Introduction

OPTIMIZING THE MANAGEMENT OF ED Urological and Medical Evaluation of Men with Erectile Dysfunction Culley C. Carson, MD Department of Surgery, Division of Urology, University of North Carolina, Chapel Hill, NC As the medical understanding of erectile dysfunction has evolved, the approach to its evaluation must also change. A good doctor/patient rapport is crucial to making patients more comfortable talking about their sexual function. Questionnaires help elicit specific information on which to base the diagnosis and find the etiology, along with examination of the genitals and hormone and other assays. If oral therapy is unsuccessful, other studies may find underlying conditions, leading to appropriate treatment. [Rev Urol. 2002;4(suppl 3):S2–S8] © 2002 MedReviews, LLC Key words: Duplex Doppler ultrasonography • Erectile dysfunction • Hypogonadism • Low libido • Nocturnal penile tumescence monitoring ver the past two decades, the concept of erectile dysfunction has evolved from that of a disorder referred to as impotence and considered predominantly psychogenic to that of erectile dysfunction (ED), a well-understood physiologic result of multiple risk factors, both organic and psychological, which result in inadequate erectile function for coitus. Masters and Johnson suggested in 1970 that the majority of ED cases were psychogenic in nature, with less than 10% involving organic abnormalities.1 In 1972, Finkle and Thompson wrote that “pragmatic counseling" rather than psychotherapy renewed sexual function.2 These clinicians suggested that “congestive prostatitis" was associated with a psychological burden, a “problem in the head." The first extensive epidemiologic study of male sexual behavior in the United States was reported in 1948 by Kinsey and colleagues.3 They concluded that the prevalence of ED was less than 1% in men O S2 VOL. 4 SUPPL. 3 2002 REVIEWS IN UROLOGY Evaluation of Men with ED younger than 30 years, less than 3% in those 30–45, 6.7% in those 45–55, 13.5% in those 55–65, 25% in those 65 and up, and up to 80% in those 80 years of age or more. tionship issues; self-esteem; moral and cultural values; and patient fears about their bodies, aging, and psychological health. Clearly, appropriate management and understanding The problems of sexuality overlap into relationship issues; self-esteem; moral and cultural values; and patient fears about their bodies, aging, and psychological health. Unfortunately, however, their sample of patients older than 55 was small, and the results for older ages not significant. It was not until the Massachusetts Male Aging Study in 1987 to 1989 and the National Health and Social Life Survey in 1992 that prevalence of ED in men in the United States was accurately measured as more than 50% in those above 40 and 31% in men overall.4,5 Similarly, the term impotence has been supplanted by the term erectile dysfunction, defined by the 1992 National Institutes of Health Consensus Panel as “the inability to achieve and maintain an erection sufficient for satisfactory sexual function."6 With the introduction of new, effective, oral, noninvasive medications, such as sildenafil, to treat ED in 1998, the field of ED has been revolutionized. Indeed, the evaluation of men with ED has changed from an extensive, invasive series of procedures necessary to identify those patients who could be treated by injection therapy or surgery to an evaluation scheme to identify those patients at risk for ED, modify the risk factors, and provide a trial of oral therapy as the first line of treatment. Despite the emphasis on organic ED, pure psychogenic ED occurs, and in those patients with organic ED an emotional aspect of sexual function is virtually always present. The problems of sexuality overlap into rela- of psychological issues are essential for appropriately evaluating and treating patients, gaining their trust, and providing state-of-the-art therapy for patients with sexual concerns and dysfunction. Setting and Approach As a first step, a physician/patient dialogue must be initiated to fully evaluate the clinical abnormalities associated with ED. This begins with a face-to-face interview, a sympathetic history taking with privacy and physician concern to maintain patient trust, comfort, and openness. A knowledgeable professional medical staff must be available to answer questions that patients may be initially embarrassed to ask physicians. Facilitating this interaction using a standardized questionnaire may open such outcomes questionnaires as the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) may be useful.9 The BSFI is composed of 11 questions developed to measure sexual drive, erectile function, problem assessment, and overall sexual satisfaction. It is a brief, clinically validated, and standardized self-administered questionnaire that works well in the office setting. The IIEF, a cross-culturally and psychometrically validated questionnaire, is widely used in clinical trials for medications and other interventions for ED. This 15-item questionnaire is evaluated for multiple domains, including erectile function, ejaculatory function, and desire. Erectile function is graded by severity, based on a scale from 6 to 30. The shorter 5-question SHIM is, perhaps, the easiest for patients to take and for physicians to evaluate as a screening instrument. The EDITS questionnaire, not designed for initial evaluation, is useful for quantifying patient and partner satisfaction with treatment modalities initiated for ED. In addition to a comfortable, safe environment for the patient to discuss the issue with the physician, an interview with the patient’s partner may be helpful in evaluating ED. The partner may provide insight into An emotional aspect of sexual function is virtually always present. discussion, provide comfort for the patient in initiating conversation, and allow physicians to evaluate the severity of ED. Standardized questionnaires available include the Brief Male Sexual Function Inventory for Urology (BSFI); the more frequently used International Index of Erectile Function (IIEF); and its short form, the five-question Sexual Health Inventory for Men (SHIM).7,8 After initiating treatment, sexual difficulties, relationship problems, and underlying health concerns that the patient may be uneasy about discussing. This may also identify the partner’s approach to and valuing of intimacy and sexual function in their relationship.10 The physician/patient interaction, relationship, and interview have been discussed widely, and Marwick has documented that patients are clearly uneasy about bringing up the VOL. 4 SUPPL. 3 2002 REVIEWS IN UROLOGY S3 Evaluation of Men with ED continued subject of ED or sexual problems with their physicians.11 Marwick demonstrated that more than 70% of patients felt that it would be embarrassing to discuss sexual problems and that the physician would be also be embarrassed and find the problems of ED trivial or insignificant. The burden is, therefore, on the physician to initiate questioning and begin the ifying these risk factors will facilitate further treatment with oral agents. History A full medical history is critical, with special attention to risk factors and medications. This should be followed by a thorough physical examination, laboratory studies, and appropriate clinical diagnostic studies. ED may The partner may provide insight into sexual difficulties, relationship problems, and underlying health concerns that the patient may be uneasy about discussing. discussion of erectile function in patients seen either for routine visits or for treatment of diagnoses associated with risk factors for ED. The use of the SHIM in the office prior to the visit may facilitate this interaction and help the physician initiate a conversation regarding ED. Clinical Evaluation The concept of what constitutes an adequate evaluation for ED continues to evolve. Prior to the introduction of sildenafil, there was an emphasis on a “goal-directed" approach to male sexual dysfunction, which included careful identification of the etiology of ED. The goal of this approach was to identify a specific etiology, after which more invasive, costly, uncomfortable treatments could be used based on the patient’s treatment goals. In the era of managed care, cost consciousness, and minimally invasive safe and effective oral medications, extensive evaluation of patients is no longer the first-line approach for patients presenting with ED. It is critically important, however, to review the patient’s history carefully to identify underlying physiologic risk factors, medications, and lifestyle factors that may contribute to ED, with the hope that mod- S4 VOL. 4 SUPPL. 3 2002 have any of a variety of etiologies or combinations of causative factors. History taking should include a careful sexual history to elicit these possible causes.6 Patients should be queried regarding morning erections, nocturnal erections, erectile quality, erections during masturbation, and ejaculatory function. Open-ended questions are best for this purpose, as they provide the most spontaneous, accurate, and detailed information regarding the current status of erectile function, onset of ED, and surrounding precipitating factors. For patients who complain of loss of libido or sexual desire, hypogonadism may be considered as a possible cause. low testosterone and high prolactin levels.12 These abnormalities can be addressed by medical treatment to decrease prolactin and increase testosterone levels. A history of ejaculatory dysfunction must also be elicited to identify patients with premature or delayed ejaculation. Younger men more often complain of premature ejaculation, whereas those in the older age group more often have difficulties with retarded or even absent ejaculation. This may be caused by natural aging, lack of androgen, neurological abnormalities, medications, or pelvic surgery. Patients with retrograde ejaculation must be suspected to have diabetes mellitus; they also may be using  adrenergic receptor agonist medication or may have had previous urological or neurological surgery. Medical problems associated with ED may include those listed in Table 1. Each of these should be discussed with the patient during history taking. Any condition associated with cardiac disease, hypertension, diabetes, or lipid abnormalities can be associated with ED. Atherosclerosis is, indeed, a risk factor for ED in 70% of men more than 60 years of age, and ED occurs in diabetic men at 10–15 years after onset in 50% of diabetic men.6 ED in type 1 diabetes often has a neurogenic Extensive evaluation of patients is no longer the first-line approach for patients presenting with ED. Low libido, however, may also be caused by medications, hypochondriasis, stress, anxiety, or depression. Low libido clearly requires evaluation in order to identify patients with androgen deficiency of the aging male or other causes of hypogonadism. Those with chronic renal failure, especially if they are on chronic dialysis, may have low libido caused by REVIEWS IN UROLOGY etiology, whereas type 2 diabetics more often have vascular problems or combinations of etiologies. Medications are also frequently causes of ED. Some of the medications associated with ED are listed in Table 2. Most often, antihypertensive and antidepressive medications are culprits. Recreational drugs, such as cocaine, marijuana, and cigarettes Evaluation of Men with ED Table 1 Risk Factors for ED Diabetes mellitus Cardiovascular disease Hyperlipidemia Spinal cord injury Cigarette smoking Depression Atherosclerosis Hypertension Pelvic surgery/trauma Medications Arthritis Peripheral vascular disease Renal failure Substance abuse Endocrine abnormalities Peptic ulcer disease also have the potential to cause ED. Additional history should include history of penile trauma, priapism, curvature of the penis from Peyronie’s disease or congenital corporal disproportion. Depression and anxiety can often be identified in this initial phase of the examination. Physical Examination Physical examination of patients with ED should be focused on the genitalia. A general inspection of body size and consistency, as well as penile anatomy, should be examined carefully. In patients with small or soft testes, hypogonadism should be suspected, and lesions of the shaft of the penis can be identified in patients with Peyronie’s disease. A brief neurological examination should be carried out, with evaluation of sensation in the lower extremities, deep tendon reflexes, and perineal sensation. A bulbocavernosus or cremasteric reflex and sphincter tone on rectal examination can be quantified. Digital rectal examination for prostate size, consistency, nodularity, pain, or prostatitis should be carried out. If questions arise regarding penile sensation, vibratory sensation of the glans penis and penile shaft can be carried out in the office with a biothesiometer.13 Results should be compared with an age-adjusted nomogram to identify patients with decreased glans penis sensation. Laboratory Tests Once a careful physical examination is completed, laboratory investigation should be tailored to the individual patient and goals of therapy. In patients who have not had a recent health evaluation, fasting blood glucose should be measured to identify patients at risk for diabetes mellitus. This is especially important in patients with a family history of diabetes or those with personal histories Recreational drugs, such as cocaine, marijuana, and cigarettes also have the potential to cause ED. habitus to identify hair distribution, overweight, and secondary sex characteristics should be carried out. Patients with severe obesity should be suspected to have sleep apnea or high estrogen levels, either of which may be associated with ED. Testicular of polyuria or polydipsia. In known diabetics, a hemoglobin A1c assay can evaluate control and medical compliance with diabetic therapy. Similarly, laboratory studies can include a lipid profile to identify hypercholesterolemia. In those patients Table 2 Medications Associated with ED -adrenergic-receptor antagonists Thiazide Verapamil Naproxen Amitriptyline Digoxin Phenytoin Hydralazine Clofibrate Indomethacin Cimetidine Omeprazole Metoclopramide Famotidine Lithium Selective serotonin reuptake inhibitor antidepressants Antiandrogen hormones Recreational drugs (marijuana, cocaine, and heroin) with a suggestive history, a thyroid profile can be obtained as well. Most important, however, is an evaluation of hormone status. Hypogonadism, though found in only a small number of patients, should be tested for in all patients with ED.14 An initial screening of morning total testosterone should be performed to quantify testosterone level. It is important to perform this as a morning evaluation, because the daily testosterone concentration peak occurs between 8 and 10 AM. Repeat testosterone levels with free testosterone, luteinizing hormone, and prolactin levels should be performed if the initial testosterone level is suspicious. Buvat and Lemaire reviewed endocrine screening results in 1022 VOL. 4 SUPPL. 3 2002 REVIEWS IN UROLOGY S5 Evaluation of Men with ED continued Table 3 Diagnostic Tests for ED Body System Neurological Somatic nerves Autonomic nerves Vascular Arteriogenic Venoocclusive Psychogenic Example Biothesiometry Nerve conduction velocities Evoked potentials Cardiovascular reflex tests Sympathetic skin response Corpus cavernosum electromyography Thermal threshold testing Urethroanal reflex latency Penile brachial index Pharmacopenile duplex ultrasonography Selective pudendal arteriography Intracavernous injections Pharmacopenile duplex ultrasonography Dynamic infusion cavernosometry and cavernosography Nocturnal penile tumescence patients with ED and found that limiting testosterone evaluation to patients with abnormal physical examinations or decreased libido would miss 40% of patients with low testosterone.15 They recommend testosterone determinations for all men over 50 years of age. Other hormonal studies appropriate for men with decreased libido and decreased sexual function include dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). Reiter and colleagues have demonstrated that replacement of DHEA in patients with low DHEA and normal testosterone levels may improve sexual desire and libido substantially in addition to improving sexual performance and erectile function.16 With this basic group of studies, in addition to the history, physical examination, and questionnaires, the majority of patients having ED can be identified and started on appropriate oral medications. S6 VOL. 4 SUPPL. 3 2002 Other Tests If oral medications are unsuccessful, if patients are interested in their underlying ED etiology, or if surgical intervention is contemplated, further evaluation may be required (Table 3). This evaluation may include the standard studies of nocturnal penile tumescence (NPT) monitoring and arterial and venous studies, including color Doppler arterial studies and ultimately cavernosography and selective pudendal arteriography. NPT monitoring was first described in the 1970s by Fisher13 for distinguishing organic and psychogenic ED patients. It is well known that normal men have significant erectile activity during rapid eye movement sleep. A total of four to six erections occur during the usual night’s sleep, with base and tip rigidity greater than 55% sustained for at least 10 minutes. The RigiScan recording device (Timm Medical, Augusta, GA) is an econom- REVIEWS IN UROLOGY ical, safe, noninvasive home monitoring device for evaluating NPT.13 Although controversy remains regarding the diagnostic accuracy of NPT evaluation, it may be useful in differentiating patients with organic and psychogenic ED and for use in medical legal situations. False-negative results may occur in patients having depression, sleep disorders, or sleep apnea or using sleep-altering medications, tobacco, or caffeine. The overall accuracy of NPT monitoring is approximately 80%.17 An abnormal NPT test should be confirmed with at least two nights’ study and subsequent independent validation studies, such as duplex Doppler ultrasound after intracavernosal injection of alprostadil studies. Although specific widely available clinical studies for neurogenic testing (except for tactile testing) have limited availability, such studies as dorsal nerve conduction velocities and sacral nerve evoked potentials may be useful in some patients and are available at research institutes and ED centers. Vascular studies of the arterial and venous systems can be used to obtain accurate determination of vascular function and anatomy. Older studies using hand-held Doppler with penile brachial index identification appear to be inaccurate and poorly reproducible. The use of duplex ultrasound color Doppler flow studies with intracavernosal injection of vasoactive agents, however, can facilitate careful evaluation of both the arterial and the venous systems that produce erections in a functional fashion. In 1985, Lue and colleagues reported that the combination of intracavernous injections of vasoactive agents with duplex ultrasonography provided high-resolution sonography and pulsed Doppler blood flow analysis to evaluate the penile arteries and provide information regarding venous outflow Evaluation of Men with ED incompetence.18 This noninvasive technique measures cavernous arterial diameter, detects abnormalities in cavernous bodies, such as fibrosis and calcifications, and evaluates venous outflow. In 1990, Mueller and associates compared selective internal iliac arteriography with duplex Doppler ultrasonography for the diagnosis of arteriogenic ED.19 In the 43 men evaluated, selective arteriography and duplex sonography correlated with duplex ultrasound in 91% of cases, providing higher diagnostic accuracy than selective arteriography alone. Duplex ultrasonography can also indirectly identify venous leak or venoocclusive ED. If venoocclusive dysfunction is suspected from initial studies, dynamic infusion cavernosography and cavernosometry can be performed to identify areas of venoocclusive dysfunction and indicate whether surgical or nonsurgical intervention is appropriate. In patients with suspected traumatic injuries to the arteries supplying the penis, selective pudendal arteriography in combination with intracavernous injection can provide an accurate review of the penile arterial anatomy and identify those who are candidates for arterial revascularization. Duplex Doppler studies can identify those in whom arteriography may be helpful. Ideal candidates for this procedure include those with a solitary obstruc- tive lesion of the pudendal arterial system who are less than 40 years of age and nonsmokers who have no other significant vascular disease risk factors, such as diabetes or hypercholesterolemia. 6. 7. 8. Conclusions ED is currently treatable with safe, effective oral medication that can restore not only erectile function but quality of life for men with sexual problems. The most important part of evaluation of patients with ED is asking them about their erectile status. Although clinical diagnostic studies, laboratory studies, and physical examination may provide many possible findings, the most important part of evaluation and treatment is taking an adequate history and eliciting information on an erectile problem from patients. An adequate physician/patient rapport is the most important starting point for successful treatment of ED. References 1. 2. 3. 4. 5. Masters WH, Johnson VE. Human Sexual Inadequacy. Boston: Little Brown and Company; 1970. Finkle AL, Thompson R. Urologic counseling in male sexual impotence. Geriatrics. 1972;27:67–72. Kinsey AC, Pomeroy WB, Martin CE. Sexual Behavior in the Human Male. Philadelphia: WB Saunders; 1948. Feldman H, Goldstein I, Hatzichristou D. Impotence and its medical and psychological correlates: results of the Massachusetts Male Aging Study. J Urol. 1994;151:54–61. Laumann EO, Paik AM, Rosen RC. Sexual dys- 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 18. function in the United States: prevalence and predictors. JAMA. 1999;281:537–546. Chun J, Carson CC. Physician/patient dialogue and clinical evaluation of erectile dysfunction. Urol Clin N Am. 2001;28:249–258. O’Leary M, Fowler FJ, Lenderking WR, et al. Brief Male Sexual Function Inventory for Urology. Urology. 1995;46:697–703. Rosen RC, Riley A, Wagner G, et al. The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology. 1997;49:822–828. Althof SE, Corty EW, Levine SB, et al. EDITS: development of questionnaires for evaluating satisfaction with treatments for erectile dysfunction. Urology. 1999;53:793–799. McCullough AR, Fine JL: Psychosexual issues in the man, woman, and couple. In: Hellstrom WJ, ed. The Handbook of Sexual Dysfunction. San Francisco: The American Society of Andrology; 1999:53. Marwick C. Survey says patients expect little help on sex. JAMA. 1999;281:2173–2174. Carson CC, Patel MP. The epidemiology, anatomy, physiology, and treatment of erectile dysfunction in chronic renal failure patients. Adv Ren Replace Ther. 1999;6:296–309. Kirby RS. Basic assessment of the patient with erectile dysfunction. In: Carson CC, Kirby RS, Goldstein I, eds. Textbook of Erectile Dysfunction. Oxford: ISIS Medical Publishers; 1999:195–205. Morales A, Heaton JWP, Carson CC. Andropause: a misnomer for a true clinical entity. J Urol. 2000;163:705–712. Buvat J, Lemaire A. Endocrine screening in 1022 men with erectile dysfunction: clinical significance and cost effective strategy. J Urol. 1997;158:1764–1769. Reiter WJ, Pycha A, Schatzl G. Serum dehydroepiandrosterone concentrations in men with erectile dysfunction. Urology. 2000;55:755–758. Allen RP, Smolev JK, Engel RM, et al. Comparison of RigiScan and formal nocturnal penile tumescence testing in the evaluation of erectile rigidity. J Urol. 1993;149:1265–1268. Lue TF, Hricak H, Marich KW, Tanagho EA. Evaluation of arteriogenic impotence with intracorporeal injection of papaverine and the duplex ultrasound scanner. Semin Urol. 1985;3:43–48. Mueller SC, Wallenberg HV, Voges GE, et al. Comparison of selective internal iliac pharmacoangiography, penile brachial index, and duplex sonography with pulsed Doppler analysis for the evaluation of vasculogenic impotence. J Urol. 1990;143:928–939. Main Points • Erectile dysfunction (ED) has a variety of possible etiologies, including combinations of factors. • Having the physician bring up the subject and the use of a standardized questionnaire may help elicit information from patients who are uncomfortable discussing ED. • Medical conditions associated with ED include cardiac disease, hypertension, diabetes, and lipid abnormalities; medications, especially antihypertensives and antidepressants, can also increase the risk. • Physical examination should focus on the genitals and may include a neurological evaluation in addition to the routine overall exam. • Evaluation of hormone status is the most important part of laboratory studies for ED, but blood glucose and cholesterol tests should also be performed to identify underlying conditions. • Nocturnal penile tumescence monitoring, further neurological testing, and vascular studies may be appropriate if initial oral treatment fails. VOL. 4 SUPPL. 3 2002 REVIEWS IN UROLOGY S7 Evaluation of Men with ED continued Summary of Discussion Following Dr. Carson’s Presentation Dr. Carson summarized the main points of his presentation as: 1) Ask the question. The most important thing is to ask patients if they have erectile dysfunction and to begin the history; 2) Do the appropriate physical examination and appropriate laboratory studies. Dr. McCullough asked Dr. Carson if he felt that the working paradigm for the urologist had changed, given that 86% of men with ED are being diagnosed primarily by non-urologists, and that urologists are now seeing more complicated patients, many who have failed oral therapy. What, he asked, should the urologist to do at this point? Carson replied that at that point it depends on the individual patient and the needs of the referring physicians. The first thing to do is to make sure that the patient is taking the oral agents appropriately. Also, often patients do not have a hormone profile when the urologist sees them. Carson asserted that a hormone profile is extremely important in these patients, because he thinks androgen deficiency is underdiagnosed in many patients. If the androgen profile is normal and the patient still is not responding to sildenafil, at that stage a vascular diagnostic schema can begin if the patient or his primary physician want to investigate the S8 VOL. 4 SUPPL. 3 2002 underlying cause of the ED. “I think," Carson said, “at that stage we go back to what was described by Tom Lue in the early 1990s as the goal-oriented approach to erectile dysfunction." The patient should be asked what they are interested in, where do they want to go with treatment? If they are interested in proceeding and trying injection therapy, then an inoffice injection will identify the patient who will respond to that particular treatment. If the patient responds to injection and that is as far as he wants to go, then he has a treatment that works for him. McCullough countered, “The primary care clinician sent him to you to find out why he failed sildenafil. Have you answered that question?" Carson responded, that if that is the question that the patient, the partner, and the physician want to know the answer to, then at that stage a Doppler study or NPT is appropriate. Those are good tests, either taken together or done separately. But the point is that the majority of patients really are not interested, and the majority of referring physicians are more interested in a successful treatment outcome. If the urologist is convinced that the patient took the oral medication correctly, that the patient doesn’t have a relationship problem and is not depressed, and it therefore seems that the ED is organic in etiology, there is REVIEWS IN UROLOGY no need for diagnostics. Testing is not necessary in any of those patients unless the patient says, “I want to know if I have vascular disease." Dr. Steers agreed, stating his opinion that testing does not tell much, in terms of ruling out vascular disease. The role of testing would be great, he said, if there were tests that had very high specificity and sensitivity, but there are not. In the absence of those tests, the only reason to do injections in the office is to teach patients how to do them and as a predictor of response to injection therapy. Carson returned to the theme of the goal-oriented approach. The patient that walks in the door may not really want to know what the etiology of his ED is. He wants something that will work; he wants treatment. Is it worthwhile for the physician to go through a very complicated diagnostic algorithm, costing several of thousands of dollars, only at the end to say, “Well, we’re not really sure what’s going on?" Then the patient is back to starting injection therapy, despite the workup. The specificity and sensitivity of the tests available now are not adequate to warrant putting every patient through them, and the tests do not tell which therapy is going to work. Dr. Montague echoed the need for a good history and the lack of utility of diagnostic tests in men undergoing implant surgery unless there are medico-legal issues.