The role of the endothelium in ED has been noted for a number of years and the overlapping of ED and other conditions, especially coronary heart disease, CVD, affecting endothelial function/dysfunction, is clearly present. The endothelial cell is now known to affect vascular tone and impact the process of atherosclerosis, and impacting ED, CVD and peripheral vascular disease.16
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.
Arterial vascular diseases account for nearly half of all cases of ED in men older than 50 years of age. Arterial vascular disease includes atherosclerosis (fatty deposits on the walls of arteries, also called hardening of the arteries), which may affect the heart (history of heart attacks, angina, coronary artery disease, myocardial infarct) or blood vessels in the legs, peripheral vascular disease (problems with blood circulation to the legs), as well as other areas of the body including blood vessels supplying blood to the penis and high blood pressure. Prolonged tobacco use (smoking) is considered an important risk factor for ED because it is associated with poor circulation and reduced blood flow in the penis. This is related to microvascular damage (stiffening of the artery as well as smaller caliber vessel size secondary to endovascular atherosclerotic plaques).

Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.
Other form of sexual dysfunction, such as premature ejaculation and loss of libido (decreased sexual desire), are also very common. The NHSLS found that 28.5% of men 18-59 years of age reported premature ejaculation, and 15.8% lacked interest during the past year. An additional 17% reported anxiety about sexual performance, and 8.1% indicated a lack of pleasure from sexual activity.

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All of these medicines work by relaxing smooth muscles and increasing blood flow in the penis during sexual stimulation. You should not take any of these medicines to treat ED if you are taking nitrates to treat a heart condition. Nitrates widen and relax your blood vessels. The combination can lead to a sudden drop in blood pressure, which may cause you to become faint or dizzy, or fall, leading to possible injuries.
Nearly every primary care physician, internist and geriatrician now understand that many older men retain an interest in sexual activity as they age. Some primary care physicians think that sexual potency in older men is the norm, and that if it is lacking, it is ‘all in the head.’ This viewpoint has not been supported by current literature. The Massachusetts Male Aging Study (MMAS) found that 52% of men between 40 and 70 years old reported having some form of erectile dysfunction (ED).1 The reality is that ED is a natural part of ageing and that the prevalence increases with age. In the MMAS, they found that roughly 50% of men at 50 years old, 60% of men at 60 years old and 70% of men at 70 years old had ED. Thus, nearly all men who live long enough should develop ED. The myths that surround the problems of impotence or ED confound the attempts of patients to receive treatment and the attempts of physicians to help them.1
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 Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) study, designed to determine whether an individual man’s sexual outcomes after most common treatments for early-stage prostate cancer could be accurately predicted on the basis of baseline characteristics and treatment plans, found that 2 years after treatment, 177 (35%) of 511 men who underwent prostatectomy reported the ability to attain functional erections suitable for intercourse. [45]

A number of herbs have been promoted for treating impotence. The most widely touted herbs for this purpose are Coryanthe yohimbe (available by prescription as yohimbine, with the trade name Yocon) and gingko (Gingko biloba), although neither has been conclusively shown to help the condition in controlled studies. In addition, gingko carries some risk of abnormal blood clotting and should be avoided by men taking blood thinners such as coumadin. Other herbs promoted for treating impotence include true unicorn root (Aletrius farinosa), saw palmetto (Serenoa repens), ginseng (Panax ginseng), and Siberian ginseng (Eleuthrococcus senticosus). Strychnos Nux vomica has been recommended, especially when impotence is caused by excessive alcohol, cigarettes, or dietary indiscretions, but it can be very toxic if taken improperly, so it should be used only under the strict supervision of a physician trained in its use.
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.
Several pathways have been described to explain how information travels from the hypothalamus to the sacral autonomic centers. One pathway travels from the dorsomedial hypothalamus through the dorsal and central gray matter, descends to the locus ceruleus, and projects ventrally in the mesencephalic reticular formation. Input from the brain is conveyed through the dorsal spinal columns to the thoracolumbar and sacral autonomic nuclei.
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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
There are treatments available to help you to get and maintain an erection. In addition, making healthy changes to your lifestyle could help with impotence. Switching to a healthier balanced diet, taking more exercise and cutting down on or giving up alcohol and cigarettes could help you to see an improvement in sexual function. If you think that the problem may be related to stress or anxiety, counselling can also help.
An alprostadil cream that patients apply into the tip of the penis (the urethral meatus, the opening that urine passes through) is currently available in the UK and Europe. It is currently under review by the U.S. Food and Drug Administration (FDA). After application of the cream, an erection occurs within five to 30 minutes, and the erection lasts one to two hours in men who respond to the cream. Doctors recommend that one use the cream for a maximum frequency of two to three times per week and no more frequent than once every 24 hours. It has essentially the same contraindications and side effects as the other formulations of alprostadil. The cream may cause vaginal burning in roughly 4% of partners. Men should not use alprostadil cream for sexual intercourse with women of childbearing potential unless a condom is used. Researchers have performed controlled trial studies to evaluate the safety and effectiveness of this drug. Overall, 52% of men reported improvement in their erections compared to 20% of men receiving placebo. A later analysis demonstrated that 36% of men using the alprostadil cream had a clinically relevant improvement in vaginal penetration ability and 31% clinically relevant improvement in ability to have successful intercourse to ejaculation.
Alprostadil should not be used in men with urethral stricture (scarring and narrowing of the tube that urine and the ejaculate pass through), balanitis (inflammation/infection of the glans [tip] of the penis, 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).
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]

Much of the emphasis on erectile pathophysiology has been placed on penile smooth muscle function and cavernosal hemodynamics. The neuroanatomy and neurophysiology of erection can be characterized but its full extent is poorly understood. Neurologic disease does not always reproducibly affect erections in a uniform manner compared to other types of sexual dysfunction (SD). This offers many obstacles to understanding the role the nervous systems plays in SD and consequently obscures what treatment options readily optimize erections specific to the neurologic insult.


Quitting smoking, exercising regularly, losing excess weight, curtailing excessive alcohol consumption, controlling hypertension, and optimizing blood glucose levels in patients with diabetes are not only important for maintaining good health but also may improve or even prevent progression of erectile dysfunction. It is unclear if such lifestyle changes can reverse erectile dysfunction. However, lifestyle improvements may prevent progression of the erectile dysfunction. Some studies suggest that men who have made lifestyle improvements experience increased rates of success with oral medications.
Although not proven, it is likely that erectile dysfunction can be prevented by good general health, paying particular attention to body weight, exercise, and cigarette smoking. For example, heart disease and diabetes are problems that can cause erectile dysfunction, and both are preventable through lifestyle changes such as sensible eating and regular exercise. Furthermore, early diagnosis and treatment of associated conditions like diabetes, hypertension and high cholesterol may prevent or delay erectile dysfunction, or stop the erectile dysfunction from getting more serious.
While pills for ED are convenient, some men sustain stronger erections by injecting medication directly into the penis. Drugs approved for this purpose work by widening the blood vessels, causing the penis to become engorged with blood. Another option is inserting a medicated pellet into the urethra. The pellet can trigger an erection within 10 minutes.
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