The neurovascular events that ultimately occur result in the inhibition of adrenergic tone and the release of the nonadrenergic, noncholinergic neurotransmitter, nitric oxide. Nitric oxide is believed to be released from nonadrenergic, noncholinergic nerves and endothelial cells. It subsequently stimulates the guanylate cyclase enzyme system in penile smooth muscle. This results in increased levels of cyclic guanosine monophosphate (cGMP) and ultimately in smooth muscle relaxation, enhancement of arterial inflow, and veno-occlusion, producing adequate firmness for sexual activity.
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.
Palmer MR, Holt SK, Sarma AV, Dunn RL, Hotaling JM, Cleary PA, Braffett BH, Martin C, Herman WH, Jacobson AM, Wessells H; Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications Research Group. Longitudinal Patterns of Occurrence and Remission of Erectile Dysfunction in Men With Type 1 Diabetes. J Sex Med. 2017 Oct;14(10):1187-1194. Doi: 10.1016/j.jsxm.2017.07.012. Epub 2017 Aug 26.
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).
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.  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.
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).
First, medical conditions need to be ruled out. Let’s assume that you have never been diagnosed with a medical condition that is physically linked to erectile dysfunction, such as type 2 diabetes, obesity or heart disease. In this case you’re probably looking at a case of psychological impotence, given that there are no physical explanations for your difficulties.
In comparison, 37% of men who had received external radiotherapy as their primary therapy reported the ability to attain functional erections suitable for intercourse, along with 43% of men who had received brachytherapy as primary treatment. Pretreatment sexual health-related quality of life score, age, serum prostate-specific antigen (PSA) level, race or ethnicity, body mass index, and intended treatment details were associated with functional erections 2 years after treatment. 
Due to the risk of hypotension, caution should be used in patients using alpha blockers for prostate hyperplasia and patients using other antihypertensive medications and alpha blockers, which should not be co-administered with PDE5 inhibitors. In patients who take 50 mg of sildenafil or more and use alpha blockers, sildenafil dosing should be avoided for at least 4 hours after the dose of the alpha blocker. In patients who take 25 mg of sildenafil, use of any alpha blockers is considered safe.
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.
Traditionally, erectile impotence (the classical definition of impotence) is the failure to achieve penile erection during intercourse. It may have either physical or psychological causes. Alcoholism, endocrine disease, and neurological disorders are typical physical causes. Psychological causes include anxiety over performance, hostility or other negative feelings toward the sexual partner, and stress, anxiety, depression, or other emotional conflicts outside of the relationship. Erectile impotence occasionally occurs with age and, although attributed by the individual to the aging process itself, it is usually secondary to disorders of aging, such as faulty blood circulation or prostate disease. In cases of impotence caused by blood vessel dysfunction, an insufficient supply of blood flows into the penis, or the blood diffuses out into adjacent tissues.
If a trial of oral ED therapy and withdrawal of offending medications prove to be ineffective in restoring erectile function, it is appropriate for most primary care practitioners to consider referral to a specialist for additional evaluation and discussion of alternative treatment options. These include intracavernous injection therapy, vacuum constriction devices, intraurethral therapy, and possible surgery.
There are many different body parts that play an important role for a man to get and maintain an erection during sexual intercourse. Beyond the physical causes that can lead to ED, it has been reported that 20% of ED is related to psychological causes.2 With so many possibilities leading to erectile dysfunction, it becomes particularly important to find a specialist who can correctly diagnosis the direct cause of your ED and find a treatment option that is right for you.
Centrally active compounds such as apomorphine have been used in men with ED whose cardiovascular comorbidity may prohibit PDE5i use, or in men who have concurrent apomorphine use for its anti-parkinsonian properties. Unfortunately, its side effect profile and poor effectiveness compared to other ED treatments have impaired its mainstream utilization (118). It is suspected that the side effects of apomorphine relate to its D2 receptor affinity. D4 receptor agonists, such as ABT-724 and azulenylmethylpiperazines, may not have the same associated side effects and show potent pro-erectile effects in animal models compared to apomorphine (32,119).
I suffered from sporadic limp dick in my 20s. It was usually when I was nervous because I was with a girl I actually liked. A doctor prescribed me Viagra. When I took it, my whole body went bright red, my nose became so congested that I had to breath through my mouth—almost impossible to do while kissing—and I stayed hard for an uncomfortably long nine hours.
Alteration of NO levels is the focus of several approaches to the treatment of ED. Inhibitors of phosphodiesterase, which primarily hydrolyze cGMP type 5, provided the basis for the development of the PDE5 inhibitors. Chen et al administered oral L-arginine and reported subjective improvement in 50 men with ED.  These supplements are readily available commercially. Reported adverse effects include nausea, diarrhea, headache, flushing, numbness, and hypotension.
In a prospective study from the Prostate Cancer Prevention Trial database, Thompson et al reported that men presenting with ED had a significantly higher chance of developing a cardiovascular event over a 7-year follow-up period.  The hazard ratio was 1.45, which is in the range of risk associated with current smoking or a family history of MI.
Qaseem, A., Snow, V., Denberg, T. D., Casey, D. E., Forciea, M. A., Owens, D. K., & Shekelle, P. (2009). Hormonal testing and pharmacologic treatment of erectile dysfunction: A clinical practice guideline from the American College of Physicians. Annals of internal medicine, 151(9), 639-649. Retrieved from http://annals.org/aim/article/745155/hormonal-testing-pharmacologic-treatment-erectile-dysfunction-clinical-practice-guideline-from
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…have traditionally been classified as impotence (inability of a man to achieve or maintain penile erection) and frigidity (inability of a woman to achieve arousal or orgasm during sexual intercourse). Because these terms—impotence and frigidity—have developed pejorative and misleading connotations, they are no longer used as scientific classifications, having been…
The venous constriction device is a device designed to compress the veins that drain blood flow out of the penis to keep blood in the penis. These devices may help individuals who have a "venous leak." In these individuals, although blood flow is coming into the penis, it is draining out at the same time and this persistent drainage prevents a fully rigid erection. These devices may be used with other forms of medical therapy, such as medications, injection therapy, or the vacuum device.
Garlic is considered to help effectively in dealing with the impotence and ED problems because it has high levels of allicin which can help to improve blood flow and blood circulation. A small research of Dr. Graham Jackson, consultant cardiologist at Guys and St Thomas’ NHS Trust discovered that consuming 4 cloves of garlic every day for 3 months can help much in improving the erection in 6 out of 7 volunteers struggling with impotence.
PDE5i for ED in patients with MS can be considered as reasonably effective and safe. Fowler et al. performed a randomized, multicenter, double-blind, flexible dose trial with open label extensions comparing sildenafil to placebo (75). A nearly 4-fold increase in effective erections was noted in the treatment arm, 96% vs. 24%. Sexual satisfaction and overall satisfaction were also improved in the treatment group based on IIEF scores, and quality of life assessments. Lombardi et al. evaluated tadalafil use in men with MS (71). Seventy eight percent of the men responded with improved erections, better quality of life with regards to sexual function, partner relationship and family life. Just less than half the men who responded to the tadalafil did so at the lower dosage of 10 mg. Subjects in either studies did not have any significant adverse side effects beyond flushing, and headache with PDE5i use.
Following a detailed discussion about the history of erectile dysfunction and its risk factors, your doctor will examine the testicles and penis to help determine the cause of erectile dysfunction. Your doctor will check reflexes and pulses in the area to see if problems with blood vessels or nerves are contributing to the erectile dysfunction. If necessary, your doctor will order tests to help diagnose erectile dysfunction.