Understanding Erectile Dysfunction and Its Causes

health professionals found the prevalence of sexual dysfunction in men to be 12 percent in those younger than 59 years, 22 percent in those 60 to 69 years of age, and 30 percent in those older than 69 years.3 Persons with type 2 diabetes mellitus have a threefold greater risk of ED compared with the general population.4 Depression increases the risk of ED, but it is not clear if this relationship is causal.5 ED may result from organic causes (e.g., vascular, neurogenic, hormonal, anatomic, drug-induced), psychological causes, or a combination of both. A normal sexual erectile response results from the interaction between neurotransmitter, biochemical, and vascular smooth muscle responses initiated by parasympathetic and sympathetic neuronal triggers that integrate physiologic stimuli of the penis with sexual perception and desire. Nitric oxide produced from endothelial cells after parasympathetic stimuli triggers a molecular cascade that results in smooth muscle relaxation and arterial influx of blood into the corpus cavernosum. This is followed by compression of venous return, which produces an erection.6 There is no preferred, first-line diagnostic test for ED, and routine screening is not recommended. History and physical examination are sufficient in making an accurate diagnosis of ED in most cases.

Penile duplex ultrasonography is not a useful diagnostic test for ED.7 The American Urological Association (AUA) recommends that the initial evaluation of ED include a complete medical, sexual, and psychosocial history.8 The medical history may reveal comorbid conditions, risk factors related to ED (Table 1),9 or medications that contribute to ED (Table 2).6 Sexual history should focus on erection adequacy, altered libido, quality and timing of orgasm, volume and appearance of ejaculate, presence of sexually-induced genital pain or penile curvature (Peyronie disease), and partner sexual function.

Lifestyle Changes

Patients should be counseled regarding risks, benefits, and expectations of this procedure. The AUA does not endorse penile venous reconstructive surgery or surgeries to limit venous outflow premature ejaculation treatment from the penis. Penile arterial reconstructive surgery is controversial and more rigorous trials are needed to prove short- and long-term effectiveness.16 Korean red ginseng (Panax ginseng) at 900 mg three times daily has been reported to improve erections but not overall sexual experience.33 Yohimbine has shown superiority over placebo for treatment of ED with limited adverse effects,34 but is not recommended by the AUA because of questions about its safety and effectiveness.8 Some dietary supplements marketed for treatment of ED obtainable via the Internet (e.g., Super X, Stamina-Rx) contain PDE5 inhibitors (sildenafil 30 mg and tadalafil 20 mg, respectively). Although these and other similar products claim to be free of any adverse effects, they have the same risks as PDE5 inhibitors.35 When there is no obvious medical etiology for ED, psychosocial factors should be explored. The potential clue that psychosocial factors may be a cause is that a man is able to achieve normal erections and orgasm through masturbation or sex with a partner other than the “index case” partner with whom he has erectile dysfunction (e.g., a spouse with whom there is substantial conflict).

BEHAVIOR THERAPY

Group or individual cognitive behavior therapy; psychosexual therapy, including sensate focus technique; and therapy aimed at improving relationship difficulties may help to improve sexual dysfunction in men. A 2007 Cochrane review found that men who received group therapy plus sildenafil had more successful intercourse and were less likely to drop out of the study compared with those who received only sildenafil.36 When comparing psychosocial interventions versus alprostadil injections and vacuum pump devices, no differences in effectiveness were found.36 In some cases, education about medical and psychosocial etiologies of ED in conjunction with physician reassurance may prove adequate to restore normal male sexual function. The five-item version of the International Index of Erectile Function Questionnaire is a validated survey instrument that can be used to assess the severity of ED symptoms (Table 3).10 The physical examination should assess blood pressure and heart rate; body habitus, for central obesity; and cardiovascular, neurologic, and genitourinary systems, including penile, testicular, and digital rectal examinations (Figure 1).8,9,11–14 The AUA and World Health Organization recommend limited diagnostic testing in men with ED. First-line therapy for ED is aimed at lifestyle changes and modifying pharmacotherapy that may contribute to ED8 (Table 26). Sedentary lifestyle, a significant risk factor for cardiovascular disease, may also be a modifiable risk factor for ED.15 Obesity nearly doubles the risk of ED3; one study determined that one third of men who were obese improved their ED with moderate weight loss and an increase in the amount and duration of regular exercise.14 The risk of moderate or total ED is almost double in men who smoke compared with nonsmokers.16 Patient education should be aimed at increasing exercise, losing weight to achieve a body mass index (BMI) less than 30 kg per m2, and stopping smoking. Phosphodiesterase type 5 (PDE5) inhibitors are the most effective oral drugs in the treatment of ED,9,12 and should be considered first-line therapy.8,14,17 Retail sales of sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) approached $1.48 billion in 2007.18 Sildenafil has been found to be effective and safe in cases of ED associated with diabetes mellitus17,19 and spinal cord injury,20 and in men with sexual dysfunction secondary to antidepressant therapy.21 Compared with placebo, sildenafil has been shown to improve erections (74 versus 21 percent; number needed to treat [NNT] = 2)22 and results in more frequent intercourse attempts (57 versus 21 percent; NNT = 3).23 Approximately one third of men with ED do not respond to therapy with PDE5 inhibitors. These agents are not effective for improving libido.24 The three PDE5 inhibitors are considered to be relatively similar in effectiveness, but there are differences in dosing, onset of action, and duration of therapeutic effect (Table 6).25 There are no rigorous data to suggest that one PDE5 inhibitor is superior to another.

An open-label fildena super active 100 trial found that patients preferred tadalafil and vardenafil over sildenafil,26 yet most evidence supports equal effectiveness between sildenafil and vardenafil.27 PDE5 inhibitors are generally well tolerated, with mild transient adverse effects of headache, flushing, dyspepsia, rhinitis, and abnormal vision. Headache is the most commonly reported adverse effect, occurring in approximately 10 percent of patients.

• Lifestyle changes can improve ED symptoms significantly.
• Regular exercise boosts blood flow and sexual health.
• Quitting smoking enhances erectile function.
• Limiting alcohol intake can prevent worsening ED.
• Maintaining a healthy weight reduces risk factors.
• Managing stress improves overall sexual performance.

Rare but important adverse effects include dizziness, syncope, and nonarteritic anterior optic neuropathy (predominantly from crossover phosphodiesterase type 6 inhibition). PDE5 inhibitors should not be taken concomitantly with nitrates because this may lead to a synergistic effect, resulting in a potentially serious, even fatal, decrease in blood pressure. PDE5 inhibitors are metabolized by the cytochrome P450 3A4 and may affect metabolism of protease inhibitors and antifungal medications.

ED Treatment Options

LIFESTYLE MODIFICATIONS

Intracavernosal pressure and PDE5 activity are androgen-dependent.

The big four

It should initially be administered in the physician's office at the lowest dose and sequentially titrated to an adequate erectile response while monitoring for syncope. The physicians should also provide education on self-administration.8 Intra-cavernosal alprostadil is more effective, better tolerated, and preferred by men over the intraurethral buy vardenafil 40mg form.32 Common adverse effects of intraurethral alprostadil include local penile pain, urethral bleeding, dizziness, and dysuria. Common adverse effects of intracavernosal alprostadil include penile pain, edema and hematoma, palpable nodules or plaques, and priapism. Patients should be informed about the potential for occurrence of prolonged erections and should seek emergent medical evaluation for rigid erections lasting longer than four hours. Priapism is most commonly treated with aspiration of blood from the corpus cavernosum under local anesthetic.

Can you use baking soda for erectile dysfunction treatment?

If this treatment is insufficient, then intra-cavernosal injections of phenylephrine should be performed with hemodynamic monitoring to watch for severe hypertension, tachycardia, or arrhythmia. Vacuum pump devices are a noninvasive second-line option (Figure 2). They are contraindicated in men with sickle cell anemia or blood dyscrasias, and in those taking anticoagulants. If used properly, adverse effects and potential risks are negligible, yet there may be a substantial learning curve. When first- and second-line therapies have failed, surgical implantation of an inflatable penile prosthesis can be considered in consultation with a urologist (Figure 3). The prevalence of hypogonadism (defined as a morning serum total testosterone level less than 300 ng per dL [10.41 nmol per L]) in men with ED is estimated to be 5 to 10 percent.13,28 In men with hypogonadism, testosterone supplementation is superior to placebo in improving erections and sexual function. Response rates are higher in primary versus secondary testicular failure, and with transdermal versus oral or intramuscular testosterone.13 Supplementation is also associated with improved satisfaction with erectile function and sexual desire.29 Men with hypogonadism who failed a trial of sildenafil were found to have significant improvement in erectile function with the addition of testosterone supplementation.30 Testosterone supplementation may result in erythrocytosis, elevated serum trans-aminase levels, exacerbation of untreated sleep apnea, benign prostatic hyperplasia, and an increased risk of adenocarcinoma of the prostate. Men receiving testosterone supplementation require more frequent monitoring of hemoglobin, serum transaminase, and prostate-specific antigen levels, and prostate examinations.31 Alprostadil (Caverject) is a viable second-line therapeutic option for the treatment of ED. It should initially be administered in the physician's office at the lowest dose and sequentially titrated to an adequate erectile response while monitoring for syncope. The physicians should also provide education on self-administration.8 Intra-cavernosal alprostadil is more effective, better tolerated, and preferred by men over the intraurethral buy vardenafil 40mg form.32 Common adverse effects of intraurethral alprostadil include local penile pain, urethral bleeding, dizziness, and dysuria. Common adverse effects of intracavernosal alprostadil include penile pain, edema and hematoma, palpable nodules or plaques, and priapism. Patients should be informed about the potential for occurrence of prolonged erections and should seek emergent medical evaluation for rigid erections lasting longer than four hours. Priapism is most commonly treated with aspiration of blood from the corpus cavernosum under local anesthetic. If this treatment is insufficient, then intra-cavernosal injections of phenylephrine should be performed with hemodynamic monitoring to watch for severe hypertension, tachycardia, or arrhythmia.

Test Your Knowledge

Vacuum pump devices are a noninvasive second-line option (Figure 2). They are contraindicated in men with sickle cell anemia or blood dyscrasias, and in those taking anticoagulants. If used properly, adverse effects and potential risks are negligible, yet there may be a substantial learning curve. When first- and second-line therapies have failed, surgical implantation of an inflatable penile prosthesis can be considered in consultation with a urologist (Figure 3). Patients should be counseled regarding risks, benefits, and expectations of this procedure. The AUA does not endorse penile venous reconstructive surgery or surgeries to limit venous outflow premature ejaculation treatment from the penis.

About the Reviewer

These agents are not effective for improving libido.24 The three PDE5 inhibitors are considered to be relatively similar in effectiveness, but there are differences in dosing, onset of action, and duration of therapeutic effect (Table 6).25 There are no rigorous data to suggest that one PDE5 inhibitor is superior to another. An open-label fildena super active 100 trial found that patients preferred tadalafil and vardenafil over sildenafil,26 yet most evidence supports equal effectiveness between sildenafil and vardenafil.27 PDE5 inhibitors are generally well tolerated, with mild transient adverse effects of headache, flushing, dyspepsia, rhinitis, and abnormal vision. Headache is the most commonly reported adverse effect, occurring in approximately 10 percent of patients. Rare but important adverse effects include dizziness, syncope, and nonarteritic anterior optic neuropathy (predominantly from crossover phosphodiesterase type 6 inhibition). PDE5 inhibitors should not be taken concomitantly with nitrates because this may lead to a synergistic effect, resulting in a potentially serious, even fatal, decrease in blood pressure.

Table 3. Five-Item Version of the International Index of Erectile Function Questionnaire

PDE5 inhibitors are metabolized by the cytochrome P450 3A4 and may affect metabolism of protease inhibitors and antifungal medications. Intracavernosal pressure and PDE5 activity are androgen-dependent. The prevalence of hypogonadism (defined as a morning serum total testosterone level less than 300 ng per dL [10.41 nmol per L]) in men with ED is estimated to be 5 to 10 percent.13,28 In men with hypogonadism, testosterone supplementation is superior to placebo in improving erections and sexual function. Response rates are higher in primary versus secondary testicular failure, and with transdermal versus oral or intramuscular testosterone.13 Supplementation is also associated with improved satisfaction with erectile function and sexual desire.29 Men with hypogonadism who failed a trial of sildenafil were found to have significant improvement in erectile function with the addition of testosterone supplementation.30 Testosterone supplementation may result in erythrocytosis, elevated serum trans-aminase levels, exacerbation of untreated sleep apnea, benign prostatic hyperplasia, and an increased risk of adenocarcinoma of the prostate. Men receiving testosterone supplementation require more frequent monitoring of hemoglobin, serum transaminase, and prostate-specific antigen levels, and prostate examinations.31 Alprostadil (Caverject) is a viable second-line therapeutic option for the treatment of ED. Penile arterial reconstructive surgery is controversial and more rigorous trials are needed to prove short- and long-term effectiveness.16 Korean red ginseng (Panax ginseng) at 900 mg three times daily has been reported to improve erections but not overall sexual experience.33 Yohimbine has shown superiority over placebo for treatment of ED with limited adverse effects,34 but is not recommended by the AUA because of questions about its safety and effectiveness.8 Some dietary supplements marketed for treatment of ED obtainable via the Internet (e.g., Super X, Stamina-Rx) contain PDE5 inhibitors (sildenafil 30 mg and tadalafil 20 mg, respectively).

Link to Cardiovascular Disease

health professionals found the prevalence of sexual dysfunction in men to be 12 percent in those younger than 59 years, 22 percent in those 60 to 69 years of age, and 30 percent in those older than 69 years.3 Persons with type 2 diabetes mellitus have a threefold greater risk of ED compared with the general population.4 Depression increases the risk of ED, but it is not clear if this relationship is causal.5 ED may result from organic causes (e.g., vascular, neurogenic, hormonal, anatomic, drug-induced), psychological causes, or a combination of both. A normal sexual erectile response results from the interaction between neurotransmitter, biochemical, and vascular smooth muscle responses initiated by parasympathetic and sympathetic neuronal triggers that integrate physiologic stimuli of the penis with sexual perception and desire. Nitric oxide produced from endothelial cells after parasympathetic stimuli triggers a molecular cascade that results in smooth muscle relaxation and arterial influx of blood into the corpus cavernosum. This is followed by compression of venous return, which produces an erection.6 There is no preferred, first-line diagnostic test for ED, and routine screening is not recommended. History and physical examination are sufficient in making an accurate diagnosis of ED in most cases.

Horny goat weed

Penile duplex ultrasonography is not a useful diagnostic test for ED.7 The American Urological Association (AUA) recommends that the initial evaluation of ED include a complete medical, sexual, and psychosocial history.8 The medical history may reveal comorbid conditions, risk factors related to ED (Table 1),9 or medications that contribute to ED (Table 2).6 Sexual history should focus on erection adequacy, altered libido, quality and timing of orgasm, volume and appearance of ejaculate, presence of sexually-induced genital pain or penile curvature (Peyronie disease), and partner sexual function. The five-item version of the International Index of Erectile Function Questionnaire is a validated survey instrument that can be used to assess the severity of ED symptoms (Table 3).10 The physical examination should assess blood pressure and heart rate; body habitus, for central obesity; and cardiovascular, neurologic, and genitourinary systems, including penile, testicular, and digital rectal examinations (Figure 1).8,9,11–14 The AUA and World Health Organization recommend limited diagnostic testing in men with ED. First-line therapy for ED is aimed at lifestyle changes and modifying pharmacotherapy that may contribute to ED8 (Table 26). Sedentary lifestyle, a significant risk factor for cardiovascular disease, may also be a modifiable risk factor for ED.15 Obesity nearly doubles the risk of ED3; one study determined that one third of men who were obese improved their ED with moderate weight loss and an increase in the amount and duration of regular exercise.14 The risk of moderate or total ED is almost double in men who smoke compared with nonsmokers.16 Patient education should be aimed at increasing exercise, losing weight to achieve a body mass index (BMI) less than 30 kg per m2, and stopping smoking. Phosphodiesterase type 5 (PDE5) inhibitors are the most effective oral drugs in the treatment of ED,9,12 and should be considered first-line therapy.8,14,17 Retail sales of sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) approached $1.48 billion in 2007.18 Sildenafil has been found to be effective and safe in cases of ED associated with diabetes mellitus17,19 and spinal cord injury,20 and in men with sexual dysfunction secondary to antidepressant therapy.21 Compared with placebo, sildenafil has been shown to improve erections (74 versus 21 percent; number needed to treat [NNT] = 2)22 and results in more frequent intercourse attempts (57 versus 21 percent; NNT = 3).23 Approximately one third of men with ED do not respond to therapy with PDE5 inhibitors. Although these and other similar products claim to be free of any adverse effects, they have the same risks as PDE5 inhibitors.35 When there is no obvious medical etiology for ED, psychosocial factors should be explored.

• Counseling may help if emotional or psychological factors cause ED.
• Psychotherapy can address performance anxiety.
• Relationship counseling improves communication.
• Stress, depression, and anxiety can affect erections.
• Mental health support can enhance treatment outcomes.
• Combining therapy with medication often yields better results.

The potential clue that psychosocial factors may be a cause is that a man is able to achieve normal erections and orgasm through masturbation or sex with a partner other than the “index case” partner with whom he has erectile dysfunction (e.g., a spouse with whom there is substantial conflict).

What can cause erectile dysfunction

Group or individual cognitive behavior therapy; psychosexual therapy, including sensate focus technique; and therapy aimed at improving relationship difficulties may help to improve sexual dysfunction in men. A 2007 Cochrane review found that men who received group therapy plus sildenafil had more successful intercourse and were less likely to drop out of the study compared with those who received only sildenafil.36 When comparing psychosocial interventions versus alprostadil injections and vacuum pump devices, no differences in effectiveness were found.36 In some cases, education about medical and psychosocial etiologies of ED in conjunction with physician reassurance may prove adequate to restore normal male sexual function.