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
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.
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Adverse effects related to PDE5i use with mild-moderate and transient (58). Furthermore, side effects usually attenuate if use is not discontinued. Autonomic dysreflexia, a life-threatening phenomenon characterized by bradycardia, hypertension, facial flushing and headaches associated with SCI lesions above T6, has not been reported with use. However, hypotension leading to dizziness in individuals treated with sildenafil has been noted with high thoracic and cervical levels of injury (72). No adverse events were noted within the study; however, the dizziness was reported by use of sildenafil 50 mg in the cervical LOI and 100 mg in the thoracic LOI patients. Headache is the most reported side effect of all PDE5i, followed by dyspepsia and flushing. Priapism, and death have not been reported after use of PDE5i by SCI patients.
As with most other organ system in the human body, changes and loss of function is normal consequence of the ageing process. This is also true of the endocrine system, specifically the levels of testosterone production from the Leydig cells of the testicle. Accompanying the decrease in testosterone is a decrease in erections which also has a component in decrease in the blood supply to the penis making erection not as frequent and not as rigid compared with a young man’s erectile function. Although these changes are in itself not life threatening, they can impact a man’s relationship with his partner, and also ED may be a harbinger of other undiagnosed conditions such as coronary artery disease (CAD), hypercholesterolaemia or diabetes mellitus.6
"Sexual relations are not only an important part of people's wellbeing. From a clinical point of view, the inability of some men to perform sexually can also be linked to a range of other health problems, many of which can be debilitating or potentially fatal," says Professor Gary Wittert, Head of the Discipline of Medicine at the University of Adelaide and Director of the University's Freemasons Foundation Centre for Men's Health.
Nerves originating in the spinal cord and peripheral ganglia innervate the penis. There are autonomic (parasympathetic and sympathetic), and somatic separate and integrated pathways. The autonomic pathways neurons originate in the spinal cord and peripheral ganglia from the sympathetic and parasympathetic systems, respectively. They merge to form the cavernous nerves that travel alongside the prostate, enter the corpora cavernosa and corpus spongiosum to affect the neurovascular events required for tumescence and detumescence. The somatic nerves send sensory information from the penile skin, glans, and urethra via the dorsal penile nerve and pudendal nerve to the spinal cord. The somatic nerves also initiate contraction of the ischio- and bulbocavernosus muscles.
Take an ED drug. Such drugs can help men maintain erections for several hours at a time. They work by enhancing the effect of nitric oxide, which the body produces naturally to relax and increase blood flow to the penis. If you're interested in taking a drug specifically geared toward treating ED, talk with your doctor about getting a prescription.
In the 14 years or so since Viagra was introduced in 1998, the number of men diagnosed with erectile dysfunction (ED) has increased by a whopping 250 percent. Men are realizing more and more that they’re not alone and that they have options. Aside from pills like Viagra, Levitra, and Cialis, for example, there are surgical, therapeutic, even do-it-yourself treatments that can bring back that lovin’ feeling. "Some older ED treatments are actually being used more than ever, especially for men who can't take the pill," says Michael Feloney, MD, a urologist at the Nebraska Medical Center in Omaha. Read on to find out about nine common remedies for ED, plus the truth about which ones live up to the hype and which fall flat.
An analysis of 14 studies involving more than 90,000 patients with ED confirmed the relation between ED and an increased risk of cardiovascular events and mortality.  Compared with patients without ED, those with ED had a 44% increased risk of cardiovascular events, a 25% increased risk of all-cause mortality, a 62% increased risk of MI, and a 39% increased risk of cerebrovascular events. Treatment of ED, either through lifestyle interventions or by pharmacologic means, may improve prognosis and reduce risk.
ED usually has something physical behind it, particularly in older men. But psychological factors can be a factor in many cases of ED. Experts say stress, depression, poor self-esteem, and performance anxiety can short-circuit the process that leads to an erection. These factors can also make the problem worse in men whose ED stems from something physical.
And surgery comes with its own serious risks, such as developing incontinence or impotence, while radiation can result in urinary problems. — Peter Loftus, WSJ, "Surgery Adds Three Years to Lives of Prostate-Cancer Patients, Study Finds," 12 Dec. 2018 Male-impotence pill Viagra began facing generic competition late last year, while the Lyrica pain treatment is expected to confront generics at the end of this year. — Jonathan D. Rockoff, WSJ, "Pfizer Narrows Guidance on Tougher Pricing, Generic Competition," 30 Oct. 2018 Arkham Horror Third Edition is a classic struggle of agency versus impotence, set in the uncanny world of H.P. Lovecraft’s Cthulhu mythos. — Charlie Theel, Ars Technica, "Arkham Horror Third Edition: The classic Lovecraft adventure returns," 24 Nov. 2018 There’s obviously a lot of anger and frustration here toward the US government at the moment—along with side effects like bottled rage and sometimes a creeping sense of ineptitude or impotence about our ability to do anything about it. — Corey Seymour, Vogue, "Pussy Riot's Nadya Tolokonnikova On Her New Guide To Activism, Raising The Next President Of Russia, And Her "Holy War" On Fairy Tales," 12 Oct. 2018 In exchange for political impotence, they would be mostly left alone and allowed to get rich. — Paul Mozur, New York Times, "Inside China’s Dystopian Dreams: A.I., Shame and Lots of Cameras," 8 July 2018 Their suspicion is compounded by rumors that the polio vaccine causes impotence, death and, ironically, paralysis. — Meher Ahmad, New York Times, "Pakistan Has Just One New Polio Case, but Isn’t Declaring Victory Yet," 20 May 2018 Fighting back, even as an exercise in impotence, did a lot for McCain. — Alex Horton, Washington Post, "John McCain rebelled at the Naval Academy — and as a POW — long before he was a Senate maverick," 3 May 2018 Feelings of desperation and impotence are being felt throughout Central America, where the lawlessness, endemic poverty and levels of gang violence akin to war zones that have driven so many families from their homes show little signs of abating. — Washington Post, "Violence keeps Central Americans coming to US despite Trump," 21 June 2018
Vardenafil and tadalafil belong to the same group of chemical compounds as sildenafil, namely phos-phodiesterase type 5 (PDE-5) inhibitors. Some men cannot benefit from sildenafil or the two newer PDE-5 inhibitors because they have low levels of nitric oxide. British investigators reported in late 2002 that three different types of compounds are being studied as possible medications for men with low levels of nitric oxide. They are Rho-kinase inhibitors, soluble guanylate cyclase activators, and nitric oxide-releasing PDE-5 inhibitors.
Talk with your doctor about going to a counselor if psychological or emotional issues are affecting your ED. A counselor can teach you how to lower your anxiety or stress related to sex. Your counselor may suggest that you bring your partner to counseling sessions to learn how to support you. As you work on relieving your anxiety or stress, a doctor can focus on treating the physical causes of ED.
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.
The dorsal artery provides for engorgement of the glans during erection, whereas the bulbourethral artery supplies the bulb and the corpus spongiosum. The cavernous artery effects tumescence of the corpus cavernosum and thus is principally responsible for erection. The cavernous artery gives off many helicine arteries, which supply the trabecular erectile tissue and the sinusoids. These helicine arteries are contracted and tortuous in the flaccid state and become dilated and straight during erection. 
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.
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.
The development of an erection is a complex event involving integration of psychologic, neurologic, endocrine, vascular, and local anatomic systems. Positron emission tomography scanning studies have suggested that sexual arousal is activated in higher cortical centers that then stimulate the medial preoptic and paraventricular nuclei of the hypothalamus.5 These signals ultimately descend through a complex neural network involving the parasympathetic nervous system and eventually activate parasympathetic nerves in the sacral area (S2 to S4).
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The use of injection therapy requires being taught how to properly inject the medication, determination of the best dose, and monitoring for side effects. It is recommended that one inject on the side of the penis at the base and to alternate sides. Injection therapy should be used no more frequently than once every 24 hours. Individuals on blood thinners must be careful with use of injection therapy.
Since endothelial dysfunction, CVD and ED are closely associated in epidemiological studies, the question for clinicians is whether to recommend the man presenting with ED undergo a cardiovascular (CV) evaluation. Clearly, based on numerous studies, ED can be considered at least a ‘marker’ for possible further vascular disease or CVD.15 In their report, Vlachopoulos and coworkers make the point that the man presenting with ED, the clinician, is offered an opportunity to attempt to improve the health of the man by addressing lifestyle modification, and consider further vascular evaluation owing to the clear relationship between endothelial dysfunction, ED and CVD.19
The FDA recommends that men follow general precautions before taking a medication for ED. Men who are taking medications that contain nitrates, such as nitroglycerin, should NOT use these medications. Taking nitrates with one of these medications can lower blood pressure too much. In addition, men who take tadalafil or vardenfil should use alpha blockers with care and only as instructed by their physician, as they could result in hypotension (abnormally low blood pressure). Experts recommend that men have a complete medical history and physical examination to determine the cause of ED. Men should tell their doctor about all the medications they are taking, including over-the-counter medications.
Recently, several advances in the uses of stem cells have bet met with great anticipation. Stem cells have the ability to differentiate into different cell lines based on the cellular signaling they receive. Bone marrow mononuclear cells in particular have been used for the treatment of ED in animal models. Yiou et al. recently delivered bone marrow-mononuclear cells (BM-MNC) into the intracavernous smooth muscle of post radical prostatectomy men (123). The open label, dose escalation phase I/II trial showed improvements in IIEF-15 assessment as well as increased vascularization of the corpora based on penile Doppler arterial velocity measurements. Although promising, further investigation in humans is required to substantiate BM-MNCs impact on erections, and erectile function recovery going forward.
Finally, gene therapy and stem cell research has widened the frontier of ED treatment proposed as possibility to even reverse ED. Specifically, gene therapy pertains to repairing the cause of ED by restoring defective gene function and/or altering the expression of the mutant gene (32). Most of the available data on gene therapy are in the animal model. However, a phase I clinical trial in men with ED undergoing intracavernous injection with a DNA plasmid carrying the alpha-subunit of the corporal smooth muscle Maxi-K channel showed promise in increased erectile function based on IIEF assessment sustained throughout the 3-month study period (122).
The primary nerve fibers to the penis are from the dorsal nerve of the penis, a branch of the pudendal nerve. The cavernosal nerves are a part of the autonomic nervous system and incorporate both sympathetic and parasympathetic fibers. They travel posterolaterally along the prostate and enter the corpora cavernosa and corpus spongiosum to regulate blood flow during erection and detumescence. The dorsal somatic nerves are also branches of the pudendal nerves. They are primarily responsible for penile sensation. 
The main surgical treatment of ED involves insertion of a penile implant (also called penile prostheses). Because penile vascular surgery is not recommended for aging males who have failed oral PDE5 inhibitors, ICI or IU therapies, implants are the next step for these patients. Although placement of a penile implant is a surgery which carries risks, they have the highest rates of success and satisfaction among ED treatment options.