Oral and intravaginal estrogens alone and in combination with alpha-adrenergic stimulation in genuine stress incontinence

Sixty postmenopausal women suffering from genuine stress incontinence were recruited into a double-blind study comparing the effects of oral and intravaginal estrogens and placebo, alone and in combination with the alpha-adrenoreceptor stimulant drug phenyl-propanolamine (PPA). Side effects were more common with orally administered estrogen, whereas symptomatic improvements were greater than the vaginal route. Plasma estrone and estradiol were both elevated more when estrogen was given by the oral (x 3–4) than vaginal (x 2) route, although the estradiol/estrone ratio was lower with oral therapy; the biochemical alterations increased with increasing chronological age and menopausal age, and were slightly enhanced by the concurrent administration of PPA. Diurnal and nocturnal urinary frequency were both reduced to a greater extent with vaginal than oral estrogen treatment, and more when used with PPA. Stress incontinence was improved subjectively in all treatment groups, although objective improvement was maximal in those treated with vaginal estrogen plus PPA.     

Electrical stimulation for stress incontinence

Electrical stimulation has been reported to be effective for stress incontinence, cure and improvement rates being reported to range from 30% to 50%, and from 6% to 90%, respectively. However, clinical application of this treatment is not common because there is little physiological and technical information. Electrodes for electrical stimulation are divided into two types: external (non-implantable) and internal (implantable), and there are two methods of stimulation: chronic (long-term, continuous) and short-term. Frequencies of 20–50 Hz, with a pulse duration of 1–5 ms, have been reported to be effective for urethral closure. The effectiveness of the treatment should be verified with placebo-controlled double-blinded trials, and four such studies using an active and a sham device have been reported. Two of these verified the superiority of the active device over the sham device, but the others did not demonstrate any significant difference between the two with regard to efficacy. Electrical stimulation has been reported to result in a long-term continuation of therapeutic effect. The effect has been explained as a re-education or a reactivation of lost functions of the pelvic floor muscles. As to adverse effects, there may be some complications in relation to anesthesia or surgical procedures, such as infection, pain and bleeding with implantable electrodes. The incidence of adverse effects in short-term electrical stimulation is less than 14%. In conclusion, short-term electrical stimulation using non-implantable anal or vaginal electrodes is the most recommendable because of safety and ease of use.     

Lack of effect of cholinergic blocking and alpha-adrenergic stimulation on nocturnal incontinence after ileocaecal bladder replacement. A controlled randomised study

A controlled randomised trial was carried out in 9 patients to examine the possibility of achieving nocturnal continence after ileocaecal bladder replacement by reducing the amplitude of the peristaltic contractions and by increasing the maximum urethral pressure pharmacologically. The trial consisted of 4 treatment periods, each of 2 weeks' duration: a single-blind placebo period was followed by 3 double-blind periods with phenylpropanolamine hydrochloride 50 mg bd (Kontexin), oxybutynin chloride 5 mg tid (Ditropan), and combined treatment. Each patient completed a frequency/volume chart before the trial and for the last 7 days of each treatment period. Filling and storage urethrocystometry was performed before treatment and at the end of each treatment period. Treatment with phenylpropanolamine and oxybutynin failed to reduce the nocturnal urine leak of about 600 ml. Treatment did not influence the maximum urethral closure pressure, which remained unchanged at about 16 cm of water with the bladder substitute at rest and filled to its maximum cystometric capacity. At storage urethrocystometry, the treatment resulted in a decrease in the amplitude of the peristaltic contractions of about 10 cm of water to approximately 45 cm of water. Accordingly, the effect of alpha-adrenergic stimulation and anticholinergic suppression was found to be insufficient to achieve nocturnal continence in patients with ileocaecal bladder replacement.     

The effect of alpha-adrenergic stimulation and blockade on perfusion of myocutaneous flaps

A porcine myocutaneous flap model was utilized to assess the development of denervation adrenergic hypersensitivity and to determine the effects of the alpha-adrenergic blocking agent--phenoxybenzamine--on flap blood perfusion. During intravenous administration of norepinephrine, blood flow to the flaps and control skin was monitored simultaneously, using laser Doppler velocimetry and dermofluorometry. A relative decrease in myocutaneous flap blood flow, as compared to control skin in response to norepinephrine infusion, was observed at between 2 and 7 days following flap elevation. This is the same time period during which norepinephrine content of skin flaps is diminished, and suggests development of an increased sensitivity to adrenergic stimulation. Administration of phenoxybenzamine blunted norepinephrine-induced pressor responses and blocked development of adrenergic hypersensitivity in the porcine myocutaneous flap model. Phenoxybenzamine significantly increased flap blood perfusion (as measured by dermofluorometry).     

The effect of phenylpropanolamine on female stress urinary incontinence

In a randomized double-blind manner, 43 women with grade I and II stress urinary incontinence were treated with either phenylpropanolamine p.o. 50 mg twice daily (Rinexin, 1 tablet b.i.d.) or placebo during two weeks. Urethral CO2 profilometry, with recording of maximum urethral closure pressure (MUCP) and functional urethral length (FUL), and subjective response were considered for effect evaluation. The subjective response of Rinexin was highly significant (p = 0.01) above that of placebo. Clinical improvement was reported by 15 of 21 women on Rinexin and by 8 of 22 women on placebo. A significant increase in MUCP, 14%, was registered in women on Rinexin treatment. This increase was more pronounced in the grade I than in the grade II incontinent women. No statistically significant correlations were obtained between subjective response and increase in MUCP. An increase in FUL was recorded in both two treatment groups, but no statistically significant difference between them was obtained. Adverse drug reactions were rare. No changes in blood pressure occurred. Based on the present study, Rinexin (1 tablet b.i.d.) is an effective and safe medication for female grade I and II stress incontinence and is also recommended as adjunctive therapy to physiotherapy before Teflon injection or operation.     

生物反馈电刺激治疗女性压力性尿失禁疗效评价（附30例报告）

目的 通过生物反馈电刺激治疗女性压力性尿失禁30例，探讨其疗效，寻找较好的保守治疗女性压力性尿失禁的方法。方法 选择30例Ⅰ～Ⅱ度女性压力性尿失禁的患者，使用生物反馈治疗仪进行生物反馈电刺激治疗，每次20min，隔日1次，10次为1个疗程，疗程结束后3个月开始观察疗效，随访6个月。结果 30例患者中治愈20例（67％），有效7例（23％），无效但未发展的3例（10％），有效率达90％。结论 生物反馈电刺激治疗Ⅰ～Ⅱ度女性压力性尿失禁是一种有效的、治愈率较高的保守治疗方法。     

The treatment of detrusor incontinence by electrical stimulation.

Cystometrograms were done on 20 patients before and during transrectal stimulation to determine if electrical stimulation increased the detrusor reflex threshold. In 4 patients the detrusor reflex threshold was increased during stimulation and urinary continence was restored. However, each patient became incontinent when transrectal stimulation was discontinued for 1 to 5 days. Thus, cyclic periods of stimulation were necessary to maintain the beneficial effects of electrical stimulation and a permanent pelvic floor stimulator was implanted since chronic transrectal stimulation was inconvenient.     

Disappointing effect of endoscopic Teflon injection for female stress incontinence.

Twenty-two women were treated with endoscopic, transurethral, submucosal Teflon injection for moderate or severe urinary stress incontinence. The short-term effect was rather good, but he long-term results were disappointing. After 5 years, only 4 patients were completely or sufficiently continent and had not required any additional treatment for incontinence. Three major complications, paraurethral abscess, urethral diverticulum and Teflon granuloma with urethral wall prolapse occurred. Subsequent suprapubic urethropexy for the patients with inadequate response did not produce the usual good results.     

Electrical stimulation for incontinence in myelomeningocele.

Urinary incontinence is the most obvious urinary tract complication in children with myelomeningocele. Incontinence is owing to a hyperreflexic (spastic) bladder and/or pelvic floor weakness, which responds to functional electrical stimulation. Of 33 incontinent children the criteria for functional electrical stimulation were absent in 21 because of denervation of the pelvic floor muscles. Of 6 children who used functional electrical stimulation 5 had a successful result. However, incontinence recurred in 3 of the 5 patients between 6 and 18 months after functional electrical stimulation treatment was completed and they are awaiting repeat treatment.     

The pathophysiology of stress incontinence

The factors contributing to stress incontinence of urine are reviewed and categorized with respect to their effects on coaptation and compression of the urethra. Intrinsic urethral dysfunction and poor anatomic support are discussed from both a functional and a pathophysiologic approach.     

Erection and NO override the vasoconstrictive effect of alpha-adrenergic stimulation in the rat penile vasculature

Studies in this laboratory are designed to determine the effects of vasoconstrictor agents on the erectile response in rats. We have previously demonstrated that the vasoconstrictor effect of endothelin-1 (ET-1) is sharply reduced by erection and by nitric oxide (NO) administration. The present study was performed to determine if vasoconstriction, resulting from alpha-adrenergic stimulation, is altered by erection and NO. During continuous monitoring of corpus cavernosum pressure (CCP) and mean arterial pressure (MAP), erection was induced by electrical stimulation of the autonomic ganglion for the innervation of the penis. When the alpha-adrenergic agonist methoxamine (METH, 10 microg/kg) was injected before erection (ie, into the non-erect penis), the subsequent erectile response (CCP/MAP) was significantly reduced from 0.68+/-0.03 before METH to 0.34+/-0.08 after METH. Injection of METH into the erect penis (ie, during erection) reduced the vasoconstrictor action of METH; CCP/MAP was 0.74+/-0.02 before METH and 0.55+/-0.05 after METH (P<0.05). The vasoconstrictor action of METH was slightly reduced when given in conjunction with NOR-1, a NO donor drug; CCP/MAP was 0.70+/-0.05 before METH, 0.55+/-0.09 after METH but this change was not significant. These results demonstrate that the response to alpha-adrenergic stimulation is attenuated during erection in response to ganglionic stimulation. Furthermore, it appears that NO, produced during erection, may serve to override agonist-induced vasoconstriction. These results support our hypothesis that NO acts to directly stimulate relaxation of cavernous smooth muscle and to inhibit the vasoconstrictor actions of agents like ET-1 and alpha-adrenergic agonists including norepinephrine.     

Transvaginal electrical stimulation in the treatment of genuine stress incontinence and detrusor instability

Electrical stimulation has been widely used in Europe to treat incontinence, but original studies and overall use of the device has been limited in North America. Forty-five patients with documented genuine stress incontinence, detrusor instability or mixed incontinence had self-administered therapy for 15 minutes twice daily, for a duration of 6 weeks. Treatment was delivered by a new stimulation device with an attached vaginal probe. Patients recorded treatment times, leak episodes and pad use. Objective measures included a pad test, standing stress test, standing CMG, and resting and dynamic urethral closure pressure profiles. The subjective success rates based on a questionnaire were 71% for genuine stress incontinence, 70% for detrusor instability, and 52% for combined incontinence. Objective testing for both types of incontinence did not show significant improvement after treatment. Four patients reported pain during use of the device, but most wished to continue the device in preference to other therapy.Supported in part by a grant from Hollister Incorporated.     

Pelvic physiotherapy in genuine stress incontinence.

In a prospective cohort study, the effect of pelvic physiotherapy on genuine stress incontinence, factors that influence therapy outcome, and patients' attitudes toward physiotherapy were studied. The study group consisted of 52 ambulatory and mentally fit Caucasian women (mean age, 53 years), suffering from genuine stress incontinence and who had no contraindications for surgery. They had physiotherapy twice weekly for ten weeks. The aim of physiotherapy was strengthening the pelvic floor muscles under control of digital vaginal palpation. Therapy outcome was assessed by a questionnaire and by the patients' self-monitoring urinary diary recording pad changes (52) and number of leakage episodes (35) before treatment and at end of therapy. The questionnaire also served to determine how patients appreciated physiotherapy. Physiotherapy had a low cure rate (+/- 25%) but a high improvement rate causing a decreased demand for surgery. At follow-up (mean 14 months) its beneficial effect was maintained. To date, only 10 patients (19%) have undergone surgery. Severity of symptoms was the only limiting factor. We conclude that every woman with urinary stress incontinence is a potential candidate for physiotherapy but surgical treatment as an option must remain open. Overall, physiotherapy was well accepted since episodes of urinary incontinence were less frequent and therefore bearable; however, changes in patients' behavior play a role.     

Maximum perineal stimulation for urinary incontinence.

Maximum stimulation of the pelvic floor has been advocated for the treatment of urinary incontinence associated with defective urethral closure mechanisms. Information in the literature was imprecise as to what constitutes a maximum stimulation. With one exception, published results are not encouraging when analysed. None of our 19 patients showed improvement. One had enhanced contraction when using an anal plug electrode following maximum stimulation, and this effect may warrant further study.     

The pathophysiology of genuine stress incontinence

Urinary continence in the female is maintained as long as intraurethral pressure exceeds bladder pressure. The elements which maintain this condition at rest and during stress include: internal urethral sphincter, external urethral sphincter, anatomic support of the urethrovesical junction, and intact innervation. Urethral junction and presence of genuine stress incontinence may be best assessed by measurement of resting and stress urethral closure pressure profiles using multichannel urodynamic testing. The findings subsequent to urethral closure pressure profilometry influence the kind of therapy selected, including types of surgery, when this treatment option is chosen.     

Acute electrical stimulation for urinary incontinence.

Acute or maximal electric stimulation of the pelvic floor muscles has been used in incontinent patients who are suitable candidates for electrical stimulation, but unwilling or unable to use the anal plug electrodes. Seventeen of 20 patients had relief or improvement of their incontinence. However 5 of these 17 patients had a relapse of symptoms on follow-up, requiring a repeat treatment with acute or maximal electrical stimulation.     

The investigation of female stress incontinence

Genuine stress incontinence is a common problem whose pathogenesis stems from a disturbance of the normal anatomy and innervation of the bladder neck and proximal urethra. A thorough understanding of this, as well as a methodical and logical investigation of the problem, will ensure correct patient selection and achieve a good long-term cure. The authors present a discussion of stress incontinence and its investigation.