Epidemiological studies have established that voiding symptoms are very common in the general population, affecting up to 57.1% of men and 48% of women over the age of 40 at some time.¹ For many years there has been a focus on bladder outlet obstruction (BOO) and in particular benign prostatic hyperplasia (BPH) as the underlying pathophysiological process causing these symptoms. Consequently, several novel pharmacotherapies and new technologies were introduced into clinical practice. By contrast detrusor underactivity (DUA) has been largely neglected as a topic for clinical and scientific research. This is emphasized by the observation that the last major advance in management was the introduction of clean intermittent self-catheterization by Jack Lapides more than 40 years ago. Over recent years there has been a resurgence of interest in investigating this problem with rising enthusiasm to better understand its epidemiology, aetio-pathogenesis and to develop new treatments.² Despite the current enthusiasm for what appears to be a “topical” clinical issue, it is clearly evident that there has been little progress in our knowledge and the therapeutic options available as evidenced by a contemporary update.³

While there has in the past been a lack of consensus on terminology with a plethora of terms being used, that recommended by the International Continence Society is DUA,⁴ as a urodynamic diagnosis which is defined as “a contraction of reduced strength and/or duration, resulting in prolonged bladder emptying and/or failure to achieve complete bladder emptying within a normal time span.” This definition is hampered by the subjective interpretation of what constitutes normal detrusor contraction strength, length and emptying time. Unlike the detrusor overactivity and its related but nonspecific storage symptom complex, the overactive bladder (OAB) is not analogous with the urodynamic diagnosis of bladder overactivity.⁵ There is currently no widely accepted symptom complex related to DUA, though some have suggested the term underactive bladder (UAB).

UAB is indeed an attractive concept, as it could lead to the identification of patients based on symptoms rather than an invasive pressure flow study. Particularly, this would facilitate epidemiological studies and generate greater interest in developing novel treatments. Unfortunately, on closer inspection of contemporary evidence, UAB is difficult to diagnose as there is significant overlap with the symptoms associated with bladder outflow obstruction (BPH and OAB) and detrusor overactivity (DO-OAB). Therefore, symptomatic diagnosis of UAB is unreliable and can lead to assumptions in studies based on a symptomatic assessment of the condition that do not represent a true picture of the prevalence of this important problem.³ It must be borne in mind that the “bladder is an unreliable witness” as lower urinary tract symptoms (LUTS) often do not accurately reflect the underlying urological abnormality. All of the terms benign prostate enlargement (BPE), OAB and UAB are nonspecific, symptom-based diagnoses, based on the objective assessments of subjective data–the converse of pressure flow urodynamics, which is subjective assessment of objective parameters. The symptomatic expression of DUA is particularly difficult as, in addition to its being predominantly a voiding dysfunction characterized by voiding symptoms, the large post-void residuals (PVRs) may lead to significant storage symptoms, including incontinence. Nevertheless, efforts are underway to develop a working definition based upon expert consensus and the available data.⁶

An important consideration in developing any definition is that it will include a diverse group of patients as the etiology of DUA is multifactorial.⁷ This is clear when one reviews the potential clinical tools which can be used to identify patients (see table).

Confirmed etiological factors include neurological disease (eg multiple sclerosis and sacral cord injury) and diabetes mellitus. While longstanding BOO has been suggested to be a potential contributory cause, studies in animal models have demonstrated DUA ensues following prolonged BOO; however, confirmatory evidence of this in man is lacking. Aging has been linked to a decline in detrusor contractile function in some animal models and in patients with LUTS; however, there has been no adequate study in healthy individuals. These diverse etiologies could logically lead to DUA by the consequence of any pathology affecting any part of the micturition reflex including the sensory nerves, the central neural control, the efferent nerves or the detrusor muscle. While the diagnostic criteria for DUA and by inference UAB are an area where consensus is lacking, numerous clinical studies have attempted to estimate its prevalence in the patients presenting with LUTS. In this group, it has been estimated that DUA affects 9%–28% of men under the age of 50 years and 48% in those older than 70. In women DUA is found in 12%–45% and is more prevalent among the institutionalized elderly.

Clearly at present based on the uncertainties noted above, a definitive diagnosis of DUA relies upon an invasive pressure flow assessment, and several derived calculations and indices are available for use (eg bladder contractility index, Watt factor). Most of these have their basis in the bladder outlet relation, which represents the inverse relationship between pressure and flow during a void, and aims to estimate iso-volmetric detrusor pressure as a surrogate for isometric contraction strength. The main problem with most of these reported measurements is the lack of validated thresholds for different patient groups, in particular women and young men, as most studies have been conducted in older men. A further issue that is relevant to clinical practice is the inability to reliably exclude the presence of BOO when the patient is unable to generate sufficient detrusor pressure.

The mainstay for the management of DUA has been the use of clean intermittent catheterization where the patient is able and willing to do this. Parasympathomimetic therapy including muscarinic agonists and anticholinesterases are the only available researched agents for this indication based on a handful of relatively low-quality studies. Analysis of these data does not support their efficacy as they are associated with significant side effects, such as tachycardia, facial flushing, salivation, diarrhea and in rare circumstances cardiac depression. Theoretically, any potential new drug therapy would work to either directly increase the contractility of the detrusor muscle or to do so indirectly by sensitizing the sensory nerves. Possible targets include the muscarinic or prostaglandins receptors or the transient receptor potential channels. At present little progress has been made in developing effective pharmacotherapeutic therapy as the most recent development programs in this area have not been successful.

In 2021, 50 years after the widespread introduction of urodynamic assessment, we need to bear in mind the limitations of symptom-based diagnoses in functional urology such as BPH and OAB, which although essential for the institution of noninvasive therapy nevertheless have their limitations. DUA remains under-researched and inadequately treated in clinical practice, except by the institution of invasive bladder drainage preferably by intermittent self-catheterization. Future work needs to be directed at better defining the true prevalence of DUA and its symptom-based correlate UAB, with the development of novel pharmacotherapeutic treatments introduced on the basis of robust clinical trial data to support their use.