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Comparative Results of Goal Oriented Therapy for Erectile Dysfunction
0022-5347/97/1576-2 135$03.00/0 JOURNAL OF UHOI.OGY
Vol. 157.2135-2138,June 1997 Printed in V.SA
&pyright 0 1997 by AMEMICAN UROLOGICAL ASSCCIATION, INC
COMPAFUTNE RESULTS OF GOAL ORIENTED THERAPY FOR ERECTILE DYSFUNCTION KAMAL A. M A S H * From the Urology and Impotence Center of Northern Virginia, McLean, Virginia
ABSTRACT
Purpose: Goal oriented therapy for erectile dysfunction, based on a complete education of the couple, was offered to 460 patients. The short-term and long-term results of the first and second treatments selected were compared. Materials and Methods: From September 1991 to March 1995, 460 patients with erectile dysfunction were evaluated and treated prospectively. The success of treatment, selected by the patient or couple, was defined as the ability to achieve and maintain good erections for successful coitus for at least 1year after the start of therapy. Sexual satisfaction of the couple was required to confirm a successful outcome. Results: The preferred first line of treatment by 322 patients was pharmacotherapy, with intracavernous injections being the second most selected therapy (80% success rate). However, there was a high long-term dropout rate for intracavernous injections. Approximately 70% of the patients were lost to followup or refused further treatment. Conclusions: Overall, this prospective study showed that goal oriented therapy is initially highly successful. However, the long-term high dropout rate and dissatisfaction of the couple cast doubt about the efficacy of the present treatment options. KEYWORDS: penile erection, impotence, penile prosthesis, prostaglandins E, drug therapy
A better understanding of the pathophysiology of erectile dysfunction has recently led to marked improvement in the diagnosis and treatment of this common health problem. Controversy prevails regarding the optimal diagnostic evaluation and proper therapy. Pathology oriented therapy is based on a thorough investigation to establish a diagnosis and tailor the treatment to a specific cause.1 On the other hand, goal oriented therapy relies on a minimum diagnostic evaluation and stratificationof all treatment options that are offeredto the patient for selection.2The advantages of goal oriented therapy include simplicity, a high success rate, lower risk and cost, and better acceptance by the couple. The major disadvantage is that reversible causes that may be treated specificallymay be missed. Several reports have conb e d the popularity, efficacy and high success rate of goal oriented therapy.*4 In a recent study pharmacotherapy was preferred by the majority of ~ a t i e n t sWe . ~ report our experience with goal oriented therapy, and compare the short-term and long-term results of various therapeutic modalities. MATERIALS AND METHODS
From September 1991 to March 1995,460patients (mean age 52 years, range 21 to 82) with erectile dysfunction at least 6 months in duration were evaluated and treated. A minimum of 1 year of followup and no previous therapy for =ma1 dysfunction were required for inclusion in this prospective study. Emphasis was placed on a detailed history and complete physical examination. A thorough interview, supplemented by a written questionnaire, was performed with the patient and sexual partner, when available.Medical history focused on diabetes mellitus or other endocrine diseases, trauma to the genitalia or perineum, cardiovascularor neurological diseases, and operations. Use of prescribed medications, nicotine consumption, alcohol or drug abuse and Accepted for ublication k e m b e r 6, 1996.
* Current adxress: Department of Urology, King F a i d Specialist Hosp~ta~ & Research Center, P.O. Box 3354, Riyadh, 11211, Kingdom of Saudi Arabia.
sleep disorders were carefully recorded. Other asof sexual dysfunction, such as loss of libido, premature ejaculation, ejaculatory incompetence, anorgasmy or dry ejaculation, were not included. The sexual problems of the partner were discussed. Psychological disorders and marital conflicts were properly screened. A complete physical examination with particular focus on the vascular, endocrine, neurological and genital systems was performed. Biothesiometryand qualitative Doppler evaluation of penile blood flow were used as screening tests in all patients. A visual sexual stimulation test (erotic videotape) with or without intracavernous injection of prostaglandin El or the triple drug mixture of prostaglandin, papaverine and phentolamine was done, if acceptable by the couple and not medically contraindicated.Laboratory investigation included determination of serum fasting glucose, glycosylated hemoglobin, cholesterol profile and urinalysis. Total and free serum testosterone levels were determined in all patients older than 50 years and in those with low libido. Additional laboratory tests were requested based on the history and physical findings. If serum testosterone, luteinizing hormone and follicle-stimulatinghormone were decreased or serum prolactin was elevated on at least 2 determinations magnetic resonance imaging of the brain and pituitary gland was requested. A 4-glass test with a smear and culture of the prostatic secretions were performed if prostatitis was suspected. Treatment, if sought by the couple, was usually tailored to the etiology of the erectile dysfunction if a reversible etiological factor was suspected or found. Reversible causes, such as hypogonadism with a low free serum testosterone, other endocrine disturbances involving the thyroid or pituitary glands, prescribed medications, alcohol, nicotine or drug abuse and genital anomalies (chordee), were specifically treated. Diabetes, hypercholesterolemia and cardiovascular diseases were treated concomitantlywith therapy for sexual dysfunction.Patients also ceased smoking or drug abuse and were treated for alcoholism.
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GOAL ORIENTED THERAPY FOR ERECTILE DYSFUNCTION
Pharmacotherapy was used empirically based on the reMen with psychogenic erectile dysfunction initially underwent psychological counseling, sex therapy and pharmaco- ported success rate. In the early years of the study yohimbine therapy. In case of failure other treatment methods, such as and isoxsuprine were the agents of choice. In the last 2 years intracavernous injections and vacuum constriction devices, trazodone alone or combined with yohimbine was preferred. were used. All therapeutic options were initially offered to Most patients were reassessed 4 to 8 weeks after the start of the couple with a thorough discussion of the success rates, therapy, and every 3 months thereafter. For those whose possible risks, side effects, complications and cost, respec- original therapy failed other treatment options were offered tively. Videotapes, charts, diagrams and written materials (table 1). Therapeutic success was defined as the ability to were provided. The techniques of intracavernous injections achieve and maintain a rigid erection of good quality for and use of the vacuum device were demonstrated in the successful vaginal penetration for at least 1 year, leading to office. Written informed consent was obtained before injec- the sexual satisfaction of the couple. Patients whose chosen therapy failed or who dropped out of the study or were lost to tions. The triple drug solution contained 10 pgJml. prostaglan- followup were considered to have treatment failure. din E l , 0.6 mgjml. papaverine and 0.1 mg./ml. phentolRESULTS amine. An arbitrary dose of 0.25 ml. of the solution was injected in patients with nonneurological erectile dysfuncDiabetes mellitus and vascular diseases were the most tion. For those suspected to have a neurological etiology common major medical conditions associated with erectile according to history,physical examination and biothesiomet- dysfunction in this series (table 2). However, it should be ric findings a lower dose of 0.15 cc was initially administered. stressed that no particular effort was made to reach a precise If the initial response was positive with the development of a diagnosis. The initial choice of treatment for the majority of rigid erection for at least 30 minutes, which almost excluded patients was pharmacotherapy despite an extensive discusa significant venous leak and severe penile arterial disease, sion regarding the controversial aspect of such therapy (table the couple was offered first line therapeutic options of non- 3). Trazodone alone or with yohimbine yielded the best recoital sexual gratification, pharmacotherapy, vacuum con- sults in patients without hypogonadism (table 4). In those striction device, intracavernous injections and/or sexual ther- whose initial therapy failed the treatment of choice was intapy plus pharmacotherapy. Properly dosed syringes or vials racavernous injections (table 1). More than 85% of the pawith the triple drugmixture were periodically provided to the tients required 0.25 to 0.75 cc (mean 0.5)of the triple drug patient. Ifthere was no response to the initial intracavernous mixture. Patients with neurological erectile dysfunction injection, additional injections of the solution in increments achieved successful intercourse with a lesser dose (mean 0.3 of O.25 were given at subsequent Visits. In case of a partid or cc). The vacuum device was successful in approximately 65% no response to 1 ml. of the triple drug solution, and provided of the patients. Penile prostheses were initially selected by 14 that the patient was younger than 50 years with occlusion of patients and as a second line treatment by 10. Multiple the pudendal, penile or cavernous artery secondary to penile component inflatable penile prostheses were preferred by 19 or perineal trauma and with no history of diabetes mellitus, patients, while 5 received malleable devices. The success rate hypercholesterolemia, atherosclerosis or nicotine abuse, color was approximately 83%. There was no incidence of infection duplex Doppler sonography with intracavernous injection of after insertion of the prostheses. The 2 complications in10 pg. prostaglandin E was performed to exclude penile cluded a mechanical failure due to kinking of the right tube vascular occlusion or a venous leak. The latter test w a ~ from the cylinder to the pump with Ultrex* inflatable prosperformed in only 9 patients who were willing to undergo theses, and insufficient firmness with a Mark I1 Mentort vascular surgery. An arterial peak flow of 30 ml. per second prosthesis. In patients whose initial therapy failed the treator more in the central arteries was used to exclude arterial ment of choice was intracavernous injections (table 1). disease. Pudendal arteriography was requested before arteFew side effects occurred with the injections, with priarial microvascular surgery. If veno-occlusive disease was sus- pism occurring in 1%,pain in 10% and corporeal fibrosis in pected on color duplex Doppler sonography, with a peak end 4% of the patients. The dropout rate was 40% after 12 diastolic flow of more than 4.5 ml. per second in the phase of months and 73% within 43 months. Most patients were lost maximal erectile response, therapeutic options included vac- to followup and did not respond to our inquiry regarding the uum constrictive devices, surgical venous ligation or penile reasons for dropout. The major reasons for dropout in 93 prostheses. If the patient elected venous ligation, caverno- responders were recovery of spontaneous erections in 13 pasometry and cavernosography with injection of 10 pg. pros- tients (14%), cost of the injection (approximately $10 per taglandin E or more were performed to achieve a fullerection injection of triple drug solution) in 30 (32%), patient and preoperatively. Vascular surgery consisted of microvascular partner discontent in 25 (27%), lack of sexual spontaneity anastomosis of the epigastric artery to the deep dorsal vein in and naturalism in 22 (24%) and no sexual partner in 3 (3%). 2 cases and ligation of leaking penile veins in 7. Penile In contrast, the dropout rate for the vacuum constriction prostheses were initially selected by a minority of patients device was greater than 30% in 2 years. Few minor compliand as a last resort in patients in whom other treatment cations were reported with pharmacotherapy. Testosterone options failed. therapy was associated with 1 case of prostatic cancer with Reassurance and noncoital techniques for sexual gratifica- metastases. Microvascular surgery for penile arterial obtion were discussed with couples who were interested in sex struction failed after 6 months in 1 patient and 1 was lost to but who refused all of the aforementioned therapeutic op- followup. In 3 patients with veno-occlusive disease penile tions. Patients with penile sensory deficit on biothesiometry venous ligation successfully restored rigid erections but with and with no other neurological signs or symptoms were in- postoperative use of intracavernous injections in 2. The restructed on penile stimulation manually, orally or with a maining 4 patients could not achieve firm erections for SUCvibrator during coitus. Hypogonadism, with a low serum free cessful vaginal penetration despite additional use of intratestosterone on at least 2 determinations, was treated with cavernous injections in 3 and vacuum constrictive devices in 200 mg. sustained action testosterone intramuscularly every 1,respectively. Penile prostheses were inserted successfully 2 to 3 weeks, or 6 mg. scrota1 testosterone patches daily for 12 in 3 of these patients. Approximately 706 of the patients weeks or longer. The prostate was monitored periodically by were lost to followup or refused further therapy within 43 digital rectal examination and serum prostate specific anti- months. gen (PSA). Transrectal ultrasound with sextant prostatic biopsies was performed in patients with an abnormal PSA or * American Medical Systems, Minnetonka, Minnesota. digital rectal examination. t Mentor Corp., Santa Barbara, California.
GOAL ORIENTED THERAPY FOR ERECTILE DYSFUNCTION
TABLE1. Comparative success rates for second choice goal directed
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pharmacotherapy, vacuum devices or intracavernous injectiom6 With the ever increasing cost consciousness, a minimum diagnostic evaluation is tailored to the history and Treatment Total No. Pts. ( 8 ) No. Success (%) physical examination findings, which contrasts with the exIntracavernous injections 102 (46) 75 (73.5) tensive evaluation used for pathology oriented therapy, alVacuum constriction devices 25 (9.5) 17 (68) Penile prostheses 10 (4.5) 8 (80) though it may yield comparable success rates a t a higher risk LOSL to followup 75 (34) and cost, since it was demonstrated that the etiology rarely Refused therapy 9 (4) has an effect on treatment.7 Total No. (%I 221 (100) 100 (45) Microvascular shunt surgery is usually reserved for young patients with traumatic arterial penile obstruction. Strict TABLE2. Medical conditions associated with erectile dysfinction in criteria for inclusion are applied. Patients younger than 50 years with no risk factors and with traumatic obetruction in 460 patients the internal pudendal, common or distal penile arteries may Cause No. Pts.(96) expect a 50 to 60% success rate after arterial vascular surDiabetes mellitus 207 (45) gery.8-9 Venous ligation for abnormal venom leakage has Smoking 169 (37) gradually waned with poor long-term results,approaching20 Vascular 151 (33) Pure psychogenic 92 (20) to 30% except in highly select patienta.10 Our inability to Medications 84 (18) differentiate accurately between sinusoidal or smooth muscle Neurogenic 69 (15) disease, which is believed to constitute the main cause of Genital 51 (11) venous leakage, and other venoua penile disorders may be DNgS 50 (11) Radical surgery 46 (10) the primary reason for the high surgical failure rate. Endocrine 46 (10) Pharmacotherapy with yohimbine andlor trazdone was Hypercholesterolemia 28 (6) the preferred initial treatment in more than 70% of our Alcoholism 23 ( 5 ) patients. The success rates were approximately 55% for traMore than 1 cause may be attributed to a patient. d o n e alone or combined with yohimbine. These agents were particularly effective in patients with psychogenic or mildly TABLE3. Comparative success rates for first choice goal directed vascular erectile dysfunction. However, since no control theraov in 460 Datients with erectile dysfunction group was used, a placebo effect for these oral medications cannot be excluded. In controlled studies 21 to 62% complete Treatment Total No. Pts.(%) No. Sut%) recovery of erection was reported.11.12 The best response was Pharmacological 322 (70) 131 (41) found in patients with psychogenic erectile dysfunction, parIntracavernous injections 69 (15) 59 (85) Vacuum constriction device 38 (8) 24 (63) ticularly when combined with sex therapy and psychological Prostheses 14 (3) 12 (85) counseling. However, other studies revealed no statistical Vascular surgery 9 (2) 3 (30) difference between yohimbine and placebo.'* Trazodone, Noncoital techniques 8 (2) 5(26) which is usually used as an antidepressant, has been sucTotal No. (%) 460 (100) 239 (60) cessful in the management of erectile dysfunction in 40 to 60% of ~ases.13.1~ Its mechanism of action is still unknown but it is recognizedto increase the level of serotonin centrally TABLE4. Pharmacotherapy and comparative results in 322 at the level of the serotonin HT-IC receptor through repatients with erectile dysfunction uptake inhibition, and it possesses peripheral a-ganglionic Treatment Total No. pts. (5%) No. Suceesa (5%) blocking action. It may also act synergistically with yohimYohimbine and isoxsuprine 79 (25) 28 (35) bine.13 Further prospective matched controlled studies with Yohimbme 67 (21.5) 20 (30) special emphasis on the efficacy, proper dosage, timing of Trazodone and yohimbine 65 (21) 27 (58) administration and duration of treatment are warranted. Trazodone 52 (17) 27 (52) Other pharmacotherapeutic agents, such as L-arginine and Sustained action testosterone in20 (6) 14 (70) tramuscular injections desquamine tablets, nitroglycerine paste or gel, prostaglanLarginine and yohimbine 15 (5) 5 (35) din E l topical cream or urethral inserts and apomorphine Testosterone transdermal patches 10 (3) 6 (60) tablets, may have important human clinical application ifthe Larginine 10 (3) 2 (20) initial reported successes are confirmed in the future.l2 The Nitroglycerin gel 4 1 1 ) l(25) new oral type 5 phosphodiesterase inhibitors seem to be Total No. (96) 322 (100) 131 (41) promising and may constitute a major breakthrough in the future oral management of nonorganic erectile dysfunction.15 Sustained action testosterone replacement for patients with DISCUSSION hypogonadism, using intramuscular or transdermal routes The ideal therapy for erectile dysfunction should be simple, for repeatedly documented low levels of free serum testosternoninvasive and nonpainful with a high success rate and few one, may be successful in more than 70% of patients.16 Howminor side effects. Unfortunately, such treatment is cur- ever, it should be used with caution in men older than 50 rently unavailable. As first described by Lue2 and confirmed years since it may cause prostatic carcinoma. A digital rectal by others, the aim of patient goal directed therapy is not to examination and serum PSA determination should be done cure the original disease but rather to allow the patient or initially and periodically every 3 to 6 months. If any of these couple to make an informed selection of the preferred therapy latter tests are abnormal, sextant prostatic biopsy should be for sexual fulfillment based on a complete understanding of performed and testosterone treatment withheld. Intracavernous injections of prostaglandin E l alone or all treatment options as thoroughly discussed with the treating urologist. Those therapeutic methods are comparable to combined with papaverine and phentolamine have been hearing aids used in hearing impaired individuals, which can highly effectiveand safe.17They were the first selected treatimprove hearing without curing the disease. Psychological ment for 15% and the second treatment of choice for 71% of counseling and sex therapy alone are not generally successful our patients who had accepted further therapy. Use of the triple drug mixture rather than prostaglandin E l alone was in the management of pure psychogenic erectile our experience this was particularly true in patients based on the reported greater success rate with a lower younger than 30 years, who constituted approximately 20% incidence of priapism, pain and fibrosis in the triple drug - O U D . ~ ~ Vacuum theram of OUT study population. Sex therapy was combined with ~~. _ - is comparably successful 65 to therapy in 221 patients whose first line of therapy failed
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GOAL ORIENTED THERAPY FOR ERECTILE DYSFUNCTION
80%of the patients.19 Penile prostheses, which may yield the best results with a success rate of 80 to 95% and a couple satisfaction rate of 80 to 85%, were the least preferred of all therapeutic treatment options, and were chosen by only 5% of patients.20 The initial high success rate is tempered by a high dropout rate or refusal of further treatment by 38% of the patients after the initial unsuccessful first line therapy, and in approximately 70% within 43 months. Since the incidence of failures after initial success is unknown, firm conclusions regarding the long-term efficacy of goal oriented therapy cannot be objectively drawn. The long-term couple dissatisfaction with the present modes of therapy, refusal of more invasive albeit more successful methods, such as prostheses, and the hope for a more natural, safer and nonpainful treatment in the future are well illustrated in our series by the patient preference and the high dropout rate. A better understanding of the etiology and pathophysiology of erectile dysfunction may lead in the future to simpler, less invasive and more efficacious therapeutic modalities that may cure the causative disease a t low cost and with few side effects. CONCLUSIONS
A minimum diagnostic evaluation based on a complete history and physical examination is appropriate for the majority of patients with erectile dysfunction. Thorough education of the couple about the various therapeutic options with respective outcomes, risks and cost is essential for an effective goal oriented therapy. Success of any therapy should include complete satisfaction of the couple. Pharmacotherapy may be the initial treatment, if selected by the patient, and it may yield good results in patients with psychogenic or mild vascular erectile dysfunction. Noncoital techniques may be accepted alternatives for some couples. Intracavernous injections, vacuum constrictive devices and penile prostheses are initially highly successful. However, the high dropout rate and refusal of further treatment in approximately 70% of patients in 43 months temper the initial success rate of goal oriented therapy and emphasize the need for a simpler, more natural, less invasive and safer treatment. REFERENCES
1. Meuleman, E. J. and Diemont, W. L.: Investigation of erectile dysfunction. Diagnostic testing for vascular factors in erectile dysfunction. Urol. Clin. N. Amer., 2 2 803,1995. 2. Lue, T.F.: Impotence: a patient’s goal-directed approach to treatment. World J. Urol., 8 67,1990. 3. Lewis, R. W. and Barrett, D. M.: Modem management of male erectile dysfunction. AUA Update Series, vol. X I V , pp. 162167,1995.
4. J ~ ~ O WJ. , P., Nana-Sinkam, P., Sabbagh, M. and Eskew, A.: Outcome analysis of goal directed therapy for impotence. J. Urol., 156:1609,1996. 5. Hanash, K A., Hopper, M. and Brown, N. F.: Perfect Lover: Understanding and Overcoming Sexual Dysfunction. New York: SPI Books, pp. 147-180,1995. 6. Vickers, M. A.,Jr., De Nobrega, A. M. and Dluhy, R. G.: Diagnosis and treatment of psychogenic erectile dysfunction in a urological setting: outcomes of 18 consecutive patients. J. Urol., 144:1258, 1993. 7. Knispel, H.H.and Huland, H.: Influence of cause on choice of therapy in 174patients with erectile dysfunction. J. Urol., 147: 1274,1992. 8. Sohn, M., Sikora, R. and Bohndorf, K.: Selective microsurgery in arteriogenic erectile failure. World J. Urol., 8 104,1990. 9. Sharaby, J. S.,Benet, A. E. and Melman, A.:Penile revascularization. Urol. Clin. N. Amer., 22: 821, 1995. 10. Lewis, R. W.: Venogenic impotence: diagnosis, management, and results. In: Problems in Urology: The Impotent Man. Edited by R. W. Lewis and D. M. Barrett. Philadelphia: J. B. Lippincott CO., VOI.5,pp. 567-576, 1991. 11. Morales, A.,Sunidge, D. H.C., Marshall, P. G. and Fenemore, J.: Nonhormonal pharmacological treatment of organic impotence. J. Urol., 128 45,1982. 12. Morales, A.,Heaton, J. P., Johnston, B. and Adam, M.: Oral and topical treatment of erectile dysfunction: present and future in impotence. Urol. Clin. N. Amer., 22: 879,1995. 13. Montorsi, F.,Strambi, L. F., Guazzoni, G., Galli, L., Barbieri, L., Rigatti, P., Pizzini, G. and Miani, A.: Effects of yohimbinetrazodone on psychogenic impotence: a randomized, doubleblind, placebo-controlled study. Urology, 44:732,1994. 14. Kurt, U., Okardes, H., Altug, U., Germiyanoglu, C., Gurdal, M. and Erol, D.: The efficacy of anti-serotoninergic agents in the treatment of erectile dysfunction. J. Urol., 152: 407,1994. 15. Gingell, C. J. C., Jardin, A.,Olsson, A. M., Dinsmore, W. W., Osterloh, I. H., Kirkpatrick, J., Cuddigan, M. and the Multicenter Study Group: UK-92,480, a new oral treatment for erectile dysfunction: a double-blind, placebo-controlled, once daily dose response study. J. Urol., part 2,155:495A,abstract 738,1996. 16. Arver, S., Dobs, A. S., Meikle, A.W., Allen, R.P., Sanders, S. W. and Mazer, N. A.: Improvement of sexuaf function in testosterone deficient men treated for 1 year with a permeation enhanced testosterone transdermal system. J . Urol., 155: 1604,1996. 17. Porst, H.: The rationale for prostaglandin E l in erectile failure: a survey of worldwide experience. J. Urol., 155: 802,1996. 18. Bechara, A., Casabe, A.,Cheliz, G., Romano, S. and Fredotovich, N.: Prostaglandin El versus mixture of prostaglandin E l , papaverine and phentolamine in nonresponders to high papaverine plus phentolamine doses. J. Urol., 156 913,1996. 19. Cookson, M. S.and Nadig, P. W.: Long-term results with vacuum constriction device. J. Urol., 149 290, 1993. 20. Lewis, R. W.: Long-term results of penile prosthetic implants. Urol. Clin. N. Amer., 2 2 847,1995.
Vol. 157.2135-2138,June 1997 Printed in V.SA
&pyright 0 1997 by AMEMICAN UROLOGICAL ASSCCIATION, INC
COMPAFUTNE RESULTS OF GOAL ORIENTED THERAPY FOR ERECTILE DYSFUNCTION KAMAL A. M A S H * From the Urology and Impotence Center of Northern Virginia, McLean, Virginia
ABSTRACT
Purpose: Goal oriented therapy for erectile dysfunction, based on a complete education of the couple, was offered to 460 patients. The short-term and long-term results of the first and second treatments selected were compared. Materials and Methods: From September 1991 to March 1995, 460 patients with erectile dysfunction were evaluated and treated prospectively. The success of treatment, selected by the patient or couple, was defined as the ability to achieve and maintain good erections for successful coitus for at least 1year after the start of therapy. Sexual satisfaction of the couple was required to confirm a successful outcome. Results: The preferred first line of treatment by 322 patients was pharmacotherapy, with intracavernous injections being the second most selected therapy (80% success rate). However, there was a high long-term dropout rate for intracavernous injections. Approximately 70% of the patients were lost to followup or refused further treatment. Conclusions: Overall, this prospective study showed that goal oriented therapy is initially highly successful. However, the long-term high dropout rate and dissatisfaction of the couple cast doubt about the efficacy of the present treatment options. KEYWORDS: penile erection, impotence, penile prosthesis, prostaglandins E, drug therapy
A better understanding of the pathophysiology of erectile dysfunction has recently led to marked improvement in the diagnosis and treatment of this common health problem. Controversy prevails regarding the optimal diagnostic evaluation and proper therapy. Pathology oriented therapy is based on a thorough investigation to establish a diagnosis and tailor the treatment to a specific cause.1 On the other hand, goal oriented therapy relies on a minimum diagnostic evaluation and stratificationof all treatment options that are offeredto the patient for selection.2The advantages of goal oriented therapy include simplicity, a high success rate, lower risk and cost, and better acceptance by the couple. The major disadvantage is that reversible causes that may be treated specificallymay be missed. Several reports have conb e d the popularity, efficacy and high success rate of goal oriented therapy.*4 In a recent study pharmacotherapy was preferred by the majority of ~ a t i e n t sWe . ~ report our experience with goal oriented therapy, and compare the short-term and long-term results of various therapeutic modalities. MATERIALS AND METHODS
From September 1991 to March 1995,460patients (mean age 52 years, range 21 to 82) with erectile dysfunction at least 6 months in duration were evaluated and treated. A minimum of 1 year of followup and no previous therapy for =ma1 dysfunction were required for inclusion in this prospective study. Emphasis was placed on a detailed history and complete physical examination. A thorough interview, supplemented by a written questionnaire, was performed with the patient and sexual partner, when available.Medical history focused on diabetes mellitus or other endocrine diseases, trauma to the genitalia or perineum, cardiovascularor neurological diseases, and operations. Use of prescribed medications, nicotine consumption, alcohol or drug abuse and Accepted for ublication k e m b e r 6, 1996.
* Current adxress: Department of Urology, King F a i d Specialist Hosp~ta~ & Research Center, P.O. Box 3354, Riyadh, 11211, Kingdom of Saudi Arabia.
sleep disorders were carefully recorded. Other asof sexual dysfunction, such as loss of libido, premature ejaculation, ejaculatory incompetence, anorgasmy or dry ejaculation, were not included. The sexual problems of the partner were discussed. Psychological disorders and marital conflicts were properly screened. A complete physical examination with particular focus on the vascular, endocrine, neurological and genital systems was performed. Biothesiometryand qualitative Doppler evaluation of penile blood flow were used as screening tests in all patients. A visual sexual stimulation test (erotic videotape) with or without intracavernous injection of prostaglandin El or the triple drug mixture of prostaglandin, papaverine and phentolamine was done, if acceptable by the couple and not medically contraindicated.Laboratory investigation included determination of serum fasting glucose, glycosylated hemoglobin, cholesterol profile and urinalysis. Total and free serum testosterone levels were determined in all patients older than 50 years and in those with low libido. Additional laboratory tests were requested based on the history and physical findings. If serum testosterone, luteinizing hormone and follicle-stimulatinghormone were decreased or serum prolactin was elevated on at least 2 determinations magnetic resonance imaging of the brain and pituitary gland was requested. A 4-glass test with a smear and culture of the prostatic secretions were performed if prostatitis was suspected. Treatment, if sought by the couple, was usually tailored to the etiology of the erectile dysfunction if a reversible etiological factor was suspected or found. Reversible causes, such as hypogonadism with a low free serum testosterone, other endocrine disturbances involving the thyroid or pituitary glands, prescribed medications, alcohol, nicotine or drug abuse and genital anomalies (chordee), were specifically treated. Diabetes, hypercholesterolemia and cardiovascular diseases were treated concomitantlywith therapy for sexual dysfunction.Patients also ceased smoking or drug abuse and were treated for alcoholism.
2135
2136
GOAL ORIENTED THERAPY FOR ERECTILE DYSFUNCTION
Pharmacotherapy was used empirically based on the reMen with psychogenic erectile dysfunction initially underwent psychological counseling, sex therapy and pharmaco- ported success rate. In the early years of the study yohimbine therapy. In case of failure other treatment methods, such as and isoxsuprine were the agents of choice. In the last 2 years intracavernous injections and vacuum constriction devices, trazodone alone or combined with yohimbine was preferred. were used. All therapeutic options were initially offered to Most patients were reassessed 4 to 8 weeks after the start of the couple with a thorough discussion of the success rates, therapy, and every 3 months thereafter. For those whose possible risks, side effects, complications and cost, respec- original therapy failed other treatment options were offered tively. Videotapes, charts, diagrams and written materials (table 1). Therapeutic success was defined as the ability to were provided. The techniques of intracavernous injections achieve and maintain a rigid erection of good quality for and use of the vacuum device were demonstrated in the successful vaginal penetration for at least 1 year, leading to office. Written informed consent was obtained before injec- the sexual satisfaction of the couple. Patients whose chosen therapy failed or who dropped out of the study or were lost to tions. The triple drug solution contained 10 pgJml. prostaglan- followup were considered to have treatment failure. din E l , 0.6 mgjml. papaverine and 0.1 mg./ml. phentolRESULTS amine. An arbitrary dose of 0.25 ml. of the solution was injected in patients with nonneurological erectile dysfuncDiabetes mellitus and vascular diseases were the most tion. For those suspected to have a neurological etiology common major medical conditions associated with erectile according to history,physical examination and biothesiomet- dysfunction in this series (table 2). However, it should be ric findings a lower dose of 0.15 cc was initially administered. stressed that no particular effort was made to reach a precise If the initial response was positive with the development of a diagnosis. The initial choice of treatment for the majority of rigid erection for at least 30 minutes, which almost excluded patients was pharmacotherapy despite an extensive discusa significant venous leak and severe penile arterial disease, sion regarding the controversial aspect of such therapy (table the couple was offered first line therapeutic options of non- 3). Trazodone alone or with yohimbine yielded the best recoital sexual gratification, pharmacotherapy, vacuum con- sults in patients without hypogonadism (table 4). In those striction device, intracavernous injections and/or sexual ther- whose initial therapy failed the treatment of choice was intapy plus pharmacotherapy. Properly dosed syringes or vials racavernous injections (table 1). More than 85% of the pawith the triple drugmixture were periodically provided to the tients required 0.25 to 0.75 cc (mean 0.5)of the triple drug patient. Ifthere was no response to the initial intracavernous mixture. Patients with neurological erectile dysfunction injection, additional injections of the solution in increments achieved successful intercourse with a lesser dose (mean 0.3 of O.25 were given at subsequent Visits. In case of a partid or cc). The vacuum device was successful in approximately 65% no response to 1 ml. of the triple drug solution, and provided of the patients. Penile prostheses were initially selected by 14 that the patient was younger than 50 years with occlusion of patients and as a second line treatment by 10. Multiple the pudendal, penile or cavernous artery secondary to penile component inflatable penile prostheses were preferred by 19 or perineal trauma and with no history of diabetes mellitus, patients, while 5 received malleable devices. The success rate hypercholesterolemia, atherosclerosis or nicotine abuse, color was approximately 83%. There was no incidence of infection duplex Doppler sonography with intracavernous injection of after insertion of the prostheses. The 2 complications in10 pg. prostaglandin E was performed to exclude penile cluded a mechanical failure due to kinking of the right tube vascular occlusion or a venous leak. The latter test w a ~ from the cylinder to the pump with Ultrex* inflatable prosperformed in only 9 patients who were willing to undergo theses, and insufficient firmness with a Mark I1 Mentort vascular surgery. An arterial peak flow of 30 ml. per second prosthesis. In patients whose initial therapy failed the treator more in the central arteries was used to exclude arterial ment of choice was intracavernous injections (table 1). disease. Pudendal arteriography was requested before arteFew side effects occurred with the injections, with priarial microvascular surgery. If veno-occlusive disease was sus- pism occurring in 1%,pain in 10% and corporeal fibrosis in pected on color duplex Doppler sonography, with a peak end 4% of the patients. The dropout rate was 40% after 12 diastolic flow of more than 4.5 ml. per second in the phase of months and 73% within 43 months. Most patients were lost maximal erectile response, therapeutic options included vac- to followup and did not respond to our inquiry regarding the uum constrictive devices, surgical venous ligation or penile reasons for dropout. The major reasons for dropout in 93 prostheses. If the patient elected venous ligation, caverno- responders were recovery of spontaneous erections in 13 pasometry and cavernosography with injection of 10 pg. pros- tients (14%), cost of the injection (approximately $10 per taglandin E or more were performed to achieve a fullerection injection of triple drug solution) in 30 (32%), patient and preoperatively. Vascular surgery consisted of microvascular partner discontent in 25 (27%), lack of sexual spontaneity anastomosis of the epigastric artery to the deep dorsal vein in and naturalism in 22 (24%) and no sexual partner in 3 (3%). 2 cases and ligation of leaking penile veins in 7. Penile In contrast, the dropout rate for the vacuum constriction prostheses were initially selected by a minority of patients device was greater than 30% in 2 years. Few minor compliand as a last resort in patients in whom other treatment cations were reported with pharmacotherapy. Testosterone options failed. therapy was associated with 1 case of prostatic cancer with Reassurance and noncoital techniques for sexual gratifica- metastases. Microvascular surgery for penile arterial obtion were discussed with couples who were interested in sex struction failed after 6 months in 1 patient and 1 was lost to but who refused all of the aforementioned therapeutic op- followup. In 3 patients with veno-occlusive disease penile tions. Patients with penile sensory deficit on biothesiometry venous ligation successfully restored rigid erections but with and with no other neurological signs or symptoms were in- postoperative use of intracavernous injections in 2. The restructed on penile stimulation manually, orally or with a maining 4 patients could not achieve firm erections for SUCvibrator during coitus. Hypogonadism, with a low serum free cessful vaginal penetration despite additional use of intratestosterone on at least 2 determinations, was treated with cavernous injections in 3 and vacuum constrictive devices in 200 mg. sustained action testosterone intramuscularly every 1,respectively. Penile prostheses were inserted successfully 2 to 3 weeks, or 6 mg. scrota1 testosterone patches daily for 12 in 3 of these patients. Approximately 706 of the patients weeks or longer. The prostate was monitored periodically by were lost to followup or refused further therapy within 43 digital rectal examination and serum prostate specific anti- months. gen (PSA). Transrectal ultrasound with sextant prostatic biopsies was performed in patients with an abnormal PSA or * American Medical Systems, Minnetonka, Minnesota. digital rectal examination. t Mentor Corp., Santa Barbara, California.
GOAL ORIENTED THERAPY FOR ERECTILE DYSFUNCTION
TABLE1. Comparative success rates for second choice goal directed
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pharmacotherapy, vacuum devices or intracavernous injectiom6 With the ever increasing cost consciousness, a minimum diagnostic evaluation is tailored to the history and Treatment Total No. Pts. ( 8 ) No. Success (%) physical examination findings, which contrasts with the exIntracavernous injections 102 (46) 75 (73.5) tensive evaluation used for pathology oriented therapy, alVacuum constriction devices 25 (9.5) 17 (68) Penile prostheses 10 (4.5) 8 (80) though it may yield comparable success rates a t a higher risk LOSL to followup 75 (34) and cost, since it was demonstrated that the etiology rarely Refused therapy 9 (4) has an effect on treatment.7 Total No. (%I 221 (100) 100 (45) Microvascular shunt surgery is usually reserved for young patients with traumatic arterial penile obstruction. Strict TABLE2. Medical conditions associated with erectile dysfinction in criteria for inclusion are applied. Patients younger than 50 years with no risk factors and with traumatic obetruction in 460 patients the internal pudendal, common or distal penile arteries may Cause No. Pts.(96) expect a 50 to 60% success rate after arterial vascular surDiabetes mellitus 207 (45) gery.8-9 Venous ligation for abnormal venom leakage has Smoking 169 (37) gradually waned with poor long-term results,approaching20 Vascular 151 (33) Pure psychogenic 92 (20) to 30% except in highly select patienta.10 Our inability to Medications 84 (18) differentiate accurately between sinusoidal or smooth muscle Neurogenic 69 (15) disease, which is believed to constitute the main cause of Genital 51 (11) venous leakage, and other venoua penile disorders may be DNgS 50 (11) Radical surgery 46 (10) the primary reason for the high surgical failure rate. Endocrine 46 (10) Pharmacotherapy with yohimbine andlor trazdone was Hypercholesterolemia 28 (6) the preferred initial treatment in more than 70% of our Alcoholism 23 ( 5 ) patients. The success rates were approximately 55% for traMore than 1 cause may be attributed to a patient. d o n e alone or combined with yohimbine. These agents were particularly effective in patients with psychogenic or mildly TABLE3. Comparative success rates for first choice goal directed vascular erectile dysfunction. However, since no control theraov in 460 Datients with erectile dysfunction group was used, a placebo effect for these oral medications cannot be excluded. In controlled studies 21 to 62% complete Treatment Total No. Pts.(%) No. Sut%) recovery of erection was reported.11.12 The best response was Pharmacological 322 (70) 131 (41) found in patients with psychogenic erectile dysfunction, parIntracavernous injections 69 (15) 59 (85) Vacuum constriction device 38 (8) 24 (63) ticularly when combined with sex therapy and psychological Prostheses 14 (3) 12 (85) counseling. However, other studies revealed no statistical Vascular surgery 9 (2) 3 (30) difference between yohimbine and placebo.'* Trazodone, Noncoital techniques 8 (2) 5(26) which is usually used as an antidepressant, has been sucTotal No. (%) 460 (100) 239 (60) cessful in the management of erectile dysfunction in 40 to 60% of ~ases.13.1~ Its mechanism of action is still unknown but it is recognizedto increase the level of serotonin centrally TABLE4. Pharmacotherapy and comparative results in 322 at the level of the serotonin HT-IC receptor through repatients with erectile dysfunction uptake inhibition, and it possesses peripheral a-ganglionic Treatment Total No. pts. (5%) No. Suceesa (5%) blocking action. It may also act synergistically with yohimYohimbine and isoxsuprine 79 (25) 28 (35) bine.13 Further prospective matched controlled studies with Yohimbme 67 (21.5) 20 (30) special emphasis on the efficacy, proper dosage, timing of Trazodone and yohimbine 65 (21) 27 (58) administration and duration of treatment are warranted. Trazodone 52 (17) 27 (52) Other pharmacotherapeutic agents, such as L-arginine and Sustained action testosterone in20 (6) 14 (70) tramuscular injections desquamine tablets, nitroglycerine paste or gel, prostaglanLarginine and yohimbine 15 (5) 5 (35) din E l topical cream or urethral inserts and apomorphine Testosterone transdermal patches 10 (3) 6 (60) tablets, may have important human clinical application ifthe Larginine 10 (3) 2 (20) initial reported successes are confirmed in the future.l2 The Nitroglycerin gel 4 1 1 ) l(25) new oral type 5 phosphodiesterase inhibitors seem to be Total No. (96) 322 (100) 131 (41) promising and may constitute a major breakthrough in the future oral management of nonorganic erectile dysfunction.15 Sustained action testosterone replacement for patients with DISCUSSION hypogonadism, using intramuscular or transdermal routes The ideal therapy for erectile dysfunction should be simple, for repeatedly documented low levels of free serum testosternoninvasive and nonpainful with a high success rate and few one, may be successful in more than 70% of patients.16 Howminor side effects. Unfortunately, such treatment is cur- ever, it should be used with caution in men older than 50 rently unavailable. As first described by Lue2 and confirmed years since it may cause prostatic carcinoma. A digital rectal by others, the aim of patient goal directed therapy is not to examination and serum PSA determination should be done cure the original disease but rather to allow the patient or initially and periodically every 3 to 6 months. If any of these couple to make an informed selection of the preferred therapy latter tests are abnormal, sextant prostatic biopsy should be for sexual fulfillment based on a complete understanding of performed and testosterone treatment withheld. Intracavernous injections of prostaglandin E l alone or all treatment options as thoroughly discussed with the treating urologist. Those therapeutic methods are comparable to combined with papaverine and phentolamine have been hearing aids used in hearing impaired individuals, which can highly effectiveand safe.17They were the first selected treatimprove hearing without curing the disease. Psychological ment for 15% and the second treatment of choice for 71% of counseling and sex therapy alone are not generally successful our patients who had accepted further therapy. Use of the triple drug mixture rather than prostaglandin E l alone was in the management of pure psychogenic erectile our experience this was particularly true in patients based on the reported greater success rate with a lower younger than 30 years, who constituted approximately 20% incidence of priapism, pain and fibrosis in the triple drug - O U D . ~ ~ Vacuum theram of OUT study population. Sex therapy was combined with ~~. _ - is comparably successful 65 to therapy in 221 patients whose first line of therapy failed
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GOAL ORIENTED THERAPY FOR ERECTILE DYSFUNCTION
80%of the patients.19 Penile prostheses, which may yield the best results with a success rate of 80 to 95% and a couple satisfaction rate of 80 to 85%, were the least preferred of all therapeutic treatment options, and were chosen by only 5% of patients.20 The initial high success rate is tempered by a high dropout rate or refusal of further treatment by 38% of the patients after the initial unsuccessful first line therapy, and in approximately 70% within 43 months. Since the incidence of failures after initial success is unknown, firm conclusions regarding the long-term efficacy of goal oriented therapy cannot be objectively drawn. The long-term couple dissatisfaction with the present modes of therapy, refusal of more invasive albeit more successful methods, such as prostheses, and the hope for a more natural, safer and nonpainful treatment in the future are well illustrated in our series by the patient preference and the high dropout rate. A better understanding of the etiology and pathophysiology of erectile dysfunction may lead in the future to simpler, less invasive and more efficacious therapeutic modalities that may cure the causative disease a t low cost and with few side effects. CONCLUSIONS
A minimum diagnostic evaluation based on a complete history and physical examination is appropriate for the majority of patients with erectile dysfunction. Thorough education of the couple about the various therapeutic options with respective outcomes, risks and cost is essential for an effective goal oriented therapy. Success of any therapy should include complete satisfaction of the couple. Pharmacotherapy may be the initial treatment, if selected by the patient, and it may yield good results in patients with psychogenic or mild vascular erectile dysfunction. Noncoital techniques may be accepted alternatives for some couples. Intracavernous injections, vacuum constrictive devices and penile prostheses are initially highly successful. However, the high dropout rate and refusal of further treatment in approximately 70% of patients in 43 months temper the initial success rate of goal oriented therapy and emphasize the need for a simpler, more natural, less invasive and safer treatment. REFERENCES
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4. J ~ ~ O WJ. , P., Nana-Sinkam, P., Sabbagh, M. and Eskew, A.: Outcome analysis of goal directed therapy for impotence. J. Urol., 156:1609,1996. 5. Hanash, K A., Hopper, M. and Brown, N. F.: Perfect Lover: Understanding and Overcoming Sexual Dysfunction. New York: SPI Books, pp. 147-180,1995. 6. Vickers, M. A.,Jr., De Nobrega, A. M. and Dluhy, R. G.: Diagnosis and treatment of psychogenic erectile dysfunction in a urological setting: outcomes of 18 consecutive patients. J. Urol., 144:1258, 1993. 7. Knispel, H.H.and Huland, H.: Influence of cause on choice of therapy in 174patients with erectile dysfunction. J. Urol., 147: 1274,1992. 8. Sohn, M., Sikora, R. and Bohndorf, K.: Selective microsurgery in arteriogenic erectile failure. World J. Urol., 8 104,1990. 9. Sharaby, J. S.,Benet, A. E. and Melman, A.:Penile revascularization. Urol. Clin. N. Amer., 22: 821, 1995. 10. Lewis, R. W.: Venogenic impotence: diagnosis, management, and results. In: Problems in Urology: The Impotent Man. Edited by R. W. Lewis and D. M. Barrett. Philadelphia: J. B. Lippincott CO., VOI.5,pp. 567-576, 1991. 11. Morales, A.,Sunidge, D. H.C., Marshall, P. G. and Fenemore, J.: Nonhormonal pharmacological treatment of organic impotence. J. Urol., 128 45,1982. 12. Morales, A.,Heaton, J. P., Johnston, B. and Adam, M.: Oral and topical treatment of erectile dysfunction: present and future in impotence. Urol. Clin. N. Amer., 22: 879,1995. 13. Montorsi, F.,Strambi, L. F., Guazzoni, G., Galli, L., Barbieri, L., Rigatti, P., Pizzini, G. and Miani, A.: Effects of yohimbinetrazodone on psychogenic impotence: a randomized, doubleblind, placebo-controlled study. Urology, 44:732,1994. 14. Kurt, U., Okardes, H., Altug, U., Germiyanoglu, C., Gurdal, M. and Erol, D.: The efficacy of anti-serotoninergic agents in the treatment of erectile dysfunction. J. Urol., 152: 407,1994. 15. Gingell, C. J. C., Jardin, A.,Olsson, A. M., Dinsmore, W. W., Osterloh, I. H., Kirkpatrick, J., Cuddigan, M. and the Multicenter Study Group: UK-92,480, a new oral treatment for erectile dysfunction: a double-blind, placebo-controlled, once daily dose response study. J. Urol., part 2,155:495A,abstract 738,1996. 16. Arver, S., Dobs, A. S., Meikle, A.W., Allen, R.P., Sanders, S. W. and Mazer, N. A.: Improvement of sexuaf function in testosterone deficient men treated for 1 year with a permeation enhanced testosterone transdermal system. J . Urol., 155: 1604,1996. 17. Porst, H.: The rationale for prostaglandin E l in erectile failure: a survey of worldwide experience. J. Urol., 155: 802,1996. 18. Bechara, A., Casabe, A.,Cheliz, G., Romano, S. and Fredotovich, N.: Prostaglandin El versus mixture of prostaglandin E l , papaverine and phentolamine in nonresponders to high papaverine plus phentolamine doses. J. Urol., 156 913,1996. 19. Cookson, M. S.and Nadig, P. W.: Long-term results with vacuum constriction device. J. Urol., 149 290, 1993. 20. Lewis, R. W.: Long-term results of penile prosthetic implants. Urol. Clin. N. Amer., 2 2 847,1995.