Impotence (Erectile Dysfunction)

Description

Medications

There are three oral medications 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 causes the smooth muscles of the penis to relax and increases 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 it (such as the use of nitrates or alpha-blockers; see higher-risk candidates in this section.)

Effectiveness of PDE5 Inhibitors.

• Tadalafil (Cialis). Approved by the FDA in November 2003, tadalafil appears to take effect in 15 to 30 minutes. It is the only oral ED treatment shown to improve erectile dysfunction for up to 36 hours in most men. A randomized study of 2,102 men in the British Journal of Urology found that those nearly two-thirds of those receiving 20 mg reported successful intercourse attempts 24 to 36 hours after taking the drug.
• Vardenafil (Levitra). Extensive clinical studies have shown that vardenafil improves erectile dysfunction in up to 85% of men with the condition. It also has shown to be work well in diabetic patients and in those who have had a radical prostatectomy.
• Sildenafil (Viagra). Studies indicated that overall, sildenafil may help more than 70% of patients achieve sexual function, with results depending on indication conditions.

Studies indicate Viagra is safe and effective for many men whose erectile dysfunction is related to the following conditions:

• Hormonal problems or psychologically induced impotence. These men achieve the highest success rates (80% to 100%). Furthermore, in one study, among men with mild to moderate depression who responded to the drug, symptoms of depression eased in 76% of them.
• Stable heart disease, with symptoms responsive to drug therapy, but who are not taking nitrates.
• Controlled diabetes (type 1 or 2). Diabetes has been associated with a lower than average response to Viagra. Still, in a 2002 study over half of patients with type 2 diabetes achieved at least one successful sexual event.
• Controlled hypertension.
• Kidney conditions, including those that require chronic dialysis and kidney transplantation.
• Parkinsons disease. There is even some evidence that sildenafil may even have properties that improve depression and help brain functions (attention, memory).
• Mild to moderate congestive heart failure. (A randomized study in the March 8, 2004 Archives of Internal Medicine found that men with moderate congestive heart failure and ED can safely use sildenafil to improve their sexual function and overall quality of life, provided the men are not taking nitrates for their heart condition. In addition to exhibiting improvements in ED, the study participants taking Viagra also showed higher scores on depression screening exams. Other research has also suggested that Viagra is safe for this group of men and may even improve exercise capability.)
• Taking antidepressant agents that can cause sexual dysfunction, notably the popular serotonin reuptake inhibitors, such as Prozac.

Sildenafil may also help restore erectile dysfunction in some (but fewer) men who have had the following conditions or treatments:

• Treatments for prostate cancer. In men who have had radiation, advanced techniques, such as 3D conformal therapy, along with sildenafil offer the best chances for success (70% in one study). In men who have had surgery, sildenafil is most effective in younger men who were potent before surgery and who had bilateral nerve-sparing procedures. It is unlikely to be effective for men over 55 who had unilateral or non-nerve-sparing procedures. Starting first with alprostadil injections right after treatment, followed by sildenafil, may be the best approach and considerably improve success rates.
• Colon surgeries for cancer or inflammatory bowel disease.
• Spina bifida, a congenital defect of the spinal cord.
• Spinal cord injury. Sildenafil can be very effective in many of these men, especially those in which there is some erectile response and when the injuries are in the upper part of the spine.

Higher-Risk Candidates. PDE5 inhibitors aren't suitable for everyone. Those taking nitrate drugs for angina and/or alpha-blockers (other than Flomax 0.4 mg once daily) for hypertension and BPH should not take selective enzyme inhibitors. Men with the following conditions should not take PDE inhibitors without the recommendation of their physicians and even then should use them with caution:

• Severe heart disease, such as unstable angina, a history of heart attack, or arrhythmias. Sildenafil increases nerve activity associated with cardiovascular function, especially during physical and mental stress. Men with heart disease may benefit from an exercise test to determine whether resuming sexual activity increases their risk of a heart attack.
• Recent history of stroke.
• Hypotension (very low blood pressure).
• Uncontrolled diabetes.
• Uncontrolled hypertension.
• Taking anticoagulant therapy.
• Severe heart failure.
• Retinitis pigmentosa. (With this genetic disease, people do not produce phosphodiesterase-5 and do not respond to sildenafil.)

Administration and Effect. PDE inhibitors work only when the man experiences some sexual arousal. They are generally effective within 30 to 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. One study suggested that crushing a Viagra tablet and letting it dissolve under the tongue may speed up its actions. Its effects may last for several hours. PDE inhibitors should not be used more than once a day.

It should be noted that success rates increase with the number of attempts, so a man should not be discouraged if the drug does not work at first. In fact, one study suggested that it should be tried at least eight times using the appropriate dose. In such cases, success rates are over 80%.

Sildenafil (Viagra) can also be used together with injections, though side effects can be quite intense when the combination is used. A recent study in the Journal of Urology found that combo therapy with sildenafil (Viagra) and the testosterone gel Androgel may help restore sexual function in men with low testosterone levels who did not respond to Viagra alone.

Side Effects and Other Limitations. Common side effects of PDE inhibitors include flushing, gastrointestinal distress, headache, nasal congestion, back pain, and dizziness.

Effects on the Heart. There were early reports of fatal heart attacks in a small percentage of men taking sildenafil (Viagra). Notably, Viagra can cause drops in blood pressure that can be sudden and possibly dangerous when the drug is taken with nitrates, such as nitroglycerine, which are used for angina. Such effects have been fatal in some men. Other effects on the heart and blood vessels are not wholly known. For example, although some studies report improved blood flow to the heart, a 2001 study reported that the drug may excite the nerves associated with heart function. Nevertheless the most recent studies have not found a higher risk from Viagra for adverse heart events in men with heart disease who are not taking nitrates. In fact, some evidence suggests it may be safe for men with congestive heart failure who have the physical capacity for sexual intercourse. The bottom line is that no one taking nitrates, including the recreational drug amyl nitrate, should take sildenafil or any other PDE inhibitors. Caution is still warranted for men with severe heart disease, all evidence is reassuring on its safety for the heart.

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 sildenafil 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.

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. The drug poses a very low risk for priapism in most men. (Priapism is sustained, painful, and unwanted erection.) Exceptions are young men with normal erectile function who take sildenafil.

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

Decrease in Effectiveness. Over time, sildenafil may lose effectiveness. A 2001 study found that after two years, 20% of patients had increased their dose to achieve the same effect, and 17% had discontinued sildenafil due to loss of efficacy. It is possible that these men were suffering from heart disease or other problems that was making their impotence worse. An earlier study found that 96% of men who had been taking sildenafil for two to three years remained satisfied with the treatment. In addition, a randomized trial of 282 men with erectile dysfunction found that sildenafil treatment is less effective in men with diabetes.

Angiotensin-Receptor Blockers for Men with Hypertension

Recent drugs known as angiotensin-receptor blockers (ARBs), also known as angiotensin II receptor antagonists are being used to lower blood pressure in men with hypertension. In one study after 12 weeks of treatment with an ARB called losartan (Cozaar), 88% of hypertensive males with sexual dysfunction reported improvement in at least one area of sexuality. The number of men reporting impotence declined from 75.3% to 11.8%. Other ARBs include candesartan (Atacand), telmisartan (Micardis), and valsartan (Diovan).

Testosterone Replacement Therapy

Testosterone replacement therapy may be helpful for some men, particularly those with hypogonadism. Forms of testosterone therapy include the following:

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

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

Testosterone replacement is used or investigated in the following:

• Replacement Therapy for Hypogonadism. Testosterone replacement therapy may be effective in inducing puberty in adolescent boys with hypogonadism and may also be helpful for some adult patients with the condition. Either the skin patch or gel achieves normal testosterone levels in between 67% and 90% of men. The gel is proving to be more effective than the patch at improving sexual desire and well being. It may also be more effective in boosting energy and mood and increasing muscle mass and weight in men with testosterone deficiencies.
• Replacement for Older Men with Androgen Deficiencies. Some experts believe testosterone replacement therapy may be helpful for older men whose androgen (male hormone) levels are deficient.
• Testosterone in Men with Normal Levels. Testosterone therapy is not recommended for men with testosterone levels that are normal for their age group. One 2003 study did report that short-term (one-month) use of the patch in men with low-normal testosterone levels improved their response to sildenafil (Viagra).

There is some concern that replacement therapy may increase the risk for the following adverse effects, particularly in men with normal testosterone levels:

• Lower HDL (the so-called good cholesterol).
• Rapid growth of prostate tumors in men with existing prostate cancers. (Taking testosterone does not appear to increase the risk for prostate cancer, but experts remain concerned.)
• Lower sperm count.
• Possible cause of sleep apnea.
• Possible increased risk for polycythemia, an abnormal increase in red blood cells.
• Possible increased risk for benign prostatic hyperplasia.

In men with normal male hormone levels, replacement therapy also does not appear to improve bone mass or muscle strength.

DHEAS. Dehydroepiandrosterone sulfate (DHEAS) is a male hormone involved in the production of testosterone. Levels of this hormone decrease as a man ages. In a 2000 study, men under 60 years old with erectile dysfunction tended to have lower DHEAS levels than their peers. In one small study, those who took DHEAS for 16 weeks experienced some improvement in erectile dysfunction. It is available as a supplement but should not be taken without the recommendation of a physician. The long-term effects of this potent hormone are unknown but may be similar to those of testosterone replacement.

Experimental Agents

Oral Phentolamine. Phentolamine is an agent that has been used in injections for achieving erection. The drug blocks adrenaline (epinephrine), which dilates blood vessels. An oral form of phentolamine (Vasomax) has been developed that may be of some benefit for men with mild impotence. The drug is not as effective as sildenafil (Viagra) and it has more side effects. However, Vasomax works faster and it does not interact with nitrates. Studies suggest that it produces erections within 20 to 40 minutes in 40% to 50% of men with mild to moderate erectile dysfunction. Side effects include nasal congestion, headache, light-headedness, low blood pressure, tachycardia (increased heart rate), and nausea.

Apomorphine. Apomorphine (Spontane, Uprima), which is taken as a tablet under the tongue, causes a sexual signal in the brain to trigger an erection, although it is not an aphrodisiac. Studies report improved erectile function in 40% to 60% of men, with the better results occurring at the higher doses. High doses, however, also cause severe side effects, including nausea (in between 15% to a third of patients), yawning, fatigue, dizziness, sweating, excitability, and aggression. Apomorphine appears to be safe for men with diabetes or stable heart disease, and is well tolerated by men with high blood pressure. However, a recent European study of men with erectile dysfunction who had never received therapy found that Viagra worked better than apomorphine. It is not approved for use in the United States. It is available in Europe but not in the US.

Opioid Antagonists. Opioid antagonists, such naltrexone (ReVia), are used to help maintain abstinence in alcoholism. Naltrexone may be helpful for erectile dysfunction in men with inhibited sexual desire. A clinical trial is underway using naltrexone and yohimbe, the common alternative remedy for impotence. The most common side effect of naltrexone is nausea, which is usually mild and temporary. High doses can cause liver damage. The drug should not be administered to anyone who has used narcotics within a week to 10 days.

Intranasal melanocortin receptor agonist (PT-141). Findings presented at the 2004 American Urological Association Annual Meeting suggest that the nasal spray PT-141 may be an effective for treatment of erectile dysfunction. PT-141 works on the central nervous system instead of the vascular system. Unlike oral treatments, it does not require stimulation for erection to occur. It is currently undergoing clinical trials.