Erectile Dysfunction in Men
Erectile dysfunction is the inability to achieve and maintain an erection sufficient for satisfactory sexual intercourse. It is estimated to affect 20 to 30 million men in the US and is definitely age-related.
It may result from any one of the following factors: psychological, neurologic, hormonal, arterial, and venous. Recently it has become quite clear that, in many cases, erection dysfunction can be a “silent marker” for the later development of cardiovascular disease.
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The Penile Erection
Penile erection is an event that has physiological, psychological and hormonal aspects to it. Upon sexual stimulation, nerve impulses from the cavernous nerves in the penis stimulate relaxing factors from cells inside the penis, resulting in relaxation of smooth muscle in the arteries of the penis with a 20 fold increase in blood flow into the penis. What follows is relaxation of the smooth muscle lined spaces within the penis and rapid filling and expansion of these spaces causing penile enlargement. Due to this, the small veins that normally drain the penis become compressed thus stopping outflow of blood from the penis. These events effectively trap the blood within the penis and raise the penis from flaccid to erect position. Before ejaculation, a reflex is triggered (bulbocavernosus) which causes the muscles that surround the penis to forcefully compress the penis, such that the blood pressure within the penis reaches levels that exceed that found elsewhere in the body. The penis falls when there are no more energy molecules available, or due to nervous system discharge during ejaculation. This discharge results in a latency period or “down time” during which it is difficult to achieve another erection. Once this sympathetic discharge is complete, then an erection is again possible.
Nitric oxide is the principal neurotransmitter responsible for penile erection. Within the muscle lining the cells inside the penis, nitric oxide causes higher levels of cyclic guanosine monophosphate (GMP). Cyclic GMP results in a block in calcium influx, smooth muscle relaxation, and an erection. Sildenafil, vardenafil tadalafil, and avanafil are drugs currently FDA approved to treat erection dysfunction and they work by blocking the breakdown of the energy molecule cyclic GMP. More cGMP around means more erection. Essentially these drugs work by giving the same stimulatory effect that coffee has on the body, but to the penis instead.
Causes of Erectile Dysfunction
Erectile dysfunction can be classified as organic and non-organic causes. These are listed in Table 1. Organic causes include medication-related ED, or that due to medical, vascular or neurological disease. Non-organic causes are the most commonly observed and are also termed psychogenic. They are related to stress (emotional or physical), performance anxiety, strained relationship, lack of sexual arousability, and to depression and schizophrenia.
Hormonally, a low testosterone state results in a decrease in nighttime erections and decreases sex drive. However it is the sole cause of ED in only about 6% of men. High prolactin levels are a medically important cause of both decreased sex drive and poor erections in young men and is medically treatable.
Table 1. Classification and causes of erectile dysfuntion
Erectile Dysfunction Risk Factors
The penis is essentially a complex blood vessel that fills and empties in response to nerve and hormonal signals. It is made up of the same cells that make up other blood vessels and is subject to the same changes with age and disease as are other blood vessels. It is now clear that the same risk factors that occur for heart attacks and strokes, termed cardiovascular risks factors, are also important in the development of erectile dysfunction. These risk factors include: high blood pressure, elevated cholesterol and lipid levels, obesity, cigarette smoking and diabetes mellitus. Many of these symptoms have now been termed the “metabolic syndrome.” For this reason, men with otherwise unexplained erectile dysfunction and who harbor such risk factors should also be evaluated for cardiovascular risk.
So, erectile dysfunction is not just a sexual health issue. In many men, ED may be a serious harbinger of life-threatening cardiovascular conditions. A recent study in the Journal of the American Medical Association followed men age 55 and older for over 7 years and assessed them for both erectile dysfunction and cardiovascular disease, including heart attacks and strokes. In patients with new erectile dysfunction there was a 25% increased risk for heart attacks, strokes, chest pain, or mini-strokes, compared to men with no erectile dysfunction. In fact, ED is as important a cardiovascular disease risk factor as is smoking or a family history of heart disease. Indeed, it is also true that among patients who seek medical care for ED, nearly 20% have undiagnosed high blood pressure, 15% have diabetes, and 5% may have significant heart disease.
It is also true that sexual function progressively declines in “healthy” men with age. As men age, the latency period between erections after ejaculation increases, erections are less firm, ejaculation is less forceful, and the semen volume decreases. There is also a decrease in serum testosterone concentration in men with age but it is not felt to be the major contributor to the changes in erections as men age.
Erectile Dysfunction Symptoms
Erectile dysfunction can be the presenting symptom for a variety of diseases such as diabetes mellitus, heart disease, hyperlipidemia, high blood pressure, spinal-cord compression, and pituitary tumor. Therefore, a thorough patient history, physical examination and appropriate lab tests aimed at detecting these diseases are undertaken. Standardized, validated survey instruments such as the SHIM-5 are now available to assess erectile dysfunction (Figure 1). Often, the characteristics of the erection problem can help with the diagnosis: with arterial problems, more stimulation may be needed to achieve an erection, whereas with venous leak, an erection is easily achieved but lost very quickly. Recommended lab tests include urinalysis, complete blood count, and measurement of fasting blood glucose, cholesterol and triglycerides, and testosterone. If cardiovascular risk factors exist, then patients should be recommended to undergo cardiac evaluation before treatment is considered.
Erectile Dysfunction Treatment
It is important to understand the goals and preferences of the patient when treating erectile dysfunction, as this issue largely drives therapy. This “goal directed” approach is further outlined in Figure 2.
In general, ED treatments should proceed from least to most invasive. Healthy lifestyle changes like quitting smoking, losing excess weight, gaining better control of diabetes and increasing physical activity may improve overall health and also help some men regain sexual function. Discontinuing drugs with harmful side effects is another effective treatment. If an isolated low testosterone level is found, then testosterone replacement may be the treatment of choice.
Until other treatments became more popular in the 1980s and 1990s, psychotherapy was the mainstay of ED treatment. Psychotherapy attempts to treat ED by decreasing the anxiety associated with intercourse. The patient’s partner can help by gradually developing better intimacy and stimulation.
Drugs for treating ED can be taken orally, injected directly into the penis, or inserted into the urethra at the tip of the penis. In 1998, the FDA approved sildenafil (Viagra), the first pill to treat ED. Since that time, vardenafil (Levitra), tadalafil (Cialis), and avanafil (Stendra) have also been approved. These drugs are all phosphodiesterase (PDE) inhibitors. Taken an hour before sexual activity, they work by enhancing the effects of nitric oxide, which relaxes smooth muscles in the penis during sexual stimulation and allows increased blood flow. While these drugs improve the response to sexual stimulation, they do not trigger an automatic erection. The majority of men with ED will respond to these drugs and for this reason, they are considered first line therapy for ED.
No PDE inhibitor should be used more than once a day. Men who take nitrate-based drugs such as nitroglycerin for heart problems should not use these drugs because the combination can cause a sudden drop in blood pressure. One of these medications may cause a sudden drop in blood pressure when taken with an alpha-blocker.
Testosterone pills can reduce ED in some men with low natural testosterone levels, but it is often ineffective and may cause liver damage. Other forms of testosterone may be safer than oral testosterone; however, only a small proportion of ED (estimated at 6%) is due to low testosterone. Other drugs (including yohimbine hydrochloride, dopamine and serotonin agonists, and trazodone) may be effective for ED, but studies to substantiate these claims are inconsistent.
Many men achieve stronger erections by injecting drugs into the penis, causing it to become engorged with blood. Drugs such as papaverine hydrochloride, phentolamine, and alprostadil (prostaglandin E2) dilate blood vessels by a mechanism slightly different than the phosphodiesterase inhibitors and can help induce and maintain erections. These drugs may create unwanted side effects, however, including persistent erection (known as priapism) and scarring.
A system for inserting a pellet of alprostadil into the urethra is marketed as MUSE. The system uses a prefilled applicator to deliver the pellet about an inch deep into the urethra. An erection will begin within 8 to 10 minutes and may last 30 to 60 minutes. The most common side effects are penile pain, warmth or burning sensation in the urethra; redness from increased blood flow to the penis; and minor urethral bleeding or spotting.
VACUUM ERECTION DEVICES
Mechanical vacuum devices induce erections by creating a partial vacuum, which draws blood into the penis, engorging and expanding it. The devices have three components: a plastic cylinder, into which the penis is placed; a pump, which draws air out of the cylinder; and an elastic band, which is placed around the base of the penis to maintain the erection after the cylinder is removed and during intercourse by preventing blood from flowing back into the body.
Surgical procedures to improve erections are performed for 3 reasons: to implant a device that can cause the penis to become erect, to reconstruct arteries and increase penile blood flow, and to occlude veins that allow blood to leak out of the penis and cause ED. Implanted devices, known aspenile prostheses, are excellent at restoring erections. Implants are devices, however and have complications that include mechanical breakdown, erosion and infection. Malleable implants consist of solid rod that is inserted surgically into the penis. The user manually adjusts the position of the penis and, therefore, the rods. Adjustment does not affect the width or length of the penis. Inflatable implants consist of paired cylinders that are surgically inserted inside the penis and then expanded using pressurized fluid from a co-implanted fluid reservoir and a pump. The cylinders are inflated by pressing on the scrotal pump and reproduce a more natural erection with expansion of both the width and length of the penis.
Surgery to repair arteries can reduce ED caused by blockages. The best candidates for such surgery are young men with a well-defined blockage of an artery because of pelvis injury or fracture. The procedure is almost never successful in older men with diffuse vascular disease due to atherogenesis. Surgery to tie off veins permitting blood to leak from the penis has the opposite goal: to reduce leakage of blood out of the penis that causes ED. Given the complexity of the venous drainage patterns from the penis, this type or penile surgery is rarely done in men with mild to moderate ED.
- Thompson IM, Tangen CM, Goodman PJ et al. JAMA. 2005, 294:2996-3002.