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Impotence (Erectile dysfunction)

Highlights

Erectile Dysfunction

Erectile dysfunction, also called impotence, can affect men of all ages, although it is much more common among older men. It is normal for men to occasionally experience erectile dysfunction. However, if the problem becomes chronic, it can have adverse effects on relationships, emotional health, and self-esteem. Erectile dysfunction may also be a symptom of an underlying health condition. If erectile dysfunction becomes an on-going problem, it is important to talk to your doctor.

Causes of Erectile Dysfunction

• Psychological causes of erectile dysfunction include anxiety, depression, stress, and problems in relationships.
• Lifestyle factors that increase risk for erectile dysfunction include smoking, alcohol use, and other substance abuse.
• Physical causes may include heart disease, high blood pressure, diabetes, neurological disease, and other health conditions. Some of the medications used to treat these conditions can also cause erectile dysfunction.

Treatment

Many treatments are available for erectile dysfunction. They include oral medications, injections, mechanical devices, surgery, and psychotherapy. Any health condition that may be associated with erectile dysfunction should also be addressed. Doctors recommend that a man’s partner be involved in the discussion of treatment options.

PDE5 Inhibitors

The most common medical treatment for erectile dysfunction is PDE5 inhibitor drugs, which include sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). These drugs are generally safe and effective for most men. These medications may not be appropriate for men with certain health conditions, such as severe heart disease, heart failure, history of stroke, or uncontrolled high blood pressure or diabetes. Men who take nitrate drugs cannot use PDE5 inhibitors, and these drugs can also interact with other medications. Talk to your doctor about whether PDE5 inhibitor drugs are a safe choice for you.

Drug Warning

In general, PDE5 inhibitors have few severe side effects. A small number of men have experienced problems with vision. In 2007, the Food and Drug Administration (FDA) added a warning to these drugs’ labels concerning sudden hearing loss, often accompanied by ringing in the ears or dizziness. If you have these side effects, you should immediately contact your doctor.

Introduction

Erectile dysfunction (impotence) is the inability to achieve or maintain an erection sufficiently rigid for sexual intercourse, ejaculation, or both. Sexual drive and the ability to have an orgasm are not necessarily affected. Because all men have erection problems from time to time, doctors consider impotence to be present if attempts at intercourse fail at least 25% of the time.

Erectile dysfunction is not new in either medicine or human experience, but it is not easily or openly discussed. Cultural expectations of male sexuality inhibit many men from seeking help for a disorder that can usually benefit from medical treatment.

The Penis and Erectile Function

The Structure of the Penis. The penis is composed of the following structures:

• Two parallel columns of spongy tissue called the corpus cavernosa, or erectile bodies.
• A central spongy chamber called the corpus spongiosum, which contains the urethra, the tube that carries urine from the bladder through the penis.

These structures are made up of erectile tissue. Erectile tissue is rich in tiny pools of blood vessels called cavernous sinuses. Each of these vessels are surrounded by smooth muscles and supported by elastic fibrous tissue composed of a protein called collagen.

Erectile Function and Nitric Oxide. The penis is either flaccid or erect depending on the state of arousal. In the flaccid, or unerect, penis, the following normally occurs:

• Small arteries leading to the cavernous sinuses contract, reducing the inflow of blood.
• The smooth muscles regulating the many tiny blood vessels also stay contracted, limiting the amount of blood that can collect in the penis.

During arousal the following occurs:

• The man's central nervous system stimulates the release of a number of chemicals, including nitric oxide, which is now considered the main contributor for eliciting and maintaining erection.
• Nitric oxide stimulates production of cyclic GMP, a chemical that relaxes the smooth muscles in the penis. This allows blood to flow into the tiny pool-like cavernous sinuses, flooding the penis.
• This increased blood flow nearly doubles the diameter of the spongy chambers.
• The veins surrounding the chambers are squeezed almost completely shut by this pressure.
• The veins are unable to drain blood out of the penis and so the penis becomes rigid and erect.
• After ejaculation or arousal, cyclic GMP is broken down by an enzyme called phosphodiesterase-5 (PDE5), and other compounds are released that cause the penis to become flaccid (unerect) again.

Important Substances for Erectile Health

A proper balance of certain chemicals, gases, and other substances is critical for erectile health.

Collagen. The protein collagen is the major component in structural tissue in the body, including in the penis. Excessive amounts, however, form scar tissue, which can impair erectile function.

Oxygen. Oxygen-rich blood is one of the most important components for erectile health. Oxygen affects two substances that are important in achieving erection:

• Oxygen suppresses transforming growth factor beta 1 (TGF-B1). TGF-B1 is a component of the immune system called a cytokine and is produced by smooth muscle cells. It appears to stimulate collagen production in the corpus cavernosum, which can lead to erectile dysfunction.
• Oxygen enhances the activity of prostaglandin E1. Prostaglandin E1 is produced during erection by the muscle cells in the penis. It activates an enzyme that initiates calcium release by the smooth muscle cells, which relaxes them and allows blood flow. Prostaglandin E1 also suppresses production of collagen.

Oxygen levels vary widely from reduced levels in the flaccid state to very high in the erect state. During sleep, oxygen levels are high and a man can normally have three to five erections per night, each one lasting 20 - 40 minutes.

Testosterone and Other Hormones. Normal levels of hormones, especially testosterone, are essential for erectile function, though their exact role is not clear.

Erectile Dysfunction and Oxygen Deprivation

Erectile dysfunction most commonly occurs when the penis is deprived of oxygen-rich blood. When oxygen levels to the penis are low, an imbalance occurs in two important substances, TGF-B1 and prostaglandin E1:

• TGF-B1 levels increase, which trigger production of collagen, a tough protein that forms all types of connective tissue, including scar tissue.
• In addition, there is a reduction in prostaglandin E1, a chemical that suppresses collagen production and relaxes the smooth muscles to allow blood flow, resulting in an erection.

When TGF-B1 levels increase and prostaglandin E1 levels decrease, smooth muscles waste away and collagen is overproduced, causing scarring, loss of elasticity, and reduced blood flow to the penis. A number of conditions can deprive the penis of oxygen-rich blood.

Blockage of Blood Vessels (Ischemia). The primary cause of oxygen deprivation is ischemia -- the blockage of blood vessels. The same conditions that lead to heart problems may also contribute to erectile dysfunction. For example, when cholesterol and other factors are imbalanced, a fatty substance called plaque forms on artery walls. As the plaque builds up, the arterial walls gradually narrow, reducing blood flow. This process, known as atherosclerosis, is the major contributor to the development of coronary heart disease. It may also play a role in the development of erectile dysfunction.

Risk Factors

More than 18 million American men over age 20 have erectile dysfunction, and about 600,000 men age 40 - 70 experience erectile dysfunction to some degree each year.

For most men, erectile dysfunction is primarily associated with older age. While ED affects less than 10% of men in their 20s, and 5 - 17% of men in their 40s, about 15 - 34% of men in their 70s have ED. Nevertheless, impotence is not inevitable with age. In a survey of men over 60 years old, 61% reported being sexually active, and nearly half derived as much if not more emotional benefit from their sex lives as they did in their 40s.

Severe erectile dysfunction often has more to do with disease than age itself. In particular, older men are more likely to have heart disease, diabetes, and high blood pressure than younger men. Such conditions and some of their treatments are major risk factors for erectile dysfunction. Smoking and obesity are also prime risk factors for ED.

Many physical and psychological situations can cause erectile dysfunction, and brief periods of impotence are normal. Every man experiences erectile dysfunction from time to time. Nevertheless, if the problem is persistent, men should seek professional help, particularly since erectile dysfunction is usually treatable and may also be a symptom of an underlying health problem.

Lifestyle or Psychological Causes

Over the past decades, the medical perspective on the causes of erectile dysfunction has shifted. Common wisdom used to attribute almost all cases of impotence to psychological factors. Now investigators estimate that up to 85% of impotence cases are caused by medical or physical problems. Only 15% are psychologically based.

It is often difficult to determine if the cause of erectile dysfunction is a physical or psychological one, or even some combination. The following may be helpful:

• Physical impotence can be caused by internal medical causes (such as diabetes or high blood pressure) or by external causes (such as surgery, injury, or medications). Erectile dysfunction due to medical conditions usually develops gradually over time. If impotence persists over a 3-month period and is not due to a stressful event, drug use, alcohol, or known medical conditions, the patient needs medical attention by a urologist specializing in impotence.
• Psychological impotence tends to develop rapidly and be related to a recent situation or event. The patient may be able to have an erection in some circumstances but not in others. Being able to have or maintain an erection upon waking up in the morning suggests that the problem is psychological rather than physical.

In virtually every case of erectile dysfunction there are emotional issues that can seriously affect the man's self-esteem and relationships. Negative emotions may even perpetuate erectile dysfunction that has been caused by a medical condition that has been successfully treated. Many men tend to fault themselves for their impotence even if it is clearly caused by physical problems over which they have little or no control.

Emotional Disorders Associated with Erectile Dysfunction

Anxiety. Anxiety has both emotional and physical consequences that can affect erectile function. It is among the most frequently cited contributors to psychological impotence. Excessive concern about sexual performance is often referred to as performance or "honeymoon" anxiety and may provoke an intense fear of failure and self-doubt. It can sometimes set off a cycle of chronic impotence. In response to anxiety, the brain releases chemicals known as neurotransmitters that constrict the smooth muscles of the penis and its arteries. This constriction reduces the blood flow into, and increases the blood flow out of, the penis. Even simple stress may promote the release of brain chemicals that disrupt potency in a similar way.

Depression. Depression is strongly associated with erectile dysfunction. Depression can certainly reduce sexual desire, but it is often not clear which condition comes first.

Problems in Relationships

Troubles in relationships often have a direct impact on sexual functioning. Partners of men with erectile dysfunction may feel rejected and resentful, particularly if the affected man does not confide his own anxieties or depression. Both partners commonly experience guilt for what they each perceive as a personal failure. Tension and anger frequently arise between people who are unable to discuss sexual or emotional issues with each other. It can be very difficult for the man to perform sexually when both partners harbor negative feelings.

Smoking

Smoking contributes to the development of impotence, mainly because it increases the effects of other blood vessel disorders, including high blood pressure and atherosclerosis.

Alcohol

Alcohol has also been implicated in causing impotence. A small amount releases inhibitions, but having more than one drink can depress the central nervous system and impair sexual function.

Lack of Frequent Erections

Infrequent erections deprive the penis of oxygen-rich blood. Without daily erections, collagen production increases and eventually may form a tough tissue that interferes with blood flow. The spontaneous erections men have while sleeping or awake may be a natural protection against this process.

Physical Causes

A number of conditions share a common problem with erectile dysfunction -- the impaired ability of blood vessels to open and allow normal blood flow.

The following conditions are highly associated with erectile dysfunction:

Heart Disease

Heart disease, atherosclerosis, and high cholesterol levels are major risk factors for erectile dysfunction. In fact, erectile problems may be a warning sign of these conditions in men at risk for atherosclerosis. Men who experience ED may have a greater risk for angina, heart attack, or stroke. Patients with ED should be evaluated for cardiovascular problems. [For more information, see In-Depth Report #3: Coronary artery disease.]

High Blood Pressure (Hypertension)

Erectile dysfunction is a very common problem in men with high blood pressure, possibly because of the age group itoccurs in. More than 40% of men with erectile dysfunction have hypertension. The disease process is the major contributor to impotence, but many of the drugs used to treat hypertension (such as calcium channel blockers and beta-blockers) also cause it. [For more information, see In-Depth Report #14: High blood pressure.]

Diabetes

Diabetes is a major risk factor for erectile dysfunction. Between 30 - 50% of all men with diabetes report some form of sexual difficulty. Blocked arteries and nerve damage are both common complications of diabetes. When the blood vessels or nerves of the penis are involved, erectile dysfunction can result. Diabetes is also associated with heart disease, another risk factor for ED. [For more information, see In-Depth Report #60: Diabetes type 2.]

Obesity

Obesity increases the risk for diabetes, heart disease, and erectile dysfunction.

Metabolic Syndrome

Metabolic syndrome -- a cluster of conditions that includes obesity and abdominal fat, unhealthy cholesterol and triglyceride levels, high blood pressure, and insulin resistance -- is also a risk factor for erectile dysfunction in men older than 50 years.

Benign Prostatic Hyperplasia

Lower urinary tract symptoms associated with benign prostatic hyperplasia can decrease nitric oxide in the penis. Surgery and drug treatments, such as finasteride (Proscar), can also increase the risk for impotence. [For more information, see In-Depth Report #71: Benign prostatic hyperplasia.]

Neurologic Conditions

Diseases that affect the central nervous system can cause erectile dysfunction. These conditions include Parkinson’s disease, multiple sclerosis, and stroke. [For more information, see In-Depth Reports #51: Parkinson’s disease; #17: Multiple sclerosis; #45: Stroke.]

Endocrinologic and Hormonal Conditions

Low levels of the male hormone testosterone can be a contributing factor to erectile dysfunction in men who have other risk factors. (Low testosterone as the sole cause of erectile dysfunction affects only about 5% of men. In general, low testosterone levels are more likely to reduce sexual desire than to cause impotence.) Abnormalities of the pituitary gland that cause high levels of the hormone prolactin are also associated with erectile dysfunction. Other hormonal and endocrinologic causes of erectile dysfunction include thyroid and adrenal gland problems.

A varicocele is an enlarged (varicose) vein in the cord that connects to the testicle. Varicoceles are found in 15 - 20% of all men and in 25 - 40% of infertile men. When varicoceles occur in both testicles, they may contribute to hormone imbalances that cause erectile dysfunction.

Physical Trauma and Injury

Spinal cord injury and pelvic trauma, such as a pelvic fracture, can cause nerve damage that results in impotence. Other conditions that can injure the spine and effect impotence include spinal cord tumors, spina bifida, and a history of polio.

Surgery

Surgery for Prostate Cancer. Radical prostatectomy can cause loss of sexual function. Nerve-sparing surgical procedures are proving to be helpful in reducing the risk of impotence. (Radiation treatments for prostate cancer, especially external-beam radiation, may cause fewer problems than surgery.) [For more information, see In-Depth Report # 33: Prostate cancer.]

Surgery for Colon and Rectal Cancers. Surgical and radiation treatments for colorectal cancers can cause impotence in some patients. In general, colostomy does not usually affect sexual function. However, wide rectal surgery can cause short-term or long-term sexual dysfunction. [For more information, see In-Depth Report #55: Colon and rectal cancers.]

Surgical Treatment of Inflammatory Bowel Disease. Rectal excision for inflammatory bowel disease (IBD) can cause impotence, but rates are low (2 - 4%).

Fistula Surgery. Surgery to repair anal fistulas can affect the muscles that control the rectum (external anal sphincter muscles), sometimes causing impotence. (Repair of these muscles may restore erectile function.)

Orthopedic Surgery. Erectile dysfunction can sometimes result from orthopedic surgery that affects pelvic nerves.

Note: Vasectomy does not cause erectile dysfunction.

Medications

Many medications increase the risk for erectile dysfunction. They include:

• High blood pressure medications, particularly diuretics, beta-blockers, and calcium-channel blockers.
• Heart or cholesterol medications such as digoxin, gemfibrozil, or clofibrate.
• Psychotropic medication used to treat depression and bipolar disorder such as selective serotonin-reuptake inhibitors (SSRIs), tricyclic antidepressants, monoamine oxidase inhibitors, and lithium. Certain types of antipsychotic medication, such as phenothiazines (like compazine) and butyrophenones (like haloperidol), can also cause erectile dysfunction.
• Gastroesophagelal reflux disorder (GERD) medications, used to reduce stomach acid, such as rantidine (Zantac) and cimetidine (Tagamet).
• Hormone drugs such as estrogens, corticosteroids, and 5-alpha reductase inhibitors.
• Chemotherapy drugs such as methotrexate.

Other Problems in Sexual Function

Premature Ejaculation. Premature ejaculation is the most common male sexual dysfunction and occurs in as many as 40% of men. It is defined as the inability to delay ejaculation to the point where both partners are satisfied. This can vary widely depending on the preferences of the partners. Younger men tend to have this problem more than older men. Anxiety is a major factor at any age. In general, the longer the duration between ejaculations, the faster they are. Various techniques are available to help delay orgasm.

The standard medications used for this condition are selective serotonin reuptake inhibitors (SSRIs), which include Prozac and Paxil. Some studies suggest that sildenafil (Viagra) in combination with an SSRI may be helpful. There is still no drug specifically approved for treating premature ejaculation.

Peyronie's Disease. Peyronie's disease is an accumulation of scar tissue within the penis shaft, which causes it to curve. The curvature can make erection and intercourse difficult and painful. This condition may be associated with an injury to the penis, but no clear information exists on its origin. The disease often goes into a type of spontaneous remission, and some individuals who had previously experienced erectile dysfunction are able to resume sexual activity. Scarring may still cause erection problems, however, even in these cases.

Treatment options include oral drugs, injections, and surgery. Penile implants may also be beneficial.

Not all men need treatment for Peyronie’s disease. Sometimes the condition improves on its own without treatment.

Priapism. Priapism is a sustained, painful, and unwanted erection that persists despite a lack of sexual stimulation. Generally, priapism results when the smooth muscle tissue remains relaxed so that a constant flow of blood into the vessels of the penis occurs with no leakage back out. The development of priapism has been associated with urinary stones, certain medications, neurologic disorders, and, more recently, with self-injection therapy used for impotence.

If priapism occurs, applying ice for 10-minute periods to the inner thigh may help reduce blood flow. Erections that last 4 hours or longer require emergency care.

Prognosis

Temporary erectile dysfunction is very common and is usually not a worrisome problem. Nevertheless, if the condition is persistent, psychological effects can be significant. Erectile dysfunction can have a devastating impact on a relationship and can cause extreme depression, which may become chronic if not treated. When a consistent pattern of sexual dysfunction extends over a prolonged period of time, a serious physical or emotional disorder may be present.

It is important to treat any underlying medical condition that may be causing erectile dysfunction.

Diagnosis

The doctor typically interviews the patient about many physical and psychological factors.

Medical and Personal History. The doctor should take a medical and personal history and may ask about the following:

• Past and present medical problems
• Medications or drugs being used
• Any history of psychological problems, including stress, anxiety, or depression

Sexual History. In addition the doctor will ask about the patient's sexual history, which may include:

• The nature of the onset of the dysfunction
• The frequency, quality, and duration of any erections, and whether they occur at night or in the morning
• The specific circumstances when erectile dysfunction occurred
• Details of technique
• The patient's motivation for and expectations of treatment
• Whether problems exist in the current relationship

Interviewing the Sexual Partner. If appropriate, the doctor may also interview the sexual partner. In fact, including the partner in the counseling process is proving to be an important component in making the best treatment choices.

Physical Examination

The doctor should perform a careful physical exam, including examination of the genital area and a digital rectal examination (the doctor inserts a gloved and lubricated finger into the patient's rectum) to check for prostate abnormalities.

Trials Using Treatments for Erectile Function

A useful approach is to administer a treatment for erectile dysfunction and then observe the response. Doctors usually recommend a trial of sildenafil (Viagra) to test for an erection response 30 - 60 minutes after the drug is administered. This drug is replacing more invasive and expensive tests, such as injections of papaverine or prostaglandin E1. These medicines dilate blood vessels in the penis and produce an erection in about 15 minutes.

After administering the treatment and waiting the appropriate amount of time, the doctor then observes the erectile response, curvature of the penis, and response after erection, sometimes using an ultrasound scanner to assess blood flow.

Laboratory Tests

Blood Tests for Hormonal Abnormalities. Blood tests may be used to measure testosterone levels and, if necessary, prolactin levels to determine if there are hormone problems. The doctor may also screen for thyroid and adrenal gland dysfunction. In addition, various specific tests for erectile dysfunction can be performed.

Tests for Medical Conditions That May be Causing Erectile Dysfunction. Evidence of other medical conditions should be sought, particularly high blood pressure, diabetes, atherosclerosis, and nerve damage.

Monitoring Nighttime Erections

Tests that monitor nighttime erections may be used to determine if the causes of erectile dysfunction are more likely to be psychological than physical.

Snap-Gauge Test. The snap-gauge test monitors the man's ability to achieve an erection during sleep. It is a very simple test.

• When the man goes to bed, he places bands around the shaft of his penis.
• If one or more breaks during the course of the night, it provides evidence of an erection. In this case, a psychological basis for the erectile dysfunction is likely.

RigiScan Monitor. A more sophisticated and expensive device is the RigiScan monitor, which makes repetitive measurements of rigidity around the base and tip of the penis. This test is quite accurate but may fail to detect mild cases of erectile dysfunction.

Penile Brachial Index

The penile brachial index is a measurement that compares blood pressure in the penis with the blood pressure taken in the arm. Problems with the arterial flow to the penis can be detected using this method.

Imaging Techniques

Imaging tests may be used in certain cases where problems with blood flow are possible, but they are expensive and often limited to younger men. Anyone considering these tests should have them done in a specialized setting by professionals experienced in their use. Tests include combined intracavernous injection and stimulation (CIS), dynamic infusion cavernosometry and cavernosography (DICC), duplex Doppler ultrasound, and penile angiography.

Treatment

The cause of impotence dictates the mode of treatment. The first step is to define the cause, if possible, and then try the simplest and least-risky solution.

Before a certain treatment is prescribed, the following factors should be considered:

• Any pre-existing illnesses and medications
• The degree of comfort with the treatment method
• Partner satisfaction and safety profiles need to be considered. Experts strongly recommend that the patient's partner be involved to help with any necessary sexual adjustment.

No matter what the treatment, embarking on a healthy lifestyle is the first and critical step for maintaining and restoring erectile function.

Treatment Choices

Medical and Surgical Treatments. Sildenafil (Viagra), the first effective oral drug for erectile dysfunction, has been on the market since 1998 and rapidly became the treatment of choice for most men with erectile dysfunction. In 2003, the FDA approved two other oral medications, vardenafil (Levitra) and tadalafil (Cialis), for the treatment of erectile dysfunction.

Men who cannot or choose not to take the drugs still have many other options, including:

• Medications inserted or injected into the penis
• Vacuum devices
• Intracavernosal injection therapy
• Invasive procedures, such as penile implants or surgery (limited to those for whom other treatments haven't worked and who have been carefully screened)

Ultimately, how successful the medical treatment is and how well it is accepted depends, in large part, on the man's expectations and how he and his partner both adapt to the procedure.

Psychotherapies. Some form of psychological, behavioral, or sexual therapy is often recommended for individuals suffering from severe impotence, regardless of cause.

Lifestyle Changes

Because many cases of erectile dysfunction are due to reduced blood flow from blocked arteries, it is important to maintain the same lifestyle habits as those who face an increased risk for heart disease.

Diet and Exercise

Diet. Everyone should eat a diet rich in fresh fruits and vegetables, whole grains, and fiber and low in saturated fats and sodium. Because erectile dysfunction may be related to circulation problems, diets that benefit the heart are especially important.

Foods that some people claim to have qualities that enhance sexual drive include chilies, chocolate, scallops, oysters, olives, and anchovies. No hard evidence exists for these claims.

Exercise. A regular exercise program can be helpful.

Alcohol and Smoking. Men who drink alcohol should do so in moderation. Quitting smoking is essential.

Stay Sexually Active

Staying sexually active can help prevent impotence. Frequent erections stimulate blood flow to the penis. It may be helpful to note that erections are firmest during deep sleep right before waking up. Autumn is the time of the year when male hormone levels are highest and sexual activity is most frequent.

Change or Reduce Medications

If medications are causing impotence, the patient and doctor should discuss alternatives or reduced dosages.

Psychotherapy and Behavioral Therapy

Even if erectile dysfunction is caused by a physical problem, interpersonal, supportive, or behavioral therapy are often helpful for patients. Therapy may also ease the adjustment period after the initiation or completion of treatment. It is beneficial to have the partner involved in this process.

Oral Medications (PDE5 Inhibitors)

Three medicines taken by mouth are approved for the treatment of erectile dysfunction:

• Sildenafil (Viagra)
• Vardenafil (Levitra)
• Tadalafil (Cialis)

These drugs appear equal in their effectiveness. All three are known as phosphodiesterase-5 (PDE5) inhibitors. By blocking the PDE-5 enzyme, these drugs help the smooth muscles of the penis to relax and increase blood flow.

PDE5 inhibitors are generally the first choice of treatment for erectile dysfunction.

Candidates for PDE5 Inhibitors

PDE5 inhibitors are a good choice for men at any age and in any ethnic group who are in good health and who do not have conditions that preclude taking them.

However, PDE5 inhibitors are not suitable for everyone. Men who take nitrate drugs for angina, or certain types of alpha-blockers for high blood pressure and benign prostatic hyperplasia, should not take PDE5 inhibitors. The PDE5 inhibitors are less effective in men with diabetes and in men who have been treated for prostate cancer.

Men with the following conditions should not take PDE5 inhibitors without the recommendation of their doctors and even then should use them with caution:

• Severe heart disease, such as unstable angina, a recent heart attack, or arrhythmias. Men with heart disease may benefit from an exercise test to determine whether resuming sexual activity increases their risk of a heart attack.
• Recent history of stroke
• Hypotension (very low blood pressure)
• Uncontrolled hypertension (high blood pressure)
• Uncontrolled diabetes
• Severe heart failure
• Retinitis pigmentosa. (With this genetic disease, people do not produce phosphodiesterase-5 and do not respond to PDE5 inhibitors.)

Administration and Effect

PDE5 inhibitors work only when the man experiences some sexual arousal. They are generally effective within 15 - 45 minutes. Sildenafil should be taken on an empty stomach; vardenafil and tadalafil may be taken with or without food. The effects of these drugs may last for several hours, and tadalafil may last for up to 36 hours. PDE5 inhibitors should not be used more than once a day.

Success rates increase with the number of attempts, so a man should not be discouraged if the drug does not work at first.

PDE5 inhibitors can also be used in combination with testosterone replacement therapy for men with hypogonadism (low testosterone levels).

Side Effects

Common side effects of PDE inhibitors include flushing, upset stomach, headache, nasal congestion, back pain, and dizziness.

Effects on the Heart. There have been reports of fatal heart attacks in a small percentage of men taking sildenafil (Viagra). Viagra can cause sudden and dangerous drops in blood pressure when the drug is taken with nitrate drugs, such as nitroglycerine, which are used for angina. No one taking nitrates, including the recreational drug amyl nitrate, should take sildenafil or any other PDE5 inhibitors.

Intercourse itself involves an increase in physical exertion and a small risk of heart attack for patients with known heart disease or those at risk.

Visual Effects. About 2.5% of men have vision problems that include seeing a blue haze, temporary increased brightness, and even temporary vision loss in a few cases. Experts believe that visual disturbances are related to the inhibition of phosphodiesterase enzymes in the retina, but the effect appears to be temporary and insignificant, lasting a few minutes to several hours. Men at risk for eye problems who take PDE5 inhibitors regularly should have frequent eye examinations with an ophthalmologist. Men should also see an eye doctor if visual problems last more than a few hours.

In 2005, the FDA began investigating reports of partial vision loss in men who took sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). The vision loss was caused by non-arteric anterior ischemic optic neuropathy (NAION), a condition that occurs from poor blood flow to optic nerves. However, experts note that erectile dysfunction is itself linked to the same vascular problems that cause NAION. Patients who suffer from diabetes, high blood pressure, and heart disease are at higher risk for erectile dysfunction as well as other vascular problems such as NAION. Information concerning vision loss has been added to the labels of these drugs, but the risk of blindness appears small. Still, patients who use this medication and experience a sudden loss of vision should immediately stop taking the drug and contact their doctor.

Hearing Loss. In 2007, the FDA added a warning about potential hearing loss associated with PDE5 inhibitors. A small number of men have experienced sudden hearing loss in one ear, sometimes accompanied by ringing in the ears and dizziness. If you have this symptom, immediately contact your doctor.

Seizures. There have been a few reports of seizures in men taking sildenafil. These are rare occurrences and it is not clear if there is any causal association.

Risk of Priapism. PDE5 inhibitors pose a very low risk for priapism in most men. (Priapism is sustained, painful, and unwanted erection.) Exceptions are young men with normal erectile function.

Interactions with Other Drugs. In addition to serious interactions with nitrates, PDE5 inhibitors may also interact with certain antibiotics, such as erythromycin, and acid blockers, such as cimetidine (Tagamet). Patients should tell their doctor about any medications they are taking.

Injections or Topical Treatments

Treatments Using Alprostadil

Alprostadil is derived from a natural substance, prostaglandin E1, and opens blood vessels. This medicine is an effective treatment for some men. It can be administered by:

• Injection into the erectile tissue of the penis (such as Caverject or Edex)
• A system that administers the drug in pellets placed in the urethra (MUSE system)

Candidates. Regardless of how it is administered, alprostadil works in many men with a wide range of medical disorders related to erectile dysfunction, including men with:

• Diabetes
• Prostate cancer treatments (early use of alprostadil injections after prostate cancer treatment, particularly when followed by a PDE5 inhibitor, may be helpful)
• Cholesterol problems treated with nitrates
• Injury

Alprostadil is not an appropriate choice for men with:

• Severe circulatory or nerve damage
• Bleeding abnormalities or men who are taking medications that thin the blood, such as heparin or warfarin
• Penile implants

Injected Alprostadil. Injected alprostadil (Caverject, Edex) uses a very small needle that the man injects into the erectile tissue of his penis. About 80% of men describe the pain of administering the injection as very mild.

The drug should not be injected more than 3 times a week or more than once within a 24-hour period.

MUSE System. The MUSE system delivers alprostadil through the urethra. It works in the following way:

• The device is a thin plastic tube with a button at the top.
• The man inserts the tube into his urethral opening right after urination. (Urinating or urine leakage right after administration may reduce the amount of medication.)
• He presses the button, which releases a pellet containing alprostadil.
• The man rolls his penis between his hands for 10 - 30 seconds to evenly distribute the drug. To avoid discomfort, the man should keep the penis as straight as possible during administration.
• The man should be upright, either sitting, standing or walking for about 10 minutes after administration. By that time, he should have achieved an erection that lasts 30 - 60 minutes. (If a man lies on his back too soon after administration, blood flow to the penis may decrease and the erection may be lost.)
• The erection may continue after orgasm.

The MUSE system should not be used more than twice a day and is not appropriate for men with abnormal penis anatomy.

Side Effects of Most Alprostadil Methods. Certain side effects are common to all methods of administration, although they may differ in severity depending on how the drug is given:

• Pain and burning at the application site. In one study half of the men who injected alprostadil experienced some burning and pain at the injection site.
• Scarring of the penis (Peyronie's disease), which is most likely to occur with injections.
• Sudden, low blood pressure. Symptoms include dizziness, lightheadedness, and fainting. If these symptoms occur, the man should lie down immediately with his legs raised.
• Priapism (prolonged erection). Possible with any method, but less chance with the MUSE system than with injections. If priapism occurs, applying ice for 10-minute periods to the inner thigh may help reduce blood flow. Erections that last 4 hours or longer require emergency care.
• Women partners may experience vaginal burning or itching. The drug may have toxic effects if it reaches the fetus in pregnant women, so men should not use alprostadil for intercourse with pregnant women without the use of a condom or other barrier contraceptive device.
• Other side effects. Other side effects include minor bleeding or spotting, redness in the penis, and aching in the testicles, legs, and area around the anus.

Injections Using Papaverine and Phentolamine

Until the introduction of alprostadil, the two drugs used for injection therapy had been papaverine (Pavabid, Cerespan) and phentolamine (Regitine). Adverse reactions are usually minor but include pain, ulcers, and prolonged erections (priapism). These drugs are rarely used now.

Testosterone Replacement Therapy

Testosterone replacement therapy works best for men with ED who have been diagnosed with hypogonadism (low testosterone levels). Men who have ED and normal testosterone levels are not likely to benefit from testosterone therapy. Studies indicate that testosterone therapy can modestly improve erectile function and libido.

Forms of testosterone therapy include:

• Muscle injections using testosterone enanthate (such as Andryl or Delatestryl) or cypionate (Andro-Cyp, Depo-Testosterone, or Virion). This has been the standard administration.
• Skin patch (Testoderm, Testoderm TTS, or Androderm). Depending on the brand, patches may be applied to the skin of the scrotum every 24 hours or to the abdomen, back, thighs, or upper arm. In the latter case, two patches are required every 24 hours. Testoderm and Testoderm TTS may cause less skin irritation than Androderm.
• Skin gel (such as Androgel or Testim). The gel is applied only to the same parts of the body as the patch. A gel applied to the penile skin is being investigated for men with hypogonadism and erectile dysfunction. Pregnant women must avoid contact with the gel because the testosterone may harm the fetus.

Oral forms of testosterone are not recommended because of the risk for liver damage when taken for long periods of time.

Testosterone therapy may increase the risk for the following adverse effects, particularly in men with normal testosterone levels:

• Lowering of HDL ("good" cholesterol)
• Rapid growth of prostate tumors in men with existing prostate cancers. (Taking testosterone does not appear to increase the risk for prostate cancer, but experts remain concerned.)
• Lower sperm count
• Sleep apnea
• Polycythemia, an abnormal increase in red blood cells
• Benign prostatic hyperplasia

Other Treatments

Vacuum devices, or external management systems, are effective, safe, and simple to use for all forms of impotence except when severe scarring has occurred from Peyronie's disease.

Using the Device. Patients must receive thorough instructions in the proper use of such devices. They typically work as follows:

• The man places the penis inside a plastic cylinder.
• A vacuum is created, which causes blood to flow into the penis, thereby creating an erection.
• A band is tightly secured around the base of the penis, which retains the erection, and the cylinder is removed.
• It takes about 3 - 5 minutes to produce an erection.

Lack of spontaneity is this method's major drawback. The erection involves only part of the penis shaft, and the process will certainly seem peculiar in the beginning. When these psychological obstacles are overcome, many couples find the result highly satisfactory.

Success Rates. Studies have found that success with the vacuum device is about equal to other methods. Up to two-thirds of men using it reported the device to be effective.

Side Effects. Side effects include blocked ejaculation and some discomfort during pumping and from use of the band. Minor bruising may occur, although infrequently. It is very important to use a medically approved pump. There have been reports of injury from vacuum devices that do not have a pressure-release valve or other safety elements.

Venous Flow Controllers

Vacuum-less devices that trap blood within the penis are also available. They are called venous flow controllers or simple constricting devices. These devices are typically rubber or silicone rings or tubes that are placed at the base of the erect penis to trap the erection. They can be used by men who can achieve erections but lose them easily. These devices should not be used for longer than 30 minutes or lack of oxygen can damage the penis, and they should not be used by patients who have bleeding problems or are taking anticoagulant medicines ("blood thinners").

Penile Implants

Penile implants are available for men who cannot take medication or for who less invasive treatments do not work. In general, they work well in restoring sexual function, and men are usually satisfied with the results.

Three types of surgical implants are used for the treatment of erectile dysfunction:

• A hydraulic implant consists of two cylinders placed within the erection chambers of the penis and a pump. The pump releases a saline solution into the chambers to cause an erection, and removes the solution to deflate the erection.
• A penile prosthesis is composed of two semi-rigid but bendable rods that are placed inside the erection chambers of the penis. The penis can then be manipulated to an erect or non-erect position.
• A third implant uses interlocking soft plastic blocks that can be inflated or deflated using a cable that passes through them.

There appear to be no long-term immune problems related to the silicon or other materials in the devices.

Limitations. Erectile tissue is permanently damaged when these devices are implanted, and these procedures are irreversible. Although uncommon, mechanical breakdown can occur, or the device can slip or bulge, especially if the patient coughs or vomits vigorously after the operation. In addition, a less than optimal quality of erection may result. (Using the MUSE system may restore or improve the function of a penile prosthesis in patients with a failed device.)

Complications. Infection is the major concern with these devices. Redness and fever often accompany a full-blown infection. Any intermittent pain that continues to occur after an implant may be an indicator of a low-grade infection. If the infection can be caught early enough, implant failure can be prevented. Most infections are treated with antibiotics for at least 10 - 12 weeks. If antibiotics fail, a surgical exchange, in which the infected implant is simultaneously replaced with a new one, should be considered. This is a complex procedure, but some surgeons have reported a 90% success rate.

Vascular Surgery

For men whose impotence is caused by damage to the arteries or blood vessels, vascular surgery might be an option. Two types of operations are available: revascularization (bypass) surgery, and venous ligation. The American Urologic Association stresses that vascular surgery is still investigational.

Revascularization. The revascularization procedure usually involves taking an artery from a leg and then surgically connecting it to the arteries at the back of the penis, bypassing the blockages and restoring blood flow. In a related procedure called deep dorsal vein arterialization, a penile vein is used for the bypass. Young men with local sites of arterial blockage or those with pelvic injuries generally achieve the best results. In studies of selected patients erectile function improved in 50 - 75% of men after 5 years.

Venous Ligation. Venous ligation is performed when the penis is unable to store a sufficient amount of blood to maintain an erection. This operation ties off or removes veins that are causing an excessive amount of blood to drain from the erection chambers. The success rate is estimated at 40 - 50% initially, but drops to 15% over the long term. It is important to find an experienced surgeon. In a variation of this technique, called venous ablation, ethanol is injected into the deep dorsal vein, the main vein that drains blood from the penis. The ethanol causes scarring that closes off smaller veins and prevents blood leakage, thereby bolstering erectile function.

Natural Remedies

Herbs and Supplements

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any herbal remedies or dietary supplements.

There are several special concerns for people taking alternative remedies for erectile dysfunction.

Yohimbe. Yohimbe, which is similar to yohimbine, is derived from the bark of a West African tree. Side effects include nausea, insomnia, nervousness, and dizziness. Large doses of yohimbe can increase blood pressure and heart rate and may cause kidney failure.

Gamma-Butyrolactone (GBL). GBL is found in products marketed for improving sexual function (Verve, Jolt). This substance can convert to a chemical that can cause toxic and life-threatening effects, including seizures and even coma.

Gingko. Although the risks for gingko appear to be low, there is an increased risk for bleeding at high doses and interaction with vitamin E, anti-clotting medications, and aspirin and other NSAIDs. Large doses can cause convulsions. Commercial gingko preparations have also been reported to contain colchicine, a substance that can be harmful in people with kidney or liver problems.

L-arginine (also called arginine). Arginine may cause gastrointestinal problems. It can also lower blood pressure and change levels of certain chemicals and electrolytes in the body. It may increase the risk for bleeding. Some people have an allergic reaction to it, which in some cases may be severe. It may worsen asthma.

Dehydroepiandrosterone (DHEA). DHEA is a supplement related to certain male and female hormones. Studies show inconclusive results in its treatment for erectile dysfunction. DHEA may interact dangerously with other medications.

Aphrodisiacs. Aphrodisiacs are substances that are supposed to increase sexual drive, performance, or desire. Examples include:

• Viramax is a well-marketed product that contains yohimbine and three herbal aphrodisiacs: catuaba, muira puama, and maca. It has not been proven to be either effective or safe, and interactions with medications are unknown.
• Spanish fly, or cantharides, which is made from dried beetles, is the most widely-touted aphrodisiac but can be particularly harmful. It irritates the urinary and genital tract and can cause infection, scarring, and burning of the mouth and throat. In some cases, it can be life threatening. No one should try any aphrodisiac without consulting a doctor.

Other Alternative Products Marketed for Erectile Dysfunction. Vinarol is an over-the-counter supplement that was recalled by the FDA in 2003 after reports surfaced that it contained the same ingredients found in Viagra. Herbal supplements sold as Viagro and Vaegra have no association with Viagra.

There are numerous other products marketed as “all-natural” dietary supplements and promoted as treatments for erectile dysfunction and sexual enhancement. The FDA has not approved any of these products and has issued many warnings concerning them. In recent years, the FDA has warned that “True Man,” “Energy Max,” “Rhino Max,” “VMax,” Libidus,” and similar dietary supplements contain illegal chemicals that can interact with prescription drugs and cause dangerously low blood pressure. These products are particularly dangerous for men with diabetes, high blood pressure, high cholesterol, or heart disease who take prescription drugs that contain nitrates.

Resources

• www.niddk.nih.gov -- National Kidney and Urologic Diseases Information
• www.auanet.org -- American Urologic Association
• www.urologyhealth.org -- Urology Health

References

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Boloña ER, Uraga MV, Haddad RM, Tracz MJ, Sideras K, Kennedy CC, et al. Testosterone use in men with sexual dysfunction: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc. 2007 Jan;82(1):20-8.

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McVary, K. T.. Clinical practice. Erectile dysfunction. N Engl J Med. 2007 Dec; 357(24): 2472-81.

Melnik T, Soares BG, Nasselo AG. Psychosocial interventions for erectile dysfunction. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004825.

Miles CL, Candy B, Jones L, Williams R, Tookman A, King M. Interventions for sexual dysfunction following treatments for cancer. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005540.

Müller A, Mulhall JP. Cardiovascular disease, metabolic syndrome and erectile dysfunction. Curr Opin Urol. 2006 Nov;16(6):435-43.

Saad F, Grahl AS, Aversa A, Yassin AA, Kadioglu A, Moncada I, et al. Effects of testosterone on erectile function: implications for the therapy of erectile dysfunction. BJU Int. 2007 May;99(5):988-92. Epub 2007 Feb 19.

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