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Assessment and treatment of impotence
COMMON MEDICAL PROBLEMS IN AMBULATORY CARE
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ASSESSMENT AND TREATMENT OF IMPOTENCE Mary O'Keefe, MD, and Debra K. Hunt, MD, MSPH
Impotence is defined as the inability to achieve and sustain an erection of sufficient rigidity for intercourse. In the Massachusetts Male Aging Study,12 a cross-sectional survey of men from ages 40 to 70 in the Boston area, the prevalence of impotence was 52%, and this increased from 40% at age 40 to 67% at age 70. The probability that impotence would occur was three times greater in treated diabetics than in nondiabetics and increased in men with heart disease, hypertension, and low high-density lipoproteins and those taking antihypertensive, vasodilating, cardiac, or hypoglycemic medicines. Smoking increased the risk associated with cardiovascular disease and medications. This information suggests that impotence is a common problem with multiple preventable and treatable causes. In this article, the physiology, diagnosis, and treatment of impotence are reviewed. Diagnostic testing is recommended only in cases when specific treatment is available. Only impotence is discussed. Difficulty with libido, orgasm, or ejaculation is not addressed. PHYSIOLOGY
Erection may be initiated reflexively through direct tactile stimulation or through a more complex pathway involving other types of stimulation (i.e., visual). The process of erection is mediated by somatic, sympathetic, and parasympathetic nerves and sympathetic tone. Penile arteriolar dilation leads to increased inflow, and a simultaneous relaxation of corporal sinusoids causes increased corporal size. The enlarged From the Department of Medicine, University of Texas Health Science Center at San Antonio; and Audie Murphy Memorial Veterans Administration Hospital (MO), San Antonio, Texas MEDICAL CLINICS OF NORTH AMERICA VOLUME 79 • NUMBER 2 • MARCH 1995
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corpora compress the draining veins against the tunica albuginea, which decreases (relatively) the venous outflow (Fig. 1).18 Thus, the normal erection depends at least on psychological, neurologic, hormonal, and vascular processes. EVALUATION OF IMPOTENCE Psychogenic Impotence
Classic features suggesting psychogenic impotence include sudden onset preceded by a specific event, normal morning erections, and ab-
A Dorsal a. ---......,..~"".;
Cavernous a.
Circumflex a. Bulbourethral a. -
----'''' Buck's fascia
B Superficial dorsal v.
vV'~?:~~il~:~ '-
Deep dorsal (Cavernous at hilum of penis) Circumflex v.
Subtunical -~~·,V" venular plexus
Bulbourethral v.
cavernosum Tunica albuginea Urethra ----- - Corpus spongiosum
Figure 1. Arterial supply (A) and venous drainage (8) of the penis. Transverse view. (From Lue TF: Physiology of erection and pathophysiology of impotence. In Walsh P, Gittes R, Perlmutter A, et al (eds): Campbell's Urology, ed 6. Philadelphia, W.B. Saunders, 1992, p 709.)
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sence of chronic health problems or medications. A 1984 study measured the ability of some of these clinical characteristics to distinguish organic from psychogenic impotence. 25 The sensitivity and specificity of selected findings compared to diagnosis by nocturnal penile tumescence monitoring and psychiatric interviews are shown in Table 1. In this relatively small study, reporting good-quality early morning erections was a specific finding for psychogenic impotence. The absence of a disease and absence of medication known to cause impotence were sensitive findings for psychogenic disease. Nocturnal Penile Tumescence
The theoretic basis for nocturnal penile tumescence (NPT) monitoring is that an intact erectile mechanism must exist to produce an erection during sleep. Thus, if erectile dysfunction is due to psychological inhibition during sexual activity, nocturnal erections should be normal. The normal man experiences three to five erections per night, each lasting 25 to 35 minutes. A formal NPT study involves monitoring for three consecutive nights in a sleep laboratory. Nocturnal erections occur only during rapid eye movement (REM) sleep, so electroencephalographic, electro-oculographic, and electromyographic activity is recorded to document sleep quality and to avoid a false-negative study. In addition, penile circumference is measured with strain gauges at the base and tip of the penis. When an erection is detected, the patient is awakened and axial rigidity is measured by assessing the resistance of the penis to buckling when a known weight is applied to the glans penis. A positive test is "normal" or suggestive of a psychogenic cause of impotence. 33, 96 A number of concerns about the validity of NPT monitoring have been raised. 64 First, there are methodologic problems with the early studies. Patients were included in study groups partly based on their NPT results, thus inflating differences between groups. One small study that avoided this flaw found that NPT results agreed with the diagnosis Table 1. CLINICAL CHARACTERISTICS OF PSYCHOGENIC VERSUS ORGANIC IMPOTENCE IN 67 PATIENTS Psychogenic Disease Sensitivity
(%)
Specificity
Characteristic
Normal early morning erection Sexual erection of good quality but not maintained Sudden onset No current illness' No medications'
52 27
100 100
30
90 94
(%)
76 76 41
'Likely to interfere with erections. Adapted from Condra M, Morales A, Surridge D, et al: Evaluation of the urologic assessment in impotence: Findings with a new diagnostic rating scale. J Urol 131 :486, 1984; with permission.
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established by clinical criteria 80% of the time. 58 Second, the gold standard for diagnosing psychogenic impotence is unclear. This problem has led to case reports of patients diagnosed with psychogenic impotence by NPT later presenting with a pituitary adenoma 101 or patients with depression being diagnosed with organic impotence by NPT and nocturnal erections normalized after treatment of the depression?8. 90 Finally, nocturnal erections may not reflect the erectile potential in the erotic or sexual situation. Organic conditions such as sensory neuropathy may increase latency to erection during sexual activity but have no effect on nocturnal erections. Despite these problems with NPT monitoring, it became a widely accepted diagnostic tool in the evaluation of impotence, but more convenient, less expensive methods were desired. The first home monitoring method developed was the stamp test. 9• 56. 57 Four postage stamps were wrapped snugly around the penis, overlapping by at least one half of a stamp. The patient simply noted if the perforations were broken by morning. Although simple and inexpensive, studies have not found the test accurate enough for clinical use. The Snap-Gauge device (Dacomed Corp., Minneapolis, MN) was introduced in 1982. Small studies suggest that the sensitivity is around 90% with a specificity of 40% to 50%.4. 7. 24 At a cost of only $12, compared with over $700 for NPT monitoring, many authors believe this instrument may be useful for screening purposes. The most recent device to become available is the RigiScan (Dacomed Corp., Minneapolis, MN). This is a battery-powered device that is strapped to the patient's thigh and uses two mercury strain gauges to measure penile circumference. The circumference is sampled every 15 seconds throughout the night, and these values are stored in the memory of the attached recording device. Preliminary results suggest that this device may not be able to detect mild abnormalities in erectile dysfunction, but more study is needed. s NPT monitoring is not relied on heavily to distinguish organic from psychogenic impotence. At this time, clinical characteristics are used to separate these two groups, and use of the Snap-Gauge is considered only in a limited number of cases. Drug-Induced Impotence It has been reported that 25% of impotence in clinic patients is due to a drug side effect.43 Antihypertensives are often implicated (Table 2). This may be a drug-specific side effect or due to a therapeutic decrease in blood pressure and thus a decrease in penile perfusion. In large placebo-controlled trials comparing sexual side effects for various antihypertensives, few or no significant differences in incidence are found. 28, 29. 92 This finding suggests that a decreased perfusion pressure plays at least some part in causing impotence. Psychiatric medications also are a common cause of impotence (Table 3). It may be difficult to determine
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Table 2. SEXUAL DYSFUNCTION WITH SELECTED ANTIHYPERTENSIVE AGENTS Percentage of Patients with Impotence
Drug Thiazide Spironolactone
4-32% 2-30%
Sympatholytics (methyldopa, clonidine, guanethidine, reserpine) 13-Blockers
8-80% (most often 20-30%) 0-43%
a-Blockers Labetalol Angiotensin converting enzyme inhibitors Vasodilators (hydralazine, minoxidil) Calcium channel-blockers
Minimal Minimal Minimal Minimal Minimal
Comment Dose dependent; gynecomastia common Decreased libido Dose dependent; lowest with 13, specific agents (pindolol, nadolol, atenolol); also reported with ophthalmic drops May induce priapism Ejaculatory changes common Some patients report aphrodisiac effects of hydralazine
Data from references 15, 16, and 86.
whether impotence is due to the psychiatric disease or the medication, particularly because onset is typically abrupt in both cases. Use of recreational drugs is also commonly associated with impotence. Up to 75% of patients in alcohol rehabilitation programs reported impotence in the preceding 6 months, both during and after alcohol use. Other commonly implicated drugs include cimetidine, digoxin, and anabolic steroids, and there are case reports of impotence with most medications.
Table 3. SEXUAL DYSFUNCTION WITH SELECTED PSYCHIATRIC MEDICATIONS Drug Antipsychotics Monoamine oxidase inhibitors Tricyclics Selective serotonin reuptake inhibitors Benzodiazepines
Percentage of Patients with Impotence 0-54% 16-31% Significant 8-16% Reported
Data from references 15, 16, and 86.
Comment More common with greater a-adrenergic and anticholinergic effects Also anorgasmia Also decreased libido, anorgasmia. May be less common with desipramine
Also decreased libido, ejaculatory changes
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Hormonal Causes of Impotence
The true incidence of endocrine dysfunction as the cause of impotence is unclear. Estimates range from 2% to 35%.44 Early review articles called for hormonal evaluation in all patients, but more recent work, described subsequently, has called this practice into question. Testosterone
Testosterone levels vary diurnally (lowest in the afternoon) and are diminished by stress, anxiety, or depression, For these reasons, testosterone levels should be measured only on fasting morning specimens, If the first level is low, it should be repeated, and some authors think three low levels are needed, Similar to other hormones, testosterone is highly protein bound, so total testosterone levels are affected by the availability of binding proteins, Bioavailable testosterone is a measure of the loosely bound and unbound testosterone, which is physiologically active and is a better indicator of hormone status, In 1992, Johnson and Jarow44 reported results of the evaluation of 300 men referred to an impotence clinic. They found seven cases of endocrinopathy. Of these seven, all had either bilateral testicular atrophy or decreased libido, leading the authors to recommend obtaining screening testosterone levels only in patients with one of these two findings, Luteinizing Hormone and Follicle-Stimulating Hormone
Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels may be useful in distinguishing primary from secondary hypogonadism but are not necessary for initial screening,69 Prolactin
Prolactinomas can cause impotence, One study found that 3 out of
212 (1.4%; Cl 95 [0-3,0%]) men evaluated for impotence had elevated
prolactin levels,2 Of these three, two had low testosterone levels, and the third had renal insufficiency, which is known to elevate serum prolactin levels. The authors concluded that it would be cost-effective to measure prolactin only in impotent men with low testosterone levels, Thyroid Hormone
Both hypothyroidism and hyperthyroidism have been implicated as causes of impotence. 14, 45, 103 Prepubertal hypothyroidism can affect male gonadal function and if left untreated may lead to testicular atrophy. In adults, hypothyroidism appears to be an infrequent cause of impotence, and it is unclear whether it can be the presenting complaint. Thus, the utility of screening all impotent patients for hypothyroidism is uncertain. Hyperthyroidism has also been implicated as a cause of impotence.
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In one small study four of seven hyperthyroid men complained of impotence. 45 Again, it is unclear whether impotence can be the only manifestation of hyperthyroidism. Patients presenting with impotence should be questioned further for symptoms of thyroid dysfunction, but routine screening seems unnecessary. Vascular Disease
Many tests are available for the diagnosis of vascular impotence, but all must be correlated with the clinical picture. 30,55 As is discussed later, vascular surgery is a widely accepted treatment option only for young patients without concomitant illness. Most of these tests should therefore be reserved for these patients. Arterial Insufficiency
The most invasive technique used to detect arterial insufficiencyinduced impotence is selective pudendal pharmacoarteriographyY' 104 This technique requires local anesthesia with intravenous sedation and so has attendant risk. Occasionally, serious complications such as intimal dissection of the hypogastric artery occur. A number of less invasive tests have been developed for arterial insufficiency, the least invasive of which is the penile-brachial index (PBI). The PBI is a ratio between the penile and brachial systolic pressure detected by a Doppler probe. The PBI is calculated in the flaccid state and does not convey the pressure available for erection. A value of 0.60 is considered low, whereas 0.90 or more is usually considered normal. Studies of the PBI suggest that it may lack the accuracy of a good screening tesU' 22, 67, 80 No raw data were provided to calculate sensitivity and specificity, but two studies reported correlation coefficients of 0.3; one study found no correlation. Another study reported low interobserver reliability: Fewer than 80% of patients were classified the same by two observers. Doppler ultrasonography may also be used to diagnose arterial insufficiency. Changes in the diameter of the cavernosal artery and the velocity of blood flow are measured after intracavernosal injection of vasoactive agents. Published studies are fairly small, and many did not perform the gold standard study on all patients. 21 , 31, 35, 40, 52, 81 One study of 30 patients who received both Doppler ultrasonography and selective pharmacoarteriography reported a sensitivity of 100% and a specificity of 46% for Doppler ultrasonography.95 Venous Disease
The venous compression of a normal erection may be evaluated clinically by pharmacocavernosometry and cavernosography.3o,55 These
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studies evaluate the adequacy of corporal venous outflow resistance and therefore must always be performed following intracavernosal injection of vasoactive agents. The diagnostic accuracy of these tests is unclear?6 Cavernosometry measures (1) the intracavernosal flow rate of saline required to create or sustain an erection and (2) the rate of fall in intracavernosal pressure after the infusion is stopped. When veno-occlusive dysfunction is present, there is either a high flow rate needed to maintain an erection or a rapid fall in intracavernosal pressure after cessation of saline infusion. Cavernosography is used to visualize the veins draining the corporal bodies during erection. Images are obtained following intracavernosal injection of radiopaque contrast material into the erect penis. When corporal veno-occlusive function is normal, little or no venous drainage is seen. Neurologic Disease
Tests are available to diagnose neurologic impotence, but it is unclear who should undergo testing. 3D The two tests most commonly used are the bulbocavernosus reflex (BCR) and pudendal-evoked responses (PER)Y· 51. 70 The BCR measures the electromyographic activity of the bulbocavernosus muscles in response to electrical stimulation of the glans penis. According to one study of 299 impotent patients, an absent response was indicative of a sacral spinal cord lesion. 12 A more recent study has questioned the accuracy of this test. 51 The PER measures suprasacral neurologic disease. Electroencephalogram leads are placed over the scalp, and electrodes are placed over the L-1 vertebra. The penis is then electrically stimulated, just as for a BCR, but readings are taken at the lumbar and cortical levels. Again, delayed responses are considered abnormal, but accuracy is unproven?O These tests are not used to screen for an occult neurologic lesion but rather to determine whether known neurologic disease is the cause of the impotence. TREATMENT OF IMPOTENCE Psychogenic Impotence
There are several types of therapy for psychogenic impotence, including psychoanalysis, behavior modification, and intensive symptomoriented sex therapy. The last-mentioned was pioneered by Masters and Johnson,59 who reported a 74% success rate for secondary impotence. Further study rarely duplicates this initial success and has in particular shown poor results for older patients and those with impotence of longer duration and insidious onset. 41 • 53 Results are confounded by difficulty in selecting patients with psychogenic not organic impotence, as discussed earlier.
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Thus, it seems reasonable to refer patients for sex therapy if the clinical index of suspicion of psychogenic impotence is high. Therapy is less likely to be helpful in older patients, with a history or risk factors suggesting organic disease. Drug-Induced Impotence If impotence is believed to be a drug effect, a trial off medication is reasonable. If the medication is implicated, the physician and patient must decide whether the benefits of treatment outweigh this side effect.
Hormonal Causes of Impotence Testosterone If hypogonadism is diagnosed, treatment with testosterone may be elected, but its use is not well supported. In a critical review, Mulligan and Schmitt68 concluded that testosterone increases sexual interest, frequency of sexual acts (although not necessarily penetration), and frequency of nocturnal erections. Thus, it is beneficial for decreased libido but of questionable benefit for impotence. Testosterone is available in three forms. Oral testosterone is not recommended owing to the frequency of hepatitis and hyperlipidemia. Most patients are treated with 200 mg of testosterone cypionate intramuscularly administered every 2 to 6 weeks. The cost of transdermal testosterone may be prohibitive (wholesale cost of $1.88 for 4 or 6 mg daily patch). When treatment with testosterone is elected, it is important to remember two side effects. First, testosterone stimulates the growth of prostate cancer. Second, testosterone increases libido. Patients inappropriately treated with testosterone may experience the frustration of an increased libido without an improvement in erection.
Pro/actin
Patients with prolactinomas are generally referred to a specialist for treatment. Treatment with the dopamine agonist bromocriptine restores potency in most patients. 91 Although testosterone levels are low, it should not be supplemented because it may stimulate the pituitary adenoma. Thyroid Hormone
Although impotence is commonly associated with thyroid disease, the authors are unaware of studies reporting the rate of improvement with treatment. 45 It is reasonable to treat the underlying thyroid disorder before considering other options for the impotence.
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Vascular Disease Surgery
The use of surgery for vasculogenic impotence is controversial in the majority of patients. Two main types of surgery are available and may be used together: revascularization and veno-occlusive reconstruction. Cookson and colleagues27 studied revascularization surgery with or without venous reconstruction: Of 898 patients referred to a urology practice, 50 were selected to undergo surgery. Of these, 24 had return of sexual function (48%), and 20 had return with the use of penile selfinjection, which had previously been ineffective (40%). In assessing these results, it is important to note that this was a highly selected group; only 6% of those referred were offered surgery. Mean age was 38, only 1 had diabetes, none were smokers, and none had hypertension. Additionally the study was not controlled. In similar uncontrolled studies of selected patients, success rates are reported between 54% and 800/0.17, 34, 38, 39, 46, 60, 74, 79, 82, 99
Wespes and Schulman100 reviewed results of surgery for venous incompetence without revascularization. Cure rates varied: 57% for venous embolization, 10% to 90% for various venous ligation procedures, and 0 to 60% for a variety of other techniques. Again, this is a select group of patients, and the authors of the study specifically suggest excluding those with arterial insufficiency. In view of these results, it seems prudent to reserve consideration of vascular surgery for those who have failed more conservative treatment or for young patients without concomitant illness. Pentoxifylline
Korenman and Viosca47 studied pentoxifylline as a treatment for vasculogenic impotence. Twenty-four patients, with an average of 6.2 years of impotence, were randomized to receive placebo or pentoxifylline in a double-blind trial. Four of 8 patients on pentoxifylline had at least one successful coital event, compared with 0 of 10 on placebo. Of note, patients were selected for consideration for the study based on an abnormal PBI, which is a test of questionable utility as previously discussed. These results are promising, but more study is needed. Neurologic Disease
There is no specific treatment for impotence of neurologic etiology. TREATMENTS UNRELATED TO CAUSE OF IMPOTENCE
In addition to those disease-specific treatments already discussed, several other options are available regardless of cause. These treatments
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should be considered for patients with neurogenic impotence, those with mixed etiology, and those that do not respond to disease-specific treatments. The choice depends on patient preference as well as cost, risk, benefits, and side effects. Vacuum Constriction Devices
Vacuum erection aids consist of a hollow tube, a manual vacuum pump, and a constriction ring. The tube is placed over the penis, and a seal is formed at the pubic wall. A vacuum is created with the manual pump, so that arterial inflow increases and erection is achieved. The constricting ring is placed over the base of the penis so that venous return is reduced and an erection is maintained when the tube is removed. Erection lasts until the ring is removed (recommended 30 to 60 minutes). These devices cost $300 to $400 and may be purchased from the manufacturer with a prescription. Common side effects include bruising (especially in patients using antiplatelet agents), entrapment of scrotal tissue in the vacuum tube, decreased penile skin temperature, impaired ejaculation owing to urethral blockage, discomfort from the pump or band, and pivoting of the penis (owing to lack of erection at the band). Use is contraindicated in patients with sickle cell disease or on anticoagulants. In studies of patients with impotence of mixed etiology, patients who choose to try vacuum devices have satisfaction rates of 66% to 93% (Table 4). In studies of selected groups, satisfaction rates are also high in patients with an organic cause, patients with venous leak, patients with a neurologic cause, and patients who have failed a prosthesis. Satisfaction rates are lower in patients who have failed self-injection, sexual counseling, and other treatments (Table 5). Although some patients are unwilling to use this device, the authors recommend it as a relatively safe, inexpensive first option for treatment, which may be offered without referral to a specialist.
Table 4. SATISFACTION WITH VACUUM DEVICES FOR IMPOTENCE PATIENTS WITH MIXED ETIOLOGY
Study
No. of Patients
Witherington 102 Cookson & Nadig26 Sidi et al 83 Van Thillo & Delaere 97 Turner et al 94 Turner & Althof93 Sidi & Lewis 84 Papp et al 73
1517 161 100 30 36 36 31 48
Average Follow-up (months)
8.6 3 7.9 6 6 6 3
one use in office
Satisfied or with Adequate Erection (%)
92 82 68 66 89 81 93 71
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Table 5. SATISFACTION WITH VACUUM DEVICES FOR IMPOTENT PATIENTS: SELECTED POPULATIONS
No. of Patients
Study
Satisfied or with Adequate Erection (%)
3
100 75 73 69 75
17 11 17
21 1 6
83 91 94
45 74
3 3 weeks
27 30
Korenman et al Aloui et al 6 AI-Juburi & 0'Donnell 3 Blackard et al" Arauz-Pacheco et al 8
20 16 44 47 12
Helier et al 43 Moul & McLeod 65 Korenman & Viosca 48 Gilbert & GingelP6 Meinhardt et al 61
49
Average Follow-up (months)
6 3 6
unknown
Patient Characteristics Abnormal snap gauge Organic cause Organic cause Venous leak Diabetes; no vascular disease, hypertension, or other endocrine disease Various neurologic causes Explanted prosthesis Status post pelvic radiation or surgery on unsuccessful implant Failed self-injection Failed sexual counseling, self-injection, venous surgery, or prosthesis
Penile Self-Injection Therapy
Another treatment option is penile self-injection of various vasoactive medications. Medications commonly used include phentolamine, an et antagonist; papaverine, a nonspecific smooth muscle relaxant; and prostaglandin E. All act by dilating arterioles and thus increasing arteriolar inflow. Most often, a combination of agents is used to minimize side effects. Erection results within minutes of injection, and dosage is titrated so erection lasts 30 to 60 minutes. This usually requires several office visits. The wholesale cost of the medication alone is abOllt $2 per treatment. Side effects include hematoma, fibrosis, nodule at the injection site, and priapism. Although this form of treatment is widespread, none of these agents is approved by the Food and Drug Administration for this use. In his review of the use of injection therapy, Lue54 reports successful treatment for psychogenic, neurogenic, and, to a lesser extent, vasculogenic impotence. In two representative reports on the use of injection therapy, only 10% of patients selected this treatment when informed of their options. 50, 98 Of those that continued treatment, approximately 90% were satisfied, although a significant number developed hematoma or fibrosis at the site of injection. Injection therapy is selected by a minority of patients but is effective for patients with various causes of impotence. There is a significant
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incidence of side effects, although this seems to be reduced with newer drugs and combinations of drugs. 54 Penile Prostheses
Penile prostheses are designed to provide sufficient penile rigidity for intercourse. Patients often mistakenly believe that the prostheses provide an erection similar to their prior normal erections and that they also correct problems with libido, orgasm, and ejaculation. It is important to discuss realistic expectations so that patients may make an informed decision. There are three commonly used types of prostheses. The semirigid rod maintains a constant shape and size but may be curved either up or down. The malleable rod maintains a constant size but may be straightened and curved as desired. The inflatable prosthesis consists of a pumping mechanism often placed in the scrotum, which transfers fluid from a retrocystic reservoir to the prosthesis. With pumping, the prosthesis enlarges and straightens. The major cost of penile prostheses is related to surgical implantation. Common complications include postoperative infection, perforation of the uretha or corpora, extrusion of the device, and mechanical problems. Also, because of disruption of normal anatomy, patients who fail this treatment are often unable to benefit from other options. In their review, Petrou and Barrete5 report surgical success rates of 82% to 98% with various types of prostheses. The authors believe penile prostheses are an appropriate treatment option for patients with normal libido, who are willing to accept the surgical risk and unwilling to try or unable to achieve success with more conservative treatments. Yohimbine
Yohimbine is an (X2 agonist and acts by inhibiting (Xl activity. This inhibition leads to decreased arteriolar tone and thus increased penile inflow. The recommended dosage is 5.4 mg three times a day, at a wholesale cost of about 1511' a day. The major side effect is a central nervous system excitatory state, which can lead to increased blood pressure and pulse rate, exacerbation of angina, anxiety, dizziness, and nausea. Morales and colleagues63 studied 100 patients with organic impotence as determined by abnormal nocturnal penile tumescence and evaluation by a urologist and psychologist. Patients received yohimbine or placebo in a double-blind trial. Forty-three percent reported response to yohimbine compared with 28% for placebo. The response rate was unaffected by age, penile brachial index, testosterone, FSH, or prolactin levels or the coexistence of diabetes, paresthesias, peripheral vascular disease, or use of insulin or antihypertensives.
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Sonda and associates 87 studied 40 patients with impotence in a placebo-controlled cross-over trial. Of 33 patients completing the trial, 49% reported a satisfactory response to yohimbine and 33% to placebo. Of 20 patients with a negative snap-gauge test, 40% improved on yohimbine, compared with 0 on placebo (P < 0.01). The overall response rate to yohimbine and placebo is similar in the two studies, although Morales studied only organic impotence and Sonda studied both organic and psychogenic impotence. Interestingly, there was a significant response to yohimbine in organic impotence in Sonda's study. The difference may be the method of classification of organic impotence or other unreported differences in study methods. With this and other available data, the authors would suggest a trial of yohimbine only in patients without coronary disease or moderate-tosevere hypertension, who are unwilling to try other treatment options. EXPERIMENTAL THERAPY Nitroglycerin
The majority of reports of the use of nitroglycerin for treatment of impotence are case reports or uncontrolled studies. 3 ?, 42, 62, 66, 71, 88 Additionally, there are positive results from controlled studies done in the laboratory, using strain gauge and duplex results as end points. 72 Claes and Baert23 performed a placebo-controlled, double-blinded, cross-over clinical trial of nitroglycerin patches. Patches were applied before intercourse, and results were assessed by patient report. Of 26 patients, 21 reported a response to nitroglycerin, and 5 reported a response to placebo. Twelve complained of headache associated with nitroglycerin. There are also reports of headache in the sexual partners of men using nitroglycerin. 89 Because of the scarcity and small size of clinical trials, nitroglycerin should not be considered an established treatment for impotence. Minoxidil
Topical minoxidil, a vasodilator, has been proposed as a treatment for impotence. The authors are unaware of any controlled trials of the use of minoxidil in a home setting. Uncontrolled studies yield mixed results. lO, 20, 77 CavallinP9 compared minoxidil, nitroglycerin, and placebo in 33 patients with arterial or neurogenic impotence in a double-blind trial. Diameter, rigidity, and arterial flow were compared. In all measures, minoxidil was more effective than nitroglycerin, which was more effective than placebo. Side effects were comparable with minoxidil and placebo and significantly greater with nitroglycerin. Although these data are promising, minoxidil cannot yet be recommended.
ASSESSMENT AND TREATMENT OF IMPOTENCE
New drug or drug commonly causing impotence?
429
- - - - y e s - - - - - - i Change or discontinue if possible
I
No Check TSH I - - - - y e s - - - - - - I Treat thyroid disease if present
Normal morning erections? Any erections with normal ngidity, duration, and latency? Sudden onset of impotence? No current illness or medication?
Consider psychogenic - - - y e s - - - - - I etiology, counseling
I I
No Symptoms or signs of hypogonadism? (Decreased libido? Decreased testicular size?)
1----yes----~-;C~h:e:ck~te:s:to:s:te:r:o:n:e:le:v:e~I-~
I
Normal
No Consider bromocriptine, image pituitary
Vascular etiology suspected
I
Consider referral for _ _ _ _ _-1 revascularization, especially young healthy patients
No
I
Etiology likely neurogenic, vascular, psychogenic, drug induced or combination, or treatments ineffective. Consider vacuum constriction device, penile self injection therapy, penile prosthesis, perhaps yohimbine, nitrates, minoxidil.
Figure 2. Evaluation and treatment of impotence algorithm.
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SUMMARY
Impotence is a common problem. History is primarily relied on to diagnose psychogenic impotence. Sex therapy is an effective treatment. Antihypertensive and psychiatric medicines often cause impotence, but most medicines should be considered a cause if this is supported by the history. Hormonal causes should be suspected in a patient with decreased libido or decreased testicular size, and testosterone should be measured in these cases. Hormone replacement may restore sexual function in hypogonadal men. Doppler sonogram or arteriography should be used to diagnose vascular impotence for men who would be good surgical candidates. Only young men without other illness are considered. There is little need to test neurologic function because there is no specific treatment for neurogenic impotence. These patients and patients who do not respond to the aforementioned treatments should be offered the vacuum erection device, penile self-injection therapy, or penile prosthesis. Choice depends on comorbid illness as well as patient preference. A basic algorithm for the evaluation and treatment of impotence is given in Figure 2. References 1. Aitchison M, Aitchison J, Carter R: Is the penile brachial index a reproducible and useful measurement? Br J Urol 66:202, 1990 2. Akpunonu BE, Mutgi AB, Federman DJ, et al: Routine prolactin measurement is not necessary in the initial evaluation of male impotence. J Gen Intern Med 9:336, 1994 3. Al-Juburi AZ, O'Donnell PD: Synergist erection system: Clinical experience. Urology 35:304, 1990 4. Alien R, Brendler CB: Snap-gauge compared to a full nocturnal penile tumescence study for evaluation of patients with erectile impotence. J Urol 143:51, 1990 5. Alien RP, Smolev JK, Engel RM, et al: Comparison of Rigiscan and formal nocturnal penile tumescence testing in the evaluation of erectile rigidity. J Urol 149:1265, 1993 6. Aloui R, Iwaz J, Kokkidis MJ, et al: A new vacuum device as alternative treatment for impotence. Br J Urol 70:652, 1992 7. Anders EK, Bradley WE, Krane RJ: Nocturnal penile rigidity measured by the snapgauge band. J Urol 129:964, 1983 8. Arauz-Pacheco C, Basco M, Ramirez LC, et al: Treatment of diabetic impotence with a vacuum device: Efficacy and effects on psychological status. Am J Med Sci 303:281, 1992 9. Barry JM, Glank B, Boileau M: Nocturnal penile tumescence monitoring with stamps. Urology 15:171, 1989 10. Beretta G, Sultarelli 0, Marzott OM, et al: Transcutaneous minoxidil in the treatment of erectile dysfunctions in spinal cord injured men. Acta Eur Fertil 24:27, 1993 11. Blackard CE, Borkon WD, Lima JS, et al: Use of vacuum tumescence device for impotence secondary to venous leakage. Urology 41:225,1993 12. Blaivas JG, Zayed AAH, Labib KB: The bulbocavernosus reflex in urology: A prospective study of 299 patients. J Urol 126:197, 1981 13. Bookstein JJ, Valji K, Parsons L, et al: Pharmacoarteriography in the evaluation of impotence. J Urol 137:333, 1987 14. Braverman LE, Utiger RD: Thyroid diseases: Thyrotoxicosis. In Braverman LE, Utiger RD (eds): The Thyroid: A Fundamental and Clinical Text, ed 6. Philadelphia, JB Lippincott, 1991, p 645 15. Brock GB, Lue TF: Drug induced male sexual dysfunction. Drug Safety 8:414, 1993
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16. Buffum J: Prescription drugs and sexual function. Psychiatr Med 10:181, 1992 17. Carmignani G, Pirozzi F, Spano G, et al: Cavernous artery revascularization in vasculogenic impotence: New simplified technique. Urology 30:23, 1987 18. Carrier S, Brock G, Kour NW, et al: Pathophysiology of erectile dysfunction. Urology 42:468, 1993 19. Cavallini G: Minoxidil versus nitroglycerin: A prospective double-blind controlled trial in transcutaneous erection facilitation for organic impotence. J Urol 146:50, 1991 20. Chancellor MB, Rivas DA, Panzer DE, et al: Prospective comparison of topical minoxidil to vacuum constriction device and intracorporeal papaverine injection in treatment of erectile dysfunction due to spinal cord injury. Adult Urol 43:365, 1994 21. Chiang PH, Chiang CP, Wu Cc, et al: Color duplex sonography in the assessment of impotence. Br J Urol 68:181, 1991 22. Chiu AW, Chen KK, Chen MT, et al: Penile brachial index in impotent patients with coronary artery disease. Eur Urol 19:213, 1991 23. Claes H, Baert L: Transcutaneous nitroglycerin therapy in the treatment of impotence. Urol Int 44:309, 1989 24. Condra M, Fenemore J, Reid K, et al: Screening assessment of penile tumescence and rigidity. Clinical test of snap-gauge. Urology 29:254, 1987 25. Condra M, Morales A, Surridge D, et al: Evaluation of the urological assessment in impotence: Findings with a new diagnostic rating scale. J Urol 131:486, 1984 26. Cookson MS, Nadig PW: Long-term results with vacuum constriction device. J Urol 149:290, 1993 27. Cookson MS, Phillips DL, Huff ME, et al: Analysis of microsurgical penile revascularization results by etiology of impotence. J Urol 149:1308, 1993 28. Curb DJ, Nemat OB, Blaszkowski TP, et al: Long-term surveillance for adverse effects of antihypertensive drugs. JAMA 253:3263, 1985 29. Croog SH, Levine S, Sudilovsky A, et al: Sexual symptoms in hypertensive patients. Arch Intern Med 148:788, 1988 30. De Palma RG, Schwab FJ, Emsellem HA, et al: Noninvasive assessment of impotence. Surg Clin North Am 70:119, 1990 31. Dow JA, Gluck RW, Golimbu M, et al: Multiphasic diagnostic evaluation of arteriogenic, venogenic, and sinusoidogenic impotency. Value of noninvasive tests compared with penile duplex ultrasonography. Urology 38:402, 1991 32. Feldman HA, Goldstein I, Hatzichristou DG, et al: Impotence and its medical and psychosocial correlates: Results of the Massachusetts Male Aging Study. J Urol 151:54, 1994 33. Fisher C, Schiavi RC, Edwards A, et al: Evaluation of nocturnal penile tumescence in the differential diagnosis of sexual impotence. A qualitative study. Arch Gen Psychiatry 36:431, 1979 34. Pitch WP: Three-year experience using penile revascularization [abstr]. J Urol143(part 2):318A, 1990 35. Gilbert HW, Desai KM, Gingell JC: Non-invasive assessment of arteriogenic impotence: A comparative study. Br J Urol 67:512,1991 36. Gilbert HW, Gingell JC: Vacuum constriction devices: Second-line conservative treatment for impotence. Br J Urol 70:81, 1992 37. Godec CJ, Narkhede N, Tomasula JJ: The use of nitroglycerin in impotent patients [abstr]. J Urol 137(part 2):184A, 1987 38. Goldstein I: Arterial revascularization procedures. Sem Urol 4:252, 1986 39. Goldstein I, Levine F, Gasior B, et al: Role of vascular reconstructive surgery in impotence: A review of 335 patients over 7 years [abstr]. J Urol143(part 2):318A, 1990 40. Hampson SJ, Cowie AGA, Rickards D, et al: Independent evaluation of impotence by colour Doppler imaging and cavernosometry. Eur Urol 21:27, 1992 41. Hangeveld MW: Erectile dysfunction: A sexological and psychiatric review. World J Urol 1:227, 1983 42. Heaton JPW, Morales A, Owen J, et al: Topical glyceryltrinitrate causes measurable penile arterial dilation in impotent men. J Urol 143:729, 1990 43. Helier L, Keren 0, Aloui R, et al: An open trial of vacuum penile tumescence: Constriction therapy for neurological impotence. Paraplegia 30:550, 1992
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44. Johnson AR, Jarow JP: Is routine endocrine testing of impotent men necessary? J Urol 147:1542,1992 45. Kidd GS, Glass AR, Vigersky RA: The hypothalmic-pituitary-testicular axis in thyrotoxicosis. J Clin Endocrinol Metab 48:798, 1979 46. Konnak jW, Ohl DA: Microsurgical penile revascularization using the central corporeal penile artery. J Urol 142:305, 1989 47. Korenman SG, Viosca SP: Treatment of vasculogenic sexual dysfunction with pentoxifylline. J Am Geriatr Soc 41:363, 1993 48. Korenman SG, Viosca SP: Use of a vacuum tumescence device in the management of impotence in men with a history of penile implant or severe pelvic disease. J Am Geriatr Soc 40:61, 1992 49. Korenman SG, Viosca SP, Kaiser FE, et al: Use of a vacuum tumescence device in the management of impotence. J Am Geriatr Soc 38:217,1990 50. Lakin MM, Montague DK, Vander Brug Medendorp S, et al: Intercavernous injection therapy: Analysis of results and complications. J Urol 143:1138, 1990 51. Lavoisier P, Proulx J, Courtois F, et al: Bulbocavernous reflex: Its validity as a diagnostic test of neurogenic impotence. J UroI141:311, 1989 52. Lopez JA, Espeland MA, Jarrow JP: Interpretation and quantification of penile blood flow studies using duplex ultrasonography. J Urol 146:1271, 1991 53. LoPiccolo L Stock WE: Treatment of sexual dysfunction. Journal of Consulting and Clinical Psychology 54:158, 1986 54. Lue TF: Intercavernous drug administration: Its role in diagnosis and treatment of impotence. Semin Urol 8:100,1990 55. Lue TF: Physiology of erection and pathophysiology of impotence. In Walsh P, Gittes R, Perlmutter A, et al (eds): Campbell's Urology, ed 6. Philadelphia, WB Saunders, 1992, p 709 56. Marshall PG, Earls C Morales A, et al: Nocturnal penile tumescence recording with stamps: A validity study. J Urol 128:946, 1982 57. Marshall PG, Morales A, Phillips P, et al: Nocturnal penile tumescence with stamps: A comparative study under sleep laboratory conditions. J Urol 130:88, 1983 58. Marshall P, Surridge D, Delva N: The role of nocturnal penile tumescence in differentiating between organic and psychogenic impotence. Arch Sex Behav 10:1, 1981 59. Masters WH, Johnson YE: Human sexual inadequacy. Boston, Little, Brown, 1970 60. McDougal WS, Jeffrey RF: Microscopic penile revascularization. J Urol 129:517, 1983 61. Meinhardt W, Lycklama AAB, Kropman RF, et al: The negative pressure device for erectile disorders: When does it fail? J Urol 149:1285, 1993 62. Meyholt HH, Rosenkilde P, Bodker A: Non-invasive management of impotence with transcutaneous nitroglycerin. Br J Urol 69:88, 1992 63. Morales A, Condra M, Owen jA, et al: Is yohimbine effective in the treatment of organic impotence? Results of a controlled trial. J Urol 137:1168, 1987 64. Morales A, Condra M, Reid K: The role of nocturnal penile tumescence monitoring in the diagnosis of impotence: A review. J Urol 143:441, 1990 65. Moul JW, McLeod DG: Negative pressure devices in the explanted penile prosthesis population. J Urol 142:729, 1989 66. Mudd JW: Impotence responsive to glyceryl trinitrate. Am J Psychiatry 134:922, 1977 67. Mueller SC, Wallenberg-Pachaly HV, Voges GE, et al: Comparison of selective internal iliac pharmaco-angiography, penile brachial index and duplex sonography with pulsed Doppler analysis for the evaluation of vasculogenic (arteriogenic) impotence. J Urol 143:928, 1990 68. Mulligan T, Schmitt B: Testosterone for erectile failure. J Gen Intern Med 8:517, 1993 69. NIH Consensus Development Panel on Impotence: Impotence. JAMA 270:83,1990 70. Nogueira MC, Herbaut AG, We spes E: Neurophysiological investigations of two hundred men with erectile dysfunction. Eur Urol 18:37, 1990 71. Nunez BD, Anderson DC Jr: Nitroglycerin ointment in the treatment of impotence. J Urol 150:1241, 1993 72. Owen JA, Saunders F, Harris C et al: Topical nitroglycerin: A potential treatment for impotence. J Urol 141:546, 1989 73. Papp GY, Hoznek A, Juhasz E, et al: Vacuum therapy in the treatment of erectile impotence. Acta Chir Hung 32:331, 1991
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74. Pearl RM, McGhee RD: Penile re vascularization in the treatment of vasculogenic impotence. Plast Reconstr Surg 80:284, 1987 75. Petrou SP, Barrett DM: The use of penile prosthesis in erectile dysfunction. Semin Urol 8:138, 1990 76. Puyau FA, Lewis RW: Corpus cavernosography pressure flow and radiograph. Invest Radiol 18:517, 1983 77. Randomski SB, Herschorns, Rangaswamy S: Topical minoxidil in the treatment of male erectile dysfunction. J Urol 151:1225, 1994 78. Roose SP, Glassman AH, Walsh BT, et al: Reversible loss of nocturnal penile tumescence during depression: A preliminary report. Neuropsychobiology 8:284, 1982 79. Sarramon JP, Rischman P, Lemba N, et al: Microsurgery reconstruction for pure vascular impotence [abstr]. J Urol 143(part 2):303A, 1990 80. Schwartz AN, Lowe MA, Ireton R, et al: A comparison of penile brachial index angiography: Evaluation of corpora cavernosa arterial inflow. J Urol 143:510, 1990 81. Shabsigh R, Fishman II, Shotland Y, et al: Comparison of penile duplex ultrasonography with nocturnal penile tumescence monitoring for the evaluation of erectile impotence. J UroI143:924, 1990 82. Shaw WW, Zorgniotti AW: Surgical techniques in penile revascularization. Urology 23:76, 1984 83. Sidi AA, Becher EF, Zhang G, et al: Patient acceptance of and satisfaction with an external negative pressure device for impotence. J Urol 144:1154, 1990 84. Sidi AA, Lewis JH: Clinical trial of a simplified vacuum erection device fot impotence treatment. Urology 39:526, 1992 85. Slag M, Morley J, Elson M, et al: Impotence in medical clinic outpatients. JAMA 249:1736-1740,1983 86. Smith PI, Talbert RL: Sexual dysfunction with antihypertensive and antipsychotic agents. Clin Pharmacol 5:373, 1986 87. Sonda LP, Mazo R, Chancellor MB: The role of yohimbine for the treatment of erectile impotence. J Sex Marit Ther 16:15, 1990 88. Sonksen I, Biering-Sorensen F: Transcutaneous nitroglycerin in the treatment of erectile dysfunction in spinal cord injured. Paraplegia 30:554, 1992 89. Talley JD, Crawley IS: Transdermal nitrate, penile erection and spousal headache [letter]. Ann Intern Med 103:804, 1985 90. Thase ME, Reynolds CF, Glaney LM, et al: Nocturnal penile tumescence in depressed men. Am J Psychiatry 144:89, 1987 91. Thorner NO, Vance ML, Horvath E, et al: The anterior pituitary. In Wilson JD, Foster DW (eds): Williams' Textbook of Endocrinology, ed 8. Philadelphia, WB Saunders, 1992, p 221 92. Treatment of Mild Hypertension Research Group: The treatment of mild hypertension study. Arch Intern Med 151:1413, 1991 93. Turner LA, Althof SE: The clinical effectiveness of self injection and external vacuum devices in the treatment of erectile dysfunction: A six month comparison. Psychiatr Med 10:283, 1992 94. Turner LA, Althof SE, Levine SB, et al: Treating erectile dysfunction with external vacuum devices: Impact upon sexual, psychological and marital functioning. J Urol 144:79, 1990 95. Valji K, Bookstein JJ: Diagnosis of arteriogenic impotence: Efficacy of duplex sonography as a screening tool. AJR Am J Roentgenol 160:65, 1993 96. Van Nueten J, Verheyden B, Van Camp K: Role of penile nocturnal tumescence and rigidity measurement in the diagnosis of erectile impotence. Eur UroI22:119, 1992 97. Van Thillo EL, Delaere KPJ: The vacuum erection device: A non-invasive treatment for impotence. Acta Urol Belg 60:9, 1992 98. Virag R, Showkry K, Floresco I, et al: Intercavernous self-injection of vasoactive drugs in the treatment of impotence: 8-year experience with 615 cases. J Urol 145:287, 1991 99. Virag R, Zwang G, Dermange H, et al: Vasculogenic impotence: A review of 92 cases with 54 surgical operations. Vasc Surg 15:9, 1981 100. Wespes E, Schulman C: Venous impotence: Pathophysiology, diagnosis and treatment. J Urol 149:1238, 1993
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101. Wesserman MD, Pollack CP, Spielman AI, et al: The differential diagnosis of impotence. The measurement of nocturnal penile tumescence. JAM A 243:2038, 1980 102. Witherington R: Vacuum constriction device for management of erectile impotence. J Urol 141:320, 1989 103. Wortsman I, Rosner W, Dufau M: Abnormal testicular function in men with primary hypothyroidism. Am J Med 82:207, 1987 104. Zorgniotti A W, Padula G, Shaw WW: Selective arteriography for vascular impotence. World J Urol 1:213, 1983
Address reprint requests to Mary O'Keefe, MD Office of Ambulatory Care (11C) Audie Murphy Veterans Hospital 7400 Merton Minter Boulevard San Antonio, TX 78284
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ASSESSMENT AND TREATMENT OF IMPOTENCE Mary O'Keefe, MD, and Debra K. Hunt, MD, MSPH
Impotence is defined as the inability to achieve and sustain an erection of sufficient rigidity for intercourse. In the Massachusetts Male Aging Study,12 a cross-sectional survey of men from ages 40 to 70 in the Boston area, the prevalence of impotence was 52%, and this increased from 40% at age 40 to 67% at age 70. The probability that impotence would occur was three times greater in treated diabetics than in nondiabetics and increased in men with heart disease, hypertension, and low high-density lipoproteins and those taking antihypertensive, vasodilating, cardiac, or hypoglycemic medicines. Smoking increased the risk associated with cardiovascular disease and medications. This information suggests that impotence is a common problem with multiple preventable and treatable causes. In this article, the physiology, diagnosis, and treatment of impotence are reviewed. Diagnostic testing is recommended only in cases when specific treatment is available. Only impotence is discussed. Difficulty with libido, orgasm, or ejaculation is not addressed. PHYSIOLOGY
Erection may be initiated reflexively through direct tactile stimulation or through a more complex pathway involving other types of stimulation (i.e., visual). The process of erection is mediated by somatic, sympathetic, and parasympathetic nerves and sympathetic tone. Penile arteriolar dilation leads to increased inflow, and a simultaneous relaxation of corporal sinusoids causes increased corporal size. The enlarged From the Department of Medicine, University of Texas Health Science Center at San Antonio; and Audie Murphy Memorial Veterans Administration Hospital (MO), San Antonio, Texas MEDICAL CLINICS OF NORTH AMERICA VOLUME 79 • NUMBER 2 • MARCH 1995
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corpora compress the draining veins against the tunica albuginea, which decreases (relatively) the venous outflow (Fig. 1).18 Thus, the normal erection depends at least on psychological, neurologic, hormonal, and vascular processes. EVALUATION OF IMPOTENCE Psychogenic Impotence
Classic features suggesting psychogenic impotence include sudden onset preceded by a specific event, normal morning erections, and ab-
A Dorsal a. ---......,..~"".;
Cavernous a.
Circumflex a. Bulbourethral a. -
----'''' Buck's fascia
B Superficial dorsal v.
vV'~?:~~il~:~ '-
Deep dorsal (Cavernous at hilum of penis) Circumflex v.
Subtunical -~~·,V" venular plexus
Bulbourethral v.
cavernosum Tunica albuginea Urethra ----- - Corpus spongiosum
Figure 1. Arterial supply (A) and venous drainage (8) of the penis. Transverse view. (From Lue TF: Physiology of erection and pathophysiology of impotence. In Walsh P, Gittes R, Perlmutter A, et al (eds): Campbell's Urology, ed 6. Philadelphia, W.B. Saunders, 1992, p 709.)
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sence of chronic health problems or medications. A 1984 study measured the ability of some of these clinical characteristics to distinguish organic from psychogenic impotence. 25 The sensitivity and specificity of selected findings compared to diagnosis by nocturnal penile tumescence monitoring and psychiatric interviews are shown in Table 1. In this relatively small study, reporting good-quality early morning erections was a specific finding for psychogenic impotence. The absence of a disease and absence of medication known to cause impotence were sensitive findings for psychogenic disease. Nocturnal Penile Tumescence
The theoretic basis for nocturnal penile tumescence (NPT) monitoring is that an intact erectile mechanism must exist to produce an erection during sleep. Thus, if erectile dysfunction is due to psychological inhibition during sexual activity, nocturnal erections should be normal. The normal man experiences three to five erections per night, each lasting 25 to 35 minutes. A formal NPT study involves monitoring for three consecutive nights in a sleep laboratory. Nocturnal erections occur only during rapid eye movement (REM) sleep, so electroencephalographic, electro-oculographic, and electromyographic activity is recorded to document sleep quality and to avoid a false-negative study. In addition, penile circumference is measured with strain gauges at the base and tip of the penis. When an erection is detected, the patient is awakened and axial rigidity is measured by assessing the resistance of the penis to buckling when a known weight is applied to the glans penis. A positive test is "normal" or suggestive of a psychogenic cause of impotence. 33, 96 A number of concerns about the validity of NPT monitoring have been raised. 64 First, there are methodologic problems with the early studies. Patients were included in study groups partly based on their NPT results, thus inflating differences between groups. One small study that avoided this flaw found that NPT results agreed with the diagnosis Table 1. CLINICAL CHARACTERISTICS OF PSYCHOGENIC VERSUS ORGANIC IMPOTENCE IN 67 PATIENTS Psychogenic Disease Sensitivity
(%)
Specificity
Characteristic
Normal early morning erection Sexual erection of good quality but not maintained Sudden onset No current illness' No medications'
52 27
100 100
30
90 94
(%)
76 76 41
'Likely to interfere with erections. Adapted from Condra M, Morales A, Surridge D, et al: Evaluation of the urologic assessment in impotence: Findings with a new diagnostic rating scale. J Urol 131 :486, 1984; with permission.
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established by clinical criteria 80% of the time. 58 Second, the gold standard for diagnosing psychogenic impotence is unclear. This problem has led to case reports of patients diagnosed with psychogenic impotence by NPT later presenting with a pituitary adenoma 101 or patients with depression being diagnosed with organic impotence by NPT and nocturnal erections normalized after treatment of the depression?8. 90 Finally, nocturnal erections may not reflect the erectile potential in the erotic or sexual situation. Organic conditions such as sensory neuropathy may increase latency to erection during sexual activity but have no effect on nocturnal erections. Despite these problems with NPT monitoring, it became a widely accepted diagnostic tool in the evaluation of impotence, but more convenient, less expensive methods were desired. The first home monitoring method developed was the stamp test. 9• 56. 57 Four postage stamps were wrapped snugly around the penis, overlapping by at least one half of a stamp. The patient simply noted if the perforations were broken by morning. Although simple and inexpensive, studies have not found the test accurate enough for clinical use. The Snap-Gauge device (Dacomed Corp., Minneapolis, MN) was introduced in 1982. Small studies suggest that the sensitivity is around 90% with a specificity of 40% to 50%.4. 7. 24 At a cost of only $12, compared with over $700 for NPT monitoring, many authors believe this instrument may be useful for screening purposes. The most recent device to become available is the RigiScan (Dacomed Corp., Minneapolis, MN). This is a battery-powered device that is strapped to the patient's thigh and uses two mercury strain gauges to measure penile circumference. The circumference is sampled every 15 seconds throughout the night, and these values are stored in the memory of the attached recording device. Preliminary results suggest that this device may not be able to detect mild abnormalities in erectile dysfunction, but more study is needed. s NPT monitoring is not relied on heavily to distinguish organic from psychogenic impotence. At this time, clinical characteristics are used to separate these two groups, and use of the Snap-Gauge is considered only in a limited number of cases. Drug-Induced Impotence It has been reported that 25% of impotence in clinic patients is due to a drug side effect.43 Antihypertensives are often implicated (Table 2). This may be a drug-specific side effect or due to a therapeutic decrease in blood pressure and thus a decrease in penile perfusion. In large placebo-controlled trials comparing sexual side effects for various antihypertensives, few or no significant differences in incidence are found. 28, 29. 92 This finding suggests that a decreased perfusion pressure plays at least some part in causing impotence. Psychiatric medications also are a common cause of impotence (Table 3). It may be difficult to determine
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Table 2. SEXUAL DYSFUNCTION WITH SELECTED ANTIHYPERTENSIVE AGENTS Percentage of Patients with Impotence
Drug Thiazide Spironolactone
4-32% 2-30%
Sympatholytics (methyldopa, clonidine, guanethidine, reserpine) 13-Blockers
8-80% (most often 20-30%) 0-43%
a-Blockers Labetalol Angiotensin converting enzyme inhibitors Vasodilators (hydralazine, minoxidil) Calcium channel-blockers
Minimal Minimal Minimal Minimal Minimal
Comment Dose dependent; gynecomastia common Decreased libido Dose dependent; lowest with 13, specific agents (pindolol, nadolol, atenolol); also reported with ophthalmic drops May induce priapism Ejaculatory changes common Some patients report aphrodisiac effects of hydralazine
Data from references 15, 16, and 86.
whether impotence is due to the psychiatric disease or the medication, particularly because onset is typically abrupt in both cases. Use of recreational drugs is also commonly associated with impotence. Up to 75% of patients in alcohol rehabilitation programs reported impotence in the preceding 6 months, both during and after alcohol use. Other commonly implicated drugs include cimetidine, digoxin, and anabolic steroids, and there are case reports of impotence with most medications.
Table 3. SEXUAL DYSFUNCTION WITH SELECTED PSYCHIATRIC MEDICATIONS Drug Antipsychotics Monoamine oxidase inhibitors Tricyclics Selective serotonin reuptake inhibitors Benzodiazepines
Percentage of Patients with Impotence 0-54% 16-31% Significant 8-16% Reported
Data from references 15, 16, and 86.
Comment More common with greater a-adrenergic and anticholinergic effects Also anorgasmia Also decreased libido, anorgasmia. May be less common with desipramine
Also decreased libido, ejaculatory changes
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Hormonal Causes of Impotence
The true incidence of endocrine dysfunction as the cause of impotence is unclear. Estimates range from 2% to 35%.44 Early review articles called for hormonal evaluation in all patients, but more recent work, described subsequently, has called this practice into question. Testosterone
Testosterone levels vary diurnally (lowest in the afternoon) and are diminished by stress, anxiety, or depression, For these reasons, testosterone levels should be measured only on fasting morning specimens, If the first level is low, it should be repeated, and some authors think three low levels are needed, Similar to other hormones, testosterone is highly protein bound, so total testosterone levels are affected by the availability of binding proteins, Bioavailable testosterone is a measure of the loosely bound and unbound testosterone, which is physiologically active and is a better indicator of hormone status, In 1992, Johnson and Jarow44 reported results of the evaluation of 300 men referred to an impotence clinic. They found seven cases of endocrinopathy. Of these seven, all had either bilateral testicular atrophy or decreased libido, leading the authors to recommend obtaining screening testosterone levels only in patients with one of these two findings, Luteinizing Hormone and Follicle-Stimulating Hormone
Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels may be useful in distinguishing primary from secondary hypogonadism but are not necessary for initial screening,69 Prolactin
Prolactinomas can cause impotence, One study found that 3 out of
212 (1.4%; Cl 95 [0-3,0%]) men evaluated for impotence had elevated
prolactin levels,2 Of these three, two had low testosterone levels, and the third had renal insufficiency, which is known to elevate serum prolactin levels. The authors concluded that it would be cost-effective to measure prolactin only in impotent men with low testosterone levels, Thyroid Hormone
Both hypothyroidism and hyperthyroidism have been implicated as causes of impotence. 14, 45, 103 Prepubertal hypothyroidism can affect male gonadal function and if left untreated may lead to testicular atrophy. In adults, hypothyroidism appears to be an infrequent cause of impotence, and it is unclear whether it can be the presenting complaint. Thus, the utility of screening all impotent patients for hypothyroidism is uncertain. Hyperthyroidism has also been implicated as a cause of impotence.
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In one small study four of seven hyperthyroid men complained of impotence. 45 Again, it is unclear whether impotence can be the only manifestation of hyperthyroidism. Patients presenting with impotence should be questioned further for symptoms of thyroid dysfunction, but routine screening seems unnecessary. Vascular Disease
Many tests are available for the diagnosis of vascular impotence, but all must be correlated with the clinical picture. 30,55 As is discussed later, vascular surgery is a widely accepted treatment option only for young patients without concomitant illness. Most of these tests should therefore be reserved for these patients. Arterial Insufficiency
The most invasive technique used to detect arterial insufficiencyinduced impotence is selective pudendal pharmacoarteriographyY' 104 This technique requires local anesthesia with intravenous sedation and so has attendant risk. Occasionally, serious complications such as intimal dissection of the hypogastric artery occur. A number of less invasive tests have been developed for arterial insufficiency, the least invasive of which is the penile-brachial index (PBI). The PBI is a ratio between the penile and brachial systolic pressure detected by a Doppler probe. The PBI is calculated in the flaccid state and does not convey the pressure available for erection. A value of 0.60 is considered low, whereas 0.90 or more is usually considered normal. Studies of the PBI suggest that it may lack the accuracy of a good screening tesU' 22, 67, 80 No raw data were provided to calculate sensitivity and specificity, but two studies reported correlation coefficients of 0.3; one study found no correlation. Another study reported low interobserver reliability: Fewer than 80% of patients were classified the same by two observers. Doppler ultrasonography may also be used to diagnose arterial insufficiency. Changes in the diameter of the cavernosal artery and the velocity of blood flow are measured after intracavernosal injection of vasoactive agents. Published studies are fairly small, and many did not perform the gold standard study on all patients. 21 , 31, 35, 40, 52, 81 One study of 30 patients who received both Doppler ultrasonography and selective pharmacoarteriography reported a sensitivity of 100% and a specificity of 46% for Doppler ultrasonography.95 Venous Disease
The venous compression of a normal erection may be evaluated clinically by pharmacocavernosometry and cavernosography.3o,55 These
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studies evaluate the adequacy of corporal venous outflow resistance and therefore must always be performed following intracavernosal injection of vasoactive agents. The diagnostic accuracy of these tests is unclear?6 Cavernosometry measures (1) the intracavernosal flow rate of saline required to create or sustain an erection and (2) the rate of fall in intracavernosal pressure after the infusion is stopped. When veno-occlusive dysfunction is present, there is either a high flow rate needed to maintain an erection or a rapid fall in intracavernosal pressure after cessation of saline infusion. Cavernosography is used to visualize the veins draining the corporal bodies during erection. Images are obtained following intracavernosal injection of radiopaque contrast material into the erect penis. When corporal veno-occlusive function is normal, little or no venous drainage is seen. Neurologic Disease
Tests are available to diagnose neurologic impotence, but it is unclear who should undergo testing. 3D The two tests most commonly used are the bulbocavernosus reflex (BCR) and pudendal-evoked responses (PER)Y· 51. 70 The BCR measures the electromyographic activity of the bulbocavernosus muscles in response to electrical stimulation of the glans penis. According to one study of 299 impotent patients, an absent response was indicative of a sacral spinal cord lesion. 12 A more recent study has questioned the accuracy of this test. 51 The PER measures suprasacral neurologic disease. Electroencephalogram leads are placed over the scalp, and electrodes are placed over the L-1 vertebra. The penis is then electrically stimulated, just as for a BCR, but readings are taken at the lumbar and cortical levels. Again, delayed responses are considered abnormal, but accuracy is unproven?O These tests are not used to screen for an occult neurologic lesion but rather to determine whether known neurologic disease is the cause of the impotence. TREATMENT OF IMPOTENCE Psychogenic Impotence
There are several types of therapy for psychogenic impotence, including psychoanalysis, behavior modification, and intensive symptomoriented sex therapy. The last-mentioned was pioneered by Masters and Johnson,59 who reported a 74% success rate for secondary impotence. Further study rarely duplicates this initial success and has in particular shown poor results for older patients and those with impotence of longer duration and insidious onset. 41 • 53 Results are confounded by difficulty in selecting patients with psychogenic not organic impotence, as discussed earlier.
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Thus, it seems reasonable to refer patients for sex therapy if the clinical index of suspicion of psychogenic impotence is high. Therapy is less likely to be helpful in older patients, with a history or risk factors suggesting organic disease. Drug-Induced Impotence If impotence is believed to be a drug effect, a trial off medication is reasonable. If the medication is implicated, the physician and patient must decide whether the benefits of treatment outweigh this side effect.
Hormonal Causes of Impotence Testosterone If hypogonadism is diagnosed, treatment with testosterone may be elected, but its use is not well supported. In a critical review, Mulligan and Schmitt68 concluded that testosterone increases sexual interest, frequency of sexual acts (although not necessarily penetration), and frequency of nocturnal erections. Thus, it is beneficial for decreased libido but of questionable benefit for impotence. Testosterone is available in three forms. Oral testosterone is not recommended owing to the frequency of hepatitis and hyperlipidemia. Most patients are treated with 200 mg of testosterone cypionate intramuscularly administered every 2 to 6 weeks. The cost of transdermal testosterone may be prohibitive (wholesale cost of $1.88 for 4 or 6 mg daily patch). When treatment with testosterone is elected, it is important to remember two side effects. First, testosterone stimulates the growth of prostate cancer. Second, testosterone increases libido. Patients inappropriately treated with testosterone may experience the frustration of an increased libido without an improvement in erection.
Pro/actin
Patients with prolactinomas are generally referred to a specialist for treatment. Treatment with the dopamine agonist bromocriptine restores potency in most patients. 91 Although testosterone levels are low, it should not be supplemented because it may stimulate the pituitary adenoma. Thyroid Hormone
Although impotence is commonly associated with thyroid disease, the authors are unaware of studies reporting the rate of improvement with treatment. 45 It is reasonable to treat the underlying thyroid disorder before considering other options for the impotence.
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Vascular Disease Surgery
The use of surgery for vasculogenic impotence is controversial in the majority of patients. Two main types of surgery are available and may be used together: revascularization and veno-occlusive reconstruction. Cookson and colleagues27 studied revascularization surgery with or without venous reconstruction: Of 898 patients referred to a urology practice, 50 were selected to undergo surgery. Of these, 24 had return of sexual function (48%), and 20 had return with the use of penile selfinjection, which had previously been ineffective (40%). In assessing these results, it is important to note that this was a highly selected group; only 6% of those referred were offered surgery. Mean age was 38, only 1 had diabetes, none were smokers, and none had hypertension. Additionally the study was not controlled. In similar uncontrolled studies of selected patients, success rates are reported between 54% and 800/0.17, 34, 38, 39, 46, 60, 74, 79, 82, 99
Wespes and Schulman100 reviewed results of surgery for venous incompetence without revascularization. Cure rates varied: 57% for venous embolization, 10% to 90% for various venous ligation procedures, and 0 to 60% for a variety of other techniques. Again, this is a select group of patients, and the authors of the study specifically suggest excluding those with arterial insufficiency. In view of these results, it seems prudent to reserve consideration of vascular surgery for those who have failed more conservative treatment or for young patients without concomitant illness. Pentoxifylline
Korenman and Viosca47 studied pentoxifylline as a treatment for vasculogenic impotence. Twenty-four patients, with an average of 6.2 years of impotence, were randomized to receive placebo or pentoxifylline in a double-blind trial. Four of 8 patients on pentoxifylline had at least one successful coital event, compared with 0 of 10 on placebo. Of note, patients were selected for consideration for the study based on an abnormal PBI, which is a test of questionable utility as previously discussed. These results are promising, but more study is needed. Neurologic Disease
There is no specific treatment for impotence of neurologic etiology. TREATMENTS UNRELATED TO CAUSE OF IMPOTENCE
In addition to those disease-specific treatments already discussed, several other options are available regardless of cause. These treatments
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should be considered for patients with neurogenic impotence, those with mixed etiology, and those that do not respond to disease-specific treatments. The choice depends on patient preference as well as cost, risk, benefits, and side effects. Vacuum Constriction Devices
Vacuum erection aids consist of a hollow tube, a manual vacuum pump, and a constriction ring. The tube is placed over the penis, and a seal is formed at the pubic wall. A vacuum is created with the manual pump, so that arterial inflow increases and erection is achieved. The constricting ring is placed over the base of the penis so that venous return is reduced and an erection is maintained when the tube is removed. Erection lasts until the ring is removed (recommended 30 to 60 minutes). These devices cost $300 to $400 and may be purchased from the manufacturer with a prescription. Common side effects include bruising (especially in patients using antiplatelet agents), entrapment of scrotal tissue in the vacuum tube, decreased penile skin temperature, impaired ejaculation owing to urethral blockage, discomfort from the pump or band, and pivoting of the penis (owing to lack of erection at the band). Use is contraindicated in patients with sickle cell disease or on anticoagulants. In studies of patients with impotence of mixed etiology, patients who choose to try vacuum devices have satisfaction rates of 66% to 93% (Table 4). In studies of selected groups, satisfaction rates are also high in patients with an organic cause, patients with venous leak, patients with a neurologic cause, and patients who have failed a prosthesis. Satisfaction rates are lower in patients who have failed self-injection, sexual counseling, and other treatments (Table 5). Although some patients are unwilling to use this device, the authors recommend it as a relatively safe, inexpensive first option for treatment, which may be offered without referral to a specialist.
Table 4. SATISFACTION WITH VACUUM DEVICES FOR IMPOTENCE PATIENTS WITH MIXED ETIOLOGY
Study
No. of Patients
Witherington 102 Cookson & Nadig26 Sidi et al 83 Van Thillo & Delaere 97 Turner et al 94 Turner & Althof93 Sidi & Lewis 84 Papp et al 73
1517 161 100 30 36 36 31 48
Average Follow-up (months)
8.6 3 7.9 6 6 6 3
one use in office
Satisfied or with Adequate Erection (%)
92 82 68 66 89 81 93 71
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Table 5. SATISFACTION WITH VACUUM DEVICES FOR IMPOTENT PATIENTS: SELECTED POPULATIONS
No. of Patients
Study
Satisfied or with Adequate Erection (%)
3
100 75 73 69 75
17 11 17
21 1 6
83 91 94
45 74
3 3 weeks
27 30
Korenman et al Aloui et al 6 AI-Juburi & 0'Donnell 3 Blackard et al" Arauz-Pacheco et al 8
20 16 44 47 12
Helier et al 43 Moul & McLeod 65 Korenman & Viosca 48 Gilbert & GingelP6 Meinhardt et al 61
49
Average Follow-up (months)
6 3 6
unknown
Patient Characteristics Abnormal snap gauge Organic cause Organic cause Venous leak Diabetes; no vascular disease, hypertension, or other endocrine disease Various neurologic causes Explanted prosthesis Status post pelvic radiation or surgery on unsuccessful implant Failed self-injection Failed sexual counseling, self-injection, venous surgery, or prosthesis
Penile Self-Injection Therapy
Another treatment option is penile self-injection of various vasoactive medications. Medications commonly used include phentolamine, an et antagonist; papaverine, a nonspecific smooth muscle relaxant; and prostaglandin E. All act by dilating arterioles and thus increasing arteriolar inflow. Most often, a combination of agents is used to minimize side effects. Erection results within minutes of injection, and dosage is titrated so erection lasts 30 to 60 minutes. This usually requires several office visits. The wholesale cost of the medication alone is abOllt $2 per treatment. Side effects include hematoma, fibrosis, nodule at the injection site, and priapism. Although this form of treatment is widespread, none of these agents is approved by the Food and Drug Administration for this use. In his review of the use of injection therapy, Lue54 reports successful treatment for psychogenic, neurogenic, and, to a lesser extent, vasculogenic impotence. In two representative reports on the use of injection therapy, only 10% of patients selected this treatment when informed of their options. 50, 98 Of those that continued treatment, approximately 90% were satisfied, although a significant number developed hematoma or fibrosis at the site of injection. Injection therapy is selected by a minority of patients but is effective for patients with various causes of impotence. There is a significant
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incidence of side effects, although this seems to be reduced with newer drugs and combinations of drugs. 54 Penile Prostheses
Penile prostheses are designed to provide sufficient penile rigidity for intercourse. Patients often mistakenly believe that the prostheses provide an erection similar to their prior normal erections and that they also correct problems with libido, orgasm, and ejaculation. It is important to discuss realistic expectations so that patients may make an informed decision. There are three commonly used types of prostheses. The semirigid rod maintains a constant shape and size but may be curved either up or down. The malleable rod maintains a constant size but may be straightened and curved as desired. The inflatable prosthesis consists of a pumping mechanism often placed in the scrotum, which transfers fluid from a retrocystic reservoir to the prosthesis. With pumping, the prosthesis enlarges and straightens. The major cost of penile prostheses is related to surgical implantation. Common complications include postoperative infection, perforation of the uretha or corpora, extrusion of the device, and mechanical problems. Also, because of disruption of normal anatomy, patients who fail this treatment are often unable to benefit from other options. In their review, Petrou and Barrete5 report surgical success rates of 82% to 98% with various types of prostheses. The authors believe penile prostheses are an appropriate treatment option for patients with normal libido, who are willing to accept the surgical risk and unwilling to try or unable to achieve success with more conservative treatments. Yohimbine
Yohimbine is an (X2 agonist and acts by inhibiting (Xl activity. This inhibition leads to decreased arteriolar tone and thus increased penile inflow. The recommended dosage is 5.4 mg three times a day, at a wholesale cost of about 1511' a day. The major side effect is a central nervous system excitatory state, which can lead to increased blood pressure and pulse rate, exacerbation of angina, anxiety, dizziness, and nausea. Morales and colleagues63 studied 100 patients with organic impotence as determined by abnormal nocturnal penile tumescence and evaluation by a urologist and psychologist. Patients received yohimbine or placebo in a double-blind trial. Forty-three percent reported response to yohimbine compared with 28% for placebo. The response rate was unaffected by age, penile brachial index, testosterone, FSH, or prolactin levels or the coexistence of diabetes, paresthesias, peripheral vascular disease, or use of insulin or antihypertensives.
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Sonda and associates 87 studied 40 patients with impotence in a placebo-controlled cross-over trial. Of 33 patients completing the trial, 49% reported a satisfactory response to yohimbine and 33% to placebo. Of 20 patients with a negative snap-gauge test, 40% improved on yohimbine, compared with 0 on placebo (P < 0.01). The overall response rate to yohimbine and placebo is similar in the two studies, although Morales studied only organic impotence and Sonda studied both organic and psychogenic impotence. Interestingly, there was a significant response to yohimbine in organic impotence in Sonda's study. The difference may be the method of classification of organic impotence or other unreported differences in study methods. With this and other available data, the authors would suggest a trial of yohimbine only in patients without coronary disease or moderate-tosevere hypertension, who are unwilling to try other treatment options. EXPERIMENTAL THERAPY Nitroglycerin
The majority of reports of the use of nitroglycerin for treatment of impotence are case reports or uncontrolled studies. 3 ?, 42, 62, 66, 71, 88 Additionally, there are positive results from controlled studies done in the laboratory, using strain gauge and duplex results as end points. 72 Claes and Baert23 performed a placebo-controlled, double-blinded, cross-over clinical trial of nitroglycerin patches. Patches were applied before intercourse, and results were assessed by patient report. Of 26 patients, 21 reported a response to nitroglycerin, and 5 reported a response to placebo. Twelve complained of headache associated with nitroglycerin. There are also reports of headache in the sexual partners of men using nitroglycerin. 89 Because of the scarcity and small size of clinical trials, nitroglycerin should not be considered an established treatment for impotence. Minoxidil
Topical minoxidil, a vasodilator, has been proposed as a treatment for impotence. The authors are unaware of any controlled trials of the use of minoxidil in a home setting. Uncontrolled studies yield mixed results. lO, 20, 77 CavallinP9 compared minoxidil, nitroglycerin, and placebo in 33 patients with arterial or neurogenic impotence in a double-blind trial. Diameter, rigidity, and arterial flow were compared. In all measures, minoxidil was more effective than nitroglycerin, which was more effective than placebo. Side effects were comparable with minoxidil and placebo and significantly greater with nitroglycerin. Although these data are promising, minoxidil cannot yet be recommended.
ASSESSMENT AND TREATMENT OF IMPOTENCE
New drug or drug commonly causing impotence?
429
- - - - y e s - - - - - - i Change or discontinue if possible
I
No Check TSH I - - - - y e s - - - - - - I Treat thyroid disease if present
Normal morning erections? Any erections with normal ngidity, duration, and latency? Sudden onset of impotence? No current illness or medication?
Consider psychogenic - - - y e s - - - - - I etiology, counseling
I I
No Symptoms or signs of hypogonadism? (Decreased libido? Decreased testicular size?)
1----yes----~-;C~h:e:ck~te:s:to:s:te:r:o:n:e:le:v:e~I-~
I
Normal
No Consider bromocriptine, image pituitary
Vascular etiology suspected
I
Consider referral for _ _ _ _ _-1 revascularization, especially young healthy patients
No
I
Etiology likely neurogenic, vascular, psychogenic, drug induced or combination, or treatments ineffective. Consider vacuum constriction device, penile self injection therapy, penile prosthesis, perhaps yohimbine, nitrates, minoxidil.
Figure 2. Evaluation and treatment of impotence algorithm.
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SUMMARY
Impotence is a common problem. History is primarily relied on to diagnose psychogenic impotence. Sex therapy is an effective treatment. Antihypertensive and psychiatric medicines often cause impotence, but most medicines should be considered a cause if this is supported by the history. Hormonal causes should be suspected in a patient with decreased libido or decreased testicular size, and testosterone should be measured in these cases. Hormone replacement may restore sexual function in hypogonadal men. Doppler sonogram or arteriography should be used to diagnose vascular impotence for men who would be good surgical candidates. Only young men without other illness are considered. There is little need to test neurologic function because there is no specific treatment for neurogenic impotence. These patients and patients who do not respond to the aforementioned treatments should be offered the vacuum erection device, penile self-injection therapy, or penile prosthesis. Choice depends on comorbid illness as well as patient preference. A basic algorithm for the evaluation and treatment of impotence is given in Figure 2. References 1. Aitchison M, Aitchison J, Carter R: Is the penile brachial index a reproducible and useful measurement? Br J Urol 66:202, 1990 2. Akpunonu BE, Mutgi AB, Federman DJ, et al: Routine prolactin measurement is not necessary in the initial evaluation of male impotence. J Gen Intern Med 9:336, 1994 3. Al-Juburi AZ, O'Donnell PD: Synergist erection system: Clinical experience. Urology 35:304, 1990 4. Alien R, Brendler CB: Snap-gauge compared to a full nocturnal penile tumescence study for evaluation of patients with erectile impotence. J Urol 143:51, 1990 5. Alien RP, Smolev JK, Engel RM, et al: Comparison of Rigiscan and formal nocturnal penile tumescence testing in the evaluation of erectile rigidity. J Urol 149:1265, 1993 6. Aloui R, Iwaz J, Kokkidis MJ, et al: A new vacuum device as alternative treatment for impotence. Br J Urol 70:652, 1992 7. Anders EK, Bradley WE, Krane RJ: Nocturnal penile rigidity measured by the snapgauge band. J Urol 129:964, 1983 8. Arauz-Pacheco C, Basco M, Ramirez LC, et al: Treatment of diabetic impotence with a vacuum device: Efficacy and effects on psychological status. Am J Med Sci 303:281, 1992 9. Barry JM, Glank B, Boileau M: Nocturnal penile tumescence monitoring with stamps. Urology 15:171, 1989 10. Beretta G, Sultarelli 0, Marzott OM, et al: Transcutaneous minoxidil in the treatment of erectile dysfunctions in spinal cord injured men. Acta Eur Fertil 24:27, 1993 11. Blackard CE, Borkon WD, Lima JS, et al: Use of vacuum tumescence device for impotence secondary to venous leakage. Urology 41:225,1993 12. Blaivas JG, Zayed AAH, Labib KB: The bulbocavernosus reflex in urology: A prospective study of 299 patients. J Urol 126:197, 1981 13. Bookstein JJ, Valji K, Parsons L, et al: Pharmacoarteriography in the evaluation of impotence. J Urol 137:333, 1987 14. Braverman LE, Utiger RD: Thyroid diseases: Thyrotoxicosis. In Braverman LE, Utiger RD (eds): The Thyroid: A Fundamental and Clinical Text, ed 6. Philadelphia, JB Lippincott, 1991, p 645 15. Brock GB, Lue TF: Drug induced male sexual dysfunction. Drug Safety 8:414, 1993
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16. Buffum J: Prescription drugs and sexual function. Psychiatr Med 10:181, 1992 17. Carmignani G, Pirozzi F, Spano G, et al: Cavernous artery revascularization in vasculogenic impotence: New simplified technique. Urology 30:23, 1987 18. Carrier S, Brock G, Kour NW, et al: Pathophysiology of erectile dysfunction. Urology 42:468, 1993 19. Cavallini G: Minoxidil versus nitroglycerin: A prospective double-blind controlled trial in transcutaneous erection facilitation for organic impotence. J Urol 146:50, 1991 20. Chancellor MB, Rivas DA, Panzer DE, et al: Prospective comparison of topical minoxidil to vacuum constriction device and intracorporeal papaverine injection in treatment of erectile dysfunction due to spinal cord injury. Adult Urol 43:365, 1994 21. Chiang PH, Chiang CP, Wu Cc, et al: Color duplex sonography in the assessment of impotence. Br J Urol 68:181, 1991 22. Chiu AW, Chen KK, Chen MT, et al: Penile brachial index in impotent patients with coronary artery disease. Eur Urol 19:213, 1991 23. Claes H, Baert L: Transcutaneous nitroglycerin therapy in the treatment of impotence. Urol Int 44:309, 1989 24. Condra M, Fenemore J, Reid K, et al: Screening assessment of penile tumescence and rigidity. Clinical test of snap-gauge. Urology 29:254, 1987 25. Condra M, Morales A, Surridge D, et al: Evaluation of the urological assessment in impotence: Findings with a new diagnostic rating scale. J Urol 131:486, 1984 26. Cookson MS, Nadig PW: Long-term results with vacuum constriction device. J Urol 149:290, 1993 27. Cookson MS, Phillips DL, Huff ME, et al: Analysis of microsurgical penile revascularization results by etiology of impotence. J Urol 149:1308, 1993 28. Curb DJ, Nemat OB, Blaszkowski TP, et al: Long-term surveillance for adverse effects of antihypertensive drugs. JAMA 253:3263, 1985 29. Croog SH, Levine S, Sudilovsky A, et al: Sexual symptoms in hypertensive patients. Arch Intern Med 148:788, 1988 30. De Palma RG, Schwab FJ, Emsellem HA, et al: Noninvasive assessment of impotence. Surg Clin North Am 70:119, 1990 31. Dow JA, Gluck RW, Golimbu M, et al: Multiphasic diagnostic evaluation of arteriogenic, venogenic, and sinusoidogenic impotency. Value of noninvasive tests compared with penile duplex ultrasonography. Urology 38:402, 1991 32. Feldman HA, Goldstein I, Hatzichristou DG, et al: Impotence and its medical and psychosocial correlates: Results of the Massachusetts Male Aging Study. J Urol 151:54, 1994 33. Fisher C, Schiavi RC, Edwards A, et al: Evaluation of nocturnal penile tumescence in the differential diagnosis of sexual impotence. A qualitative study. Arch Gen Psychiatry 36:431, 1979 34. Pitch WP: Three-year experience using penile revascularization [abstr]. J Urol143(part 2):318A, 1990 35. Gilbert HW, Desai KM, Gingell JC: Non-invasive assessment of arteriogenic impotence: A comparative study. Br J Urol 67:512,1991 36. Gilbert HW, Gingell JC: Vacuum constriction devices: Second-line conservative treatment for impotence. Br J Urol 70:81, 1992 37. Godec CJ, Narkhede N, Tomasula JJ: The use of nitroglycerin in impotent patients [abstr]. J Urol 137(part 2):184A, 1987 38. Goldstein I: Arterial revascularization procedures. Sem Urol 4:252, 1986 39. Goldstein I, Levine F, Gasior B, et al: Role of vascular reconstructive surgery in impotence: A review of 335 patients over 7 years [abstr]. J Urol143(part 2):318A, 1990 40. Hampson SJ, Cowie AGA, Rickards D, et al: Independent evaluation of impotence by colour Doppler imaging and cavernosometry. Eur Urol 21:27, 1992 41. Hangeveld MW: Erectile dysfunction: A sexological and psychiatric review. World J Urol 1:227, 1983 42. Heaton JPW, Morales A, Owen J, et al: Topical glyceryltrinitrate causes measurable penile arterial dilation in impotent men. J Urol 143:729, 1990 43. Helier L, Keren 0, Aloui R, et al: An open trial of vacuum penile tumescence: Constriction therapy for neurological impotence. Paraplegia 30:550, 1992
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44. Johnson AR, Jarow JP: Is routine endocrine testing of impotent men necessary? J Urol 147:1542,1992 45. Kidd GS, Glass AR, Vigersky RA: The hypothalmic-pituitary-testicular axis in thyrotoxicosis. J Clin Endocrinol Metab 48:798, 1979 46. Konnak jW, Ohl DA: Microsurgical penile revascularization using the central corporeal penile artery. J Urol 142:305, 1989 47. Korenman SG, Viosca SP: Treatment of vasculogenic sexual dysfunction with pentoxifylline. J Am Geriatr Soc 41:363, 1993 48. Korenman SG, Viosca SP: Use of a vacuum tumescence device in the management of impotence in men with a history of penile implant or severe pelvic disease. J Am Geriatr Soc 40:61, 1992 49. Korenman SG, Viosca SP, Kaiser FE, et al: Use of a vacuum tumescence device in the management of impotence. J Am Geriatr Soc 38:217,1990 50. Lakin MM, Montague DK, Vander Brug Medendorp S, et al: Intercavernous injection therapy: Analysis of results and complications. J Urol 143:1138, 1990 51. Lavoisier P, Proulx J, Courtois F, et al: Bulbocavernous reflex: Its validity as a diagnostic test of neurogenic impotence. J UroI141:311, 1989 52. Lopez JA, Espeland MA, Jarrow JP: Interpretation and quantification of penile blood flow studies using duplex ultrasonography. J Urol 146:1271, 1991 53. LoPiccolo L Stock WE: Treatment of sexual dysfunction. Journal of Consulting and Clinical Psychology 54:158, 1986 54. Lue TF: Intercavernous drug administration: Its role in diagnosis and treatment of impotence. Semin Urol 8:100,1990 55. Lue TF: Physiology of erection and pathophysiology of impotence. In Walsh P, Gittes R, Perlmutter A, et al (eds): Campbell's Urology, ed 6. Philadelphia, WB Saunders, 1992, p 709 56. Marshall PG, Earls C Morales A, et al: Nocturnal penile tumescence recording with stamps: A validity study. J Urol 128:946, 1982 57. Marshall PG, Morales A, Phillips P, et al: Nocturnal penile tumescence with stamps: A comparative study under sleep laboratory conditions. J Urol 130:88, 1983 58. Marshall P, Surridge D, Delva N: The role of nocturnal penile tumescence in differentiating between organic and psychogenic impotence. Arch Sex Behav 10:1, 1981 59. Masters WH, Johnson YE: Human sexual inadequacy. Boston, Little, Brown, 1970 60. McDougal WS, Jeffrey RF: Microscopic penile revascularization. J Urol 129:517, 1983 61. Meinhardt W, Lycklama AAB, Kropman RF, et al: The negative pressure device for erectile disorders: When does it fail? J Urol 149:1285, 1993 62. Meyholt HH, Rosenkilde P, Bodker A: Non-invasive management of impotence with transcutaneous nitroglycerin. Br J Urol 69:88, 1992 63. Morales A, Condra M, Owen jA, et al: Is yohimbine effective in the treatment of organic impotence? Results of a controlled trial. J Urol 137:1168, 1987 64. Morales A, Condra M, Reid K: The role of nocturnal penile tumescence monitoring in the diagnosis of impotence: A review. J Urol 143:441, 1990 65. Moul JW, McLeod DG: Negative pressure devices in the explanted penile prosthesis population. J Urol 142:729, 1989 66. Mudd JW: Impotence responsive to glyceryl trinitrate. Am J Psychiatry 134:922, 1977 67. Mueller SC, Wallenberg-Pachaly HV, Voges GE, et al: Comparison of selective internal iliac pharmaco-angiography, penile brachial index and duplex sonography with pulsed Doppler analysis for the evaluation of vasculogenic (arteriogenic) impotence. J Urol 143:928, 1990 68. Mulligan T, Schmitt B: Testosterone for erectile failure. J Gen Intern Med 8:517, 1993 69. NIH Consensus Development Panel on Impotence: Impotence. JAMA 270:83,1990 70. Nogueira MC, Herbaut AG, We spes E: Neurophysiological investigations of two hundred men with erectile dysfunction. Eur Urol 18:37, 1990 71. Nunez BD, Anderson DC Jr: Nitroglycerin ointment in the treatment of impotence. J Urol 150:1241, 1993 72. Owen JA, Saunders F, Harris C et al: Topical nitroglycerin: A potential treatment for impotence. J Urol 141:546, 1989 73. Papp GY, Hoznek A, Juhasz E, et al: Vacuum therapy in the treatment of erectile impotence. Acta Chir Hung 32:331, 1991
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