Overactive bladder syndrome, polyuria, and nocturia

Terminology, prevalence, epidemiology, and economic impact

The International Continence Society (ICS) is the governing body that has historically taken the lead in the standardization of terminology. The terminology used to describe OAB and associated symptoms has changed numerous times. The ICS recommends the use of symptoms, signs, and validated investigations to form workable diagnoses. In 2020, the ICS used the following terms:

• • Increased daytime urinary frequency: Complaint that voiding occurs more frequently during waking hours than previously deemed normal by the individual (or caregivers) ( ).

• • Nocturia:The number of times urine is passed during the main sleep period. Having woken to pass urine for the first time, each urination must be followed by sleep or the intention to sleep ( ).

• • Urgency: Complaint of sudden, compelling desire to pass urine that is difficult to defer ( ).

• • Overactive bladder (urgency) syndrome: Urinary urgency, usually accompanied by daytime frequency and/or nocturia, with or without urinary incontinence, in the absence of UTI or other obvious pathology ( ).

• • Urgency urinary incontinence (UUI): Complaint of involuntary loss of urine associated with urgency ( ).

• • Detrusor overactivity (DO): The occurrence of detrusor contraction(s) during filling cystometry. These contractions, which may be spontaneous or provoked, produce a waveform of variable duration and amplitude on the cystometrogram (CMG). The contractions may be phasic or terminal. They may be suppressed by the patient or be uncontrollable. Symptoms, for example, urgency and/or urgency incontinence or perception of the contraction, may or may not occur ( ). DO may be further qualified as neurogenic, when there is a relevant neurologic condition, or idiopathic, when the cause is unknown.

It is important to note that, although the current definition of OAB is based on symptoms, DO is a urodynamic observation. By definition, to diagnose a patient with DO, one must observe involuntary detrusor contractions during the filling phase of CMG during urodynamics testing. OAB and DO are thus not interchangeable terms, and it is important that the clinician use each term correctly.

The number of individuals affected by OAB is difficult to establish. The populations studied vary substantially from one publication to another, and the symptoms or signs used to define OAB may also vary between publications. Overall, however, the incidence of OAB is high, ranging between 7% and 27% in males and between 9% to 43% in females ( ; ).

Based on data from the EPIC study, 10.7% of the world’s population was found to be affected by OAB (i.e., almost 250 million women and over 200 million men) ( ). The Epidemiology of Lower Urinary Tract Symptoms (EpiLUTS) study, a cross-sectional, population-representative survey of men and women over 40 years old conducted via the internet in the United States, the United Kingdom, and Sweden, revealed the distribution of individual and the combination of various lower urinary tract symptoms (LUTS) within the OAB symptom complex by gender ( ; ). In this large study that included 4562 women and 2559 men with OAB, 20.2% of women and 15.6% of men reported combined urgency, UUI, nocturia, and frequency.

In the United States alone, OAB has been estimated to affect up to 33 million people. However, it is estimated that only 15% of these patients with incontinence and OAB symptoms seek medical help. The National Overactive Bladder Evaluation program ( ) contacted more than 5000 households by telephone and, among those who responded, the overall prevalence of OAB was 16.6%. Men and women had a similar overall prevalence of OAB (16.0% and 16.9%, respectively) as defined by the ICS. The prevalence of symptoms increased sharply with age in both men and women ( Fig. 31.1 ).

Men were shown to have a higher prevalence of “OAB dry,” or OAB without UUI (13.4% vs. 7.6% in women), and women had a higher prevalence of “OAB wet,” or OAB with UUI (9.3% vs. 2.6% in men) ( Fig. 31.2 ). In women, the presence of “OAB wet” rose from 2% in the youngest group (ages 18–24 years) to 19.1% in those 65 to 74 years of age ( ).

In a secondary analysis of data from the EpiLUTS survey, examined whether there were racial differences in the prevalence of OAB amongst men and women in the United States. Of the 20,000 US adults surveyed, OAB was found to be most prevalent in Black men and women. In this study, the prevalence of OAB in Black, Caucasian, Hispanic, and Asian women was 45.9%, 43.4%, 42.0%, and 26.6%, respectively.

Given that women between the ages of 60 and 80 are the most rapidly growing segment of the US population, and that up to 50% of women in this age group meet criteria for OAB syndrome, treatment of this condition clearly has a significant economic impact on our society. Using population prevalence estimates from the EpiLUTS study, estimated the total cost at $24.9 billion annually. Another study estimated the current direct (medical and nonmedical) and indirect costs of OAB in the United States ( ). In 2007, average annual per capita costs of OAB were $1925 ($1433 in direct medical, $66 in direct nonmedical, and $426 in indirect costs). When applied to 34 million people in the United States with OAB, the total national costs were $65.9 billion ($49.1 billion direct medical, $2.3 billion direct nonmedical, and $14.6 billion indirect). This study, published in 2010, also predicted annual per capita costs to rise to $1944 in 2015 and $1969 in 2020, with total annual national costs rising to $76.2 billion in 2015 and $86.2 billion in 2020.

OAB can also have a significant impact on quality of life. Both men and women with bothersome OAB were more likely to report that their bladder condition caused them at least some problems ( ). These subjects reported worse scores on health-related quality of life questionnaires, anxiety assessments, and depression assessments. Men and women with bothersome OAB also had a greater number of health care visits annually compared to those with OAB without bother and those with minimal to no symptoms ( ).

Neurophysiology of the lower urinary tract

To better understand the etiology and pharmacologic management of OAB, a brief review of the neurophysiology of the lower urinary tract is presented (see Chapter 3 for further details).

Autonomic pathways.

Sympathetic nerves, which help to control bladder relaxation, exit the spinal cord at levels T10 through L2 and synapse in paravertebral ganglions. Noradrenaline, the neurotransmitter of the sympathetic system, binds to α- and β-adrenergic receptors, and then postganglionic fibers travel to the bladder via the hypogastric nerve ( Fig. 31.3 ). When norepinephrine binds to β-receptors on the bladder, it activates adenylate cyclase, which increases levels of cyclic adenosine monophosphate (AMP), thereby relaxing the detrusor muscle of the bladder ( Fig. 31.4 ).

The parasympathetic nerves, which are important in the control of bladder contractility, exit the spinal cord at levels S2, S3, and S4. Preganglionic fibers travel to the bladder via the pelvic nerve, synapse close to the bladder, and then send short postganglionic fibers to the bladder (see Fig. 31.3 ). The parasympathetic system uses acetylcholine as its neurotransmitter and muscarinic receptors at target organs. Five subtypes of muscarinic receptors are known, with a predominance of M ₂ and M ₃ receptor subtypes in the bladder. Release of acetylcholine by postganglionic parasympathetic nerves activates both M ₂ and M ₃ receptor subtypes. M ₂ receptors make up approximately 80% of the muscarinic receptors in the bladder. Activation of M ₂ receptors negatively affects adenylate cyclase, thereby decreasing cyclic AMP, and ultimately inhibiting relaxation caused by the sympathetic system. M ₃ subtypes, which make up the remaining 20% of muscarinic bladder receptors, activate phospholipase C, increase inositol triphosphate, and subsequently cause detrusor muscle contraction.

Central regulation.

The central regulation of micturition is controlled by several neurotransmitters, including acetylcholine, γ-aminobutyric acid (GABA), glycine, serotonin, dopamine, and noradrenaline. The pontine micturition center (Barrington nucleus or M region) is involved in regulating voiding and incontinence by projecting directly to bladder motor neurons and indirectly to urethral motor neurons. The bladder motor neurons are preganglionic and parasympathetic (S2, S3, and S4) and located in the intramediolateral cell column of the sacral spinal cord. The urethral motor neurons are located in the sacral ventral horn (Onuf’s nucleus). When the pontine micturition center is stimulated, the urethral motor neurons are inhibited, leading to a decrease in urethral pressure, and the bladder motor neurons are stimulated, leading to an increase in intravesical pressure, thus resulting in coordinated micturition between the bladder and the outlet ( Fig. 31.5 ).

The pontine continence center projects to urethral sphincter motor neurons and, when stimulated, increases urethral sphincter tone. During the filling or storage phase, the pontine continence center sends continuous stimulation to urethral sphincter motor neurons to maintain urethral closure (see Fig. 31.5 ).

Afferent information.

Afferent sensory information is sent from the bladder via the pelvic nerve to the sacral dorsal root ganglia located within the spinal cord. These nerves are primarily made up of myelinated A and D fibers and unmyelinated C fibers. The A and D fibers respond to distension and active contraction, whereas C fibers respond to chemical irritation and pain ( Fig. 31.6 ). There are several receptors that have been identified on these nerves, such as vanilloid, tachykinin, purinergic, and prostanoid receptors, which may have a role in the development of OAB syndrome and may be potential pharmacotherapy targets ( ).

Etiology of overactive bladder

Although there are numerous neurologic diseases associated with symptoms of OAB, the majority of women who present with this syndrome are neurologically intact. There are many conditions that are associated with OAB syndrome ( Box 31.1 ) and the symptoms of this condition; however, the pathophysiology remains unknown for many patients, and the syndrome as a whole can have a heterogeneous presentation.