Erectile Dysfunction - Workup and Management Tactics
Causes of ED | About Diagnosis | Workup | Medical Therapy | Clinical Highlights
Abstract: Organic conditions are the most common cause of erectile dysfunction (ED), particularly in men older than 50 years. ED may signal an underlying, treatable disorder such as hypertension, diabetes mellitus, hypercholesterolemia, heart disease, or peripheral vascular disease. Other major risk factors are aging, obesity, cigarette smoking, medications (e.g., tranquilizers, antiulcer agents, antidepressants, antihistamines, and antihypertensives), and injury to the pelvic region. Psychological factors play a role in a small percentage of long-term cases. Examine the external genitalia fo revidence of Peyronie's disease, balanitis, and phimosis. Medical treatment options include sildenafil, testosterone therapy (for men with hypogonadism), vacuum devices, and prostaglandin therapy.
Nearly all primary care providers have men in their practice who suffer from erectile dysfunction (ED). Severe or complete ED -- the total inability to achieve or maintain an erection sufficient for sexual performance -- may affect as many as 20 to 30 million men in the United States. About 10% of men between the ages of 40 and 70 years have severe or complete ED, and an addtional 25% of men in this age group have moderate or intermittent erectile difficulties.
The disorder is highly age-dependent; the combined prevalence of moderate to complete ED rises from approximately 22% at age 40 years to 49% by age 70 years. Although less common in younger men, ED affects 5% to 10% of men who are younger than 40
ED also has a profound effect on the man's sex partner and their relationship. Consequently, ED is strongly related to both physical and psychological health.
In this article, the focus is on evaluating and treating ED in the primary care setting. I review common risk factors, discuss which tests enhance the workup, and weigh the pros and cons of available therapies.
Causes of ED
ED no longer is considered primarily a psychological disorder. Organic or physicial conditions are the most common causes, particularly in men older than 50 years. ED may be a symptom of an underlying, treatable disorder, such as hypertension, diabetes mellitus, hypercholesterolemia, heart disease, or peripheral vascular disease. Other major risk factors for ED are age, obesity, cigarette smoking, medications, and injury to the pelvic region.
Psychological factors play a role in a small percentage of long-term cases (those that persist for more than one year)1. Stress, anxiety, depression and bereavement can cause ED; management consists of medical therapy for both ED and the psychological disorder. Refer patients with severe psychopathology to a psychiatrist.
Physicial conditions that disrupt blood flow are the most common causes of ED. More than half of patients older than 50 years suffer from vascular disease2. Diabetes, hypertension, and atherosclerosis decrease blood flow or cause deterioration of arteries, thus reducing the blood supply to the corporal bodies of the penis. Cigarette smoking also reduces blood flow.
Peyronie disease causes fibrosis of the corporal bodies of the penis and restricts the blood supply, which results in angulation of the penis and decreased rigidity beyond the fibrotic plaque. Aging often affects venous outflow; blood that enters the corporal bodies leaves the penis at the same rate. This makes it difficult to maintain an erection.
Damage to the cavernous nerves that originate in the pelvis can inhibit the initiation of sufficient stimuli to achieve an erection. Such damage may result from lower spinal cord injury and from non-nerve-sparing radical prostatectomy. Any significant injury to the penis, prostate, or surrounding area that leads to neural pathway damage also may produce ED. Multiple sclerosis is among the neurologic diseases that inhibit neural stimuli1.
Abnormal hormone levels.
Low testosterone levels -- which are usually responsible for a decrease in libido -- are frequently associated with aging and can cause ED. Abnormal thyroid hormone levels (both hypothyroidism and hyperthyroidism) and elevated prolactin levels are also associated with an increased incidence of ED. Endocrine disorders other than diabetes -- such as hypogonadism, thyroid disease, and hyperprolactinemia -- are a less common cause of ED; however, they can be readily treated3. Screen your patient for these conditions.
Several classes of drugs have been linked to ED; medication may be the cause of the disorder in as many as 25% of patients2. Tranquilizers and agents used to treat ulcers, depression, and allergies are among the most common culprits. Antihypertensive agents, particularly thiazides and beta-blockers, can produce ED; calcium channel blockers and the angiotensin-converting enzyme inhibitiors are less likely to cause the problem4. The use of alcohol, cocaine, and other substances of abuse also may lead to ED.
How Is Impotence Diagnosed?
Medical and sexual histories help define the degree and nature of impotence. A medical history can disclose diseases that lead to impotence. A simple recounting of sexual activity might distinguish among problems with erection, ejaculation, orgasm, or sexual desire.
A history of using certain drugs can suggest a chemical cause. Drug effects account for 25 percent of cases of impotence. Cutting back on or substituting certain medications often can alleviate the problem.
A physical examination can give clues for systemic problems. Careful attention must be paid the the circulatory and neurological systems (blood vessels and nerves) and, of course, the genitals (penis and testicles). Unusual characteristics of the penis itself could suggest the root of the impotence--for example, bending of the penis during erection could be the result of Peyronie's disease.
Several laboratory tests can help diagnose impotence. For cases of low sexual desire, measurement of testosterone in the blood and other hormones made in the brain that control the levels of testosterone can yield information about problems with the endocrine system. These may include luetenizing hormone (LH), follicle stimulating hormone (FSH) and prolactin. Tests for systemic diseases may include thyroid hormone levels, blood counts, urinalysis, lipid profile, and measurements of kidney and liver function.
Monitoring erections that occur during sleep (nocturnal penile tumescence or NPT) can help rule out certain psychological causes of impotence. Healthy men have involuntary erections during sleep. If nocturnal erections do not occur, then the cause of impotence is likely to be physical rather than psychological.
In some cases, a psychosocial examination, using an interview and questionnaire, reveals psychological factors. The man's sexual partner may also be interviewed to determine expectations and perceptions encountered during sexual intercourse. These interveiws may be performed by a special sex therapist, psychologist, psychiatrist, or any health provider with an interest in the psychological aspects of sexual problems.
Overview: What to include in the workup of erectile dysfunction
Obtain complete medical, sexual, and medication histories.
Inspect the general habitus, escutcheon, and external genitalia.
Perform a focused neruovascular examination; assess the cremasteric reflex and pinprick and light-touch responses.
Evaluate the bulbocavernosus reflex and sphincter tone during the rectal examination to assess S2 through S4 nerve function.
Palpate the pulses in the lower extremities to evaluate the vascular system.
Order a complete blood cell count, lipid profile, and urinalysis.
Measure a serum testosterone if you suspect hypogonadism.
If the testosterone level is at or below the lower limit of normal, measure serum prolactin and luteinizing hormone levels.
Assess glucose level and renal and liver function if these studies have not been done within the past year.
Most patients want to discuss sexual problems with their primary care physician. In a study of men referred to a urologist for ED, only 22% reported that their primary care physician took a sexual history. The remaining 78% said that they would have preferred to discuss their problems more extensively with their primary care physician before being referred5.
Capitalize on your relatioship and rapport with your patient. Reassure your patient that you are not embarrassed by sexual issues and that you do not undervalue his sexual concerns.
Ask about your patient's sexual health at every office visit. "Do you have any intimacy problems with your partner?" is a nonthreatening question that does not offend patients regardless of their marital status, level of sexual involvement, or gender preference. This question lets the patient know that he is welcome to discuss this sensitive subject with you.
If the man admits to a sexual problem, ask additional questions such as:
- "Is the problem partner-specific?"
- "Do you have erections at night or on awakening in the morning?"
- "Do you have erections with masturbation or self-stimulation?"
The absence of nocturnal erections or the lack of erections with masturbation strongly suggests a physical cause of the patient's ED.
Inspect the general habitus, escutcheon, and external genitalia. Assess the glans penis for balanitis and for the ability to retract the prepuce. Inability to retract the foreskin (phimosis) and balanitis can be early signs of diabetes mellitus. About 50% of men with diabetes have ED; thus, ED can be a presenting complaint of undiagnosed diabetes7.
Palpate the shaft of the penis to determine whether hard, plaque-like structures are lodged within that may prevent a normal erection (Peyronie disease). These fibrous structures can make achieving erection painful and penetration during sexual intercourse impossible.
Examine the scrotum and its contents. The normal testis is approximately 3x5 cm. Atrophic testes may be associated with a decreased serum testosterone level and a diminished libido.
A digital rectal examination is recommended for al lmen older than 50 years. Note the size, contour, consistency, and mobility of the prostate gland. A normal gland feels like a pencil eraser -- firm, smooth, and slightly movable.
Perform a focused neurovascular examination; assess the cremasteric reflex and pinprick and light-touch responses. During the rectal examination, evaluate the bulbocavernosus reflex and sphincter tone to assess S2 through S4 nerve root function.
To evaluate the patient's vascular system, palpate the pulses in the lower extremities.
Order a complete blood cell count, urinalysis and lipid profile. To avoid unnecessary tests and costs, tailor the laboratory workup to the patient's condition. 1) For example, serum testosterone measurement is probably unnecessary for a patient with normal-sized testes and an intact libido. On the other hand, this test is valuable in a patient with a solitary testis that has become smaller after an episode of epididymo-orchitis. If the testosterone level is at or below the lower limit of normal, measure serum prolactin and luteinizing hormone (LH) levels. Order an MRI scan of the head to rule out a pituitary tumor in patients with an elevated prolactin or decreased LH level.
If the patient has not been tested for diabetes within the past year, assess the glycohemoglobin level. Urinalysis can demonstrate glycosuria or infection. Glycosuria and/or a history of polyuria and polydipsia warrant a workup for diabetes mellitus.
Overview - Medical treatment options for erectile dysfunction
- Testosterone therapy (available in injectable, tablet, patch, and topical gel forms) for men with hypogonadism
- Vacuum devices
- Prostaglandin therapy (via intracavernous injection or urethral suppository)
Until the 1970s, ED was usually treated with a penile prosthesis or implant. During the past three decades, less invasive therapies have been introduced -- including oral medications, testosterone replacement therapy, vacuum devices, urethral suppositories and self-injections (Table 2).
Perhaps the most significant advance in the oral treatment of ED was the release of sildenafil in 19988. More than 6 million men in the United States have taken this drug.
Sildenafil inhibits phosphodiesterase, the enzyme that breaks down cyclic guanosine monophosphate (cGMP) to guanosine monophosphate (GMP). With increased levels of cGMP, the smooth muscle in the corporal bodies remains relaxed longer, thereby increasing the blood flow to the penis and extending the duration of the erection (box).
The potential side effects of sildenafil, including headache, visual disturbances, and indigestion, are generally mild. However, prescribe this drug with caution for men who have a history of cardiac problems; conduct a careful examination before prescribing the drug9.
Because sildenafil is often used by men who have cardiovascular risk factors, such as hypertension, hyperlipidemia, and diabetes, the effect of the drug on cardiovascular events is an important concern. An analysis of 18 placebo-controlled trials that included 4,274 men showed no difference in the incidence of myocardial infarction, angina, and coronary artery disease between sildenafil users and those who took placebo. Similar results were found in the 2,199 men who participated in open-label extensions. Blood pressure and heart rate were unaffected10.
Sildenafil is available in 25-, 50-, and 100-mg tablets. The usual starting dose is 50 mg, which is taken 30 minutes to 1-2 hours before the patient engages in sexual intimacy. For an erection to occur, genital stimulation is required. Sildenafil is usually effective for 6-8 hours after the drug is taken.
A high-fat meal may delay the absorption of the drug and extend its onset of action by 1-1/2 to 2 hours. Advise the patient to take sildenafil on an empty stomach or before eating a high-fat meal.
Prescribe a starting dose of 25 mg for patients who have significant liver or renal impairment and for those who use drugs that are metabolized by the cytochrome P450 eA4 enzyme -- such as cimetidine, erythromycin, and fluconazole. The enzyme prolongs the metabolism of sildenafil.
Sildenafil is contraindicated in patients who take nitroglycerin. The interaction of the two agents may cause a precipitous drop in blood pressure and lead to a fatal myocardial infarction or cerebrovascular accident. Warn patients who use oral or transdermal nitroglycerin to avoid taking sildenafil.
Mechanism of a Normal Erection
An erection requires coordination of the neurologic, endocrine, and vascular systems. When parasympathetic simulation and decreased sympathetic tone cause the trabecular smooth muscles in the corporal bodies of the penis to relax and the helicine arteries to dilate, increased blood flow fills the cavernosal spaces. Heightened pressure within these spaces enables the penis to become erect. Compression of the venules against the tunica albuginea causes penile pressure to approximate arterial pressure, which produces rigidity. Arterial inflow is then reduced to a level that matches venous outflow13. In many patients, erectile dysfunction results from an adequate penile blood flow to the corporal bodies or failure of the veins to trap the blood in the corporal bodies.
At the biochemical level, smooth muscle relaxation is mediated through the release of nitric oxide from the nerves that supply the penis. The gas activates guanylate cyclase to produce cyclic guanosine monophosphate (cGMP), which allows smooth muscle relaxation through a decrease in intracellular calcium. Phosphodiesterase (PDE) catalyzes the conversion of cGMP to guanosine monoophosphate (GMP), which deactivates cGMP. As cGMP is converted to GMP under the influence of PDE, the erection subsides. The principal PDE in human penile tissue is type 514.
Low levels of testosterone, or hypogonadism, may result from primary failure of the testis to produce the hormone or from secondary failure caused by pituitary factors (for example, decreased LH production associated with a tumor of the anterior pituitary gland). Reserve hormone supplementation for the small percentage of patients whose ED is caused directly by testosterone deficiency. The goal of replacement therapy is to raise testosterone levels and thus restore the sex drive and the ability to maintain an erection. Because testosterone induces prostate epithelial growth, replacement therapy is contraindicated in men who have prostate cancer or an elevated prostate-specific antigen level11.
Supplemental testosterone is available in injectable, tablet, patch, and topical gel forms. Although usually given by a physician, intramuscular injections of testosterone may be self-administered by properly trained patients. The injections are given every two weeks. Most patients respond to a dose of 200 to 300 mg of testosterone cypionate or enanthate. Advise patients that testosterone therapy is a lifelong commitment.
Oral testosterone appears to be less effective than the injectable form; it is rapidly absorbed and does not remain in circulation long enough to produce an adequate result. Thus, oral therapy is used less frequently than other forms of testosterone.
Transdermal patches, such as Androderm (testosterone, 2.5 or 5 mg) and Testoderm TTS (testosterone, 5 mg) can be applied to the arms, back, abdomen, or thighs. Each patch contains a physiologic dose that lasts for 24 hours. Recommend that the patient place the patch in a different area each day so that it is not in the same location more than once a week.
Although testosterone gels are simpler to apply, more research is needed to evaluate possible side effects experienced by the partner from the transfer of the medication during intercourse8.
Negative pressure created by these devices allows blood to be drawn into the corporal bodies of the penis. The blood is maintained in the organ with a rubber ring, or band, placed around the base of the penis. Some men find this treatment inconvenient, since they must apply the device just before intercourse. Side effects include irritation to the penis and ejaculation problems2.
This vasodiolator can be administered into the urethra via suppository or more frequently, directly into the corporal bodies of the penis by self-injection with a 25-gauge needle. Problems with such injection therapy include persistent erection, or priapism, and penile soreness or aching. Injections of prostaglandin are now commonly used as secondary therapy for men who do not respond to oral sildenafil.
Prostaglandin E1 is the only intrapenile drug the FDA has approved for ED. The injectable formulation is available in 10- and 20-microgram vials; doses are titrated upward in 5-microgram increments. Between 75% and 90% of men who use prostaglandin E1 achieve an erection12.
WHEN TO REFER
Most men with ED can be treated in the primary care setting. Indications for referral to a urologist or a psychiatrist include:
- Failure of medical therapy
- Peyronie's disease
- Severe vasculogenic ED
- Current nitroglycerin therapy that precludes use of sildenafil
- Severe depression or psychogenic ED
The absence of nocturnal erections or the lack of erections with masturbation or self-stimulation strongly suggest a physical cause of the patient's erectile dysfunction (ED).
Inspect the general habitus, escutcheon, and external genitalia. Assess the penis for balanitis and phimosis, which can be an early sign of diabetes mellitus. Look for evidence of Peyronie's disease by palpating the shaft of the penis to determine whether hard, plaque-like structures have formed within.
Measure serum testosterone level since patients with abnormal testes and/or diminished libido. If the level is at or below the lower limit of normal, obtain serum prolactin and luteinizing hormone (LH) levels. Order an MRI scan of the head to rule out a pituitary tumor in patients with an elevated prolactin level or a decreased LH level.
The usual starting dose of sildenafil is 50 mg, which is taken 45 to 60 minutes before engaging in sexual intimacy. Prescribe a starting dose of 25 mg for patients who have significant liver or renal impairment and for those who use drugs that are metabolized by the cytochrome P450 3A4 enzyme -- such as cimetidine, erythromycin, and fluconazole. The enzyme prolongs the metabolism of sildenafil. Sildenafil is contraindicated in patients who take nitroglycerin.
- Reserve hormone supplementation for the small percentage of patients whose ED is caused directly by testosterone deficiency. Because testosterone induces prostate epithelial growth, replacement therapy is contraindicated in men who have prostate cancer or an elevated prostate-specific antigen level.
Published in Consultant, October 2001.
Dr. Baum is associate clinical professor of urology at Tulane University School of Medicine and Louisiana State University School of Medicine, both in New Orleans.
- Morgentaler A. Male impotence. Lancet. 1999;354:1713-1718.
- Kaiser FE. Erectile dysfunction in the aging man. Med Clin North Am. 1999;83:1267-1278.
- Zonszein J. Diagnosis and management of endocrine disorders of erectile dysfunction. Urol Clin North Am. 1995;22:789-802.
- Drug-induced sexual dysfunction and infertility. Pharmaceutical Journal. 1999;262:780-784.
- Baldwin KC, Ginsberg PC, Harkaway RC. Under-reporting of erectile dysfunction and men with unrelated urologic conditions. J Urol. 2000;163(suppl):243. Abstract 1080.
- Marwick C. Survey says patients expect little physician help on sex. JAMA. 1999;281:2173-2174.
- Hakim LS, Goldstein I. Diabetic sexual dysfunction. Endocrinol Metab Clin North Am. 1996;25:379-400.
- Burnett A, Rowland D. Pharmacotherapy in the treatment of male sexual dysfunction. J. Sex Res. 2000;37:226.
- Cheitlin MD, Hutter Am Jr, Brindiws RG et al. Use of sildenafil (Viagra) in patients with cardiovascular disease. Circulation. 1999;99:168-177.
- Morales A, Gingell C, Collins M, et al. Clinical safety of oral sildenafil citrate (Viagra) in the treatment of erectile dysfunction. Int J Impot Res. 1998;10:69-74.
- Lue TF. Erectile dysfunction. N Engl J Med. 2000;342:1802-1813.
- Sparwasser C, Drescher P, Pust RA, Madsen PO. Long-term results of therapy with intracavernosal injections and penile venous surgery in chronic erectile dysfunction. Scand J Urol Nephrol Suppl. 1994;157:107-112.
- NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA. 1993;270:83-90.
- Naylor AM. Endogenous neurotransmitters mediating penile erection. Br J Urol. 1998;81:424-431.
Dr. Baum gratefully acknowledges the assistance of Lindsay Leuthen, BS, in the preparation of this article. Ms. Leuthen is a study coordinator in Dr. Baum's private practice in New Orleans.
Reprinted with permission from Neil Baum MD, neilbaum.com and Dialog Medical, dialogmedical.com.
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