paired rods, inserted surgically into each of the corpora cavernosa. The rods are stiff, and to have an erection, one bends them up and then when finished with intercourse one bends them down. They do not change in length or width. The malleable implants are the least mechanical and thus have the lowest risk of malfunction. However, also have the least "normal appearance."
Erections are neurovascular events, meaning that nerves and blood vessels (arteries and veins) are involved in the process of an erection and all must work properly to develop a hard erection that lasts long enough. Erection begins with sexual stimulation. Sexual stimulation can be tactile (for example, by a partner touching the penis or by masturbation) or mental (for example, by having sexual fantasies, viewing porn). Sexual stimulation or sexual arousal causes the nerves going to the penis to release a chemical, nitric oxide. Nitric oxide increases the production of another chemical, cyclic GMP (cGMP), in the muscle of the corpora cavernosa. The cGMP causes the muscles of the corpora cavernosa to relax, and this allows more blood to flow into the penis. The incoming blood fills the corpora cavernosa, making the penis expand.
L-arginine, an amino acid that is naturally present in the body and helps make nitric oxide, supports a successful erection. Nitric oxide is responsible for making the blood vessels relax, which helps sustain an erection for men. A 1999 study, observed the effects of six weeks of high-dose (5 grams/day) orally administered nitric oxide (NO) donor L-arginine on men with organic ED. Thirty-one percent of those who took 5 grams/day of L-arginine experienced significant improvements in sexual function. Burns told Medical Daily, “l-arginine and deer antler velvet” have been the most popular go-to natural treatments for men.
The availability of phosphodiesterase-5 (PDE5) inhibitors—sildenafil, vardenafil, tadalafil, and avanafil—has fundamentally altered the medical management of ED. In addition, direct-to-consumer marketing of these agents over the last 15 years has increased the general public’s awareness of ED as a medical condition with underlying causes and effective treatments.
Penile injection therapy, intracavernous injection, involves the injection of a vasodilator (a chemical that relaxes arteries to increase blood flow) into the penis. Penile injected therapy is recognized as the most effective nonsurgical treatment for erectile dysfunction. However, due to the invasive nature, it is often used in men who have failed or have contraindications to other treatments such as oral therapies.
Positron emission tomorgraphy (PET), and functional magnetic resonance imaging (fMRI) have led to a greater understanding to which center are activated during arousal. These imaging studies measure increases in cerebral blood flow or changes in cerebral activity on a real-time basis. Studies are performed when male subject are aroused by visual cues (usually sexual explicit photos or videos) and compared to images obtained during exposure to sexually neutral cues differences can be measured. Several studies have identified that the inferior frontal lobes, inferior temporal lobes and insular gyrus, and occipital lobes are involved with processing arousal cues, although each are likely to process different stimuli (20-23).
Ultimately, PDE5i have had a significant impact on the treatment of ED in men with SCI. The ease of use and tolerability of the medication has also led to improved satisfaction and quality of life that had been previously affected by SD. Head to head trials evaluating specific PDE5i within the SCI population are required to further elucidate drug preference. PDE5i should be considered first line therapy, however men with high thoracic and cervical lesions should be warned about an increased chance of dizziness with sildenafil and possibly other PDE5i use.
Soler et al. compared sildenafil to vardenafil and tadalafil (69). Sildenafil was effective in 85% of SCI patients, 74% of the patients on vardenafil and 72% of the patients on tadalafil. Sildenafil was associated with more rigid and longer lasting erections. Additionally, 50 mg of sildenafil was effective in 55% of patients compared to more than 70% of the patients on vardenafil and tadalafil requiring 20 mg for a similar response. Men who used tadalafil were able to achieve erections 24 hours after administration, improving overall satisfaction related to the possible spontaneity of sexual encounters. Del Popolo also evaluated the time/duration effectiveness of PDE5i sildenafil 50 mg versus tadalafil 10 mg (64). Tadalafil 10 mg significantly increased the percentage of successful intercourse attempts at 12–24 hours compared with sildenafil. One can suspect that vardenafil, which has a longer half-life than sildenafil, could offer a similar benefit but a study investigating this occurrence has yet to be performed.
Using the correct size of tension ring is critical in obtaining the best possible result from this type of treatment. If the ring is too tight, it can be uncomfortable. If too large a ring is used, the erection may not last. The tension ring should not be left in place longer than 30 minutes. Leaving the ring in place for longer than 30 minutes can cause damage to the penis and further aggravate the cause of the erectile dysfunction.
Acupuncture may help treat psychological ED, though studies are limited and inconclusive. You’ll likely need several appointments before you begin to notice any improvements. When choosing an acupuncturist, look for a certified practitioner who uses disposable needles and follows U.S. Food and Drug Administration guidelines for needle disposal and sterilization.
If you are taking medications (alpha-blockers) for problems with an enlarged prostate, you should discuss your prostate medications with your doctor. Alpha-blockers also can cause lowering of the blood pressure. Thus your doctor will need to carefully watch your blood pressure when you start the PDE5 inhibitor. Common alpha-blockers include doxazosin (Cardura), terazosin (Hytrin), and tamsulosin (Flomax).
Viagra is available in three strengths: 25 mg, 50 mg, and 100 mg. Viagra works best if taken on an empty stomach about 30-45 minutes before sexual activity. Optimal results may not be realized until the medication has been tried six to eight times. Viagra may be used cautiously with alpha-blocker medications as long as sufficient time has passed between their dosing.
Additionally, the physiologic processes involving erections begin at the genetic level. Certain genes become activated at critical times to produce proteins vital to sustaining this pathway. Some researchers have focused on identifying particular genes that place men at risk for ED. At present, these studies are limited to animal models, and little success has been reported to date.  Nevertheless, this research has given rise to many new treatment targets and a better understanding of the entire process.
Erectile dysfunction - (ED) or impotence is sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual activity. A penile erection is the hydraulic effect of blood entering and being retained in sponge-like bodies within the penis. The process is most often initiated as a result of sexual arousal, when signals are transmitted from the brain to nerves in the penis.
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.
Patients with both ED and cardiovascular disease who receive treatment with an oral PDE5 inhibitor require education regarding what to do if anginal episodes develop while the drug is in their system. Such education includes stressing the importance of alerting emergency care providers to the presence of the drug so that nitrate treatment is avoided.
MSA is a neurodegenerative disease of undetermined etiology, where ED is an early prominent sign occurring in 40% of men at the time of diagnosis (46,47). ED occurs in the majority of patients and the exact cause of it is unknown (48). Like PD, MSA likely affects the dopaminergic pathways within the brain essential for arousal (49). Orthostatic hypotension (OH) as a causal factor has been refuted by evidence that sildenafil can overcome reduced filling pressures, and the ED usually precedes the development of OH (46,49,50). Similar to other neurologic disorders that lead to ED, other disease related factors such as psychosocial stress, the burden of chronic illness, changed appearance, fatigue, decreased fine motor movement of fingers, immobility and diminished self-esteem due to loss of independence may contribute as well (51).
Before pursuing ED treatments, though, bear in mind that improving heart health by losing weight, eating a healthier diet, exercising more and quitting smoking typically enhances erectile performance as well as one’s overall health. In addition, sex therapy counseling sessions can often ease or eradicate ED symptoms, if the underlying cause is psychological in nature, says Drogo Montague, M.D., director of the Center for Genitourinary Reconstruction at the Cleveland Clinic.
Research is mixed on the effectiveness of acupuncture as an erectile dysfunction cure, but one study published in November 2013 in the Journal of Alternative and Complementary Medicine found that acupuncture can be beneficial for men experiencing erectile dysfunction as a side effect of antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs).
Capogrosso, P., Colicchia, M., Ventimiglia, E., Castagna, G., Clementi, M. C., Suardi, N., ... Salonia, A. (2013, July). One patient out of four with newly diagnosed erectile dysfunction is a young man — worrisome picture from the everyday clinical practice. The journal of sexual medicine. 10(7), 1833–1841. Retrieved from https://onlinelibrary.wiley.com/doi/full/10.1111/jsm.12179
In prescribing sildenafil, a doctor considers the age, general health status, and other medication(s) the patient is taking. The usual starting dose for most men is 50 mg, however, the doctor may increase or decrease the dose depending on side effects and effectiveness. The maximum recommended dose is 100 mg every 24 hours. However, many men will need 100 mg of sildenafil for optimal effectiveness, and some doctors are recommending 100 mg as the starting dose.
The mechanisms by which testosterone plays a role in erectile function are not completely understood. A study evaluating the effect of testosterone on erections in surgically castrated rabbits and control animals, in which the rabbits’ intracavernosal pressures were compared after cavernosal nerve stimulation, determined that castrated rabbits had much lower pressures after stimulation than control rabbits did.  Notably, the pressures increased when castrated rabbits received exogenous testosterone replacement.
Melanocortin receptor agonists were found to induce erections serendipitously. A study investigating the dermatologic use of Melanotan-II (MT-II) was found to generate erections unexpectedly leading to the development of MTII derivatives for ED treatment (120). MT-II was initially used to induce pigment changes in the skin for artificial tanning but has been suspected to induce melanoma, however (121).
According to a review of all randomized controlled trials evaluating sildenafil by the American Urological Association (AUA) Consensus Panel on Erectile Dysfunction, 36% to 76% of patients receiving the drug were "able to achieve intercourse" during treatment. For tadalafil, four randomized controlled trials revealed that 11% to 47% of patients were "able to achieve intercourse." Similar efficacy has been observed with vardenafil, although studies are fewer.19 A meta-analysis published in 2013 clearly demonstrated increased efficacy over placebo for all PDE5 inhibitors.24 Head-to-head comparison suggested that tadalafil outperforms sildenafil on validated measures of erectile dysfunction, including the international index of erectile function and sexual encounter profile-2 and -3.
Ultrasound with Doppler imaging (ultrasound plus evaluation of blood flow in the arteries and veins) can provide additional information about blood flow of the penis and may help in the evaluation of patients prior to surgical intervention. This study is typically performed after the injection of a chemical that causes the arteries to open up, a vasodilator (prostaglandin E1), into the corpora cavernosa in order to cause dilation of blood vessels and promote blood flow into the penis. The rate of blood flow into the penis can be measured along with an evaluation of problems with compression of the veins.
Suppositories “were developed so men wouldn’t have to use needles,” Bivalacqua says. They contain the drug alprostadil (also known as prostaglandin E1) and are sold under the brand name Muse. If they are going to work, it takes about five to 10 minutes. However, Muse produces erections in only 30 to 40 percent of patients, usually those with mild ED, because some of the drug is absorbed systemically and diverted from its function of opening penile arteries to allow more blood to flow in. The out-of-pocket cost is around $20 to $30 per suppository.
One of the first steps is to distinguish between physiological and psychological ED. Determining whether involuntary erections are present is important in eliminating the possibility of psychogenic causes for ED. Obtaining full erections occasionally, such as nocturnal penile tumescence when asleep (that is, when the mind and psychological issues, if any, are less present), tends to suggest that the physical structures are functionally working. Similarly, performance with manual stimulation, as well as any performance anxiety or acute situational ED, may indicate a psychogenic component to ED.