Erectile dysfunction (ED) is the inability to acquire or sustain a penile erection of sufficient rigidity for sexual intercourse. The condition affects close to 20% of males over 20 years old in the United States.[1] Over time, erections may take longer to develop, be less rigid, or require more direct stimulation. Orgasms may be less intense, the volume of ejaculate frequently decreases, and the refractory period increases.

Related disorders include abnormal curvature of the penis during erection due to fibrosis (Peyronie’s disease), decreased libido, anejaculation or retrograde ejaculation, and premature ejaculation. Any disorder that impairs blood flow to the penis (e.g., atherosclerosis) or causes injury to the penile nerves, smooth muscle, or fibrous tissue has the potential to cause ED.[2]

Changes in erectile function are common. But unexplained ED should not be regarded as benign. ED is often a sign of vascular disease and should be taken as a sign that vascular disease is likely present elsewhere in the body.[2] Patients should be screened for cardiovascular risk factors and treated appropriately in order to prevent myocardial infarction, stroke, or other vascular events.

Some cases are related to endocrine abnormalities, medications (e.g., sympathetic blockers, antidepressants, and antihypertensives), or psychogenic issues. Prostate surgery may lead to ED, but that may improve over the first 18 months after surgery if nerve-sparing techniques are used. However, irreversible ED is still common after prostate surgery.

Risk Factors

Vascular disease. Cardiovascular disease and its risk factors increase the risk of ED.[3] Atherosclerosis reduces blood flow and may contribute to 50-60% of cases. PET imaging of prostate cancer patients reveals a significant correlation between calcified plaques in penile arteries and the diagnosis or future development of ED.[4] ED can be an early warning sign of future cardiovascular disease.[5],[6]

Age. ED is most common in men older than 65. About 5% of 40-year-old men and 15-25% of 65-year-old men experience some degree of ED. This is not the consequence of age per se, but of accumulated vascular disease, medications, etc.

Diabetes mellitus. At least half of patients with long-standing diabetes experience ED, due to damage of small blood vessels and nerves. Middle aged men with ED should be screened for underlying diabetes.[7]

Chronic kidney disease (CKD). Similar to diabetes, patients with CKD are more likely to have comorbid peripheral neuropathy, autonomic dysfunction, depression, or peripheral vascular disease that contribute to ED.

Neurologic conditions. Several neurologic conditions result in ED, including spinal cord and brain injuries, stroke, multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease.

Endocrine disorders. Thyroid disorders, testosterone deficiency (primary or secondary), and hyperprolactinemia can result in loss of libido and ED.

Surgery. Colon, prostate, bladder, and rectum surgery may damage erectile nerves and blood vessels. Cryotherapy of the prostate may lead to high rates of impotence while nerve-sparing techniques decrease impotence incidence to ~ 50%.

Radiation therapy. Radiation treatment for prostate or bladder cancer causes ED in ~ 50% of treated men. The use of brachytherapy may reduce this number.

Medications. More than 200 commonly prescribed drugs are known to cause ED. These include thiazides, antihistamines (e.g., cimetidine), antidepressants (e.g., SSRIs), spironolactone, sympathetic blockers, ketoconazole, and appetite suppressants.

Substance abuse. Excessive use of alcohol, tobacco, marijuana, methylenedioxymethamphetamine (MDMA, better known as Ecstasy), and other recreational drugs can cause ED, which may be irreversible in some cases. For example, excessive tobacco use can permanently damage penile arteries.

Obesity. Excess body fat weight contributes to ED by increasing estrogen activity and aggravating diabetes and lipid disorders.

Psychosocial factors. Stress and depression may contribute to sexual dysfunction, including ED.

Diagnosis

A careful medical and sexual history is essential for diagnosis. Sexual history should include onset of symptoms, presence of spontaneous erections (i.e., morning erections), and risk factors. A psychiatric interview and questionnaire may reveal psychological factors, such as depression and anxiety. In some cases, it may be helpful to interview the patient’s sexual partner.
Physical examination can provide clues to systemic problems, such as neurologic abnormalities (e.g., visual field defects that occur with pituitary tumor), vascular abnormalities (e.g., decreased peripheral pulses), developmental abnormalities (e.g., abnormal secondary sex characteristics, penile curvature, gynecomastia), and primary testicular failure (bilaterally small, absent, or undescended testes).
Laboratory evaluation may include serum testosterone, prolactin, and thyroid function tests to evaluate for hormonal abnormalities, particularly if libido is poor. Patients should also be screened for diabetes with fasting glucose or glycated hemoglobin (A1C), kidney and liver function with a comprehensive metabolic profile, and cardiovascular risk factors with a lipid profile.
Nocturnal penile tumescence testing can help rule out psychological etiologies, but it is rarely performed because of the ready availability of ED medications. Doppler ultrasound or angiography of the penile arteries may be used to identify arterial occlusion or venous leak, but neither is likely to alter the choice of therapy.

Treatment

Treatment is aimed at restoring the ability to acquire and sustain erections and reactivating the libido. Diet and lifestyle factors are central to ED treatment and to the prevention of associated cardiovascular conditions, which may be life-threatening.

Smoking cessation and controlling diabetes and hypertension are also essential.

Stopping and/or changing medications that might be causing ED is important.

The most commonly used class of medications is phosphodiesterase-5 (PDE5) inhibitors (e.g., sildenafil, vardenafil, tadalafil, avanafil). These medications are contraindicated in men taking nitrates and are less likely to be effective in men with diabetes or those who have had prostatectomy.

Hormonal therapy with testosterone may be effective but is only recommended in a small number of patients with documented hypogonadism.

Yohimbine may improve erections and increase libido by stimulating the parasympathetic nervous system, especially in psychogenic ED, but given limited data and the availability of effective phosphodiesterase-5 inhibitors (PDE5) inhibitors, this medication is rarely used.[8] (See Nutritional Considerations.)

Treatment of comorbid psychiatric disorders may improve sexual functioning. Between 20-50% of men with impotence have symptoms of depression, which may contribute to ED. Self-esteem may also suffer as a result of ED. Individual or couples psychotherapy may be a helpful part of impotence treatment.[9]

Vacuum devices, intraurethral therapies (alprostadil), and vasodilating penile injections may be beneficial but are used as second-line treatments when there is no improvement with PDE5 inhibitors.

Surgical interventions include implantable prostheses and correction of penile curvature.

Nutritional Considerations

Impotence is often the result of vascular disease, and risk factors for cardiovascular disease are commonly found in patients with ED. Risk factors for ED include elevated cholesterol and triglyceride levels, hypertension, obesity, smoking, age, increased waist circumference, indices of low-grade inflammation, ischemic disease, and metabolic syndrome.[10],[11],[12],[13] Moreover, ED should be viewed as a sign that other cardiovascular problems may manifest in the future, and that diet and lifestyle changes to help prevent these problems are essential. Reduced nitric oxide availability, secondary to obesity and endothelial dysfunction plays a role in cardiometabolic disease as well as ED.

Although the evidence on nutritional treatment is limited, interventions that reduce cardiovascular risk factors or improve blood vessel reactivity (diet, exercise, and certain dietary supplements) may improve symptoms. Weight loss, whether a result of a diet restricted in calories or low in fat, improves ED, as revealed by the International Index of Erectile Function 5-item score (IIEF).[14] Previous research found that a low-fat, low-cholesterol diet combined with exercise resulted in normal sexual function in 31% of men with ED, compared with about 5% in a control group. This combination also significantly reduced several vascular risk factors, including obesity, high blood pressure, elevated serum lipids, and elevated blood glucose and insulin concentrations.[15]

See Coronary Heart Disease chapter for dietary factors to prevent or treat cardiovascular disease.

Dietary supplements are not a substitute for a healthful diet and lifestyle because they do not address the cause of vascular disorders. Nonetheless, dietary supplements, including L-arginine, ginseng, and pycnogenol, have proven effective in treating ED in clinical trials. These appear to work by enhancing nitric oxide release and increasing cyclic guanosine monophosphate (cGMP), which allows penile arterial relaxation and engorgement.

Arginine has appeared in numerous clinical trials to work more effectively in combination with other agents, including adenosine monophosphate, pycnogenol, and yohimbine. In a double-blind, placebo-controlled, two-way crossover, randomized clinical trial in which arginine was given in high doses (8 g/day) in combination with 200 mg of adenosine monophosphate, IIEF scores in the active treatment improved significantly compared with placebo.[16] Pycnogenol, a standardized extract of French maritime pine bark, is a catalyst for endothelial nitric oxide synthase (eNOS). In a double-blind, placebo-controlled clinical trial of 124 men with mild to moderate ED, a daily combination of 80 mg pycnogenol and 2.8 g of arginine resulted in significant improvement in the IIEF score compared with placebo.[17]

Panax ginseng also contains active ingredients (ginsenosides) that increase the release of nitric oxide. Controlled clinical studies have found that mean scores on the IIEF were significantly higher in patients treated with ginseng than in those who received placebo.[18] A meta-analysis concluded that the effects of ginseng on ED are significant but that the methodologic quality of studies makes drawing definitive conclusions difficult.[19] Additional controlled clinical studies are needed to definitively establish a role for ginseng in ED treatment.

Dietary supplements should be used only under medical supervision, due to the possibility of medication interactions. Certain over-the-counter supplements for ED that contain yohimbine, an alpha 2-adrenoreceptor antagonist, have led to at least two deaths.[20]

Dietary interventions that boost nitric oxide availability may be more feasible and less expensive while providing other benefits by reducing risk or improving hypertension, osteoporosis, COPD, and protecting against certain types of cancer. Foods that have high nitrate and nitrite concentrations include beets, spinach, radishes, celery, lettuce, and broccoli.[21]

Orders

See chapters on Basic Diet Orders and Coronary Heart Disease and Diabetes Mellitus.

Smoking cessation.

Exercise prescription.

Referral for psychiatric evaluation, as appropriate.

What to Tell the Family

Discussion with family members regarding the patient’s medical problems should only be done with permission from the patient, particularly in the case of sensitive diagnoses such as ED. With the patient’s permission, however, the sexual partner may be included in discussions of treatment options.

Patients with impotence are commonly at risk for other cardiovascular problems. Dietary changes, especially a low-fat, vegan diet, along with smoking cessation and exercise, can alter these risk factors. To the extent that the entire family adopts such a diet, patient adherence is facilitated, and the patient and family are all likely to benefit.

References