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Management of Recurrent Priapism With Epinephrine Self-Injection and Gonadotropin-Releasing Hormone Analogue
0022-5347/95/153 1-0152$03.00/0 Tm:JOURNAL OF UROLOGY Copyright 0 1995 by AMERICAN UROLOGIC& ASSOCIATION,INC.
Vol. 153,152-153,January 1995 Printed in V.S.A.
MANAGEMENT OF RECURRENT PRIAPISM WITH EPINEPHRINE SELFINJECTION AND GONADOTROPIN-RELEASING HORMONE ANALOGUE JEFFREY STEINBERG*
AND
ROBERT C . EYRE
From the Division of Urology, Deaconess Hospital and Haruard Medical School, Boston, Massachusetts
ABSTRACT
A case of recurrent priapism in a young black man without sickle cell anemia is reported. Due to almost daily episodes of prolonged painful erections, the patient was instructed in intracorporeal injection using an epinephrine self-injection kit, which provided complete detumescence on 31 occasions. The patient refused surgical intervention and was treated with monthly intramuscular gonadotropin-releasinghormone analogue. Priapism episodes completely abated by the second and final monthly gonadotropin-releasinghormone analogue injection without recurrence during 4 months of followup. Normal erectile function was maintained during and after gonadotropin-releasing hormone analogue therapy. Epinephrine self-injection and gonadotropinreleasing hormone analogue may be effective treatment modalities in select cases of recurrent priapism. KEYWORDS:priapism, pituitary hormone-releasing hormones, epinephrine,trazodone, penis
Priapism is a difficult clinical problem which, if not treated in a timely fashion, can result in permanent erectile dysfunction. Intracorporeal injection of an a-adrenergic agent is commonly used to achieve detumescence. We report a case of recurrent priapism that was treated by self-injection of epinephrine using a commercially available injection kit. Due to frequent recurrences the patient elected to undergo a limited course of treatment with a gonadotropin-releasing hormone analogue. The priapism episodes subsequently resolved with preservation of normal erectile function during and after treatment with gonadotropin-releasing hormone analogue. CASE REPORT
K. W., a 32-year-old black man, presented to the emergency room with a sustained painful erection 25Vz hours in duration after sexual intercourse. Due to feelings of depression he had taken 1 nonprescribed dose of 50 mg. trazodone hydrochloride 12 hours before this episode. He denied any previous episodes of sustained erections or previous use of trazodone. Medical history was otherwise unremarkable. Physical examination was notable for bilaterally rigid corpora cavernosa with a soft glans and corpus spongiosum. After initial aspiration of the corpora and hand irrigation with 1 1. dilute epinephrine solution (0.3 mg. in 1 1. normal saline) only partial detumescence was achieved. He was subsequently hospitalized for continuous corporeal irrigation with this solution via bilateral 21 gauge butterfly needles at the rate of 50 cc per hour. Full detumescence was achieved within 36 hours. Chemistry studies, complete blood count and coagulation studies were normal. Hemoglobin electrophoresis was negative for sickle cell anemia. The patient presented 6 weeks later with recurrent priapism 12 hours in duration. He denied any further medication ingestion since the initial episode of priapism. ARer hospitalization and corporeal irrigation with epinephrine the erection fully subsided within 16 hours. Repeat hemoglobin electrophoresis was again negative for sickle cell hemoglobin. The patient presented an additional 6 times in the next 2 months with prolonged erections more than 3 hours in duration, mostly occurring in the morning without sexual activity. These episodes were treated with oral nifedipine and intraAccepted for publication March 25, 1994. * Requests for reprints: Division of Urology, Suite 6E, 110 Francis St., Boston, Massachusetts 02215.
muscular narcotics with limited success. Simple intracorporeal injection of 1 cc 1/1,000 (0.3 mg.) epinephrine solution was repeatedly successful without the need for aspiration or prolonged irrigation. These injections were performed in the emergency room with continuous blood pressure monitoring; hospital admission was not required. Further outpatient diagnostic evaluation included abdominal and pelvic computerized tomography, which was negative for occult abdominal or pelvic pathology. Due to the increasing frequency of priapism episodes the patient was taught to self-inject the phallus with 0.3 mg. epinephrine using an auto-injector designed for allergic reactions and anaphylaxis. He successfully performed self-injection with full detumescence 23 times during the next 45 days. The only reported side effect from epinephrine injection was a mild headache, which resolved with acetaminophen. Since sustained erections were occurring almost daily the patient was offered surgical intervention with a corpora cavernosa to corpus spongiosum shunting procedure. He refused surgery due to the fear of permanent erectile dysfunction. However, he consented t o hormonal intervention with intramuscular injection of 7.5 mg. leuprolide acetate. Only 9 prolonged erections occurred during the ensuing month in the first 10 days after leuprolide injection and they fully resolved with self-injection of epinephrine. One month after the first leuprolide injection total serum testosterone was 12 ng./dl. (normal 270 to 1,070). After the second and final monthly injection priapism did not recur. Libido remained normal during the 2 months of leuprolide therapy and the patient was able to engage in intercourse without prolonged erection. He denied any significant side effects, such a s the hot flashes, gynecomastia or edema occasionally associated with hormonal therapy. At followup 4 months after cessation of therapy erections continue to be adequate for intercourse without prolonged tumescence. No further treatment has been necessary. DISCUSSION
Priapism is the occurrence of a prolonged painful erection without sexual stimulation, which does not resolve with ejaculation. Several predisposing factors have been identified, including sickle cell anemia, occult malignancy, pelvic trauma and ingestion of medication. A large group of patients have idiopathic priapism with no identifiable cause. As many 152
EPINEPHRINE SELF-INJECTIONAND GONADOTROPIN-RELEASING HORMONE ANALOGUE FOR PRIAPISM
as 30% of cases of priapism may occur as a result of ingestion of medication, including antipsychotics, antidepressants, antihypertensives, hypnotics and anticoagulants.' Patients who perform intracorporeal injection of vasoactive agents for the treatment of erectile dysfunction are a growing segment of the population with drug-induced priapism. Since 1983 trazodone hydrochloride, an antidepressant, has been associated with priapism.' Its a-adrenergic blocking action, which causes impairment of corporeal smooth muscle contraction, has been implicated as the mechanism of sustained ere~tion.~ Various medical and surgical therapies exist for the treatment of priapism. A common intervention consists of intracorporeal instillation or irrigation with an a-adrenergic agonist. Epinephrine is a commonly used agent for this treatment despite its marked /3-adrenergic side effects of tachycardia and hypertension. This drug is readily available in most emergency rooms. For patients at risk for anaphylaxis or allergic reactions epinephrine is available by prescription in ready to use self-injection form. Currently, no pure a-adrenergic agent is commercially available in this prepackaged form for self-administration. The injection technique is easily learned by most patients without any previous medical background. Our patient used the auto-injector for corporeal instillation for recurrent episodes of priapism. During injection he was instructed to place the needle deeply into the cavernosal body and feel for the characteristic puncture of the tunica albuginea to ensure proper placement of the medication. He became quite adept at the technique, achieving full detumescence on all injections. One previous report described a patient who lived on an island without emergency services who performed this self-injection technique with epinephrine for recurrent priapism? Hauri et a1 were the first to categorize priapism into high and low flow state^.^ High flow priapism is characterized by adequate arterial inflow but a postulated defect in autonomic regulation prevents detumescence. Low flow priapism occurs due to failure of contraction of corporeal smooth muscle, leading to stasis and sludging of blood within the cavernosal sinusoids. Lue et a1 further characterized these types of priapism as nonischemic and ischemic states, depending on intracorporeal pressure monitoring and blood gas determinatiomx6 Although these determinations were not performed in our patient, initial presentation was most consistent with high flow (nonischemic)priapism based on the appearance of bright red blood on corporeal aspiration and repeatedly prompt response to the a-adrenergic agent. Abber et al found that intracorporeal injection of trazodone in dogs was associated with increases in intracorporeal pressure, and arterial inflow and venous outflow oc~lusion.~ Although trazodone ingestion appears to be the precipitating factor in the initial presentation, the numerous subsequent episodes in our case occurred without further medication. The etiology of these recurrences may be explained by the development of corporeal smooth muscle fibrosis from the initial prolonged episode. Repeated episodes may have propagated further cavernosal fibrosis. Ultimately, smooth muscle contractility may have been significantly impaired, resulting in abnormally high compliance of cavernosal sinusoids. Hormonal manipulation for treatment of recurrent priapism was initially described by Sejeant et al in 1985 for patients with sickle cell anemia.7 These episodes of "stuttering" priapism generally lasted 2 to 6 hours and responded to treatment with diethylstilbestrol. Although the mechanism was not fully elucidated, these authors postulated a neutralizing effect on the male hormonal axis or a possible direct cellular alteration of the defective sickled erythrocytes by diethylstilbestrol. Gonadotropin-releasing hormone ana-
153
logues were used by Levine and Guss for recurrent priapism Ln a patient with sickle cell anemia who was treated for more than 1 year with a tapering monthly dose of leuprolide acetate.' Although libido was maintained, he had no erectile function with a total serum testosterone level of less than 20 ng./dl. When the authors suspended gonadotropin-releasing hormone analogue therapy priapism recurred. The patient elected to continue treatment rather than risk recurrent episodes of priapism. To our knowledge our patient was the first without sickle cell disease to be treated with a gonadotropin-releasing hormone analogue for recurrent priapism. The duration of priapism episodes was initially significantly longer (up to 251/2 hours) than the short "stuttering" pattern noted in the 2 previous reports on sickle cell patients. In addition, despite short followup priapism has not recurred after discontinuation of therapy. Although intracorporeal self-injection was effective in achieving detumescence, the frequency of these injections was burdensome to our patient and was not an optimal long-term solution. Fearing permanent erectile dysfunction from a surgical shunting procedure, he consented to gonadotropin-releasing hormone analogue administration, realizing that it was a temporary form of chemical castration. During leuprolide therapy libido and erectile function were surprisingly well preserved despite a serum testosterone level in the castrate range. Similarly, preservation of sexual function has been reported in patients undergoing various forms of hormonal therapy for prostate cancer. In s u m m a r y , we report on a patient with recurrent priapism and no sickle cell disease who was treated with a combination of intracorporeal epinephrine self-injection and intramuscular gonadotropin-releasing hormone analogue. After proper instruction, commercially available epinephrine self-injection kits may be a safe treatment tool in otherwise healthy patients with recurrent priapism. However, this modality must be used with extreme caution in patients with cardiovascular disease, cardiac arrhythmia or hypertension. Initiation of this therapy should be considered only after a thorough medical evaluation, instruction in proper injection technique and discussion of possible adverse reactions. Gonadotropin-releasing hormone analogue therapy is an attractive option for short-term or long-term therapy for recurrent priapism. In our case sexual function was preserved during therapy. In addition, it may be optimal therapy in those patients who are concerned about future sexual dysfunction from surgical intervention. REFERENCES
1. Baiios,J. E., Bosch, F. and F a d , M.: Drug-induced priapism.Its aetiology, incidence and treatment. Med. Toxicol. Adverse Drug Exp., 4: 46,1989. 2. Scher, M.,Krieger, J. N. and Juergens, S.: Trazodone and priapism. Amer. J. Psychiat., 140: 1362,1983. 3. Abber, J. C., Lue, T. F., Luo, J.-A, Juenemann, K-P. and Tanagho, E. A.: Priapism induced by chlorpromazine and trazodone: mechanism of action. J. Urol., 131: 1039,1987. 4. van Driel, M.F., Joosten, E. A. and Mensink, H. J.: Intracorporeal self-injectionwith epinephrine as treatment for idiopathic recurrent priapism. Eur. Urol., 11: 95,1990. 5. Hauri, D.,Spycher, M. and Briihlmann, W.: Erection and priapism: a new physiopathological concept. Urol. Int., 38: 138, 1983. 6. Lue, T. F., Hellstrom, W. J. G., McAninch, J. W. and Tanagho, E. A.: Priapism: a refined approach to diagnosis and treatment. J. Urol., 1 3 6 104,1986. 7. Sejeant, G.R.,deCeulaer,K. and Maude, G. H.: Stilboestroland stuttering priapism in homozygous sicklesell disease. Lancet, 2 1274,1985. 8. Levine, L. A. and Guss,S. P.: Gonadotropin-releasing hormone analogues in the treatment of sickle cell anemia-associated priapism. J. Urol., 1M): 475,1993.
Vol. 153,152-153,January 1995 Printed in V.S.A.
MANAGEMENT OF RECURRENT PRIAPISM WITH EPINEPHRINE SELFINJECTION AND GONADOTROPIN-RELEASING HORMONE ANALOGUE JEFFREY STEINBERG*
AND
ROBERT C . EYRE
From the Division of Urology, Deaconess Hospital and Haruard Medical School, Boston, Massachusetts
ABSTRACT
A case of recurrent priapism in a young black man without sickle cell anemia is reported. Due to almost daily episodes of prolonged painful erections, the patient was instructed in intracorporeal injection using an epinephrine self-injection kit, which provided complete detumescence on 31 occasions. The patient refused surgical intervention and was treated with monthly intramuscular gonadotropin-releasinghormone analogue. Priapism episodes completely abated by the second and final monthly gonadotropin-releasinghormone analogue injection without recurrence during 4 months of followup. Normal erectile function was maintained during and after gonadotropin-releasing hormone analogue therapy. Epinephrine self-injection and gonadotropinreleasing hormone analogue may be effective treatment modalities in select cases of recurrent priapism. KEYWORDS:priapism, pituitary hormone-releasing hormones, epinephrine,trazodone, penis
Priapism is a difficult clinical problem which, if not treated in a timely fashion, can result in permanent erectile dysfunction. Intracorporeal injection of an a-adrenergic agent is commonly used to achieve detumescence. We report a case of recurrent priapism that was treated by self-injection of epinephrine using a commercially available injection kit. Due to frequent recurrences the patient elected to undergo a limited course of treatment with a gonadotropin-releasing hormone analogue. The priapism episodes subsequently resolved with preservation of normal erectile function during and after treatment with gonadotropin-releasing hormone analogue. CASE REPORT
K. W., a 32-year-old black man, presented to the emergency room with a sustained painful erection 25Vz hours in duration after sexual intercourse. Due to feelings of depression he had taken 1 nonprescribed dose of 50 mg. trazodone hydrochloride 12 hours before this episode. He denied any previous episodes of sustained erections or previous use of trazodone. Medical history was otherwise unremarkable. Physical examination was notable for bilaterally rigid corpora cavernosa with a soft glans and corpus spongiosum. After initial aspiration of the corpora and hand irrigation with 1 1. dilute epinephrine solution (0.3 mg. in 1 1. normal saline) only partial detumescence was achieved. He was subsequently hospitalized for continuous corporeal irrigation with this solution via bilateral 21 gauge butterfly needles at the rate of 50 cc per hour. Full detumescence was achieved within 36 hours. Chemistry studies, complete blood count and coagulation studies were normal. Hemoglobin electrophoresis was negative for sickle cell anemia. The patient presented 6 weeks later with recurrent priapism 12 hours in duration. He denied any further medication ingestion since the initial episode of priapism. ARer hospitalization and corporeal irrigation with epinephrine the erection fully subsided within 16 hours. Repeat hemoglobin electrophoresis was again negative for sickle cell hemoglobin. The patient presented an additional 6 times in the next 2 months with prolonged erections more than 3 hours in duration, mostly occurring in the morning without sexual activity. These episodes were treated with oral nifedipine and intraAccepted for publication March 25, 1994. * Requests for reprints: Division of Urology, Suite 6E, 110 Francis St., Boston, Massachusetts 02215.
muscular narcotics with limited success. Simple intracorporeal injection of 1 cc 1/1,000 (0.3 mg.) epinephrine solution was repeatedly successful without the need for aspiration or prolonged irrigation. These injections were performed in the emergency room with continuous blood pressure monitoring; hospital admission was not required. Further outpatient diagnostic evaluation included abdominal and pelvic computerized tomography, which was negative for occult abdominal or pelvic pathology. Due to the increasing frequency of priapism episodes the patient was taught to self-inject the phallus with 0.3 mg. epinephrine using an auto-injector designed for allergic reactions and anaphylaxis. He successfully performed self-injection with full detumescence 23 times during the next 45 days. The only reported side effect from epinephrine injection was a mild headache, which resolved with acetaminophen. Since sustained erections were occurring almost daily the patient was offered surgical intervention with a corpora cavernosa to corpus spongiosum shunting procedure. He refused surgery due to the fear of permanent erectile dysfunction. However, he consented t o hormonal intervention with intramuscular injection of 7.5 mg. leuprolide acetate. Only 9 prolonged erections occurred during the ensuing month in the first 10 days after leuprolide injection and they fully resolved with self-injection of epinephrine. One month after the first leuprolide injection total serum testosterone was 12 ng./dl. (normal 270 to 1,070). After the second and final monthly injection priapism did not recur. Libido remained normal during the 2 months of leuprolide therapy and the patient was able to engage in intercourse without prolonged erection. He denied any significant side effects, such a s the hot flashes, gynecomastia or edema occasionally associated with hormonal therapy. At followup 4 months after cessation of therapy erections continue to be adequate for intercourse without prolonged tumescence. No further treatment has been necessary. DISCUSSION
Priapism is the occurrence of a prolonged painful erection without sexual stimulation, which does not resolve with ejaculation. Several predisposing factors have been identified, including sickle cell anemia, occult malignancy, pelvic trauma and ingestion of medication. A large group of patients have idiopathic priapism with no identifiable cause. As many 152
EPINEPHRINE SELF-INJECTIONAND GONADOTROPIN-RELEASING HORMONE ANALOGUE FOR PRIAPISM
as 30% of cases of priapism may occur as a result of ingestion of medication, including antipsychotics, antidepressants, antihypertensives, hypnotics and anticoagulants.' Patients who perform intracorporeal injection of vasoactive agents for the treatment of erectile dysfunction are a growing segment of the population with drug-induced priapism. Since 1983 trazodone hydrochloride, an antidepressant, has been associated with priapism.' Its a-adrenergic blocking action, which causes impairment of corporeal smooth muscle contraction, has been implicated as the mechanism of sustained ere~tion.~ Various medical and surgical therapies exist for the treatment of priapism. A common intervention consists of intracorporeal instillation or irrigation with an a-adrenergic agonist. Epinephrine is a commonly used agent for this treatment despite its marked /3-adrenergic side effects of tachycardia and hypertension. This drug is readily available in most emergency rooms. For patients at risk for anaphylaxis or allergic reactions epinephrine is available by prescription in ready to use self-injection form. Currently, no pure a-adrenergic agent is commercially available in this prepackaged form for self-administration. The injection technique is easily learned by most patients without any previous medical background. Our patient used the auto-injector for corporeal instillation for recurrent episodes of priapism. During injection he was instructed to place the needle deeply into the cavernosal body and feel for the characteristic puncture of the tunica albuginea to ensure proper placement of the medication. He became quite adept at the technique, achieving full detumescence on all injections. One previous report described a patient who lived on an island without emergency services who performed this self-injection technique with epinephrine for recurrent priapism? Hauri et a1 were the first to categorize priapism into high and low flow state^.^ High flow priapism is characterized by adequate arterial inflow but a postulated defect in autonomic regulation prevents detumescence. Low flow priapism occurs due to failure of contraction of corporeal smooth muscle, leading to stasis and sludging of blood within the cavernosal sinusoids. Lue et a1 further characterized these types of priapism as nonischemic and ischemic states, depending on intracorporeal pressure monitoring and blood gas determinatiomx6 Although these determinations were not performed in our patient, initial presentation was most consistent with high flow (nonischemic)priapism based on the appearance of bright red blood on corporeal aspiration and repeatedly prompt response to the a-adrenergic agent. Abber et al found that intracorporeal injection of trazodone in dogs was associated with increases in intracorporeal pressure, and arterial inflow and venous outflow oc~lusion.~ Although trazodone ingestion appears to be the precipitating factor in the initial presentation, the numerous subsequent episodes in our case occurred without further medication. The etiology of these recurrences may be explained by the development of corporeal smooth muscle fibrosis from the initial prolonged episode. Repeated episodes may have propagated further cavernosal fibrosis. Ultimately, smooth muscle contractility may have been significantly impaired, resulting in abnormally high compliance of cavernosal sinusoids. Hormonal manipulation for treatment of recurrent priapism was initially described by Sejeant et al in 1985 for patients with sickle cell anemia.7 These episodes of "stuttering" priapism generally lasted 2 to 6 hours and responded to treatment with diethylstilbestrol. Although the mechanism was not fully elucidated, these authors postulated a neutralizing effect on the male hormonal axis or a possible direct cellular alteration of the defective sickled erythrocytes by diethylstilbestrol. Gonadotropin-releasing hormone ana-
153
logues were used by Levine and Guss for recurrent priapism Ln a patient with sickle cell anemia who was treated for more than 1 year with a tapering monthly dose of leuprolide acetate.' Although libido was maintained, he had no erectile function with a total serum testosterone level of less than 20 ng./dl. When the authors suspended gonadotropin-releasing hormone analogue therapy priapism recurred. The patient elected to continue treatment rather than risk recurrent episodes of priapism. To our knowledge our patient was the first without sickle cell disease to be treated with a gonadotropin-releasing hormone analogue for recurrent priapism. The duration of priapism episodes was initially significantly longer (up to 251/2 hours) than the short "stuttering" pattern noted in the 2 previous reports on sickle cell patients. In addition, despite short followup priapism has not recurred after discontinuation of therapy. Although intracorporeal self-injection was effective in achieving detumescence, the frequency of these injections was burdensome to our patient and was not an optimal long-term solution. Fearing permanent erectile dysfunction from a surgical shunting procedure, he consented to gonadotropin-releasing hormone analogue administration, realizing that it was a temporary form of chemical castration. During leuprolide therapy libido and erectile function were surprisingly well preserved despite a serum testosterone level in the castrate range. Similarly, preservation of sexual function has been reported in patients undergoing various forms of hormonal therapy for prostate cancer. In s u m m a r y , we report on a patient with recurrent priapism and no sickle cell disease who was treated with a combination of intracorporeal epinephrine self-injection and intramuscular gonadotropin-releasing hormone analogue. After proper instruction, commercially available epinephrine self-injection kits may be a safe treatment tool in otherwise healthy patients with recurrent priapism. However, this modality must be used with extreme caution in patients with cardiovascular disease, cardiac arrhythmia or hypertension. Initiation of this therapy should be considered only after a thorough medical evaluation, instruction in proper injection technique and discussion of possible adverse reactions. Gonadotropin-releasing hormone analogue therapy is an attractive option for short-term or long-term therapy for recurrent priapism. In our case sexual function was preserved during therapy. In addition, it may be optimal therapy in those patients who are concerned about future sexual dysfunction from surgical intervention. REFERENCES
1. Baiios,J. E., Bosch, F. and F a d , M.: Drug-induced priapism.Its aetiology, incidence and treatment. Med. Toxicol. Adverse Drug Exp., 4: 46,1989. 2. Scher, M.,Krieger, J. N. and Juergens, S.: Trazodone and priapism. Amer. J. Psychiat., 140: 1362,1983. 3. Abber, J. C., Lue, T. F., Luo, J.-A, Juenemann, K-P. and Tanagho, E. A.: Priapism induced by chlorpromazine and trazodone: mechanism of action. J. Urol., 131: 1039,1987. 4. van Driel, M.F., Joosten, E. A. and Mensink, H. J.: Intracorporeal self-injectionwith epinephrine as treatment for idiopathic recurrent priapism. Eur. Urol., 11: 95,1990. 5. Hauri, D.,Spycher, M. and Briihlmann, W.: Erection and priapism: a new physiopathological concept. Urol. Int., 38: 138, 1983. 6. Lue, T. F., Hellstrom, W. J. G., McAninch, J. W. and Tanagho, E. A.: Priapism: a refined approach to diagnosis and treatment. J. Urol., 1 3 6 104,1986. 7. Sejeant, G.R.,deCeulaer,K. and Maude, G. H.: Stilboestroland stuttering priapism in homozygous sicklesell disease. Lancet, 2 1274,1985. 8. Levine, L. A. and Guss,S. P.: Gonadotropin-releasing hormone analogues in the treatment of sickle cell anemia-associated priapism. J. Urol., 1M): 475,1993.