THE JOURNAL OF UROLOGY
Vol. 115, May Printed in U.S.A.
Copyright© 1976 by The Williams & Wilkins Co.
STRESS INCONTINENCE: CONSERVATIVE THERAPY WITH SYMPATHOMIMETIC DRUGS BRUCE H. STEWART, LYNN H. W. BANOWSKY
AND
DROGO K. MONTAGUE
From the Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio
ABSTRACT
There were 77 women with mild to moderate stress urinary incontinence treated with the sympathomimetic agent, phenylpropanolamine hydrochloride, combined with chlorpheniramine maleate and isopropamide iodide in a sustained release capsule (Ornade). The majority of these patients achieved significant improvement 3 months to 3 years after beginning therapy. A trial of conservative therapy is advisable for stress incontinence, especially when symptoms are mild or when the patients are in a poor risk category. Similar management of post-prostatectomy stress incontinence in men was disappointing. However, the occasional excellent results in patients with mild symptoms appear to justify a trial of conservative therapy before considering operative intervention in this group of patients. Recent experimental evidence and clinical experience have demonstrated the importance of sympathetic innervation to the vesical neck and posterior urethra. Blockade of alphaadrenergic receptors in the smooth muscle of these structures can result in a decrease in proximal urethral resistance. Several investigators, using reserpine or phenoxybenzamine, have documented improved bladder emptying in patients with abnormally high vesical neck resistance owing to hyperactivity of smooth muscle in this area. 1-5 In addition, it is generally agreed that removal of the sympathetic nerve supply to the region of the bladder neck can also result in retrograde ejaculation. Conversely, stimulation of the sympathetic fibers in the hypogastric nerve of the male patient results in closure of the bladder neck, contraction of the posterior urethra and antegrade ejaculation. Tanagho and Meyers demonstrated increases in proximal urethral resistance with the administration of sympathomimetic agents. 6 Lap ides, and Diokno and Taub have improved urinary control in a variety of patients with incontinence by giving oral ephedrine medication. 7 • 8 Stewart and Bergant have restored antegrade ejaculation with phenylpropanolamine in patients with altered sympathetic innervation owing to diabetic neuropathy, and Hinman has reported similar results with ephedrine in patients with retrograde ejaculation following retroperitoneal lymphadenectomy. 9 • 10 During the last 3 years patients with stress urinary incontinence have been treated with the oral sympathomimetic drug, phenylpropanolamine. This agent has been combined with the antihistamine chlorpheniramine maleate and the drying agent isopropamide iodide in a sustained release capsule.* This report summarizes our initial experience with non-operative management of stress incontinence. MATERIAL AND METHODS
Seventy-seven women with classic urinary stress incontinence were placed on 1 spansule containing phenylpropanolamine twice a day. Diagnosis was confirmed by cystoscopy and cystometric studies in 32 patients. The presence of a typical history, a negative urinalysis and residual urine, and a positive stress test were considered to be sufficient to establish the Accepted for publication August 15, 1975. Read at annual meeting of North Central Section, American Urological Association, Phoenix, Arizona, October 5-12, 1975. * Ornade, Smith, Kline & French Laboratories, Philadelphia, Pennsylvania 19101.
diagnosis in the remainder of the patients. Of interest is the fact that 2 patients had mild persistent leakage after anterior urethropexy and 1 patient suffered significant stress incontinence after internal urethrotomy. All patients were followed for 3 months to 3 years on treatment. Eleven men with post-prostatectomy stress incontinence were treated also with 1 spansule containing phenylpropanolamine twice a day. Diagnosis was confirmed in all patients prior to therapy by cystoscopic and cystometric studies. RESULTS
Results of treatment in all patients are summarized in the table. In general, 59 per cent of the women were significantly improved on conservative therapy and would not consider operation for correction of their difficulty. An additional 8 per cent of the patients had only fair control and yet most of these patients thought that their symptoms were still insufficient to justify an operation. Thirty-three per cent of the patients had persistent or progressively severe symptoms and, therefore, discontinued therapy. Four patients initially thought to have an excellent result suffered recurrent and progressively severe stress incontinence while on therapy and 1 of these has undergone anterior urethropexy. Of the 25 patients whose symptoms were unchanged on treatment 10 have subsequently undergone a corrective operation either by anterior urethropexy or Scott's artificial sphincter. The remaining patients are significantly symptomatic but for a variety of reasons have not been considered good surgical candidates. Of the 2 patients with persistent leakage after anterior urethropexy and the 1 patient who suffered stress incontinence after internal urethrotomy all had excellent relief of symptoms on treatment with phenylpropanolamine. Of the 77 women 6 complained of drowsiness, lightheadedness, rash or fever as a result of medication and, therefore, discontinued its use. Two of these patients resumed therapy with 25 mg. ephedrine 4 times a day and had good results. Three patients were disturbed by excessive dryness of the mouth but this was satisfactorily controlled by reducing the dosage to 1 spansule per day and all 3 remained continent. Only 3 of the 11 men with post-prostatectomy stress incontinence (27 per cent) achieved significant relief of symptoms. All of these patients had mild post-prostatectomy incontinence and would probably not have been considered for operative intervention in any event. However, it is interesting to note that all 3 men became completely dry on phenylpropanolamine 558
559
STRESS H•,JCONTJNENCE
Resu,lts of phenylpropanolarnine t.herapy in patierits with stress incontinence
cured better Slightly better Unchanged Totals
Women
Men
No.(%)
No.(%)
18 (23) 28(36) 6 (8) 25 (33)
1 (9) 2(18) 1 (9) 7(64) 11
77
medication and were delighted to be rid of the nuisance of mild urinary leakage. One additional patient has had some improvement in the urinary control and he does not wish to consider further surgery at this time even though he still has significant leakage. Seven men had no improvement in the severe stress incontinence. Two of these patients have achieved satisfactory control with the Scott internal sphincter and 2 with the Kaufman perinea! prosthesis. The remaining 3 patients have refused further operations. DISCUSSION
Preliminary experience has demonstrated the effectiveness of oral sympathornimetic medication in women with stress urinary incontinence. The phenylpropanolamine-containing spansule was selected as the drug of choice because of its ease of administration and also because it tends to diminish coughing or sneezing. Occasional drowsiness or weakness necessitated a reduction in or change to ephedrine, which was usually well tolerated. Most patients so treated were poor risk or elderly with only mild to moderate symptoms of stress incontinence. The majority of these patients have achieved significant benefits from alpha-adrenergic stimulation and remain on treatment. In deficient patients the application of prernarin cream to the urethral area twice daily has been considered to augment the effect of phenylpropanolamine therapy. Generally, the results of sympathomimetic medication in men with post-prostatectomy incontinence has been discouraging. a few patients with mild symptoms have been this type of medication thereof non-operative therapy is believed to be fully with this type of incontinence. Early treatment spansule
or ephedrine well hasten the resolution of incontinence in those patients who would otherwise regain control several weeks or months after operation. Patients who have not responded to conservative therapy have appreciated the triai of non-operative treatment and, as a result, have been more cooperative and satisfied patients during subsequent operative intervention. The results of our study still must be considered preliminary but the therapeutic benefits and lack of serious side effects should justify a more extensive trial of sympathomimetic therapy in patients with urinary stress incontinence. REFERENCES
1. Kleeman, F. J.: The physiology of the internal urinary sphincter. J. Urol., 104: 549, 1970. 2. Krane, R. J. and Olsson, C. A.: Phenoxybenzamine in neurogenic bladder dysfunction. I. A theory of micturition. J. Urol., HO: 650, 1973. 3. Krane, R. J. and Olsson, C. A.: Phenoxybenzamine in neurogenic bladder dysfunction. II. Clinical considerations. J. Urol., HO: 653, 1973. 4. Donker, P. J., Ivanovici, F. and Noach, E. L.: Analyses of the
5. 6. 7. 8. 9.
10.
urethral pressure profile by means of electromyography and the administration of drugs. Brit. J. Urol., 44: 180, 1972. Diokno, A. C. and Taub, M.: Unpublished data. Tanagho, E. A. and Meyers, F. H.: The "internal sphincter": is it under sympathetic control 9 Invest. Urol., 7: 79, 1969. Lapides, J.: Micturition and the adrenergic system. Urologists' Letter Club, ,!,§: 49, 1974. Diokno, A. C. and Taub, !vi.: Ephedrine in the treatment of urinary incontinence. Urology, 5: 624, 1975. Stewart, B. H. and Bergant, J. A.: Correction of retrograde ejaculation by sympathomimetic medication: preliminary report. Fertil. Steril., 25: 1073, 1974. Hinman, F., Jr.: Personal communication, 1974. COMMENT
The experiences of these authors with pheny!propanolamine in the treatment of stress incontinence are quite similar to our findings with ephedrine sulfate. Urethral resistance is increased sufficiently with alpha-adrenergic drugs to markedly improve mild cases of stress incontinence regardless of etiology. Similar therapy in severe cases is usually ineffectual. We heartily agree with the idea of a trial of medical therapy prior to surgical intervention. Jack Lapides University Hospital Ann Arbor, 11,fichigan
Vol. 115, May Printed in U.S.A.
Copyright© 1976 by The Williams & Wilkins Co.
STRESS INCONTINENCE: CONSERVATIVE THERAPY WITH SYMPATHOMIMETIC DRUGS BRUCE H. STEWART, LYNN H. W. BANOWSKY
AND
DROGO K. MONTAGUE
From the Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio
ABSTRACT
There were 77 women with mild to moderate stress urinary incontinence treated with the sympathomimetic agent, phenylpropanolamine hydrochloride, combined with chlorpheniramine maleate and isopropamide iodide in a sustained release capsule (Ornade). The majority of these patients achieved significant improvement 3 months to 3 years after beginning therapy. A trial of conservative therapy is advisable for stress incontinence, especially when symptoms are mild or when the patients are in a poor risk category. Similar management of post-prostatectomy stress incontinence in men was disappointing. However, the occasional excellent results in patients with mild symptoms appear to justify a trial of conservative therapy before considering operative intervention in this group of patients. Recent experimental evidence and clinical experience have demonstrated the importance of sympathetic innervation to the vesical neck and posterior urethra. Blockade of alphaadrenergic receptors in the smooth muscle of these structures can result in a decrease in proximal urethral resistance. Several investigators, using reserpine or phenoxybenzamine, have documented improved bladder emptying in patients with abnormally high vesical neck resistance owing to hyperactivity of smooth muscle in this area. 1-5 In addition, it is generally agreed that removal of the sympathetic nerve supply to the region of the bladder neck can also result in retrograde ejaculation. Conversely, stimulation of the sympathetic fibers in the hypogastric nerve of the male patient results in closure of the bladder neck, contraction of the posterior urethra and antegrade ejaculation. Tanagho and Meyers demonstrated increases in proximal urethral resistance with the administration of sympathomimetic agents. 6 Lap ides, and Diokno and Taub have improved urinary control in a variety of patients with incontinence by giving oral ephedrine medication. 7 • 8 Stewart and Bergant have restored antegrade ejaculation with phenylpropanolamine in patients with altered sympathetic innervation owing to diabetic neuropathy, and Hinman has reported similar results with ephedrine in patients with retrograde ejaculation following retroperitoneal lymphadenectomy. 9 • 10 During the last 3 years patients with stress urinary incontinence have been treated with the oral sympathomimetic drug, phenylpropanolamine. This agent has been combined with the antihistamine chlorpheniramine maleate and the drying agent isopropamide iodide in a sustained release capsule.* This report summarizes our initial experience with non-operative management of stress incontinence. MATERIAL AND METHODS
Seventy-seven women with classic urinary stress incontinence were placed on 1 spansule containing phenylpropanolamine twice a day. Diagnosis was confirmed by cystoscopy and cystometric studies in 32 patients. The presence of a typical history, a negative urinalysis and residual urine, and a positive stress test were considered to be sufficient to establish the Accepted for publication August 15, 1975. Read at annual meeting of North Central Section, American Urological Association, Phoenix, Arizona, October 5-12, 1975. * Ornade, Smith, Kline & French Laboratories, Philadelphia, Pennsylvania 19101.
diagnosis in the remainder of the patients. Of interest is the fact that 2 patients had mild persistent leakage after anterior urethropexy and 1 patient suffered significant stress incontinence after internal urethrotomy. All patients were followed for 3 months to 3 years on treatment. Eleven men with post-prostatectomy stress incontinence were treated also with 1 spansule containing phenylpropanolamine twice a day. Diagnosis was confirmed in all patients prior to therapy by cystoscopic and cystometric studies. RESULTS
Results of treatment in all patients are summarized in the table. In general, 59 per cent of the women were significantly improved on conservative therapy and would not consider operation for correction of their difficulty. An additional 8 per cent of the patients had only fair control and yet most of these patients thought that their symptoms were still insufficient to justify an operation. Thirty-three per cent of the patients had persistent or progressively severe symptoms and, therefore, discontinued therapy. Four patients initially thought to have an excellent result suffered recurrent and progressively severe stress incontinence while on therapy and 1 of these has undergone anterior urethropexy. Of the 25 patients whose symptoms were unchanged on treatment 10 have subsequently undergone a corrective operation either by anterior urethropexy or Scott's artificial sphincter. The remaining patients are significantly symptomatic but for a variety of reasons have not been considered good surgical candidates. Of the 2 patients with persistent leakage after anterior urethropexy and the 1 patient who suffered stress incontinence after internal urethrotomy all had excellent relief of symptoms on treatment with phenylpropanolamine. Of the 77 women 6 complained of drowsiness, lightheadedness, rash or fever as a result of medication and, therefore, discontinued its use. Two of these patients resumed therapy with 25 mg. ephedrine 4 times a day and had good results. Three patients were disturbed by excessive dryness of the mouth but this was satisfactorily controlled by reducing the dosage to 1 spansule per day and all 3 remained continent. Only 3 of the 11 men with post-prostatectomy stress incontinence (27 per cent) achieved significant relief of symptoms. All of these patients had mild post-prostatectomy incontinence and would probably not have been considered for operative intervention in any event. However, it is interesting to note that all 3 men became completely dry on phenylpropanolamine 558
559
STRESS H•,JCONTJNENCE
Resu,lts of phenylpropanolarnine t.herapy in patierits with stress incontinence
cured better Slightly better Unchanged Totals
Women
Men
No.(%)
No.(%)
18 (23) 28(36) 6 (8) 25 (33)
1 (9) 2(18) 1 (9) 7(64) 11
77
medication and were delighted to be rid of the nuisance of mild urinary leakage. One additional patient has had some improvement in the urinary control and he does not wish to consider further surgery at this time even though he still has significant leakage. Seven men had no improvement in the severe stress incontinence. Two of these patients have achieved satisfactory control with the Scott internal sphincter and 2 with the Kaufman perinea! prosthesis. The remaining 3 patients have refused further operations. DISCUSSION
Preliminary experience has demonstrated the effectiveness of oral sympathornimetic medication in women with stress urinary incontinence. The phenylpropanolamine-containing spansule was selected as the drug of choice because of its ease of administration and also because it tends to diminish coughing or sneezing. Occasional drowsiness or weakness necessitated a reduction in or change to ephedrine, which was usually well tolerated. Most patients so treated were poor risk or elderly with only mild to moderate symptoms of stress incontinence. The majority of these patients have achieved significant benefits from alpha-adrenergic stimulation and remain on treatment. In deficient patients the application of prernarin cream to the urethral area twice daily has been considered to augment the effect of phenylpropanolamine therapy. Generally, the results of sympathomimetic medication in men with post-prostatectomy incontinence has been discouraging. a few patients with mild symptoms have been this type of medication thereof non-operative therapy is believed to be fully with this type of incontinence. Early treatment spansule
or ephedrine well hasten the resolution of incontinence in those patients who would otherwise regain control several weeks or months after operation. Patients who have not responded to conservative therapy have appreciated the triai of non-operative treatment and, as a result, have been more cooperative and satisfied patients during subsequent operative intervention. The results of our study still must be considered preliminary but the therapeutic benefits and lack of serious side effects should justify a more extensive trial of sympathomimetic therapy in patients with urinary stress incontinence. REFERENCES
1. Kleeman, F. J.: The physiology of the internal urinary sphincter. J. Urol., 104: 549, 1970. 2. Krane, R. J. and Olsson, C. A.: Phenoxybenzamine in neurogenic bladder dysfunction. I. A theory of micturition. J. Urol., HO: 650, 1973. 3. Krane, R. J. and Olsson, C. A.: Phenoxybenzamine in neurogenic bladder dysfunction. II. Clinical considerations. J. Urol., HO: 653, 1973. 4. Donker, P. J., Ivanovici, F. and Noach, E. L.: Analyses of the
5. 6. 7. 8. 9.
10.
urethral pressure profile by means of electromyography and the administration of drugs. Brit. J. Urol., 44: 180, 1972. Diokno, A. C. and Taub, M.: Unpublished data. Tanagho, E. A. and Meyers, F. H.: The "internal sphincter": is it under sympathetic control 9 Invest. Urol., 7: 79, 1969. Lapides, J.: Micturition and the adrenergic system. Urologists' Letter Club, ,!,§: 49, 1974. Diokno, A. C. and Taub, !vi.: Ephedrine in the treatment of urinary incontinence. Urology, 5: 624, 1975. Stewart, B. H. and Bergant, J. A.: Correction of retrograde ejaculation by sympathomimetic medication: preliminary report. Fertil. Steril., 25: 1073, 1974. Hinman, F., Jr.: Personal communication, 1974. COMMENT
The experiences of these authors with pheny!propanolamine in the treatment of stress incontinence are quite similar to our findings with ephedrine sulfate. Urethral resistance is increased sufficiently with alpha-adrenergic drugs to markedly improve mild cases of stress incontinence regardless of etiology. Similar therapy in severe cases is usually ineffectual. We heartily agree with the idea of a trial of medical therapy prior to surgical intervention. Jack Lapides University Hospital Ann Arbor, 11,fichigan
