Erectile dysfunction - InDepth

An in-depth report on the causes, diagnosis, treatment, and prevention of erectile dysfunction.

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Highlights

Erectile Dysfunction

Erectile dysfunction (ED), formerly 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 ED. However, if the problem becomes chronic, it can have adverse effects on relationships, emotional health, and self-esteem.

ED can be a symptom of an underlying health condition. If ED becomes an on-going problem, it is important to talk to your doctor.

Causes of Erectile Dysfunction

• Physical causes are the main reasons for ED. They include atherosclerosis (which also causes heart disease and peripheral artery disease), high blood pressure, diabetes, neurological disorders, medication side effects, prostate surgery, radiation treatment to the pelvis, and other health conditions.
• Psychological causes of ED include anxiety, depression, stress, and problems in relationships.
• Lifestyle factors that increase risk for ED include smoking, alcohol use, illicit drug use and other substance abuse.

Phosphodiesterase-5 (PDE5) Inhibitors

ED is usually treated with a PDE5 inhibitor drug such as:

• Sildenafil (Viagra)
• Vardenafil (Levitra, Staxyn)
• Tadalafil (Cialis)
• Avanafil (Stendra)

These drugs are generally safe and effective for most men. They may not be appropriate for men with certain health conditions, such as severe heart disease, heart failure, uncontrolled high blood pressure, diabetes, or a history of stroke or heart attack. Men who take nitrate drugs cannot use PDE5 inhibitors. PDE5 inhibitors can also interact with other medications. Talk to your doctor about whether PDE5 inhibitor drugs are a safe choice for you.

Other Treatments

Other treatments for ED include:

• Alprostadil injections or suppositories
• Injections into penis of a combination of other medications
• Testosterone replacement therapy (for men with low testosterone levels)
• Vacuum erection devices
• Penile implants
• Vascular surgical procedures

It is very important to treat any underlying health conditions that may be causing ED. It is also important to engage in healthy lifestyle behaviors by eating right, staying physically active, reducing stress, and stopping smoking and substance abuse.

Testosterone Products: Safety Risks

The FDA has issued a warning that testosterone products may increase the risk for heart attack, stroke, and death from cardiovascular causes. The FDA has also required that all testosterone products' labels include information on increased risk for blood clots in the veins. These products can have other serious health risks as well.

Testosterone products are approved to treat men who have hypogonadism (low testosterone levels). ED can be one of the symptoms of low testosterone. However, it is not clear if these products are helpful for ED in men who have hypogonadism. They should not be prescribed to men who have normal testosterone levels. Doctors are concerned that these products are being overprescribed due to increased advertising, and not medical need.

Introduction

Erectile dysfunction (formerly called impotence) is the inability to achieve or maintain an erection that is sufficiently rigid for sexual intercourse. Sexual drive and the ability to have an orgasm are not necessarily affected. Because all men have erection problems from time to time, doctors diagnose erectile dysfunction if a man fails to maintain an erection satisfactory for intercourse on at least 25% of attempts. Worldwide, erectile dysfunction occurs in close to 20% of men.

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

The Penis and Erectile Function

The Structure of the Penis

The penis is composed of the following structures:

• Two outer parallel columns of spongy tissue called the corpora cavernosa, or erectile bodies.
• A central spongy chamber called the corpus spongiosum, which contains the urethra, the tube that carries urine as well as sperm through the penis. The corpus spongiosum ends in an expansion called glans penis, which contains the opening of the urethra.

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 tissue composed of a protein called elastin.

Erectile Function and Nitric Oxide (NO)

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 muscle tissues surrounding the many tiny blood vessels inside the corpus cavernosum also stay contracted, keeping the vessels narrowed and limiting the amount of blood that can collect in the penis.

During erection the following occurs:

• The man's central nervous system stimulates the release of a number of chemicals, including nitric oxide, which is essential for producing and maintaining erection. Nitric oxide is produced from L-arginine by an enzyme called nitric oxide synthase.
• 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 increase in blood flow nearly doubles the diameter of the spongy chambers of the cavernosum and spongiosum.
• The veins surrounding the chambers are squeezed almost completely shut against the rigid walls of the penis by this increase in pressure.
• The veins are unable to drain blood out of the penis and so the penis becomes rigid and erect.
• After ejaculation, cyclic GMP is broken down by an enzyme called phosphodiesterase-5 (PDE5), causing the penis to become flaccid (unerect) again.

Other 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. However, excessive amounts of collagen can form scar tissue, which can impair erectile function.

Oxygen

Oxygen-rich blood is one of the most important components for erectile health. Oxygen levels vary widely from very low levels in the flaccid state to very high levels in the erect state. During sleep, a man can normally have 3 to 5 erections per night, bringing oxygen-rich blood to the penis. The primary cause of oxygen deprivation is ischemia, or the blockage of blood vessels. Blood flow-reducing conditions that lead to heart disease, such as atherosclerosis, may also contribute to ED.

Calcium

Calcium is an essential ion for the normal contraction and relaxation of smooth muscle tissues which regulate blood flow in the corpus cavernosum.

Testosterone and Other Hormones

Normal levels of hormones, especially testosterone, are essential for libido (sex drive) and erectile function, although their exact role is not clear.

Causes

Over the past decades, the medical perspective on the causes of erectile dysfunction (ED) has shifted. Doctors used to think that almost all cases of ED were related to psychological factors. Now doctors believe that up to 85% of ED cases are caused by medical or physical problems. Only around 15% cases of ED are due to psychological factors. Sometimes, ED is due to a combination of physical and psychological causes.

In general, psychologically-based ED is more likely to develop suddenly with complete, immediate loss of function. This problem may be present most of the time or only in certain situations. These men will often still have erections upon awakening.

ED from organic or medical causes occurs gradually over time and progressively becomes worse. ED is present with most or all sexual interactions and these men either lack an erection upon awakening, or have poor erections.

A number of medical conditions share a common problem with ED, such as the impaired ability of blood vessels to open and allow normal blood flow.

Heart Disease, Atherosclerosis, and High Blood Pressure

Heart disease, atherosclerosis, high blood pressure, and high cholesterol levels are major risk factors for ED. Peripheral artery disease (PAD), a form of atherosclerosis, is very common in men who have ED. In fact, erectile problems may be a warning sign of these conditions in men at risk for atherosclerosis. Men who experience ED due to vascular causes have a greater risk for angina, (chest pain due to low oxygen levels in the blood), heart attack, and stroke.

ED is also a very common problem in men with high blood pressure. Many of the drugs used to treat hypertension (diuretics, calcium channel blockers, and beta-blockers) may also cause ED.

Diabetes

Diabetes is a major risk factor for ED. Damage to blood vessels and nerves is a common complication of diabetes. When the blood vessels or nerves of the penis are involved, ED can result. Diabetes is also associated with heart disease and chronic kidney disease, which are other risk factors for ED.

Obesity

Obesity increases the risk for diabetes, heart disease, and ED.

Metabolic Syndrome

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

Benign Prostatic Hyperplasia

There appears to be a relationship between ED and the lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH or "enlarged prostate"). Men who have one condition often have the other. Both conditions share common risk factors including older age, high blood pressure, and diabetes. In addition, surgical and drug treatments for BPH can increase the risk for ED.

Neurologic Conditions

Neurologic diseases, such as Parkinson disease, multiple sclerosis, and stroke, can cause ED.

Endocrinologic and Hormonal Conditions

Endocrinologic conditions include diseases or conditions that involve abnormalities of the glands and hormonal imbalance. Hypogonadism, known informally as "low T," is a medical condition that results from low levels of the male hormone testosterone (androgen deficiency). Symptoms of hypogonadism can include reduced sexual desire (low libido) and ED.

However, low testosterone as the sole cause of ED likely affects only a small percentage of men. Hypogonadism is also associated with very small or shrinking testicles, loss of muscle mass, increased body fat, reduced bone density, fatigue, anemia, and declining sperm production. Many men with hypogonadism are infertile.

Hypogonadism is classified as either primary or secondary. Primary hypogonadism is caused by diseases or defects in the testicles that affect the production of testosterone. Secondary hypogonadism is due to problems in the hypothalamus or pituitary gland that cause high levels of the hormone prolactin. Hypothalamus and pituitary abnormalities also cause low levels of other hormones such as follicle-stimulating hormone and luteinizing hormone. These hormonal imbalances can result in low libido and ED.

Other hormonal and endocrinologic causes of ED include thyroid and adrenal gland problems.

Physical Trauma and Injury

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

Surgery

Certain types of surgery and radiation treatments can increase the risk for erectile dysfunction:

• Surgery for Prostate Diseases. Radical prostatectomy for prostate cancer is a common cause of ED. Nerve-sparing techniques can help reduce the loss of sexual function. Radiation treatments for prostate cancer also cause ED. Some surgical treatments for benign prostatic hyperplasia (BPH) can also cause ED, but this complication is relatively uncommon.
• Surgery for Colon and Rectal Cancers. Surgical and radiation treatments for colorectal cancers may cause ED.
• Fistula Surgery. Surgery to repair anal fistulas can affect the muscles that control the rectum (external anal sphincter muscles), sometimes causing ED. (Repair of these muscles may restore erectile function.)
• Orthopedic Surgery. ED can sometimes result from orthopedic surgery that affects pelvic nerves.

Note: Vasectomy does NOT cause ED.

Medications

ED can be a side effect of certain medications. They include:

• High blood pressure medications, particularly diuretics, beta-blockers, and calcium-channel blockers.
• Heart or cholesterol medications, such as digoxin, gemfibrozil, or clofibrate.
• Finasteride (Proscar) and dutasteride (Avodart), which are used to treat BPH. A lower-dose form of finasteride (Propecia), which is used to treat male pattern baldness, may also cause ED. ED may persist even after these medications are stopped.
• Medications 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 ED.
• Gastroesophageal reflux disorder (GERD) medications, used to reduce stomach acid, such as ranitidine (Zantac) and cimetidine (Tagamet).
• Hormone drugs, such as estrogens, corticosteroids, and 5-alpha reductase inhibitors.
• Chemotherapy drugs, such as methotrexate.
• Morphine and opioid drugs.

Psychological Causes

Anxiety

Anxiety has both emotional and physical consequences that can affect erectile function. It is among the most frequently cited contributors to psychological ED.

Stress

Stress, whether caused by major life events, daily hassles, or health problems, can affect sexual function. Post-traumatic stress disorder (PTSD), a mental condition caused by exposure to traumatic events, is strongly associated with ED.

Depression

Depression can reduce sexual desire and is associated with ED.

Relationship Problems

Troubles in relationships often have a direct impact on sexual function.

Risk Factors

Age

For most men, ED is primarily associated with older age. However, ED is not inevitable with age. Severe ED often has more to do with age-related 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 causes of ED.

Lifestyle Factors

Smoking

Smoking contributes to the development of ED, mainly because it increases the effects of other blood vessel disorders, including high blood pressure and atherosclerosis. Smokers have an increased risk for ED compared with non-smokers. ED is more likely in those who smoke for longer periods of time or who are heavier smokers. In turn, quitting smoking can reduce this risk.

Alcohol Use

Heavy drinking can cause ED. Alcohol depresses the central nervous system and impairs sexual function.

Drug Abuse

Heroin, cocaine, methamphetamines, and marijuana can affect sexual function. Opioid use is associated with the development of erectile dysfunction.

Weight and Sedentary Lifestyle

Obesity is a risk factor for ED. Lack of exercise and a sedentary lifestyle can lead to obesity and other health problems associated with ED.

Diagnosis

Your doctor will ask about various physical and psychological factors that may be causing ED. The doctor will also perform a physical exam.

Medical History

The doctor will ask about:

• Past and present medical conditions, surgeries, and medications
• Any history of psychological problems, including stress, anxiety, or depression
• Lifestyle factors, such as alcohol, drug, and dietary supplement use

In addition, the doctor will ask about your sexual history, which may include:

• When problems with sexual function began
• The frequency, quality, and duration of any erections, including erections that occur during sleep or on awakening in the morning
• The specific circumstances when erectile dysfunction occurs
• Details of sexual technique
• Whether problems exist in the current relationship

If appropriate, the doctor may also interview your sexual partner.

Physical Examination

The doctor will perform a physical exam, including examination of the genitals and a digital rectal examination (the doctor inserts a gloved and lubricated finger into the person's rectum) to check for prostate abnormalities. The doctor will also examine your breasts and thyroid gland. The doctor should check your blood pressure and evaluate your blood circulation by checking the pulses in your legs.

Laboratory Tests

Because ED and atherosclerosis are often linked, it is important to check cholesterol levels. Similarly, the doctor may order tests for blood sugar (glucose) levels to check if diabetes is a factor. A blood test to measure total serum testosterone is usually done. This test should be done in the morning.

If your test indicates low testosterone, the doctor should retest to confirm the results. Other tests that measure hormone level involved in the brain and body's production of testosterone may be needed if testosterone levels are low. A diagnosis of hypogonadism requires clinical signs and symptoms associated with the condition in addition to low testosterone levels in the blood.

The doctor may also test for thyroid and adrenal gland dysfunction. For more sophisticated tests, the doctor may refer you to specialist such as an urologist or endocrinologist.

A number of tests are available that can help identify the cause. However, unless the presenting symptoms and findings are unusual or complex, this type of testing is not required or useful for most people. Some tests with more supportive evidence behind them include:

• Dynamic infusion cavernosometry and cavernosography (DICC)
• Intracavernous injection pharmacotesting (ICI)
• Color duplex ultrasound
• Nocturnal penile tumescence and rigidity (NPTR)
• Bulbocavernosus reflex latency
• Measurement of calculated bioavailable testosterone (free testosterone and albumin-bound testosterone)
• Psychologic evaluation and possible interview with partner

Treatment

Many physical and psychological situations can cause ED, and brief periods of ED are normal. Every man experiences ED from time to time. Nevertheless, if the problem persists, men should seek professional help, particularly since ED is usually treatable and may also be a symptom of an underlying health problem. It is important to treat any medical condition that may be causing ED.

Overall treatment approach includes:

• Education of patient and partner, if available.
• Evaluation of possible lifestyle factors such as smoking, alcohol, or other substance use.
• Management of comorbid illnesses, such as diabetes, obesity, or heart and vascular disease.
• Review of potential changes in medications - always consult with your physician.
• If appropriate, trial of various psychosexual therapies and interpersonal therapies may be tried. Treatments can be provided along with these therapies.

Before treatment, men with ED should be assessed for their risk for cardiovascular disease. Men found to be at high risk include those with angina, recent history of heart attack, certain abnormal heart rhythms, and poorly controlled high blood pressure. These men should be evaluated and treated first before a trial of therapy for ED. Any risk factors for heart disease should be addressed in all men.

Treatment Choices

Drug therapy with oral PDE5 inhibitors is the main treatment for ED. Sildenafil (Viagra), vardenafil (Levitra, Staxyn), tadalafil (Cialis), and avanafil (Stendra) are the PDE5 inhibitor drugs approved for treating ED. In general, if a man is a candidate for PDE5 inhibitor therapy and is satisfied with the results, no further treatment is necessary.

PDE5 inhibitors are not safe or effective for all men. Men who cannot or choose not to take the drugs may have other options, including:

• Medications inserted or injected into the penis
• Vacuum devices
• Surgery (limited to rare cases)

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.

Psychotherapy

Some form of psychological, behavioral, or sexual therapy may be recommended for certain men.

Lifestyle Changes

No matter what the treatment, a healthy lifestyle is important for restoring and maintaining erectile function. This includes a heart-healthy diet, regular exercise, and engaging in activities that help reduce stress.

Oral Medications (PDE5 Inhibitors)

PDE5 inhibitor drugs are generally the first choice of treatment for ED. They are:

• Sildenafil (Viagra)
• Vardenafil (Levitra, Staxyn)
• Tadalafil (Cialis)
• Avanafil (Stendra)

All of these drugs are known as phosphodiesterase-5 (PDE5) inhibitors and are approved for treatment of ED. By blocking the PDE-5 enzyme, these drugs stop degradation of the cyclic GMP molecule, which keeps the smooth muscle relaxed, helping arteries widen and increase blood flow and improving erection.

PDE5 inhibitor drugs come in pill form and are taken by mouth. Vardenafil is available as a standard pill (Levitra) or as a quickly dissolving tablet (Staxyn).

These medicines augment an erection but do not actually induce the erectile response.

These drugs all work equally well. A doctor usually selects one of the brands based on the person's individual preference, ease of use, and cost of medication.

Candidates for PDE5 Inhibitors

PDE5 inhibitors are a good choice for men of any age who are in good health and who do not have conditions that prevent taking them.

However, PDE5 inhibitors are not suitable for everyone. Men who take nitrate drugs for angina cannot take PDE5 inhibitors. The PDE5 inhibitors are less effective in men with diabetes and in men who have been treated for prostate cancer. Men who take certain alpha-blockers for high blood pressure or benign prostatic hyperplasia (BPH) should take PDE5 inhibitors with extra care if at all. Tadalafil (Cialis) is approved to treat symptoms of enlarged prostate in men who have both BPH and erectile dysfunction.

Men with the following conditions should not take PDE5 inhibitors:

• Heart problems, including chest pain (angina), irregular heartbeat (arrhythmias), or heart failure.
• Recent history of heart attack or stroke.
• High or low blood pressure (hypertension or hypotension).
• Uncontrolled diabetes.
• Liver or kidney problems.
• Blood cell problems (sickle cell anemia and leukemia).
• Retinitis pigmentosa. With this genetic disease, people do not produce PDE5 enzyme and do not respond to PDE5 inhibitors.

Administration and Effect

PDE5 inhibitors work only when the man experiences some sexual arousal. The pill should be taken about 1 hour before sexual intercourse. It generally starts to work within 10 to 30 minutes. The availability of these drugs may last for several hours in the bloodstream, and tadalafil may last for up to 36 hours. The erection should not last for more than 4 hours. If it does, it becomes an emergency (called priapism) and men should seek medical attention.

Do not take more than one pill a day. Sildenafil should be taken on an empty stomach. Vardenafil, tadalafil, and avanafil may be taken with or without food.

Success rates increase with the number of attempts, so don't be discouraged if the drug does not work at first.

PDE5 inhibitors are also sometimes used in combination with testosterone replacement therapy for men with hypogonadism (low testosterone levels). Some research indicates that the addition of testosterone provides little benefit.

As described above, these drugs are primarily used to induce an erection. Some have proposed taking these drugs in a regularly scheduled manner after prostate surgery in the hope of helping recovery of erectile function. However, this method has not been proven in randomized controlled trials.

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 PDE5 inhibitors. These medications can cause sudden and dangerous drops in blood pressure when the drug is taken with nitrate drugs, which are used for angina. Common nitrate drugs include nitroglycerine (Nitrostat), isosorbide mononitrate (Monoket), isosorbide dinitrate (Dilartrate-SR), and sodium nitroprusside (Nitropress). Men who use nitrates, including related substances such as amyl nitrate ("poppers"), should never take sildenafil, vardenafil, tadalafil, or avanafil.

Sexual intercourse itself involves an increase in physical exertion and a very small risk for heart attack for people with heart disease or heart disease risk factors. If you have heart disease or have recently had a heart attack, talk with your doctor about whether you can safely have sex.

Visual Effects

In rare cases, men who take these drugs develop vision problems that include seeing a blue haze, temporary increased brightness, and even temporary vision loss in a few cases. The effect is usually temporary, lasting a few minutes to several hours. Men at risk for eye problems who take PDE5 inhibitors should have regular eye examinations with an ophthalmologist. Men should also see an eye doctor if visual problems last more than a few hours.

In a few cases, these drugs have been associated with partial vision loss. The vision loss is caused by non-arteritic anterior ischemic optic neuropathy (NAION), a condition that occurs from poor blood flow to optic nerves. However, ED is itself linked to the same vascular problems that cause NAION. Men who have diabetes, high blood pressure, and heart disease are at higher risk for ED as well as other vascular problems such as NAION. Although the risk of blindness appears small, men who experience a sudden loss of vision should immediately stop taking the drug and contact their doctor.

Hearing Loss

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.

Priapism

Priapism is sustained, painful, and unwanted erection that lasts for longer than 4 hours. PDE5 inhibitors pose a very low risk for priapism in most men with the exception of young men with normal erectile function. Priapism is an emergency situation that requires prompt treatment to prevent permanent damage to the penis.

Drug Interactions

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, generic). Inform your doctor about all medications you take.

Other Concerns

Some preliminary research suggested that men who take sildenafil may be at increased risk for developing skin cancer (melanoma). A more recent review of data does not support sildenafil as a cause for melanoma. Men who have had melanoma or are at risk for it should discuss this issue with their doctors.

Injections and Topical Treatments

Treatments Using Alprostadil

Alprostadil is derived from a natural substance, prostaglandin E1, which opens (relaxes) blood vessels. This medicine is an effective treatment for many men with ED. It can be administered by:

• Injection into the erectile tissue of the penis (Caverject or Edex)
• Suppository pellets placed in the urethra through an applicator (MUSE system)

Alprostadil is not an appropriate choice for men with:

• Penile implants or abnormally shaped penis
• Blood cell conditions that may cause priapism (abnormally long-lasting erections) such as sickle cell anemia, leukemia, or multiple myeloma
• Bleeding abnormalities or the use of medications that thin the blood, such as heparin or warfarin

Injected Alprostadil

Injected alprostadil (Caverject, Edex) is delivered through a very small needle that the man inserts into the erectile tissue of his penis. Although this treatment is very effective, some men find the injections to be painful or uncomfortable.

The drug should not be injected more than 3 times a week and no more than once within 24-hour period.

Suppository Alprostadil

The MUSE system delivers alprostadil with a device inserted through the urethra using suppository pellets. The device is a thin applicator tube with a button at the top. It works in the following way:

• You insert the tube into your urethral opening right after urination. (Urinating or urine leakage immediately after administration may reduce the amount of medication.)
• Press the button to release a pellet containing alprostadil.
• Roll your penis between your hands for 10 to 30 seconds to evenly distribute the drug. To avoid discomfort, keep your penis as straight as possible during administration.
• Stay upright (sitting, standing or walking) for about 10 minutes after administration. By that time, you should have achieved an erection that lasts 30 to 60 minutes. (If you lie on your 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 alprostadil administration, although they may differ in severity depending on how the drug is given:

• Pain and burning at the application site.
• Scarring of the penis (Peyronie disease), which is most likely to occur with injections.
• Sudden, low blood pressure. Symptoms include dizziness, lightheadedness, and fainting. If these symptoms occur, lie down immediately with your legs raised.
• Priapism (prolonged erection). Possible with any method, but less likely 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. For the suppository form of alprostadil, a condom must be used with a pregnant woman to help protect the fetus from the drug.
• Other side effects may include minor bleeding or spotting, redness in the penis, and aching in the testicles, legs, and area around the anus.

Other Injectable Treatments

Your doctor may prescribe another injectable option made up of a combination of 3 or 4 other medications including papaverine, phentolamine mesylate, prostaglandin E1, and atropine sulfate. Side effects and precautions are similar to those of alprostadil. This treatment is usually ordered through a compounding pharmacy.

Testosterone Replacement Therapy

Studies have been inconclusive as to whether testosterone replacement therapy is helpful for men with ED. Men with hypogonadism (low testosterone levels and impaired sperm production or function) may benefit, but men who have ED and normal testosterone levels are not likely to benefit from testosterone therapy. Before considering testosterone therapy, men should be sure that their hormone levels have been measured correctly and accurately and found to be low on at least two separate occasions.

Men should be wary of advertising that pushes testosterone replacement therapy for "low T," an informal term for low testosterone that many doctors regard with skepticism. Testosterone levels decrease with aging and there is no scientific consensus on what testosterone levels constitute "low T". Furthermore, male hypogonadism is a condition that involves more than simply low testosterone levels.

There is also no definitive evidence that testosterone treatment helps improve symptoms such as sexual function in men who have low testosterone levels. While the benefits of testosterone treatment are unclear, there is proven evidence of potential health risks. If you are considering testosterone replacement therapy, be sure to discuss with your doctor all of its possible risks and benefits.

Forms of testosterone therapy include:

• Implanted pellets. Subcutaneous pellets (Testopel) are surgically implanted under the skin and slowly release testosterone for 3 to 4 months. Implanted pellets have less flexibility for dosing adjustment and require surgical removal if testosterone therapy needs to be stopped.
• Injections. Muscle injections using testosterone enanthate (Andryl or Delatestryl), cypionate (Andro-Cyp, Depo-Testosterone, or Virion), or undecanoate (Aveed).
• Skin patches (Testoderm, Testoderm TTS, and Androderm). Depending on the brand, patches may be applied daily to the skin of the scrotum or to the abdomen, back, thighs, or upper arm.
• Skin gel (Androgel, Fortesta, or Testim). The gel is applied only to the shoulders, upper arms, or abdomen, not directly to the penis. It is extremely important that men thoroughly wash their hands with soap and water after applying the gel, and cover the application site with clothing once it dries. Testosterone gel can cause serious side effects (premature development and genital enlargement) in children who come in contact with it through secondary exposure. Pregnant women must avoid contact with the gel because the testosterone can harm the fetus.
• Nasal spray. Testosterone nasal gel (Natesto) is approved for treatment of hypogonadism. It uses a metered-dose pump and the drug is inhaled through the nose.
• Buccal tablet. Some testosterone products (Striant) are administered as tablets that are applied to the gums and kept in the mouth, where they release testosterone over a period of hours.
• Oral forms of testosterone are available, but generally not recommended because of the risk for liver damage when taken for long periods of time.

Side effects may include acne, breast enlargement or soreness, high blood pressure, and mood swings. Testosterone therapy can also increase cholesterol levels, prostate specific antigen (PSA) levels, red blood cell count. If you take testosterone therapy, your doctor should monitor your cholesterol, PSA, and hematocrit (red blood cell) levels, and liver function.

Serum testosterone levels should be followed during treatment. An initial 3 months trial is most often recommended. Prostate specific antigen testing or PSA (for prostate cancer) must be done before treatment and periodically after that. Liver functions test and lipid profiles should also be monitored.

Testosterone therapy may increase the risk for the following serious side effects:

• Breast and prostate cancers. Testosterone should not be used by men who have breast cancer, or who have or are at risk for prostate cancer. (It can cause rapid growth of prostate tumors in men with existing prostate cancers.)
• Development or worsening of urinary symptoms associated with benign prostatic hyperplasia (BPH), or enlargement of the prostate gland.
• Heart attack, stroke, and death from cardiovascular disease. The FDA is currently reviewing the cardiovascular risks of all testosterone products. They have issued a warning that testosterone therapy may increase the risk for these events - www.fda.gov/Drugs/DrugSafety/ucm436259.htm.
• Blood clots in the veins (venous thromboembolism), which can result from abnormal increases in red blood cell count. The FDA has added a warning about this risk to all testosterone products' labels.
• Swelling of the ankles, feet, or body due to edema (water retention). This is especially dangerous for men who have heart, kidney, or liver disease.
• Worsening of sleep apnea.
• Reduced sperm count and infertility with high amounts of testosterone.

Surgery and Devices

Vacuum Erection Devices

Vacuum erection devices, also called vacuum constriction devices, are another option for men with ED. They are available without prescription and have a high success rate, but are cumbersome and may be difficult to use for some men. They typically work as follows:

• The man places his penis inside a plastic cylinder.
• A vacuum is created, which causes blood to flow into the penis, thereby creating an erection.
• Once an erection is achieved, the man places an elastic ring around the base of the penis to retain the erection. The ring should remain in place for no more than 30 minutes.

Lack of spontaneity is the major drawback to this method. There are few side effects.

Penile Implants

Penile implants are an option for men who cannot take medication or have not been helped by less invasive treatments. In general, implants work well in restoring sexual function, and men are usually satisfied with the results.

Two types of surgical implants are used for the treatment of ED:

• A hydraulic implant consists of a pump, reservoir, and two cylinders placed within the erection chambers of the penis. The pump releases a saline solution from the reservoir to the chambers to cause an erection and later removes the solution to deflate the erection. There is also a model that only has the pump and two cylinders.
• 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 unerect position.

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. In addition, a less than optimal quality of erection may result. The erection achieved with these implants is often not as wide or as long as a natural erection. Infection is a rare, but serious, complication.

Vascular Surgery

In rare cases, penile vascular surgery may be considered as treatment for ED. Two types of operations are most commonly performed:

• Revascularization (bypass) surgery
• Venous ligation

These surgeries may be tried where there is clear evidence of narrowing of the blood supply to the penis. The ideal candidates who are felt most likely to benefit from this type of surgery are younger men with no cardiovascular disease and isolated narrowing of an artery supplying the penis usually caused by pelvic trauma.

According to the American Urological Association, men who smoke or who have the following conditions are not candidates for penile vascular surgeries:

• Insulin-dependent diabetes
• Widespread atherosclerosis
• Consistently high blood cholesterol levels
• Injured nerves or damaged blood vessels

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. Penile arterial revascularization is mainly used for young men (under age 45) who have blood vessel injury caused by events such as blunt trauma or pelvic fracture. This type of surgery is rarely done.

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. Long-term success rates for this procedure are less than 50 percent.

Arterial Stents

Doctors are investigating the use of drug-coated stents (similar to those used in angioplasty for heart blockages) for treating ED in men who have not been helped by drug therapy. The stents are tiny, expandable metal mesh tubes that are implanted in an artery that provides blood flow to the penis. Only men with specific types of blood flow blockages caused by atherosclerosis are candidates for this procedure. These stents are currently only being studied in clinical trials. They have not yet been approved for ED treatment.

Low Intensity Extracorporeal Shock Wave Treatment (LI-ESWT)

A recent non-invasive treatment method using shock waves is under investigation as a novel ED therapy. This method is based on the idea that a type of acoustic waves focused on an organ can release molecules and help blood supply of that organ function better. Studies using LI-ESWT for ED had mixed results, and more research is needed.

Lifestyle Changes

Because many cases of ED are due to reduced blood flow from blocked arteries, it is important to maintain the same healthy lifestyle habits used to prevent heart disease.

Diet and Exercise

Diet

Eat a heart-healthy diet rich in fresh fruits and vegetables, whole grains, and fiber and low in saturated fats and sodium. Because ED is generally 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 evidence exists for these claims.

Weight Control

Being overweight can contribute to ED. Try to achieve and maintain a healthy weight.

Exercise

Regular exercise is helpful for weight control, stress reduction, and a healthy heart.

Alcohol and Smoking

If you drink alcohol, do so in moderation. Alcohol abuse can contribute to ED. Smoking is clearly correlated with ED. Quitting smoking is essential.

Stay Sexually Active

Staying sexually active may help prevent ED. Frequent erections stimulate blood flow to the penis.

Change or Reduce Medications

If medications are causing ED, discuss with your doctor whether to change to a different medication or reduce the dosage.

Psychotherapy and Behavioral Therapy

Even if ED is caused by a physical problem, interpersonal, supportive, or behavioral therapy are often helpful for men and their partners.

Warning on the Use of Herbs and Supplements

Manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Such products can be sold without any proof of efficacy or safety. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce harmful side effects. There have been a number of reported cases of serious and even lethal side effects from these products. You should always check with your doctor before using any herbal remedies or dietary supplements.

There is no evidence that any herbal product, vitamin, or dietary supplement can improve erections or sexual performance in men or women. Despite this, many herbs and dietary supplements are marketed as aphrodisiacs. Aphrodisiacs are substances that are claimed to increase sexual drive, performance, or desire. Recently, the FDA has warned that several products being sold over the counter as aphrodisiac supplements actually contain hidden ingredients, such as varying amounts of prescription PDE-5 inhibitors, and are not safe for use. There are several specific concerns for people taking alternative remedies for ED.

Yohimbe

Yohimbe 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. However, yohimbe has not been shown to be any better than placebo for enabling sexual intercourse.

Viramax is a commercial product that contains yohimbine, the active chemical ingredient of yohimbe, and three other herbs: catuaba, muira puama, and maca. It has not been proven to be either effective or safe, and interactions with medications are unknown.

Gamma-Butyrolactone (GBL)

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

Gingko Biloba

Although the risks for gingko biloba 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 precursor hormone to male and female sex hormones. DHEA from soy or yam is sold as a supplement. Studies show inconclusive results in its treatment for ED. DHEA may interact dangerously with other medications.

Spanish Fly

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 Dietary Supplements Marketed for ED

There are numerous products marketed as "all-natural" dietary supplements and promoted as treatments for ED and sexual enhancement. The FDA has not approved any of these products. In recent years, the FDA has banned many of these dietary supplements and warns that they contain the same or similar chemical ingredients used in PDE5 inhibitor prescription drugs.

Resources

• National Institute of Diabetes and Digestive and Kidney Diseases -- www.niddk.nih.gov
• American Urological Association -- www.auanet.org
• Urology Care Foundation -- www.urologyhealth.org

Related Reports

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Review Date: 2/27/2020  

Reviewed By: Sovrin M. Shah, MD, Assistant Professor, Department of Urology, The Icahn School of Medicine at Mount Sinai, New York, NY. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.

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