- Email: [email protected]
Use of prostaglandin E1 for papaverine-failed erections
USE OF PROSTAGLANDIN
El FOR
PAPAVERINE-FAILED ERECTIONS HARRY REISS,
M.D.
From the Department of Urology, New York University School of Medicine, New York, New York
ABSTRACTThe use of prostaglandin El is introduced as a pharmacologic agent that can produce artificial erections in patients who have failed the initial papaverine test or who were on selfinjection programs and later lost rigidity.
There is a need to improve the loss of rigidity in those patients in whom a satisfactory erection does not develop with papaverine hydrochloride and/or phentolamine mesylate. One third of patients who are initially tested with pharmacologically-induced erections fail. l Others drop out of their self-injection programs after initial success due to the loss of coital rigidity.2 A method using a hand-held injector to rescue these failures has been shown to be effective3 but does not meet with patient satisfaction due to the need for an external pumping device. Herein is introduced the concept of using prostaglandin El on those patients who fail the initial papaverine test or who are on a selfinjection program and fail to achieve rigidity using maximal doses of papaverine/ phentolamine. Prostaglandin E1 for artificial erection first appeared in the urologic field in 1985 when Hedlund and Andersson4 studied the relaxation and contraction of isolated human erectile tissue. The first clinical trial in humans was introduced in Japan in 1986 by Ishii et aL5 and by Virag and Adaikan in 1987.e Material and Methods An ongoing series of patients who visited a private urologic office with a complaint of impotency were tested with 30 mg of intracavernous papaverine to evaluate their rigidity response. Not included in this study were those
UROLOGY
/ JANUARY
1989
I
VOLUME
XxX111, NUMBER
patients who responded well to papaverine: no buckling, good angle of erection, and a feeling of adequate “fullness” experienced by the patient . Ten patients whose test injection failed to produce a satisfactory erection and 2 patients in the self-injection program were selected for this study. Failure was determined by a penis that buckled under manually applied linear force and produced no visible elevation of the erection angle while the patient was standing. In the 12 patients (ages ranged from thirtytwo to sixty-seven years), all had incomplete coital erections or loss of sleep-related erections; and none experienced “fullness” with the initial test of 30 mg of papaverine or lost the erections after having used papaverine for one to six months. Patients were reinjected with 5 pg to 20 pg of prostaglandin Ei in 1 to 3 cc of normal saline at 4°C using a pre-cooled syringe and a 30G needle in the same sites and with the same technique as used with papaverine. After ten to twenty minutes, the effect of the injection was evaluated. None of the patients experienced any of the expected side effects such as headaches, flushing, nausea, or abdominal cramps. In 1 patient, transitory pain was felt at the injection site of a Peyronie plaque. Phentolamine was not used. Patients signed informed consent forms similar to those used for papaverine.
1
15
Results In all 12 patients, the quality of their erections was reported to be more than adequate for intercourse by both an objective observer and the patients themselves. The duration of this artificial erection lasted between twenty minutes and two hours. The superficial veins, the corpora spongiosa, and glans were noted to be engorged in 11 of the 12 patients to a degree never observed with papaverine. The 2 patients on self-injections are continuing in the home program using prostaglandin El. Of the 10 patients, 5 have decided to join the home self-injection program using prostaglandin E1 because they had experienced better erections between injections.
the spongiosa, a structure which has been traditionally labeled as “not involved in erection.” Therefore, prostaglandin El may be a good tool for studying the role of the spongiosa and the glans in the regulation of blood flow during erection.a The spongiosa is the largest and most readily visible arteriovenous shunt that is present in the penis. Assuming hydraulic competency or “no venous leak,” prostaglandin E, activates the venoocclusive mechanism independently of the cavernous artery9 much as papaverine does. It may also provide an additional stimulus to blood flow that allows vast amounts of blood to flow from the urethral bulb artery and corpora spongiosa into the cavernosal bodies. 142 East 16th Street New York. New York 10003
Comment The mechanism of prostaglandin El in producing erection is due to smooth muscle relaxation and vasodilation. The results are so encouraging that this form of treatment could replace any other form of self-injection therapy, since the solution is not acid as is papaverine and gives the penis a more natural look during the erection. The response to this vasoactive medication is slower and is of shorter duration than papaverine, allowing less chance for prolonged erection to occur. Prostaglandin El has interesting healing properties such as reducing inflammation, inhibiting platelet aggregation, preventing tissue damage, and stabilizing lysosome proteases. These properties may be useful in preventing the occasional papaverine-induced priapism and reducing the potential for fibrosis or Peyronie disease that might result from the injections. There are visible clinical changes that indicate that prostaglandin Er increases blood into
16
References 1. Althof SE, et al: Intracavernous injection in the treatment of impotence: a prospective study, J Sex Marital Ther 13: 155 (1987). 2. Nellans RE, and Kramer-Levien D: Pharmacological erection: diagnosis treatment applications in 69 patients, J Urol 138: 520 (1987). 3. Reiss H: Rescuing papaverine-failed erections, Third Biennial World Meeting on Impotence, Boston, October 6-9, 1988. 4. Hedlund H, and Andersson K-E: Contraction and relaxation induced by some prostanoids in isolated human penile tissue and cavernous artery, J Urol 134: 1245 (1985). 5. Ishii N, et al: Studies on male sexual impotency, Report 18: Therapeutic trial with prostaglandin El for organic impotency, NiDDOD Hinvokika Gakkia Zasshi 77: 954 (1986). 6: Virag R, and Adaikan PC: Effects of prostaglandin Er on penile erection and erectile failure (letter), J Urol 137: 1010 (1987). 7. Carlson LA, and Olsson AG: PGEl in ischemic peripheral vascular disease, in: Karim SMM (Ed): Practical Applications of Prostaglandins and Their Synthesis Inhibitors. Baltimore, University Park Press, chap 3, 1979, pp 39-51. 8. Reiss H: The role of spongiosography in study of penile veins, Urology 29: 146 (1987). 9. Delacour C, et al: The effect of papaverine on arterial and venous hemodynamics of erection, J Urol 138: 187 (1987).
UROLOGY
I
JANUARY
1989
I
VOLUME
XxX111, NUMBER
1
El FOR
PAPAVERINE-FAILED ERECTIONS HARRY REISS,
M.D.
From the Department of Urology, New York University School of Medicine, New York, New York
ABSTRACTThe use of prostaglandin El is introduced as a pharmacologic agent that can produce artificial erections in patients who have failed the initial papaverine test or who were on selfinjection programs and later lost rigidity.
There is a need to improve the loss of rigidity in those patients in whom a satisfactory erection does not develop with papaverine hydrochloride and/or phentolamine mesylate. One third of patients who are initially tested with pharmacologically-induced erections fail. l Others drop out of their self-injection programs after initial success due to the loss of coital rigidity.2 A method using a hand-held injector to rescue these failures has been shown to be effective3 but does not meet with patient satisfaction due to the need for an external pumping device. Herein is introduced the concept of using prostaglandin El on those patients who fail the initial papaverine test or who are on a selfinjection program and fail to achieve rigidity using maximal doses of papaverine/ phentolamine. Prostaglandin E1 for artificial erection first appeared in the urologic field in 1985 when Hedlund and Andersson4 studied the relaxation and contraction of isolated human erectile tissue. The first clinical trial in humans was introduced in Japan in 1986 by Ishii et aL5 and by Virag and Adaikan in 1987.e Material and Methods An ongoing series of patients who visited a private urologic office with a complaint of impotency were tested with 30 mg of intracavernous papaverine to evaluate their rigidity response. Not included in this study were those
UROLOGY
/ JANUARY
1989
I
VOLUME
XxX111, NUMBER
patients who responded well to papaverine: no buckling, good angle of erection, and a feeling of adequate “fullness” experienced by the patient . Ten patients whose test injection failed to produce a satisfactory erection and 2 patients in the self-injection program were selected for this study. Failure was determined by a penis that buckled under manually applied linear force and produced no visible elevation of the erection angle while the patient was standing. In the 12 patients (ages ranged from thirtytwo to sixty-seven years), all had incomplete coital erections or loss of sleep-related erections; and none experienced “fullness” with the initial test of 30 mg of papaverine or lost the erections after having used papaverine for one to six months. Patients were reinjected with 5 pg to 20 pg of prostaglandin Ei in 1 to 3 cc of normal saline at 4°C using a pre-cooled syringe and a 30G needle in the same sites and with the same technique as used with papaverine. After ten to twenty minutes, the effect of the injection was evaluated. None of the patients experienced any of the expected side effects such as headaches, flushing, nausea, or abdominal cramps. In 1 patient, transitory pain was felt at the injection site of a Peyronie plaque. Phentolamine was not used. Patients signed informed consent forms similar to those used for papaverine.
1
15
Results In all 12 patients, the quality of their erections was reported to be more than adequate for intercourse by both an objective observer and the patients themselves. The duration of this artificial erection lasted between twenty minutes and two hours. The superficial veins, the corpora spongiosa, and glans were noted to be engorged in 11 of the 12 patients to a degree never observed with papaverine. The 2 patients on self-injections are continuing in the home program using prostaglandin El. Of the 10 patients, 5 have decided to join the home self-injection program using prostaglandin E1 because they had experienced better erections between injections.
the spongiosa, a structure which has been traditionally labeled as “not involved in erection.” Therefore, prostaglandin El may be a good tool for studying the role of the spongiosa and the glans in the regulation of blood flow during erection.a The spongiosa is the largest and most readily visible arteriovenous shunt that is present in the penis. Assuming hydraulic competency or “no venous leak,” prostaglandin E, activates the venoocclusive mechanism independently of the cavernous artery9 much as papaverine does. It may also provide an additional stimulus to blood flow that allows vast amounts of blood to flow from the urethral bulb artery and corpora spongiosa into the cavernosal bodies. 142 East 16th Street New York. New York 10003
Comment The mechanism of prostaglandin El in producing erection is due to smooth muscle relaxation and vasodilation. The results are so encouraging that this form of treatment could replace any other form of self-injection therapy, since the solution is not acid as is papaverine and gives the penis a more natural look during the erection. The response to this vasoactive medication is slower and is of shorter duration than papaverine, allowing less chance for prolonged erection to occur. Prostaglandin El has interesting healing properties such as reducing inflammation, inhibiting platelet aggregation, preventing tissue damage, and stabilizing lysosome proteases. These properties may be useful in preventing the occasional papaverine-induced priapism and reducing the potential for fibrosis or Peyronie disease that might result from the injections. There are visible clinical changes that indicate that prostaglandin Er increases blood into
16
References 1. Althof SE, et al: Intracavernous injection in the treatment of impotence: a prospective study, J Sex Marital Ther 13: 155 (1987). 2. Nellans RE, and Kramer-Levien D: Pharmacological erection: diagnosis treatment applications in 69 patients, J Urol 138: 520 (1987). 3. Reiss H: Rescuing papaverine-failed erections, Third Biennial World Meeting on Impotence, Boston, October 6-9, 1988. 4. Hedlund H, and Andersson K-E: Contraction and relaxation induced by some prostanoids in isolated human penile tissue and cavernous artery, J Urol 134: 1245 (1985). 5. Ishii N, et al: Studies on male sexual impotency, Report 18: Therapeutic trial with prostaglandin El for organic impotency, NiDDOD Hinvokika Gakkia Zasshi 77: 954 (1986). 6: Virag R, and Adaikan PC: Effects of prostaglandin Er on penile erection and erectile failure (letter), J Urol 137: 1010 (1987). 7. Carlson LA, and Olsson AG: PGEl in ischemic peripheral vascular disease, in: Karim SMM (Ed): Practical Applications of Prostaglandins and Their Synthesis Inhibitors. Baltimore, University Park Press, chap 3, 1979, pp 39-51. 8. Reiss H: The role of spongiosography in study of penile veins, Urology 29: 146 (1987). 9. Delacour C, et al: The effect of papaverine on arterial and venous hemodynamics of erection, J Urol 138: 187 (1987).
UROLOGY
I
JANUARY
1989
I
VOLUME
XxX111, NUMBER
1