Stress urinary incontinence in women: diagnosis and medical management

Stress urinary incontinence (SUI) is the most common form of urinary incontinence in women and is associated with high financial, social, and emotional costs. The history and physical examination can identify most patients with a significant stress incontinence component without the need for urodynamic testing. A variety of pharmacologic agents have been used off-label, but an evidence-based pharmacologic treatment has not been readily available. The development of a selective serotonin and norepinephrine reuptake inhibitor will add a potentially useful drug to the primary care physician's practice for treating female patients with SUI. In August 2004, a selective serotonin and norepinephrine reuptake inhibitor, duloxetine, became the first medication approved for the treatment of women with moderate to severe SUI throughout the European Union. As of November 2005, however, duloxetine has not been approved for the treatment of SUI in the United States.     

Duloxetine: a summary of published clinical experience

Effective oral therapy for genuine stress urinary incontinence (SUI) in women has, to date, been an unattainable goal. Although oral pharmacologic agents have been used for this condition, none has ultimately been successful, because of side effects, lack of efficacy, or problematic compliance with drug ingestion. The availability of an effective oral agent for SUI would increase the range of therapeutic options for symptom management and possibly make treatment accessible to more women who otherwise feel that surgical therapy is not an option because of social, personal, or medical reasons. Duloxetine is a selective serotonin (5-HT) and norepinephrine reuptake inhibitor that has been shown to increase rhabdosphincter activity. Rhabdosphincter contractility changes are thought to occur as the result of increased stimulation of alpha(1)-adrenergic and 5-HT(2) receptors in the sacral spinal cord, resulting in increased efferent pudendal nerve activity, producing increased pelvic floor tonus. Two large-scale studies have been completed employing subjective and objective outcomes to assess the therapeutic index of duloxetine as a therapy for SUI.     

Duloxetine: a new pharmacologic therapy for stress urinary incontinence

The dual serotonin (5-HT)/norepinephrine (NE) reuptake inhibitor duloxetine shows promise as a pharmacologic therapy for stress urinary incontinence. This agent modulates lower urinary tract function through selective inhibition of 5-HT and NE receptor sites. It works centrally at Onuf's nucleus to increase activity of the pudendal nerve. Duloxetine facilitates sphincter activity during urine storage but not during voiding, maintaining the bladder-sphincter synergy. Because it inhibits both 5-HT and NE reuptake, duloxetine appears to offer an advantage over agents that inhibit reuptake of a single neurotransmitter.     

Treatment of stress urinary incontinence with duloxetine hydrochloride

Currently, there are no approved medications for the treatment of stress urinary incontinence (SUI) in the United States. The effectiveness of duloxetine in the treatment of SUI is linked to its inhibition of presynaptic neuronal reuptake of serotonin and norepinephrine in the central nervous system, resulting in elevated levels of serotonin and norepinephrine in the synaptic cleft. In animal studies, this agent leads to an increase in nerve stimulation to the urethral striated sphincter muscle. A similar mechanism in women is believed to result in stronger urethral contractions, with improved sphincter tone during urine storage and physical stress. In 3 randomized, placebo-controlled clinical trials, patients receiving duloxetine had a statistically significant and clinically relevant reduction in the number of incontinence episodes and a corresponding improvement in quality of life. If this use of duloxetine is approved by the U.S. Food and Drug Administration, as it has been by the European regulatory agencies, it will be the first drug indicated for the treatment of SUI. This pharmacologic therapy is an additional option for women and is likely to become an integral component of patient management.     

Expectations of Stress Urinary Incontinence Surgery in Patients With Mixed Urinary Incontinence

Mixed urinary incontinence is estimated to affect 30% of all women who have urinary incontinence, and it has been shown to be more bothersome to women than pure stress incontinence. Given the degree of bother, many women will undergo surgical correction for incontinence. Patients have high expectations about the success of these interventions. Understanding mixed incontinence and the effects of our interventions can help guide therapeutic choices and manage patients’ expectations.Key words: Urodynamics, Mixed urinary incontinence, Sling, Anti-incontinence surgery, Urgency incontinenceIt has been estimated that approximately 30% of women with urinary incontinence have mixed urinary incontinence (MUI). Degree of bother is higher among women with MUI compared with those who have pure stress urinary incontinence (SUI).¹ MUI can be a very challenging and costly condition to treat.^2,3 Patients with MUI are often offered conservative therapy such as physical therapy, weight-loss strategies, and behavioral modification. Some patients also benefit from treatments aimed directly at urgency, frequency, and urgency incontinence (overactive bladder), which currently include pharmacologic therapy (antimuscarinic or β-3 agonists), chemodenervation (botulinum toxin), or neuromodulation (sacral or posterior tibial nerves).⁴ However, many patients with MUI progress to surgical therapies for treatment of SUI. This article reviews the literature available that can help clinicians manage expectations of SUI surgeries on patients with MUI.     

The pathophysiology of stress urinary incontinence: a historical perspective

This article provides a historical perspective on the evolution of theories regarding the pathophysiology of stress urinary incontinence (SUI). The progression of these theories has followed the development of the diagnostic technologies that have provided insight into different aspects of urethral dysfunction. The earliest theories tied SUI to anatomic failure of urethral support. Recognition that anatomic failure impacted the interplay of intra-abdominal pressure and the bladder and urethra led to theories focused on the dynamic interaction between the bladder and urethral pressures. Investigators then began to recognize the importance of urethral sphincteric dysfunction. More recently, investigators have attempted to combine the anatomic and functional etiologies into a consolidated theory. These efforts point to a multi-factorial etiology of SUI. Continuing research has provided new insight into the neurophysiology of urethral function, opening new avenues for tailoring therapy for SUI.     

The controversies regarding the role of estrogens in urogynecology

Estrogens are crucial for the proper functioning of genitourinary tract. Hypoestrogenism related to menopause could be linked to numerous disturbances of lower urinary tract. However, the results of most well designed clinical studies do not support use of estrogen or hormone replacement therapy for the treatment of genitourinary symptoms. According to evidence base medicine stress urinary incontinence, overactive bladder syndrome or pelvic organ prolapse are best treated by the surgery or non-hormonal drug therapy.     

Association of overactive bladder and stress urinary incontinence in rats with pudendal nerve ligation injury

Approximately one-third of patients with stress urinary incontinence (SUI) also suffer from urgency incontinence, which is one of the major symptoms of overactive bladder (OAB) syndrome. Pudendal nerve injury has been recognized as a possible cause for both SUI and OAB. Therefore, we investigated the effects of pudendal nerve ligation (PNL) on bladder function and urinary continence in female Sprague-Dawley rats. Conscious cystometry with or without capsaicin pretreatment (125 mg/kg sc), leak point pressures (LPPs), contractile responses of bladder muscle strips to carbachol or phenylephrine, and levels of nerve growth factor (NGF) protein and mRNA in the bladder were compared in sham and PNL rats 4 wk after the injury. Urinary frequency detected by a reduction in intercontraction intervals and voided volume was observed in PNL rats compared with sham rats, but it was not seen in PNL rats with capsaicin pretreatment that desensitizes C-fiber-afferent pathways. LPPs in PNL rats were significantly decreased compared with sham rats. The contractile responses of detrusor muscle strips to phenylephrine, but not to carbachol, were significantly increased in PNL rats. The levels of NGF protein and mRNA in the bladder of PNL rats were significantly increased compared with sham rats. These results suggest that pudendal nerve neuropathy induced by PNL may be one of the potential risk factors for OAB, as well as SUI. Somato-visceral cross sensitization between somatic (pudendal) and visceral (bladder) sensory pathways that increases NGF expression and alpha(1)-adrenoceptor-mediated contractility in the bladder may be involved in this pathophysiological mechanism.     

电针阴部神经刺激疗法联合Kegel盆底康复训练对产后压力性尿失禁患者盆底肌力、尿流动力学和生活质量的影响

摘要 目的：探讨电针阴部神经刺激疗法联合Kegel盆底康复训练对产后压力性尿失禁（SUI）患者盆底肌力、尿流动力学和生活质量的影响。方法：选取2019年6月~2021年11月期间于我院就诊的产后SUI患者109例,按照入院就诊奇偶顺序分为两组,其中对照组54例,接受Kegel盆底康复训练,研究组55例,接受电针阴部神经刺激疗法联合Kegel盆底康复训练。对比两组疗效、漏尿量、尿失禁程度、盆底肌力、尿流动力学和生活质量。结果：研究组的临床总有效率高于对照组（P<0.05）。两组治疗后盆底肌肌力各指标（手测肌力和Ⅰ类肌纤维最大值、Ⅱ类肌纤维平均值）均升高,且研究组高于对照组（P<0.05）。两组治疗后漏尿量、尿失禁程度评分均下降,且研究组低于对照组（P<0.05）。两组治疗后尿流动力学相关指标[腹压漏尿点压（AL-PP）、最大尿流率（Qmax）和最大尿道闭合压力（MUCP）]均升高,且研究组高于对照组（P<0.05）。两组治疗后尿失禁生活质量量表（I-QOL）各维度（限制性行为、心理影响、社交活动受限）评分及总分均升高,且研究组高于对照组（P<0.05）。结论：电针阴部神经刺激疗法联合Kegel盆底康复训练可有效改善产后SUI患者的盆底肌肌力和尿失禁情况,减少漏尿量,同时可促进尿流动力学恢复,进而提高患者的生活质量。     

The role of gonadotropin-releasing hormone antagonists for the treatment of benign prostatic hyperplasia

Medical therapy is the preferred first-line approach in the management of lower urinary tract symptoms in men with benign prostatic hyperplasia. The magnitude of the improvement in lower urinary tract symptoms observed in response to combination therapy (alpha-blocker plus 5-alpha reductase inhibitors) does not approach that achieved with prostatectomy. Various drugs have been under consideration, including BXL628, lonidamine, and phosphodiesterase inhibitors, all of which have had unacceptable side effects. The gonadotropin-releasing hormone antagonist cetrorelix is associated with dose-dependent symptom improvement and reduction of prostate volume. Elucidating the mechanism for cetrorelix-mediated improvement in lower urinary tract symptoms will likely contribute to unraveling the pathophysiology of lower urinary tract symptoms in men.     

Lactobacillus rhamnosus L60, a potential probiotic isolated from the human vagina

The vagina has been increasingly viewed as an "ecosystem" whose normal microflora help protect it from invading pathogens, including those that cause urinary tract infections and sexually transmitted diseases. We tested new strains of lactobacilli as potential probiotics for maintenance of urogenital tract health, as well as prevention and therapy of urogenital infections. A strain of lactobacilli isolated from the vagina of nonpregnant, healthy, premenopausal women was identified as Lactobacillus rhamnosus L60 by 16S rDNA sequence homology. L60 was evaluated for antimicrobial activity, in vitro antibiotic resistance, autoaggregation, surface hydrophobicity, co-aggregation with other bacterial species, hydrogen peroxide (H(2)O(2)) production, and bacterial adherence. It displayed a wide spectrum of antimicrobial activity against urogenital pathogens, and resistance to antibiotics commonly prescribed for infections caused by these pathogens. L60 produced H(2)O(2), adhered to vaginal epithelial cells, co-aggregated with Escherichia coli and Candida albicans, and displayed self-aggregation. In view of these characteristics, L60 is considered a potential probiotic, and will be further evaluated for preventive and therapeutic application locally in the vaginal tract.     

Medical treatment of benign prostatic hyperplasia

Medical therapy for the treatment of benign prostatic hyperplasia (BPH) became an accepted standard of care in the 1990s following the reports of randomized, double-blind, placebo-controlled studies showing that finasteride, a 5-α reductase inhibitor, and terazosin, an α-blocker, significantly improved lower urinary tract symptoms and increased peak urinary flow rates in men with BPH. This article reviews novel approaches to the pharmacological treatment of BPH.     

EMG biofeedback for functional bladder-sphincter dyssynergia: A case study

The present study utilized EMG biofeedback in the treatment of functional bladder-sphincter dyssynergia, a learned incoordination of bladder and urethral sphincter activity during voiding. The condition is usually associated with a history of painful urination due to bladder infections, surgery, or harsh toilet training. The subject was an 8-year-old girl with chronic diurnal urinary frequency, urge incontinence, and nocturnal enuresis. Treatment consisted of intensive instruction in alternately tensing and relaxing her lower pelvic musculature, as well as relaxing during voiding. These exercises were accompanied by EMG biofeedback from perianal and perivaginal surface electrode sites. Home practice consisted of the tense-relax exercise, relaxation during voiding, and self-monitoring and record-keeping. There were 17 sessions over a period of 9 months. No medication was used. Marked reduction (to normal levels) in diurnal urgency and frequency occurred by the 3rd week of therapy, and complete recovery of normal function, including nocturnal continence without waking, occurred by the 13th therapy session, 5 months after therapy began. Follow-up 1 year after therapy revealed that these gains were being maintained. Pre- and posttherapy urodynamic studies corroborated the achievement of normal urinary function.     

Ciprofloxacin and therapy of urinary tract infections, including those due to Staphylococcus saprophyticus]

Staphylococcus saprophyticus is one of the main pathogens of cystitis in young women. The human biotopes are contaminated by the staphylococcus on direct contacts with domestic animals or after using not properly cooked food of animal origin. Young women are more susceptible to colonization of the urinary tract by S. saprophyticus vs. the other contingents. Sexual intercourse is conducive to the colonization and infection. Shifts in the urinary tract microflora due to the use of spermicide, as well as candidiasis promote colonization of the urinary tract by S. saprophyticus. At present fluoroquinolones are considered as a significant independent group of chemotherapeutics within the class of quinolones, inhibitors of DNA gyrase, characterized by high clinical efficacy in the treatment of urinary tract infections. Especially significant clinical experience with ciprofloxacin in the therapy of urinary tract infections is available.     

The definition, prevalence, and risk factors for stress urinary incontinence

Stress urinary incontinence (SUI) has an observed prevalence of between 4% and 35%. Whereas the clinical definition of SUI has been established by the International Continence Society, the epidemiologic definition has not been established, leading to a broad disparity in reported prevalence rates. Numerous risk factors for SUI have been identified. Aging, obesity, and smoking appear to have consistent causal relationships with the condition, whereas the roles of pregnancy and childbirth remain controversial. The prevalence of many of these risk factors is increasing in the adult female population of the United States. These population changes, combined with increasing physician awareness and the availability of nonsurgical therapy, will likely increase the number of women receiving care for SUI over the next 3 decades.     

Bulking agents in the treatment of stress urinary incontinence: history, outcomes, patient populations, and reimbursement profile

Stress urinary incontinence (SUI) can be defined as involuntary loss of urine during a period of increased abdominal pressure and in the absence of detrusor activity. Bulking agents used in the urethra are one of the newer but established technologies for the treatment of SUI. An understanding of the demographics of SUI will help in the selection of patients for bulking agent therapy. Knowledge of available materials, including their positive and negative aspects, is also required. Autologous fat, silicone beads, collagen, carbon particles, and polytetrafluoroethylene paste have all demonstrated success to some degree, but none have met both criteria for success (remaining efficacious over time and maintaining a low side-effect profile). An implantable solution of ethylene vinyl alcohol suspended in dimethyl sulfoxide, currently in clinical testing and review, shows minimal foreign body reaction and is one option being investigated to address patient needs for improved bulking therapy.     

Treatment of stress urinary incontinence with adipose tissue-derived stem cells

Background aimsEffective treatment for stress urinary incontinence (SUI) is lacking. This study investigated whether transplantation of adipose tissue-derived stem cells (ADSC) can treat SUI in a rat model.MethodsRats were induced to develop SUI by postpartum vaginal balloon dilation and bilateral ovariectomy. ADSC were isolated from the peri-ovary fat, examined for stem cell properties, and labeled with thymidine analog BrdU or EdU. Ten rats received urethral injection of saline as a control. Twelve rats received urethral injection of EdU-labeled ADSC and six rats received intravenous injection of BrdU-labeled ADSC through the tail vein. Four weeks later, urinary voiding function was assessed by conscious cystometry. The rats were then killed and their urethras harvested for tracking of ADSC and quantification of elastin, collagen and smooth muscle contents.ResultsCystometric analysis showed that eight out 10 rats in the control group had abnormal voiding, whereas four of 12 (33.3%) and two of six (33.3%) rats in the urethra-ADSC and tail vein-ADSC groups, respectively, had abnormal voiding. Histologic analysis showed that the ADSC-treated groups had significantly higher elastin content than the control group and, within the ADSC-treated groups, rats with normal voiding pattern also had significantly higher elastin content than rats with voiding dysfunction. ADSC-treated normal-voiding rats had significantly higher smooth muscle content than control or ADSC-treated rats with voiding dysfunction.ConclusionsTransplantation of ADSC via urethral or intravenous injection is effective in the treatment and/or prevention of SUI in a pre-clinical setting.     

不同治疗方式对产后压力性尿失禁的疗效评估

目的:探究不同方法治疗产后压力性尿失禁(stress urinary incontinence,SUI)的临床疗效,并分析其相关的产科影响因素,为该病的预防和治疗提供相关的依据。方法:选取2015年1月至2016年1月在汉川市人民医院于产后42天返院行盆底功能筛查时诊断为产后SUI同时符合纳入标准的初产妇103例,并将其按患者的意愿分为3个治疗组,随访观察组(I组)有30例患者,盆底肌锻炼组(II组)有35例患者,生物反馈联合电刺激治疗组(III组)有38例患者。分别治疗8周后,通过国际尿失禁咨询委员会尿失禁问卷表(ICI-Q-SF)问卷调查、尿垫试验及盆底肌力测定进行疗效评价,并分析生物反馈联合电刺激疗效的影响因素。结果:治疗前,三组间盆底肌力无显著性差异(P0.05);治疗后,三组间两两比较均有显著性差异(P0.05)。治愈率而言,III组与II组和I组比较,差异有统计学意义(P0.05)。单因素分析显示:孕期体重增加量与产后SUI严重程度和抑郁评分对生物反馈联合电刺激治疗疗效显著相关(P0.05),而年龄、产前BMI、新生儿出生体重等对治疗疗效无显著相关性(P0.05)。多因素非条件Logistic回归分析显示:孕期体重增加量与产后SUI严重程度是影响生物反馈联合电刺激治疗疗效的独立因素。结论:电刺激联合生物反馈治疗对产后SUI的疗效与单纯盆底肌锻炼治疗和单纯随访观察相比具有明显的优势,可作为临床治疗产后SUI的首选方案。影响其疗效的主要因素为孕期体重增加量与产后SUI严重程度,故控制孕期体重可能会促进电刺激对产后SUI的疗效。     

Hypogammaglobulinemia: therapeutic rationale.

Hypogammaglobulinemia is a feature of several B-cell disorders and is manifested clinically by recurrent infection, most commonly chronic upper and lower respiratory tract disease. Immunoglobulin replacement therapy is available, with at least four different routes of administration. There are as yet no convincing data that allow comparison of the cost-effectiveness of these methods. However, by individualizing therapy for each patient, it is possible to prevent life-threatening acute infections, reduce the severity of chronic upper and lower respiratory tract disease, improve pulmonary function and achieve normal levels of IgG. These are the currently acceptable goals of therapy in patients with hypogammaglobulinemia.