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Intracavernous Injection of Prostaglandin E1 in Impotent Men
0022-534 7/88/1401-0066$2.00/0 THE JOURNAL OF UROLOGY
Vol. 140, July
Copyright © 1988 by The Williams & Wilkins Co.
Printed in U.S.A.
INTRACAVERNOUS INJECTION OF PROSTAGLANDIN El IN IMPOTENT MEN WALTER STACKL,* RUDOLF HASUN AND MICHAEL MARBERGER From the Department of Urology, Rudolfstiftung, Vienna, Austria
ABSTRACT
Intracavernous injection of prostaglandin El was used in 210 men as a screening test for the differential diagnosis of vasculogenic impotence. Of these 210 patients 112 entered an autoinjection protocol for treatment of erectile dysfunction. Prostaglandin El appears to be effective in the diagnosis and treatment of nonvasculogenic impotence because it is a physiological agent that is metabolized locally within the cavernous tissue. Additionally, in our series neither systemic reactions nor priapism occurred, nor was fibrosis of cavernous tissue or scar formation observed after up to 90 injections. (J. Urol., 140: 66-68, 1988) The intracavernous injection of vasoactive drugs is in the center of the diagnostic evaluation and treatment of patients with erectile dysfunction. 1- 3 The agents used for this purpose, mainly phenoxybenzamine, 4 papaverine or a combination of papaverine and phentolamine,3 • 5 • 6 are known to induce severe side effects, including fibrosis and priapism, and 1 death has been reported.7 In the presence of venous leakage systemic reactions, such as hot flashes, dizziness or hypertension, may occur. Stimulated by the report of Hedlund and Andersson, 8 we evaluated prostaglandin El as an agent for intracavernous injection. Prostaglandin El is a smooth muscle relaxant that produces vasodilatation and occurs naturally in high concentrations in the seminal fluids. Its precise physiological action is unknown and until now its only clinical use has been to treat infants with patent ductus arteriosus. 9
between 10 and 20 µ,g. according to the desired response. Those who injected less than 20 µ,g. were instructed to discard the surplus amount. After every 10 injections the patients were reexamined with a careful history and a physical examination of the penis. Because at this time prostaglandin El was used only at our institution the patients had to return for regular evaluations if they wished to continue treatment. RESULTS
Prostaglandin El test. A positive result to the 20 µ,g. test dosage was noted in 143 of the 210 patients (68.1 per cent), with the onset of erection after 2 to 15 minutes (mean 7.5) and a duration of 0.5 to 7 hours (mean 2.3). The erections of longest duration (more than 5 hours) were observed in the patients with paraplegia (6 hours) and amyotrophic lateral sclerosis (7 hours). The side effects included pain at the injection site in 17 (8.1 per cent), pain during erection in 8 (3.8 per cent), pain with injection and erection in 10 (4.8 per cent) and hematoma at the injection site in 10 (4.8 per cent). In the remaining 67 patients (31.9 per cent) a second injection of 40 µ,g. was given and 8 (3.8 per cent) achieved an erection lasting more than 30 minutes. The other 59 patients underwent Doppler studies of the penile arteries and cavernosography: 52 had venous leakage and 7 had an abnormal arterial mechanism. The criteria for the diagnosis of venous leakage were a negative response to prostaglandin El testing, abnormal findings on pharmacocavernosography with prostaglandin El and detection of 4 penile arteries by Doppler sonography. Arteriogenic impotence was diagnosed in patients with a negative response to prostaglandin El testing, normal results on cavernosography, 3 or fewer penile arteries evident on Doppler sonography and abnormal findings on arteriography. In 20 patients with venous leakage blood pressure was measured before and 5 minutes after injection of 40 µ,g. prostaglandin El into the cavernous body and no significant difference was found. All patients who underwent pelvic surgery had a positive prostaglandin El test result.
PATIENTS AND METHODS
Between July 1986 and April 1987 we studied 210 men with erectile dysfunction. Patient age and duration of impotence are shown in table 1. Risk factors detected by history included smoking more than 20 cigarettes per day in 17 patients (8 per cent), diabetes in 18 (8.6 per cent) and hypertension in 24 (11.4 per cent). More than 1 risk factor was noted in 23 patients (11 per cent). Prior pelvic operations among 18 impotent men included radical cystectomy (10), radical prostatectomy (4), proctectomy (2) and implantation of a bifurcation prosthesis (2). One patient was a paraplegic and 1 had amyotrophic lateral sclerosis. For each patient a meticulous history was recorded but no other diagnostic procedures were done before the intracavernous injection of prostaglandin El. Prostaglandin El test. For all patients 20 µ,g. prostaglandin El were dissolved in 1 ml. normal saline and injected into 1 cavernous body with a 26 gauge needle. After injection the penis was squeezed for approximately 5 seconds to ensure the transfer of the drug to the contralateral corpus. No tourniquet was used. The result was defined as positive if full erection was achieved after intracavernous injection and maintained for at least 30 minutes without sexual stimulation. Patients with negative results received a larger test dosage (40 µ,g.) 1 to 3 weeks later. Autoinjection of prostaglandin El. Of 151 patients who had an erection after injection ofprostaglandin El 112 were selected for autoinjection before sexual activity and they or their partners were instructed in the technique of intracavernous injection. Prostaglandin El (20 µ,g. in 1 ml. normal saline) was prepared in a 1 ml. disposable syringe with a 26 or 28 gauge needle no longer than 3 months before use. Patients injected
TABLE 1.
Accepted for publication October 30, 1987. * Requests for reprints: Juchgasse 25, A-1030, Vienna, Austria.
66
Age and duration of impotence in 210 men
Age (yrs.)
No.
Mean Yrs. of Impotence (range)
16-20 20-29 30-39 40-49 50-59 60-69 70-79 80-83
3 18 25 47 59 49 7 2
5.2 3.3 5.7 4.6 4.8 3.6 7.6 2.5
(4-6) (0.2-10) (0.5-15) (0.2-25) (0.3-20) (0.2-10) (1-20) (2-3)
INTRACAVERNOUS INJECTION OF PROSTAGLANDIN El IN IMPOTENT MEN TABLE 2.
Dosages of prostaglandin El for autoinjection in 112 patients Dosage (µg.)
No. Pts. 2
5
18
10 15 20
27
56
40 Variable
6
3
Prostaglandin El autoinjection. The dosages each patient injected for the desired response are listed in table 2. The recommended dosage was calculated from the response to the prostaglandin El test. For example, if a patient achieved an erection lasting 2 hours with 20 µg. prostaglandin El and he desired a 1-hour erection a 10 µg. dosage was recommended for autoinjection. In 2 patients 5 µg. caused tumescence, which resulted in a sufficient erection with sexual stimulation. In this group detumescence occurred after ejaculation. All 10 patients who entered the autoinjection protocol among 18 with pelvic surgery injected 10 µg. prostaglandin El. Varying risk factors had no effect on response. The duration of the erection ranged from 0.5 to 4 hours (mean 1.2 hours), with a linear correlation between dosage and duration. Three patients varied the dosages: 2 because of different sexual partners and 1 with varying sexual desire. The injection frequency ranged from once a month to 4 times a week. To date the longest followup has been 8 months (mean 4.5 months), with the greatest number of injections totaling 90 (mean 15 injections). Complications in the autoinjection group. No patients in the autoinjection group experienced pain during erection. There were no systemic side effects, such as dizziness or facial flushing, and none required treatment for prolonged erection or priapism. Eleven patients reported ecchymosis at the site of injection but this did not cause them to forego sexual intercourse and all cases of ecchymosis resolved without further problems. Twelve patients (10.7 per cent) encountered problems with the techniques owing to injection into either the corpus spongiosum or subcutaneous tissue but no side effects were noted. Two women did not accept the autoinjection treatment because they considered this erection to be artificial. No patient had fibrosis or scarring of the cavernous tissue. DISCUSSION
Prostaglandin El is a natural constituent of many mammalian tissues. 10 In humans it is found in high concentrations in the seminal vesicle and seminal plasma. 11 Roy and associates reported that human cavernous tissue can generate prostaglandins and thromboxanes in vitro. 12 Generally, prostaglandins cause contraction of smooth muscle in vivo and in vitro. Intracavernous injection of prostaglandin El appears to act as does that of papaverine by relaxing the cavernous and arteriolar smooth muscles, thus, bypassing neurogenic influence. 2 Intracavernously or arterially administered prostaglandin El is metabolized rapidly and distributed throughout the body except for the central nervous system where distribution, although detectable, is reduced markedly. The primary organs for metabolism and inactivation of prostaglandin El are the lung, liver and kidney. In a single pass through the lung about 70 per cent of the prostaglandin El is metabolized. 13 The absence of prolonged erections or priapism suggests that prostaglandin El also is metabolized within the cavernous tissue. 12 The rapid metabolism of prostaglandin El is responsible for the lack of systemic reactions. Not even in our patients with venous leakage were changes in blood pressure or systemic reactions found. These occasionally occur after intracavernous
67
injection of papaverine, 2 which either alone or in combination with phentolamine is used widely for diagnostic as well as therapeutic purposes. 2 • 3 • 5 ' 6 · 14 Abber and associates demonstrated that injection of papaverine is a better screening technique for the differential diagnosis of vasculogenic impotence than the penile brachial index or nocturnal penile tumescence monitoring. 1 The reported therapeutic dosages range between 30 and 160 mg. 5 • 6 Low dose treatment produces tumescence but sexual stimulation is required for a full erection. Higher doses of papaverine or the addition of phentolamine causes full erection but a prolonged erection can be expected in about 4 per cent of the patients. 15 Recently, a death of pulmonary embolism with thrombosis of the dorsal vein and the cavernous bodies was reported. 7 In our limited experience with papaverine we found that the therapeutic range is small, and there is no linear correlation between dosage and duration of erection. Therefore, patients in an autoinjection program might easily modify the recommended range and run the risk of priapism. None of our patients experienced a painful prolonged erection that required treatment after injection of prostaglandin El. Two patients with neurogenic impotence had erections of 6 and 7 hours, respectively, but these subsided spontaneously without sequelae. Therefore, in such patients we recommend only 10 µ,g. prostaglandin El for diagnostic testing. It is noteworthy that no patient in the autoinjection group had a painful or prolonged erection. The rate of positive responses (68.1 per cent) in our series is relatively low compared to the 83 per cent reported by Sidi and associates, who used papaverine and phentolamine. 3 However, 55 of their 100 patients had neurogenic or combined neurogenic and vasculogenic impotence-a highly selected group that is not typical of the patient population seen in a practice devoted to impotence. It is well known that almost all patients with neurogenic impotence respond to intracavernous injection of vasoactive drugs, although all of our patients with a previous pelvic operation had a positive prostaglandin El test result. If a patient responds to prostaglandin El a full erection develops that is linearly dosage related and does not require sexual stimulation. Therefore, the patient can vary the dosage depending on the sexual desire. For example, 1 of our patients with 3 different sexual partners uses 10, 15 and 20 µg. prostaglandin El for erections lasting 1, 1.5 or 2 hours, depending on the desire of the partner. The quality of erection is unchanged after ejaculation. Zorgniotti, 16 and Lue and Tanagho 2 reported fibrosis of the corpus cavernosum and angulation of the tunica albuginea after repeated papaverine injections. It remains questionable whether fibrosis is caused by the drug, trauma from the injection needle or organized hematoma. In our series this complication has not been apparent after 90 prostaglandin El injections but the followup is short. In conclusion, from our experience in 210 patients it is evident that prostaglandin El is an effective diagnostic and therapeutic agent in erectile dysfunction. The lack of priapism and other severe side effects, such as fibrosis and angulation of the penis, even with a relatively short followup recommends prostaglandin El for further clinical trials.
REFERENCES 1. Abber, J.C., Lue, T. F., Orvis, B. R., McClure, R. D. and Williams,
R. D.: Diagnostic tests for impotence: a comparison ofpapaverine injection with the penile-brachia! index and nocturnal penile tumescence monitoring. J. Urol., 135: 923, 1986. 2. Lue, T. F. and Tanagho, E. A.: Physiology of erection and pharmacological management of impotence. J. Urol., 137: 829, 1987. 3. Sidi, A. A., Cameron, J. S., Duffy, L. M. and Lange, P. H.: lntracavernous drug-induced erections in the management of male erectile dysfunction: experience with 100 patients. J. U rol., 135: 704, 1986.
68
STACKL, HASUN AND MARBERGER
4. Brindley, G. S.: Pilot experiments on the actions of drugs injected into the human corpus cavernosum penis. Brit. J. Pharmacol., 87: 495, 1986. 5. Virag, R., Frydman, D., Legman, M. and Virag, H.: Intracavernous injection of papaverine as a diagnostic and therapeutic method in erectile failure. Angiology, 35: 79, 1984. 6. Zorgniotti, A. W. and Lefleur, R. S.: Auto-injection of the corpus cavernosum with a vasoactive drug combination for vasculogenic impotence. J. Urol., 133: 39, 1985. 7. Hashmat, A. I., Abrahams, J., Fani, K. and Nostrand, I.: Papaverine induced priapism, a lethal complication. J. Urol., submitted for publication. 8. Hedlund, H. and Andersson, K.-E.: Contraction and relaxation induced by some prostanoids in isolated human penile erectile tissue and cavernous artery. J. Urol., 134: 1245, 1985. 9. Coceani, F., Olley, P. M. and Lock, J. E.: Prostaglandins, ductus arteriosus, pulmonary circulation: current concepts and clinical potential. Eur. J. Clin. Pharmacol., 18: 75, 1980. 10. Piper, P. J.: Distribution and metabolism. In: The Prostaglandins: Pharmacological and Therapeutic Advances. Edited by M. F.
11. 12. 13. 14.
15. 16.
Cuthbert. Philadelphia: J. B. Lippincott Co., chapt. III, p. 125, 1973. Hamberg, M.: Biosynthesis of prostaglandin El by human seminal vesicles. Lipids, 11: 249, 1976. Roy, A. C., Tan, S. M., Kottegoda, S. R. and Ratman, S. S.: Ability of human corpora cavernosa muscle to generate prostaglandins and thromboxanes in vitro. IRCS Med. Sci., 12: 608, 1984. Golub, M., Zia, P., Matsuno, M. and Horton, R.: Metabolism of prostaglandins Al and El in man. J. Clin. Invest., 59: 1404, 1975. Bauhren, W., Stief, Ch., Scherb, W., Gall, H., Gallwitz, A. and Altwein, J.: Rationelle Diagnostik der erectilen Dysfunktion unter Anwendung eines pharmakologischen Testes. Akt. Urol., 17: 177, 1986. Halsted, D. S., Weigel, J. W., Noble, M. J. and Mebust, W. K.: Papaverine-inducedpriapism: 2 case reports. J. Urol., 136: 109, 1986. Zorgniotti, A. W.: Corpus cavernosum blockade for impotence: practical aspects and results in 250 cases. J. Urol., part 2, 135: 306A, abstract 808, 1986.
Vol. 140, July
Copyright © 1988 by The Williams & Wilkins Co.
Printed in U.S.A.
INTRACAVERNOUS INJECTION OF PROSTAGLANDIN El IN IMPOTENT MEN WALTER STACKL,* RUDOLF HASUN AND MICHAEL MARBERGER From the Department of Urology, Rudolfstiftung, Vienna, Austria
ABSTRACT
Intracavernous injection of prostaglandin El was used in 210 men as a screening test for the differential diagnosis of vasculogenic impotence. Of these 210 patients 112 entered an autoinjection protocol for treatment of erectile dysfunction. Prostaglandin El appears to be effective in the diagnosis and treatment of nonvasculogenic impotence because it is a physiological agent that is metabolized locally within the cavernous tissue. Additionally, in our series neither systemic reactions nor priapism occurred, nor was fibrosis of cavernous tissue or scar formation observed after up to 90 injections. (J. Urol., 140: 66-68, 1988) The intracavernous injection of vasoactive drugs is in the center of the diagnostic evaluation and treatment of patients with erectile dysfunction. 1- 3 The agents used for this purpose, mainly phenoxybenzamine, 4 papaverine or a combination of papaverine and phentolamine,3 • 5 • 6 are known to induce severe side effects, including fibrosis and priapism, and 1 death has been reported.7 In the presence of venous leakage systemic reactions, such as hot flashes, dizziness or hypertension, may occur. Stimulated by the report of Hedlund and Andersson, 8 we evaluated prostaglandin El as an agent for intracavernous injection. Prostaglandin El is a smooth muscle relaxant that produces vasodilatation and occurs naturally in high concentrations in the seminal fluids. Its precise physiological action is unknown and until now its only clinical use has been to treat infants with patent ductus arteriosus. 9
between 10 and 20 µ,g. according to the desired response. Those who injected less than 20 µ,g. were instructed to discard the surplus amount. After every 10 injections the patients were reexamined with a careful history and a physical examination of the penis. Because at this time prostaglandin El was used only at our institution the patients had to return for regular evaluations if they wished to continue treatment. RESULTS
Prostaglandin El test. A positive result to the 20 µ,g. test dosage was noted in 143 of the 210 patients (68.1 per cent), with the onset of erection after 2 to 15 minutes (mean 7.5) and a duration of 0.5 to 7 hours (mean 2.3). The erections of longest duration (more than 5 hours) were observed in the patients with paraplegia (6 hours) and amyotrophic lateral sclerosis (7 hours). The side effects included pain at the injection site in 17 (8.1 per cent), pain during erection in 8 (3.8 per cent), pain with injection and erection in 10 (4.8 per cent) and hematoma at the injection site in 10 (4.8 per cent). In the remaining 67 patients (31.9 per cent) a second injection of 40 µ,g. was given and 8 (3.8 per cent) achieved an erection lasting more than 30 minutes. The other 59 patients underwent Doppler studies of the penile arteries and cavernosography: 52 had venous leakage and 7 had an abnormal arterial mechanism. The criteria for the diagnosis of venous leakage were a negative response to prostaglandin El testing, abnormal findings on pharmacocavernosography with prostaglandin El and detection of 4 penile arteries by Doppler sonography. Arteriogenic impotence was diagnosed in patients with a negative response to prostaglandin El testing, normal results on cavernosography, 3 or fewer penile arteries evident on Doppler sonography and abnormal findings on arteriography. In 20 patients with venous leakage blood pressure was measured before and 5 minutes after injection of 40 µ,g. prostaglandin El into the cavernous body and no significant difference was found. All patients who underwent pelvic surgery had a positive prostaglandin El test result.
PATIENTS AND METHODS
Between July 1986 and April 1987 we studied 210 men with erectile dysfunction. Patient age and duration of impotence are shown in table 1. Risk factors detected by history included smoking more than 20 cigarettes per day in 17 patients (8 per cent), diabetes in 18 (8.6 per cent) and hypertension in 24 (11.4 per cent). More than 1 risk factor was noted in 23 patients (11 per cent). Prior pelvic operations among 18 impotent men included radical cystectomy (10), radical prostatectomy (4), proctectomy (2) and implantation of a bifurcation prosthesis (2). One patient was a paraplegic and 1 had amyotrophic lateral sclerosis. For each patient a meticulous history was recorded but no other diagnostic procedures were done before the intracavernous injection of prostaglandin El. Prostaglandin El test. For all patients 20 µ,g. prostaglandin El were dissolved in 1 ml. normal saline and injected into 1 cavernous body with a 26 gauge needle. After injection the penis was squeezed for approximately 5 seconds to ensure the transfer of the drug to the contralateral corpus. No tourniquet was used. The result was defined as positive if full erection was achieved after intracavernous injection and maintained for at least 30 minutes without sexual stimulation. Patients with negative results received a larger test dosage (40 µ,g.) 1 to 3 weeks later. Autoinjection of prostaglandin El. Of 151 patients who had an erection after injection ofprostaglandin El 112 were selected for autoinjection before sexual activity and they or their partners were instructed in the technique of intracavernous injection. Prostaglandin El (20 µ,g. in 1 ml. normal saline) was prepared in a 1 ml. disposable syringe with a 26 or 28 gauge needle no longer than 3 months before use. Patients injected
TABLE 1.
Accepted for publication October 30, 1987. * Requests for reprints: Juchgasse 25, A-1030, Vienna, Austria.
66
Age and duration of impotence in 210 men
Age (yrs.)
No.
Mean Yrs. of Impotence (range)
16-20 20-29 30-39 40-49 50-59 60-69 70-79 80-83
3 18 25 47 59 49 7 2
5.2 3.3 5.7 4.6 4.8 3.6 7.6 2.5
(4-6) (0.2-10) (0.5-15) (0.2-25) (0.3-20) (0.2-10) (1-20) (2-3)
INTRACAVERNOUS INJECTION OF PROSTAGLANDIN El IN IMPOTENT MEN TABLE 2.
Dosages of prostaglandin El for autoinjection in 112 patients Dosage (µg.)
No. Pts. 2
5
18
10 15 20
27
56
40 Variable
6
3
Prostaglandin El autoinjection. The dosages each patient injected for the desired response are listed in table 2. The recommended dosage was calculated from the response to the prostaglandin El test. For example, if a patient achieved an erection lasting 2 hours with 20 µg. prostaglandin El and he desired a 1-hour erection a 10 µg. dosage was recommended for autoinjection. In 2 patients 5 µg. caused tumescence, which resulted in a sufficient erection with sexual stimulation. In this group detumescence occurred after ejaculation. All 10 patients who entered the autoinjection protocol among 18 with pelvic surgery injected 10 µg. prostaglandin El. Varying risk factors had no effect on response. The duration of the erection ranged from 0.5 to 4 hours (mean 1.2 hours), with a linear correlation between dosage and duration. Three patients varied the dosages: 2 because of different sexual partners and 1 with varying sexual desire. The injection frequency ranged from once a month to 4 times a week. To date the longest followup has been 8 months (mean 4.5 months), with the greatest number of injections totaling 90 (mean 15 injections). Complications in the autoinjection group. No patients in the autoinjection group experienced pain during erection. There were no systemic side effects, such as dizziness or facial flushing, and none required treatment for prolonged erection or priapism. Eleven patients reported ecchymosis at the site of injection but this did not cause them to forego sexual intercourse and all cases of ecchymosis resolved without further problems. Twelve patients (10.7 per cent) encountered problems with the techniques owing to injection into either the corpus spongiosum or subcutaneous tissue but no side effects were noted. Two women did not accept the autoinjection treatment because they considered this erection to be artificial. No patient had fibrosis or scarring of the cavernous tissue. DISCUSSION
Prostaglandin El is a natural constituent of many mammalian tissues. 10 In humans it is found in high concentrations in the seminal vesicle and seminal plasma. 11 Roy and associates reported that human cavernous tissue can generate prostaglandins and thromboxanes in vitro. 12 Generally, prostaglandins cause contraction of smooth muscle in vivo and in vitro. Intracavernous injection of prostaglandin El appears to act as does that of papaverine by relaxing the cavernous and arteriolar smooth muscles, thus, bypassing neurogenic influence. 2 Intracavernously or arterially administered prostaglandin El is metabolized rapidly and distributed throughout the body except for the central nervous system where distribution, although detectable, is reduced markedly. The primary organs for metabolism and inactivation of prostaglandin El are the lung, liver and kidney. In a single pass through the lung about 70 per cent of the prostaglandin El is metabolized. 13 The absence of prolonged erections or priapism suggests that prostaglandin El also is metabolized within the cavernous tissue. 12 The rapid metabolism of prostaglandin El is responsible for the lack of systemic reactions. Not even in our patients with venous leakage were changes in blood pressure or systemic reactions found. These occasionally occur after intracavernous
67
injection of papaverine, 2 which either alone or in combination with phentolamine is used widely for diagnostic as well as therapeutic purposes. 2 • 3 • 5 ' 6 · 14 Abber and associates demonstrated that injection of papaverine is a better screening technique for the differential diagnosis of vasculogenic impotence than the penile brachial index or nocturnal penile tumescence monitoring. 1 The reported therapeutic dosages range between 30 and 160 mg. 5 • 6 Low dose treatment produces tumescence but sexual stimulation is required for a full erection. Higher doses of papaverine or the addition of phentolamine causes full erection but a prolonged erection can be expected in about 4 per cent of the patients. 15 Recently, a death of pulmonary embolism with thrombosis of the dorsal vein and the cavernous bodies was reported. 7 In our limited experience with papaverine we found that the therapeutic range is small, and there is no linear correlation between dosage and duration of erection. Therefore, patients in an autoinjection program might easily modify the recommended range and run the risk of priapism. None of our patients experienced a painful prolonged erection that required treatment after injection of prostaglandin El. Two patients with neurogenic impotence had erections of 6 and 7 hours, respectively, but these subsided spontaneously without sequelae. Therefore, in such patients we recommend only 10 µ,g. prostaglandin El for diagnostic testing. It is noteworthy that no patient in the autoinjection group had a painful or prolonged erection. The rate of positive responses (68.1 per cent) in our series is relatively low compared to the 83 per cent reported by Sidi and associates, who used papaverine and phentolamine. 3 However, 55 of their 100 patients had neurogenic or combined neurogenic and vasculogenic impotence-a highly selected group that is not typical of the patient population seen in a practice devoted to impotence. It is well known that almost all patients with neurogenic impotence respond to intracavernous injection of vasoactive drugs, although all of our patients with a previous pelvic operation had a positive prostaglandin El test result. If a patient responds to prostaglandin El a full erection develops that is linearly dosage related and does not require sexual stimulation. Therefore, the patient can vary the dosage depending on the sexual desire. For example, 1 of our patients with 3 different sexual partners uses 10, 15 and 20 µg. prostaglandin El for erections lasting 1, 1.5 or 2 hours, depending on the desire of the partner. The quality of erection is unchanged after ejaculation. Zorgniotti, 16 and Lue and Tanagho 2 reported fibrosis of the corpus cavernosum and angulation of the tunica albuginea after repeated papaverine injections. It remains questionable whether fibrosis is caused by the drug, trauma from the injection needle or organized hematoma. In our series this complication has not been apparent after 90 prostaglandin El injections but the followup is short. In conclusion, from our experience in 210 patients it is evident that prostaglandin El is an effective diagnostic and therapeutic agent in erectile dysfunction. The lack of priapism and other severe side effects, such as fibrosis and angulation of the penis, even with a relatively short followup recommends prostaglandin El for further clinical trials.
REFERENCES 1. Abber, J.C., Lue, T. F., Orvis, B. R., McClure, R. D. and Williams,
R. D.: Diagnostic tests for impotence: a comparison ofpapaverine injection with the penile-brachia! index and nocturnal penile tumescence monitoring. J. Urol., 135: 923, 1986. 2. Lue, T. F. and Tanagho, E. A.: Physiology of erection and pharmacological management of impotence. J. Urol., 137: 829, 1987. 3. Sidi, A. A., Cameron, J. S., Duffy, L. M. and Lange, P. H.: lntracavernous drug-induced erections in the management of male erectile dysfunction: experience with 100 patients. J. U rol., 135: 704, 1986.
68
STACKL, HASUN AND MARBERGER
4. Brindley, G. S.: Pilot experiments on the actions of drugs injected into the human corpus cavernosum penis. Brit. J. Pharmacol., 87: 495, 1986. 5. Virag, R., Frydman, D., Legman, M. and Virag, H.: Intracavernous injection of papaverine as a diagnostic and therapeutic method in erectile failure. Angiology, 35: 79, 1984. 6. Zorgniotti, A. W. and Lefleur, R. S.: Auto-injection of the corpus cavernosum with a vasoactive drug combination for vasculogenic impotence. J. Urol., 133: 39, 1985. 7. Hashmat, A. I., Abrahams, J., Fani, K. and Nostrand, I.: Papaverine induced priapism, a lethal complication. J. Urol., submitted for publication. 8. Hedlund, H. and Andersson, K.-E.: Contraction and relaxation induced by some prostanoids in isolated human penile erectile tissue and cavernous artery. J. Urol., 134: 1245, 1985. 9. Coceani, F., Olley, P. M. and Lock, J. E.: Prostaglandins, ductus arteriosus, pulmonary circulation: current concepts and clinical potential. Eur. J. Clin. Pharmacol., 18: 75, 1980. 10. Piper, P. J.: Distribution and metabolism. In: The Prostaglandins: Pharmacological and Therapeutic Advances. Edited by M. F.
11. 12. 13. 14.
15. 16.
Cuthbert. Philadelphia: J. B. Lippincott Co., chapt. III, p. 125, 1973. Hamberg, M.: Biosynthesis of prostaglandin El by human seminal vesicles. Lipids, 11: 249, 1976. Roy, A. C., Tan, S. M., Kottegoda, S. R. and Ratman, S. S.: Ability of human corpora cavernosa muscle to generate prostaglandins and thromboxanes in vitro. IRCS Med. Sci., 12: 608, 1984. Golub, M., Zia, P., Matsuno, M. and Horton, R.: Metabolism of prostaglandins Al and El in man. J. Clin. Invest., 59: 1404, 1975. Bauhren, W., Stief, Ch., Scherb, W., Gall, H., Gallwitz, A. and Altwein, J.: Rationelle Diagnostik der erectilen Dysfunktion unter Anwendung eines pharmakologischen Testes. Akt. Urol., 17: 177, 1986. Halsted, D. S., Weigel, J. W., Noble, M. J. and Mebust, W. K.: Papaverine-inducedpriapism: 2 case reports. J. Urol., 136: 109, 1986. Zorgniotti, A. W.: Corpus cavernosum blockade for impotence: practical aspects and results in 250 cases. J. Urol., part 2, 135: 306A, abstract 808, 1986.