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Erectile Dysfunction (ED): Impotence, Causes, Symptoms & Treatment

Erectile dysfunction (ED, impotence) facts

Erectile dysfunction or impotence is a man's inability to achieve and maintain a penile erection suitable for sexual intercourse.Erectile dysfunction or impotence is a man's inability to achieve and maintain a penile erection suitable for sexual intercourse.

Erectile dysfunction (ED), also known as impotence, is the persistent inability to have an erection that is hard enough for penetration and/or a hard erection that lasts long enough for completion of sexual activity.

  • ED may have a significant effect on the sex life of a man and his partner.
  • Symptoms of erectile dysfunction include lack of an erection hard enough for penetration and/or lasting long enough for completion of sexual activity.
  • ED may occur with or without other sexual dysfunction, including decreased libido (decreased interest in sexual activity), orgasmic dysfunction (troubles achieving an orgasm/climax), and ejaculatory dysfunction (problems with the fluid released during sex, including lack of ejaculation [anejaculation], small volume ejaculate, ejaculation that occurs too quickly [premature ejaculation], ejaculate that goes backward into the bladder [retrograde ejaculation] and pain with ejaculation).
  • Erectile dysfunction is common, and the risk of developing ED increases with age. Experts have estimated that erectile dysfunction affects 30 million men in the United States.
  • The causes of erectile dysfunction include aging, high blood pressure, diabetes mellitus, cigarette smoking, atherosclerosis (hardening of the arteries), depression, nerve or spinal cord damage, medication side effects, alcoholism or other substance (drug) abuse, pelvic surgery including radical prostatectomy, pelvic radiation, penile/perineal/pelvic trauma such as pelvic fracture, Peyronie's disease (a disorder that causes curvature of the penis and sometimes painful erections), and low testosterone levels.
  • Erectile dysfunction is treatable in all age groups.
  • Treatments include psychotherapy, adopting a healthy lifestyle, oral phosphodiesterase type V (PDE5) inhibitors (Viagra, Levitra, Cialis, Stendra, and Staxyn), intraurethral prostaglandin E1 (MUSE), intracavernosal injections (prostaglandin E1 [Caverject, Edex], Bimix and Trimix), vacuum devices, penile prosthesis and vascular surgery, and (in some cases) changes in medications when appropriate.
  • Discuss over-the-counter products and/or supplements with a doctor before using them.
  • New research is ongoing in the field of erectile dysfunction to find improved and effective therapies.

Erectile Dysfunction Home Remedies

Lifestyle changes can improve ED

No matter what erectile dysfunction treatment or treatments (whether herbal remedies or not) a man ultimately decides upon, experts say it’s important to eat healthily and to avoid smoking and heavy drinking. Moreover, adequate exercise, stress reduction, and sleep can improve erectile dysfunction in many.

Learn more about impotence remedies »

What is erectile dysfunction (ED)?

Erectile DysfunctionErectile dysfunction (ED) is treatable in all age groups.

Erectile dysfunction (ED), also known as impotence, is the inability to achieve or sustain a hard enough erection for satisfactory completion of sexual activity. Erectile dysfunction is different from other health conditions that interfere with male sexual function, such as lack of sexual desire (decreased libido) and problems with ejaculation release of the fluid from the penis (ejaculatory dysfunction) and orgasm/climax (orgasmic dysfunction), and penile curvature (Peyronie's disease), although these problems may also be present. ED affects about 50% of men age 40 and over. This article focuses on the evaluation and treatment of erectile dysfunction.

What is normal penis anatomy?

Picture of arteries and veins involved in erectile dysfunction (ED)Picture of arteries and veins involved in erectile dysfunction (ED); SOURCE: NIH

The penis contains three cylinders, the two corpora cavernosa, which are on the top of the penis (see figure 1 below). These two cylinders are involved in erections. The third cylinder contains the urethra, the tube that the urine and ejaculate passes through, runs along the underside of the penis. The corpus spongiosum surrounds the urethra. Spongy tissue that has muscles, fibrous tissues, veins, and arteries within it makes up the corpora cavernosa. The inside of the corpora cavernosa is like a sponge, with potential spaces that can fill with blood and distend (known as sinusoids). A layer of tissue that is like Saran Wrap, called the tunica albuginea, surrounds the corpora. Veins located just under the tunica albuginea drain blood out of the penis.




QUESTION

Erectile dysfunction (ED) is…
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How common is erectile dysfunction?

Who Gets Erectile Dysfunction?While erectile dysfunction can occur at any age, the risk of developing erectile dysfunction increases with age.

Erectile dysfunction (ED, impotence) varies in severity; some cannot have an erection at all, whereas other men sometimes have troubles getting a hard erection, and others get a hard erection but it only lasts for a short period of time. Approximately 50% of men over the age of 40 have troubles with erectile dysfunction.

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.

How does erection occur?

Erections are neurovascular events, meaning that nerves and blood vessels (arteries and veins) are involved in the process of an erection and all must work properly to develop a hard erection that lasts long enough. Erection begins with sexual stimulation. Sexual stimulation can be tactile (for example, by a partner touching the penis or by masturbation) or mental (for example, by having sexual fantasies, viewing porn). Sexual stimulation or sexual arousal causes the nerves going to the penis to release a chemical, nitric oxide. Nitric oxide increases the production of another chemical, cyclic GMP (cGMP), in the muscle of the corpora cavernosa. The cGMP causes the muscles of the corpora cavernosa to relax, and this allows more blood to flow into the penis. The incoming blood fills the corpora cavernosa, making the penis expand.

How does a man sustain an erection?

As blood flows into the penis, the corpora cavernosa swell, and this swelling compresses the veins (blood vessels that drain the blood out of the penis) against the tunica albuginea. Compression of the veins prevents blood from leaving the penis. This creates a hard erection. When the amount of cGMP decreases by the action of a chemical called phosphodiesterase type 5 (PDE5), the muscles in the penis tighten, and the blood flow into the penis decreases. With less blood coming into the penis, the veins are not compressed, allowing blood to drain out of the penis, and the erection goes down.

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What causes erectile dysfunction?

The ability to achieve and sustain erections requires the following:

  1. A healthy nervous system that conducts nerve impulses in the brain, spinal column, and penis
  2. Healthy arteries in and near the corpora cavernosa that when stimulated can bring increased blood flow into the penis
  3. Healthy muscles and fibrous tissues within the corpora cavernosa, which can distend to allow the penis to fill with blood
  4. Adequate levels of nitric oxide in the penis
  5. Normal-functioning tunica albuginea that allows for compression of the veins
  6. Appropriate psychosocial interactions

Erectile dysfunction can occur if a man doesn't meet one or more of these requirements. The following are 13 common causes of erectile dysfunction, and many men have more than one potential cause:

  • Aging: There are two reasons why older men are more likely to experience erectile dysfunction than younger men. First, older men are more likely to develop diseases (such as heart attacks, angina, cardiovascular disease, strokes, diabetes mellitus, and high blood pressure) that are associated with erectile dysfunction. Second, the aging process alone can cause erectile dysfunction in some men by causing changes in the muscle and tissue within the penis.
  • 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.
  • Hypertension (high blood pressure): Men with high blood pressure have an increased risk of developing erectile dysfunction. Hypertension can cause trouble with erections related to atherosclerosis or from low levels of nitric oxide production from the arteries in the penis. Medications to treat hypertension may cause erectile dysfunction.
  • Cardiovascular diseases: The most common cause of cardiovascular diseases in the United States is atherosclerosis, the narrowing, and hardening of arteries that reduces blood flow. Atherosclerosis (a type of vascular disease) typically affects arteries throughout the body; hypertension, high blood cholesterol levels, cigarette smoking, and diabetes mellitus aggravate atherosclerosis. Hardening of the arteries to the penis and pelvic organs, atherosclerosis, causes insufficient blood flow into the penis. There is a close correlation between the severity of atherosclerosis in the coronary arteries and erectile dysfunction. For example, men with more severe coronary artery atherosclerosis (hardening of the arteries in the heart) also tend to have more erectile dysfunction than men with mild or no coronary artery atherosclerosis. Some doctors suggest that men with new onset erectile dysfunction undergo evaluation for silent coronary artery diseases (advanced coronary artery atherosclerosis that has not yet caused angina or heart attacks).
  • Metabolic syndrome is associated with multiple risk factors for erectile dysfunction including diabetes, abnormal lipid profile, hypertension, and obesity.
  • Cigarette smoking: Cigarette smoking aggravates atherosclerosis and can cause vasospasm (spasms of the arteries) and thereby increases the risk for erectile dysfunction.
  • Nerve or spinal cord damage: Damage to the spinal cord and nerves in the pelvis can cause erectile dysfunction. Nerve damage can be due to disease, trauma, or surgical procedures. Examples include injury to the spinal cord from automobile accidents, injury to the pelvic nerves from prostate surgery for cancer (prostatectomy), and some surgeries for colorectal cancer, radiation to the prostate, surgery for benign prostatic enlargement, multiple sclerosis (a neurological disease with the potential to cause widespread damage to nerves), and long-term diabetes mellitus.
  • BPH: Benign enlargement of the prostate is associated with erectile dysfunction.
  • Trauma: Trauma to the pelvis, including pelvic fracture, may cause erectile dysfunction, and an untreated penile fracture may result in erectile dysfunction.
  • Substance abuse: Marijuana, heroin, cocaine, methamphetamines, crystal meth, and narcotic and alcohol abuse contribute to erectile dysfunction. Alcoholism, in addition to causing nerve damage, can lead to atrophy (shrinking) of the testicles and lower testosterone levels.
  • Low testosterone levels: Testosterone (the primary sex hormone in men) is not only necessary for sex drive (libido) but also is necessary to maintain nitric oxide levels in the penis. Therefore, men with hypogonadism (low testosterone with symptoms) can have a low sex drive and erectile dysfunction.
  • Medications: Many common medicines produce erectile dysfunction as a side effect. Medicines that can cause erectile dysfunction include many used to treat high blood pressure, antihistamines, antidepressants, tranquilizers, and appetite suppressants. Examples of common medicines that can cause erectile dysfunction include propranolol (Inderal) or other beta-blockers, hydrochlorothiazide, digoxin (Lanoxin), amitriptyline (Elavil), famotidine (Pepcid), cimetidine (Tagamet), metoclopramide (Reglan), naproxen, indomethacin (Indocin), lithium (Eskalith, Lithobid), verapamil (Calan, Verelan, Isoptin), phenytoin (Dilantin), gemfibrozil (Lopid), amphetamine/dextroamphetamine (Adderall), and phentermine. Prostate cancer medications that lower testosterone levels such as leuprolide (Lupron) may affect erectile function. Some chemotherapies such as cyclophosphamide (Cytoxan) may affect erectile function.
  • Recreational drugs: Recreational drugs, including alcohol, amphetamines, barbiturates, marijuana, nicotine, heroin, and cocaine, are associated with erectile dysfunction.
  • Depression and anxiety: Psychological factors may be responsible for erectile dysfunction. These factors include stress, anxiety, guilt, depression, widower syndrome, low self-esteem, posttraumatic stress disorder, and fear of sexual failure (performance anxiety). It is also worth noting that many medications used for the treatment of depression and other psychiatric disorders may cause erectile dysfunction or ejaculatory problems.

What are erectile dysfunction risk factors?

The common risk factors for ED include the following:

  • Advanced age
  • Cardiovascular disease
  • Hypertension
  • Diabetes mellitus
  • High cholesterol
  • Cigarette smoking
  • Recreational drug use
  • Depression or other psychiatric disorders
  • Pelvic surgery, including radical prostatectomy and colorectal surgery
  • Pelvic radiation, such as for prostate cancer and some colorectal cancers
  • Trauma to the pelvis (pelvic fracture), penis (penile fracture), and perineum

What are erectile dysfunction symptoms and signs?

Signs and symptoms of erectile dysfunction may include the following:

  • Penile erection occurs, but the penis does not remain hard enough for completion of sex.
  • Penile erections are not hard enough for penetration.
  • There is an inability to obtain a penile erection.
  • One can still achieve an orgasm and ejaculate with erectile dysfunction.

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How do health care professionals diagnose erectile dysfunction?

Patient health history

Physicians make a diagnosis of erectile dysfunction in men who complain of troubles having a hard enough erection or a hard erection that does not last long enough. It is important as you talk with your doctor that you be candid in terms of when your troubles started, how bothersome your erectile dysfunction is, how severe it is, and discuss all your medical conditions along with all prescribed and nonprescribed medications that you are taking. Your doctor will ask several questions to determine if your symptoms are suggestive of erectile dysfunction and to assess its severity and possible causes. Your doctor will try to get information to answer the following questions:

  1. Is the patient suffering from erectile dysfunction or from some other form of sexual dysfunction such as loss of libido or a disorder of ejaculation (for example, premature ejaculation) or orgasm, or problems with penile curvature/pain (Peyronie's disease)?
  2. Is your erectile dysfunction due to psychological (stress, relationship problems, etc.) or physical factors? Your doctor may ask if you note erections at night or in the early morning. Men have involuntary erections in the early morning and during REM sleep (a stage in the sleep cycle with rapid eye movements). Men with psychogenic erectile dysfunction (erectile dysfunction due to psychological factors such as stress and anxiety rather than physical factors) usually maintain these involuntary erections. Men with physical causes of erectile dysfunction (for example, atherosclerosis, smoking, and diabetes) usually do not have these involuntary erections. Men with psychogenic erectile dysfunction may relate the onset of problems to a "stressor," such as failed relationship. Your doctor may suggest a test to determine if you have erections during sleep, which may suggest that there may be a psychological cause of the erectile dysfunction.
  3. 3. Are there physical causes of erectile dysfunction? Erectile dysfunction may be a symptom of underlying medical conditions, which if not detected may cause further medical problems. A prior history of cigarette smoking, heart attacks, strokes, and poor circulation in the extremities (for example, intermittent claudication or cramping in your leg[s] when you walk) suggest atherosclerosis as the cause of the erectile dysfunction. Loss of sexual desire and drive, lack of sexual fantasies, gynecomastia (enlargement of breasts), and diminished facial hair suggest low testosterone levels. A prior history of pelvic surgery or radiation and trauma to the penis/pelvis/perineum can cause problems with the nerves and blood vessels. Symptoms of intermittent claudication of the lower extremities with exercise may suggest a vascular problem as a cause of the erectile dysfunction.
  4. Is the patient taking medications that can contribute to erectile dysfunction (see causes above), including prescribed, over-the-counter, or recreational drugs? It is important to discuss your prescribed medications, as well as over-the-counter medications and drugs of abuse such as opiates, alcohol, etc.

Physical examination

The physical examination can reveal clues for physical causes of erectile dysfunction. A doctor will perform an assessment of BMI and waist circumference to evaluate for abdominal obesity. A genital examination is part of the evaluation of erectile dysfunction. The examination will focus on the penis and testes. The doctor will ask you about penile curvature and will examine the penis to see if there are any plaques (hard areas) palpable. The doctor will examine the testes to make sure they are in the proper location in the scrotum and are normal in size. Small testicles, lack of facial hair, and enlarged breasts (gynecomastia) can point to hormonal problems such as hypogonadism with low testosterone levels. A health care provider may check pulses in your groin and feet to determine if there is a suggestion of hardening of the arteries that could also affect the arteries to the penis.

Laboratory tests

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.

A doctor may ask for the following laboratory tests in the evaluation of erectile dysfunction:

  • Complete blood counts
  • Urinalysis: A high level of sugar (glucose) in the urine may be a sign of diabetes mellitus, and high protein in the urine may suggest kidney damage, which can cause erectile troubles.
  • Lipid profile: High levels of LDL cholesterol (bad cholesterol) in the blood can cause atherosclerosis.
  • Blood glucose levels: Abnormally high blood glucose (sugar) levels may be a sign of diabetes mellitus.
  • Blood hemoglobin A1C: Abnormally high levels of blood hemoglobin A1C in patients with diabetes mellitus indicate that there is poor control of blood glucose levels.
  • Serum creatinine: An abnormal serum creatinine, a chemical that reflects kidney function, may be the result of kidney damage.
  • Liver enzymes and liver function tests: Liver disease (cirrhosis) can cause low testosterone. Thus, a physician may need to test some men for liver disease.
  • Total testosterone levels: Health care professionals should obtain a patient's blood samples for total testosterone levels in the early morning (before 8 a.m.) because the testosterone levels go up and down throughout the day. If you have a low testosterone level, a health care professional should check it again to confirm that it is truly low. In some men, a specialized test measuring the active form of testosterone (free or bioavailable testosterone) may be recommended.
  • Other hormone levels: Measurement of other hormones beside testosterone (luteinizing hormone [LH], prolactin level, and cortisol level) may provide clues to other underlying causes of testosterone deficiency and erectile problems, such as pituitary disease or adrenal gland abnormalities. Doctors may check thyroid levels in some individuals as both hypothyroidism (low thyroid function) and hyperthyroidism (overactive thyroid function) can contribute to erectile dysfunction.
  • PSA levels: PSA (prostate specific antigen) blood levels and prostate examination to exclude prostate cancer is important before starting testosterone treatment since testosterone can aggravate prostate cancer.
  • Other blood tests: Evaluation for hemochromatosis, lupus, scleroderma, zinc deficiency, sickle cell anemia, and cancers (leukemia, colon cancer) are some of the other potential tests that a physician may perform based on each individual's health history and symptoms.

Imaging tests

Health care professionals do not routinely obtain imaging tests in the evaluation of erectile dysfunction.

Ultrasound with Doppler imaging (ultrasound plus evaluation of blood flow in the arteries and veins) can provide additional information about blood flow of the penis and may help in the evaluation of patients prior to surgical intervention. This study is typically performed after the injection of a chemical that causes the arteries to open up, a vasodilator (prostaglandin E1), into the corpora cavernosa in order to cause dilation of blood vessels and promote blood flow into the penis. The rate of blood flow into the penis can be measured along with an evaluation of problems with compression of the veins.

Rarely, a doctor may perform an angiogram (injecting a dye into the arteries that supply the penis and taking X-rays to look for areas of narrowing of the arteries) in cases in which possible vascular surgery could be beneficial.

Other health tests

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.

Psychosocial examination

If there seems to be a psychological cause contributing to your erectile dysfunction, the doctor may ask the patient questions to help determine stressor, events, and relationship issues that may be causing your erectile troubles. It may be helpful to have your sexual partner involved in this assessment.

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What drugs treat erectile dysfunction?

A number of medical treatment options exist for erectile dysfunction include the following:

  • Oral phosphodiesterase type 5 (PDE5) inhibitors (sildenafil [Viagra], vardenafil [Levitra and the generic formulation Staxyn], tadalafil [Cialis]), and avanafil [Stendra])
  • Intracavernosal injections (papaverine, phentolamine, and PGE1 [Trimix], Bimix, and alprostadil injection [Caverject, Edex])
  • Intraurethral suppositories (MUSE)
  • Testosterone in individuals with ED and other signs/symptoms of hypogonadism and an unequivocally low serum testosterone

A doctor can help decide what medication(s) may be the best for the patient. This is an important step to do so the doctor can help choose the best and safest drug(s) and other treatments so that men with other medical problems can get individualized care appropriate for their medical conditions.

What is the treatment for erectile dysfunction?

The following are treatment options for erectile dysfunction:

First-line treatment options

  1. Working with doctors to modify current medications to select medications that do not cause troubles with erectile function when possible
  2. Making lifestyle improvements (for example, quitting smoking and exercising more) may help improve symptoms or prevent the erectile dysfunction from getting worse.
  3. Taking oral therapies (drugs/medications) to treat ED, such as sildenafil (Viagra), vardenafil (Levitra, Staxyn), tadalafil (Cialis), or avanafil (Stendra)
  4. Psychotherapy

Second-line treatment options

  1. Inserting medications into the urethra (intraurethral suppositories [MUSE])
  2. Injecting medications into the corpora cavernosa (intracavernosal injections)
  3. Vacuum constrictive devices for the penis

Third-line treatment options

  1. Penile prostheses
  2. Rarely vascular surgery to improve blood flow to the penis

Adjusting medications that may cause or contribute to erectile dysfunction

Many common medications for treating hypertension, depression, and high blood lipids (high cholesterol) can contribute to erectile dysfunction (see above). Treatment of hypertension is an example. There are many different types (classes) of medications for high blood pressure; these include beta-blockers, calcium channel blockers, diuretics (medications that increase urine volume), angiotensin converting enzyme inhibitors (ACE inhibitors), and angiotensin receptor blockers (ARBs). Patients may use these medications alone or in combination to control blood pressure. Some of these medications can cause troubles with erections. For example, Inderal (a beta-blocker) and hydrochlorothiazide (a diuretic) cause erectile dysfunction, while calcium channel blockers and ACE inhibitors do not seem to affect erectile function. On the other hand, other medications (such as angiotensin receptor blockers [ARB] including losartan [Cozaar] and valsartan [Diovan]) may actually help with erections. Therefore, if possible, you may benefit from changing your medications, but this requires approval by your prescribing health care provider.

Lifestyle improvements

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.

What are erectile dysfunction treatments for men with cardiovascular disease?

ED is often the result of atherosclerosis, and as a result, men with ED frequently have cardiovascular disease. Sexual activity is associated with increased physical exertion, which in some men may increase the risk of having a heart attack (myocardial infarction or MI). The major risk factors associated with cardiovascular disease are age, hypertension, diabetes mellitus, obesity, smoking, abnormal lipid/cholesterol levels in the blood, and lack of exercise. Individuals with three or more of these risk factors are at increased risk for a heart attack during sexual activity. The Princeton Consensus Panel developed guidelines for treating ED in men with cardiovascular disease. Thus, if you have ED and cardiovascular disease (for example, angina or prior heart attack), you should discuss whether or not treatment of ED and sexual activity are appropriate for you.

Oral phosphodiesterase type 5 (PDE5) inhibitors

What are oral phosphodiesterase type 5 (PDE5) inhibitors?

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).

How do oral phosphodiesterase type 5 (PDE5) inhibitors work?

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.

Who should not use oral phosphodiesterase type 5 (PDE5) inhibitors?

Some men should not take PDE5 inhibitors. They can cause hypotension (abnormally low blood pressure that can lead to fainting and even shock) when given to patients who are taking nitrates (medications taken for heart disease). Therefore, patients taking nitrates daily should not take any of the PDE5 inhibitors. Nitrates relieve angina (chest pain due to insufficient blood supply to the heart muscle because of narrowing of the coronary arteries); these include nitroglycerine tablets, patches, ointments, sprays, and pastes, as well as isosorbide dinitrate and isosorbide mononitrate. Other nitrates such as amyl nitrate and butyl nitrate also are in some recreational drugs called "poppers."

If you are taking medications (alpha-blockers) for problems with an enlarged prostate, you should discuss your prostate medications with your doctor. Alpha-blockers also can cause lowering of the blood pressure. Thus your doctor will need to carefully watch your blood pressure when you start the PDE5 inhibitor. Common alpha-blockers include doxazosin (Cardura), terazosin (Hytrin), and tamsulosin (Flomax).

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.

What are side effects of oral phosphodiesterase type 5 (PDE5) inhibitors?

The various PDE5 inhibitors for the treatment of ED share several common side effects, including headache, flushing, nasal congestion, nausea, dyspepsia (stomach discomfort), and diarrhea. Differences exist in side effects of the different PDE5 inhibitors, and thus it is important to be familiar with the prescribing information of the PDE5 inhibitor you are prescribed.

There have been rare reports of priapism (prolonged and painful erections lasting more than six hours) with the use of PDE5 inhibitors such as sildenafil, vardenafil, and tadalafil. Patients with blood cell diseases such as sickle cell anemia, leukemia, and multiple myeloma have higher than normal risks of developing priapism. Untreated priapism can cause injury to the penis and lead to permanent impotence. Therefore, if your erection lasts four hours, you should seek emergency medical care.

Rare side effects of all PDE5 inhibitors include a sudden loss of vision in one or both eyes (nonarteritic anterior ischemic optic neuropathy [NAION]) and sudden loss of hearing. Patients have reported these rare side effects with all of the PDE5 inhibitors. Seek immediate medical care if you develop loss of vision or hearing.

Doctors have not tested the PDE5 inhibitors in patients with retinitis pigmentosa, an eye condition that affects the retina and can cause blindness, and so caution is recommended if you have this health condition.

Sildenafil (Viagra)

What is sildenafil (Viagra)?

Sildenafil (Viagra) was the first oral phosphodiesterase type 5 (PDE5) inhibitor approved by the FDA in the United States for the treatment of erectile dysfunction (it is not approved for women). Sildenafil inhibits PDE5, which is an enzyme that destroys cGMP. By inhibiting the destruction of cGMP by PDE5, sildenafil allows cGMP to accumulate. The cGMP in turn prolongs relaxation of the smooth muscle of the corpora cavernosa. Relaxation of the corpora cavernosa smooth muscle allows blood to flow into the penis resulting in increased engorgement of the penis. In short, sildenafil increases blood flow into the penis and decreases blood flow out of the penis.

How effective is sildenafil (Viagra)?

Sildenafil treats erectile dysfunction of either physical or psychological cause. It is effective in treating erectile dysfunction in men with coronary artery disease, diabetes mellitus, hypertension, depression, coronary artery bypass grafting (CABG), and men who are taking antidepressants and several classes of antihypertensives.

In randomized placebo-controlled trials, an estimated 60% of men with diabetes, and 80% of men without diabetes experienced improved erections with sildenafil.

How do patients take sildenafil (Viagra)?

Sildenafil is available as oral tablets at doses of 25 mg, 50 mg, and 100 mg. Patients should take sildenafil approximately one hour before sexual activity. In some men, the onset of action of the drug may be as early as 11-20 minutes. It's best for men to take sildenafil on an empty stomach for best results since absorption and effectiveness of sildenafil can be diminished if it is taken shortly after a meal, particularly a meal that is high in fat. Sildenafil and the other PDE5 inhibitors don't cause an immediate erection. Sexual stimulation is necessary for these medications to work.

What is the dose of sildenafil (Viagra)?

In prescribing sildenafil, a doctor considers the age, general health status, and other medication(s) the patient is taking. The usual starting dose for most men is 50 mg, however, the doctor may increase or decrease the dose depending on side effects and effectiveness. The maximum recommended dose is 100 mg every 24 hours. However, many men will need 100 mg of sildenafil for optimal effectiveness, and some doctors are recommending 100 mg as the starting dose.

Aging, liver and kidney problems, and concurrent use of certain medications (such as erythromycin [an antibiotic] and protease inhibitors for HIV) slows the metabolism (breakdown) of sildenafil. Slowed breakdown allows sildenafil to accumulate in the body and potentially may increase the risk of side effects. Therefore, in men over 65 years of age, in men with significant kidney and liver disease, and in men who also are taking medications called protease inhibitors, the doctor will initiate sildenafil at a lower dose (25 mg) to avoid accumulation of sildenafil in the body. A protease inhibitor ritonavir (Norvir) is especially potent in increasing the accumulation of sildenafil, thus men who are taking Norvir should not take sildenafil doses higher than 25 mg and at a frequency of no greater than once in 48 hours. Other medications that may affect the level of sildenafil include erythromycin and ketoconazole.

What are the side effects of sildenafil (Viagra) that may be different from some of the other PDE5 inhibitors?

Sildenafil (Viagra) may affect another phosphodiesterase enzyme in the eye causing transient abnormal vision (seeing a bluish hue or brightness).

Vardenafil (Levitra and the generic formulation Staxyn)

What is vardenafil (Levitra, Staxyn)?

Vardenafil (Levitra) was the second oral medicine approved by the U.S. FDA for the treatment of erectile dysfunction. Like sildenafil (Viagra), vardenafil (Levitra) inhibits PDE5, which destroys cGMP (as discussed earlier). It is the only PDE 5 inhibitor that has a generic form available.

How effective is vardenafil (Levitra, Staxyn)?

Vardenafil is effective in men of all ages, different nationalities, and in men with such medical conditions as diabetes mellitus and erectile dysfunction after prostate surgery.

How should patients take vardenafil (Levitra, Staxyn)?

The recommended starting dose of vardenafil is 10 mg taken orally approximately one hour before sexual activity. A doctor may adjust the dose higher or lower depending on efficacy and side effects. The maximum recommended dose is 20 mg, and the maximum recommended dosing frequency is no more than once per day. Patients can take vardenafil with or without food. As with sildenafil, for vardenafil to be effective, sexual stimulation must occur.

What are the side effects of vardenafil (Levitra, Staxyn)?

Vardenafil shares the same side effects as sildenafil but is not associated with the abnormal vision that may occur with sildenafil.

Who should not use vardenafil (Levitra, Staxyn)?

The same concerns regarding the use of sildenafil with nitrates and alpha-blockers apply to vardenafil.

Men with a rare heart condition known as long QT syndrome should not take vardenafil since this may lead to abnormal heart rhythms. The QT interval is the time it takes for the heart's muscle to recover after it has contracted. An electrocardiogram (EKG) measures the QT interval. Some people have longer than normal QT intervals, and they may develop potentially life-threatening abnormal heart rhythms, especially when given certain medications. Men with a family history of long QT syndrome should not take vardenafil, as it is possible to inherit long QT syndrome. Furthermore, vardenafil is not recommended for men who are taking medications that can affect the QT interval such as quinidine (Quinaglute, Quinidex), procainamide (Pronestyl, Procan-SR, Procanbid), amiodarone (Cordarone), and sotalol (Betapace).

There is insufficient information on the safety of vardenafil in men with the following health disorders:

  • Unstable angina (chest pain due to coronary artery disease that occurs at rest or with minimal physical exertion)
  • Low blood pressure (a resting systolic blood pressure less than 90 mm Hg)
  • Uncontrolled high blood pressure (greater than 170/110 mm Hg)
  • Recent stroke or heart attack (within six months)
  • Uncontrolled, potentially life-threatening abnormal heart rhythms
  • Severe liver disease
  • Severe kidney failure requiring dialysis
  • Severe heart failure or disease of the heart's valves, for example, aortic stenosis (hardening of the main artery in the body)
  • Retinitis pigmentosa (a condition that affects the retina of the eye and can cause blindness)

Therefore, men with these health conditions should not use vardenafil without having these conditions evaluated and stabilized first. For example, men with uncontrolled high blood pressure should have their blood pressure controlled; and men with potentially life-threatening abnormal heart rhythms should have these rhythms controlled.

When there is angina or heart failure, the doctor may need to determine whether the heart has enough reserve to carry out the work necessary for sexual activity by performing cardiac treadmill stress testing.

What precautions should patients take when using vardenafil (Levitra, Staxyn)?

Metabolism (breakdown) of vardenafil can be slowed by aging, liver disease, and concurrent use of certain medications (such as erythromycin [an antibiotic], ketoconazole [Nizoral, a medication for fungal/yeast infections], and protease inhibitors [medications used to treat AIDS]). Slowed breakdown allows vardenafil to accumulate in the body and potentially increase the risk for side effects. Therefore, in men over 65 years of age with liver disease, or who are also taking medication(s) that can slow the breakdown of vardenafil, the doctor will initiate vardenafil at low doses to avoid its accumulation. For example,

  • men taking erythromycin or ketoconazole should not take more than 5 mg of vardenafil in a 24-hour period;
  • men taking high doses of ketoconazole (Nizoral) should not take more than 2.5 mg of vardenafil in a 24-hour period;
  • men with moderately severe liver disease also should not take more than a 5 mg dose of vardenafil in a 24-hour period;
  • men taking the protease inhibitor (for the treatment of HIV/AIDS) indinavir (Crixivan) should not take more than 2.5 mg of vardenafil in a 24-hour period; and
  • men taking another protease inhibitor ritonavir (Norvir), erythromycin, or ketoconazole, should not take more than 2.5 mg of vardenafil every 72 hours.

Tadalafil (Cialis)

What is tadalafil (Cialis)?

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).

How effective is tadalafil (Cialis)?

Tadalafil is effective in treating erectile dysfunction in men of all ages and has been shown to be effective in men with diabetes mellitus and erectile dysfunction after prostate cancer surgery. Studies demonstrated that tadalafil improved the ability to get a hard erection and to have the hard erection last long enough.

How should patients take tadalafil (Cialis)?

Patients may take tadalafil as needed as with sildenafil, vardenafil, and avanafil or once a day. It is the only ED oral medication that patients can take on a daily basis.

The recommended starting dose of tadalafil for use as needed for most patients is 10 mg taken orally approximately one hour before sexual activity. A doctor may adjust the dose higher to 20 mg or lower to 5 mg depending on efficacy and side effects. Doctors recommended that patients take tadalafil no more frequently than once per day. Some patients can take tadalafil less frequently since the improvement in erectile function may last 36 hours. Patients may take tadalafil with or without food. Tadalafil is currently the only PDE5 inhibitor that is FDA-approved for daily use for erectile dysfunction and is available in 2.5 mg or 5 mg dosages for daily use.

What are the side effects of tadalafil (Cialis)?

Tadalafil shares the common side effects of the PDE5 inhibitors, however, due to its effect on PDE11, another phosphodiesterase located in muscle, tadalafil has been associated with muscle aches. Back pain and muscle aches occur in less than 7% of men taking tadalafil and in most patients will go away without treatment within 48 hours. When treatment was necessary, acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Motrin, Advil) or naproxen (Aleve) were effective. Rarely do the muscle aches and back pain cause men to stop using tadalafil.

Who should not use tadalafil (Cialis)?

Men taking nitrates should not use tadalafil as with the other PDE5 inhibitors.

Tadalafil should not be used with alpha-blockers (except Flomax), medicines used to treat high blood pressure, and benign prostate hypertrophy (BPH) because the combination of tadalafil and an alpha-blocker may lower the blood pressure greatly and lead to dizziness and fainting. Examples of alpha-blockers include tamsulosin (Flomax), terazosin (Hytrin), doxazosin (Cardura), alfuzosin (Uroxatral), and prazosin (Minipress). Tamsulosin (Flomax) is the only alpha-blocker that patients can use safely with tadalafil. When tadalafil (20 mg) was given to healthy men taking 0.4 mg of Flomax daily, there was no significant decrease in blood pressure and so patients on this dose of tamsulosin (Flomax) can be prescribed tadalafil. The only alpha-blocker not tested with tadalafil is alfuzosin (Uroxatral), and no recommendations can be made regarding the interaction between the two.

As with vardenafil, doctors do not recommend tadalafil for men with the following conditions:

  • Unstable angina (chest pain due to coronary artery disease that occurs at rest or with minimal physical exertion)
  • Low blood pressure (a resting systolic blood pressure less than 90 mm Hg)
  • Uncontrolled high blood pressure (greater than 170/110 mm Hg)
  • Recent stroke or heart attack (within six months)
  • Uncontrolled, potentially life-threatening abnormal heart rhythms
  • Severe liver disease
  • Severe heart failure or disease of the heart valves (for example, aortic stenosis)
  • Retinitis pigmentosa

Therefore, men with these health conditions should not use tadalafil without having these conditions evaluated and stabilized first. For example, men with uncontrolled high blood pressure should have their blood pressure controlled; and men with potentially life-threatening abnormal heart rhythms should have these rhythms controlled.

When there is angina or heart failure, the doctor may need to determine whether the heart has enough reserve to carry out the work necessary for sexual activity by performing cardiac treadmill stress testing.

What precautions should patients take when using tadalafil?

In most healthy men, some of the drug will remain in the body for more than two days after a single dose of tadalafil. Metabolism (clearing of the drug from the body) of tadalafil can be slowed by liver disease, kidney disease, and concurrent use of certain medications (such as erythromycin, ketoconazole, and protease inhibitors). Slowed breakdown allows tadalafil to stay in the body longer and potentially increase the risk for side effects. Therefore, doctors have to lower the dose and frequency of tadalafil in the following examples:

  • Medications such as erythromycin, ketoconazole (Nizoral), itraconazole (Sporanox), ritonavir (Norvir), and indinavir (Crixivan) can slow the breakdown of tadalafil. Therefore, men taking these medications should not take more than 10 mg of tadalafil and should not take tadalafil more frequently than every 72 hours.
  • If you have kidney troubles, your doctor may recommend that you try a lower dose of tadalafil or change how often you use the tadalafil depending on your kidney function. Men with severe liver disease should not take tadalafil. Men with mild to moderate liver disease should not exceed tadalafil dose of 10 mg once daily.

Avanafil (Stendra)

Avanafil is the most recently FDA-approved PDE5 inhibitor to treat erectile dysfunction.

How effective is Avanafil?

Avanafil has been demonstrated to be effective in treating ED in men of various ages and has been shown to be effective in men with ED related to diabetes mellitus.

How should patients take Avanafil?

The recommended starting dose is 100 mg taken as early as 15 minutes prior to sexual activity, no more than once a day. The maximum dose is 200 mg. Avanafil may be taken with or without food. As with the other PDE5 inhibitors, sexual stimulation is necessary for avanafil to work.

Cautions with use of Avanafil:

If an individual is taking ketoconazole, erythromycin, or ritonavir, it is recommended that the maximum dose of avanafil not exceed 50 mg in 24 hours.

Similarly, if you are taking an alpha-blocker for prostate symptoms, the recommended starting dose of avanafil is 50 mg.

What are the side effects of Avanafil?

Avanafil shares the common PDE5 inhibitor side effects, contraindications, and cautions. No changes in dose are need for men with mild or moderate kidney disease. Individuals with severe kidney disease, severe liver disease, or those on kidney dialysis should not use avanafil.

What are intracavernosal injections?

Patient can inject medications directly into the corpora cavernosa to help attain and maintain erections. Medications such as papaverine hydrochloride, phentolamine, and prostaglandin E1 (alprostadil) can be used alone or in combinations to attain erections. All of these medications are vasodilators and work by increasing blood flow into the penis. Prostaglandin E1 (Caverject, Edex) is easier to obtain; however, it is associated with penile pain in some individuals. The use of combinations of two or three of these medications can decrease the risk of having penile pain.

Risks associated with injection therapy including bleeding, pain with injection, penile pain, priapism, and corporal fibrosis (scarring inside of the corpora cavernosa). There is also concern that repetitive injections in the same area could cause scar tissue to build up in the tunica albuginea that could create penile curvature. Thus, doctors recommended that one alternate sides with injection and perform injections no more frequent than every other day.

If you are on a blood thinner, you must be careful. After injection, patients should pressure to the site to minimize bleeding.

Patients should start with a low dose and increase in small doses until the dose that results in a rigid enough erection for completion of sexual activity is achieved. If one injects and there is an inadequate response, one should not reinject another dose of the medication at that time, due to the risk of priapism.

What are intraurethral suppositories?

Prostaglandin E1 (intraurethral alprostadil or MUSE) can be inserted in a pellet (suppository) form into the urethra to attain erections. It is available in four dosage strengths: 125 mcg, 250 mcg, 500 mcg, and 1,000 mcg. Most individuals need 500 mcg to 1,000 mcg for a satisfactory response.

How does intraurethral prostaglandin E1 work?

The prostaglandin E1 is contained in a small suppository located at the tip of an applicator. You should urinate first as this lubricates the urethra and makes it easier to insert the applicator into the tip of the urethra (urethral meatus, the opening at the tip of the penis that urine passes through). A patient can release the suppository into urethra by gently wiggling the applicator and pressing the button at the end. Rubbing the penis allows the suppository to dissolve, and the prostaglandin is absorbed through the tissue of the urethra into the penis. It takes 15 to 30 minutes for this occur. Once into the penis, the prostaglandin causes increased blood flow into the penis. The prostaglandin can be present in the ejaculate, and thus doctors recommend that men use a condom when having intercourse with a pregnant partner. Men may need to use a condom if vaginal irritation occurs in female partner.

It is recommend that the first trial of intraurethral prostaglandin be performed in the doctor's office due to the risk of hypotension with this medication.

Who should not use intraurethral prostaglandin E1?

Men with a known hypersensitivity to alprostadil should not use intraurethral prostaglandin E1.

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).

Alprostadil should not be used in men at higher risk for priapism (erection lasting longer than six hours) including men with sickle cell anemia, thrombocytopenia (low platelet count), polycythemia (increased red blood cell count), multiple myeloma (a cancer of the white blood cells), and is contraindicated in men prone to venous thrombosis (blood clots in the veins) or hyperviscosity syndrome who are at increased risk for priapism.

How effective is alprostadil?

Patients report success rates up to 65% with intraurethral alprostadil.

What are side effects of intraurethral alprostadil?

Side effects of intraurethral alprostadil include pain in the penis and sometimes in the testicles, mild urethral bleeding, dizziness, and vaginal itching in the sex partner. Patients rarely report syncopal (fainting) episodes with initial use, and thus the first trial of this medication should be performed in the physician's office.

What is the role of testosterone therapy in the treatment of erectile dysfunction?

In patients with low testosterone, testosterone treatment can improve libido and erectile dysfunction, but many men still may need additional oral medications such as sildenafil, vardenafil, or tadalafil. Some studies suggest that men with ED and low testosterone may respond better to PDE5 inhibitors when given testosterone therapy; however, this is controversial.

Men with ED without hypogonadism (a low testosterone level and symptoms related to this) should not use testosterone therapy.

Prior to starting testosterone therapy, it is important for a doctor to perform a thorough evaluation on the patient.

Evaluation should include a breast examination, rectal examination of the prostate, and a PSA level (prostate specific antigen) blood test. Patients who have breast and prostate cancers should not use testosterone.

Patients should continue testosterone therapy only if there is improvement in the symptoms of hypogonadism and should be monitored regularly. You will need periodic blood tests for testosterone levels and blood tests to monitor your blood count and PSA. Testosterone therapy has health risks, and thus doctors should closely monitor its use. Testosterone therapy can worsen sleep apnea and congestive heart failure.

A variety of testosterone therapies are available, including oral, topical (gel, spray, patch), intramuscular, and pellets. Patient should review the advantages and disadvantages of each of these with a physician, as well as the health risks and benefits of testosterone therapy.

Certain medications can alter testicular function, including some diuretics (water pills), some seizure medications, long-acting oral opiate pain medications, antipsychotic medications, and oral steroids.

Can a penis pump (vacuum device) help erectile dysfunction?

Mechanical vacuum devices cause an erection by creating a vacuum around the penis that draws blood into the penis, engorging it, and expanding it. The devices have three components:

  1. A plastic cylinder, in which the individual places his penis
  2. A pump, which draws air out of the cylinder
  3. 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 (see figure 2).
  4. The vacuum device may be operated by hand or be battery operated.

Picture of vacuum-constrictor device for erectile dysfunction (ED)Picture of a penis pump for erectile dysfunction (ED); SOURCE: NIH

How does the vacuum device work?

The vacuum device creates a vacuum to pull blood into the penis. Unlike a normal erection, the inflow of blood does not continue once the individual removes the vacuum device. The rubber band placed at the base of the penis constricts the penis to prevent the blood from leaving the penis. As there is no inflow or outflow of blood when the rubber band is in place, it is uncommon for the tip of the penis (the glans) to appear a little blue and the penis to be cooler. Once intercourse is completed, the individual removes the rubber band and the blood drains out of the penis.

Is the vacuum device effective?

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.

What are the risks of the vacuum device?

Individuals must remove the rubber band immediately after completing intercourse. Leaving the band on too long can harm the penis. Rarely, bruising of the penis or blood in the ejaculate/urine may occur.

What about psychological therapy for erectile dysfunction?

Experts often treat psychologically based impotence using techniques that decrease anxiety associated with intercourse. The patient's partner can help apply the techniques, which include gradual development of intimacy and stimulation. Such techniques also can help relieve anxiety during treatment of physical impotence. If these simple behavioral methods at home are ineffective, a doctor may refer an individual to a sex counselor.

Surgery for erectile dysfunction

Surgery for erectile dysfunction may have the following as its goal:

  1. to reconstruct arteries in order to increase the flow of blood to the penis; and
  2. to block veins that drain blood from the penis (currently not recommended).
  3. 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.

Penile prosthesis

Currently, there are several different types of penile prostheses. The simplest is the malleable penile prosthesis and the most complex, the three-piece inflatable penile prosthesis.

Malleable implants usually consist of paired rods, inserted surgically into each of the corpora cavernosa. The rods are stiff, and to have an erection, one bends them up and then when finished with intercourse one bends them down. They do not change in length or width. The malleable implants are the least mechanical and thus have the lowest risk of malfunction. However, also have the least "normal appearance."

The most common inflatable prosthesis is the three-piece penile prosthesis. It is composed of paired cylinders, which doctors surgically insert inside the penis. Patients can expand the cylinders using pressurized fluid (see figure 3). Tubes connect the cylinders to a fluid reservoir and pump, which doctors also surgically implant. The reservoir is usually in the pelvis. A doctor places the pump in the scrotum. By pressing on the pump, sterile fluid transfers from the reservoir into the cylinders in the penis. An erection is produced primarily by expansion of the width of the penis, however, one model can increase in length a small amount also. Lock-out valves in the tubing prevent the fluid from leaving the cylinder until a release valve is pressed. By pressing the relief valve and gently squeezing the penis, the fluid within the cylinders transfers back into the reservoir.

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.

Penile prostheses are very effective, and most patients who have a prosthesis placed are satisfied with the prosthesis. However, placement of a prosthesis causes scarring of the tissue within the corpora cavernosa, and if the prosthesis requires removal, other forms of therapy, except for the vacuum device, are often not effective. Thus, most physicians reserve placement of a prosthesis for men who have tried and failed or have contraindications to other therapies.

Complications of penile prosthesis placement

Infection is a concern after placement of a prosthesis and is a reported complication in 8%-20% of men undergoing placement of a penile prosthesis. If a prosthesis becomes infected (redness, pain, and swelling of the penis and sometimes purulent drainage are signs of infection), the prosthesis must be removed. Depending on the timing and severity of the infection and your surgeon's preference, the area can be irrigated extensively with antibiotic solutions and a new prosthesis placed at the same time or removal of the infected prosthesis and an attempt to place a new prosthesis made at a later time when the infection is totally cleared.

Mechanical malfunction is another risk of the prosthesis. However, advancements including lock-out valves and special covering over areas of the tubing have decreased the risk of mechanical malfunction.

Erosion of the prosthesis, whereby it presses through the corporal tissue into the urethra, may occur. Symptoms and signs may include pain, blood in the urine, discharge, abnormal urine stream, and malfunction. If the prosthesis erodes into the urethra, a physician must remove it. If the other cylinder remains intact, it can be left in place. A physician leaves a catheter in place to allow the urethra to heal.

Other risks of penile prosthesis include over- or undersizing of the prosthesis, which can cause an abnormal appearance to the erect penis or reservoir or pump migration into abnormal locations.

Picture of an inflatable implant for erectile dysfunctionPicture of an inflatable implant for erectile dysfunction; SOURCE: NIH

Surgery to repair arteries (penile arterial reconstructive surgery) can reduce impotence caused by obstructions that block the flow of blood to the penis. The best candidates for such surgery are young men with discrete blockage of an artery because of a physical injury to the pubic area or a fracture of the pelvis. The procedure is less successful in older men with widespread blockage of arteries.

Physicians do not recommend surgery on the penile veins.

Can over-the-counter (OTC) and/or natural or home remedies treat erectile dysfunction?

The U.S. FDA (Food and Drug Administration) has a list of 29 OTC products that claim to treat erectile dysfunction. Patients should avoid these because many contain harmful ingredients. Other natural or herbal remedies such as DHEA, L-arginine, ginseng, and yohimbe are supplements that have been used but have not been proven safe and effective according to some researchers. Before using such compounds, individuals should consult their doctor. According to some experts, acupuncture does not effectively treat erectile dysfunction. Other home remedies for reducing ED symptoms include diet changes such as eating blueberries and citrus fruits and drinking red wine.

Is it possible to prevent erectile dysfunction?

Prevention of some of the causes that contribute to the development of erectile dysfunction can decrease the chances of developing the problem. For example, if a person decreases their chances of developing diabetes, heart disease, and hypertension, they will decrease their chances of developing erectile dysfunction. Other things like stopping smoking, eating a healthy diet (heart healthy with adequate vitamin intake), and exercising daily may reduce a person's risk.

What is the prognosis for erectile dysfunction?

Currently, there are no therapies that cure erectile dysfunction. However, a number of effective therapies are available that allow an individual to have an erection when desired. Depending on the cause of the erectile dysfunction, certain therapies may be more effective than others. Although there is limited data on lifestyle modification, intuitively, decreasing risk factors for erectile dysfunction may help prevent progression of disease.

What erectile dysfunction studies are under way? What are future treatment options?

Combination therapy for the treatment of erectile dysfunction has been under investigation. Most of these studies have been small trials, and long-term data regarding their effectiveness and safety are lacking. However, with thorough evaluation and counseling, there may be a use for combination therapy for certain individuals with ED.

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.

Other medical therapies under evaluation include ROCK inhibitors and soluble guanyl cyclase activators. Melanocortin receptor agonists are a new set of medications being developed in the field of erectile dysfunction. Their action is on the nervous system rather than the vascular system. PT-141 is a nasal preparation that appears to be effective alone or in combination with PDE5 inhibitors. The main side effects include flushing and nausea. These drugs are currently not approved for commercial use.

Research in stem cell therapy and gene therapy for erectile dysfunction is also ongoing.

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