If PDE5 drugs don't work or cannot be used because of potential side effects, your doctor can recommend other therapies. The drug alprostadil (Caverject, Edex, Muse) allows blood to flow more freely in the penis, leading to an erection. The drug can be injected with a tiny needle into your penis. Or, a small pellet (suppository) can be inserted into the opening of the penis. Suppositories and injections are effective in the majority of men.


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.
Diabetes mellitus: Erectile dysfunction tends to develop 10 to 15 years earlier in diabetic men than among nondiabetic men. The increased risk of erectile dysfunction among men with diabetes mellitus may be due to the earlier onset and greater severity of atherosclerosis (hardening of the arteries) that narrows the arteries and thereby reduces the delivery of blood to the penis. Atherosclerosis can affect the arteries in the penis, as well as the arteries in the pelvis that supply the penile arteries. Diabetes mellitus also causes erectile dysfunction by damaging nerves that go to the penis, much like the effect of diabetes on nerves in other areas of the body (diabetic neuropathy). Diabetes can also affect the muscles in the penis, leading to troubles with erections. Smoking cigarettes, obesity, poor control of blood glucose levels, and having diabetes mellitus for a long time further increase the risk of erectile dysfunction in people with diabetes.
For obvious reasons, ED can be a sensitive subject, one that until relatively recently men were more likely to try to hide than to deal with. Fortunately, a deeper understanding of the variety of causes of erectile dysfunction has led to medications, therapies, and other treatments that can be more individualized and more likely to be effective—and more open discussion about addressing the concern.
There are also alternative treatments, such as using a penis pump or a penile injection. Penis pumps work by creating a vacuum and thereby causing more blood to flow to your penis. Penile injections need to be used shortly before intercourse. They contain a medication which widens your blood vessels. A doctor’s prescription is needed for the injections.
Another potential new treatment consists of penile low-intensity shock wave lithotripsy. This consists of 1500 shocks twice a week for 3–6 weeks. The purpose is to stimulate neovascularisation to the corporal bodies with improvement in penile blood flow and endothelial function. The use of low-intensity shock wave lithotripsy may convert PDE5 inhibitor non-responders to responders.47
For obvious reasons, ED can be a sensitive subject, one that until relatively recently men were more likely to try to hide than to deal with. Fortunately, a deeper understanding of the variety of causes of erectile dysfunction has led to medications, therapies, and other treatments that can be more individualized and more likely to be effective—and more open discussion about addressing the concern.

Before taking any medication for erectile dysfunction, including over-the-counter supplements and herbal remedies, get your doctor's OK. Medications for erectile dysfunction do not work in all men and might be less effective in certain conditions, such as after prostate surgery or if you have diabetes. Some medications might also be dangerous if you:
The vascular processes that produce an erection are controlled by the nervous system and certain prescription medications may have the side effect of interfering with necessary nerve signals. Among the possible culprits are a variety of stimulants, sedatives, diuretics, antihistamines, and drugs to treat high blood pressure, cancer, or depression. But never stop a medication unless your doctor tells you to. In addition, alcohol, tobacco, and illegal drugs, such as marijuana, may contribute to the dysfunction.
NO is produced by the enzyme NO synthase (NOS). [13] NOS plays many roles, ranging from homeostasis to immune system regulation. To date, 3 subtypes have been identified: nNOS, iNOS, and eNOS, which are produced by the genes NOS1, NOS2, and NOS3, respectively. This nomenclature is derived from the sources of the original isolates: neuronal tissue (nNOS), immunoactivated macrophage cell lines (iNOS), and vascular endothelium (eNOS). The subtypes are not, however, limited to the tissues from which they were first isolated.
Oral medicines: The best known ED medications are the Big Three: Viagra (sildenafil citrate, made by Pfizer, Inc.), Levitra (vardenafil HCl, made by Bayer and GlaxoSmithKline), and Cialis (tadalafil, made by Eli Lilly). The three are chemically very similar, and all have proven very effective. Because they are effective, convenient, and relatively inexpensive (about nine dollars per pill), these medicines have become the treatment of choice for most men experiencing ED.
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In some cases, ED can be a warning sign of more serious disease. One study suggests ED is a strong predictor of heart attack, stroke, and death from cardiovascular disease. The researchers say all men diagnosed with ED should be evaluated for cardiovascular disease. This does not mean every man with ED will develop heart disease, or that every man with heart disease has ED, but patients should be aware of the link.
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
Phosphodiesterase type V inhibitors (PDE-5 inhibitors) are the most commonly used therapy for erectile dysfunction. These medications work by preventing the breakdown of chemicals that stimulate increased blood flow into the penis. Several different PDE-5 inhibitors are available, which differ slightly in how to use them and their side effects. They appear to be equally effective in the treatment of erectile dysfunction in general, but some individuals may respond to one of these medications more effectively than another.
The lab testing obtained for the evaluation of erectile dysfunction may vary with the information obtained on the health history, physical examination, and recent lab testing. A testosterone level is not necessary in all men; however, a physician will order labs to determine a patient's testosterone level if other signs and symptoms of hypogonadism (low testosterone) such as decreased libido, loss of body hair, muscle loss, breast enlargement, osteoporosis, infertility, and decreased penile/testicular size are present.
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.
A vacuum erection device helps draw blood into the penis by applying negative pressure. This type of device is sometimes referred to as penis pump and may be used just prior to sexual intercourse. Several types of FDA approved vacuum therapy devices are available under prescription. When pharmacological methods fail, a purpose-designed external vacuum pump can be used to attain erection, with a separate compression ring fitted to the base of the penis to maintain it. These pumps should be distinguished from other penis pumps (supplied without compression rings) which, rather than being used for temporary treatment of impotence, are claimed to increase penis length if used frequently, or vibrate as an aid to masturbation. More drastically, inflatable or rigid penile implants may be fitted surgically.
"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.
Once implanted, the pumps become “part of their body,” Montague explains. “No out-of-pocket cost per use. Predictable response. Works every time.” Pills, even when they work, might be less effective if you’ve had more than a couple drinks or are out of sorts for other reasons. Injections are slightly more reliable than pills but, Montague says, are still subject to variability.
With the pumps, erections last until the user hits the deflate button, which Kohler says “doesn’t happen” accidentally. He adds that pump prostheses “are locker-room proof: Nobody can see that you have one.” (Obviously, this is not the case with the always-on malleable rod option.) Implanted pumps are reliable, experts say, with more than 90 percent of the devices working for 12 to 15 years. 
Chronic stress dumps adrenaline in your system multiple times a day. And that can lead to high blood pressure, heart disease, obesity, and diabetes. Chronic stress is like red-lining your car all day long. When you drive 100 mph all the time, something is going to break down. A high-stress environment can actually change the way your brain sends messages to your body. Dumping too much adrenaline into your bloodstream can affect blood flow and severely limit your ability to achieve and maintain an erection.
A vacuum constriction device (left) is a cylinder that is placed over the penis. The air is pumped out of the cylinder, which draws blood into the penis and causes an erection. The erection is maintained by slipping a band off of the base of the cylinder and onto the base of the penis. The band can stay in place for up to 30 minutes. The vacuum device can be safely used to treat most causes of erectile failure. Lack of spontaneity, discomfort, and cumbersomeness of the device seem to be the biggest concerns of patients.
The surgery for placement of a penile prosthesis is typically an outpatient surgery. Doctors often perform a penile prosthesis through a single incision, and all of the components are hidden under the skin. Health care professionals often give patients antibiotics at the time of surgery and often after the surgery to decrease the risk of developing an infection. Depending on your health history, a health care provider may leave a catheter in your penis to drain your bladder overnight.
3. Testosterone replacement. Before oral medications like Viagra, testosterone was routinely used to treat erectile dysfunction as it is central in the male sexual response, including the desire for sex and the process of getting an erection. Testosterone can be administered in a number of ways, for example orally, by means of an injection, skin patch, or subcutaneous (under the skin) pellet. 
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).
In some cases, however, these drugs may be unsuitable for patients with heart disease. If you are considering one of these drugs and you have heart disease, as many diabetics do, be sure to tell your doctor. In rare cases, the pills may create “priapism,” a prolonged and painful erection lasting six hours or more (although reversible with prompt medical attention).
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Your doctor will ask you questions about your symptoms and health history. They may do tests to determine if your symptoms are caused by an underlying condition. You should expect a physical exam where your doctor will listen to your heart and lungs, check your blood pressure, and examine your testicles and penis. They may also recommend a rectal exam to check your prostate. Additionally, you may need blood or urine tests to rule out other conditions.
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).
PDE5 inhibitors, the primary second-line therapy, have been the mainstay of ED treatment since the release of sildenafil (Viagra) in 1998, with the subsequent development of many others, and still more in the development stage. These medications do improve erectile quality for the majority of men, and they work by enhancing blood flow in the corpora cavernosa. These medications are generally used on demand and need to be taken about an hour before sexual intimacy. Tadalafil (Cialis) is longer acting and does come in a daily preparation potentially eliminating the ‘on-demand’ need. The daily dosing of tadalafil, 2.5–5 mg\day, has also been approved by the FDA for treatment of symptoms of BPH.41 PDE5 inhibitors are contraindicated in men taking nitrates, but otherwise PDE5 inhibitors are very safe and effective. When PDE5 inhibitors are coadministered with nitrates, pronounced systemic vasodilation and severe hypotension are possible. Many patients with ED are elderly and have the same risk factors as patients with CAD, so these drug combinations are commonly considered or encountered in clinical practice.42
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.
There are hundreds of medications that have the side effect of ED and/or decreased libido. Examples of drugs implicated as a cause of ED include hydrochlorothiazides and beta-blocking agents. Medications used to treat depression, particularly the SSRIs such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Prozac Weekly, Sarafem), fluvoxamine (Luvox, Luvox CR), paroxetine (Paxil, Paxil CR, Pexeva) and sertraline (Zoloft), may also contribute to ED.9 Bupropion (Wellbutrin) which has a predominant effect on blocking the reuptake of dopamine is an antidepressant with lower incidence of ED.10 The side effects of 5ARIs occurring in fewer than 5% of patients can include gynaecomastia, ED, loss of libido and ejaculatory dysfunction.11
Using a tiny needle and syringe, the man injects a small amount of medicine into the side of his penis. The medicine relaxes the blood vessels, allowing blood to flow into the penis. This treatment has been widely used and accepted since the early 1980s. The three most common medicines are prostaglandin E1 (alprostadil), papaverine (Papacon®), and phentolamine (Regitine®).
There are myriad factors, both mental and physical, that may contribute to your erectile dysfunction symptoms. Some of the most common impotence causes include diabetes, hypertension, prostate problems, low testosterone and obesity, which can not only put a damper on your sexual enjoyment, but play a key role in your total male vitality, too. (Even medications that are often prescribed to control some of the aforementioned issues can be behind some of the frustrating symptoms of ED.) There are factors like depression, stress and anxiety that can leave you longing for your glory days, and the coping mechanisms like alcohol and tobacco that can make a roll in the sheets less satisfying for you and your partner. We’ll listen to you with a compassionate ear and thoughtfully consider what may be contributing to your ED symptoms, then draw up your perfect, personalized treatment.

It is important to understand that ED is frequently, if not usually, directly related to endothelial dysfunction, and that the release of NO by the vasculature of the penile arteries is directly related to the function of intact, healthy endothelium. In the face of endothelial dysfunction, the process of erection fails to occur in a normal fashion.16
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.
Conditions associated with reduced nerve and endothelium function (eg, aging, hypertension, smoking, hypercholesterolemia, and diabetes) alter the balance between contraction and relaxation factors (see Pathophysiology). These conditions cause circulatory and structural changes in penile tissues, resulting in arterial insufficiency and defective smooth muscle relaxation. In some patients, sexual dysfunction may be the presenting symptom of these disorders.
The nerves and endothelium of sinusoids and vessels in the penis produce and release transmitters and modulators that control the contractile state of corporal smooth muscles. Although the membrane receptors play an important role, downstream signaling pathways are also important. The RhoA–Rho kinase pathway is involved in the regulation of cavernosal smooth muscle contraction. [12]
With the pumps, erections last until the user hits the deflate button, which Kohler says “doesn’t happen” accidentally. He adds that pump prostheses “are locker-room proof: Nobody can see that you have one.” (Obviously, this is not the case with the always-on malleable rod option.) Implanted pumps are reliable, experts say, with more than 90 percent of the devices working for 12 to 15 years. 
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.
Alprostadil is injected into the side of penis with a very fine needle. It's of great value to have the first shot in the doctor's office before doing this on your own. Self-injection lessons should be given in your doctor's office by an experienced professional. The success rate for getting an erection firm enough to have sex is as high as 85% with this treatment. Many men who do not respond to oral PDE5 inhibitors can be ‘rescued' with ICI.
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