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What could be causing your guy's erectile dysfunction?

By webMD.com
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What is erectile dysfunction?
Erectile dysfunction (ED), also known as impotence, is the inability to achieve or sustain an erection for satisfactory sexual activity. Erectile dysfunction is different from other conditions that interfere with male sexual intercourse, such as lack of sexual desire (decreased libido) and problems with ejaculation and orgasm (ejaculatory dysfunction). This article focuses on the evaluation and treatment of erectile dysfunction.

How common is erectile dysfunction?
Erectile dysfunction (ED, impotence) varies in severity; some men have a total inability to achieve an erection, others have an inconsistent ability to achieve an erection, and still others can sustain only brief erections. The variations in severity of erectile dysfunction make estimating its frequency difficult. Many men also are reluctant to discuss erectile dysfunction with their doctors due to embarrassment, and thus the condition is underdiagnosed.

While erectile dysfunction can occur at any age, it is uncommon among young men and more common in the elderly. By age 45, most men have experienced erectile dysfunction at least some of the time. According to the Massachusetts Male Aging Study, complete impotence increases from 5% among men 40 years of age to 15% among men 70 years and older. Population studies conducted in the Netherlands found that some degree of erectile dysfunction occurred in 20% of men between ages 50-54, and in 50% of men between ages 70-78. In 1999, the National Ambulatory Medical Care Survey counted 1,520,000 doctor-office visits for erectile dysfunction. Other studies have noted that approximately 35% of men 40-70 years of age suffer from moderate to severe ED, and an additional 15% may have milder forms.

What is normal penis anatomy?
The penis contains two chambers, called the corpora cavernosa, which run the length of the upper side of the penis. The urethra, which is the channel for urine and ejaculate, runs along the underside of the corpora cavernosa. Filling the corpora cavernosa is a spongy tissue consisting of smooth muscles, fibrous tissues, spaces, veins, and arteries. A membrane, called the tunica albuginea, surrounds the corpora cavernosa. Veins located in the tunica albuginea drain blood out of the penis.

How does erection occur?
Erection begins with sexual stimulation. Sexual stimulation can be tactile (for example, by touching the penis) or mental (for example, by having sexual fantasies). Sexual stimulation or sexual arousal generates electrical impulses along the nerves going to the penis and causes the nerves to release nitric oxide, which in turn increases the production of cyclic GMP (cGMP) in the smooth muscle cells of the corpora cavernosa. The cGMP causes the smooth muscles of the corpora cavernosa to relax and allow rapid blood flow into the penis. The incoming blood fills the corpora cavernosa, making the penis expand.

How is erection sustained?
The pressure from the expanding penis compresses the veins (blood vessels that drain the blood out of the penis) in the tunica albuginea, helping to trap the blood in the corpora cavernosa, thereby sustaining erection. Erection is reversed when cGMP levels in the corpora cavernosa fall, causing the smooth muscles of the corpora cavernosa to contract, stopping the inflow of blood and opening veins that drain blood away from the penis. The levels of the cGMP in the corpora cavernosa fall because it is destroyed by an enzyme called phosphodiesterase type 5 (PDE5).

What are some of the risk factors for erectile dysfunction?

The common risk factors for ED include the following:

• Advanced age
• Cardiovascular disease
• Diabetes mellitus
• High cholesterol
• Cigarette smoking
• Recreational drug use
• Depression or other psychiatric diseases
What are the causes of erectile dysfunction?

The ability to achieve and sustain erections requires

1. a healthy nervous system that conducts nerve impulses in the brain, spinal column, and penis,

2. healthy arteries in and near the corpora cavernosa,

3. healthy smooth muscles and fibrous tissues within the corpora cavernosa,

4. adequate levels of nitric oxide in the penis.
Erectile dysfunction can occur if one or more of these requirements are not met. The following are causes of erectile dysfunction:

• Aging: There are two reasons why older men are more likely to experience erectile dysfunction than younger men. First, older men are more likely to develop diseases (such as heart attacks, angina, cardiovascular disease, strokes, diabetes mellitus, and high blood pressure) that are associated with erectile dysfunction. Second, the aging process alone can cause erectile dysfunction in some men, primarily by decreasing the compliance of the tissues in the corpora cavernosa, although it has been suggested, but not proven, that there is also decreased production of nitric oxide in the nerves that innervate the corporal smooth muscle within the penis.

• Diabetes mellitus: Erectile dysfunction tends to develop 10-15 years earlier in diabetic men than among nondiabetic men. In a population study of men with type I diabetes for more than 10 years, erectile dysfunction was reported by 55% of men 50-60 years of age. The increased risk of erectile dysfunction among men with diabetes mellitus may be due to the earlier onset and greater severity of atherosclerosis that narrows the arteries and thereby reduces the delivery of blood to the penis. When insufficient blood is delivered to the penis, it is not possible to achieve an erection.

Diabetes mellitus also causes erectile dysfunction by damaging both sensory and autonomic nerves, a condition called diabetic neuropathy. Smoking cigarettes, obesity, poor control of blood glucose levels, and having diabetes mellitus for a long time further increase the risk of erectile dysfunction in diabetes. In addition to atherosclerosis and/or neuropathy causing ED in diabetes, many men with diabetes also develop a myopathy (muscle disease) as their cause of ED in which the compliance of the muscles in the corpora cavernosa is decreased, and clinically this presents as an inability to maintain the erection.

• Hypertension (high blood pressure): People with essential hypertension or arteriosclerosis have an increased risk of developing erectile dysfunction. Essential hypertension is the most common form of hypertension; it is called essential hypertension because it is not caused by another disease (for example, by kidney disease). It is not clearly known how essential hypertension causes erectile dysfunction; however, those with essential hypertension have been found to have low production of nitric oxide by the arteries of the body, including the arteries in the penis. High blood pressure also accelerates the progression of atherosclerosis, which in turn can contribute to erectile dysfunction. Scientists now suspect that the decreased levels of nitric oxide in patients with essential hypertension may contribute to erectile dysfunction.

• Cardiovascular diseases: The most common cause of cardiovascular diseases in the United States is atherosclerosis, the narrowing and hardening of arteries that reduces blood flow. Atherosclerosis typically affects arteries throughout the body and is aggravated by hypertension, high blood cholesterol levels, cigarette smoking, and diabetes mellitus. When coronary arteries (arteries that supply blood to the heart muscle) are narrowed by atherosclerosis, heart attacks and angina occur. When cerebral arteries (arteries that supply blood to the brain) are narrowed by atherosclerosis, strokes occur. Similarly, when arteries to the penis and the pelvic organs are narrowed by atherosclerosis, insufficient blood is delivered to the penis to achieve an erection. There is a close correlation between the severity of atherosclerosis in the coronary arteries and erectile dysfunction. For example, men with more severe coronary artery atherosclerosis also tend to have more erectile dysfunction than men with mild or no coronary artery atherosclerosis. Some doctors suggest that men with new onset erectile dysfunction should be evaluated for silent coronary artery diseases (advanced coronary artery atherosclerosis that has not yet caused angina or heart attacks).

• Cigarette smoking: Cigarette smoking aggravates atherosclerosis and thereby increases the risk for erectile dysfunction.

• Nerve or spinal cord damage: Damage to the spinal cord and nerves in the pelvis can cause erectile dysfunction. Nerve damage can be due to disease, trauma, or surgical procedures. Examples include injury to the spinal cord from automobile accidents, injury to the pelvic nerves from prostate surgery for prostate cancer (prostatectomy), radiation to the prostate, surgery for benign prostatic enlargement, multiple sclerosis (a neurological disease with the potential to cause widespread damage to nerves), and long-term diabetes mellitus.

• Substance abuse: Marijuana, heroin, cocaine, methamphetamines, crystal meth, and alcohol abuse contribute to erectile dysfunction. Alcoholism, in addition to causing nerve damage, can lead to atrophy (shrinking) of the testicles and lower testosterone levels.

• Low testosterone levels: Testosterone (the primary sex hormone in men) is not only necessary for sex drive (libido) but also is necessary to maintain nitric oxide levels in the penis. Therefore, men with hypogonadism (diminished function of the testes resulting in low testosterone production) can have low sex drive and erectile dysfunction.

• Medications: Many common medicines produce erectile dysfunction as a side effect. Medicines that can cause erectile dysfunction include many used to treat high blood pressure, antihistamines, antidepressants, tranquilizers, and appetite suppressants. Examples of common medicines that can cause erectile dysfunction include propranolol (Inderal) or other beta-blockers, hydrochlorothiazide, digoxin (Lanoxin), amitriptyline (Elavil), famotidine (Pepcid), cimetidine (Tagamet), metoclopramide (Reglan), indomethacin (Indocin), lithium (Eskalith, Lithobid), verapamil (Calan, Verelan, Isoptin), phenytoin (Dilantin), and gemfibrozil (Lopid).

• Depression and anxiety: Psychological factors may be responsible for erectile dysfunction. These factors include stress, anxiety, guilt, depression, widower syndrome, low self-esteem, posttraumatic stress disorder, and fear of sexual failure (performance anxiety). It is also worth noting that many medications used for treatment of depression and other psychiatric disorders may cause erectile dysfunction or ejaculatory problems.

How is erectile dysfunction diagnosed?
Patient history
A diagnosis of erectile dysfunction is made in men who have repeated inability to achieve and/or maintain an erection for satisfactory sexual performance for at least three months. Candid communication between the patient and the doctor is important in establishing the diagnosis of erectile dysfunction, assessing its severity, and determining the cause. During patient interviews, doctors try to answer the following questions:

1. Is the patient suffering from erectile dysfunction or from loss of libido or a disorder of ejaculation (for example, premature ejaculation)?

2. Is erectile dysfunction due to psychological or physical factors? Healthy men have involuntary erections in the early morning and during REM sleep (a stage in the sleep cycle with rapid eye movements). Men with psychogenic erectile dysfunction (erectile dysfunction due to psychological factors such as stress and anxiety rather than physical factors) usually maintain these involuntary erections. Men with physical causes of erectile dysfunction (for example, atherosclerosis, smoking, and diabetes) usually do not have these involuntary erections.

3. Are there physical causes of erectile dysfunction? A prior history of cigarette smoking, heart attacks, strokes, and poor circulation in the extremities suggest atherosclerosis as the cause of the erectile dysfunction. Diminished sensation of the penis and the testicles, bladder dysfunction, and decreased sweating in the lower extremities may suggest diabetic nerve damage. Loss of sexual desire and drive, lack of sexual fantasies, gynecomastia (enlargement of breasts), and diminished facial hair suggest low testosterone levels.

4. Is the patient taking medications that can contribute to erectile dysfunction?

Physical examination
The physical examination can reveal clues for physical causes of erectile dysfunction. For example, if the penis does not respond as expected to touching, a problem in the nervous system may be the cause. Small testicles, lack of facial hair, and enlarged breasts (gynecomastia) can point to hormonal problems such as hypogonadism with low testosterone levels. A reduced flow of blood as a result of atherosclerosis can sometimes be diagnosed by finding diminished arterial pulses in the legs or listening with a stethoscope for bruits (the sound of blood flowing through narrowed arteries).

Unusual characteristics of the penis itself could suggest the root of the erectile dysfunction, for example, bending of the penis with painful erection could be the result of Peyronie's disease. Particular attention is paid to any underlying risk factors for erectile dysfunction.

Laboratory tests
The following are common laboratory tests to evaluate erectile dysfunction:

• Complete blood counts
• Urinalysis: An abnormal urinalysis may be a sign of diabetes mellitus and kidney damage.

• Lipid profile: High levels of LDL cholesterol (bad cholesterol) in the blood promotes atherosclerosis.

• Blood glucose levels: Abnormally high blood glucose levels may be a sign of diabetes mellitus.

• Blood hemoglobin A 1c: Abnormally high levels of blood hemoglobin A 1c in patients with diabetes mellitus establish that there is poor control of blood glucose levels.

• Serum creatinine: An abnormal serum creatinine may be the result of kidney damage due to diabetes.

• Liver enzymes and liver function tests: Advanced liver disease (cirrhosis) can result in hormonal imbalance and gonad dysfunction leading to low testosterone levels. Thus, evaluation for liver disease may be necessary in cases of erectile dysfunction.

• Total testosterone levels: Blood samples for total testosterone levels should be obtained in the early morning (before 8 a.m.) because of wide fluctuations in the testosterone levels throughout the day. A low total testosterone level suggests hypogonadism. Measurement of bio-available testosterone may be a better measurement than total testosterone, especially in obese men and men with liver disease, but measurement of bio-available testosterone is not widely available.

• Other hormone levels: Measurement of other hormones beside testosterone (luteinizing hormone (LH), prolactin level, and cortisol level) may provide clues to other underlying causes of testosterone deficiency and erectile problems, such as pituitary disease or adrenal gland abnormalities. Thyroid levels may be routinely checked as both hypothyroidism and hyperthyroidism can contribute to erectile dysfunction.

• PSA levels: PSA (prostate specific antigen) blood levels and prostate examination to exclude prostate cancer is important before starting testosterone treatment since testosterone can aggravate prostate cancer.

• Other blood tests: Evaluation for hemochromatosis, lupus, scleroderma, zinc deficiency, sickle cell anemia, cancers (leukemia, colon cancer) are some of the other potential tests that may be performed based on each individual's history and symptoms.

Imaging tests
In a setting of a previous pelvic trauma, X-rays may be performed to assess various bony abnormalities. Ultrasound of the penis and testicles is done occasionally to check for testicular size and structural abnormalities. Ultrasound with Doppler imaging can provide additional information about blood flow of the penis. Rarely, an angiogram may be performed in cases in which possible vascular surgery could be beneficial.

Other tests
Prostaglandin E1 injection test is sometimes performed to determine the penile blood flow. Prostaglandin is directly injected into the corpora cavernosa in order to cause dilation of blood vessels and promote blood flow into the penis. If erection ensues, it confirms normal or adequate blood flow to the penis. This can also provide information about possible therapeutic options.

Monitoring erections that occur during sleep (nocturnal penile tumescence) can help distinguish between erectile dysfunction of psychological and physical causes. A band is worn around the penis for two to three successive nights and it can signal intensity and duration of erections if they occur. If nocturnal erections do not occur, then the cause of erectile dysfunction is likely to be physical rather than psychological, however, tests of nocturnal erections are not completely reliable. Scientists have not standardized the tests and have not determined in whom they should be done.

Direct vibrational stimulation (biothesiometry) is occasionally done to evaluate penile nerve function. Small electromagnetic electrodes are placed on the shaft of the penis and vibration amplitude is slightly adjusted until sensation is noted by the patient. Although this test does not measure the exact nerve function, it serves as a screening method to detect any sensory nerve deficit as the cause of ED.

Psychosocial examination
A psychosocial examination using an interview and questionnaire may reveal psychological factors contributing to erectile dysfunction. The sexual partner also may be interviewed to determine expectations and perceptions encountered during sexual intercourse.

What are the treatments for erectile dysfunction?

The following are treatments for erectile dysfunction:

1. Working with doctors to select medications that do not impair erectile function

2. Making life style improvements (for example, quitting smoking and exercising more)

3. Taking drugs to treat ED such as sildenafil (Viagra), vardenafil (Levitra) or tadalafil (Cialis)

4. Inserting medications into the urethra (intraurethral suppositories)

5. Injecting medications into the corpora cavernosae (intracavernosal injections)

6. Vacuum constrictive devices for the penis
7.Penile prostheses
8. Psychotherapy
Adjusting medications
Many common medications for treating hypertension, depression, and high blood lipids can contribute to erectile dysfunction (see above). Treatment of hypertension is an example. There are many different types (classes) of anti-hypertensive medications (medications that lower blood pressure); these include beta-blockers, calcium channel blockers, diuretics (medications that increase urine volume), angiotensin converting enzyme inhibitors (ACE inhibitors), and angiotensin receptor blockers (ARBs). Anti-hypertensives may be used alone or in combination to control blood pressure. Different classes of anti-hypertensives have different effects on erectile function. Inderal (a beta blocker) and hydrochlorothiazide (a diuretic) are known to cause erectile dysfunction, while calcium channel blockers and ACE inhibitors do not seem to affect erectile function. On the other hand, angiotensin receptor blockers (ARBs) such as losartan (Cozaar) and valsartan (Diovan) may actually increase sexual appetite, improve sexual performance, and decrease erectile dysfunction. Therefore, choosing an optimal anti-hypertensive combination is an important part of treating erectile dysfunction.

Lifestyle improvements
Quitting smoking, exercising regularly, losing excess weight, curtailing excessive alcohol consumption, controlling hypertension, and optimizing blood glucose levels in patients with diabetes are not only important for maintaining good health but also may improve or even prevent erectile function. Some studies suggest that men who have made lifestyle improvements experience increased rates of success with oral medications.

What medications are used to treat erectile dysfunction?

Medications for erectile dysfunction include
• testosterone,
• oral phosphodiesterase type 5 (PDE5) inhibitors (sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis),

• intracavernosal injections,
• intraurethral suppositories.
Oral phosphodiesterase type 5 (PDE5) inhibitors
The common PDE5 drugs approved in the United States are sildenafil (Viagra), vardenafil (Levitra), or tadalafil (Cialis). Actual head-to-head trials between these drugs have not been done to date to see which is the superior drug. Details on each of these medications for erectile dysfunction are outlined below.

Sildenafil (Viagra)
What is sildenafil (Viagra)?

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

How effective is sildenafil (Viagra)?
Sildenafil is used for the treatment of erectile dysfunction of either physical or psychological cause. It has been found to be effective in treating erectile dysfunction in men with coronary artery disease, diabetes mellitus, hypertension, depression, coronary artery bypass surgery, and men who are taking antidepressants and several classes of anti-hypertensives.

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

How should sildenafil (Viagra) be administered?

Sildenafil is available as oral tablets at doses of 25, 50, and 100 mg. It should be taken approximately one hour before sexual activity. In some men, the onset of action of the drug may be as early as 11-20 minutes. Sildenafil should be taken on an empty stomach for best results since absorption and effectiveness of sildenafil can be diminished if it is taken shortly after a meal, particularly a meal that is high in fat.

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

Metabolism (breakdown) of sildenafil is slowed by aging, liver and kidney dysfunction, and concurrent use of certain medications (such as erythromycin -- an antibiotic, and protease inhibitors, for HIV). Slowed breakdown allows sildenafil to accumulate in the body and potentially may increase the risk of side effects. Therefore in men over 65, in men with substantial kidney and liver disease, and in men who also are taking protease inhibitors, the doctor will initiate sildenafil at a lower dose (25 mg) to avoid accumulation of sildenafil in the body. A protease inhibitor ritonavir (Norvir) is especially potent in increasing the accumulation of sildenafil, thus men who are taking Norvir should not take sildenafil doses higher than 25 mg and at a frequency of no greater than once in 48 hours.

What are the side effects of sildenafil (Viagra)?

Sildenafil has been found to be well tolerated without important side effects. The reported side effects are usually mild and include headache, flushing, nasal congestion, nausea, dyspepsia, (stomach discomfort), diarrhea, and abnormal vision (seeing a bluish hue or brightness).

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

Sildenafil should be used cautiously in men on alpha blockers such as doxazosin (Cardura), terazosin (Hytrin), and tamsulosin (Flomax). There have been occasional reports of low blood pressure in men who have taken the two classes of drugs simultaneously and therefore it is recommended that there be at least a span of four to six hours between the ingestion of sildenafil and alpha blockers.

There have been rare reports of priapism (prolonged and painful erections lasting more than six hours) with the use of PDE5 inhibitors such as sildenafil, vardenafil, and tadalafil, especially when sildenafil is used in combination with injection of medications into the corpora cavernosa or intraurethral suppositories. Patients with blood cell diseases such as sickle cell anemia, leukemia, and multiple myeloma have higher than normal risks of developing priapism. Untreated priapism can cause injury to the penis and lead to permanent impotence. Therefore, sildenafil should not be used in combination with intraurethral suppositories and corpora cavernosa injections. If there is prolonged erection (longer than four hours), immediate medical assistance should be obtained.

Is it safe for men with heart disease to use sildenafil (Viagra)?

Sildenafil has been found to be effective and safe in the treatment of erectile dysfunction in men with stable heart disease due to atherosclerosis of the coronary arteries, provided that they are not on any type of nitrates. The real concern is not as much the safety of sildenafil but the risk of sexual activity in triggering heart attacks or abnormal heart rhythms in patients with heart disease.

The risk of developing heart attacks or abnormal heart rhythms during sex is low in men with well-controlled hypertension, mild disease of the heart valves, well-controlled heart failure, mild and stable angina (with a favorable treadmill stress test), successful coronary stenting or bypass surgery, and a remote history of heart attack (more than eight weeks previously). Sildenafil can be used safely in men in these low-risk groups.

The risk of heart attack or abnormal heart rhythms during sex is higher in men with unstable angina (angina that occurs at rest or with minimal exertion), poorly controlled hypertension, moderate to severe heart failure, moderate to severe disease of the heart valves, recent heart attack (less than two weeks previously), potentially life-threatening disorders of heart rhythm such as recurrent ventricular tachycardia, and moderate to severe disease of the heart muscles. In these men, doctors usually stabilize or treat the heart conditions before prescribing sildenafil.

Before starting sildenafil for erectile dysfunction, a doctor may need to determine whether the heart can safely achieve the workload necessary for sexual activity. For example, in men with coronary artery heart disease, a doctor may perform a treadmill stress test to determine whether there is adequate blood supply to the heart muscle while exercising at levels comparable to sexual activity.

Vardenafil (Levitra)
What is vardenafil (Levitra)?

Vardenafil (Levitra) was the second oral medicine approved by the U.S. FDA for the treatment of erectile dysfunction. Like sildenafil (Viagra), vardenafil (Levitra) inhibits PDE5 which destroys cGMP (as discussed earlier).

How effective is vardenafil (Levitra)?
Vardenafil was evaluated in four multicenter, randomized, placebo-controlled trials involving more than 2,400 men (78% white, 7% black, 2% Asian, 3% Hispanic) with erectile dysfunction. Two of these trials were conducted in special erectile dysfunction populations; one in men with diabetes mellitus, another in men who developed erectile dysfunction after prostate surgery. The doses of vardenafil in the four studies were 5 mg, 10 mg, and 20 mg.

In all four studies, vardenafil was significantly better than placebo in improving men's ability to achieve and maintain erections in all age categories (less than 45, 45-65, and greater than 65 years of age) and in all races.

How should vardenafil (Levitra) be administered?

The recommended starting dose of vardenafil is 10 mg taken orally approximately one hour before sexual activity. The dose may be adjusted higher or lower depending on efficacy and side effects. The maximum recommended dose is 20 mg, and the maximum recommended dosing frequency is no more than once per day. Vardenafil can be taken with or without food.

What are the side effects of vardenafil (Levitra)?

Vardenafil is generally well tolerated with only mild side effects. These side effects include headache, flushing, nasal congestion, dyspepsia, body aches, dizziness, nausea, and increased blood levels of the muscle enzyme creatine kinase.

There have been rare reports of priapism (prolonged and painful erections lasting more than six hours) with the use of oral PDE5 inhibitors such as vardenafil, sildenafil, and tadalafil. Men with blood cell diseases such as sickle cell anemia, leukemia, and multiple myeloma have higher than normal risks of developing priapism. Untreated priapism can cause injury to the penis tissue and lead to permanent loss of potency. If there is prolonged erection (longer than four hours), immediate medical assistance should be sought.

Who should not use vardenafil (Levitra)?
Vardenafil (Levitra) can cause hypotension (abnormally low blood pressure, which can lead to fainting and even shock) when given to patients who are taking nitrates. People taking nitrates daily should not take vardenafil. Most commonly used nitrates are medications to relieve angina (chest pain due to insufficient blood supply to heart muscle because of narrowing of the coronary arteries). These include nitroglycerine tablets, patches, ointments, sprays, pastes, and isosorbide dinitrate and isosorbide mononitrate. Other nitrates such as amyl nitrate and butyl nitrate are found in some recreational drugs called "poppers."

Vardenafil should not be used with alpha-blockers, medicines used to treat high blood pressure and benign prostate hypertrophy (BPH), because the combination of vardenafil and an alpha-blocker may lower the blood pressure greatly and lead to dizziness and fainting. Examples of alpha-blockers include tamsulosin (Flomax), terazosin (Hytrin), doxazosin (Cardura), alfuzosin (Uroxatral), and prazosin (Minipress).

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

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

• unstable angina (chest pain due to coronary artery disease that occurs at rest or with minimal physical exertion),

• low blood pressure (a resting systolic blood pressure less than 90mm Hg),

• uncontrolled high blood pressure (greater than 170/110 mm Hg),

• recent stroke or heart attack (within six months),

• uncontrolled, potentially life-threatening abnormal heart rhythms,

• severe liver disease,
• severe kidney failure requiring dialysis,
• severe heart failure or disease of the heart's valves, for example, aortic stenosis,

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

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

What precautions should be taken when using vardenafil (Levitra)?

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

• Men taking erythromycin or ketoconazole should not take more than 5 mg of vardenafil in a 24-hour period.

• Men taking high doses of ketoconazole (Nizoral) should not take more than 2.5 mg of vardenafil in a 24-hour period.

• Men with moderately severe liver disease also should not take more than a 5 mg dose of vardenafil in a 24-hour period.

• Men taking the protease inhibitor (for the treatment of HIV/AIDS) indinavir (Crixivan) should not take more than 2.5 mg of vardenafil in a 24-hour period.

• Men taking another protease inhibitor ritonavir (Norvir) should not take more than 2.5 mg of vardenafil every 72 hours.

Tadalafil (Cialis)
What is tadalafil (Cialis)?

Tadalafil (Cialis) is the third oral medicine approved by the U.S. FDA for the treatment of erectile dysfunction. Like sildenafil (Viagra) and vardenafil (Levitra), tadalafil inhibits PDE5 (as described earlier).

How effective is tadalafil (Cialis)?
The safety and efficacy of tadalafil in the treatment of erectile dysfunction was evaluated in 22 clinical trials involving more than 4,000 men. Seven of these trials were randomized, prospective, placebo-controlled studies of 12 weeks' duration. Two of these studies (involving 402 men) were conducted in the United States, and the other five studies (involving 1,112 men) were conducted outside the United states. Two of these trials were conducted in special populations with erectile dysfunction; one in men with diabetes mellitus, another in men who developed erectile dysfunction after nerve-sparing prostate cancer surgery.

Effectiveness of tadalafil in these studies was assessed using a sexual function questionnaire. Study participants also were asked if they were able to achieve vaginal penetration and to maintain erections long enough for successful intercourse.

In all seven trials, tadalafil was significantly better than placebo in improving men's ability to achieve and maintain erections. Improvements in erectile function was observed in some patients at 30 minutes after taking a dose; and improvements can last for up to 36 hours after taking Cialis when compared to placebo.

How should tadalafil (Cialis) be administered?

The recommended starting dose of tadalafil for most patients is 10 mg taken orally approximately one hour before sexual activity. The dose may be adjusted higher to 20 mg or lower to 5 mg depending on efficacy and tolerability. The maximum recommended dosing frequency is once per day, although for many patients tadalafil can be taken less frequently since the improvement in erectile function may last 36 hours. Tadalafil may be taken with or without food.

What are the side effects of tadalafil (Cialis)?

Tadalafil is generally well tolerated with only mild side effects. The most common side effects reported include headache, indigestion, back pain, muscle aches, facial flushing, and nasal congestion.

Back pain and muscle aches occurred in less than 7% of patients and usually occurred 12-24 hours after taking tadalafil. The back pain and muscle aches associated with tadalafil were characterized by mild to moderate muscle discomfort in the lower back, buttocks, and thighs, often aggravated by lying down. The back and muscle aches resolved in most patients without treatment within 48 hours. When treatment was necessary, acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs) such as Motrin, Advil, or Aleve were effective. Approximately 0.5% of all the patients using tadalafil discontinued the drug due to back pain or muscle aches.

Reports of abnormal vision were rare; it occurred in less than 0.1% of patients using tadalafil.

There have been rare reports of priapism (prolonged and painful erections lasting more than six hours) with the use of oral PDE5 inhibitors such as vardenafil, sildenafil, and tadalafil. Men with blood cell diseases such as sickle cell anemia, leukemia, and multiple myeloma have higher than normal risks of developing priapism. Untreated priapism can cause injury to the penile tissue and lead to permanent loss of potency. If there is prolonged erection (longer than four hours), immediate medical assistance should be sought.

Who should not use tadalafil (Cialis)?
Tadalafil can cause hypotension (abnormally low blood pressure, which can lead to fainting and even shock) when given to patients who are taking nitrates. Patients taking nitrates daily should not take tadalafil. Most commonly used nitrates are medications to relieve angina (chest pain due to insufficient blood supply to heart muscle because of narrowing of the coronary arteries). These include nitroglycerine tablets, patches, ointments, sprays, pastes, and isosorbide dinitrate and isosorbide mononitrate. Other nitrates such as amyl nitrate and butyl nitrate are found in some recreational drugs called "poppers."

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

Tadalafil is not recommended for men with the following conditions:

• unstable angina (chest pain due to coronary artery disease that occurs at rest or with minimal physical exertion),

• low blood pressure (a resting systolic blood pressure less than 90mm Hg),

• uncontrolled high blood pressure (greater than 170/110 mm Hg),

• recent stroke or heart attack (within six months),

• uncontrolled, potentially life-threatening abnormal heart rhythms,

• severe liver disease,
• severe heart failure or disease of the heart valves, for example, aortic stenosis,

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

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

What precautions should be taken when using tadalafil?

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

• Medications such as erythromycin, ketoconazole (Nizoral), itraconazole (Sporanox), ritonavir (Norvir), and indinavir (Crixivan) can slow the breakdown of tadalafil. Therefore men taking these medications should not take more than 10 mg of tadalafil and should not take tadalafil more frequently than every 72 hours.

• No tadalafil dose adjustment is necessary for men with only mild kidney disease. Men with moderately severe kidney impairment should start tadalafil at 5 mg every 24 hours and not to exceed the maximum dose of 10 mg taken every 48 hours. In men with severe kidney disease and on dialysis, the maximum dose should not exceed 5 mg.

• Men with severe liver disease should not take tadalafil. Men with mild to moderate liver disease should not exceed tadalafil dose of 10 mg once daily.

Intracavernosal injections
What are intracavernosal injections?

Medications can be injected directly into the corpora cavernosa to attain and maintain erections. Medications such as papaverine hydrochloride, phentolamine, and prostaglandin E1 (alprostadil) can be used alone or in combinations to attain erections. Combining small amounts of each drug is preferred over using a single drug because of increased efficacy and fewer side effects. Even though such injections can be effective in the management of erectile dysfunction (success rate of around 80%), they are not widely used because of their potential complications. These injections are painful, can cause scarring of the penis, and have a higher risk of developing priapism.

Intraurethral suppositories
What are intraurethral suppositories?

Prostaglandin E1 (intraurethral alprostadil or MUSE) can be inserted in a pellet (suppository) form into the urethra to attain erections. This technique also is not popular because of occasional side effects of pain in the penis and sometimes in the testicles, mild urethral bleeding, dizziness, and vaginal itching in the sex partner. Men also need to remain standing after inserting the pellet in order to increase blood flow to the penis, and it may take 15-30 minutes to attain an erection. Prostaglandin can cause uterine contractions and should not be used by men having intercourse with pregnant women unless condoms or other barrier devices are used. This drug is now rarely used since the introduction of oral medications, however, it may play a role in management of erectile dysfunction in those who are not a candidate for oral PDE5 medications.

How effective is testosterone in treating erectile dysfunction?

In patients with hypogonadism, testosterone treatment can improve libido and erectile dysfunction, but the response of erectile dysfunction in men with hypogonadism to testosterone is not complete; many men still may need additional oral medications such as sildenafil, vardenafil, or tadalafil.

In men 40 years of age or older, a breast examination, digital examination of the prostate, and a PSA level (prostate specific antigen) blood test should be done to exclude breast and prostate cancer before starting testosterone treatment since testosterone can aggravate breast and prostate cancers. Patients who have breast and prostate cancers or are suspected of having them should not use testosterone.

Blood testosterone levels can be measured to detect deficiency. Although, there is no clear cut testosterone level to define hypogonadism, levels lower than 250 nanograms per deciliter are considered low, and levels of greater than 350 nanograms per deciliter are considered normal. Testosterone levels in between these numbers may be labeled indeterminate.

Certain medications can alter the gonadal function, including thiazide diuretics, some seizure medications, long-acting oral opiate pain medications, antipsychotic medications, and oral steroids.

Can low testosterone level be replaced?
Because of potential adverse effects and complex metabolism, the use of testosterone replacement therapy (TRT) is limited to men with symptoms of erectile dysfunction and a testosterone level of less than 200 nanogram per deciliter. Preparations available in the U.S. are topical, injectable, and transbuccal (placing inside mouth between the cheek and upper gum) testosterone. Oral preparations are not available in the U.S.

Common side effects of testosterone replacement therapy include local irritations, prostate enlargement, breast tissue enlargement, aggravation of breast and prostate cancers, depression, elevation of red blood cell count (polycythemia), or worsening of congestive heart failure.

Vacuum devices
What are vacuum devices?

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

1. a plastic cylinder, in which the penis is placed;

2. a pump, which draws air out of the cylinder;
3. an elastic band, which is placed around the base of the penis, to maintain the erection after the cylinder is removed and during intercourse by preventing blood from flowing back into the body (see figure 2).

One variation of the vacuum device involves a semi-rigid rubber sheath that is placed on the penis and remains there after attaining erection and during intercourse.

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

1. to implant a device that causes the penis to become erect;

2. to reconstruct arteries in order to increase the flow of blood to the penis;

3. to block veins that drain blood from the penis.
Implantable devices, known as prostheses, can cause erections in many men with impotence.

Malleable implants usually consist of paired rods, which are inserted surgically into the corpora cavernosa, the twin chambers running the length of the penis. The user manually adjusts the position of the penis and, therefore, the rods. Adjustment does not affect the width or length of the penis.

Inflatable implants consist of paired cylinders, which are surgically inserted inside the penis and can be expanded using pressurized fluid. Tubes connect the cylinders to a fluid reservoir and pump, which also are surgically implanted. The patient inflates the cylinders by pressing on the small pump, located under the skin in the scrotum. Inflatable implants can expand the length and width of the penis somewhat. They also leave the penis in a more natural state when not inflated.

Possible problems with prostheses include mechanical breakdown and infection. Mechanical problems have diminished in recent years because of technological advances.

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

What about psychological therapy?
Experts often treat psychologically based impotence using techniques that decrease anxiety associated with intercourse. The patient's partner can help apply the techniques, which include gradual development of intimacy and stimulation. Such techniques also can help relieve anxiety when physical impotence is being treated. If these simple behavioral methods at home are ineffective, referral to a sex counselor may be advised.

What will the future bring for erectile dysfunction?

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

Yohimbine is an older medication used for erectile dysfunction, but the data to support its effectiveness remain mixed. In practice, clinicians sometimes choose yohimbine in the setting of psychogenic erectile dysfunction.

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

Several other medications are being studied for treating erectile dysfunction; these include IC351 (another PDE5 inhibitor), sublingual apomorphine, and the combination of yohimbine and L-arginine. Scientists also are researching gene therapy to treat erectile dysfunction.






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