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WHAT ARE THE ORAL TREATMENTS FOR ERECTILE DYSFUNCTION?
Sildenafil (Viagra)
Sildenafil (Viagara) was originally developed for heart disease but was found to have a unique mechanism of action that targeted factors specific to the penis. The drug blocks the enzyme phosphodiesterase-5 (PDE5). This action maintains persistent levels of cyclic GMP, a chemical that is produced in the penis during sexual arousal and which is the primary chemical that relaxes smooth muscles and increases blood flow.
Good Candidates for Sildenafil. Sildenafil (Viagra) is now prescribed in over 90% of erectile dysfunction cases. It is a good choice for any man in good health who does not have conditions that preclude taking it. Studies indicate that overall, it may help more than 70% of patients achieve sexual function, with results depending, however, on individual conditions. It should be noted that other good options are still available for many men who do not respond to sildenafil.
Studies are indicating that sildenafil 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). Success rates in one study were 69%.
Controlled hypertension.
Kidney conditions, including those that require chronic dialysis and kidney transplantation.
Parkinson's disease. There is even some evidence that Sildenafil may have properties that help brain functions (attention, memory).
Sildenafil may also help restore erectile dysfunction in some men who have had the following conditions or treatments:
Spina bifida, a congenital defect of the spinal cord.
Spinal cord injury with some erectile response.
Radiation therapy for local prostate cancer. Advanced radiation techniques, such as 3D conformal therapy, along with sildenafil offer the best chances for success (70% in one study).
Nerve-sparing radical prostatectomy. Sildenafil restores potency in an average of 30% of patients who have had this surgery for prostate cancer. It may be considerable more 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. When it works, it may take nine months or longer, so men might benefit from alprostadil injections starting right after surgery. They help prevent scarring and preserve elasticity.
Higher-Risk Candidates. Men with the following conditions should not take sildenafil without the recommendation of their physicians and even then should use it with caution:
Severe heart disease, such as unstable angina, a history of heart attack, or arryhthmias. 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. [See also Effects on the Heart, below.]
Recent history of stroke.
Hypotension (very low blood pressure).
Uncontrolled diabetes.
Uncontrolled hypertension.
Taking anticoagulant therapy.
Heart failure.
Retinitis pigmentosa. (With this genetic disease, people do not produce phosphodiesterase-5 and do not respond to sildenafil.)
Administration and Effect. Sildenafil is effective within 20 to 40 minutes; its effects may last for several hours. The drug works only when the man experiences some sexual arousal. Patients usually take 50 mg, although lower doses (e.g., 25 mg) may be appropriate in some groups, such as elderly patients. Sildenafil should not be used more than once a day and the dose should not exceed 100 mg. It may help men who did not respond to initial therapy with penile injections. and can also be used together with injections, though side effects can be quite intense when the combination is used.
Side Effects and Other Limitations. Common side effects include flushing, gastrointestinal distress, headache, nasal congestion, and dizziness.
Effects on the Heart. There were early reports of fatal heart attacks in a small percentage of men taking the drug. While more recent studies are not finding a higher risk for heart attack so far in men who take Viagara, its effects on the heart and circulation are mixed. On the one hand, a small 2001 study reported that it may improve blood flow to the heart. However, another 2001 study reported that the drug may excite the nerves associated with heart function. And it is known to cause small drops in blood pressure. Of specific concern in this regard are sudden and possibly dangerous drops in blood pressure when Viagara is taken with nitrates, such as nitroglycerine, which are used for angina. The effects have been fatal in some men. No one taking nitrates, including the recreational drug amyl nitrate, should take sildenafil. The bottom line is that caution is still warranted for men with severe heart disease until more research has been conducted.
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.
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.
New Generation PDE5 Inhibitors
Researchers are investigating a newer version of drugs that inhibit the enzyme targeted by sildenafil, phosphodiesterase-5 (PDE5).
IC351 (Cialis). Cialis is a potent and highly selective PDE5 inhibitor and may not affect other parts of the body, including the brain, heart, kidney and eyes. Clinical trials are reporting significant success rates in up to 88% of patients. It appears to take effect in 15 minutes and the effects last up to 24 hours. Improved results were reported in men suffering from erectile dysfunction of varying severity and causes. Common side effects include headache, muscle pain, stomach upset following meals, and back pain. Additional trials of the drug are under way.
Vardenafil. Vardenafil is another PDE5 inhibitor currently being investigated. One small study concluded that it increased penile rigidity and tumescence. Another found that it may aid men who have impotence because of prostate cancer surgery. Further evaluation is warranted.
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
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. Some experts believe testosterone replacement therapy also may be helpful for older men whose testosterone levels are deficient. Over the course of about three months, it may gradually heighten sexual interest. It can also improve bone density, boost energy and mood, and increase muscle mass and weight.
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. The skin patch achieves normal testosterone levels in between 67% and 90% of men.
Skin gel (Androgel). At this time, the gel is applied only to the same parts of the body as the patch. In one study the gel produced normal testosterone levels in 87% of men. 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 in Men with Normal Levels. Testosterone therapy is not recommended for men with testosterone levels that are normal for their age group. In such men, replacement therapy does not appear to have any benefits for increased bone mass or muscle strength. There is also some concern that replacement therapy in men with normal testosterone levels may increase the risk for the following adverse effects:
Lower HDL (the so-called good cholesterol).
Rapid growth of prostate tumors in men with existing prostate cancers. (Although some studies indicate that taking testosterone does not increase the risk for prostate cancer, some 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.
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.
Yohimbine
Yohimbine (Yocon, Yohimex) is derived from an herbal remedy. It appears to boost erectile function by improving blood flow. Studies have been inconclusive about its benefits, but a recent analysis of seven trials reported that between 34% and 75% of men achieved favorable results when taking 5 mg to 10 mg. Side effects include nausea, insomnia, nervousness, and dizziness. Large doses of yohimbine can increase blood pressure and heart rate. One death has been reported from taking tablets of the standard dosage (5.4 mg). More rigorous studies are needed to confirm its effectiveness, and men suffering from anxiety or hypertension are cautioned against its use. To boost success rates, some doctors suggest combining it with the antidepressant drug trazodone if a patient is also depressed.
The American Urologic Association does not recommend yohimbine for treating impotence, although some experts believe it is an inexpensive and reasonable option for some men. It should be noted, that Yohimbine is available over the counter as an herbal remedies. It is not government regulated and brands vary in effectiveness and quality. [See What Are the Alternative Treatments for Impotence?]
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), but it does not interact with nitrates. In some studies, it was effective in producing 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 (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. It is available in Europe but the manufacturer withdrew the drug application in the US.
Alpha-MSH Agents. Researchers are investigating drugs that are derived from a natural substance released in the brain called alpha-MSH, which increases sexual behavior. One agent called Melanotan II is showing promise in investigative studies. In one study, 60% of men achieved erections after injections of Melanotan II, but up to 20% of men experience severe nausea. It appears to increase sexual desire and takes over an hour to take effect. Another promising agents is a nasal spray called PT-141 that may enhance erectile function by stimulating receptors in the hypothalamus section of the brain. This area of the brain is associated with emotions and sexual arousal.
Review Date: 6/30/2002
Reviewed By: Harvey Simon, MD, Editor-in-Chief, Well-Connected reports; Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.
Sildenafil (Viagra)
Sildenafil (Viagara) was originally developed for heart disease but was found to have a unique mechanism of action that targeted factors specific to the penis. The drug blocks the enzyme phosphodiesterase-5 (PDE5). This action maintains persistent levels of cyclic GMP, a chemical that is produced in the penis during sexual arousal and which is the primary chemical that relaxes smooth muscles and increases blood flow.
Good Candidates for Sildenafil. Sildenafil (Viagra) is now prescribed in over 90% of erectile dysfunction cases. It is a good choice for any man in good health who does not have conditions that preclude taking it. Studies indicate that overall, it may help more than 70% of patients achieve sexual function, with results depending, however, on individual conditions. It should be noted that other good options are still available for many men who do not respond to sildenafil.
Studies are indicating that sildenafil 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). Success rates in one study were 69%.
Controlled hypertension.
Kidney conditions, including those that require chronic dialysis and kidney transplantation.
Parkinson's disease. There is even some evidence that Sildenafil may have properties that help brain functions (attention, memory).
Sildenafil may also help restore erectile dysfunction in some men who have had the following conditions or treatments:
Spina bifida, a congenital defect of the spinal cord.
Spinal cord injury with some erectile response.
Radiation therapy for local prostate cancer. Advanced radiation techniques, such as 3D conformal therapy, along with sildenafil offer the best chances for success (70% in one study).
Nerve-sparing radical prostatectomy. Sildenafil restores potency in an average of 30% of patients who have had this surgery for prostate cancer. It may be considerable more 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. When it works, it may take nine months or longer, so men might benefit from alprostadil injections starting right after surgery. They help prevent scarring and preserve elasticity.
Higher-Risk Candidates. Men with the following conditions should not take sildenafil without the recommendation of their physicians and even then should use it with caution:
Severe heart disease, such as unstable angina, a history of heart attack, or arryhthmias. 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. [See also Effects on the Heart, below.]
Recent history of stroke.
Hypotension (very low blood pressure).
Uncontrolled diabetes.
Uncontrolled hypertension.
Taking anticoagulant therapy.
Heart failure.
Retinitis pigmentosa. (With this genetic disease, people do not produce phosphodiesterase-5 and do not respond to sildenafil.)
Administration and Effect. Sildenafil is effective within 20 to 40 minutes; its effects may last for several hours. The drug works only when the man experiences some sexual arousal. Patients usually take 50 mg, although lower doses (e.g., 25 mg) may be appropriate in some groups, such as elderly patients. Sildenafil should not be used more than once a day and the dose should not exceed 100 mg. It may help men who did not respond to initial therapy with penile injections. and can also be used together with injections, though side effects can be quite intense when the combination is used.
Side Effects and Other Limitations. Common side effects include flushing, gastrointestinal distress, headache, nasal congestion, and dizziness.
Effects on the Heart. There were early reports of fatal heart attacks in a small percentage of men taking the drug. While more recent studies are not finding a higher risk for heart attack so far in men who take Viagara, its effects on the heart and circulation are mixed. On the one hand, a small 2001 study reported that it may improve blood flow to the heart. However, another 2001 study reported that the drug may excite the nerves associated with heart function. And it is known to cause small drops in blood pressure. Of specific concern in this regard are sudden and possibly dangerous drops in blood pressure when Viagara is taken with nitrates, such as nitroglycerine, which are used for angina. The effects have been fatal in some men. No one taking nitrates, including the recreational drug amyl nitrate, should take sildenafil. The bottom line is that caution is still warranted for men with severe heart disease until more research has been conducted.
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.
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.
New Generation PDE5 Inhibitors
Researchers are investigating a newer version of drugs that inhibit the enzyme targeted by sildenafil, phosphodiesterase-5 (PDE5).
IC351 (Cialis). Cialis is a potent and highly selective PDE5 inhibitor and may not affect other parts of the body, including the brain, heart, kidney and eyes. Clinical trials are reporting significant success rates in up to 88% of patients. It appears to take effect in 15 minutes and the effects last up to 24 hours. Improved results were reported in men suffering from erectile dysfunction of varying severity and causes. Common side effects include headache, muscle pain, stomach upset following meals, and back pain. Additional trials of the drug are under way.
Vardenafil. Vardenafil is another PDE5 inhibitor currently being investigated. One small study concluded that it increased penile rigidity and tumescence. Another found that it may aid men who have impotence because of prostate cancer surgery. Further evaluation is warranted.
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
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. Some experts believe testosterone replacement therapy also may be helpful for older men whose testosterone levels are deficient. Over the course of about three months, it may gradually heighten sexual interest. It can also improve bone density, boost energy and mood, and increase muscle mass and weight.
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. The skin patch achieves normal testosterone levels in between 67% and 90% of men.
Skin gel (Androgel). At this time, the gel is applied only to the same parts of the body as the patch. In one study the gel produced normal testosterone levels in 87% of men. 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 in Men with Normal Levels. Testosterone therapy is not recommended for men with testosterone levels that are normal for their age group. In such men, replacement therapy does not appear to have any benefits for increased bone mass or muscle strength. There is also some concern that replacement therapy in men with normal testosterone levels may increase the risk for the following adverse effects:
Lower HDL (the so-called good cholesterol).
Rapid growth of prostate tumors in men with existing prostate cancers. (Although some studies indicate that taking testosterone does not increase the risk for prostate cancer, some 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.
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.
Yohimbine
Yohimbine (Yocon, Yohimex) is derived from an herbal remedy. It appears to boost erectile function by improving blood flow. Studies have been inconclusive about its benefits, but a recent analysis of seven trials reported that between 34% and 75% of men achieved favorable results when taking 5 mg to 10 mg. Side effects include nausea, insomnia, nervousness, and dizziness. Large doses of yohimbine can increase blood pressure and heart rate. One death has been reported from taking tablets of the standard dosage (5.4 mg). More rigorous studies are needed to confirm its effectiveness, and men suffering from anxiety or hypertension are cautioned against its use. To boost success rates, some doctors suggest combining it with the antidepressant drug trazodone if a patient is also depressed.
The American Urologic Association does not recommend yohimbine for treating impotence, although some experts believe it is an inexpensive and reasonable option for some men. It should be noted, that Yohimbine is available over the counter as an herbal remedies. It is not government regulated and brands vary in effectiveness and quality. [See What Are the Alternative Treatments for Impotence?]
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), but it does not interact with nitrates. In some studies, it was effective in producing 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 (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. It is available in Europe but the manufacturer withdrew the drug application in the US.
Alpha-MSH Agents. Researchers are investigating drugs that are derived from a natural substance released in the brain called alpha-MSH, which increases sexual behavior. One agent called Melanotan II is showing promise in investigative studies. In one study, 60% of men achieved erections after injections of Melanotan II, but up to 20% of men experience severe nausea. It appears to increase sexual desire and takes over an hour to take effect. Another promising agents is a nasal spray called PT-141 that may enhance erectile function by stimulating receptors in the hypothalamus section of the brain. This area of the brain is associated with emotions and sexual arousal.
Review Date: 6/30/2002
Reviewed By: Harvey Simon, MD, Editor-in-Chief, Well-Connected reports; Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.