Authors: Macfarlane, Michael T.
Title: Urology, 4th Edition
Copyright 2006 Lippincott Williams & Wilkins
> Table of Contents > Part One - Chief Presentations > Chapter 8 - Erectile Dysfunction
Erectile dysfunction (ED), defined as the inability to maintain an erect penis with sufficient rigidity for sexual intercourse, is an increasingly common presenting complaint and is estimated to affect 10 million men in the United States. ED can include partial or brief erections to complete ED (impotence). With basic knowledge about the physiology and neuropharmacology of erection, we can approach the problems systematically and logically.
In brief, the neurovascular mechanism of erection involves the following. In the flaccid state, cavernosal smooth muscle tone is high, causing an increased resistance to incoming blood. Erection occurs via stimulation by parasympathetic fibers of the pelvic plexus and cavernous nerves. Resulting arteriolar dilation and sinusoidal smooth muscle relaxation within the corpora cavernosa allow increased arterial blood flow. As the cavernosal sinusoids distend with incoming blood, the subtunical venular plexuses become compressed, thus reducing venous outflow. With stretching of the tunica albuginea to its capacity, the emissary veins eventually close within the tunical layers, further decreasing venous outflow to a minimum. The direct inducer of sinusoidal smooth muscle relaxation has been identified as endothelium-derived relaxing factor, now known to be nitric oxide, by way of its action on cyclic guanosine monophosphate (cGMP). Tonic sinusoidal smooth muscle contraction of the normally flaccid penis may be mediated by the neurotransmitter endothelin-1. Thus physiologic erections are the result of nitric oxide induced cGMP. cGMP is broken down by the enzyme phosphodiesterase type 5 (PD-5).
Some drugs known to produce erections include papaverine, nitroglycerin, -blockers such as phentolamine, prostaglandin
Psychological causes (e.g., performance anxiety, depression) used to be considered the most common reason for ED but are now thought to be the primary factors in only a few cases. Secondary psychological components can be expected in all cases.
Organic (50% 90%)
Vasculogenic. This is the most common single cause and is due to either poor inflow (e.g., arterial insufficiency, large-vessel atherosclerosis, or small-vessel diabetes) or enhanced outflow (e.g., venous leak).
Endocrine. Hypogonadotropic males with small atrophic testes and low serum testosterone levels.
Neurologic. Common neurologic etiologies include diabetic neuropathy, spinal cord injury, and development after surgery.
End-organ failure. Priapism or Peyronie's disease can cause cavernosal injury, which can result in ED.
Medications. Drug-induced impotence was reported to constitute 25% of cases in one review. Patients taking medications affecting the autonomic nervous system or vascular systems may benefit from attempts to change or modify these medications; however, modification is frequently neither successful nor an option because of the patient's poor cardiovascular status. Alcoholism, a common cause of impotence, may result in decreased testosterone and increased estrogen levels and alcoholic polyneuropathy. Cigarette smoking may induce vasoconstriction and sinusoidal smooth muscle contraction. Psychotropic agents such as phenothiazines, butyrophenones, tricyclic antidepressants, and monoamine oxidase inhibitors have been implicated in ED.
Pelvic surgery. Damage to pelvic nerves or pudendal arteries during pelvic surgery (e.g., after a radical prostatectomy, cystectomy, or abdominal perineal resection) can result in ED.
History and Physical Examination
Question patients concerning recent life crises such as deaths, divorce, financial problems, or loss of job. Determine whether the patient ever has an erection (e.g., on arising in the morning) and when his last normal erection was. Take a careful drug history, including alcohol, tobacco, and illegal drugs. Question for evidence of vascular disease (e.g., claudication, coronary artery disease, hypertension, or diabetes). Ask about a history of pelvic or perineal trauma or surgery. Examination should include evidence of secondary sexual characteristics, peripheral pulses, neurologic examination, and general genitourinary examination, with attention to possible plaques along the shaft of the penis (i.e., Peyronie's disease; see Chapter 9).
Fasting blood glucose screening for diabetes
Serum free testosterone (hypogonadism) and prolactin (hyperprolactinemia) levels
Penile rigidity monitoring gives an objective, noninvasive assessment of both tumescence and rigidity.
Vasoactive intracavernous injection. The ability to have a full erection within 10 to 15 minutes of an intracavernous papaverine or PGE1 injection essentially eliminates significant arterial or venous impairment. Further vascular evaluation is probably unnecessary.
Duplex ultrasound and color Doppler analysis (before and after papaverine injection) evaluates cavernosal anatomy and artery flow.
Dynamic cavernosography and cavernosometry. Monitoring intracavernous pressures while performing corpora
Pudendal arteriography (after papaverine injection) has been used to evaluate posttraumatic impotence.
The introduction of oral PD-5 inhibitors has revolutionized the workup and management of ED. PD-5 inhibitors have generally replaced the use of specialized studies in most men with ED. A trial of a PD-5 inhibitor is often the first approach in men without contraindications to these agents.
PD-5 inhibitors enhance the effects of nitric oxide activated increases in cGMP by inhibiting the breakdown of cGMP. PD-5 inhibitors are contraindicated in patients taking nitrates or those who have serious cardiovascular compromise. They also should be avoided or used with caution when taken with -blockers. PD-5 inhibitors have a number of other adverse drug interactions, which must be cautioned against (refer to prescribing inserts). Common side effects include headache, flushing of the face, and upset stomach. Some of the serious side effects include myocardial infarction, stroke, and loss of vision. PD-5 inhibitors should be used with caution.
Sildenafil (Viagra) was the first PD-5 inhibitor on the market. Sildenafil should be effective approximately 30 to 60 minutes after an oral dose. Dosages are 25, 50, or 100 mg.
Vardenafil (Levitra) was the second PD-5 inhibitor released. It has a shorter onset of action. Dosages are 2.5, 5, 10, or 20 mg.
Todalafil (Cialis) is the most recent PD-5 inhibitor. It boasts a longer half-life and thus may last for up to 36 hours. Dosages are 5, 10, or 20 mg.
Mechanical Vacuum Constriction Devices
External vacuum-pump devices have proven successful for many patients and are a good initial approach before more invasive modalities.
Testosterone injections (testosterone enanthate 200 mg IM q3wk) have occasionally been shown to be effective in patients with documented low testosterone levels. Caution should be used in elderly patients suspected of having prostate cancer.
Vasoactive Intracavernous Injections
Self-administered intracavernous PGE1 combination therapy (papaverine 12 mg/mL, PGE1 9 g/mL, and phentolamine 1 mg/mL) has been demonstrated to be beneficial. Complications include dizziness, flushing, hypotension, local pain, infection, hematomas, priapism, and fibrosis of the corpora cavernosa.
Referral to a sexual-dysfunction clinic is indicated for patients with a clear psychological etiology.
Vascular causes have been treated with various procedures to either improve arterial inflow or slow venous outflow from the corpora cavernosa. These techniques have met with limited success even in highly specialized hands. Large-vessel stenosis, such as in the hypogastrics, has occasionally been treated with balloon dilatation. Isolated venous leaks have been successfully treated with vein ligation.
Prostheses remain a form of therapy for patients with erectile impotence that cannot be managed with less invasive techniques. Success is generally good, with few complications. The most frequent complications include infection (which necessitates removal of prosthesis), erosion, and malfunction. Prostheses should be used with caution to treat patients for whom psychotherapy failed. Patients should be warned that no return to normal erection is possible once a prosthesis has been used. Be sure to correct any bladder-outlet obstruction (e.g., benign prostatic hyperplasia) before a prosthesis is inserted. Transurethral surgery can be a challenge with a penile prosthesis in place.