The PDE5 inhibitors sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis) are prescription drugs which are taken orally.: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. Penile injections, on the other hand, can involve one of the following medications: papaverine, phentolamine, and prostaglandin E1, also known as alprostadil.:25
Impotence is a common problem among men and is characterized by the consistent inability to sustain an erection sufficient for sexual intercourse or the inability to achieve ejaculation, or both. Erectile dysfunction can vary. It can involve a total inability to achieve an erection or ejaculation, an inconsistent ability to do so, or a tendency to sustain only very brief erections.
The common PDE5 inhibitor drugs approved in the United States are sildenafil (Viagra), vardenafil (Levitra and Staxyn, the generic form), tadalafil (Cialis), or avanafil (Stendra). All of the currently approved PDE5 inhibitors work in the same way. They differ in the number of available doses, how quickly they work and last in your system, the dosing, and to some extent in the side effects. However, they generally share the same indications and contraindications. Currently, tadalafil is the only medication that patients can take on a daily basis and is approved for the treatment of both ED and BPH (benign enlargement of the prostate).
A meta-analysis of 36 744 men with ED in 12 prospective cohort studies found that the presence of ED significantly increased the risk of CVD, CAD, stroke and all-cause mortality, and the presence of ED was an independent risk factor for CVD. Ponholzer et al found that men with moderate to severe ED had a 65% increased relative risk for developing symptomatic CAD compared with men who did not have ED.26
The views expressed in this article intend to highlight alternative studies and induce conversation. They are the views of the author and do not necessarily represent the views of hims, and are for informational purposes only, even if and to the extent that this article features the advice of physicians and medical practitioners. This article is not, nor is it intended to be, a substitute for professional medical advice, diagnosis, or treatment, and should never be relied upon for specific medical advice.
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.
Replacement testosterone is available as oral pills, intramuscular injections, skin patches, and a gel that is rubbed into the skin. Men with low sexual desire and ED may have low testosterone (male hormone) levels. Hormone replacement may occasionally be of some benefit, especially when used in combination with other therapies. Testosterone supplementation alone is not particularly effective in treating erectile dysfunction. Sexual desire and an overall sense of well-being are likely to improve when serum testosterone levels (the levels in the blood) are restored. This can take several months after starting testosterone replacement.
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Under normal circumstances, when a man is sexually stimulated, his brain sends a message down the spinal cord and into the nerves of the penis. The nerve endings in the penis release chemical messengers, called neurotransmitters, that signal the corpora cavernosa (the two spongy rods of tissue that span the length of the penis) to relax and fill with blood. As they expand, the corpora cavernosa close off other veins that would normally drain blood from the penis. As the penis becomes engorged with blood, it enlarges and stiffens, causing an erection. Problems with blood vessels, nerves, or tissues of the penis can interfere with an erection.
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.
Instead of the hesitation with which he had accosted the cardinal a quarter of an hour before, there might be read in the eyes of the young king that will against which a struggle might be maintained, and which might be crushed by its own impotence, but which, at least, would preserve, like a wound in the depth of the heart, the remembrance of its defeat.
Somatomotor penile innervation originates in Onuf’s nucleus in the S2-4 spinal segments. These nerves travel to the ischiocavernosus and bulbocavernosus muscles when activated lead to contraction necessary for the rigid-erection phase. Several animal studies show that stimulation of the somatomotor pathways may also be under sympathetic control, and adrenergic stimulation may lead to contraction of these muscles during ejaculation (13,14). Somatomotor spinal reflexes may also be initiated by genital stimulation. For instance, the well-known bulbocavernosus reflex is evidence this reflex exists; however the clinical significance of its absence in the neurological assessment of ED has not been substantiated (15).
Since the advent of PDE5i, many other selective and non-selective peripheral acting compounds have been developed or are in development. Avanafil has shown promising results in treating ED in post-prostatectomy patients with suspected cavernous nerve injury (111). Other PDE5i marked in Asia such as udenafil, and mirodenafil also effective at treating ED may minimize side effects due to shorter half-lives (112-114). Soluable guanylate-cyclase inhibitors and potassium channel activators are compounds that have induced erections in animal models but remain experimental requiring further investigation (115-117).
While erectile dysfunction can occur at any age, the risk of developing erectile dysfunction increases with age. According to the Massachusetts Male Aging Study, the prevalence of erectile dysfunction was 52% in men 40-70 years of age. The prevalence of complete erectile dysfunction increases from 5% at 40 years of age to 15% among men 70 years of age and older.
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
A common and important cause of ED is vasculogenic. Many men with ED have comorbid conditions such as hyperlipidemia, hypercholesterolemia, tobacco abuse, diabetes mellitus, or coronary artery disease (CAD).  The Princeton III Consensus recommends screening men who present with ED for cardiovascular risk factors; ED may be the earliest presentation of atherosclerosis and vascular disease. 
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.
The inflatable type of device consists of cylinders that are implanted in the corpora cavernosa, a fluid reservoir implanted in the abdomen, and a pump placed in the scrotum. The man squeezes the pump to move fluid into the cylinders and cause them to become rigid. (He reverses the process by squeezing the pump again.) While these devices allow for intermittent erections, they have a slightly higher malfunction rate than the silicon rods.
Your healthcare provider will ask about your symptoms, medical history, and medicines. He or she will examine your abdomen, penis, and testicles. A rectal exam may also be done to check for an enlarged prostate. Blood and urine tests are done to check for medical conditions that may have caused your ED. You may also need tests to check your blood flow and nerve function.
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.
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.
Certain feelings can interfere with normal sexual function, including feeling nervous about or self-conscious about sex, feeling stressed either at home or at work, or feeling troubled in your current sexual relationship. In these cases, treatment incorporating psychological counseling with you and your sexual partner may be successful. One episode of failure, regardless of cause, may propagate further psychological distress, leading to further erectile failure.
Certain types of blood pressure medications, antiulcer drugs, antihistamines, tranquilizers (especially before intercourse), antifungals (hetoconazole), antipsychotics, antianxiety drugs, and antidepressants, known as selective serotonin reuptake inhibitors (SSRIs, including Prozac and Paxil), can interfere with erectile function. Smoking, excessive alcohol consumption, and illicit drug use may also contribute. In rare cases, low levels of the male hormone testosterone may contribute to erectile failure. Finally, psychological factors, such as stress, guilt, or anxiety, may also play a role, even when the impotence is primarily due to organic causes.
Cavallini, G., Modenini, F., Vitali, G., & Koverech, A. (2005, November). Acetyl-L-carnitine plus propionyl-L-carnitine improve efficacy of sildenafil in treatment of erectile dysfunction after bilateral nerve-sparing radical retropubic prostatectomy. Urology, 66(5), 1080-5. Retrieved from http://www.sciencedirect.com/science/article/pii/S0090429505006515
MUSE should not be used in men with a history of urethral stricture (narrowing of the tube in the penis that urine and semen pass through), inflammation or infection of the glans (tip) of the penis (balanitis), severe hypospadias (a condition where the opening of the urethra is not at the tip of the penis, rather on the underside of the penis), penile curvature (abnormal bend to the penis), and urethritis (inflammation/infection of the urethra).
Currently, placement of a penile prosthesis is the most common surgical procedure performed for erectile dysfunction. Penile prosthesis placement is typically reserved for men who have tried and failed (either from efficacy or tolerability) or have contraindications to other forms of therapy including PDE5 inhibitors, intraurethral alprostadil, and injection therapy.
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.
Because the burning side effect is triggered by alprostadil, the formulations with the least alprostadil — tri-mix and certain versions of bi-mix — could work for men who experience burning with the single-drug formula. But some men might choose alprostadil alone because the multi-drug cocktails can cost more and must be dispensed by a compounding pharmacy — one that is authorized to mix medications on site — which could mean the added hassle of a long drive to pick up the drug.
If the structure of the penis is healthy (not fibrosed or scarred), the use of injectable drugs is almost always effective. If one chooses this therapy, a doctor or nurse will teach the individual how to perform the injections, and the urologist (specialist) must determine the appropriate dose. The dosage is adjusted to achieve an erection with adequate rigidity for no more than 90 minutes.
Long-term predictions based on an aging population and an increase in risk factors (eg, hypertension, diabetes, vascular disease, pelvic and prostate surgery, benign prostatic hyperplasia, and lower urinary tract symptoms) suggest a large increase in the number of men with ED. In addition, the prevalence of ED is underestimated because physicians frequently do not question their patients about this disorder.
Tadalafil (Cialis) is the third oral medicine approved by the U.S. FDA for the treatment of erectile dysfunction. Like sildenafil (Viagra) and vardenafil (Levitra), tadalafil inhibits PDE5 (as described earlier). Unlike the other PDE 5 inhibitors, patients should take tadalafil once daily and is approved for the treatment of BPH (benign enlargement of the prostate).
Alprostadil, a synthetic PGE1, is the most commonly used single drug for injections into the penis as a treatment for ED. It works well in the majority of men who try it. In one study of 683 men with ED, 94% reported having erections suitable for penetration after PGE1 injections. When PGE1 is used in combination with papaverine and Regitine, the mixture is called Trimix, which has roughly twice the effectiveness of alprostadil alone. However, Trimix is quite expensive and is usually not covered by insurance, while PGE1 is often a covered benefit in most insurance medication plans. The main side effects are pain from the medication (not from the injection), priapism (persistent or abnormally prolonged erection), and scarring at the site of the injection. It is recommended that one alternate the side of the penis being injected to help decrease the risk of penile scarring. Many men are uncomfortable with penile injection therapy even though the injection itself is painless. The injection cannot be done more often than every other day. Men on anticoagulant medications (blood thinners) must be careful with injection therapy.
In a randomized double-blind, parallel, placebo-controlled trial, sildenafil plus testosterone was not superior to sildenafil plus placebo in improving erectile function in men with ED and low testosterone levels.  The objective of the study was to determine whether the addition of testosterone to sildenafil therapy improves erectile response in men with ED and low testosterone levels.
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.
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Usually there will not be a specific treatment that will lead to the improvement of erectile dysfunction. However, there are treatments that will allow erections to happen and can be used to allow sexual activity to take place. There are three main types of treatments: non-invasive treatments such as tablet medicines and external devices (e.g. vacuum device); penile injections; or for men who have not had success with other treatments, surgery may be an option.