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  Impotence (Erectile dysfunction)HighlightsFDA Warns about Dietary Supplements In 2006 and 2007, the FDA issued numerous warnings about “natural” dietary supplements promoted for erectile dysfunction and sexual enhancement. These products -- marketed under names such as “True Man,” “Energy Max,” “Rhino Max”-- contain illegal substances that can interact with prescription drugs and dangerously lower blood pressure. The interaction risks are greatest for men with diabetes, high blood pressure, high cholesterol, or heart disease who take prescription drugs that contain nitrates. The FDA has not approved any of these products and warns that consumers should not buy or use them. Viagra and Similar Drugs Safe for Men with Diabetes Phosphodiesterase inhibitors (PDE-5 inhibitors) are generally safe and often effective for men with diabetes, at least in the short term, according to a 2007 review published in the Cochrane Database. However, there is not enough evidence to determine if these drugs are safe for men with diabetes if used on a long-term basis. PDE-5 inhibitors include sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). These drugs should be used with caution in men who have unstable heart disease, poorly controlled high blood pressure, or history of stroke. Discuss with your doctor whether a PDE-5 inhibitor drug is safe for you. Testosterone Therapy Guidelines In 2007, the Endocrine Society issued guidelines for testosterone treatment. The Endocrine Society advises that testosterone therapy works best for men who have been diagnosed with low testosterone levels and who demonstrate clear clinical symptoms such as erectile dysfunction. For patients with low libido or erectile dysfunction, but normal testosterone levels, it is unclear that testosterone therapy offers any benefits. Most experts recommend that patients with low testosterone levels and erectile dysfunction combine testosterone replacement therapy with a PDE-5 inhibitor drug. Metabolic Syndrome Increases Risk for Erectile Dysfunction Metabolic syndrome is a risk factor for erectile dysfunction, according to several recent studies. Metabolic syndrome is a cluster of conditions that include abdominal obesity, unhealthy cholesterol and triglyceride levels, high blood pressure, and insulin resistance. IntroductionErectile 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 experience 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 new in neither medicine nor 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, in most cases, benefit from medical treatment. The term "impotence" comes from Latin and means loss of power; a more accurate term is "erectile dysfunction." The Penis and Erectile FunctionThe Structure of the Penis. The penis is composed of the following structures:
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:
During arousal the following occurs:
Important Substances for Erectile HealthA 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 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 from 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 DeprivationErectile 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:
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 cause blockage in the blood vessels leading 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 FactorsMore 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 20 – 46% of men age 40 – 69, about 80% of men age 75 or older 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 in elderly men may have 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 a more widespread problem. Lifestyle or Psychological CausesOver 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:
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 DysfunctionAnxiety. 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. In one study, 82% of men who reported moderate-to-severe erectile dysfunction also had symptoms of depression. Depression can certainly reduce sexual desire, but it is often not clear which condition came first. Problems in RelationshipsTroubles 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. Socioeconomic IssuesLosing a job or having lower income or education increases the risk for impotence. SmokingSmoking contributes to the development of impotence, mainly because it increases the effects of other disorders of the blood vessels, including high blood pressure and atherosclerosis. A 2006 study found that men who smoked at least a pack a day were 39% more likely to experience ED than non-smokers. Research presented at the 2006 meeting of the American Urological Association indicated that quitting smoking helps reverse ED. AlcoholAlcohol 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. Exposure to Estrogen-Like ChemicalsSome evidence suggests that exposure to estrogen-like chemicals, such as those found in DDT and other pesticides, may contribute to erectile dysfunction. (Such chemicals have been associated with low sperm counts and infertility in men.) Lack of Frequent ErectionsInfrequent 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 CausesA number of conditions share a common problem with erectile dysfunction -- the impaired ability of blood vessels to open and allow normal blood flow. Such conditions include diabetes, hypertension, coronary artery disease, kidney failure, peripheral artery disease, and stroke. Increasingly, researchers are studying the role of nitric oxide, which plays a major role in keeping blood vessels open, in all of these disorders. The following diseases are highly associated with erectile dysfunction:
Other Common Medical Conditions that Contribute to Erectile DysfunctionParkinson's Disease. As a risk factor for impotence, Parkinson's disease (PD) is an under-appreciated problem. It is estimated that about a third of men with PD experience impotence. The physical cause of PD-related impotence is most likely an impaired nervous system. Depression and lowered self-esteem also contribute to erectile dysfunction in these patients. Multiple Sclerosis. Multiple sclerosis (MS), which affects the central nervous system, also precipitates sexual dysfunction in as many as 78% of male patients. (Corticosteroids, which are common treatments for MS, may improve sexual function.) Other Common Medical Conditions. Other medical conditions that have been associated with erectile dysfunction include allergies, thyroid problems, lung disease, and epilepsy. Prostate Cancer and Its TreatmentsAdvanced prostate cancer can damage nerves needed for erectile function. Prostate surgery and surgical and radiation treatments for prostate cancer can also cause impotence. A number of treatments for sexual dysfunction are available that may help some men. [See In-Depth Report #33: Prostate cancer.] Prostate Cancer Surgery (Radical Prostatectomy). The first nationally representative study to evaluate long-term outcomes after radical prostatectomy concluded that impotence occurs far more frequently than previously reported. Those who have so-called nerve-sparing surgeries have better results than those whose surgeries affect the nerves around the prostate. Some evidence also suggests that sexual function rates might improve if the nerve-sparing prostate surgeries also spare the ducts that carry semen. Some studies suggest that impotence after prostate surgery may in part be due to injury to the smooth muscles in the blood vessels. Early treatments to maintain penile blood flow may help restore erectile function. Some men may benefit from PDE5 inhibitor drugs such as sildenafil (Viagra), tadalafil (Cialis), or vardenafil (Levitra). Other men may need alprostadil injections or suppositories. The vacuum pump is another option. Radiation. Although it is generally believed that radiation poses a lower risk for impotence than does surgery, studies have reported similar rates after 3 years. Experts suggest radiation injures the blood vessels, leading to erectile dysfunction over time. Some studies report a lower risk for impotence from brachytherapy, a radiation technique that involves the implantation of radioactive "seeds" compared to external-beam radiation. Still, there have been very few studies that have lasted more than 2 years. One 5-year study reported a high long-term rate of impotence (53%) with brachytherapy, which is close to that of standard externally administered radiation. Early use of alprostadil injections and sildenafil (Viagra) may help these men as well as those who had surgery. Drug Treatments. Prostate cancer medical treatments commonly employ androgen-suppressive treatments, which cause erectile dysfunction. Surgical Treatments that Affect Intestinal TractsSurgery 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. Total mesorectal excision (TME) may pose fewer risks than standard surgery. Sildenafil (Viagra) may help many men who experience this after surgery. Surgical Treatment of Inflammatory Bowel Disease. Rectal excision for inflammatory bowel disease (IBD) can cause impotence, but rates are low (2 - 4%). Sildenafil (Viagra) is very effective in restoring potency after IBD surgery. Operations for Fistulas. 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.) Treatments for Benign Prostatic Hyperplasia (BPH)Surgery and drug treatments for benign prostatic hyperplasia (BPH) can also increase the risk for impotence, although to a much lesser degree than surgery for prostate cancer.
MedicationsAbout a quarter of all cases of impotence can be attributed to medications. Many drugs pose a risk for erectile dysfunction. Some experts think that nearly every drug, prescription or nonprescription, can be a cause of temporary erectile dysfunction. Drugs that commonly cause impotence may include:
Drugs that sometimes cause impotence include:
Physical Trauma, Stress, or InjuryInjury to the Spine. 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. Orthopedic surgery. Erectile dysfunction can sometimes result from orthopedic surgery. A study of young men who underwent surgical repair (“intramedullary nailing”) for a broken thighbone reported that about 40% of these patients experienced erectile dysfunction after surgery. The researchers theorized that the surgery affected pelvic nerves that play a key role in erection. Patients who received a higher dose of muscle relaxant during surgery had better sexual function outcomes. Bicycling. Studies have indicated that frequent bicycling may pose a risk for erectile dysfunction by reducing blood flow to the penis. The greatest risk is in cyclers who sit upright while cycling. In addition, a 2004 report in the Journal of Urology found that long distance cyclers may reduce their risk by riding a road bike instead of a mountain bike and by choosing saddles without a cutout. Note: Vasectomy does not cause erectile dysfunction. When impotence occurs after this procedure, it is often in men whose female partners were unable to accept the operation. Hormonal AbnormalitiesHypogonadism (Testicular Failure). Hypogonadism in men is a deficiency in male hormones, usually due to an abnormality in the testicles, which secrete these hormones. It affects 4 - 5 million men in the United States. In addition to impotence, hypogonadism causes reductions in energy, sex drive, lean body mass, and bone density. Hypogonadism can be caused by a number of different conditions. Among them are:
Low Testosterone Levels. Only about 5% of men who see a doctor about erectile dysfunction have low levels of testosterone, the primary male hormone. In general, lower testosterone levels appear to reduce sexual interest, not cause impotence. Other Hormonal Abnormalities. Other hormonal abnormalities that can lead to erectile dysfunction include:
VaricocelesA 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. Other Problems in Sexual FunctionPremature 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. A new serotonin-related drug, dapoxetine, showed promise in several clinical trials but was ultimately rejected by the FDA in 2005. 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. Some men may not even be aware that they have it, and there is some evidence that it may be more common than currently believed. In one study, 6.7% of men with an average age of 62 had signs of curvature, but only 2.2% were aware of any difficulties. 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 for Peyronie's Disease. If Peyronie's disease is treated early, ultrasound, heat application, and anti-inflammatory drugs may help reduce scar formation. Some experts believe that the extracorporeal shock wave therapy (ESWT) is the safest and most effective first-line therapy. ESWT uses sound waves to break up scar tissue. It has been used with some success. Studies also suggest that the calcium channel blocker verapamil may be very beneficial. It can be administered using injection, as a gel patch, or through a process called electromotive drug administration (EMDA), also referred to as iontophoresis. EMDA delivers the drug through an electrical transport of charged molecules. Some studies are reporting good success with EMDA delivery of verapamil along with the steroid dexamethasone. In severe cases of scarring, the only treatment is surgery to straighten the penis and reduce the curve. Penile implants may also be beneficial. 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. Treatment of Priapism. 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. PrognosisTemporary erectile dysfunction is very common and usually not a serious 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. Persistent impotence may also be a symptom of a serious medical condition, such as heart disease, diabetes, hypertension, sleep disorders, or circulatory problems. For example, in a study of men who had suffered heart attacks, 75% of them had experienced erectile dysfunction on average 68 months before the heart attack. Erectile dysfunction can also indicate the presence of injuries or the long-term effects of smoking, heavy drinking, or unhealthy diet. DiagnosisThe 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:
Sexual History. In addition the doctor will ask about the patient's sexual history, which may include:
Interviewing the Sexual Partner. If appropriate, the doctor might 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 ExaminationThe 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 FunctionA 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 an injection of papaverine or prostaglandin E1, medications that dilate blood vessels in the penis. They 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 TestsBlood 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 ErectionsTests 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.
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 IndexThe 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 TechniquesImaging tests may be used in certain cases, 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. Dynamic Infusion Cavernosometry and Cavernosography. Dynamic infusion cavernosometry and cavernosography (DICC) is usually given only to young men in whom some blockage of the penis or physical injury of the pelvic area is suspected. After an erection is induced with drugs, the following four steps are taken:
Unfortunately, this test and other similar imaging techniques used to determine blood flow in the penis are not very effective or accurate in diagnosing and determining treatment. Duplex Doppler Ultrasound. An ultrasound technique called duplex Doppler ultrasound may be useful alone or with sildenafil (Viagra) in determining the severity of condition and also to determine impaired blood flow through the arteries. TreatmentThe 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:
No matter what the treatment, embarking on a healthy lifestyle is the first and critical step for maintaining and restoring erectile function. Treatment ChoicesMedical 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:
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 ChangesBecause 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. 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 is often 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 is extremely important. One study reported that older men who ran 40 miles a week boosted their testosterone levels by 25% compared to their inactive peers. Another study found that men who burned 200 calories or more a day in physical activity (which can be achieved by 2 miles of brisk walking) cut their risk of erectile dysfunction by half compared to men who did not exercise. A study in the Journal of the American Medical Association found that adopting healthy lifestyle changes improved sexual function in obese men (BMI less than 30) with erectile dysfunction. After 2 years, a third of the study participants on the reduced calorie diet and an increased exercise regimen regained sexual function. Limit Alcohol and Quit Smoking. Men who drink alcohol should do so in moderation. Quitting smoking is essential. Stay Sexually ActiveStaying 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. Kegel ExercisesThe Kegel exercise is a simple exercise commonly used by people who have urinary incontinence and by pregnant women. It may also be helpful for men whose erectile dysfunction is caused by impaired blood circulation. The exercises consist of tightening and releasing the pelvic muscle that controls urination:
It may be several months before the patient sees significant improvement. Changing or Reducing MedicationsIf medications are causing impotence, the patient and doctor should discuss alternatives or reduced dosages. Psychotherapy and Behavioral TherapyEven 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. MedicationsThree medicines taken by mouth are approved for the treatment of erectile dysfunction: Sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). All three belong to a class of drugs called selective enzyme inhibitors. Sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis) block the enzyme phosphodiesterase-5 (PDE5). Blocking this enzyme helps maintain levels of cyclic guanosine monophosphate (GMP), a chemical produced in the penis during sexual arousal. Balanced levels of GMP cause the smooth muscles of the penis to relax and increase blood flow. Good 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 (such as the use of nitrates or alpha-blockers; see Higher-risk candidates in this section.) Effectiveness of PDE5 Inhibitors.
Studies indicate that PDE5 inhibitors are safe and effective for many men whose erectile dysfunction is related to the following conditions:
PDE5 inhibitors may also help restore erectile dysfunction in some men who have had the following conditions or treatments:
Higher-Risk Candidates. PDE5 inhibitors are not suitable for everyone. Men who take nitrate drugs for angina, anticoagulants for heart conditions, or certain types of alpha-blockers for high blood pressure and benign prostatic hyperplasia (BPH), should not take PDE5 inhibitors. Men with the following conditions should not take PDE5 inhibitors without the recommendation of their doctors and even then should use them with caution:
Administration and Effect. PDE5 inhibitors work only when the man experiences some sexual arousal. They are generally effective within 30 - 120 minutes when taken on an empty stomach. 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. 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, but this combination may cause a number of side effects. Side Effects and Other Limitations. 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. Visual Effects. About 2.5% of men experience abnormal visual effects 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. 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. Decrease in Effectiveness. Over time, PDE5 inhibitors may lose effectiveness. A 2001 study found that after 2 years, 20% of patients had increased their dose of sildenafil to achieve the same effect, and 17% had discontinued the drug due to loss of efficacy. It is possible that these men were suffering from heart disease or other problems that made their impotence worse. An earlier study found that 96% of men who had been taking sildenafil for 2 - 3 years remained satisfied with the treatment. In addition, some research indicates that sildenafil treatment may be less effective in men with diabetes. Investigational DrugsOther PDE5 Inhibitors. Avanafil and SLX-2101 are new PDE5 inhibitors that are showing promising results in clinical trials. Melanocortin receptor agonists. Melanocortin receptor agonists work on the central nervous system instead of the vascular system. Bremelanotide (formerly PT-141) is the first of these drugs to be investigated in clinical trials. Researchers are testing the drug as a nasal spray given either alone or in combination with a PDE5 inhibitor. Gene Therapy. Researchers are investigating gene transfer therapy as a possible cure for erectile dysfunction. Promising results from the first human trial were presented at the 2006 American Urological Association meeting. The gene-based therapy, called hMaxi-K, uses injections of a gene that helps the body manufacture proteins to improve smooth muscle relaxation. The treatment requires injections twice a year. It is still in the very early stages of research. Injections or Topical TreatmentsPenile injections have now largely been replaced by PDE5 inhibitors, such as sildenafil. Nevertheless, injection therapies use various drugs that have properties that help achieve erection, even in many men who do not succeed with PDE5 inhibitors. The standard drugs used in injections include:
Although any or all of these drugs are very effective, injections or other invasive methods of administration are awkward and uncomfortable. Treatments Using AlprostadilAlprostadil is derived from a natural substance, prostaglandin E1, and acts by opening blood vessels. It is an effective treatment for some men. It can be administered by:
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:
Alprostadil is not an appropriate choice for men with:
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. Edex is a newer and less expensive form of injected alprostadil. In one 12-month study of 894 patients, Edex injections achieved erections in 95% of attempts. 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 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:
Injections Using Papaverine and PhentolamineUntil 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). Testosterone Replacement TherapyAccording to 2006 guidelines from the Endocrine Society, testosterone replacement therapy works best for men with erectile dysfunction who have been diagnosed with hypogonadism (low testosterone levels). For these men, experts recommend combination of testosterone and other ED treatments, such as PDE-5 inhibitors. Men who have ED and normal testosterone levels are not likely to benefit from testosterone therapy. Forms of testosterone therapy include:
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:
Other TreatmentsVacuum 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:
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. Between 56 - 67% of men using it reported the device to be effective. In one study of men who had used the vacuum device for many years, almost 79% reported improvement in their relationships with their sexual partners, and 83.5% said they had intercourse whenever they chose. Nevertheless, dropout rates are high. In one study, for example, the overall drop out rate was 65%. Even in a high-success group, over half stopped using it. 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 ControllersVacuum-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 ImplantsPenile implants are available for men who cannot take medication or who fail less invasive treatments. A 2006 study reported that penile implants helped restore sexual function to 89% of men who had the procedure, and 81% of men were satisfied with the results. Three types of surgical implants are used for the treatment of erectile dysfunction:
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 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 SurgeryFor 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 there was improvement in erectile dysfunction 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 between 40 - 50% initially, but drops to 15% over the long term. It is important to find a surgeon experienced in this surgery. 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 RemediesHerbs and SupplementsGenerally, 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. The following are 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. 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:
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 2006 and 2007, the FDA 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
ReferencesBhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2006 Jun;91(6):1995-2010. Epub 2006 May 23. Heidler S, Temml C, Broessner C, Mock K, Rauchenwald M, Madersbacher S, et al. Is the metabolic syndrome an independent risk factor for erectile dysfunction? J Urol. 2007 Feb;177(2):651-4. Selvin E, Burnett AL, Platz EA. Prevalence and risk factors for erectile dysfunction in the US. Am J Med. 2007 Feb;120(2):151-7. Vardi M, Nini A. Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus. Cochrane Database Syst Rev. 2007 Jan 24(1):CD002187.
Review Date:
6/27/2007 Reviewed By: Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-
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