Conferences and Reviews New Developments in the Diagnosis and Treatment of Impotence

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1 54 Conferences and Reviews New Developments in the Diagnosis and Treatment of Impotence RALPH G. DE PALMA, MD, Reno, Nevada New developments in the diagnosis and treatment of impotence or erectile dysfunction are increasingly based on better understanding of the erectile process. In 1978 it was thought that the failure of arterial inflow was the main cause of male erectile dysfunction. Emphasis was placed on methods of corpus cavernosal revascularization. In recent years, interest has shifted to abnormal cavernosal smooth muscle function. An understanding of the erectile process was greatly enhanced by intracavernosal administration of vasoactive agents in 1982 and, more recently, the use of prostaglandin E1. These agents promote erection by causing smooth muscle to relax. The intracavernosal administration of vasoactive agents is now used in diagnosis and in therapy. Standard approaches to diagnosis and therapy still vary, but more rational steps are evolving. Considerable progress has been made in quantifying penile blood flow. Increasingly effective therapies are available for an estimated 10 million American men suffering from erectile dysfunction. Therapies include the use of drugs, administering vasoactive agents intracavernosally, vacuum constrictor devices, and vascular interventions in highly selected cases of arterial or venous disease. These procedures are being carefully reevaluated. Critical analysis of recent results suggests that about 7% of men are amenable to vascular interventions, with success rates approximating 70% when supplemental therapy is used. (DePalma RG: New developments in the diagnosis and treatment of impotence. West j Med 1996; 164:54-61) Although precise data are unavailable, an estimated 10 million American men are impotent, with the incidence increasing with age.t By age 65, 25% of men are impotent, and by age 80, about 80% of men are. Whereas impotence is primarily a dysfunctional vascular phenomenon, a number of mechanisms acting alone or interactively contribute to erectile failure. In this review, I consider current developments in its diagnosis and treatment. History In the past two decades, interest in the diagnosis and treatment of impotence has increased dramatically. Beginning with Leriche's 1923 observation that aortoiliac occlusion caused impotence due to failure of the perfusion of the corporal bodies,2 surgeons became interested in the relationship between potency and cavernosal perfusion.3 Aortic surgical interventions often produced impotence,4 and in the 1970s, techniques were developed to minimize this complication.' It was also realized that vascular surgical procedures could be applied for corpus cavernosal revascularization.'7 Consequently, corpus cavemosal revascularization was emphasized in the late 1970s and early 1980s. In 1982, however, it was found that erection could be stimulated by the intracorporal administration of the vasoactive agents papaverine and phentolamine."9 This discovery helped to illuminate the processes of cavernosal smooth muscle function. Administering these agents intracorporally led to effective methods of testing and quantifying various aspects of erectile dysfunction as well as providing an important tool now used widely in diagnosis and treatment. Emphasis shifted from simple mechanistic efforts for increasing arterial inflow toward sophisticated investigations of corporal smooth muscle function. Important recent contributions include elaboration of the roles of nitric oxide and oxygen tension in normal erection and the delineation of mediators of corporal muscle contraction and relaxation.'0"1 Physiology of Penile Erection Penile erection results from a neurally mediated increase of arterial inflow into the corporal bodies along with a reduction or cessation of venous outflow. Recent findings support the idea that endothelially derived relaxant factor is involved in nonadrenergic, noncholinergic neural transmission, which leads to cavernosal smooth muscle relaxation required for normal erection."0 Histochemically, nerve fibers positive for the reduced form of nicotinamide-adenine dinucleotide phosphate and diaphorase are found in human penile tissue, indicating nitric oxide synthase activity.'2 Other neurotrans- From the Department of Surgery, University of Nevada School of Medicine and the Department of Veterans Affairs Medical Center, Reno. Reprint requests to Ralph G. DePalma, MD, Dept of Surgery, Veterans Affairs Medical Center, 1000 Locust St (112), Reno, NV

2 6,N.1i WJM, WI,Jnay19-o January 1996-Vol 164, No. 1 Diagnosing n andn Treating raigiptnedpla5 Impotence-DePalma 55 g o s ABBREVIATIONS USED IN TEXT CAOP = cavernosal artery occlusion pressure DICC = dynamic infusion cavernosometry and cavernosography NPT = nocturnal penile tumescence PBI = penile brachial index PG = prostaglandin mitters such as vasoactive intestinal polypeptide and fibers positive for acetylcholinesterase are also present. When the penis is flaccid, the corporal smooth muscle is contracted; contraction is due to a normally present overriding adrenergic tone.'3 With erection, smooth muscle relaxation occurs. Various other receptors are present in penile smooth muscle, including those responsive to vasoactive intestinal polypeptide, dopamine, histamine, prostaglandin (PG), and probably several other substances. It has recently been reemphasized that the initiating event of penile erection is vasodilation."' With increased intracavemosal flow, an increased amount of oxygen is thought to stimulate nitric oxide synthesis by cavernosal nerves and endothelium. Cavernosal oxygenation promotes penile erection, whereas hypoxemia is inhibitory. Testosterone, in addition to its central effects, has been shown experimentally to stimulate nitric oxide synthase activity in corporal tissue,'4 enhancing sensitivity to cavernosal nerve stimulation in animals. Hemodynamics and Diagnosis The hemodynamics of the erectile process are shown in Figure 1. In flaccidity, the corporal smooth muscle and cavernosal arteries are contracted, and the emissary and pudendal veins are open. The intracavernosal pressure is equivalent to venous pressure; the blood in the intracavemosal spaces is desaturated. It is important to understand this physiologic process, which has recently been reviewed." Current diagnostic methods such as dynamic infusion cavernosometry and cavemosography (DICC) are designed to measure penile pressure and flow changes. At low intracavemosal pressure in the flaccid state, a cavernosal or venous leak will always be detected radiographically. In the next stage, the intracavernosal pressure increases to 80 to 90 mm of mercury synchronously with Cavernous artery Penis Flaccid Pendant Cavernous smooth muscle relaxed Vein occluded Cavernous artery open Cavernous smoothmuscle relaxed Cavernous flow ceases Pressure: mm of mercury Vt' Pressure > 120 mm of mercury with perineal/muscle contraction Pen is Erect Horizontal Penis ~~~Erect Upward Figure 1.-The current theory of penile erection is illustrated. Three stages of erection are characterized by pressure measurements during dynamic infusion cavernosometry and cavernosography and after the intracavernosal administration of vasoactive agents. Note the vein occlusion in the second stage.

3 January 1996-Vol 164, No WJM, January 1996-Vol 164, No. 1 Diagnosing and Treating Impotence-DePalma Gluteal (superior) artery Greater sciatic notch, Internal iliac artery Ischial 4 spine / Ischial (inferior-- gluteal) artery Exit of-' Alcock's canal -Ischiopudendal trunk Internal pudendal... I Dorsal penile artery Accessory deep branch (variable) Deep cavernosal artery Penile bulb and artery 'Branch of superficial perineal artery and scrotal arteries Figure 2.-A right oblique schematic is shown of the internal iliac artery and the pudendal artery and its branches. This view will be seen on highly selective angiography. Note the landmarks. progressive smooth muscle relaxation, facilitating an increase in the arterial inflow. With full relaxation, the penile veins become obstructed due to the occluding action of the subalbugineal smooth muscle. A fully rigid erection on a vascular basis occurs with intracavernosal pressures of about 100 mm of mercury. The cavernosal artery occlusion pressure (CAOP) in full erection tends to equilibrate with the intracavernosal pressure while flow is markedly reduced. With pelvic muscular contraction, suprasystolic pressures are generated, maximum rigidity occurs, and cavernosal artery flow ceases transiently at this stage. For diagnostic purposes, flow changes can be measured at time intervals after the intracavernosal administration of vasoactive agents using duplex sonography.'6 During DICC, the pressure at which the cavernosal artery flow ceases is detected by a Doppler probe placed at the penile base. This method uses artificial erection generated by a roller pump infusion of warm normal saline solution. The pressure at which the signal returns on pump flow reduction is taken as the CAOP. This value normally ranges from 80 to 90 mm of mercury, with a gradient of less than 30 mm of mercury as compared with a simultaneously obtained brachial pressure."7"8 The CAOP is an indirect assessment of the adequacy of arterial flow. Both large-vessel aortoiliac disease and abnormalities of the pudendal arterial supply (Figure 2) cause arteriogenic impotence. The flow to maintain erection is a measure of venous efflux provided complete smooth muscle relaxation has been obtained. The flow to maintain erection considered normal by our group is less than 40 ml per minute with pressure drops of less than 1 mm of mercury per second on flow cessation. The standardization of DICC depends on maximum muscular relaxation using the intracavernosal administration of vasoactive agents. With our method, 60 mg of papaverine hydrochloride and 2.5 mg of phentolamine were used. Readministration during DICC has recently been recommended to achieve maximal muscular relaxation and linear pressure-flow relationships."9 An understanding of this process is also important for demonstrating penile arterial anatomy. When the intracavernosal administration of vasoactive agents produces full erection, radiographic artifacts due to cavernosal artery flow reduction occur. For penile artery visualization, the aim of this procedure is tumescence, not full erection; therefore, smaller doses must be used. General Causes of Impotence Although vasculogenic abnormalities are common, erectile failure is also caused by endocrine, metabolic, neurologic, and psychogenic factors. As can be seen from the physiology of erection, erectile failure is a vascular dysfunction. Some form of arterial inflow abnormality was associated with this complaint in about 45% of patients screened in a noninvasive vascular laboratory.'5 Endocrine causes of impotence were less common: 3% to 4% of patients demonstrated lowered testosterone levels. In screening more than 1,000 men, I found only 2 cases of pituitary prolactinomas. In both men, medical treatment was successful. This experience is similar to that in a study of 6,428 men.20 The investigators also reported that specific endocrine disorders were uncommon. They found 20 cases of prolactinomas and noted that the restoration of a euthyroid state in 6 men failed to restore erectile function. The most common associations with arteriogenic impotence are diabetes mellitus and the use of antihypertensive drugs. Men with diabetes can show neu-

4 WJM, January 1996-Vol 164, No. 1 Diagnosing and Treating Impotence-DePalma Impotence-DePaima 57 ropathy when the vascular system appears to be normal by noninvasive testing. Overall, 28% of men screened neurologically for impotence exhibited one or more abnormalities in pudendal or tibial evoked potentials or bulbocavernosal reflex times.2' The importance of these findings in contributing to impotence is difficult to assess, as some of these men also have existing vascular abnormalities. These techniques measure somatic nerve reflexes, but when present, abnormalities point to neurogenic deficits involving the genitourinary tract. Such men are often exquisitely sensitive to the intracavemosal administration of vasoactive drugs. The detection of nerve conduction deficits is to be a warning to avoid initially high doses of these agents, which could cause priapism. Psychogenic problems are also often present in impotent men. Often anxiety and enhanced adrenergic tone are sufficient to override intracavernosally administered vasoactive agents in office settings. Cigarette smoking just before this procedure has been shown to inhibit erection in normal men after the administration of 80 mg of papaverine hydrochloride.22 Despite limitations of the procedure, with the use of PGE, (up to 30 p,g), it is a key diagnostic and therapeutic tool.'," An erectile response after this procedure suggests that the arterial system is capable of delivering adequate flow and that corporal relaxation and venous closure are relatively functional. Although neural or vascular abnormalities may be present, the observation of an effective erection after the administration of vasoactive agents also recommends its use as therapy. Such therapy can be effective regardless TABLE 1.-Factors in Vasculogenic Impotence Factor Proboble Cause Cavernosal Arteriolar... Functional or anatomic; helicine vessel abnormalities; blood pressure medication Fibrosis... Postpriapic; drug administration Peyronie's disease.... Deformity invading cavernosal smooth muscle; venous leakage Refractory smooth muscle... Venous leakage Acquired... through tunica albuginea Hormonal: prolactinemia, low testosterone level; blood pressure medication; metabolic: diabetes mellitus, uremia Abnormal tunica albuginea; traumatic lesions Congenital... Isolated leakage from corpora cavernosum into the spongiosum Arterial Aortoiliac atherosclerosis Steal due to external iliac disease Occlusive disease of pudendal arteries... Atherosclerotic Occlusive disease of peni le arteries.... Atherosclerotic; idiopathic proliferative Atheroembolization of the cause of erectile failure. It is important to better delineate possible etiologic factors as far as practicable in individual patients. The reasons for this are that occult aortic aneurysms and metabolic disorders such as uremia, diabetes mellitus, or other endocrinopathies can cause impotence. Impotence due to nerve damage or possible arterial compromise often follows prostatic, rectal, or aortic operations. Radiation therapy for prostate cancer can cause late arterial inflow restriction. Arterial inflow compromise, in turn, causes venous leakage. Dynamic infusion cavernosometry and cavernosography alone, even with CAOP measurement, cannot with certainty suffice for the diagnosis of venous leakage. When both DICC and pudendal arteriography were used, 23% of men with normal noninvasive studies and suspected venous leakage were found to have associated arterial obstructive lesions.?' These men (average age, 48.8 years) had lesions involving the pudendal and penile arteries. Table 1 summarizes the many mechanisms that can cause vasculogenic impotence. Approach to Diagnosis Various noninvasive or invasive alternatives are used to investigate cases of erectile dysfunction. There is as yet no universally accepted approach. One approach begins with a limited patient goal-directed approach, depending on responsiveness or unresponsiveness to initial therapy.?5 If simple measures such as oral medications fail, more elaborate investigations are advised.',26 Should the intracavernosal administration of vasoactive agents fail or vacuum constrictor devices prove ineffective, workup would then progress to invasive delineations of abnormal physiology. Figure 3 illustrates such a sequence. A diagnostic sequence based on noninvasive neurovascular screening can also be used before the office visit for a detailed history and physical examination.-, Depending on the initial findings and a patient's desires, at this time, erectile function can be observed directly by administering PGE, intracavernosally. At the same time, blood specimens are obtained for prolactin, testosterone, glucose, and prostatic-specific antigen levels. As noted, initial noninvasive neurovascular testing can help determine the diagnostic category-that is, arteriogenic or neurogenic. This method of testing will be described further. Noninvasive vascular testing in the flaccid penile state uses a penile brachial index (PBI), which is a ratio between the systolic pressure detected by a Doppler probe placed distal to an inflated 2.5-cm cuff.'," The reappearance of Doppler signals in the dorsal artery branches just proximal to the glans signals reflow. This pressure is normally systemic. A PBI of 0.75 suggests that no major occlusion exists between the aorta and the distal measurement point. A PBI of less than 0.6 relates to major aortoiliac occlusion and almost always to erectile dysfunction. Penile pulse waves are then recorded using a pneumoplethysmographic cuff with a contained transducer. This procedure measures total pulsations of

5 58 WJM, January 1996-Vol 164, No. 1 Diagnosing and Treating 58 WJM, January 1996-Vol 164, No. I Diagnosing and Treating Impotence-DePalma Impotence-DePalma~~~~~~~~~~~~~~~~~ Complaint of Impotence Noninvasive neuro- L - History and physical vascular testing examination A~~ Risk factor modification Drugs isoxsuprine HCI and yohimbine Intracavernosal injection Nonresponsive Further testing Effective response No further testing Duplex scanning DICC - CAOP Surgical Arteriography treatment Arterial Venous Prosthetic Large-vessel reconstruction Interruption Dorsal artery bypass Transcatheter Dorsal vein arterialization occlusion Figure 3.-A flow diagram is given showing a branched logic chain for the diagnosis and treatment of vasculogenic impotence. The dotted lines indicate optional pre-examination testing. See text. CAOP = cavernosal artery occlusion pressure, DICC = dynamic infusion cavernosometry and cavernosography, HCI = hydrochloride all penile arteries as the cuff compresses the penile tissue at a mean arterial pressure. Variables recorded are crest time, waveform, and the presence or absence of a dicrotic notch on a polygraph with a chart speed of 25 mm per second and a sensitivity setting of 1. In normal men, the upstroke of the waveform is completed by 0.2 second (that is, a 5-mm space at a chart speed of 25 mm per second), and normal waveforms vary from 5 to 30 mm in height. Although these noninvasive vascular laboratory tests help define arteriogenic impotence, impotence due to venous leak and other causes are not detected. In later studies, the sensitivity of these tests was shown to predict an abnormal arteriogram in 85% of cases."8 Specificity-the percentage of true-negative tests-was 70%. The advantage of plethysmographic testing lies in the ability to define arteriogenic inflow problems before the office visit. These tests can be simply and inexpensively done by a vascular technologist. Neurologic testing uses pudendal evoked potentials, which have been shown to yield consistently reproducible values.2"2930 Because many impotent patients have diabetes, pudendal responses are compared with spinal and cortical evoked responses from tibial nerve stimulation. Mean bulbocavernosal reflex times of 28.3 to 37.5 milliseconds compare with measured values from other laboratories.' Although this type of testing is more timeconsuming and expensive than penile pressure and waveform analysis, it also provides important pretreatment data. This testing is useful in planning initial doses for the intracavernosal administration of vasoactive agents, in determining candidacy for further vascular studies, and in demonstrating the presence of neurologic disorders affecting the lower genitourinary tract. These data facilitate a careful history and goaldirected physical examination. A history of a gradual onset of erectile failure in the absence of traumatic life events implies organicity. The complaint of claudication or physical findings of aortoiliac disease, aneurysmal or occlusive, suggest a diagnosis of arteriogenic impotence, supported by abnormalities seen on noninvasive arterial testing.27 A recent and novel observation is that small aneurysms occasionally relate to an abrupt onset of impotence. This event due to atheroembolism can be documented by noninvasive studies.3' The presence of risk factors for atherosclerosis, mainly smoking, hyperlipidemia, hypertension, and diabetes, suggests a diagnosis of arteriogenic impotence, as does a history of pelvic or perineal trauma. The onset of impotence immediately after pelvic or arterial surgical therapy is critical. Finally, the presence of diabetes and any drug or alcohol use must be assessed. Physical examination is often unrevealing when small-vessel arterial disease causes impotence. Legpulse deficits or femoral bruits suggest macroarterial disease. Sensory testing of extremities, perineum, and the glans occasionally detects neuropathy, but neurologic laboratory testing is much more sensitive. After examining the prostate and rectum, palpating the corporal bodies for Peyronie's plaques and the testes completes the examination. At this time, 10 to 30 jig of PGE, should be administered intracavemosally to observe the quality of erection achieved and to assess the response to therapy. The patient should remain in the office for at least an hour following this procedure. Duplex sonography can be used at this point to scan the penile vessels after administering the vasoactive agent.'6'-2 Control values for normal men are required for this procedure. For example, in middle-aged men after the administration of PGE, and visual sexual stimulation, a 70% increase in deep cavernosal arterial diameter and a systolic peak blood flow velocity in the range of 30 cm per second have been described as normal. Duplex scanning can also detect venous leakage with high diastolic flows, although here the data are less secure. Considerable interest exists in using this type of testing for selecting invasive procedures such as arteriography or DICC. My approach is to observe the quality of erection after increasing intracavernosal doses; when failure occurs or a Peyronie's plaque is found, duplex scanning is recommended. Ultrasonography can also scan for previously undetected abdominal aneurysms. Duplex scanning after the intracavernosal administration of a vasoactive agent, however, is more time-consuming than noninvasive vascular studies and requires a physician's presence before and after administering the agent. A recent study shows the diagnostic problems of evaluating the veno-occlusive mechanism. Duplex scanning with the evaluation of end-diastolic flow showed

6 1 WJM, January 1996-Vol 164, No. I Diagnosing and Treating Impotence-DePalma Impotence-DePaima 59 22% false-positive results.33 When abnormalities of veno-occlusions were diagnosed using end-diastolic flow, subsequent nocturnal penile tumescence (NPT) monitoring proved to be normal in 8 of 37 men. The findings suggested anxiety in the clinical setting where duplex scanning was done. I do not use NPT monitoring routinely, but select this test when psychogenic impotence is likely or in cases of injury with continuing medicolegal problems. It is done optimally in a formal sleep laboratory with three nights of monitoring and the measurement of penile rigidity when erection occurs.3'normal penile rigidity or pressure is taken at 400 to 500 grams of axial buckling pressure. This test is both time-consuming and expensive, but it is important because a normal sleep erection virtually rules out organic erectile dysfunction. For screening purposes, a Rigiscan home NPT monitor is also employed. This may help by minimizing both the expense and anxiety in the clinical situation. Treatment At the outset, men with erectile dysfunction can be treated nonsurgically. Avoiding cigarette smoking, alcohol abuse, and drug use are first steps. Currently available oral drug therapy includes isoxsuprine hydrochloride, an ao,-adrenergic blocker; yohimbine hydrochloride; a presynaptic adrenergic-receptor agonist, trazodone hydrochloride; and vacuum constrictor devices. Four trials have been done with yohimbine with varying results, some patients showing improvement compared with those taking placebos.3" The time to improvement has ranged from three days to three weeks, and this drug appears to be effective mainly when psychogenic factors are present. External vacuum devices have been reported to be effective in men for whom administering vasoactive agents intracavernosally had failed, as measured by patient rating and device returnm. Although self-administering PGE, is common, a search continues for locally or intraurethrally applicable materials to avoid the need for intracavernosal administration.37' 8 It is now clear that orally administered drugs can induce erection and even cause priapism.'3 The mechanism of action of these drugs is likely an inactivation of a-adrenoceptor activity in cavernosal smooth muscle. For patients with diabetes and men with neurovascular dysfunction, prosthetic devices can be recommended for those refractory to intracavernosal PGE, administration. The advantages and disadvantages of these devices have been summarized.39 Over the past two decades, an estimated 250,000 men in the United States have received penile prostheses. Modern physiologic inflatable prostheses are self-contained with a built-in cylinder pump (a 2-piece device) or are three-piece devices. These consist of two cylinders connected to a scrotal pump without connectors because these were often the cause of failure. An outcome analysis was done from January 1984 to December 1993 of 328 implants, with follow-up data being obtained in 246, for a 75% followup rate. The infection rate for primary implants was 4.3%; for secondary implants, it was 10.8%. Depending on the prosthetic type, 82% to 90% of patients reported satisfactory prosthetic function, but only 71% of men were satisfied with the device. An interesting new development is the soft Subrini implant.404' This is neither inflatable nor is it meant to provide rigidity. Rather, the device fills the cavernosal body to allow normal tumescence in naturally erotic situations. Vascular Interventions Were implants totally satisfactory, they would be more widely used. A functional vascular reconstruction is a more satisfactory option, but microvascular reconstructions of penile vessels and venous ligation procedures are being reassessed.42 Skepticism exists regarding the many variants of penile revascularization or venous ablation because reported success rates range from 33% to 100%. Little life-table data exist to support these claims,43 and no uniform methods of postoperative surveillance have been agreed on. Thus, in 1996 the true success rates of corporal revascularization or venoablative procedures are as yet unknown.' This situation is similar to the early period of coronary artery revascularization operations. Clearly, penile microvascular bypasses and venous interruption are evolving procedures. Better diagnostic criteria, techniques, and follow-up methods are needed. Aortoiliac surgical techniques that perfuse the internal iliac arteries and spare autonomic nerves are less controversial.'" Not only can iatrogenic impotence be avoided, but potency can be restored in 58% of men. In our recent report of ten years of experience with vascular intervention for impotence, men with the sole complaint of impotence underwent interventions for aortoiliac aneurysms or occlusive disease.4' In these men, 58% resumed spontaneous function over follow-up periods ranging from 33 to 48 months; an additional 15% functioned with intracavernosally administered agents or vacuum constrictor devices. These men with aortoiliac disease averaged 61 years of age. In contrast, during the same period, men selected for microvascular procedures for penile artery bypass, deep dorsal vein arterialization, and venous ligation had an average age of 42 to 47.3 years. This age difference was statistically significant at a P value of.001 by analysis of variance. A significant difference between observed and expected frequencies of spontaneous erection was shown between those undergoing aortoiliac interventions and men having penile arterial or venous procedures. At 33 to 48 months after these operations, only 27% to 33% of men reported spontaneous erection. When intracavernosal administration of PGE, or vacuum constrictor devices were added, however, 72% to 77% reported functional erections that could not be previously obtained. When the diagnostic screening sequences previously described were used'814,7 and patients with diabetes mellitus and those with hypertension were excluded, 6% to 7% among a group of 1,094 men became candidates for vascular interventions of differing types. A later analysis

7 1996-Vol 164, No WJM, January 1996-Vol 164, No. I Diagnosing and Treating Impotence-DePalma was done of 1,145 cases of male impotence, and in a subset of 23 men with the primary complaint of impotence, 11 were found to have aneurysms and 12 had aortoiliac occlusions.3' Noninvasive studies suggested that three probably had internal iliac or pudendal artery embolization that appeared to relate to the abrupt onset of impotence. About 1% of men with the complaint of impotence in this series have an associated aortic aneurysm. In men with risk factors such as smoking or hypertension and when abdominal palpation is inconclusive, ultrasound screening is useful to examine the aortoiliac segments. This small but important subgroup of older men demands careful workup because enlarging aneurysms are potentially lethal. The Future Most men with erectile dysfunction can be treated medically. The main modalities of therapy are the intracavernosal administration of PGE, and the use of vacuum constriction devices. The search for locally applicable or oral agents promises to be intense. Drug testing will rely on an enhanced knowledge of cavernosal smooth muscle function and will require more precise methods of objective documentation of results. The likely mechanisms of action of new agents will relate to an inhibition of ox-adrenergic activity and the potentiation of other endogenous inhibitors of smooth muscle contraction.'3 These drugs might also be found to exert beneficial effects in peripheral vessels. The process responsible for declining erectile function with age needs to be more clearly delineated. This process is not, as previously thought, a simple progression of arterial insufficiency and may not even be a manifestation of disease. Changes in the structure and function of aging cavernosal smooth muscle and neurotransmitters are as yet poorly documented.' Decreased nitric oxide synthase has been shown in cavernosal tissue of aging rats.4" The local changes in penile tissue occur in conjunction with age-related decrements in noctumal penile tumescence in frequency and degree, along with decreased sexual desire and coital frequency.48 The diagnosis and treatment of erectile dysfunction continue to advance. A well-disciplined diagnostic and therapeutic approach will rely less frequently on vascular interventions, except in the interesting subgroup of those with aortoiliac disease who require surgical intervention. Opportunities exist for improving prosthetic devices and refining choices and techniques of microvascular procedures. The treatment of men with erectile dysfunction requires a unique sensitivity to the needs and aspirations of each person, along with attention to details of diagnosis and therapy. Outcomes are satisfying as effective diagnostic methods and treatment have become better defined. REFERENCES 1. Krane RJ, Goldstein 1. Saenz de Tejada 1: Impotence. N Engl J Med 1989: 321: Leriche R: Des obliterations arterielle hautes (obliteration de la termination de l aorte) comme cause de insufficances circulatoire des membres inferiurs (Abstr). Bull Mem Soc Chir 1923: 49: Leriche R, Morel A: The syndrome of thrombotic obliteration of the aortic bifurcation. Ann Surg 1948; 127: May AG. DeWeese JA, Rob CG: Changes in sexual function following operation on the abdominal aorta. Surgery 1969: 65: DePalma RG, Levine SB, Feldman S: Preservation of erectile function after aortoiliac reconstruction. Arch Surg 1978; 1 13: DePalma RG, Kedia K, Persky L: Surgical options in the correction of vasculogenic impotence. Vasc Surg 1980; 14: Michal V, Kramar L, Pospichal J, Hejel L: Gefasschirurgia erektiver Impotenz. Sex Med Sondertr 1976; 5: Virag R: Intracavernous injection of papaverine for erectile failure (Letter). Lancet 1982; 2: Brindley GS: Pilot experiments on the actions of drugs injected into the human corpus cavernosum penis. Br J Pharmacol 1986; 87: Rajfer J, Aronson WJ, Bush PA. Dorey FJ, Ignarro LJ: Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic. noncholinergic neurotransmission. N EngI J Med 1992; 326: Azadzoi KM, Nehra A, Siroky MB: Effects of cavemosal hypoxia and oxygenation on penile erection (Abstr). Int J Impot Res 1994; 6(suppl I):D4 12. Gopalakrishnakone P, Adaikan PG, Ponraj G, Ratnam SS: NADPHdiaphorase and VIP positive nerve fibres in human penile erectile tissue (Abstr). Int J Impot Res 1994: 6(suppl I):A Adaikan PG: Physiopharmacological basis of treatment for erectile dysfunction (Abstr). Int J Impot Res 1994; 6(suppl 1):PLI 14. Brock GB. Zvara P. Sioufi R, Begin LR, Schipper HM: Nitric oxide synthase is testosterone dependent (Abstr). Int J Impot Res 1994; 6(suppl I):D DePalma RG: Mechanisms of vasculogenic impotence, chap 32, In White RA, Hollier LA (Eds): Vascular Surgery-Basic Science and Clinical Correlations. Philadelphia, Pa, JB Lippincott, 1994, pp Lue TF, Hricak H. Marich KW, Tanagho EA: Vasculogenic impotence evaluated by high-resolution ultrasonography and pulsed Doppler spectrum analysis. Radiology 1985; 155: Goldstein 1: Vasculogenic impotence, its diagnosis and treatment, In de Vere White (Ed): Problems in Urology-Sexual Dysfunction. Philadelphia, Pa, JB Lippincott, pp DePalma RG, Schwab FJ, Emsellem HA, Massarin E, Bergsrud D: Noninvasive assessment of impotence. Surg Clin North Am 1990; 70: Udelson D, Hatzichristou DG, Saenz de Tejada 1, et al: A new methodology of pharmacocavemosometry which enables hemodynamic analysis under conditions of known corporal smooth muscle relaxation (Abstr). Int J Impot Res 1994: 6(suppl l):a Keogh ET, Earle CM, Chew KK, et al: Medical management of impotence (Abstr). 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