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Inside the cell, NOS catalyzes the oxidation of L-arginine to NO and L-citrulline. Endogenous blockers of this pathway have been identified. The gaseous NO that is produced acts as a neurotransmitter or paracrine messenger. Its biologic half-life is only 5 seconds. NO may act within the cell or diffuse and interact with nearby target cells. In the corpora cavernosa, NO activates guanylate cyclase, which in turn increases cyclic guanosine monophosphate (cGMP). Relaxation of vascular smooth muscles by cGMP leads to vasodilation and increased blood flow.
Other factors leading to erectile dysfunction are diabetes mellitus, which is a well-known cause of neuropathy).[2] ED is also related to generally poor physical health, poor dietary habits, obesity, and most specifically cardiovascular disease, such as coronary artery disease and peripheral vascular disease.[2] Screening for cardiovascular risk factors, such as smoking, dyslipidemia, hypertension, and alcoholism is helpful.[2]
The first stem cell study for the treatment of ED was published in 2004. This study used embryonic stem cells to treat ED. At this time, there is a total of 36 published basic studies assessing stem cell therapy for ED, with two clinical trials. The mechanism of action of stem cells is to generate angiogenesis with subsequent increase in cavernosal smooth muscle cells within the corporal bodies.46
Erectile dysfunction may be an unpleasant condition that no one really wants to talk about, failing to acknowledge it won’t make the problem go away. Your best defense against health problems like this is to learn everything you can about it so you can tackle the problem at the root. If you’re ready to stop living in embarrassment about your sexual function, become an advocate for yourself and your own health and talk to your doctor.
Monitoring erections that occur during sleep (nocturnal penile tumescence) can help you and your doctor to understand if the erectile dysfunction is due to psychological or physical causes. The nocturnal penile tumescence test is a study to evaluate erections at night. Normally men have three to five erections per eight hours of sleep. The test can be performed at home or in a sleep lab. The most accurate way to perform the test involves a special device that is connected to two rings. The rings are placed around the penis, one at the tip of the penis and the other at the bottom (base) of the penis. The device records how many erections occur, how long they last, and how rigid they are. The test is limited in that it does not assess the ability to penetrate.
Does drinking water improve erectile dysfunction? Erectile dysfunction or ED is a common concern for men. Everyday factors, such as hydration levels, may affect a person's ability to get or maintain an erection. Drinking water may, therefore, help some men with ED. In this article, learn about the link between hydration and ED, and other factors that can cause ED. Read now
Robbins, C. L., Schick, V., Reece. M., Herbenick, D., Sanders, S. A. Dodge, B., & Fortenberry J. D., (2011, December 1). Prevalence, frequency, and associations of masturbation with partnered sexual behaviors among US adolescents. JAMA Pediatrics, 165(12), 1087–1093. Retrieved from https://jamanetwork.com/journals/jamapediatrics/fullarticle/1107656
Oral therapies via the PDE5i sildenafil, vardenafil, and tadalafil have been proven to be generally safe and effective in select NED populations. The majority of the treatment effectiveness data has been generated in the SCI population. Data regarding the use of PDE5i outside of the SCI population is lacking (58). Furthermore, the ED that exists in the population with neurologic disorders is often multifactorial and may be caused by psychogenic, psychosocial, hormonal, medication-related and disability-related factors. A careful evaluation of each patient must be performed to isolate these factors prior to initiating vasoactive therapy.
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.
ED can also occur among younger men. A 2013 study found that one in four men seeking their first treatment for ED were under the age of 40. The researchers found a stronger correlation between smoking and illicit drug use and ED in men under 40 than among older men. That suggests that lifestyle choices may be a main contributing factor for ED in younger men.
Alprostadil injections, which produce an erection in five to 20 minutes that lasts for about an hour. Patients use a fine needle to inject alprostadil (commonly known by the brand names Caverject Impulse and Edex) into the base or side of the penis. Side effects can include bleeding or fibrous tissue formation at the injection site as well as prolonged erection, according to the Mayo Clinic.
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.
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).
Organic Impotence. Diabetes mellitus, thyroid disease, and dysfunction of the pituitary gland or testes can cause impotence, as can certain medications. Other organic causes include arterial ischemia associated with atherosclerosis of the aorta and common iliac arteries, extensive pelvic surgery such as radical prostatectomy, spinal cord injury and other neurologic disorders, and a history of cigarette smoking. Because certain medications can cause impotence, it is recommended that in cases of recent impotence it be determined whether the patient has started on a new drug. The most common offenders are diuretics, antihypertensives, and vasodilators. Alcohol, which sometimes is ignored as a drug, is often a contributor to the problem of impotence.
There are many different treatment options for erectile dysfunction but your individual diagnosis will determine which treatment option is right for you. It is important to realize that not all treatment options will work for everyone. A doctor who has specialized in men’s sexual health (typically a urologist) will be the most qualified to discuss all of your treatment options with you. Many specialists will often encourage you to schedule additional follow up appointments to review how your treatment is working for you or if a different option may be more beneficial.
When sexually stimulated there is a release of a chemical, nitric oxide (NO) in the blood vessels of the corpus cavernosum. The NO stimulates the production of a compound called cGMP, which causes relaxation of the smooth muscle in the blood vessels supplying the corpus cavernosum. PDE 5 is an enzyme that breaks down cGMP. By inhibiting the breakdown of cGMP by PDE5, these medications allow cGMP to build up in the penis. cGMP causes muscles in the corpora cavernosa of the penis to relax. When the muscle is relaxed, more blood can flow into the penis and fill the spaces in the penis. As the penis fills with blood, the veins in the penis are compressed, and this results a hard erection. When the effect on PDE5 decreases, the cGMP levels go down and the muscle in the penis contracts, causing less blood to flow into the penis and allowing the veins to open up and drain blood out of the penis.
Yes, the vacuum device is effective. In fact, with use of the vacuum device, 88% of men will have an erection that is satisfactory for completion of sexual activity. The vacuum device may be the only therapy that is effective after the removal of a penile prosthesis. Patients also use vacuum devices as part of penile rehabilitation after radical prostatectomy to help preserve the tissue of the penis and prevent scarring within the penis and loss of penile length. Its use, however, is limited by the mechanical nature of it and the time taken to pump the device and apply the band. Sex partners may complain of the penis being cool to touch.
The PDE5 inhibitors sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis) are prescription drugs which are taken orally.[22]:20–21 Additionally, a cream combining alprostadil with the permeation enhancer DDAIP has been approved in Canada as a first line treatment for erectile dysfunction.[25] Penile injections, on the other hand, can involve one of the following medications: papaverine, phentolamine, and prostaglandin E1, also known as alprostadil.[22]:25
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PDE5i use in PD has not been well studied; however its benefits have been shown. Raffaele performed an open label, prospective study evaluating the efficacy of sildenafil 50 mg on demand and depressive symptoms experienced by the PD patient (73). Erections were improved in approximately 85% of men and 75% noted improvements in their depressive symptoms as well. Sildenafil was well tolerated without significant side effects. Zesiewicz et al., performed a shorter study showing improvements in erectile function but no change in depression and parkinsonisms after ED treatment (74).
PDE 5 inhibitors are broken down primarily by enzyme, cytochrome P450enzyme CYP3A4. Medications that decrease or increase the activity of CYP3A4 may affect levels and effectiveness of PDE 5 inhibitors. Such drugs include medications for the treatment of HIV (protease inhibitors) and the antifungal medications ketoconazole and itraconazole. Thus caution is recommended.
In the short term, alcohol relaxes muscles in the penis, letting blood to flow in (which is a good thing). However, alcohol also prevents other blood vessels from closing and trapping all the extra blood. Erections depend on trapping increased blood flow in the erectile tissue of the penis. If you don’t trap that extra blood, you don’t get an erection. In the long run, excessive alcohol consumption can cause liver scarring, high blood pressure, and can damage your blood vessels resulting in erectile dysfunction.

Vacuum therapy devices have a few disadvantages. One must interrupt foreplay to use them. You must use the correct-size tension ring and remove it, to prevent penile bruising, after sustaining the erection for 30 minutes. Initial use may produce some soreness. Such devices may be unsuitable for men with certain bleeding disorders. In general, vacuum constriction devices are successful in management of long-term ED.

Low-intensity extracorporeal shock wave therapy has been proposed as a new non-invasive treatment for erectile dysfunction caused by problems with blood vessels. Shock wave therapy machines are now available in some medical practices in Australia. Although there is some evidence that it may help a proportion of men with erectile dysfunction, more research is needed before clear recommendations on its use can be made.
The observation that TRT enhances the efficacy of PDE5 inhibitors in hypogonadal men taking these therapies with suboptimal response to the PDE5 inhibitors alone has been reported.33 In addition, investigators have demonstrated that TRT in hypogonadal men can improve erectile function even without the benefit of PDE5 inhibitors.33 In addition, guidelines for managing ED in hypogonadal men by the European Association of Urology recommend controlling the man to a eugonadal state prior to initiation of PDE5 inhibitor therapy.36 Testosterone measurement consists of a serum specimen which should be ideally obtained in the morning because of the normal diurnal variation of testosterone which is at its peak in the morning. Since TRT is relatively safe, and men can potentially see an improvement in erectile function, it seems prudent to consider this issue when presented with a patient suffering from ED.
Herbal supplements such as ginkgo biloba, saw palmetto, and yohimbe have been touted as sexual enhancers, and some men have been tempted to try them to treat erectile dysfunction. Bennett warns, however, that none has been approved by the FDA or even shown by any reliable studies to prevent, treat, or improve erectile dysfunction. Moreover, supplements are unregulated and can have many side effects or interfere with prescribed medications you’re already taking. Don’t jeopardize your health by taking a supplement to treat erectile dysfunction without first talking with your doctor.
Recognized risk factors for ED include cardiovascular disease (CVD) (hypertension, atherosclerosis, and hyperlipidemia), diabetes, depression, alcohol use, smoking, pelvic/perineal surgery or trauma, neurologic disease, obesity, pelvic radiation, and Peyronie’s disease. One study suggested that the relationship between arterial disease and ED is very strong, with 49% (147 of 300) of patients with coronary artery disease noted on cardiac catheterization reporting significant erectile dysfunction.6 Endothelial dysfunction has been indicated as the pathophysiologic mechanism responsible for both CVD and ED.7 The Boston Area Community Health survey demonstrated a dose-response between smoking and incidence of erectile dysfunction.8 Animal studies have demonstrated both smooth-muscle disruption and decreased production of neural nitric oxide synthase in cigarette-exposed animals.9
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. [14] These supplements are readily available commercially. Reported adverse effects include nausea, diarrhea, headache, flushing, numbness, and hypotension.
"Medications that create blood flow to the penis can't help when an erection is blocked by the fear or anxiety of the fight-or-flight response,” says Feloney. “This type of erectile dysfunction probably has a lot to do with evolution — men didn't need an erection when a dinosaur was chasing them." The best way to treat erectile dysfunction caused by performance anxiety, depression, a poor relationship, or stress may be with a combination of ED drug treatment and sex therapy, individual therapy, or couples therapy from sexual health professionals.
The first line and by far the most common treatment today is with the prescription drug sildenafil citrate, sold under the brand name Viagra. An estimated 20 million prescriptions for the pill have been filled since it was approved by the FDA in March 1998. It is also the most effective treatment with a success rate of more than 60%. The drug boosts levels of a substance called cyclic GMP, which is responsible for widening the blood vessels of the penis. In clinical studies, Viagra produced headaches in 16% of men who took it, and other side effects included flushing, indigestion, and stuffy nose.

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.
Conditions that may be associated with ED include diabetes, [25, 26, 27] hypertension, [28] , and CAD, as well as neurologic disorders, endocrinopathies, benign prostatic hyperplasia, [29] , sleep apnea [30] , COPD, [31] and depression (see Table 1 below). [32, 33, 34, 35] In fact, almost any disease may affect erectile function by altering the nervous, vascular, or hormonal systems. Various diseases may produce changes in the smooth muscle tissue of the corpora cavernosa or influence the patient’s psychological mood and behavior.
The American Urological Association Guideline on the Management of ED states oral PDE5i are considered first line therapy for the treatment of ED, unless contraindicated (57). Sildenafil, the first oral PDE5i, was introduced in 1998 and has revolutionized ED therapy due to its broad applicability, effectiveness and safety profile. PDE5i work by preventing hydrolysis of cGMP by the PDE5 enzyme in the smooth muscle of the corpora cavernosa. cGMP degradation typically leads to smooth muscle contraction and detumescence prevented by PDE5i administration. Two other PDE5i, vardenafil and tadalafil are other PDE5i with different pharmacokinetics, PDE receptor selectivity and side effect profiles.

The idea of using low-energy shock waves to treat erectile dysfunction comes from studies that show that these types of shocks help heart blood vessels regrow, a process called revascularization. Shock wave therapy may also work on the penis, and there have been some promising results, but it’s not currently an approved ED treatment. "It’s similar to the type of shock waves used to break up kidney stones, and it may cause revascularization,” says Bennett. “However, there are not yet any good controlled studies to recommend it to patients."

The link between chronic disease and ED is most striking for diabetes. Men who have diabetes are two to three times more likely to have erectile dysfunction than men who do not have diabetes. Among men with erectile dysfunction, those with diabetes may experience the problem as much as 10 to 15 years earlier than men without diabetes. Yet evidence shows that good blood sugar control can minimize this risk. Other conditions that may cause ED include cardiovascular disease, atherosclerosis (hardening of the arteries), kidney disease, and multiple sclerosis. These illnesses can impair blood flow or nerve impulses throughout the body.
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