|Year : 2006 | Volume
| Issue : 3 | Page : 215-219
Current and future standards in evaluation of erectile dysfunction
Raymond W Pak, Gregory A Broderick
Mayo Clinic College of Medicine, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, India
Raymond W Pak
Mayo Clinic College of Medicine, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Sexual dysfunction and more specifically erectile dysfunction (ED) can be a harbinger of serious occult medical conditions. ED can be considered a clinical manifestation of generalized vascular disease and therefore shares similar risk factors: aging, hypertension, diabetes mellitus, hypercholesterolemia and smoking. The initial evaluation of men with ED should be thorough. Studies of normal and abnormal penile tumescence have led to the discovery of many important pathways. The greatest medical advance in the management of male sexual dysfunction since the identification of androgens have been the discoveries that nitric oxide (NO) is the primary neuro-modulator of penile smooth muscle relaxation and that oral phosphodiesterase type 5 inhibitors enhance erection quality through the NO mechanism. As a consequence of oral pharmacotherapies, the role of invasive diagnostics has diminished. Most guidelines recommend only history, physical exam and limited laboratory testing prior to instituting oral therapies for ED. In 2006 we still have unanswered questions about ED and these will frame the role of future diagnosis and therapy: can lifestyle changes alone improve erectile function; is ED a marker for the development of atherosclerotic heart disease, do lower urinary tract symptoms of benign prostatic hypertrophy and ED share a common pathway?
Keywords: Erectile dysfunction, evaluation, vascular testing
|How to cite this article:|
Pak RW, Broderick GA. Current and future standards in evaluation of erectile dysfunction. Indian J Urol 2006;22:215-9
| Introduction|| |
Over the last three decades medical science has developed and employed numerous tests to diagnose and manage erectile dysfunction. The evolution of these diagnostics has mirrored changes in our understanding of the physiology and neuro-pharmacology of erection. The greatest medical advance in the management of male sexual dysfunction since the identification of androgens has been the discovery that nitric oxide is the primary neuro-modulator of penile smooth muscle relaxation and that administration of phosphodiesterase type 5 inhibitors can enhance erection quality.
The introduction of sildenafil in 1998 dramatically changed practice patterns in erectile dysfunction (ED):
increasing the number of patients acknowledging the complaint and shifting the burden of evaluation and management away from the urologist and toward the family practitioner. Currently both the American Urological Association and the First International Consultation on ED recommend sildenafil for patients with a good sexual history and who have undergone assessment of medical risks and physical examination [Table - 1]. The primary purpose of establishing a specific diagnosis is to formulate a treatment plan; in most cases of ED this can be done without extensive testing. Conversely, without diagnostic testing, efficacy and satisfaction with pharmacotherapies becomes a matter of chance. Effectiveness of sildenafil in the average ED patient ranges from 60 to 80% and declines as the number of risk factors the patient has increases. The next decade will see the development of multiple oral agents for the management of vascular ED.
Currently with only one class of agents widely available (phosphodiesterase type-5 inhibitors), clinicians categorize patients as PDE-5 inhibitor successes or PDE-5 inhibitor failures. Patients failing first-line therapy by primary caregivers or confused by the variety of options should be encouraged to seek the expertise of specialists. They may simply want to know what is wrong with them or which specific agent is best for them or why a PDE-5 inhibitor has failed to reverse their ED. Optimally, ED testing needs to create vascular profiles to predict which drug or combination of drugs (oral, cutaneous, urethral, intracavenosal) will effectively restore erection; spare patients the frustration and the potential side effects of multiple empiric trials; and determine whether patients would best be served by a mechanical or surgical solution.
The truth is that majority of patients do not need testing, but there are specific patients who do benefit from penile vascular evaluation: failure to respond to oral agents, complex medical /sexual histories, trauma or penile deformity [Table - 2]. Moreover, in practice ED is subcategorized as organic, psychologic or mixed - based on medical history of risk factors (age, hypertension, atherosclerosis, diabetes mellitus, smoking, dyslipidemia) and sexual history.
| Evolution of Diagnostic Testing in Erectile Dysfunction|| |
It was the late Robert J. Krane, MD who in 1986 wrote in his chapter Sexual Function and Dysfunction: "It is self-evident that, during formation of an erection, the amount of blood entering the cavernosal spaces must exceed the amount of blood leaving the tissue". Characterizing this observation has been the goal of every vascular diagnostic applied to ED. Several key questions posed by Dr. Krane have been answered in the last twenty years both in the laboratory and as a result of clinical investigations:
- What is the mechanism that brings about preferential filling of the corporal spaces?
- Quantitatively, what is the blood flow through the corpora in the flaccid state and how does it differ during an erection?
- What happens to the venous drainage during formation and maintenance of an erection?
In the 2002 text of his chapter physiology of penile erection, Dr. Tom Lue answers Dr. Krane's questions. I believe both these experts writing nearly 20 years apart would acknowledge that what we have learned about the physiology of erection and pathophysiology of ED is not only a direct result of advances in basic science but also of multiple trials and errors of clinical diagnostics.
Numerous diagnostic tests have been employed to evaluate penile hemodynamics including penile plethysmography, penile blood pressures, penile brachial index, duplex Doppler sonography, color duplex Doppler sonography, power Doppler sonography, dynamic infusion cavernosometry/cavernosography, radioisotope penography, penile angiography, infrared spectrophotometry, computer tomographic angiography (CTA), magnetic resonance imaging and angiography (MRI, MRA) [Table - 3].
In the 1970's and on into the early 1980's resting penile blood pressure assessments were thought useful. Britt et al were the first to describe penile plethysmography: a 1 inch pneumatic cuff was used to occlude the base of the flaccid penis and a circular strain gauge attached distally to assess volume change with pulse and penile systolic pressure. Abelson, in 1975, used the Doppler stethoscope to measure penile blood pressure in the flaccid penis and compared this value with systolic brachial pressures to yield the penile-brachial index (maximal systolic penile pressure/systolic brachial artery pressure, PBI) PBI and measurement of penile systolic pressures in the flaccid penis had both experimental and conceptual flaws: normal patients overlapped with those from ED patients.
Infusion cavernosography and subsequently dynamic infusion cavernosometry and cavernosography (DICC) for assessing penile venous outflow and veno-occlusion was described in 1955 and modified extensively in the 1980's.,, DICC is now reserved for the evaluation of young men who may be candidates for vascular surgery (ED secondary to pelvic or perineal trauma) or young men who have a history of primary, life-long ED.
In 1982, during the course of vascular operation Ronald Virag noted that infusion of papaverine into the hypogastric artery produced erection; he subsequently reported the benefits of both diagnosis and treatment of ED by penile injections., Drug combinations for diagnosis and therapy (a trimixture of papaverine, phentolamine and prostaglandin) were explored to exploit specific relaxing properties of different intracavernous agents, to reduce the risk of corporal fibrosis and hepatic dysfunction (8%) associated with papaverine monotherapy, to minimize the cost/volume of a penile injection and to minimize pain associated with PGE1 monotherapy. In July 1995, Food and Drug Administration (FDA) approved injectable alprostadil for the diagnosis and treatment of male impotence.
All vascular evaluations have the goal of identifying and quantifying penile arterial inflow and veno-occlusion. Pudendal arteriography for the identification and management of penile inflow disease was pioneered by the works of Michal, Ginestie and Bookstein.,, Arteriography provides the best anatomic information about pelvic inflow; this invasive testing is indicated in young men with ED secondary to focal traumatic occlusion / laceration (pelvic fracture) or perineal compression injury. CTA and MRA can provide equivalent or better information without invasive arterial access., Penile arteriography, CTA and MRA provide vascular 'roadmaps' but do not assess erection hemodynamics: the ability to initiate and sustain rigidity.
| Modern Diagnostic Evaluation|| |
When vascular testing is called for in the evaluation of complex ED patients, a penile blood flow study using intracavernous or oral vasoactive medication (pharmacotesting) coupled with assessment of erection by color duplex Doppler ultrasound is the most informative and least invasive technology., Penile pharmacotesting is the most commonly performed office diagnostic for ED. Pharmacotesting advanced our ability to define the etiology of ED beyond assessment of history; this early simple diagnostic classified 'impotence' as 20-30% psychologic and 50-80% organic. Earlier literature had attributed 'impotence' largely to psychologic causes.,
All vascular evaluations are aimed at identifying and quantifying arterial and veno-occlusive erectile function. The primary causes of arteriogenic ED are atherosclerotic vascular disease and traumatic arterial occlusion (following pelvic or perineal trauma). The quality of penile inflow has been directly related to common vascular comorbidities of age, diabetes mellitus, hypertension, atherosclerotic coronary/peripheral vascular disease, hyperlipidemia and cigarette smoking. Veno-occlusion is a no less essential hydraulic phenomenon regulating intrapenile pressure changes by penile outflow. The quality of veno-occlusion depends on the tone of cavernous smooth muscle. Clinically imaging and quantifying venoocclusion is more difficult than documenting penile arterial inflows. Regulation of cavernosal smooth muscle (CSM) tone is complex; specific clinical risk factors for veno-occlusive ED have not yet been identified. The forces at play include neuropharmacologically mediated adrenergic tone, smooth muscle versus extracellular matrix composition, molecular mediators of contraction and cell-to-cell communication.
Pharmacotesting consists of intracavernous injection and visual rating of erectile response (quality of rigidity and duration of response). It is performed without expensive monitoring equipment and observation is made of the quality of rigidity. Theoretically to produce a normal erection with pharmacotesting, arterial dilation, sinusoidal relaxation and decreased venous outflow must each occur. Pharmacotesting has been shown to be normal (false negative) in as many as 20% of patients with borderline arterial inflows (as determined by duplex Doppler testing, when normal is defined as > 35 cm/sec and borderline 25-35 cm/sec flows). This means that one in five patients may have organic ED secondary to borderline arterial insufficiency and still be categorized as normal by pharmacotesting and visual rating of erection quality. Conversely a false positive or poor erection may be a result of testing anxiety, which heightens sympathetic CSM tone. To maximize erectile responses to pharmacotesting: a patient should be made comfortable in a warm-private-secure setting, with visual sexual stimulation or repeated intracavernous dosing until the response is similar to his best erection at home. An initial dosage of 10 micrograms of PGE1 followed by self-stimulation plus visual stimulation has been shown equivalent or better to re-dosing with 10 micrograms.,
The parameters used to define integrity of cavernous inflow and venous occlusion are well established and have been validated through other more invasive methodologies such as arteriography and DICC. The specific advantages of the color duplex. Doppler technology are: minimal invasion; ability to asses erection physiology and anatomy simultaneously; rapid acquisition of Doppler flow data; real time visualization of vessels / corpora / tunica anatomy; and compatibility with pharmacologic and/or erotic stimulation. Pharmacotesting may be done with penile injection oral PDE5-Inhibitors, alone or in combination with visual sexual stimulation. Current Doppler technology employs power Doppler imaging and can show three orders of branching distal to the main cavernous arteries. Vessel localization is aided by color; the hue and brightness of the Doppler signal is a function of the number and speed of flowing red cells in the vessel. The hardware is now small, portable and durable. Over the years these machines have been made considerably more affordable and suitable for a specialty urology practice. The device I currently use is SonoSite 180Plus (SonoSite, Inc, Bothell WA.).
ED is a recognized comorbidity of cardiovascular disease and many of the risk factors for atherosclerotic heart disease are shared by ED., We look toward ED vascular diagnostics in the future to refine our perceptions on the severity and progress of ED as it is related to aging, hypertension, atheroslcerosis, diabetes, dyslipidemia and smoking.
| Future Challenges for Penile Diagnostics|| |
In 2006 we still have unanswered questions about ED and these will frame the role of future penile vascular diagnostics: can lifestyle changes alone improve erectile function; is ED a marker for the development of atherosclerotic heart disease; what are the specific effects of known cardiovascular morbidities on penile vascular integrity?, Using the penile blood flow study, as described above, recent studies show: 1. heavy smokers are predisposed to have penile arterial insufficiency, while diabetics have both arterial insufficiency and venous leakage; 2. Sildenafil response rates in large clinical trials based on subjective questionnaires are reported from 70-80%, but for ED patients with significant abnormalities on penile blood flow study sildenafil response rates may be as low as 53%. 3. Furthermore, when Doppler penile blood flow data are stratified as either arterial insufficiency, venous insufficiency or mixed insufficiency - sildenafil response rates are 65, 25 and 6% respectively.,
Is ED a harbinger of atherosclerotic heart disease and if so will diagnosing impairment in penile blood flow give clinicians significant lead time to intervene on the development of large vessel disease? Flow mediated dilation in the brachial artery following distal arterial occlusion and release is currently being investigated as a tool to assess endothelial cell integrity. FMD is calculated as the percentage increase in brachial artery diameter in response to increased brachial artery flow, following occlusion (by pressure cuff) and release. Flow mediated arterial dilation is an endothelium dependent function and is typically assessed in the brachial artery in response to reactive hyperemia, using high-resolution Doppler ultrasound.
Endothelial cell dysfunction is considered a marker for cardiovascular disease; FMD is a non-invasive clinical test used to evaluate cardiovascular risks. FMD has been used to correlate other serologic markers of endothelial cell function and dysfunction. Similar degrees of FMD impairment have been noted in diabetics and non-diabetics with heart disease, implying a CAD risk-equivalence in diabetics. FMD is an index of nitric oxide-dependent endothelial function; improvements have been noted following acute and prolonged sildenafil dosing, with effects persisting 24 hours after last dosage.
Endothelial dysfunction is currently viewed as a harbinger of atherosclerosis. Impairment of FMD is now being used as a surrogate end point for measuring relative cardiovascular risks versus potential benefits to cardiovascular health of: diabetes mellitus, dyslipidemia, body mass index, body fat distribution, smoking, nicotine use, mental stress and aging versus exercise, lipid control and medications. Along these very lines a recent study has noted that in patients with ED and no other significant cardiac risks both FMD vasodilation and nitroglycerin mediated vasodilation of brachial arteries were reduced in 30 ED patients compared to age-matched controls without ED.
| Conclusion|| |
Comprehensive evaluation of ED patients serves to identify underlying comorbidities that may limit efficacy of selected treatments and to ensure patient satisfaction with the ED specialist. Urologists managing ED must step up to these new challenges: oral drug therapy failures, correlating risk factors with specific penile vascular abnormalities, managing patients with penile curvature/trauma, defining the relationship between ED and the progression to large vessel cardiovascular diseases and optimally treating BPH and LUTS. Any physician can prescribe a pill based on sexual and medical history. It is left to the specialists to go beyond empiric medicine and address these many challenges; penile vascular testing can benefit a few select patients in 2006 but the clinical insights gained from these few may eventually benefit the many.
| References|| |
|1.||Krane RJ. Sexual function and dysfunction. In : Campbell's urology. 5th ed. WB Saunders: St. Louis; 1986. p. 700-35. |
|2.||Broderick GA. Evaluation and nonsurgical management of erectile dysfunction and priapism. In : Campbell's urology. 8th ed. WB Saunders: St. Louis; 2002. p. 1619-63. |
|3.||Britt DB, Kemmerer WT, Bobison JR. Penile blood flow determination by mercury strain gauge plethysmogrphy. Invest Urol 1971;8:673-8. |
|4.||Abelson D. Diagnostic value of the penile pulse and blood pressure: A doppler study of impotence in diabetics. J Urol 1975;113:636-9. [PUBMED] |
|5.||May F, Hirtl H. Das cavernosogramm. Urol Int 1955;2:120. |
|6.||Wespes E, Delcour C, Struyven J, Schulman CC. Cavernosometry-cavernosography: Its role in organic impotence. Eur Urol 1984;10:229-32. [PUBMED] |
|7.||Hatzichristou DG, Saenz de Tejada I, Kupferman S, Namburi S, Pescatori ES, Udelson D, et al . In vivo assessment of trabecular smooth muscle tone, its application in pharmacocavernosmetry and analysis of intracavernous pressure determinations. J Urol 1995;153:1126-35. |
|8.||Virag R. Intracavernous injection of papaverine for erectile failure. Lancet 1982;2:398. |
|9.||Virag R, Frydman D, Legman M, Virag H. Intracavernous injection of papaverine as a diagnostic and therapeutic method in erectile failure. Angiology 1984;35:79-87. [PUBMED] |
|10.||Bennett AH, Carpenter AJ, Barbada JH. An improved vasoactive drug combination for a pharmacological erection program. J Urol 1991;146:1564-5. |
|11.||Michal V, Pospichal J. Phallarteriography in the diagnosis of erectile impotence. World J Surg 1978;2:239-48. [PUBMED] |
|12.||Ginestie JF, Romieu A. L'exporation Radiologique de l'impuissance. Paris: Maloine; 1976. |
|13.||Bookstein JJ, Valji K, Parsons L, Kessler W. Pharmacoarteriography in the evaluation of impotence. J Urol 1987;137:333-7. [PUBMED] |
|14.||Kawanishi Y, Lee KS, Kimura K, Kojima K, Yamamoto A, Numata A. Feasibility of multi-slice computed tomography in the diagnosis of arteriogenic erectile dysfunction. BJU Int 2001;88:390-5. [PUBMED] [FULLTEXT]|
|15.||Kawanishi Y, Kimura K, Nakanishi R, Fukawa T, Numata A. A minimally invasive method for harvesting the epigastric artery for penile revascularization. BJU 2004;94:1391-6. [PUBMED] [FULLTEXT]|
|16.||Broderick GA. Evaluation and nonsurgical management of erectile dysfunction and priapism. In : Campbell's urology. 8th ed. WB Saunders: St. Louis; 2002. p. 1619-71. |
|17.||Broderick GA. Vascular assessment of erectile dysfunction. In : Atlas of male sexual dysfunction. Edited by Lue TF. Current Medicine: 2004. p. 37-56. |
|18.||Montague DK, James RE Jr, deWolfe VG, Martin LM. Diagnostic evaluation, classification and treatment of men with sexual dysfunction. Urology 1979;14:545-8. [PUBMED] |
|19.||Virag R. The Screening of impotence by the use of visual sexual stimulation after intracavernous injection of a small (8 mg) dose of Papaverine. Second World Meeting on Impotence. Prague: Czechoslovkia; 1986. |
|20.||Donatucci CG, Lue TF. The combined intracavernous injection and stimulation test: Diagnostic accuracy. J Urol 1992;148:61-2. |
|21.||Montorsi F, Guazzoni G, Barbieri L, Galli L, Rigatti P, Pizzini G, et al . The effect of intracoporal injection plus genital and audiovisual sexual stimulation versus second injection on penile color doppler sonography parameters. J Urol 1996;155:536-40. |
|22.||Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial ccrrelates: Result of the Massachusetts male aging study. J Urol 1994;151:54-61. |
|23.||Nicolosi A, Gaasser DB, Moreira ED, Villa M; Erectile dysfunction epidemiology cross national study group. Prevalence of erectile dysfunction and associated factors among men without concomitant diseases: A population study. Int J Impot Res 2003;15:253-7. |
|24.||Esposito K, Giuglian F, Di Palo C, Giugliano G, Marfella R, D'Andrea F, et al . Effect of lifestyle changes on erectile dysfunction in obese men: A randomized controlled trial. JAMA 2004;291:2978-84. |
|25.||Sadovsky R, Mulhall JP. The potential value of erectile dysfunction. Int J Clin Pract 2003;57:601-8. [PUBMED] |
|26.||Papadoukakis S, Alamanis C, Mitropoulos D, Chountala A, Giannopoulos A. Morphologic findings and blood flow parameters of penile vascuature in patients with erectile dysfunction. World J Urol 2004;22:285-8. [PUBMED] [FULLTEXT]|
|27.||Mulhall J, Barnas J, Aviv N, Anderson M, Parker M. Sildenafil citrate response correlates with the nature and the severity of penile vascular insufficiency. J Sex Med 2005;2:104-8. [PUBMED] [FULLTEXT]|
|28.||Betik AC, Luckham VB, Hughson RL. Flow-mediated dilation in human brachial artery after different circulatory occlusion conditions. Am J Physiol Heart Circ Physiol 2004;286:H442-8. [PUBMED] [FULLTEXT]|
|29.||Bhargava K, Hansa G, Bansal M, Tandon S, Kasliwal RR. Endothelium-dependent artery flow mediated vasodilation in patients with diabetes mellitus with and without coronary artery disease. J Assoc Physics India 2003;51:355-8. [PUBMED] |
|30.||Desouza C, Parulkar A, Lumpkin D, Akers D, Fonseca VA. Acute and prolonged effects of sildenafil on brachial artery flow mediated dilatation in type 2 diabetes. Diabetes Care 2002;25:1336-9. [PUBMED] [FULLTEXT]|
|31.||Kaiser DR, Billups K, Mason C, Wetterling R, Lundberg JL, Bank AJ. Impaired brachial artery endothelium dependent and independent vasodilation in men with erectile dysfunction and no other clinical cardiovascular disease. J Am Coll Card 2004;43:179-84. [PUBMED] [FULLTEXT]|
[Table - 1], [Table - 2], [Table - 3]