Berek Novak's Gyn 2019. Chapter 29 Urinary Tract

 Chapter 29 Urinary Tract

KEY POINTS

1 The lower urinary tract comprises of the bladder and urethra; it is under autonomic

and somatic nervous system control, and is anatomically supported by the pelvic

floor musculature.

2 Urinary incontinence, although underdiagnosed, is very common, has a significant

impact on quality of life, and is generally treated successfully with conservative or

surgical treatments.

3 Stress urinary incontinence is the most common subtype and occurs with increases in

abdominal pressure; it can be treated with pelvic floor exercises, pessaries,

behavioral modification, and surgery.

4 Urgency urinary incontinence occurs with a sudden desire to urinate that cannot be

postponed; it can be treated with bladder training, medications, behavioral

modification, bladder onabutulinumtoxinA injections, and neuromodulation.

5 Mixed urinary incontinence is the co-occurrence of stress and urgency incontinence;

it is the most bothersome and impactful subtype, and most common in late

adulthood.

6 Voiding dysfunction and bladder pain syndrome are less common than urinary

incontinence, but more challenging to treat successfully.

INTRODUCTION

[1] The urinary tract in women is comprised of the bladder that receives and

stores urine from the kidneys as it is propelled downstream via the right and

left ureters. The bladder expels the urine out of the body through the urethra

when it reaches capacity or when it is socially appropriate to do so. To help

accomplish this dual role of storage and voiding, the bladder and urethra are

enveloped with muscles whose fibers are innervated by an intricate network

of autonomous and somatic nerves, and they are anatomically supported by a

complex system of pelvic floor muscles, fascia, connective tissues, and nerves

within the pelvis.

Anatomy of the Lower Urinary Tract

In the supine position, the bladder is positioned between the pubic bone and

transversalis fascia anteriorly and the endopelvic fascia, vagina, and uterus

posteriorly. The lateral margins of the bladder abut the obturator fascia and the

condensation of muscle and connective tissue known as the arcus tendinous

muscle fascia (white line). The bladder is comprised of three layers including the

1659mucosa, detrusor (mostly smooth muscle), and serosa. The bladder mucosa

consists of the urothelium, basement membrane, and lamina propria. The latter is

composed of an extracellular matrix with different cell types, nerve endings,

lymphatic and blood vessels, all of which may play a role in maintaining bladder

compliance and act as a communication portal between the nervous system and

bladder muscle (1). The trigone, which is the base of the bladder, gets its name

from the triad of the two ureteral orifices and the proximal urethra that make up

the three corners of the triangle. The urethra is a 4-cm tubular structure

surrounded by skeletal muscles. It travels over the anterior wall of the vagina and

exits the urogenital diaphragm under the pubic symphysis as it opens into the top

of the introitus (Fig. 29-1).

Innervation of the Bladder and Urethra

The bladder is primarily innervated by the autonomic, the sympathetic and

parasympathetic, nervous systems. The sympathetic nervous system originates

from the thoracolumbar region of the spinal cord. Signal transmission occurs via

the paraspinal ganglia with norepinephrine being the primary postganglionic

neurotransmitter stimulating two different adrenergic receptor types: (a) the alpha

receptors are mostly located in the urethra and trigone; and (b) the beta receptors

are primarily located in the body of the detrusor muscle. The parasympathetic

nervous system originates from the sacral region of the spinal cord. Unlike the

sympathetic system, the parasympathetic system has long neurons that exit from

S2 to S4, synapse with their ganglia closer to the end organ (bladder), and

transmit their signals via short postganglionic neurons to the body of the detrusor

muscle. Here, transmission of messages occurs through acetylcholine

neurotransmitters stimulating muscarinic (or cholinergic) receptors. The somatic

nervous system plays a secondary role in the lower urinary tract system. It

originates from the sacral (S2–S4) region of the spinal cord via the pudendal

nerve; it provides motor innervation to the urethral sphincter and pelvic floor

muscles, and sensory innervation to the perineum (2).

1660FIGURE 29-1 Lateral view of the pelvic floor showing the anatomic location of the

bladder, urethra, vagina, and pelvic floor support structures transected at the level of the

vesical neck.

The central command of the sacral micturition center comes from impulses

generated at the level of the pontine micturition center located in the brain stem

which is regulated by signals that arise from higher levels of the cerebellum and

cortex of the brain. This complex interplay between the upper cortex, cerebellum,

and brainstem plays a key and dual role of: (a) inhibition that supports the storage

function during the filling phase; and (b) stimulation that facilitates the

micturition function of the bladder during the voiding phase (3).

The Physiology of Storage and Voiding

The primary role of the bladder is to store urine produced by the kidneys

and excreted through the ureters, and to subsequently eliminate the urine

outside the body through the urethra. The function of storage is made

possible by several factors including: (a) intrinsic factors to the bladder such

as the ability of its elastic smooth muscle fibers to stretch as the volume of

urine distends its capacity; (b) extrinsic factors to the bladder including

excitatory neurologic stimuli that constrict the proximal urethra and

urethral sphincter, and inhibitory neurologic stimuli that inhibit (or relax)

1661the detrusor muscle of the bladder. This reservoir function of the bladder,

which in effect translates into its continence mechanism, is dependent on the

proper functioning of the autonomic (sympathetic and parasympathetic)

nervous system, and the somatic nervous system (4).

Continence during storage is dependent on the integrity of the bladder

muscle, urethra, and the pelvic floor support structures surrounding the

lower urinary tract, including the levator ani muscles, endopelvic fascia, and

their attachments to the pelvic sidewall and the white line. The urethra has

several components within or around it that play an important role. These include

the striated muscles of the urethral sphincter, the smooth muscles of the urethra,

and the neurovasculature of the urethral wall, all of which help maintain elasticity

and the epithelial coaptation function of the urethra during times of bladder filling

(5,6). The extrinsic structures supporting the urethra and the intrinsic

urethral function are equally important, to the extent that a defect in the

former can lead to urinary incontinence resulting from hypermobility of the

urethrovesical junction, and a defect in the latter can lead to urinary

incontinence caused by intrinsic sphincter deficiency.

During the filling phase, the sympathetic nervous system through the lumbar

region of the spinal cord sends inhibitory signals to the beta receptors in the

bladder to relax, and excitatory signals to the smooth muscles of the trigone and

urethra to contract. As the bladder gets distended, afferent fibers from the bladder

send impulses to the central nervous system through the pelvic nerve to the sacral

spinal cord. This initiates two types of impulses: one that is transmitted

horizontally via the micturition reflex back to the bladder, and another that is

transmitted vertically up to the brain. The latter will make one of two conscious

decisions. If it is socially inappropriate to initiate micturition, it will send

excitatory impulses via the pudendal nerve to contract the pelvic floor muscles

and external urethral sphincter, and inhibitory impulses to supplement the

function of the sympathetic system (Fig. 29-2). Alternatively, the brain may

decide it is an opportune time to eliminate the urine. In this instance, it will send

voluntary impulses to the striated muscles to relax the pelvic floor and urethral

sphincter. It will also send facilitative impulses to the pontine micturition center

to release its bladder inhibition. This transmits impulses down the spinal cord to

activate the sacral micturition reflex via the parasympathetic system, resulting in

stimulation of the cholinergic receptors and bladder contraction while the urethra

is relaxed (7).

1662FIGURE 29-2 Detrusor–sphincter reflex during urine storage: The sympathetic system

promotes the bladder to relax (inhibition) and the outlet to contract (stimulation).

Concurrently, the pudendal nerve stimulates the urethral sphincter to contract. (DeGroat

WC. A neurologic basis for the overactive bladder. Urology 1997;50(Suppl 6A):36–52;

Figure 4, need permission.)

URINARY INCONTINENCE

1663[2] Disorders of urine storage are typically expressed by patients with a

limited number of bladder control symptoms that include urinary urgency,

frequency, nocturia, and urinary incontinence. Urgency is defined as a

sudden, compelling desire to pass urine which is difficult to defer (8).

Frequency (i.e., increased daytime voids) and nocturia (increased nighttime

voids) are surrogates of urgency, and they are more commonly used than

urgency in epidemiologic and clinical trials because they are easier to

measure (9). The present International Continence Society (ICS) guidelines

define nocturia as waking up one or more times to urinate; whereas

frequency occurs when the patient considers that she is going to the

bathroom more often than her normal (8).

[2] Urinary incontinence, defined as any involuntary leakage of urine, is easier

to measure or quantify than urgency. Of all the urinary storage symptoms, it tends

to be the most distressing, impactful, and costly. Although the signs and

symptoms of urinary incontinence appear to be a straightforward expression of

bladder disorder, its diagnosis and treatment is anything but simple. The

complexity of the bladder is in its simplicity. There are many underlying causes

that can potentially lead to urinary incontinence. In the following sections, we

will define urinary incontinence and its subtypes, describe its epidemiology and

impact, discuss the pathophysiology and associated risk factors, discuss

evaluation and examination of women with incontinence, explore the various

diagnostic tools, and propose available treatment modalities.

Definitions

Defining urinary incontinence has been challenging. Should urinary incontinence

be defined as any amount of urine loss, then the overwhelming majority of

women may fit the definition. Conversely, should urinary incontinence be defined

with stricter criteria, such as losing a certain volume of urine with a specific

number of episodes in a month, then only a minority of women would fit that

definition. A key consideration is to be able to distinguish normal from abnormal

lower urinary tract function. While much of the focus of clinical research is on

individuals with frank urinary incontinence, the ultimate challenge is to

understand when preclinical urinary incontinence starts, and more importantly the

trajectory it takes to progress into a clinically relevant and persistent condition.

Historically, urinary incontinence was defined as the involuntary loss of urine

represented as an objectively demonstrable event, and described to be a social or

hygienic problem (10). Although highly specific, this definition was clinically

impractical. Women who presented with subjective incontinence received little to

no attention if it was not observed by their clinicians during an examination, or if

it was not reported by patients to be a “hygienic” problem. Presently, urinary

1664incontinence is defined as the complaint of any involuntary leakage of urine

(8). Paradoxically, this new definition includes a substantial spectrum of women

who have experienced rare incidental urine loss events. Consequently, some

studies report urinary incontinence prevalence estimates of up to 60% (11).

Urinary incontinence has two main subtypes, stress and urgency urinary

incontinence, that either occur in isolation of each other, or they co-occur

and present as mixed urinary incontinence. [3] Stress urinary incontinence is

defined as loss of urine associated with activities such as coughing, sneezing,

lifting, or laughing. [4] Urgency urinary incontinence is defined as loss of

urine associated with a strong desire to urinate. Of note is that the term

“urgency” has replaced “urge” as a symptom of storage disorder; the latter is

considered to be a normal (nonpathologic) desire to void urine when the bladder

is full. [5] Mixed urinary incontinence is defined as urine loss associated with

activity and with a strong desire to urinate (8). Women with urinary

incontinence may express their symptoms continuously (continuous urinary

incontinence), with intercourse (coital incontinence), with change in position

(postural incontinence), with retention or incomplete bladder emptying

(overflow incontinence), during sleep (nocturnal enuresis), or without being

aware of it (insensible incontinence). Finally, the term functional incontinence

is used to define women who have an intact bladder function, but still report

incontinence caused by factors extrinsic to the bladder. Examples include

elderly women who have mental, psychological, or mobility ailments that prevent

them from making it to the bathroom on time. A summary of current definitions

of symptoms of lower urinary tract storage disorders is shown below (Table 29-

1).

Table 29-1 Classification and Definition of Lower Urinary Tract Symptoms in

Women

I. Abnormal

Storage

Symptoms and Signs

Incontinence

(symptom)

Any involuntary leakage of urine

Stress urinary

incontinence

(symptom)

Involuntary leakage on effort or exertion, or on sneezing or coughing

Stress urinary

incontinence

(sign)

Observation of involuntary leakage from the urethra, synchronous

with exertion/effort, or sneezing or coughing

1665Urgency

urinary

incontinence

(symptom)

Involuntary loss of urine associated with urgency

Mixed

incontinence

Involuntary loss of urine associated with urgency and also with effort

or physical exertion or on sneezing or coughing

Continuous

urinary

incontinence

Continuous involuntary loss of urine

Frequency Number of voids per day, from waking in the morning until falling

asleep at night

Increased

daytime

urinary

frequency

Micturition occurs more frequently during waking hours than

previously deemed normal by women (traditionally defined as more

than seven episodes)

Nocturia Interruption of sleep one or more times because of the need to

micturate (each void is preceded and followed by sleep)

Nocturnal

enuresis

Involuntary loss of urine that occurs during sleep

Urgency Sudden, compelling desire to pass urine, which is difficult to defer

Postural

urinary

incontinence

Involuntary loss of urine associated with change of body position, for

example, rising from a seated or lying position

Insensible

urinary

incontinence

Urinary incontinence where the women has been unaware of how it

occurred

Coital

incontinence

Involuntary loss of urine with coitus. This symptom might be further

divided into that occurring with penetration or intromission and that

occurring at organism.

Overactive

bladder

syndrome

(OAB)

Urinary urgency, usually accompanied by frequency and nocturia,

with or without urgency urinary incontinence, in the absence of

urinary tract infection or other obvious pathology

Although stress and urgency urinary incontinence are regarded as different

1666disease entities, it is important to note that women move among and between

stress and urgency urinary incontinence. In one large study of over 10,500

women, significant changes in incontinence status were reported over a 2-year

period: of those with baseline urgency urinary incontinence, 34% to 38%

remitted, 4% to 9% transitioned to stress urinary incontinence, and 16% to 20%

transitioned to mixed urinary incontinence; of those with baseline stress urinary

incontinence, 32% to 41% remitted, 4% transitioned to urgency urinary

incontinence, and 16% to 23% transitioned to mixed urinary incontinence; of

those with baseline mixed urinary incontinence, 22% to 27% remitted, 10% to

11% transitioned to urgency urinary incontinence, and 11% to 15% transitioned to

stress urinary incontinence (12).

Epidemiology of Urinary Incontinence

Prevalence

Prevalence estimates of urinary incontinence among community-dwelling

women range from 2% to 58% (11). This wide range in estimates results from

variation in definitions used, populations surveyed, age of study participants, and

other reasons. Over their lifetime, urinary incontinence affects more than one in

three women (13). Recent U.S. population data show that more than 20 million

women have urinary incontinence, and this is projected to increase by more than

50% in the coming decade (14). Although urinary incontinence prevalence overall

increases with age, prevalence patterns differ by incontinence subtype. [3] Stress

urinary incontinence peaks in the fifth decade of life and is the most common

subtype overall. Prevalence of urgency and mixed urinary incontinence is

relatively low up to the fourth decade of life, but gradually increases thereafter.

The average prevalence of stress, urgency, and mixed urinary incontinence is

13%, 5%, and 11%, respectively. [5] Mixed urinary incontinence becomes the

most dominant subtype in late adulthood (15) (Fig. 29-3).

1667FIGURE 29-3 Prevalence of stress, urgency, and mixed urinary incontinence by age. Note

the peak prevalence of stress urinary incontinence at 50 years of age followed by a decline;

also note the continuous increase in mixed urinary incontinence into late adulthood where

it becomes the most prevalent subtype. SUI, stress urinary incontinence; UUI, urgency

urinary incontinence; MUI, mixed urinary incontinence. (Minassian VA, Stewart WF,

Hirsch A. Why do stress and urge incontinence co-occur much more often than expected?

Int Urogynecol J Pelvic Floor Dysfunct 2008;19:1429–1440; Figure 1, need permission.)

Incidence and Remission

Longitudinal studies report high variations in urinary incontinence incidence

rates that range between 5% and 20%. In one meta-analysis, age-specific

incidence varied between 2/1,000 person-years before age 40 and increased to

5/1,000 person-years at age 50 (16). Remission rates of urinary incontinence

are equally high and range between 3% and 12%. Data from longitudinal

studies suggest that urinary incontinence is highly dynamic where women

cycle in and out of active disease (17–20). It is noteworthy that most

longitudinal studies that describe incidence and remission of urinary incontinence

offer little insight on the natural history of the urinary incontinence subtypes and

transition rates between stress, urgency, and mixed urinary incontinence (12).

Impact of Urinary Incontinence

Urinary incontinence is an emotionally, socially, physically, and economically

burdensome condition (21,22). It has a significant impact on quality of life

(QOL), where urinary incontinence has been shown to be associated with

embarrassment, anxiety, and depression (22–24). These emotional burdens

may lead women to adopt coping strategies that further alienate them from their

1668social environment resulting in further deterioration of QOL. There is a

downward cycle of impairment resulting in worsening psychological function.

Studies examining the burden of disease have shown that mixed urinary

incontinence is more severe, bothersome, and impactful on QOL than stress or

urgency urinary incontinence (25,26).

Despite the wide-ranging impact of urinary incontinence, only a minority of

women seek or receive care for their condition, resulting in underdiagnosis and

undertreatment. Since most women with early stages of urinary incontinence (i.e.,

mild to moderate urinary incontinence) do not seek care, when they finally

present with advanced symptoms (severe urinary incontinence), there is lost

opportunity to prevent or reverse disease progression (11). Managing urinary

incontinence is a substantial burden and cost for caregivers and the community.

Presence of urinary incontinence increases risk of nursing home admissions, and

in community-dwelling women, total urinary incontinence costs (direct and

indirect) are about $11.2 billion/year (27,28).

Pathophysiology

Stress Urinary Incontinence

Historically, the key urethral support responsible for continence was

considered to be at the bladder neck and proximal urethra. The

pubourethral ligaments, extending from the undersurface of the pubic bone

down to the urethra, were thought to be structurally important to maintain

continence (29). DeLancey used cadaveric studies to formulate the Hammock

Theory where he proposed that the primary support of the bladder neck and

urethra to be an intact vaginal wall at the base of the bladder (30). Through

its fibrous and muscular attachments to the pelvic sidewall, namely to the

condensation of the levator ani muscles, the vagina was shown to act as a

hammock to support the bladder neck, compress the urethra, and therefore

maintain continence. Loss of integrity of the hammock resulted in stress

urinary incontinence (30).

Concurrently, Petros and Ulmsten proposed the Integral Theory of

continence (31). They built on the work by DeLancey and others, and

hypothesized that stress urinary incontinence occurs as a result of connective

tissue laxity in the vagina and its supporting ligaments, namely the

pubourethral, cardinal/uterosacral, and arcus tendineus fascia pelvis. The

integral theory highlighted the role of the suspensory ligaments supporting

the proximal vagina that supports the mid-urethra. It hypothesized that the

multidirectional movement of the pelvic floor muscles coordinated the

urethral continence mechanism: (a) the forward direction of the

pubococcygeus muscle stretches the mid-vagina forward against the

1669pubourethral ligament to close the urethra from behind; (b) the backward

direction of the levator plate stretches the upper vagina and bladder base

backward and downwards in a plane around the pubourethral ligament to

close off the proximal urethra (32). In subsequent years, using urodynamic,

radiologic, and clinical observations, DeLancey proposed that the integrity of the

urethra is as, if not more, important in maintaining continence than the underlying

support structures. These structures include the epithelial coaptation of the

urethral mucosa with its neurovasculature, smooth muscles, and the striated

sphincteric muscles (6). Therefore, the current most accepted theory of stress

urinary incontinence pathogenesis is loss of integrity of structures intrinsic to

the urethra, and, to a lesser extent, the pelvic support structures in close

proximity, but extrinsic, to the urethra.

Urgency Urinary Incontinence

The pathophysiology of urgency urinary incontinence is not well-developed,

as the etiology of this condition in most women remains idiopathic. The term

“urgency urinary incontinence” is often used interchangeably with the term

“overactive bladder (OAB).” OAB is a syndrome associated with urgency,

usually accompanied by frequency, nocturia with (OAB-wet) or without

(OAB-dry) urgency urinary incontinence, and in the absence of a urinary

tract infection or other obvious pathology (8). Certain neurologic conditions

are known to be associated with urgency urinary incontinence (33). Women with

multiple sclerosis, Parkinson, or spinal cord injuries have a disruption of the

neuronal circuits at different levels of the central nervous system resulting in loss

of inhibitory control on the bladder voiding mechanism (34). The micturition

center in the brain maintains continence while the bladder fills up by suppressing

the urgency to urinate (35). Any abnormality in the pathways between the

micturition center and the bladder can lead to urgency urinary incontinence

(36).

Several theories have been developed for nonneurogenic OAB or idiopathic

urgency urinary incontinence. The epithelial hypersensitivity theory proposes

presence of chemosensitizing agents leading to bladder instability. These are

believed to be inflammatory substances such as nerve growth factor,

prostaglandins, and acetylcholine that increase detrusor muscle sensitivity and

neuronal excitability. The influence of these agents may be compounded by the

presence of a defective uroepithelium that leads to increased sensitivity of the

detrusor muscle (33,37). The myogenic theory suggests that the pelvic floor

sustains a physical strain during the developmental years. Myogenic dysfunction

ensues secondary to altered structure or disordered function of a group of

myocytes within the detrusor smooth muscle independent of its nerve supply (38).

1670Prolonged bladder outlet obstruction or bladder ischemia (from atherosclerosis or

diabetic neuropathy) can lead to denervation of detrusor muscle, muscle damage,

and increased hyperexcitability to acetylcholine (38). These and other proposed

theories are likely influenced by psychosocial disturbances, genetic

predisposition, inflammatory, and drug-induced conditions (37).

Mixed Urinary Incontinence

Mixed urinary incontinence is the most common incontinence subtype in

later adulthood. Women with mixed urinary incontinence tend to have more

severe symptoms that are bothersome and with a higher impact on QOL.

Mixed urinary incontinence may represent a combination of bladder storage

conditions of different etiologies. These may include women with independently

co-occurring stress or urgency urinary incontinence where symptoms of both

conditions are expressed on the same day or at different time periods; or stress

urinary incontinence that has predated urgency urinary incontinence or resulted in

stress-induced urgency urinary incontinence; or stress urinary incontinence

associated with urgency (OAB-dry) without incontinence. It is likely that mixed

urinary incontinence comprises different pathophysiologic subtypes that are still

not well understood (39).

Other Causes of Urinary Incontinence

Other conditions that may be associated with urinary incontinence where urine

loss occurs through the urethra include urethral diverticuli, and ectopic urethra.

A urethral diverticulum is a localized herniation of urethral mucosa into the

surrounding tissues. Diverticuli occur mostly in the distal urethra of women

between the ages of 30 and 60 years. The etiology of acquired diverticula is

unknown, but one accepted hypothesis is injury and blockage of periurethral

glands from repeated urinary tract infections with subsequent rupture into the

urethral lumen resulting in formation of a diverticulum. Diverticuli could be

congenital in nature likely representing a remnant of Gartner duct (40). Although

urine loss (dribbling) is reported with urethral diverticuli, women commonly

present with symptoms similar to urinary tract infections such as dysuria, urethral

pain, dyspareunia, and hematuria. On examination, a tender urethral mass is often

palpable (Fig. 29-4). An ectopic ureter is a congenital anomaly where the ureter

opens distally into the urethra or more commonly into the vagina. Here, the

mother of a baby girl usually presents to her pediatrician complaining of constant

wetness in the perineum of her child resulting from absence of any sphincteric

control.

1671FIGURE 29-4 Urethral diverticulum. (Iyer S, Minassian VA. Resection of urethral

diverticulum in pregnancy. Obstet Gynecol 2013;122:467–469; Figure 2, need permission.)

Extraurethral incontinence occurs when a part of the urinary system drains

through an abnormal opening bypassing the urethra. These are conditions that

could be either congenital such as bladder extrophy, or traumatic such as a fistula.

A bladder extrophy is a rare condition that involves a congenital absence of the

anterior vaginal wall and base of the bladder/urethra. This is usually identified at

birth and may require several and complicated surgical procedures to reconstruct.

A fistula is an acquired condition where there are one or more direct

communications between the vagina and ureter (ureterovaginal fistula), bladder

(vesicovaginal fistula), or the urethra (urethrovaginal fistula). The vesicovaginal

fistula is the most common, and usually arises from a prolonged obstructed labor,

1672in younger and poorly developed women in rural, underdeveloped regions of the

world. With prolonged labor, caused by malpresentation or inadequately sized

pelvis, the lower urinary tract and vagina are compressed between the head of the

unborn child and the maternal pelvic bones, sometimes for days. This leads to

ischemic injuries resulting in tissue breakdown, necrosis, and development of a

fistula (Fig. 29-5). Another obstetrics-related condition, known as Youssef

syndrome, may arise from a fistulous tract developing between the uterus and

vagina, commonly after repeated cesarean sections. Here, patients present with

cyclic hematuria, urinary incontinence, and amenorrhea.

Unlike obstetric causes of fistula formation, in the developed countries, a

genitourinary fistula usually arises from gynecologic causes. These include

pelvic malignancies, gynecologic surgeries such as hysterectomy, and pelvic

irradiation. Undiagnosed bladder or ureteral trauma, or an inadequately treated

injury during a hysterectomy (vaginal, laparoscopic, or abdominal) can result in

fistula formation, usually within the first 2 weeks after surgery. An alternate

process of fistula formation occurs from an occult injury to the bladder or ureter,

typically during a laparoscopic hysterectomy where an energy source is used to

transect the uterine pedicles. Here, the fistula may develop as a result of a latent

injury from spread of energy to the genitourinary system.

FIGURE 29-5 Vesico-vaginal fistula.

Risk Factors of Urinary Incontinence

To better understand the pathophysiology of urinary incontinence and its

1673subtypes, it is important to identify risk factors associated with, or that mediate

onset and progression of disease. Known risk factors for urinary incontinence

include: race, age, parity, obesity, diabetes, chronic cough, COPD and

smoking, previous pelvic surgery, medications, and functional and motor

impairment (Table 29-2). Evidence for an association between risk factors and

urinary incontinence is strong for some, and inconclusive for others. Race has

been shown to have a variable effect on urinary incontinence by subtype. In

general, white women have a higher prevalence and incidence of urinary

incontinence than Hispanic, Asian and black women. More specifically, across

urinary incontinence subtypes, white women are at a higher risk of developing

stress urinary incontinence, whereas black women are at a higher risk of

developing urgency urinary incontinence (41,42).

Age has a variable effect on urinary incontinence subtypes. Prevalence of

stress urinary incontinence peaks in the fifth decade and then declines

thereafter. Advancing age past the 50s is not a risk factor for stress urinary

incontinence alone (15). This is because vaginal birth is strongly associated

with stress urinary incontinence in the first two decades after childbirth, but

has little to no effect beyond that. Hence, as the time interval increases between

a woman’s age and the birth of her children, there is decreasing effect of

childbirth and onset of stress urinary incontinence (43,44). In contrast, advancing

age is a strong predictor of both urgency and mixed urinary incontinence.

Pregnancy increases the risk of stress urinary incontinence with about

50% of pregnant women reporting symptoms. Although most women report

resolution of their stress incontinence symptoms after birth, recurrence

within 5 years is high. Parity, is another strong risk factor of urinary

incontinence, and primarily for stress urinary incontinence. A recent 2016

meta-analysis showed that vaginal birth had a twofold increased risk of stress

urinary incontinence when compared with cesarean delivery (43). Parity is a risk

factor for mixed urinary incontinence; however, controlling for its association

with stress urinary incontinence in women with mixed urinary incontinence,

parity is not a risk factor for urgency urinary incontinence (45). Most

epidemiologic data suggest that having a cesarean section reduces the risk of

subsequent urinary incontinence (43,46).

Table 29-2 Common Risk Factors by Urinary Incontinence Subtype

1674Obesity is another major risk factor for urinary incontinence and its

subtypes (47,48). Similar to vaginal birth, the effect of increasing weight on the

pelvic floor may lead to pudendal nerve injury with subsequent levator ani muscle

atrophy leading to weakening of the pelvic floor urethral support structures (49).

The effect of increased weight is a risk for new-onset stress urinary

incontinence, and for urgency urinary incontinence secondary to detrusor

overactivity (50). Diabetes and obesity are strongly correlated, but controlling for

obesity, diabetes still stands out as an independent risk factor for urgency

urinary incontinence, and to a lesser extent, for stress and mixed urinary

incontinence (51). The mechanism of action of diabetes is believed to be

multifactorial including: (a) its diuretic effect leading to frequency and urgency

urinary incontinence; (b) microvascular injury to the nerves supplying the

detrusor muscle leading to detrusor overactivity; and (c) microvascular injury to

the pudendal somatic nerve supplying the urethral sphincter (37).

Risk factors such as previous pelvic surgery, chronic cough or pulmonary

disease, and smoking have potentially similar detrimental effects on the

pelvic floor resulting in urinary incontinence. For instance, previous

hysterectomy has been shown to be associated with stress and urgency

urinary incontinence (15), surgery for prolapse increases risk of new-onset

stress urinary incontinence (52), and surgery for stress urinary incontinence

1675may lead to de novo or worsening urgency urinary incontinence. History of

smoking is associated with all urinary incontinence subtypes (48). Other risk

factors, also referred to urinary incontinence caused by functional or transient

causes, are described within the DIAPPERS mnemonic (Table 29-3). These

include certain medications (e.g., psychotropic medications), urinary tract

infections, stool impaction, and psychologic and motor impairment. Unlike age,

race, and parity, these risk factors are modifiable by directly treating or altering

their effect on the individual, and more specifically on the bladder.

Table 29-3 Reversible Causes of Urinary Incontinence

D Delirium

I Infection

A Atrophic urethritis and vaginitis

P Pharmacologic causes

P Psychological causes

E Excessive urine production

R Restricted mobility

S Stool impaction

From Resnick NM, Yalla SV. Management of urinary incontinence in the elderly. N Engl

J Med 1985;313: 800–805, with permission.

Diagnosis

Historically, diagnosis of urinary incontinence required a big workup. First, a

detailed history and extensive physical and pelvic examination including Q-tip

testing were performed. Exhaustive 7-day long bladder diaries were required of

patients, and multiple urogynecologic surveys were administered. Laboratory and

bladder testing including urine analysis and urine culture, 24-hour pad test,

cystoscopy, urodynamics, and other tests were frequently performed. Mounting

evidence indicates that most of these diagnostic modalities are not cost-effective,

and unnecessary during the initial workup of a woman with urinary incontinence.

Based on the new AUA and ACOG guidelines, the workup of urinary

incontinence has become more streamlined (53,54). The urethral Q-tip test

has mostly been eliminated, and the 7-day bladder diary has been replaced

with a 2- to 3-day diary (55–57). Similarly, simpler and shorter forms of

1676QOL, bother, and sexual dysfunction questionnaires, specific to urinary

incontinence, have been developed. Cystoscopy is rarely an indication for

uncomplicated urinary incontinence, and urodynamics is no longer necessary

prior to treatment for simple urgency urinary incontinence, or prior to

surgery for uncomplicated stress urinary incontinence (58,59).

History Taking

Medical history taking from a woman with urinary incontinence should

explore the duration of time with urine loss, associated symptoms, and their

severity. Questions are asked to identify incontinence subtype based on the

circumstances surrounding the urinary incontinence episodes. Urine loss

associated mostly with activities such as coughing, sneezing, or laughing is

suggestive of stress urinary incontinence; women with stress urinary

incontinence report urine loss that occurs while they are on the trampoline

with their children, during activities such as running and jumping, and at

times, with intercourse. Symptoms associated with or immediately preceded

by an urgency episode are indicative of urgency urinary incontinence. The

latter may present with reports of increased urinary frequency, or nocturia.

Women describe symptoms of urgency with or without incontinence

provoked by the sound of running water (e.g., washing dishes), change in

temperature, getting out from the car, or as they open the door to get into

their homes. Many women, especially the older age group, report mixed

symptoms of stress and urgency urinary incontinence, and information on

bother and impact on QOL by subtype should be solicited.

Other relevant clinical information is history of previous medical or surgical

treatment for incontinence, coexisting urinary tract infection with symptoms such

as dysuria, hematuria, or suprapubic pain, fluid intake, and other health conditions

(e.g., neurologic), or medications that may be associated with incontinence. For

example, a woman with past history of stress urinary incontinence who underwent

a mid-urethral sling may now be presenting with urgency symptoms; another

woman presenting with occasional urgency urinary incontinence, a frequency of

15 episodes during the day and only once at night may admit to drinking a gallon

(about 4 L) of liquids, including coffee and soda; alternatively, a poorly

controlled diabetic woman who is a smoker may present with urgency (diuretic

effect of sugar) and stress (chronic cough effect from smoking) urinary

incontinence symptoms. Many medications taken for other medical conditions

can impact the lower urinary tract and should be discussed with patients as

potential contributors to their symptoms (Table 29-4).

Table 29-4 Medications that May Affect the Function of the Urinary Tract

16771. Sedatives such as the benzodiazepines may cause confusion and secondary

incontinence, particularly for elderly patients

2. Alcohol may have similar effects to benzodiazepines and also impairs mobility and

causes diuresis

3. Anticholinergic drugs may impair detrusor contractility and may lead to voiding

difficulty and overflow incontinence. Drugs with anticholinergic properties are

widespread and include antihistamines, antidepressants, antipsychotics, opiates,

antispasmodics, and drugs used to treat Parkinson disease

4. Alpha agonists, which are often found in over-the-counter cold remedies, increase

outlet resistance and may lead to voiding difficulty

5. Alpha blockers, sometimes used to treat hypertension (e.g., prazosin, terazosin), may

decrease urethral closure pressure and lead to stress incontinence

6. Calcium channel blockers may reduce bladder smooth muscle contractility and lead to

voiding problems or incontinence; they may also cause peripheral edema, which may

lead to nocturia or nighttime urine loss

7. Angiotensin-converting enzyme inhibitors may result in a chronic and bothersome

cough that can result in increasing stress urinary incontinence in an otherwise

asymptomatic patient

Physical Examination

All women presenting for evaluation of urinary incontinence should undergo a

routine general physical examination with particular attention given to conditions

that may impact their incontinence. These include: mental and cognitive function

(e.g., dementia and its association with urgency, frequency, and enuresis),

neurologic function (e.g., Parkinson disease and multiple sclerosis and their effect

on urgency urinary incontinence), cardiovascular status (e.g., vascular

insufficiency and lower extremity edema and their association with nocturia

secondary to night time fluid mobilization in the recumbent position), pulmonary

function (e.g., chronic obstructive pulmonary disease and its effect on stress

urinary incontinence), nutritional status (effect of obesity on stress and urgency

urinary incontinence), mobility, gait, and dexterity (urgency urinary

incontinence).

The pelvic examination includes palpation of the pelvis and lower abdomen for

presence of masses. Lower extremity (deep tendon reflexes) and perineal

sensation and sacral nerve reflexes, including the anal wink and bulbocavernosus

reflexes, are evaluated. The latter reflexes are elicited by gently stroking or

tapping the clitoral and perianal skin to elicit a contraction of the external anal

1678sphincter. The goal of the pelvic examination is to investigate the underlying

cause of urinary incontinence and to identify associated pelvic support

defects. Examination is performed in the lithotomy position, but may require

a semi-upright or standing position. Evaluation of the vulva and vagina may

reveal atrophy, vaginitis, dermatoses, or pain associated with symptoms of

incontinence, urgency, and frequency. Inspection or palpation of the urethra may

reveal tenderness or mass, suggestive of an infection or diverticulum. Prolapse

staging of the different pelvic floor compartments is performed (see Chapter

30). Integrity of the pelvic floor and levator ani muscles can be assessed.

With two fingers in the vagina, the patient is asked to contract the muscles

used to “hold urine” or to “avoid passing gas.” The ability to contract and

strength and duration of the contraction are all measured. Finally, bimanual

and rectovaginal examinations are performed to assess for pelvic or adnexal

masses, integrity of the anal sphincter, and pelvic tenderness.

Q-tip Test

The Q-tip test, which is no longer recommended, involves introducing a

cotton-tipped swab into the urethra and asking the patient to Valsalva to

measure the angle deviation of the urethra from baseline. More than a 30-

degree deviation is consistent with hypermobility of the urethra, and/or

urethrovesical angle. Minimal to no angle deviation in a woman with stress

urinary incontinence may indicate intrinsic sphincter deficiency, also known

as stove-pipe urethra. The Q-tip test is no longer recommended because of the

discomfort associated with inserting the cotton swab into the urethra. Equivalent

information can be obtained from a vaginally placed swab to measure urethral

mobility while the patient is asked to Valsalva (55).

Cough Stress Test

During the pelvic examination, a cough stress test is performed. This can be

done either with a full or an empty bladder. The advantage of doing it with a

full bladder is that it is easier to demonstrate urine loss from the urethra in a

woman with stress urinary incontinence. If history is suggestive, but urine

loss is not observed in the lithotomy position, the patient may be asked to

stand up and possibly jump and/or cough vigorously while the examiner

observes for urine loss. Note that a positive cough test with a full bladder cannot

rule out overflow incontinence; here, a patient may demonstrate objective

evidence of urine loss with a stress activity, but may concurrently have

incomplete bladder emptying. Clearly, offering a surgical intervention, like a midurethral sling, to such a patient is not ideal because it can result in urinary

retention. Alternatively, a cough test can be done after asking the patient to empty

1679her bladder. A positive empty bladder cough test is strongly indicative of stress

urinary incontinence and at times may be suggestive of intrinsic sphincter

deficiency.

Postvoid Residual

The postvoid residual (PVR) volume of urine is the amount of urine

remaining in the bladder within 10 minutes from voiding. This can be

measured either using a small-caliber catheter during the pelvic examination or

via ultrasound. The latter is less invasive and has a standard error of less than

20%, with more accuracy for smaller PVRs (i.e., less than 200 mL) (60).

Alternatively, using the catheter to measure a PVR may result in a more exact

volume of urine, especially for large bladder volumes, and has the added benefit

of testing a more sterile urine specimen for a urine analysis or urine culture, if

indicated. Normal values for PVRs are not well established; however, most

would consider a PVR <50 mL to be within normal and a PVR >150 mL to

be abnormally elevated (61,62).

Simple Bladder Testing

Other simple tests are available that can be administered before (bladder diary),

during (urinalysis), or after (pad test) a clinical encounter to assist the clinician in

making a firm diagnosis.

Bladder Diary

The bladder diary, also referred to as the voiding diary, is meant to

represent the total amount of fluid intake, by type, in a 24-hour period.

Historically, voiding diaries were administered over a 7-day period. But these

were too inconvenient for patients to complete, and evidence shows that a 2- to 3-

day diary is equally reliable (56). The information gained from fluid intake is

important because it helps put into context symptoms of urgency, frequency,

and nocturia. In addition to fluid intake, the bladder diary offers information on

various measures of urine output, urinary incontinence, and circumstances

surrounding the urinary incontinence episode(s). The patient is asked to measure

the amount of voided urine by time of day and night; here, one can assess the 24-

hour total urine output, number of voids per day, average voided volume, and

bladder capacity (largest voided volume). The patient also documents the time a

urine loss occurs, and whether the event is associated with a stress activity (e.g.,

with a cough, sneeze, or laugh) or with urgency (Fig. 29-6).

1680FIGURE 29-6 An example of a voiding diary including time and amount of urination

during the day and at night, urinary incontinence episodes and associated activity, volume,

type, and time of fluid intake.

The bladder diary helps clarify the diagnosis when information gathered

during the history and pelvic examination is inconclusive. For example, intake

of large fluid volumes or consumption of large amounts of caffeine and alcohol

can easily explain why a woman may report a physiologic increase in urinary

frequency and urgency. Alternatively, a voiding diary that shows a 24-hour fluid

intake of 50 ounces (1.5 L), and nothing to drink 3 hours before bedtime in a

patient who reports a daytime frequency of every 2 hours, nocturia of 3 to 4

times, and with small voided volumes may represent a pathologic condition like

OAB or urgency urinary incontinence.

Urinalysis

The urinalysis by simple dipstick is helpful to rule out a urinary tract

infection, especially in the presence of irritative lower urinary tract

symptoms such as urgency, frequency, nocturia, and dysuria. Presence of

nitrites, leukocytes and/or hematuria on dipstick may indicate the presence of a

1681urinary tract infection. It is important to note that hematuria on a dipstick is not

conclusive for presence of blood in the urine and should be confirmed by a formal

microscopic evaluation. A urine culture can be sent to confirm the presence of a

urinary tract infection. Treatment of a urinary tract infection may help improve

these symptoms. It is generally not recommended to treat bacteriuria in a woman

who is otherwise asymptomatic.

Pad Tests

These are not routinely performed in the clinical setting. They are helpful

objective tools used in research since they quantify the volume and frequency of

urine loss by counting and weighing the pads used in a 24- to 48-hour period. One

research application of pad tests may include a new drug trial to treat urgency

urinary incontinence. In this instance, patients may be asked to wear incontinence

pads before and after taking the medication, to determine if the drug (compared to

placebo) results in a decrease in the volume and frequency of urinary

incontinence episodes. Pad tests can be employed to help objectify the presence

of urinary incontinence that is not demonstrable in the clinical setting, even with a

full bladder (i.e., negative cough stress test). An example may be a competitive

female athlete who reports loss of urine that occurs only during strenuous exercise

and which significantly impedes her performance. The patient is given 100 mg of

phenazopyridine (changes the color of urine into orange) to take before her

exercise routine while wearing a pad. The presence of orange staining on the pad

may help in the diagnosis of stress urinary incontinence.

Table 29-5 Symptom Questionnaires for Women with Pelvic Floor Disorders

Urinary Incontinence:

• Incontinence Severity Index

• International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF)

• Urogenital Distress Inventory (UDI)

• Urogenital Distress Inventory Short Form (UDI-6)

• Kings Health Questionnaire

• Bristol Female Lower Urinary Tract Symptom Questionnaire (BFLUTS)

All pelvic floor disorders (urinary incontinence, fecal incontinence, prolapse):

• Pelvic Floor Distress Inventory (PFDI)

• Pelvic Floor Distress Inventory Short Form (PFDI-20)

Adapted from Barber MD. Questionnaires for women with pelvic floor disorders. Int

Urogynecol J Pelvic Floor Dysfunct 2007;18:461–465; permission needed?

1682Quality of Life Measures

Although urinary incontinence is a health condition with limited immediate

physical sequelae to the individual woman, it can have tremendous

psychological, social, and general health effects. Some women stop exercising

as a result of constant urine loss with activity; others limit the amount of fluids to

reduce their urgency and urinary incontinence episodes; women may stop going

out because of fear of not finding a bathroom when one is needed; yet others may

not wish to have intercourse with their partner due to embarrassment from having

an accident. Clinical evaluation is not complete without an assessment of these

behavioral changes in response to bother from urinary incontinence that can lead

to profound consequences on an individual’s psychological, sexual, social, and

ultimately her physical well-being. There are several validated questionnaires

specifically developed to better assess severity of urinary incontinence, its

bother, impact on QOL, and sexual health (63). Many of those have short

versions that can be easily administered to patients during the initial visit,

and repeated in the future after an intervention, to measure change

(improvement) over time. The following two tables list a summary of

common symptom questionnaires (Table 29-5) and QOL and sexual function

scales for women with urinary incontinence pelvic floor disorders (Table 29-

6).

Table 29-6 Quality of Life and Sexual Function Scales for Women with Pelvic Floor

Disorders

Advanced Bladder Testing

Urodynamics

The hallmark of advanced bladder testing is the urodynamics test. This test

is an adjunct to history taking, clinical examination, and simple bladder

testing. The scope of its indications and use in clinical practice has narrowed over

time as clinicians have improved their diagnostic acumen in identifying different

1683bladder control conditions. Examples where urodynamics are not necessary

include: the diagnosis of incontinence is straightforward and consistent with

history, physical examination, and simple bladder testing; a woman with

predominantly subjective stress urinary incontinence symptoms with positive

cough test and minimal PVR, irrespective of whether an anti-incontinence surgery

is planned or not; a woman with urgency urinary incontinence symptoms, even

prior to initiation of medical treatment.

When performed, urodynamics provides objective data on lower urinary

tract function and serves two purposes: the first is to help characterize

bladder storage conditions by distinguishing stress, urgency, and mixed

urinary incontinence from each other; the second is to assist in establishing a

diagnosis for bladder voiding dysfunction. Urodynamics has many useful

applications in situations where: the diagnosis is not clear because of

inconsistencies between the history, physical examination, symptom scales,

and voiding diary; women have mixed or complex symptoms where

conservative treatment options have failed; surgery for prolapse is being

planned in a woman without any symptoms of urinary incontinence, or with

a negative cough stress test, to elicit the presence or absence of occult stress

urinary incontinence; previous surgery for incontinence has failed or

symptoms of urinary incontinence have recurred; incomplete bladder

emptying is reported (high PVR); symptoms of incontinence are

compounded by the presence of neurologic conditions like multiple sclerosis

(64).

Urodynamics can be simple or complex. A summary of all the definitions and

terms used in urodynamics is shown (Table 29-7) (65). A simple urodynamics

consists of uroflowmetry, PVR, and simple filling cystometry. This may be the

procedure of choice when someone has predominant stress urinary incontinence

with a negative cough stress test.

Table 29-7 Urodynamic Definitions

I. Bladder sensation

A. First sensation First becomes aware of bladder filling

B. First desire to

void

Feeling that would lead the person to void at next

convenient moment, but voiding can be delayed if necessary

C. Strong desire to

void

Persistent desire to void without the fear of leakage

D. Sensation Classified as:

16841. Increased

2. Reduced

3. Absent

4. Nonspecific bladder sensations (other symptoms make

person aware of bladder filling, like abdominal fullness)

5. Bladder pain (is abnormal)

6. Urgency (sudden compelling desire to void)

II. Detrusor function

A. Normal Allows bladder filling with little or no change in pressure;

no involuntary phasic contractions

B. Detrusor

overactivity

Involuntary detrusor contractions during filling

1. Phasic Characteristic wave form; may or may not lead to

incontinence

2. Terminal Single involuntary detrusor contractions occurring at

cystometric capacity, which cannot be suppressed, and

results in incontinence usually resulting in bladder emptying

3. Detrusor

overactivity

incontinence

Incontinence that is due to an involuntary leakage episode

4. Neurogenic

detrusor

overactivity

There is a relevant neurologic condition (replaces term

detrusor hyperreflexia)

5. Idiopathic

detrusor

overactivity

No definite cause (replaces term detrusor instability)

C. Bladder

compliance

Fill volume/change in detrusor pressure (Pdet)

1. Calculate at start of bladder filling (usually 0)

16852. At cystometric capacity (excluding any detrusor

contraction)

D. Bladder capacity

1. Cystometric

capacity

Volume at end of cystometrogram; capacity is volume

voided together with any residual urine

2. Maximum

cystometric

capacity

Volume at which person feels she can no longer delay

voiding

III. Urethral function

A. Normal urethral

closure

mechanism

Maintains a positive urethral closure pressure during bladder

filling

B. Incompetent

urethral closure

mechanism

Allows leakage of urine in the absence of a detrusor

contraction

C. Urethral

relaxation

incontinence

Leakage that is due to urethral relaxation in the absence of

raised abdominal pressure or detrusor overactivity

D. Urodynamic stress

incontinence

Involuntary leakage of urine during increased abdominal

pressure, in the absence of detrusor contraction (replaces

term genuine stress incontinence)

E. Urethral pressure

(Pura)

Fluid pressure needed to open closed urethra

1. Pressure

profile

Pressure along length of urethra

2. Urethral

closure

pressure

P

ura – Pves

3. Maximum

urethral

closure

pressure

(MUCP)

Maximum difference between P

ura and Pves

16864. Pressure

transmission

ratio

Increment in urethral pressure on stress as percentage of

simultaneously recorded increment in intravesical pressure

F. Abdominal leak

point pressure

Intravesical pressure at which urine leakage occurs because

of increased abdominal pressure

IV. Pressure flow studies

A. Urine flow Defined as:

1. Continuous

2. Intermittent

a. Flow rate Volume voided/unit time

b. Voided volume Total volume voided

c. Maximum flow

rate

d. Voiding time Includes interruptions

e. Flow time Time over which measurable flow actually occurs

f. Average flow

rate

Voided volume/flow time

g. Closing

pressure

Pressure measured at end of measured flow

h. Detrusor

function during

voiding

Classified as:

1. Normal

2. Detrusor

underactivity

Contraction of reduced strength resulting in prolonged

bladder emptying and/or a failure to achieve complete

bladder emptying

3. Acontractile Cannot be demonstrated to contract

i. Urethral

function during

Classified as:

1687voiding

1. Normal Continuously relaxed

2. Dysfunctional

voiding

Intermittent and/or fluctuating flow rate that is due to

involuntary intermittent contractions of the periurethral

striated muscle during voiding in neurologically normal

people

3. Detrusor

sphincter

dyssynergia

Detrusor contraction concurrent with an involuntary

contraction of the urethral and/or periurethral striated muscle

4. Nonrelaxing

urethral

sphincter

obstruction

Usually occurs in people with a neurologic lesion

From Abrams P, Cardozo L, Fall M, et al. The standardization of terminology of lower

urinary tract function: Report from the Standardization Sub-committee of the International

Continence Society. Neurourol Urodyn 2002;21:167–178, with permission.

Uroflowmetry

This a study that assess voiding function. Here, the patient is asked to come

to the office with a comfortably full bladder and void while sitting on a

special commode attached to a funnel that directs the voided volume into a

spinning receptacle that measures the amount of voided volume of urine over

time. Several data points are obtained through this study that include the

total amount of voided urine, the average and peak flow of urine, the time to

peak flow, flow time, and total time to void. A normal uroflow has a

continuous bell-shaped configuration, a short time to peak flow, and a high

peak flow (Fig. 29-7); whereas an obstructed flow may have two or more

lower peaks with an interrupted flow pattern or a prolonged tail (Fig. 29-8).

1688FIGURE 29-7 Normal uroflow with a bell-shaped pattern, a short time to peak flow, and a

continuous flow with complete bladder emptying.

FIGURE 29-8 Abnormal uroflow showing a prolonged and interrupted voiding pattern

with an initial high peak followed by several smaller peaks.

1689Filling Cystometry

After completion of the uroflowmetry, the patient is placed in a lithotomy position

and a catheter is placed to measure the PVR volume, which, if normal, is

generally less than 50 mL. In a simple urodynamics, filling cystometry involves

backfilling the bladder manually through the catheter at 60 mL increments or via

a water pump at a rate of 50 to 100 mL per minute. There are several sensory

parameters that are measured during the filling phase including (with their typical

normal values): first filling sensation (50 mL); first desire to void (150 mL);

strong desire to void (250 mL), and maximum cystometric capacity (400 mL).

Reduced volumes in several of these parameters may be consistent with OAB or

urgency urinary incontinence. Once the bladder capacity is attained, the catheter

is removed, and the patient is asked to cough or Valsalva. Loss of urine associated

with an increased abdominal pressure is indicative of stress urinary incontinence.

Complex Urodynamics

Women with predominant urgency urinary incontinence, mixed or complex

symptoms, with previous failed incontinence surgery, or neurologic conditions

may be more suited for a complex urodynamics. In addition to the uroflowmetry,

this test includes complex filling cystometry, urethral pressure profilometry, and

pressure flow studies. In addition, electromyography (EMG) of the urethral

sphincter is commonly performed. Although complex urodynamics is a more

advanced form of bladder testing, it is not a perfect test. A false negative test can

occur in a woman with subjective stress urinary incontinence where no urine loss

is observed even with a full bladder in the lying or standing position; it can also

occur with urgency urinary incontinence where a patient may report sensory

urgency, but no detrusor activity is visible. A false positive is uncommon with

stress but may happen with urgency urinary incontinence where the presence of

the catheter or patient’s anxiety may provoke an iatrogenic bladder contraction.

Filling Cystometry (Complex)

Similar to the simple urodynamics, filling cystometry is performed to assess

bladder and urethral function during the filling phase. The catheter placed in the

bladder has two transducers, one is situated at the tip of the catheter measuring the

intravesical pressure, and another is positioned a few centimeters behind the tip

measuring the transurethral pressure. A pressure transducer is placed either inside

the vagina, or the rectum, to approximate the intra-abdominal pressure. Since the

intravesical pressure (Pves) is a measure of the detrusor pressure (Pdet) plus the

pressure of the abdomen and surrounding organs (Pabd), then the true detrusor

pressure is obtained by subtracting the value of the abdominal pressure from the

intravesical pressure:

1690Pdet = Pves - Pabd

The advantage of complex cystometry is a more accurate assessment of the

detrusor pressure (activity) during the filling phase. For instance, should the

patient inadvertently sneeze, Valsalva, or increase her intra-abdominal pressure

during the test, a stable Pdet in the presence of an increased Pves is expected in a

normal bladder because the rise in Pves and Pabd cancel each other.

Alternatively, if a woman develops an unprovoked bladder contraction, Pabd will

remain neutral while Pves and Pdet show a spike. In this situation detrusor

overactivity is observed (Fig. 29-9).

FIGURE 29-9 Detrusor overactivity on filling cystometrography. The patient begins to

sense urgency, accompanied by an unstable bladder contraction, when 88 mL of water are

instilled into the bladder. The detrusor pressure rises, and when 96 mL of water are

instilled, she leaks. Pabd, abdominal pressure; Pves, vesical pressure; Pdet, detrusor

pressure.

Urethral Pressure Profilometry

1691The urethral pressure profilometry is a measure of the function of the urethra.

When the bladder capacity is attained during cystometry, filling is stopped. The

pressure inside the bladder (Pves), and that of the urethra (Pure) are noted. In a

healthy normal bladder and urethra, the Pure is higher than Pves during filling,

the opposite is true during voiding. The difference between the urethral and

bladder pressures is denoted as Pclose where:

Pclose = Pure - Pves

Because the urethra is approximately 4-cm long and the urethral sphincter is

located in the proximal urethra, it is important to identify the maximum urethral

closure pressure (MUCP). The catheter inside the bladder is typically attached to

a pulley which, when engaged, will pull the catheter in and out of the bladder as

the urethral transducer measures the Pure. The MUCP is the highest value of

Pclose along the urethral pressure continuum. MUCP values of less than 20 cm of

H2O may represent intrinsic sphincter deficiency; whereas a normal urethra has

MUCP value >40 cm of H2O.

Another test of urethral integrity is known as the Valsalva leak point pressure

(VLPP) which represents the value of the intra-abdominal or intravesical pressure

at which point urine loss occurs. This is usually performed when the bladder is

comfortably filled to 200 cc and the patient is asked to Valsalva or cough with

gradually increasing force. The point at which leakage of urine is observed during

this exercise is marked and denoted as VLPP. Typically, a VLPP >60 cm of H2O

is used as a cut-off representing normal urethral function, and below which may

be consistent with diminished urethral sphincter tone (Fig. 29-10).

1692FIGURE 29-10 Valsalva leak point pressure. The abdominal Valsalva leak point pressure

(VLPP) is 114 cm H2O (the abdominal pressure at which the patient leaked urine).

Electromyography

EMG leads are usually placed around the external anus to indirectly assess the

activity in the urethral sphincter. Since the anal sphincter and urethra are

primarily innervated by the pudendal nerve, the EMG activity generally

represents a good estimation of the urethral striated muscle activity. In a normal

individual, and during the filling phase, there is increased EMG activity; during

the voiding phase, there is decreased EMG activity. In women with neurologic

conditions or spinal cord injuries with retention or dysfunctional voiding, there is

often dyssynergia between the detrusor function and the urethral muscle activity.

Pressure Flow Studies

1693The final component of a complex urodynamics study is the pressure flow study

or voiding cystometrogram. Here the Pves, Pabd, and Pure are measured

concurrently as the patient is asked to void. This study offers information on the

voiding mechanism of the bladder, presence of dysfunctional voiding, and the

potential risk for retention or incomplete bladder emptying after surgery for

incontinence. Normative values for all the components of a urodynamics study

are shown (Table 29-8).

Other Bladder Studies

Fluoroscopy

Fluoroscopy is sometimes used, but generally not recommended, in conjunction

with urodynamics (also referred to as video urodynamics) to assess for a cystocele

and hypermobility of the urethrovesical junction. This information could be

equally gathered during a pelvic examination; imaging studies do not have any

significant added value, and they expose patients to unnecessary radiation.

Moreover, the presence of funneling, or bladder neck opening with Valsalva does

not necessarily equate to stress urinary incontinence as many women with normal

functional urethras, and who are continent, show evidence of bladder neck

opening during fluoroscopy (66).

Cystoscopy

A typical office-rigid cystoscope consists of a 17-French caliber sheath, through

which the endoscope is introduced. This is attached to a fiber-optic light source,

camera, and distending medium (sterile water or normal saline). The lenses on the

endoscope are 0, 12, 30, 70, or 120 degrees. The lesser angle lenses are wellsuited to inspect the urethra (Fig. 29-11), and perform office procedures like

urethral bulking or bladder botox; whereas the 30- and 70-degree lenses are best

to identify the ureteral orifices, trigone and bladder walls, and stent the ureters.

The 120-degree scope, which is helpful to have a retroview of the bladder neck, is

not routinely used in women. Instead, a flexible cystoscope, that has a smaller

caliber and is more comfortable to patients, can be used in those instances. In fact,

many specialists preferentially use the flexible cystoscope. However, the

advantage of a rigid versus a flexible cystoscope is that the former has an

operative channel through which it is easier to take a biopsy, should an

abnormality be identified.

Table 29-8 Approximate Normal Values of Female Bladder Function

• Residual urine <50 mL

1694• First desire to void occurs between 150 and 250 mL infused

• Strong desire to void does not occur until after 250 mL

• Cystometric capacity between 400 and 600 mL

• Bladder compliance between 20 and 100 mL/cm H2O measured 60 sec after reaching

cystometric capacity

• No uninhibited detrusor contractions during filling, despite provocation

• No stress or urge incontinence demonstrated, despite provocation

• Voiding occurs as a result of a voluntarily initiated and sustained detrusor

contraction

• Flow rate during voiding is >15 mL/sec with a detrusor pressure of <50 cm H2O

From Wall LL, Norton P, DeLancey JO. Practical Urogynecology. Baltimore, MD:

Williams & Wilkins, 1993, with permission.

1695FIGURE 29-11 Cystoscopic view of a scarred urethra using a smaller angle lens.

Cystoscopy is a simple office procedure that is frequently performed in the

evaluation of various bladder conditions. But, it has a limited role in the initial

workup of basic urinary incontinence. Instances where cystoscopy is important

include stones, bladder tumors, foreign bodies, or chronic cystitis. Other

indications in women include: (a) microscopic hematuria (presence of red blood

cells in the urine) that is unrelated to a urinary tract infection; (b) OAB that is

refractory to conservative or medical treatment, especially in older women; (c)

urinary incontinence with suspected vesicovaginal fistula; (d) symptoms such as

frequency, urgency, dysuria, in the absence of a urinary tract infection; (e) women

presenting with recurrent urinary tract infections; (f) recurrent urinary

incontinence or OAB symptoms following previous anti-incontinence surgery; (g)

complications from previous vaginal mesh or sling procedures (54,67).

1696Experts agree that cystoscopy is essential intraoperatively during any prolapse,

incontinence, or bladder surgery. Injuries to the bladder and ureters are welldocumented during such procedures (68–71). For instance, incidence of ureteral

injury is as high as 11% after a high uterosacral colposuspension (69); whereas,

the incidence of cystotomy could be up to 5% after mid-urethral slings (68).

Identification of these injuries is relatively simple via the cystoscope, and

intraoperative or early treatment of the injury results in better long-term

outcomes. However, there is no consensus about performing cystoscopy

universally at the time of a hysterectomy (72–74). Rates of ureteral and bladder

injuries after hysterectomies for benign indications are reported to range between

0.02% and 1.8% and 0.85% to 2.9%, respectively (74,75).

Ultrasound and MRI of the Pelvis

Although pelvic ultrasound has been a gold standard diagnostic tool in many

areas of gynecology, its clinical utility in bladder control conditions has been

limited to research and experimental purposes. Imaging technologies such as the

pelvic ultrasound and MRI have enabled researchers to develop a better

understanding of the urinary continence mechanism, and the pathophysiology of

stress urinary incontinence (6). With the advancements of 3D and 4D imaging,

diagnostic ultrasound modalities have shown some promise in clinical practice

(76). They help in defining the morphology of the urethra and its sphincter where

women with stress urinary incontinence are noted to have shorter urethra and

smaller urethral sphincter volumes. Ultrasound can help assess changes in

morphology of the urethra, bladder neck mobility, pelvic support structures at rest

or with Valsalva, and to quantify these changes. These variations are accentuated

in women who have concomitant stress urinary incontinence and pelvic organ

prolapse. Moreover, it is possible to assess the integrity and strength of the levator

muscles during a pelvic floor contraction, and measure PVR bladder volume (77).

Other useful properties of the ultrasound include observation of urethral

coaptation after an injection of bulking agent for intrinsic sphincter deficiency,

identification of previous pubovaginal or mid-urethral sling location and

tightness, and detection of urethral diverticulum, foreign bodies or implants in the

urinary system.

MRI is another radiologic modality that has been used mostly in research to

better understand the anatomy of the pelvis and the organs within. It has played a

significant role in improving our understanding of the pathophysiology of pelvic

organ prolapse and stress urinary incontinence. Static MRI gives detailed

information of the urethral anatomy, the striated sphincter, and its surrounding

structures (78,79). Dynamic MRI can delineate compartments of the female

pelvis, including the urethra, with and without intra-abdominal straining to

1697characterize presence of prolapse (80). However, MRI is not routinely used in

clinical practice because of its expense and the availability of the simple pelvic

examination in the office that gives equally valuable information. Nonetheless,

one condition for which MRI is the diagnostic modality of choice is a urethral

diverticulum (81).

Neurophysiologic Testing

The function of the bladder, urethral sphincter, and pelvic floor are dependent on

the integrity of the nervous system, from the brain down to the terminal sensory

and motor nerve endings supplying the genitourinary system. Several imaging

and nerve conduction techniques are available to study the normal function and

pathophysiology of the neuromuscular system. These include modalities such as

functional CT and MRI scanning and somatosensory-evoked potentials (mostly

for urgency urinary incontinence), and pudendal or sacral nerve motor latency,

and EMG (mostly for stress urinary incontinence). These tests are usually

performed in specialized centers and are not routinely used in the clinical setting

during the workup of most women with urinary incontinence.

Prevention

Successful prevention and treatment strategies for all urinary incontinence

subtypes exist. Early detection is specially challenging because most patients do

not seek care, and specialists see only a small fraction of women with urinary

incontinence. Programs to mitigate onset and progression of disease should

start at the primary care level. Known risk factors that promote new-onset

urinary incontinence, such as age, BMI, and parity, have a long latent

period. There exists some evidence that early interventions may delay or

reduce risk of subsequent onset of urinary incontinence symptoms (46). One

such example is the effect of introduction of pelvic muscle training exercises

during pregnancy on prevention of urinary incontinence in the short term.

Large longitudinal population-based studies show that cesarean delivery, as

opposed to vaginal birth, may have a beneficial effect in reducing subsequent risk

of stress urinary incontinence. In the absence of other indications, promoting

elective cesarean section as the preferred method of delivery to prevent future

pelvic floor dysfunction, including stress urinary incontinence, is a topic of

debate. Other risk reduction interventions include: (a) weight loss in obese

women; (b) management of blood sugar control in diabetics; (c) reduced

consumption of high levels of alcohol and caffeine (46).

Conservative Nonpharmacologic Treatment

Conservative options should be offered to all patients as a first-line

1698treatment. To optimize treatment benefits, diagnosis should be made early during

the course of disease, and sometimes before onset of overt symptoms.

Conservative treatments are generally simple, noninvasive, readily available and

inexpensive, relatively effective and with little to no side effects. [3] Examples of

conservative nonpharmacologic interventions [4] include lifestyle

modification, counseling and patient education, bladder training (or

retraining), relaxation and urgency suppression, exercise training (e.g.,

pelvic floor muscle exercises), biofeedback, electric stimulation (E-stim),

pessaries, and urethral plugs (82).

Lifestyle Modification

This includes avoidance of risky behavior associated with urinary

incontinence, urgency, frequency, and nocturia such as smoking and alcohol

consumption. It includes staying healthy, developing an active lifestyle, being

physically fit and losing weight (if obese). In obese or overweight women, there

is ample evidence that weight loss improves both stress and urgency urinary

incontinence symptoms (83). A 10% weight loss leads to more than 50%

improvement in stress urinary incontinence symptoms (84). It requires that

women modify or alter their dietary habits, mostly the amount and type of fluid

intake. The recommended amount of fluid intake in a 24-hour period varies from

an individual to another depending on their activity level, their weight, and other

comorbidities. An assessment of a 24-hour bladder diary can help individualize

optimal amount, type, and timing of fluid intake for a particular patient. Caffeine

reduction is helpful in women with urgency and urgency urinary

incontinence (58).

Counseling and Education

This usually starts at the physician’s office, be it the patient’s primary care,

gynecologist, or female pelvic floor specialist. Patients can further be referred to a

dietician, physical therapist, counselor, or others to assist in establishing and

maintaining the health lifestyle modifications discussed above. Counseling and

education can take the form of different strategies such as supplying them with

educational material, motivational interviewing, empowering patients with tools

and coping strategies as it relates to their incontinence, and enabling patients to

take control of their condition and care for themselves (self-care or self-help).

Bladder Training

This intervention includes prompted voiding, and timed toileting and it aims

at assisting women with idiopathic OAB or urgency urinary incontinence to

minimize frequency of uncontrolled bladder urges and improve voluntary

control of urine. It is generally coupled with restricting fluids in women who

1699drink large quantities of liquid. Using her voiding diary as a guide, the

patient is asked to void at a fixed time interval that is comfortably long

enough (e.g., every 2 hours). Should she develop a strong desire to void

before the end of the time interval, she is asked to suppress the urge. Women

are instructed to double void. Here, the patient is asked to void normally in

the bathroom with a pelvic floor relaxation to allow the urine to flow; when

the flow of urine stops, the patient is instructed to voluntarily strain followed

by another relaxation period to allow additional unemptied urine to flow.

This regimented schedule of timed toileting and double voiding is continued

for a whole week and increased by an interval of 15 minutes every

subsequent week. The goal of bladder training is to prolong voiding and

improve bladder capacity while reducing urgency and incontinence episodes.

The whole intervention program usually takes up to 6 weeks and has been

shown to be effective when compared to medications (85).

Relaxation and Urgency Suppression

There are several maneuvers whereby a patient with a strong desire to void

can help mitigate the urgency sensation. One technique is to ask the patient

to do something that distracts her mind off the bladder urge, such as deep

breathing, singing silently, solving a simple mathematical problem, or

switching from the activity she was engaged in to a moment of inactivity.

Concurrently, the patient is asked to tighten her pelvic floor muscles, knee

and ankle flexion, sitting on a chair (if on her feet). Many of these can be

applied to women with history of stress urinary incontinence who anticipate

a urine loss episode with an imminent stress activity such as coughing or

sneezing.

Pelvic Floor Muscle Training

Historically, pelvic floor exercises were described by Arnold Kegel in 1948 as

a nonsurgical method to restore anatomy and function of genital relaxation

(86). Over time these exercises were structured into a physical therapy routine and

collectively termed pelvic floor muscle training (PFMT). There have been several

randomized trials demonstrating the benefits of PFMT (vs. placebo or no

treatment) in treating urinary incontinence, in general, and stress urinary

incontinence, in particular. A Cochrane review in 2015 showed that women

receiving PFMT reported improvement with fewer urine loss episodes or

cure, and a better QOL than controls. However, since most studies follow

patients up to a year or less, there is limited to no robust information on the longterm benefits of PFMT (87).

Commonly, during a PFMT program, women are encouraged to contract

1700their pelvic floor muscles for 3 seconds, 10 to 15 times per session, and 3

times a day. Helpful hints to contracting the right pelvic floor muscles

include: keeping the abdomen and hips relaxed; imagining that one is trying

to prevent passing of gas, tightening the rectum, or bringing the buttock

cheeks together. They should be done in a comfortable laying or sitting

position. It can be done while watching TV, in front of a computer on a desk,

or while driving a car. A common misconception is that women try to do

their Kegels in the bathroom every time they are voiding. However, this can

lead to voiding dysfunction and worsening OAB symptoms in the long run,

and Kegels are best done with an empty bladder.

Physical therapists often use adjunctive aids such as biofeedback and E-stim to

supplement the PFMT, especially when patients are not able to generate a good

squeeze during the physical therapy session. Biofeedback can be auditory or

visual and gives the patient a sensory feedback of the strength of her pelvic floor

squeeze. Electrical stimulation therapy delivers low levels of current via a probe

placed in the vagina or rectum. There is no evidence that biofeedback or E-stim

are superior to PFMT alone, especially when the latter are done regularly and

properly in women with stress urinary incontinence (87).

Mechanical Devices for Urinary Incontinence

Several devices are available to treat mostly women with stress urinary

incontinence (Fig. 29-12). These can be divided into two main groups:

urethral and vaginal. The urethral devices create a temporary occlusion of

the urethral meatus to prevent urine loss. One example of a urethral device is

the urethral insert FemSoft where a woman is instructed to place the insert into the

urethra and then remove it before urinating. These could be beneficial in female

competitive athletes who may have stress urinary incontinence episode only

during a sporting event (e.g., tennis). Although incontinence episodes are reported

to decrease, about one-third of women developed urinary tract infections in one

long-term follow-up study (88).

1701FIGURE 29-12 Vaginal incontinence pessaries: (clockwise from top): A: Suarez ring

(Cook Urological, Spencer, IN), B: PelvX ring (DesChutes Medical Products, Bend, OR),

C: Incontinence dish (Milex Inc., Chicago, IL), D: Incontinence dish with support (Mentor

Corp., Santa Barbara, CA), E: Introl prosthesis (was Johnson and Johnson; currently not

available), F: Incontinence ring with support (Milex Inc., Chicago, IL), (middle): G:

Incontinence dish with support (Milex Inc., Chicago, IL).

Vaginal devices consist of two categories. The first type of device is used as

an adjunct to PFMT such as vaginal weights or cones. These devices are

placed in the vagina by the patient for short periods of time in an effort to

improve the strength of the pelvic floor muscles. Alternatively, the second

type of a vaginal device is meant to be used long-term and throughout the

day to help support the bladder neck and assist in the urethral closure

mechanism of the urethral sphincter. These devices include pessaries, vaginal

sponges, or tampons. One randomized controlled trial comparing pessary use to

behavioral therapy to a combination treatment for stress urinary incontinence

showed that behavioral therapy produced greater patient satisfaction with fewer

incontinence symptoms that were bothersome at 3 months. By 12 months there

were no differences, and patient satisfaction persisted similarly in all three groups.

1702Single modality was similar to combination therapy (89). However, a recent

Cochrane review concluded that there is little evidence from controlled trials on

the role of mechanical devices on long-term sustained beneficial effects in the

management of urinary incontinence (90).

Other Treatment Options

Electric stimulation (E-stim) and magnetic stimulation (M-stim) are two

alternative conservative options that are available in specialized centers. Evidence

regarding those modalities in the management of urinary incontinence is not wellestablished and more research is needed to show whether they are more beneficial

than the traditional and less costly conservative options available.

Medications for Stress Urinary Incontinence

Historically, estrogen replacement therapy was used to treat women with

stress and urgency urinary incontinence. Based on large randomized trials

including the Women’s Health Initiative (WHI), estrogen (with or without

progesterone) has been shown to be associated with increased prevalence

(worsening incontinence) and incidence (new-onset incontinence), and with

the negative effect being more pronounced for stress than urgency urinary

incontinence (91). Similar results were found with the Heart Estrogen and

Progestin Replacement Study (HERS) comparing oral conjugated equine

estrogen and medroxyprogesterone acetate to placebo where 1,525 women

were followed for 4 years. More specifically, the HERS study showed that the

odds ratio for worsening incontinence was 1.5 among women with baseline

urinary incontinence; the odds ratio for developing new stress urinary

incontinence was 1.7, and new urgency urinary incontinence was 1.5 (92,93).

A Cochrane review on this topic confirmed these findings and concluded that

estrogen replacement therapy should not be offered to women as a treatment

for urinary incontinence, with the caveat that local (vaginal) use of estrogen

may improve symptoms of urgency and frequency in the short term (94).

Other medications have been used to treat stress urinary incontinence.

These are typically drugs that have a stimulating effect on the alphaadrenergic receptors present in the urethral sphincter. Examples include

epinephrine and norepinephrine, ephedrine and pseudoephedrine, and

phenylpropanolamine. These alpha-stimulating drugs are nonspecific and can

be associated with other systemic effects including on the heart, brain, and

blood pressure. They are not FDA approved and rarely, if ever, used purely for

stress urinary incontinence. Imipramine, a tricyclic antidepressant, has been used

with variable success, especially in women who have a coexisting stress and

urgency urinary incontinence. This may relax the bladder through its

1703anticholinergic effect, and constrict the urethra through its alpha-agonistic effect.

One other drug worthy of mention is duloxetine. It is an FDA-approved serotonin

and norepinephrine reuptake inhibitor drug to treat depression, chronic pain, and

anxiety, but not for stress urinary incontinence. Its mechanism of action on the

bladder is to increase bladder storage and improve urethral sphincter function via

its effect on the central nervous system. In one study, duloxetine was shown to be

equally effective as PFMT (95). But, but the presence of side effects (nausea,

fatigue, insomnia, somnolence, dizziness, and blurred vision) may preclude it

from being used as a first-line therapy for stress urinary incontinence.

Medications for Urgency Urinary Incontinence and Overactive Bladder

Medical treatment for urgency urinary incontinence and OAB is less

controversial than for stress urinary incontinence. Medications are usually

offered either when conservative treatment options have failed or in conjunction.

Their efficacy, however, is modest. One major medication class represents the

anticholinergic drugs. These include drugs that produce their effect by inhibiting

the stimulatory effect of the parasympathetic nervous system on the detrusor

muscle by blocking the cholinergic (acetylcholine or muscarinic) receptors.

Several of these drugs exist with similar efficacy profiles. These drugs differ

in duration of action (immediate release vs. long acting) and route of

administration (oral, patch, or gel) (Table 29-9) (58). In 2009, the Agency for

Healthcare Research and Quality published an evidence-based review of

over 230 publications on the medical treatment modalities for urgency

urinary incontinence and OAB (96). They showed that anticholinergic

medications reduced number of voids (and urinary incontinence episodes) by

1.5 to 2.2 per day, with the short-acting drugs being on the lower range, and

the long-acting drugs on the higher range. Interestingly, a relatively high

placebo effect exists in most randomized trials which is as high as 1.5 voids

per day reduction.

The immediate-release oxybutinin was the first FDA-approved

anticholinergic drug, but it has a short half-life and is taken three times a

day to be optimally effective. Extended-release medications tend to be better

tolerated because of their once daily administration, and a lower side-effect

profile (97). In general, anticholinergics are administered at a low dose, with

subsequent increase in dosage after a period of 4 to 6 weeks should there be

no significant improvement. In the presence of side effects, it is reasonable to

try another anticholinergic. Because anticholinergics are not purely specific

to the bladder muscarinic receptors, they all produce side effects with a

varying degree on other tissues or organs These include the salivary glands

resulting in dry mouth, the iris and ciliary muscles of the eyes resulting in

1704blurry vision, the gastrointestinal system resulting in constipation, the heart

resulting in altered heart rate, and the brain resulting in memory problems.

One exception may be trospium chloride, a quaternary amine anticholinergic,

which is hydrophilic with a large molecular size limiting its distribution into

the central nervous system and reducing its effect on cognition.

Table 29-9 Pharmacologic Therapies Indicated for Overactive Bladder with or

without Urgency Incontinence

Compound Usual Dose

Oxybutynin chloride (Ditropan, Ortho-McNeil–Janssen

Pharmaceuticals and available as generic formulation)

5 mg by mouth

3–4 times daily

Oxybutynin chloride extended release (Ditropan XL, OrthoMcNeil–Janssen Pharmaceuticals and available as generic

formulation)

5, 10, or 15 mg

by mouth once

daily

Oxybutynin transdermal patch (OxytroI, Watson Pharmaceuticals) One patch

applied twice

weekly

Oxybutynin gel 10% (Gelnique, Watson Pharmaceuticals) One sachet

applied daily

Tolterodine tartrate (Detrol, Pfizer) 2 mg by mouth

twice daily

Tolterodine tartrate long acting (Detrol LA, Pfizer) 4 mg by mouth

once daily

Fesoterodine fumarate (Toviaz, Pfizer)a 4 or 8 mg by

mouth once daily

Solifenacin succinate (Vesicare, Astellas Pharmaceuticals) 5 or 10 mg by

mouth once daily

Trospium chloride (Sanctura, Allergan) 20 mg by mouth

twice daily

Trospium chloride extended release (Sanctura XR, Allergan) 60 mg by mouth

once daily

Darifenacin (Enablex, Novartis Pharmaceuticals) 7.5 or 15 mg by

1705mouth once daily

aTolterodine is the active metabolite of fesoterodine.

Nygaard I. Clinical practice. Idiopathic urgency urinary incontinence. N Engl J Med

2010;363:1156–1162; Table 1, need permission.

There has been increased concern regarding the cumulative effect of

anticholinergics on cognition, dementia, and onset of Alzheimer’s disease. In

one review study of patients prescribed anticholinergic medications over a

follow-up period of 7 years, 797 participants (23%) developed dementia (of

whom, 637 developed Alzheimer’s). There was a significant 10-year

cumulative dose–response relationship for dementia and Alzheimer disease

(98). Based on this and other evidences, AUGS published a consensus

statement in 2017 recommending behavioral therapies as a first-line

treatment for urgency urinary incontinence, followed by medical

interventions. More specifically, AUGS recommends “ . . . caution in

prescribing anticholinergic medications in frail or cognitively impaired

patients” and that “ . . . providers should counsel on the associated risks,

prescribe the lowest effective dose, and consider alternative medications in

patients at risk” (99).

A second class of medications to treat urgency urinary incontinence

includes the beta agonists. This class currently includes only one FDAapproved (2012) medication known as mirabegron, which is a specific beta-3

receptor agonist. It produces its effect via the sympathetic system by stimulating

the beta receptors on the bladder, leading to relaxation of the detrusor muscle

(100). Unlike anticholinergics, it does not have dry mouth, constipation or

blurred vision as side effects, but it ought to be used with caution in women

with uncontrolled hypertension (it increases blood pressure), renal or hepatic

impairment and urinary retention. It can be used in women with cognitive

impairment. In one recent randomized trial comparing mirabegron to tolterodine,

patient tolerability for mirabegron was higher than tolterodine which was

associated with more side effects, but patient preference and OAB symptom

improvements were similar between the two drugs (101).

Medications for Nocturia and Enuresis

Nocturia, especially in the elderly, may be multifactorial. Waking up to go to

the bathroom one or more times during the night may be the consequence of

increased fluid intake, caused by bladder storage conditions like OAB, or

other comorbidities unrelated to the bladder, such as vascular insufficiency,

heart disease, or others. Desmopressin, a medication used to treat nocturia or

enuresis, is effective mostly through its central inhibitory action on reducing

1706urine production. It is available as a nasal spray and as an oral preparation.

Caution is recommended in the elderly or in women with hypertension; it

requires periodic measurement of sodium levels. Imipramine, may work

centrally to improve sleep, and peripherally on the bladder and urethra to improve

bladder storage. Anticholinergics can be used to help with nocturia, especially in

women with OAB. Diuretics like furosemide, can be helpful, especially in the

presence of vascular insufficiency and peripheral edema.

Medications to Treat Overflow Urinary Incontinence or Urinary Retention

Overflow urinary incontinence or urinary retention is a condition more

prevalent in men, and commonly occurs as a result of benign prostatic

hyperplasia. In women, in the absence of an anatomic obstruction, such as a

urethral stricture, previous anti-incontinence surgery or advanced prolapse,

overflow incontinence can occur because of bladder detrusor muscle

underactivity, diabetic neuropathy, or central nervous system conditions.

Different drugs have been used, albeit with limited success, to either stimulate the

detrusor muscle or to reduce urethral sphincter resistance, and therefore improve

voiding (102). Examples of detrusor muscle stimulants include muscarinic

receptor agonists, such as bethanechol, or cholinesterase inhibitors, such as

distigmine. There is no evidence from controlled clinical studies that these

medications offer substantial benefit, and these drugs may be associated with

significant side effects (103). A hypoactive or atonic bladder is generally not

responsive to medical treatment. Alpha-receptor blockers such as alfuzosin have

been shown to be beneficial in men by reducing the resistance in the bladder neck

and urethra to facilitate bladder emptying. Although these medications have been

used in women with urinary retention, they have produced variable results

(104,105).

Surgical Treatment of Urinary Incontinence

Pubovaginal Slings

At the turn of the 20th century, one of the earliest described surgeries reported in

Europe for stress urinary incontinence involved placing an organic sling at the

bladder neck (106). These operations, presently referred to as traditional slings,

are performed through two incisions, one in the vagina to pass the sling around

the urethra, and one through the abdomen to gain access around the space of

Retzius. The two free ends of the sling material are passed up from the vagina and

then attached commonly to the fascia of the rectus muscle (or other pelvic

structures) to create a fixed loop around the bladder neck and proximal urethra

(Fig. 29-13). This provides support to the urethral closure mechanism at times of

increased abdominal pressure (107). Over the years, use of different sling

1707materials has been described including autologous (e.g., fascia lata, rectus muscle,

or fascia harvested from the patient), allografts obtained from donors (e.g.,

cadaveric fascia lata), heterologous obtained from other species (e.g., bovine or

porcine), or synthetic (e.g., prolene or Gore-Tex) (108).

FIGURE 29-13 A completed traditional suburethral sling procedure with the fascia

located at the bladder neck with the ends of the sling tied to or above the rectus fascia. The

classic procedure uses autologous fascia; however, some surgeons use allograft or

xenograft tissue performed in a similar fashion. (Redrawn from original by Jasmine Tan.)

1708Although successful, the pubovaginal slings can result in urinary retention

requiring further surgery to resolve ensuing voiding dysfunction. Synthetic

slings can be associated with risk of erosion (109). In a large randomized

surgical study, women with stress urinary incontinence who underwent

fascial pubovaginal sling had a higher success rate than a Burch

colposuspension at 2-year follow-up (47% vs. 38%; P = 0.01). However, there

was a higher rate of complications in the pubovaginal sling group, including

voiding dysfunction, urinary tract infections, and new-onset urgency urinary

incontinence (110). Of the original 655 women in the initial randomized

clinical trial, 482 (75%) were enrolled in a follow-up study up to 7 years. The

vigorously defined composite success rate decreased from 42% to 13% in the

Burch group and 52% to 27% in the sling group (111). When success was

defined using only one criterion (e.g., 1-hour pad test), reported rates were

much higher and similar between the two groups (84% for the Burch group

and 85% for the sling group) (110). Based on this and other evidences, the

pubovaginal sling using autologous fascia remains a viable option to treat

women with predominant stress urinary incontinence (64).

Anterior Vaginal Wall Repair

A few years after the publication of the initial pubovaginal sling procedures to

treat stress urinary incontinence, Kelly reported on the anterior vaginal repair (or

anterior colporrhaphy) in 1914 (112). This operation was a simple procedure and

based on case series, it was initially thought to be a very successful surgery, and

therefore became quite popular for over half a century. The key concept of the

anterior vaginal repair is to plicate the pubovesical fascia around the bladder neck

and proximal urethra to give it the necessary support and to assist in the

sphincteric closing mechanism by preventing urine loss. Randomized controlled

trials comparing the anterior vaginal wall repair to alternative procedures revealed

that the former’s long-term success was suboptimal (113,114). The Kelly

plication (anterior vaginal wall repair) is not recommended to treat women with

stress urinary incontinence (64,109).

Needle Suspension Surgeries

One of the earliest needle suspension procedures was introduced by Pereyra in

1959 (115). The technique of this surgery and several of its subsequent

modifications involved passage of a special needle carrier introduced bilaterally

through an abdominal incision down into the vagina. Sutures were placed on both

sides of the urethra within the vaginal and underlying connective tissue, brought

up and then attached to the rectus fascia. It was presumed that this suspension

would provide lasting bladder neck support and help mitigate stress urinary

1709incontinence episodes. However, similar to the Kelly plication, long-term success

of needle suspension procedures failed to withstand the test of time in randomized

controlled trials (109,114), and they are no longer recommended for the treatment

of stress urinary incontinence (64).

Retropubic Colposuspension Surgeries

Because most women with stress urinary incontinence have hypermobility of the

bladder neck, DeLancey’s Hammock Theory made clinical sense (30). As a result,

retropubic colposuspensions (urethropexies), where the endopelvic fascia around

the bladder neck and proximal urethra is suspended to structures on the anterior

pelvis, were shown to be good surgeries to treat stress urinary incontinence (Fig.

29-14). The two most commonly performed retropubic urethropexies are the

Marshall–Marchetti–Krantz (MMK) and Burch procedures (116,117). The

procedures are similar in that the approach is abdominal, requiring entry

into the retropubic space. The MMK was initially described in a man with

urinary incontinence following prostatectomy where the endopelvic fascia

was attached to the pubic bone (116). With the Burch retropubic

urethropexy, the periurethral tissue was fixed to Cooper ligament (117).

Burch followed 143 of his patients up to 9 years and reported a success rate

of 82% (118).

FIGURE 29-14 Points of reattachment of the endopelvic fascia during retropubic bladder

neck suspensions. A: Arcus tendineus fascia pelvis (for paravaginal repair). B: Periosteum

of pubic symphysis (for Marshall–Marchetti–Krantz procedure). C: Ileopectineal, or

Cooper, ligament (for Burch colposuspension). D: Obturator internus fascia (also used for

paravaginal, or obturator shelf, repair).

1710In a randomized trial comparing the open Burch urethropexy to the midurethral sling procedure, success rate (reported as a negative 1-hour pad test) was

44/49 (90%) versus 58/72 (81%), respectively (P = 0.21) at 5 years (119).

Retropubic urethropexies can be performed laparoscopically, but there are limited

data on their long-term efficacy (120). In one randomized trial, patients were

followed for a median of 65 months (range 12 to 88 months). Here, 58% of

women reported any urinary incontinence after a laparoscopic Burch compared

with 48% after a mid-urethral sling, with no statistically significant difference

between the two groups; stress urinary incontinence bother symptoms were

reported in only 11% and 8% of women, respectively (121). Using strict criteria

to define urinary incontinence yields a higher failure rate, but most women report

significant improvement in bother symptoms and impact on QOL after

colposuspension procedures. A recent 2017 Cochrane review showed that the

open Burch and other retropubic colposuspension procedures remain very

successful operations to treat stress urinary incontinence, with long-term (5 years

or more) success rates of around 70% (120). Compared to pubovaginal slings,

open colposuspension is associated with a lower risk of voiding dysfunction,

but with a higher risk of subsequent pelvic organ prolapse (110,119).

Mid-Urethral Slings

The mid-urethral slings were developed as a direct consequence of the

integral theory that was promoted by Petros et al. (31). The polypropylene

tension-free vaginal tape (TVT) was the original mid-urethral sling described

by Ulmsten in 1996 as a simple minimally invasive outpatient procedure

under local or regional anesthesia (122). With this procedure, a synthetic

sling is placed under the mid-urethra (in contrast to pubovaginal slings that

are placed at the bladder neck) in a tension-free manner. The two ends of the

sling are not attached or sutured to a pelvic structure, but rather the urethra

is free of any tension upon placement of the sling. The TVT is commonly

placed in a bottom-up direction through a small 1 to 2 cm mid-urethral

vaginal incision, and the two free ends are passed up and behind the pubic

bone through the space of Retzius and out through two suprapubic incisions

(Fig. 29-15). As each side of the sling is advanced around the urethra using a

trocar, the bladder is deviated to the contralateral side via a guide wire placed

through a Foley catheter to minimize the risk of a cystotomy. Cystoscopy is

performed to confirm the integrity of the bladder. Although mid-urethral slings

were initially received with skepticism, over time they have proven to be very

effective surgeries with low rates of complications replacing all other procedures

as the gold standard to treat stress urinary incontinence (123,124). Of the original

90 women who underwent the TVT procedure, 78% were followed-up to 17

1711years. Of those evaluated either by a clinic visit or by phone, about 90% had

objective and 87% had subjective cure or significant improvement (125).

FIGURE 29-15 Midurethral synthetic slings involve the use of large pore, monofilament

polypropylene mesh placed after minimal dissection at the midurethra followed by

placement of a trocar through the retropubic route. A: The trocar is guided into the

previously performed midurethral incision with care to place the trocar against the pubic

bone to avoid entry into the peritoneal cavity. The trocar handle has been removed in this

view after perforation through the abdominal incision. B: The synthetic sling should rest in

the midurethra location and is brought through two stab incisions above the pubic

symphysis. (Redrawn from original by Jasmine Tan.)

In 2001, Delorme reported on the transobturator tape (TOT) where the

sling position is still mid-urethral, however its general direction is through

the ischiorectal fossa and the free ends exit via the obturator canal and out

through the genitofemoral creases bilaterally (126). The TOT sling can be

placed in an outside-in or inside-out direction. The TOT mid-urethral slings

were developed in an attempt to reduce complications associated with the

TVT procedure, including bowel, bladder, and vascular injury. Subsequent

studies have shown that women undergoing TOT procedures are still at risk

of vascular and bladder injuries, although rare. Over the past two decades,

there has been an accumulation of a large body of evidence on mid-urethral slings

from randomized controlled trials, including several meta-analyses and Cochrane

reviews (120,123,124,127,128). The overarching summary is that mid-

1712urethral slings have become the procedure of choice in treating women with

stress urinary incontinence. They have a good safety profile with a significant

improvement of QOL measures, and irrespective of route of placement, they are

highly effective in the short, medium, and long term. There is evidence to suggest

that the mid-urethral slings are more effective than the Burch colposuspension

procedure, and as effective as the autologous pubovaginal sling (123).

Concerning the choice of mid-urethral sling (retropubic vs. transobturator), data

show that the retropubic approach may be favored in terms of long-term efficacy,

but with the risk of higher overall complication rates (123,127,129). In a large

national cohort of more than 8,600 women undergoing mid-urethral slings in

Denmark over a 10-year span, the reoperation rate at 5 years was 6% for the TVT

and 9% for the TOT. In the adjusted model, the TOT sling was associated with a

twofold higher risk of reoperation (HR, 2.1; 95% CI, 1.5–2.9) than the TVT sling.

In terms of complications, urinary tract infections occur in up to 10% after midurethral slings (130). Bladder perforation is another complication that can occur

with both approaches but more commonly with the TVT. Of note is that bladder

perforations are mostly inconsequential. With universal cystoscopy at the time of

sling placement, the cystotomy, typically at the dome of the bladder, is easily

identified. Repositioning of the sling, and ensuring subsequent proper placement

is generally sufficient. In certain cases, keeping the Foley catheter in for up to a

week may be necessary. Other complications that are more common with the

TVT include bleeding (intra and postoperative), and postoperative voiding

dysfunction necessitating sling revision; in contrast, the TOT has a higher rate of

mesh erosion, and postoperative groin and leg pain (123,130). Rare complications

include bowel injuries, and patient deaths after retropubic slings, and severe

infections after transobturator slings (131).

1713FIGURE 29-16 Sling erosion into the bladder. (Bieniek JM, Holste TL, Platte RO, et al.

Cystoscopic removal of intravesical synthetic mesh extrusion with the aid of Endoloop

sutures and endoscopic scissors. Int Urogynecol J 2012;23:1137–1139; Figure 1, need

permission.)

A unique complication associated with mid-urethral slings is erosion of the

sling material (130). Although uncommon, sling erosion into the vagina

generally requires surgical repair which involves resection of the segment eroding

into the vagina and repairing the vaginal mucosa over the involved site. When the

sling erodes into the bladder (and uncommonly into the urethra), this requires

more complicated surgery to resect the eroded segment (Fig. 29-16). Rarely, the

whole sling material (TVT or TOT) may need to be removed typically because of

chronic pain resulting from placement of the sling.

Certain mid-urethral sling characteristics and indications worthy of

mention include the following: (a) with retropubic slings, the bottom-up

route may be more effective than top-down route; (b) with the exception of

leg and groin pain, fewer adverse events occur with the transobturator than

1714the retropubic approach; (c) the transobturator may be more cost-effective

compared with the retropubic sling, although studies looking at cost do not

take into account the potential impact of repeat surgery to address

recurrence of incontinence on overall cost; (d) the retropubic sling is favored

over the transobturator sling in cases of fixed immobile urethra (intrinsic

sphincter deficiency) and mixed urinary incontinence; and (e) the

transobturator approach may be favored in cases where there is previous

significant bowel or pelvic adhesive disease.

Single incision (mini) slings have been introduced with the goal of further

minimizing surgical complications while maintaining efficacy. A mid-urethral

incision is made to introduce the sling while fixing (or anchoring) the two shorter

arms to the fascia in the obturator or retropubic space. However, their short- to

mid-term results are not very promising. In a recent Cochrane review, minislings were reported to be either inferior, or they lacked enough evidence to

support their endorsement over the retropubic or transobturator slings

(132). More studies with longer-term follow-up are needed to establish their

safety profile in treating women with stress urinary incontinence without

compromising surgical success. When a mid-urethral sling is chosen as a

treatment option, the AUA guidelines recommend either a retropubic or

transobturator sling as a first choice, and if a mini-sling is to be used, patients are

to be informed that not enough short-, medium- and long-term data exist in its

support (64).

Over the past century, surgical standards of care for stress urinary incontinence

have made a full circle from slings (mostly pubovaginal) to bladder neck and

retropubic suspensions and back to slings (mostly mid-urethral). These transitions

in surgical care have occurred mostly on the heels of an in-depth understanding of

the anatomy of the pelvic floor and rigorous evidence-based epidemiologic and

clinical research.

Bulking Agents

Urethral bulking agents are an accepted treatment option for women with

stress urinary incontinence. They are typically injected around the proximal

urethra submucosally to give it bulk, either transurethrally or periurethrally,

using an operative cystoscope. When compared to the mid-urethral slings,

the colposuspension, and pubovaginal slings, there exist little data evaluating

their long-term success. Repeat operations are common after bulking agent

therapy. However, they are appropriate procedures for patients who are poor

surgical candidates, on anticoagulation therapy, with high PVRs, or in older

women with high surgical anesthesia risk (133). The advantage of injectable

agents is that they are less invasive and they can potentially be done in a clinic

1715setting without the need for general or regional anesthesia.

Available and FDA-approved bulking agents for stress urinary incontinence

treatment include pyrolytic carbon–coated zirconium oxide spheres (beads)

(Durasphere), cross-linked polydimethylsiloxane (Macroplastique), and spherical

particles of calcium hydroxylapatite (Coaptite). The glutaraldehyde cross-linked

bovine collagen (Contigen) is not being produced by its manufacturer and is no

longer available in the United States market. Injection of the bulking agent into

the urethral submucosa produces its coaptation to help maintain continence in the

presence of an increased abdominal pressure (134–136). In one review article, it

was noted that subjective success rates ranged from 66% to 90% at 12-months

follow-up, whereas objective improvement ranged from 25% to 73% (137). A

2017 Cochrane review showed that limited data exist beyond 2 years

posttreatment with urethral bulking agents. Short-term data are suggestive

of an improvement, but they lack the robust success or cure rates associated

with mid-urethral slings (138). Reported complications of the urethral

bulking agents include urinary tract infections, urinary retention, erosion

and migration of the implanted material (139).

Other Potential Future Therapies

Autologous stem cells have been used experimentally to help regain bladder

control. Most studies have used stem cells derived from muscle or adipose tissue.

The stem cells can be injected periurethrally or into the pelvic floor to regenerate

damaged urethral sphincter or repair/reconstruct pelvic support structures using

tissue engineering techniques. Although preclinical and early clinical trials have

demonstrated safety, efficacy of those techniques to treat stress urinary

incontinence is still in question (140,141). Radiofrequency applied transurethrally

to promote collagen denaturation is another modality that has been proposed as a

nonsurgical procedure to treat stress urinary incontinence. However, a Cochrane

review demonstrated no benefit (or insufficient evidence) of radiofrequency when

compared with sham treatment (142). Vaginal laser therapy is another technique

that is being marketed as a safe and office-based treatment modality for female

stress urinary incontinence. There is no evidence to support this use in clinical

practice over conventional treatment options (143).

Procedures for Urgency Urinary Incontinence

When conservative and pharmacologic options fail, second-line treatments

for urgency urinary incontinence include injection of onabotulinumtoxinA

(Botox) in the bladder, percutaneous tibial nerve stimulation (PTNS), and

sacral neuromodulation (Interstim) (144).

Botox Injections

1716OnabotulinumtoxinA (Botox) is a neurotoxin that produces its paralytic

effect on the detrusor muscle of the bladder by blocking the calcium channels

and inhibiting release of acetylcholine at the presynaptic neuromuscular

junction. Its use was initially FDA-approved in women with neurogenic detrusor

overactivity with a typical injected dose being 200 units (U) (145). In 2013, its

use was approved for idiopathic OAB and urgency urinary incontinence. The

typical dose for nonneurogenic OAB is 100 U where injection of

onabotulinumtoxinA is performed cystoscopically with about 20 injection

points within the detrusor muscle sites and mostly supratrigonal (Fig. 29-17).

When successful, the effect of the injection typically lasts for 6 months to 2

years with repeat injections needed in 50% of women within 12 months

(146).

The FDA approval decision was mostly based on a multicenter double-blind,

randomized controlled trial comparing one intradetrusor injection of 100 U of

onabotulinumtoxinA to daily oral anticholinergic medication (solifenacin or

trospium) in 249 women with urgency urinary incontinence over a period of 6

months. This study demonstrated similar reductions in daily urgency, frequency,

and urgency urinary incontinence episodes between the two groups. Complete

resolution of urgency urinary incontinence occurred in more than twice of the

onabotulinumtoxinA (27%) than the anticholinergic (13%) group, P = 0.003. Side

effects with the injection group included catheter use up to 2 months (5%) and

urinary tract infections (33%) (147).

A meta-analysis of 56 randomized controlled trials showed that patients

receiving onabotulinumtoxinA (100 U) had improvements in urgency, frequency,

and incontinence episodes similar or better than medications, and significantly

better than placebo (146). The AUA currently recommends intradetrusor

onabotulinumtoxinA (100 U) when conservative and medical treatments have

failed in women with OAB. It is noteworthy that the patient must be taught and be

willing to perform self-catheterization, if needed, after the injection. In addition to

urinary tract infections and retention, side effects include gross hematuria, dry

mouth, dysphagia, impaired vision, and muscle weakness (144).

Percutaneous Tibial Nerve Stimulation

PTNS was approved by the FDA in 2000 for OAB. PTNS involves

introducing an acupuncture-type needle electrode (34-gauge) at a 60-degree

angle around the ankle, about 3 fingerbreadths above the medial malleolus

and posterior to the tibia. The electrode is connected to a battery-charged

stimulator, and treatment involves 30-minute weekly sessions for 12 weeks. If

successful, maintenance involves once monthly sessions thereafter. A

multicenter trial of 220 women with OAB symptoms randomized to 12 weeks

1717of treatment with PTNS versus sham therapy resulted in marked

improvement of symptoms in 55% compared to 21% in the respective

groups (148).

FIGURE 29-17 Injection of onabotulinumtoxinA into the detrusor muscle. (Ginsberg D,

Gousse A, Keppenne V, et al. Phase 3 efficacy and tolerability study of

onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity. J

Urol 2012;187:2131–2139; Figure 1, need permission.)

PTNS has been compared to anticholinergic medications including longacting toleterodine and oxybutynin in different studies (149). Similar

improvements have been shown in urinary frequency, incontinence,

nocturia, bother, and QOL scores in the short term (12 weeks) between the

two treatment modalities (150). At 2- to 3-years follow-up, the medication

group reported worsening symptoms especially that many women on

anticholinergics are not compliant with taking medications long term

because of side effects (149,151). PTNS is considered an acceptable

1718alternative to medical treatment, in the short term in patients who cannot

tolerate anticholinergic side effects, or in the long term in patients who show

signs of impaired cognition and memory loss. It is important to emphasize to

patients that for optimal results, treatment sessions are administered weekly for

the initial 12 weeks, and women should have the appropriate resources to make

frequent clinic visits. Side effects of PTNS are limited and they include minor

bleeding, pain, or tingling sensation at the needle site.

Neuromodulation

Sacral nerve stimulation (also known as neuromodulation) is another FDAapproved treatment modality for refractory OAB, urgency urinary

incontinence, and voiding dysfunction in women who have failed

conventional treatment options. Sacral nerve stimulation involves an initial

phase with a 1- to 2-week trial lead placed percutaneously to evaluate

response to treatment. Those reporting at least 50% improvement in their

OAB symptoms move on to phase two where a permanent electrode lead is

introduced through the back and placed around the third sacral nerve root.

This electrode is connected to a pulse generator that is implanted in the

patient’s buttock. Unlike PTNS and onabotulinumtoxinA, sacral nerve

stimulation is a more complex procedure that generally requires fluoroscopy

in an operating room setting and is associated with a different adverse event

profile (152). It is contraindicated to perform an MRI in women with an

implanted neurostimulator.

A randomized controlled trial of 147 women compared medical treatment to

sacral nerve stimulation over a period of 6 months. At baseline, women reported

bothersome symptoms of OAB with more than two urgency incontinence

episodes within 3 days and more than eight voids per day. Results showed that

women who received the neurostimulator (61%) had significantly higher

treatment success than women receiving medical treatment (42%) (P = 0.02).

Adverse events were similar between the two group at 31% and 27%, respectively

(153). In another prospective multicenter study, 272 patients implanted with the

sacral nerve stimulation were followed for a year. Using diary data at 12 months

showed a therapeutic improvement rate of 85% including a mean reduction of

urgency incontinence episodes of 2.2 leaks/day (down from 3.1) and urinary

frequency of 5.1 voids/day (down from 12.6), both P <0.0001. Women reported

significant improvement in their QOL measures and decreased interference of

urinary symptoms with their daily activities (154). Device-related adverse events

occurred in 30% (82/272) of women with an implanted neurostimulator at 12

months. These included undesirable change in stimulation (12%), implant site

pain (7%), and implant site infection (3%). Of the 26 women with implant site

1719pain, 13 underwent surgical intervention, and two had removal of the stimulator.

Of the 13 cases with implant site infection, five received antibiotics and eight

required removal (155).

A randomized controlled trial compared 364 women with OAB who underwent

treatment either with onabotulinumtoxinA or sacral nerve stimulation. Women

who received onabotulinumtoxinA reported greater reduction in 6-month mean

number of urgency incontinence episodes per day than those who received sacral

neuromodulation (–3.9 vs. –3.3; P = 0.01). Participants treated with

onabotulinumtoxinA showed greater improvement in symptom bother (–46.7 vs.

–38.6; P = 0.002) and treatment satisfaction (68 vs. 60; P = 0.01) than those

receiving sacral neuromodulation. There were no differences in treatment

preference (92% vs. 89%; P = 0.49) or adverse events, except for urinary tract

infections which were more frequent in the onabotulinumtoxinA group (35% vs.

11%; P < 0.001). Urinary retention requiring self-catheterization was 2% at 6

months in the onabotulinumtoxinA group, and stimulator device revisions or

removals occurred in 3% (156).

Augmentation Cystoplasty and Urinary Diversion

Augmentation cystoplasty and urinary diversion, typically using segments of the

patient’s intestine, are procedures that are rarely performed to treat urinary

incontinence, and typically fall in the advance urology domain. They have been

reported in women with chronic and debilitating detrusor overactivity

unresponsive to second or third-line treatment options (157). A 2012 updated

Cochrane review found a handful of small studies with limited information to

guide clinical practice (158). As neuromodulation and cystoscopic injection with

onabotulinumtoxinA become more prevalent and better studied, there will be

limited, if any, role for augmentation cystoplasty and urinary diversion to treat

women with urgency urinary incontinence.

Surgery for Fistula Repair

Genitourinary fistula repair is commonly performed vaginally, but can be

repaired through an abdominal access, either open, laparoscopic, or

robotically. For very small pinpoint fistulae, there may be a role for

conservative options with an attempt of 10 to 14 days of transurethral

catheterization and to allow the fistula to close spontaneously. If that fails, or

for larger fistulae, surgery is the mainstay (Fig. 29-18). Proper surgical

technique involves: (a) identification of fistula (ae); (b) getting adequate

access and exposure (e.g., if a vaginal approach is preferred, a pediatric

Foley catheter can be placed vaginally and the balloon inflated to put

downward traction on the fistula for better visualization); (c) debridement of

1720nonviable tissue; (d) mobilization of fresh and viable tissue (1 to 2 cm)

around and all along the fistulous tract; (e) repair of the fistula in several

layers starting at the bladder end and going out to the vagina; (f) minimal

tension on the repaired layers; (g) 7 to 14 days of postoperative

catheterization; (h) use of tissue grafts (e.g., Martius labial fat-pad) as

needed for larger or recurrent fistulae.

Voiding Dysfunction

Definition

The mechanism of normal bladder emptying is a coordinated effort that is

initiated by the individual. It involves a detrusor muscle contraction

associated with urethral sphincter relaxation. The pressure generated by the

detrusor muscle contraction should be of an appropriate duration and a magnitude

that is higher than the pressure in the urethra to produce the desired effect of

completely emptying the bladder. The neurophysiology of micturition has

previously been described. In addition to an intact neuromuscular control and

support, voiding is dependent on the volume of urine within the bladder and

intravascular volume that gets filtered through the kidneys. One study of 165

women with no history of urologic diseases and/or pelvic surgery showed a

significant difference in the frequency and volume of urine produced in 24 hours

(range between 437 and 3,861 mL) (159). In addition to the bladder volume at the

time of voiding, the maximum urine flow rate (range between 16 and 37mL/s) is

variable and dependent on patient position, age, and menopausal status among

other factors (160).

[6] Voiding dysfunction occurs when a woman loses the ability to empty her

bladder effortlessly and completely within a limited time frame (usually

within 60 seconds or less). Objectively, voiding dysfunction can be identified

on a uroflow when the voiding time is prolonged, the flow pattern is

interrupted (see Fig. 29-8 above), or the maximum flow rate is diminished.

During complex urodynamics, additional objective measures of voiding

dysfunction include increased urethral pressure (resistance) with an increased

detrusor pressure (detrusor–sphincter dyssynergia), or a low detrusor pressure

with a normal or low urethral pressure (detrusor underactivity) at the time of

urination (65). [6] Patients with voiding dysfunction may express a host of

sensory and abnormal bladder emptying symptoms including hesitancy, slow

or intermittent urinary stream, straining on urination, feeling of incomplete

bladder emptying, reduced bladder sensation and others (Table 29-10).

Etiology

1721Acute urinary retention is a sudden and often painful inability to void despite

the sensation of a full bladder and desire to urinate. It is mostly iatrogenic

resulting from neurologic injury after radical pelvic surgery (radical

hysterectomy, radical perineal resection, colorectal extensive resections),

neurologic injury during spinal surgery or commonly after female pelvic

reconstructive surgery, and incontinence surgery (e.g., mid-urethral sling).

Rarely, and uniquely in pregnant patients, especially in the peripartum period, the

bladder is vulnerable to urinary retention; if undetected, this can lead to bladder

underactivity, recurrent urinary tract infection, and incontinence (161).

Chronic urinary retention may be caused by neurogenic (e.g., multiple

sclerosis, diabetic neuropathy) or nonneurogenic conditions (e.g., advanced

prolapse) (162). This can lead to serious conditions like hydronephrosis and

chronic renal insufficiency, but is more commonly associated with conditions

that impair an individual’s daily activities like recurrent urinary tract

infections, feelings of incomplete bladder emptying, and overflow

incontinence. Chronic urinary retention is defined as PVR of more than 300

mL persisting for more than 6 months which has been documented in two

separate occasions (162). Common conditions associated with incomplete

bladder emptying and retention in women are outlined below (Table 29-11).

1722FIGURE 29-18 Repair of apical vesicovaginal fistula. A: The fistula at the vaginal apex is

exposed with adequate retraction. A pediatric Foley can be placed into the fistula tract to

aid in traction and dissection. B: The vaginal epithelium is dissected from the fistula to

mobilize the tissue to allow for tension-free closure. In the classic Latzko procedure, the

vaginal epithelium 2 cm around the opening of the fistula is removed. C: The fistula tract

may either be completely excised, or in the Latzko procedure, the fistula edge may

freshened up slightly but is not excised. D: Interrupted absorbable sutures are placed in an

1723extramucosal location in an interrupted fashion. An additional layer of interrupted sutures

is often placed to invert the initial suture line. The vaginal epithelium is then closed over

the repair. In the classic Latzko procedure, the initial layer involves closure of the vagina

over the fistula tract, then two additional layers with the vaginal epithelium result in an

apical colpocleisis. (Redrawn from original by Jasmine Tan.)

Evaluation

Evaluation starts with a careful medical history to eliminate possible conditions

associated with voiding dysfunction (e.g., multiple sclerosis, diabetes, psychiatric

disorders) and concomitant medications. Should medical history reveal previous

surgical treatment for urinary incontinence, it is important to obtain medical

records or operative reports to determine the exact nature of the surgery. A careful

pelvic examination is conducted with special attention to urethral orifice and

anterior wall of vagina to rule out possible pelvic or vaginal masses causing

urethral obstruction. Abdominal palpation or suprapubic percussion may indicate

a full bladder. Cystoscopy can help diagnose the presence of urethral polyps or

bladder tumors, stones, or foreign bodies causing obstruction. Evaluation of the

strength of the detrusor muscle contraction during voiding and urethral outlet

relaxation, or lack thereof (i.e., urethral resistance) can be undertaken at the time

of urodynamics, including measurement of PVR.

Table 29-10 Classification and Definition of Lower Urinary Tract Symptoms in

Women

II. Abnormal Sensory Symptoms

Increased

bladder

sensation

Desire to void during bladder filling occurs earlier or is more

persistent from that previous experienced (differs from urgency by

the fact that micturition can be postponed despite the desire to void)

Reduced

bladder

sensation

Definite desire to void occurs later than that previously experienced,

despite an awareness that the bladder is filling

Absent bladder

sensation

Absence of the sensation of bladder filling and a definite desire to

void

III. Abnormal Emptying

Hesitancy Delay in initiating micturition

Straining to

void

Need to make an intensive effort (by abdominal straining, Valsalva

or suprapubic pressure) to initiate, maintain, or improve urinary

stream

1724Slow stream Urinary stream perceived as slower compared to previous

performance or in comparison with others

Intermittency Urine flow that stops and starts on one or more occasions during

voiding

Feeling of

incomplete

bladder

emptying

Bladder does not feel empty after micturition

Postmicturition

leakage

Involuntary passage of urine following the completion of

micturition

Spraying of

urinary stream

Urine passage is a spray or split rather than a single discrete stream

Positiondependent

micturition

Requiring specific positions to be able to micturate spontaneously

or to improve bladder emptying, for example, leaning forward or

backward on the toilet seat or voiding in a semi-standing position

Urinary

retention

Inability to pass urine despite persistent effort

From Haylen BT, de Ridder D, Freeman RM, et al. An International Urogynecological

Association (IUGA)/International Continence Society (ICS) joint report on the

terminology for female pelvic floor dysfunction. Neurourol Urodyn 2010;29:4–20, with

permission.

Treatment

Prior to treatment initiation for chronic urinary retention, the AUA

guidelines recommend evaluation of the upper tracts to assess the functional

integrity of the kidneys (creatinine clearance) and rule out hydronephrosis

(renal ultrasound or CT urogram) (162). Low-risk, asymptomatic individuals

can be surveilled with yearly urinalysis and urine culture with no unnecessary

treatment. [6] In symptomatic patients (e.g., recurrent urinary tract infections),

treatment is symptom driven. Patients are encouraged to double void and have

frequent trips to the bathroom (162). Patients can be referred to pelvic floor

physical therapy for bladder retraining.

Table 29-11 Conditions Associated with Voiding Dysfunction and Urinary Retention

Effect on Bladder Muscle CONTRACTION Effect on Urethra OUTFLOW

1725• Medications (anticholinergics, opioids, beta

adrenergic agonists, Ca channel blockers,

NSAIDs, tricyclic antidepressants,

benzodiazepines, antipsychotics)

• Urethral or bladder neck

stricture (post-incontinence

surgery, prior vaginal or

reconstructive surgery)

• Diabetes mellitus • Urethral narrowing, swelling or

obstruction due to sling,

urethral bulking agent or other

• Long-standing outlet obstruction • Pelvic organ prolapse (high

grade)

• Constipation • Urethral diverticulum, stones,

or tumor

• Neurologic diseases (MS) • Primary bladder neck

obstruction

• Aging • Extrinsic compression (tumors)

• Fowler syndrome • Neurologic disorders

• Acontractile bladder (Detrusor sphincter

dyssenergia)

[6] In high-risk patients, intermittent catheterization is recommended.

Although there is lack of evidence comparing intermittent selfcatheterization to indwelling catheters, expert opinion, favors intermittent

catheterization for better long-term outcomes (163). Either the patient or her

caregiver can be instructed to perform bladder self-catheterization. In the

presence of advanced prolapse, a trial of pessary can be performed with the goal

of reducing the prolapse to relieve the obstruction on the urethra resulting in

improved voiding and decreased retention (162).

[6] Acute urinary retention is addressed according to the specific situation

causing the retention. This may take the form of expectant management with an

indwelling catheter for postradical hysterectomy, pelvic reconstructive, or

incontinence surgery. The catheter can be plugged after a week of retention and

continued voiding dysfunction to allow the bladder to recover filling sensation.

When a full bladder in sensed by the patient, she is instructed to remove the plug

and drain the bladder. Alternatively, patients can be instructed to self-catheterize

until resolution of the retention (usually a PVR of volume of 100 mL or less is

acceptable). Should the patient continue to have voiding dysfunction for several

weeks after surgery, a sling revision and/or urethrolysis may be necessary (164).

[6] In the absence of an obstruction, medications can be used for urinary retention

1726caused by either detrusor underactivity or increased resistance in urethral

sphincter. These include alpha blockers or beta agonists, however these drugs

have proven to be generally ineffective and there is lack of clear evidence to

support their routine use (104,105,165).

Neuromodulation and intravesical electrical stimulation may be effective in

select patients (166). In addition to urgency, frequency, and urgency urinary

incontinence, sacral neuromodulation has been used to treat nonobstructive

voiding dysfunction in women (167). Long-term follow-up shows promising

results in idiopathic retention (Fowler syndrome, patients with multiple sclerosis

and painful bladder syndrome) with a success rate of as high as 73% (168).

Bladder Pain Syndrome

The recent IUGA/ICS report on management of pelvic floor dysfunction defines

acute pain as that related to recent trauma, infection or other disease and chronic

pain as either persistent or recurring pain for at least 6 months (82). It is important

to differentiate pain which is a sensation expressed subjectively by the individual

from tenderness which is a sensation of discomfort, with or without pain, and that

may be elucidated by palpation on a physical examination.

Definition

[6] Bladder pain syndrome is challenging to diagnose, prevent, and treat

because its basic science and pathophysiology is poorly understood. Bladder

pain is defined as the complaint of suprapubic or retropubic pain, pressure,

or discomfort related to the bladder. It usually increases in intensity with

bladder filling and may persist or disappear after voiding (8). Women with

bladder pain syndrome usually have other associated urinary symptoms,

such as urinary urgency or frequency; the pain is of a duration of at least 6

weeks or more in the absence of urinary tract infections or other identifiable

causes (169). The prevalence of bladder pain syndrome varies widely, based

on definitions used, from less than 1% to as high as 20% (170,171). Some

authors have developed an interstitial cystitis/bladder pain syndrome

questionnaire for use in epidemiologic studies (172). Based on this questionnaire,

the prevalence in adult U.S. females ranges between 3% and 7% with the peak

prevalence being in the 50’s (173).

The terms “bladder pain syndrome” and “interstitial cystitis” have been

used interchangeably in the literature, where the latter was first described as

an inflammatory bladder condition, sometimes associated with ulceration of

the bladder wall, named Hunner lesion (174). Interstitial cystitis is believed to

be associated with a defective glycosaminoglycan sulfate layer that covers the

bladder mucosa. To standardize definitions and enable comparative research, the

1727National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK)

developed strict criteria for interstitial cystitis; however, these definitions have

been shown to be too restrictive to use in clinical practice. NIDDK criteria

include the presence of pain and urgency associated with objective findings of

glomerulations or Hunner ulcers during cystoscopy and hydrodistention of the

bladder, including a small bladder capacity and terminal hematuria (175). Most

clinicians prefer to use Looser criteria when treating women with bladder pain

syndrome. The understanding of bladder pain syndrome is that it is not limited to

an inflammatory mechanism but may encompass a spectrum of conditions

including OAB, other chronic pain conditions, somatization disorders, and

neurologic diseases (176).

Diagnosis

Basic assessment in a woman with bladder pain syndrome consists of

obtaining a detailed medical history, physical examination, bladder diary

(frequency/volume chart) and urinalysis with culture (177). The workup

should be supplemented with urine cytology in older women, especially those

who report history of smoking or prior exposure to chemical. Bladder pain

syndrome is a diagnosis of exclusion. A differential diagnosis includes chronic or

recurrent urinary tract infections, urethral diverticulum, vulvovaginal atrophic,

inflammatory, allergic, or infectious conditions, chronic pelvic pain related to

endometriosis, inflammatory bowel conditions, myofascial pain, and others.

Exclusion of these diseases may require further imaging, cystoscopy,

urodynamics, and even laparoscopy.

Treatment

The initial management of bladder pain syndrome relies on patient

education, dietary modification, stress reduction, and pelvic floor relaxation

techniques (177). Women are encouraged to avoid bladder irritants such as

caffeinated beverages, alcohol, carbonated drinks, acidic drinks, and spicy foods.

When the conservative approach fails, medication, physical therapy or

intravesical treatment are implemented. Referral to a pain specialist can be

beneficial. Effectiveness of medical therapy is not well-proven, and long-term

follow-up is not well-studied. One study reviewed treatments received by 581

women enrolled in the interstitial cystitis database study group between 1993 and

1997. A total of 183 different types of treatments were reported, with the most

commonly prescribed being cystoscopy and hydrodistention, amitriptyline,

phenazopyridine, special diet, and intravesical heparin (178).

Urinary analgesics like phenazopyridine and Prosed DS have been offered to

patients with painful bladder syndrome for pain or bladder spasm relief. The latter

1728is a mixture of methenamine, methylene blue, phenyl salicylate, benzoic acid, and

hyoscyamine. Amitryptyline, a tricyclic antidepressant, has been studied for

symptom relief in women with painful bladder syndrome, and it has been shown

to be beneficial only when a dose of 50 mg or more is achieved (179).

Antihistamines have been proposed as potentially being helpful for bladder pain

syndrome since pain may be the consequence of histamine release. Hydroxyzine

is a commonly used antihistamine; however, a multicenter, randomized clinical

trial showed only a 30% versus 20% response for those who were treated with

hydroxyzine versus placebo, respectively (180). Another antihistamine includes

cimetidine; but studies on its use have included a very small number of patients

with inconclusive results (181,182).

Pentosan polysulfate (elmiron) is an FDA-approved heparinoid medication

to treat women with bladder pain syndrome/interstitial cystitis. The

recommended dose is 100 mg three times per day and symptom relief may

not be achieved for at least 3 months. The efficacy of pentosan polysulfate

has been brought to question by a placebo-controlled randomized trial

showing similar symptom relief between the two groups (183). As an

alternative to oral medications, intravesical treatment may be offered to patients

with bladder pain syndrome. Dimethylsulfoxide (DMSO) is the only FDAapproved intravesical treatment. This involves instilling the bladder with 50 mL

of 50% solution of DMSO for 20 to 30 minutes, and to be repeated weekly or

every other week for six sessions. It is believed to reduce inflammation, relax

muscles, and alleviate pain. As side effects, patients report garlic odor and

transient bladder irritation (177). Alternative intravesical instillations that have

been investigated include hyaluronic acid, chondroitin sulfate, cyclosporine A,

bacillus Calmette–Guerin, oxybutynin, bupivacaine/heparin/steroid (mix), and

others (184–188). Other treatment options include cystoscopy under anesthesia

with hydrodistention, neuromodulation, transcutaneous electrical stimulation

(TENS), and intradetrusor botulinum toxin A injection (189–191).

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