eMedicine Specialties > Urology > Incontinence

Injectable Bulking Agents for Incontinence

Author: Raymond Rackley, MD, Professor of Surgery, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University; Staff Physician, Center for Pelvic Medicine and Pelvic Reconstruction, Glickman Urological Institute, Cleveland Clinic Foundation
Coauthor(s): Michael S Ingber, MD, Clinical Fellow, Glickman Urological and Kidney Institute of the Cleveland Clinic; Farzeen Firoozi, MD, Clinical Fellow, Center for Female Urology and Pelvic Reconstructive Surgery, Glickman Urological and Kidney Institute of the Cleveland Clinic
Contributor Information and Disclosures

Updated: May 8, 2009

Introduction

Injectable therapy of bulking agents composed of synthetic materials, bovine collagen, or an autologous substance augment the urethral wall and increase urethral resistance to urinary flow. Injection of bulking agents used to treat a dysfunctional urethra is a minimally invasive method of correcting intrinsic sphincteric deficiency (ISD) that results in stress urinary incontinence (SUI).

History of the Procedure

Bulking agents have been used for the management of stress urinary incontinence for more than a decade, but their application has been limited by ease of placement, durability, and antigenicity or compatibility issues. The lack of a single reproducible injectable agent has led to the development and application of several agents that provide reasonable efficacy with minimal associated morbidity. Continuous development of injectable techniques and materials technology provide the basis for multiple new bulking agents. Clinical trials continue to provide evidence-based experience with this form of minimally invasive solutions in the treatment of stress urinary incontinence.

Problem

Urinary incontinence is an underdiagnosed and underreported medical condition. An estimated 50%-70% of women with urinary incontinence fail to seek medical evaluation and treatment because of social stigma. Only 5% of individuals who are incontinent and 2% of nursing home residents who are incontinent receive appropriate medical evaluation and treatment. Patients who are incontinent often cope with this condition for 6-9 years before seeking medical therapy.

Intrinsic sphincter deficiency is the inability of the urethra to provide adequate urethral closure pressure that prevents involuntary loss of urine during increases in abdominal pressure.

Frequency

Urinary incontinence affects approximately 13 million people in the United States, predominantly women. Approximately 10%-35% are adults. Approximately 50% of the 1.5 million nursing home residents are affected. As many as 60% of nursing home patients are incontinent, and 30% of elderly individuals living at home are incontinent.

Stress incontinence affects 15%-60% of women—both young and old individuals. More than 25% of nulliparous young college athletes experience stress incontinence when participating in sports.

Urethral hypermobility with mild-to-moderate intrinsic sphincter deficiency is the most common form of stress urinary incontinence in the overall female population; however, severe intrinsic sphincter deficiency is more prevalent in elderly women and rarely occurs spontaneously. More than 90% of women with severe intrinsic sphincter deficiency have undergone some form of pelvic surgery or trauma. Zaragoza (1996) has reported that, of 60 women undergoing pubovaginal sling surgery, 37% were diagnosed with severe intrinsic sphincter deficiency as their cause of stress urinary incontinence.¹ Morgan et al (2000) have reported a 48% incidence of severe intrinsic sphincter deficiency in women who have undergone simple hysterectomy.²

Etiology

Intrinsic sphincter deficiency can result from the aging process, trauma, surgery, or neurologic dysfunction. The most common cause of intrinsic sphincter deficiency in men is radical prostatectomy for prostate cancer or transurethral resection of the prostate to treat benign prostatic hyperplasia. A less common cause of intrinsic sphincter deficiency is trauma to the bladder neck or prostate, resulting from pelvic fracture due to high-impact deceleration injuries. In women, intrinsic sphincter deficiency may occur as a result of postmenopausal estrogen loss, previous bladder neck operations (eg, urethropexy, pubovaginal sling), or as a result of pelvic trauma. Patients with a neurogenic disorder such as myelomeningocele may have an open bladder neck that results in severe intrinsic sphincter deficiency and urinary loss.

Pathophysiology

Intrinsic sphincter deficiency is due to devascularization and/or denervation of the bladder neck and proximal urethra. The urethral sphincter may become weak after pelvic surgery (eg, failed bladder suspension surgery) because of nearby nerve damage or excessive scarring of the urethra and surrounding tissues. Additional causes of urethral dysfunction include pelvic radiation or neurologic injury, including myelomeningocele. Women with severe intrinsic sphincter deficiency do not always have the usual urethral hypermobility during a Valsalva maneuver. Paradoxically, the urethra appears well supported. This results in lead pipe urethra, where the urethra remains open at rest. Whenever intra-abdominal pressure exceeds proximal urethral pressure, involuntary urine loss ensues. Because the urethra cannot remain closed in this setting, the patient experiences almost continuous urinary incontinence.

Presentation

Patients with stress urinary incontinence due to severe intrinsic sphincter deficiency present with symptoms typical of stress incontinence, but the symptoms are much worse. Patients report involuntary urine loss when coughing, laughing, and sneezing. They also describe urine loss when standing up from a sitting position. If the problem is severe, patients describe continuous dribbling of urine and typically require a high volume of pad use.

Patients with mild intrinsic sphincter deficiency and minimal urethral hypermobility typically do not report irritative voiding symptoms such as urinary frequency, urgency, and nocturia. The presence of irritative voiding symptoms should raise an index of suspicion for overactive bladder. In addition, irritative voiding symptoms in combination with hematuria (gross or microscopic) warrant a complete bladder tumor workup.

A detailed pelvic examination in patients with stress urinary incontinence due to severe intrinsic sphincter deficiency often reveals a well-supported urethra with minimal urethral hypermobility. During a Valsalva maneuver, the resting Q-tip excursion angle is less than 30°.

Signs of estrogen deficiency such as atrophic vaginitis, vaginal mucosa with absent rugae, and thinned-out shiny vaginal epithelium may be observed. These patients demonstrate a positive finding on cough stress test either in a lithotomy or in a standing position if their bladder is relatively full.

A vaginal speculum examination in patients with mild or moderate intrinsic sphincter deficiency–caused stress urinary incontinence demonstrates a poorly supported urethra with urethral hypermobility. During a Valsalva maneuver, the resting Q-tip excursion angle is greater than 30°. The vaginal mucosa manifests normal rugae. In addition, signs of pelvic support decay also may be present. They include cystocele, rectocele, enterocele, and uterine descensus. Patients who have undergone hysterectomy may have signs of vaginal vault prolapse.

Patients with coexisting pelvic organ prolapse may report dyspareunia, vaginal pain upon ambulation, and a bulging sensation in the vagina. Patients with severe pelvic organ prolapse may experience herniation of pelvic organs out of the vaginal introitus, necessitating manual reduction. Patients with symptomatic rectoceles report severe constipation, often necessitating digital disimpaction. Severe cystoceles may drag both ureters through the true pelvis as the bladder herniates out of the vagina, causing renal azotemia. Bilateral hydroureteronephrosis is due to compression of the ureters against the bony pelvic inlet, resulting in ureteral obstruction.

Indications

Social indications for surgical intervention include any stress incontinence that interferes with the patient's quality of life. Pathological indications for correcting intrinsic sphincter deficiency include primary urethral dysfunction, failed previous bladder neck surgery, and severe attenuation of endopelvic fascia.

Treating intrinsic sphincter deficiency secondary to severe intrinsic sphincter deficiency is often more difficult than treating intrinsic sphincter deficiency induced by urethral hypermobility, which is why severe intrinsic sphincter deficiency is referred to as complex or complicated stress incontinence. If the urethra displays low outlet resistance, treatment must be designed to increase outflow resistance.

Candidates for periurethral bulking agents include women with intrinsic sphincter deficiency and men who are incontinent after prostate surgery. In women with severe intrinsic sphincter deficiency or urethral hypermobility–induced intrinsic sphincter deficiency, the best long-term results are obtained with a sling or retropubic bladder neck suspension procedure. However, periurethral injection therapy has been introduced because of excellent short-term results as a minimally invasive procedure.

In women with urethral hypermobility–induced intrinsic sphincter deficiency, early studies have reported favorable short-term results with injectables; however, long-term (>1 y) data are lacking. Incontinent men who fare best with injectable therapy are those who have stress incontinence after transurethral prostatectomy (TURP). Men with stress incontinence after radical prostatectomy have the least significant success rate with bulking agents, and these men may be treated best with a sling procedure or an artificial urinary sphincter.

Relevant Anatomy

The female urethra is a 4-cm elongated tube composed of an inner epithelial lining, a spongy submucosa, a middle smooth muscle layer, and outer fibroelastic connective tissue. The spongy submucosa contains rich vascular plexus that is responsible for providing adequate urethral occlusive pressure to create the washer effect, an important female continence mechanism. Urethral smooth muscle and fibroelastic connective tissues circumferentially augment the occlusive pressure generated by the submucosa.

Female urethral function is influenced by estrogen. The lack of estrogen at menopause leads to atrophy and replacement of submucosa (ie, vascular plexus) by fibrous tissue. Previous bladder neck operations, radiation, and neurogenic disease can affect the patient's ability to achieve a perfect seal. When estrogen is administered to postmenopausal women with atrophic vaginitis, the mucosa regains its turgor, with simultaneous up-regulation of alpha-receptors and angiogenesis of vascular plexus. Lack of estrogen is a risk factor for developing intrinsic sphincter deficiency, but estrogen replacement may reverse its effects.

In men, the urethra averages 20-22 cm in length, and its anatomy is somewhat more complex than the female urethra. The male urethra is divided into anterior and posterior portions. The anterior urethra contains the penile (or pendulous) urethra and the bulbous urethra, which are lined by pseudostratified columnar epithelium. The urethra is surrounded by the corpus spongiosum within the penis. The posterior urethra is comprised of the membranous urethra and the prostatic urethra, which contains transitional epithelium. The membranous urethra passes through the urogenital diaphragm, which contains the external urethral sphincter. Smooth muscle fibers extend into the bladder neck and preprostatic urethra to form the internal sphincter, which preserves continence and prevents retrograde flow of semen into the bladder during ejaculation.

Contraindications

Periurethral bulking agents should not be used in the setting of pure urge incontinence or bladder outlet obstruction. A patient with mixed incontinence (eg, stress and urge) in whom the urge component is the predominant problem may elect to address the symptoms of bladder overactivity prior to bulking up the urethra but may find that treatment of the stress urinary incontinence also improves the urge incontinence. Patients with a hypersensitivity to collagen, noted on skin testing prior to injection, should not undergo this type of therapy.

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