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Lower urinary tract symptoms in males

Lower urinary tract symptoms in males
Literature review current through: Jan 2024.
This topic last updated: Oct 16, 2023.

INTRODUCTION — The term "lower urinary tract symptoms" (LUTS) is nonspecific. It has been used as a general term to refer to any combination of urinary symptoms or as a more specific term to refer to those symptoms primarily associated with overactive bladder (frequency, urgency, and nocturia). An international consensus conference defined LUTS to include symptoms relating to storage and/or voiding disturbances common among aging males [1]. This topic will review the symptoms, etiology, evaluation, diagnosis, and treatment of lower urinary tract dysfunction in males.

Discussions of incontinence, benign prostatic hyperplasia, and nocturia are presented separately:

(See "Urinary incontinence in men".)

(See "Clinical manifestations and diagnostic evaluation of benign prostatic hyperplasia".)

(See "Medical treatment of benign prostatic hyperplasia".)

(See "Nocturia: Clinical presentation, evaluation, and management in adults".)

PREVALENCE AND RISK FACTORS — The prevalence of LUTS in males increases with age. A survey of over 5000 community-dwelling males age ≥65 in the United States without history of prostate cancer found that 46 percent reported moderate to severe LUTS [2]. Another community-based study found that the prevalence of LUTS increases steadily with age, affecting 70 percent of males older than 80 years [3].

Diabetes mellitus appears to be a risk factor for LUTS, but the presence of urinary symptoms is not explained by the degree of glycemic control [4]. This relationship was strongest in younger males (<70 years old) and in those with longstanding (>5 years) disease. Other conditions associated with LUTS include cardiovascular disease [5], obesity, sedentary lifestyle, and erectile dysfunction. Although the pathophysiologic connection of LUTS to erectile dysfunction is not clearly defined, this observation has resulted in new approaches to the evaluation and management of both disorders.

SYMPTOMS — LUTS are categorized as symptoms related to storage, voiding, or postmicturition [6-8]. Males with LUTS may report one or any combination of symptoms that typically fluctuate over time and may remit spontaneously [9]. LUTS can be associated with severe sleep disturbance [10], increased depressive symptoms [11], and decreased ability to perform activities of daily living [2].

Storage — Storage symptoms, experienced during the bladder filling and storage phase of micturition, include:

Urgency – A sudden, compelling desire to pass urine that is difficult to defer

Daytime frequency – A patient's perception that he voids too often by day

Nocturia – The need to wake at night one or more times to void

Incontinence – Involuntary leakage

Abnormal bladder sensation

Voiding — Voiding symptoms are those experienced at the time of urine flow and include:

Slow stream – The individual's perception of reduced urine flow, usually compared with previous performance and sometimes compared with observations of other males. Splitting or spraying of the urine stream may be reported.

Intermittent stream or intermittency – Urine flow that stops and starts, on one or more occasions, during micturition.

Hesitancy – Difficulty in initiating micturition, resulting in a delay in the onset of voiding after the individual is ready to pass urine.

Straining to void – An abdominal muscular effort used to initiate, maintain, or improve the urinary stream.

Terminal dribble – Prolongation of the final part of micturition, when the flow has slowed to a trickle/dribble [7].

Dysuria – Pain, burning sensation, or general discomfort at the time of passing urine.

Postmicturition — Postmicturition symptoms include:

A sensation of incomplete emptying after passing urine

Postmicturition dribble – The involuntary loss of urine shortly following urination, usually after leaving the toilet [7]

ETIOLOGIES OF LUTS — Traditionally, LUTS in males were primarily attributed to benign prostatic hyperplasia (BPH) and consequent bladder outlet obstruction (BOO). However, overactive bladder (OAB), characterized by involuntary contraction of the detrusor muscle, may be the principal cause or a contributory cause of LUTS in some patients [12].

Bladder outlet obstruction from BPH — LUTS with symptoms of BOO are often attributed to an enlarged prostate or benign prostatic enlargement (BPE). BPH refers to a specific histologic diagnosis; although, the term is commonly used interchangeably with BPE despite the absence of tissue confirmation. We will use BPH here as synonymous with BPE.

Clinically significant BPH presents as LUTS with a predominance of voiding symptoms. Patients experience progressive symptoms that can range from nocturia to acute urinary retention and may include incomplete emptying, urinary hesitancy, weak stream, frequency, and urgency. Long-term or chronic BOO may eventually lead to bladder/detrusor decompensation. (See "Acute urinary retention" and 'Combination OAB and BOO' below.)

Clinical manifestations and diagnostic evaluation for BPH are discussed in detail elsewhere. (See "Clinical manifestations and diagnostic evaluation of benign prostatic hyperplasia".)

Other causes of bladder outlet obstruction — Other conditions that may cause BOO include urethral stricture; primary bladder neck obstruction; bladder neck contracture; detrusor sphincter dyssynergia; prostate cancer; and, less likely, meatal stenosis.

Overactive bladder — OAB is defined by the International Continence Society as a syndrome of urinary urgency, with or without urgency incontinence, usually accompanied by increased frequency during both daytime and nighttime nocturia. Although OAB is typically associated with storage symptoms rather than voiding symptoms, OAB often accounts for symptoms in patients who are thought to have BOO but who fail to respond to therapy.

The incidence of OAB and LUTS among older adults does not differ by sex [13]. Urgency, urgency incontinence, and frequency have been reported in 10 to 13 percent of European males 50 to 59 years old and in 18 percent of American males 45 to 54 years old [14,15]. The prevalence of OAB rises with increasing age.

Typically, the storage symptoms of OAB are more bothersome than the voiding symptoms of BPH. Patients with OAB and urgency incontinence in particular have higher rates of depression and are more likely to alter activities (eg, decrease work hours, change employment, or take early voluntary retirement) compared with those with OAB who do not have incontinence [16].

OAB symptoms are often attributed to detrusor overactivity, characterized by involuntary detrusor contractions during bladder filling [17].

OAB may be classified as either neurogenic or non-neurogenic. Although the specific mechanism triggering overactivity is essentially unknown, neurogenic OAB symptoms are thought to be related to decreased suprapontine inhibition of the micturition reflex, leading to enhanced excitatory neurotransmission in the micturition reflex pathway [18]. Neurogenic causes include cerebrovascular accident, Parkinson disease, multiple sclerosis, and spinal cord injury. Non-neurogenic, or idiopathic, causes of OAB include BOO (usually secondary to BPH), postoperative pelvic surgery, and bladder stones or other foreign bodies.

Treatment modalities for OAB are directed at either blocking the muscarinic receptor, the presumed site of neurogenically mediated detrusor overactivity, or by affecting the beta-3 adrenergic receptor to increase capacity [19-21]. (See 'Initial management' below.)

Combination OAB and BOO — The incidence of detrusor overactivity and overactive bladder (OAB) with bladder outlet obstruction (BOO) has been reported to range from 30 to 60 percent [22]. Because of the similarities and the overlap in symptoms of clinical BPH and OAB, it can be difficult to separate the two conditions [22].

Animal models suggest that BOO can lead to the development of detrusor dysfunction; however, this has not been established in humans [19,23-26].

PATIENT EVALUATION — Patients who present with symptoms of LUTS should undergo an initial evaluation including history and physical examination with their primary care clinician or a urologist. It is important to determine the degree to which symptoms impact the quality of life [1,27]. This assessment can be semiquantitative but may be facilitated by use of a structured questionnaire. (See 'International Prostate Symptom Score' below.)

An algorithm for the initial management of LUTS in males has been developed by an international consortium representing multiple urologic societies from Europe, the United States, Latin America, and Asia (algorithm 1) [1].

History, physical, and initial testing — History should include the onset, duration, and severity of symptoms. Medications should be reviewed, as antidepressants, diuretics, bronchodilators, and antihistamines are associated with LUTS [28]. Factors associated with urinary incontinence should be clearly ascertained, and patients should be questioned regarding any previous neurologic symptoms, injury, or disease. (See "Urinary incontinence in men", section on 'History and examination'.)

Physical examination should include evaluation of the abdomen, pelvis, perineum, and a focused neurologic examination. A more extensive neurologic examination is indicated for patients with possible neurogenic lower urinary tract dysfunction. An attempt should be made to recreate activities that typically cause incontinence in the patient. Digital rectal examination should be performed to estimate prostate size and detect any abnormalities suggestive of prostate cancer.

Urinalysis is performed to evaluate for hematuria, glucosuria, pyuria, and bacteriuria [8]. Urine cultures are not recommended routinely but should be included if bacteriuria or pyuria are present or if there is otherwise suspicion for a urinary tract infection.

Initial laboratory studies may also include blood tests for renal function and glucose. The American Urological Association (AUA) recommends against routinely checking creatinine during the initial evaluation of LUTS. However, reasons to consider measuring creatinine include evaluation of possible upper urinary tract deterioration (eg, hydronephrosis) or high postvoid residual volumes due to bladder outlet obstruction.

The benefits and risks of prostate-specific antigen (PSA) testing should be discussed with the patient. PSA testing as a screen for prostate cancer should be considered only in patients with life expectancy greater than 10 years. Another indication for measuring PSA is as a proxy for prostate volume. PSA is also needed before treatment with a 5-alpha reductase inhibitor, and monitoring for prostate cancer should be done during treatment, with the understanding that these medications effect the PSA levels. (See "Screening for prostate cancer" and "Medical treatment of benign prostatic hyperplasia", section on '5-alpha reductase inhibitors'.)

International Prostate Symptom Score — The International Prostate Symptom Score (IPSS) is a reproducible, validated index designed to determine disease severity and response to therapy. By itself, it is not a reliable diagnostic tool for LUTS suggestive of benign prostatic hyperplasia but serves as a quantitative measure of LUTS after the diagnosis is established [29].

The IPSS, similar to the AUA Symptom Score, consists of seven questions related to voiding symptoms (table 1). Scores of 0 to 7, 8 to 19, and 20 to 35 signify mild, moderate, and severe symptoms, respectively.

In addition, the IPSS includes a quality of life score as a single 7-point scale question asking the patient how he would feel if he were to spend the rest of his life with his current urinary condition. Similarly, the International Consultation on Incontinence Modular Questionnaire - Male LUTS asks patients to rate, on a scale of 0 to 10, how much leaking urine interferes with everyday life [30].

INITIAL MANAGEMENT — Our approach to initial management includes lifestyle and behavioral interventions and presumptive therapy for benign prostatic hyperplasia (BPH) in most patients. This is consistent with recommendations from an international consortium representing multiple urologic societies from Europe, the United States, Latin America, and Asia (algorithm 1) [1].

Lifestyle and behavioral therapy for all patients — Lifestyle and behavioral interventions are essential components of care for all patients with bothersome LUTS.

Lifestyle modifications include:

Limiting fluid intake before bedtime or prior to travel

Limiting intake of mild diuretics (eg, caffeine, alcohol)

Limiting intake of bladder irritants (eg, highly seasoned or irritative foods)

Avoiding constipation

Increasing activity, including regular strenuous exercise

Weight control

Additional behavioral interventions include:

Timed voiding regimens – In patients who exhibit obstructive complaints (ie, decreased force of stream) or who are noted to carry a high postvoid residual (PVR), instructing them to attempt to empty their bladder based on a time interval rather than by the usual sensations can be effective in reducing LUTS. In our clinical experience, requesting that they urinate "by the clock" (every 90 to 120 minutes during the daytime) seems to be effective.

Double-voiding techniques – Similarly, men who complain of obstructive symptoms may benefit by following one urination by a second attempt at emptying (the double void) within a minute or two of the initial void, which can be used in combination with timed voiding.

Pelvic floor muscle training – Kegel exercises at time of urinary urgency and pelvic floor muscle training, including the use of biofeedback, may be helpful for patients with urgency symptoms that do not respond to voiding interventions. (See "Patient education: Pelvic floor muscle exercises (The Basics)".)

Data suggest that lifestyle modifications can improve LUTS. In a randomized trial of males with LUTS, an intervention that included education, lifestyle advice, and problem-solving skills resulted in less symptom worsening and less medication requirement compared with watchful waiting [31].

For individuals being treated for overactive bladder (OAB), lifestyle modifications can result in additional benefits [32,33]. As an example, in a trial among 204 males with OAB symptoms, the combination of behavioral (pelvic floor muscle training and bladder diary) and drug therapy (antimuscarinic and an alpha blocker) resulted in greater symptom improvement than drug therapy alone at 12 weeks [33].

Additional therapy

Minimal symptoms — For patients with LUTS that are minimally bothersome, we suggest no additional treatment. We reassure patients that LUTS are common and not indicative of chronic disease, and we monitor them for worsening of symptoms that may warrant treatment.

Bothersome symptoms — Most patients can be presumptively treated without extensive diagnostic testing, especially patients without significant nocturia. If nocturia is present as the predominant complaint or in the absence of the other cardinal LUTS, then frequency/volume charting quantifies the extent of polyuria to determine the approach (algorithm 1).

No significant nocturia – For patients without predominant nocturia who have ongoing symptoms despite lifestyle modifications, we suggest an initial trial of medication for BPH, since this is the most common cause of LUTS. These patients are often managed in the primary care setting. Patients with severe symptoms, recalcitrant LUTS, aversion to medications or the side effects, or concerning features warrant referral to urology. (See 'Indications for specialist referral' below.)

Alpha-adrenergic receptor blockers are first-line agents used for the treatment of symptomatic BPH (table 2). They function to relax the smooth muscle tone at the bladder neck and prostate. Alpha-adrenergic receptor antagonists are also effective for patients who have a component of OAB, so they are a good choice for presumptive therapy. Options and doses are listed in the table (table 2). Details on use of alpha-adrenergic receptor antagonists are found elsewhere. (See "Medical treatment of benign prostatic hyperplasia", section on 'Alpha-adrenergic receptor blockers for most patients'.)

Phosphodiesterase 5 (PDE-5) inhibitors can be used as an alternative to alpha-adrenergic receptor blockers for LUTS, especially in patients with erectile dysfunction. In several clinical trials, males with BPH taking PDE-5 inhibitors experienced marked improvement in LUTS compared with placebo, regardless of the presence of erectile dysfunction [34]. Details on the use of PDE-5 inhibitors are found elsewhere (table 3). (See "Medical treatment of benign prostatic hyperplasia", section on 'Phosphodiesterase type 5 inhibitors'.)

Combination therapy for the treatment of LUTS/BPH with a PDE-5 inhibitor and alpha blocker should be avoided, as it offers no advantages in symptom improvement over either agent alone and increases the risk of adverse effects [35].

Significant nocturia – These patients benefit from urology evaluation, including frequency/volume charting. If the frequency/volume chart indicates polyuria, we recommend lifestyle and behavioral interventions (see 'Lifestyle and behavioral therapy for all patients' above). Alpha-1 blockers can be trialed; however, they may offer minimal benefit in this group as symptoms are more likely to be of an upper urinary tract etiology. In patients with significant nocturnal polyuria (>33 percent output at night) desmopressin is a potential therapeutic option. (See "Nocturia: Clinical presentation, evaluation, and management in adults", section on 'Desmopressin'.)

If the above interventions are successful in alleviating symptoms, they are continued indefinitely. If symptoms persist, patients should be referred for specialty care. Additional evaluation may be warranted to clarify the etiology of the LUTS, as below.

Indications for specialist referral — Much of the initial management can be provided by the primary care provider. A referral to urology is appropriate if any of the following are present on initial evaluation or if the patient has not responded to a trial of medication for BPH:

Patients <45 years old

Abnormality on prostate examination

Presence of hematuria in the absence of infection

Patients who desire surgical treatment

Patients with incontinence

Patients with severe symptoms

Patients with prominent nocturia

PVRs >300 to 400 mL, that are increasing, or that cannot be determined in the primary care setting

Some of these patients warrant additional workup to evaluate for malignancy or additional diagnostic testing to confirm the underlying cause of LUTS, which is generally performed by a urologist. (See 'Diagnostic testing for persistent or complicated symptoms' below.)

DIAGNOSTIC TESTING FOR PERSISTENT OR COMPLICATED SYMPTOMS — There is some controversy regarding the role of diagnostic studies in the evaluation of males with LUTS who are referred to a urologist. Guidelines from the American Urological Association advise that all testing (including uroflowmetry, postvoid residual [PVR], pressure-flow urodynamics, and cystoscopy) be considered optional [36]. The 6th International Consultation on New Developments in Prostate Cancer and Prostate Diseases recommends urine flow rate measurement (Qmax) and PVR, measured by ultrasonography, prior to initiating active treatment and for subsequent monitoring [1]. Urine flow rate measurement (Qmax, uroflow) is recommended prior to invasive therapy. Pressure-flow studies are recommended for the evaluation of patients when a precise diagnosis of bladder outlet obstruction (BOO) is important. Both panels suggest cystoscopy and imaging of the prostate and upper tracts when indicated for evaluation of possible renal or malignant disease (eg, recurrent urinary infection, hematuria, renal insufficiency).

Noninvasive studies — Noninvasive studies for LUTS include uroflowmetry to measure Qmax, bladder scan or ultrasound to determine PVR, or transabdominal ultrasound to assess bladder anatomy for evidence of outlet obstruction.

Uroflowmetry — Uroflowmetry is a simple, noninvasive urodynamic measurement in which a patient urinates into a device that measures the volume/time of urine accumulation. Combined with a measurement of PVR (see 'Postvoid residual' below), it is an excellent screening tool for BOO in patients with LUTS but does not provide information regarding the presence of overactive bladder (OAB). Additionally, a diagnosis of BOO cannot be made or excluded based on uroflowmetry alone [37].

Uroflowmetry measures voided volume, voiding time, average flow rate, and Qmax. It also provides a linear analysis of the flow rate/voiding time so that the voiding pattern can be evaluated (figure 1).

Qmax is the single best measurement obtained by this study to assess voiding dysfunction. However, a low Qmax does not distinguish between BOO and decreased detrusor contractility, and a normal Qmax does not exclude BOO. Qmax may be normal in the early stages of obstruction due to compensatory increase in detrusor contractility resulting in high voiding pressures.

Approximately 85 to 90 percent of patients with a Qmax less than 10 mL/s are found to be obstructed on pressure-flow studies. BOO can be accurately diagnosed in men with a Qmax of less than 10 mL/s and an International Prostate Symptom Score greater than 16 [38].

In addition to Qmax, the flow pattern should be noted; characteristic patterns may have diagnostic relevance. Obstruction generally demonstrates a flattened flow pattern with a low Qmax, a prolonged flow time, and a slow time to maximum flow (figure 2).

Postvoid residual — Although most urologists perform a PVR as part of their assessment, PVR does not correlate with the severity of LUTS, the presence of BOO, or treatment outcomes [39]. An elevated PVR is found with obstruction but may also indicate detrusor decompensation due to various causes, including chronic BOO. PVR does not provide diagnostic information for OAB.

Measurements from uroflowmetry, and sometimes pressure-flow urodynamics, are necessary to determine the etiology of an elevated PVR [37]. As an example, a man with a low Qmax and a high PVR may have either BOO or detrusor decompensation. Urodynamic studies could determine if the etiology of the elevated PVR was due to BOO, requiring treatment with alpha blockers or surgery, or to detrusor decompensation, which might require catheter drainage or close surveillance.

For patients with an elevated PVR without obstruction, we typically check the PVR once per year. If the initial PVR is >500 mL, then patients should be checked two to three times per year.

An elevated PVR in some patients may have a secondary effect on the upper tracts. The presence of hydronephrosis and/or renal insufficiency could be evaluated with a renal ultrasound and serum creatinine. Although evidence-based cutoffs and formal consensus guidelines do not exist, we believe that upper tract imaging should be considered in patients with PVRs that are increasing and greater than 300 to 400 mL [37].

Transabdominal ultrasound — Transabdominal ultrasound can be used to assess bladder wall thickness, detrusor wall thickness, and bladder weight. Although there is no established cutoff value, increased detrusor wall thickness is associated with urodynamically confirmed BOO [40].

Invasive diagnostic studies — More invasive studies include pressure-flow urodynamic studies, cystoscopy, and measurement of prostate volume by transrectal ultrasound.

Pressure-flow studies and urodynamics — Urodynamic studies are the gold standard for diagnosis of uninhibited detrusor contractions that occur during the filling phase of voiding in OAB [41]. Urodynamics are important in the evaluation of male patients with neurologic disease and in patients who fail treatment for BOO. Urodynamics are often performed before empiric treatment, when a non-BOO etiology is suspected, or when invasive treatment is contemplated. Additionally, men under age 50 should be evaluated with urodynamic studies prior to treatment due to the high incidence of nonobstructive etiology for LUTS in this population [42].

The urodynamic evaluation involves the concurrent multichannel measurement of bladder and abdominal pressures during the filling/storage and voiding phase of micturition. Detrusor pressure is calculated as the difference between the bladder and abdominal pressures. Urodynamics are the best method to diagnose high-pressure, low-flow voiding that is typical of BOO and differentiate it from low or normal pressure low-flow voiding due to detrusor decompensation.

Several parameters are measured to assess the relationship between flow and pressure during micturition. These include the Abrams-Griffiths nomogram and the more commonly used BOO index (BOOI) [43,44]. The BOOI relates the detrusor pressure at maximum flow (Pdet) to Qmax; an elevated BOOI indicates obstruction.

The cystometrogram provides information regarding bladder storage capacity, bladder sensation, the presence or absence of detrusor overactivity, and bladder compliance (the ability of the bladder to expand and accommodate increasing volumes of urine). The role of the cystometrogram to evaluate the bladder as a source of male LUTS is often overlooked because of a focus on the prostate as the sole cause of symptoms.

Storage LUTS may result from detrusor overactivity, obstruction, or other bladder abnormalities. The cystometrogram may demonstrate a normal pattern or some combination of the following abnormalities during filling: reduced maximum cystometric capacity (<150 mL), involuntary detrusor contractions (>10 cm H20), or loss of bladder compliance. A man with urgency incontinence may demonstrate high-pressure involuntary detrusor contractions, low bladder capacity, and poor reflex contraction of the urethral sphincter mechanism [37,45].

FURTHER MANAGEMENT BY ETIOLOGY — For patients with ongoing symptoms despite initial therapy, additional management is tailored to the presence of bladder outlet obstruction (BOO), overactive bladder (OAB), or both. Diagnostic testing can assist with making this determination (see 'Diagnostic testing for persistent or complicated symptoms' above). Our approach is consistent with recommendations from an international consortium representing multiple urologic societies (algorithm 2).

Isolated bladder outlet obstruction — BOO is generally due to benign prostatic hyperplasia (BPH).

Medical treatment – In patients with mild to moderate symptoms and no clear indication for surgical intervention, we recommend alpha blockers, 5-alpha reductase inhibitors, phosphodiesterase inhibitors, or a combination of these agents; details on their use is discussed elsewhere. (See "Medical treatment of benign prostatic hyperplasia", section on 'Medical therapy for symptom relief' and "Medical treatment of benign prostatic hyperplasia", section on 'Combination of alpha-adrenergic blockers and steroid 5-alpha reductase inhibitors'.)

Surgical treatment – Surgical treatment is usually reserved for medication failure, progressive symptoms, or patient preference in avoiding medication use. Surgical options include minimally invasive surgical therapies (convective water vapor ablation, prostatic urethral lift, microwave therapy, temporary insertion of a nitinol urethral device), laser vaporization of prostate, transurethral resection of prostate, and robotic simple prostatectomy. Further detail on surgical treatment options for BOO related to BPH is discussed separately. (See "Surgical treatment of benign prostatic hyperplasia (BPH)".)

Other less common etiologies of BOO, including urethral stricture and prostate cancer, are discussed in detail elsewhere. (See "Strictures of the adult male urethra", section on 'Management' and "Localized prostate cancer: Risk stratification and choice of initial treatment".)

Isolated overactive bladder — Treatment for patients with isolated OAB is determined by postvoid residual (PVR) (algorithm 2).

OAB with normal PVR

Choice of initial agent — For patients with urodynamically proven overactive bladder (OAB) who have persistent symptoms despite lifestyle modification (see 'Lifestyle and behavioral therapy for all patients' above), both beta-3 agonists and antimuscarinic agents have similar efficacy. Because of the side effects associated with antimuscarinics, we suggest beta-3 agonists as the initial agent, especially for patients who have narrow-angle glaucoma or cognitive impairment. However, antimuscarinic medications may be more widely available and are an acceptable alternative. (See 'Antimuscarinic agents' below and 'Beta-3 adrenergic agonists' below.)

Most of these patients will have already been trialed on an alpha-adrenergic receptor antagonist for general therapy of LUTS; in such cases, the beta-3 agonist or antimuscarinic agent is added to the alpha-adrenergic receptor antagonist.

Beta-3 adrenergic agonists — Beta-3 adrenergic agonists are our preferred agent to treatment of OAB.

Options and dosingMirabegron and vibegron are available treatments. Common therapeutic dosing is presented in the table (table 3).

Efficacy – Beta-3 agonists have demonstrated efficacy for OAB symptoms in several randomized trials, most of them sponsored by the manufacturer. A 2018 systematic review of eight studies involving over 10,000 patients found that mirabegron 50 mg reduced incontinence episodes and urgency episodes compared with placebo (mean difference [MD] -0.38 and -0.053, in 24 hours, respectively) [46]. A systematic review of 44 randomized trials including over 27,000 patients found that mirabegron 50 mg was as efficacious as the other anticholinergics in reducing frequency and urinary incontinence episodes with less dry mouth [47]. An exception was that solifenacin 10 mg appeared somewhat more effective than mirabegron. A higher dose of mirabegron (100 mg) does not appear more effective than mirabegron 50 mg [46].

Adverse effectsMirabegron may increase blood pressure. Although, in a systematic review, mirabegron 50 mg was not associated with a greater risk of hypertension or arrhythmia compared with placebo; however, mirabegron 100 mg did show a slight trend toward these side effects [46]. In a phase III trial, vibegron reduced micturitions, urgency episodes, and urge incontinence and increased the volume per micturition without a risk of hypertension or need for titration [48].

Antimuscarinic agents — Beta-3 adrenergic agonists are our preferred agent to treatment of OAB (see 'Choice of initial agent' above). However, antimuscarinic agents may be more widely available or affordable and are an acceptable alternative.

Options and dosingTolterodine, oxybutynin, darifenacin, solifenacin, and fesoterodine are antimuscarinic agents used for OAB. Common oral therapeutic dosing is presented in the table (table 3). Topical and transdermal formulations are available; though, their use is uncommon.

Comparisons of different agents – If cost and accessibility are not issues, we generally use newer antimuscarinics (tolterodine) or extended-release formulations (extended-release oxybutynin), which are better tolerated with fewer adverse effects. A systematic review of 86 randomized trials and meta-analysis of 70 trials in patients with OAB symptoms compared differing doses and formulations of four anticholinergic drugs [49]. Tolterodine was better tolerated than oxybutynin and extended-release formulations of these agents were better tolerated than immediate release. Fesoterodine had better efficacy than extended-release tolterodine but caused more dry mouth leading to drug withdrawal. Solifenacin was more effective and better tolerated than immediate-release tolterodine. Data were not available for other comparisons. There were incomplete data to make conclusions about comparative costs, long-term outcomes, or the impact on quality of life.

Efficacy – In multiple randomized trials of patients with OAB, antimuscarinic agents have reduced the sensation of urgency, decreased episodes of frequency and urgency incontinence, and improved voided volume [50-56]. A 2023 systematic review found that, compared with placebo, anticholinergic drugs for OAB were more likely to improve condition-specific quality of life (MD 4.41 lower, 95% CI 5.28 lower to 3.54 lower [on a 100 point scale]), decrease voids per 24-hour period (MD 0.895, 95% CI 0.98 lower to 0.73 lower), and decrease the number of urgency episodes in 24 hours (MD 0.85, 95% CI 1.03 lower to 0.67 lower) [50].

Although some trials did not identify clear benefits of adding an anticholinergic agent to an alpha-adrenergic inhibitor [17,57], subsequent meta-analysis demonstrated improvements in quality of life, frequency, and urgency with combination therapy [58,59].

Adverse effects

Urinary retention – Anticholinergics carry a potential risk of worsening PVRs and urinary retention; therefore, they should be considered carefully when used as monotherapy in OAB. However, studies show the risk of urinary retention is low in appropriately selected patients [17,36]. Anticholinergics should be used with caution in patients with a PVR greater than 250 to 300 mL. (See 'OAB with high PVR' below.)

Risk of dementia – These medications have also been associated with an increased risk of dementia and should be avoided in patients with cognitive impairment or age >65 years [60]. A more detailed discussion of the association between anticholinergics and dementia is presented elsewhere. (See "Epidemiology, pathology, and pathogenesis of Alzheimer disease", section on 'Medications'.)

Darifenacin, solifenacin, and trospium may have less adverse cognitive effects. Darifenacin and solifenacin result in selective M3 receptor blockade, which may decrease peripheral side effects [53-55]. Trospium has limited ability to cross the blood-brain barrier and may have less impact on cognitive dysfunction [61,62].

Additional adverse effects – Additional peripheral side effects include inhibition of salivary secretion (dry mouth), blockade of the ciliary muscle of the lens to cholinergic stimulation (blurred vision for near objects), tachycardia, drowsiness, decreased cognitive function, and inhibition of gut motility. These side effects may limit drug tolerability, especially in patients with gastric retention or glaucoma.

OAB with high PVR — Patients with overactive bladder (OAB) and elevated postvoid residual (PVR) without obstruction generally have detrusor hyperactivity with impaired contractility [63]. They may need specialized lifestyle approaches as well as pharmacotherapy to optimally control symptoms:

Strategies to maximize bladder emptying – Patients may need additional measures to empty their bladder, including intermittent catheterization. Biofeedback to teach pelvic floor relaxation techniques and Valsalva or Crede voiding may also aid in bladder emptying [64]. Valsalva voiding involves tightening the lower abdominal muscles so that pressure is transmitted to the bladder to help in emptying; Crede voiding is the application of direct pressure (fist or hand) over the lower abdomen or suprapubic area to transmit pressure to the bladder.

Medication selection – For this population, beta-3 agonists are preferred to avoid exacerbating urinary retention. If antimuscarinics are chosen, PVR must be monitored closely. (See 'Antimuscarinic agents' above and 'Beta-3 adrenergic agonists' above.)

Monitoring – For patients with an elevated PVR without obstruction, we recheck the PVR once per year. If the initial PVR is >500 mL, then patients should be checked two to three times per year. A large PVR may be well tolerated if bladder compliance is normal and the patient does not become prone to urinary tract infections. Patients on antimuscarinic therapy should have PVRs monitored within three months of medication start to ensure worsening retention does not develop.

Limited role for surgery in selected patients – For patients with urodynamically proven OAB and high PVR in the absence of clear evidence for BOO, outlet reduction surgery has a limited role. However, a subset of patients in this group may have mild/equivocal BOO, and in these selected cases, outlet reduction surgery to remove the minor obstruction may improve bladder emptying when combined with other interventions. (See "Surgical treatment of benign prostatic hyperplasia (BPH)".)

Refractory OAB — If overactive bladder (OAB) symptoms persist after medical treatment or surgery (ie, in patients who have concomitant BOO), potential options include:

Sacral neuromodulation – Men with OAB symptoms refractory to medical therapy may be candidates for sacral neuromodulation (SNM). The exact mechanism of action is uncertain. Most clinical studies of these devices have focused on females with urgency urinary incontinence; the common innervation of the bladder makes it likely that clinical outcomes would be similar for males. SNM and its risks and benefits are described separately. (See "Urgency urinary incontinence/overactive bladder (OAB) in females: Treatment", section on 'Sacral nerve stimulation'.)

Botulinum toxin – Botulinum toxin can be used for neurogenic causes of detrusor overactivity (eg, spinal cord injury and multiple sclerosis). It has also been used in patients with non-neurogenic OAB but is typically reserved for patients with symptoms refractory to all medications. Cystoscopic injection of botulinum toxin directly into the detrusor muscle results in chemical denervation that is reversible after six to nine months. Botulinum toxin type A is used in the United States [65,66].

Limited data on intravesical botulinum suggest benefit but are somewhat mixed, and there are no robust data regarding safety or optimal dose. A 2007 systematic review of randomized trials of botulinum, compared with no treatment, nonpharmacologic treatment, and pharmacologic treatment for OAB, found few well-controlled trials [67]. In eight small trials including patients with predominantly neurogenic OAB, botulinum improved incontinence, bladder capacity, and quality of life compared with placebo. However, in a retrospective study of 88 males who initiated botulinum toxin A for OAB and were followed for almost six years, nearly 75 percent discontinued treatment, mostly due to lack of sufficient effect or to side effects including urinary retention, need to self-catheterize, or voiding LUTS [68].

Mixed BOO and OAB

BOO and OAB with low PVR – Symptoms of overactive bladder (OAB) with bladder outlet obstruction (BOO) and low postvoid residual (PVR) are the most common combination of findings in clinical practice. For these patients, alpha blockers can help improve symptoms of OAB and relieve obstruction by relaxing prostatic smooth muscle. On urodynamic testing, patients receiving tamsulosin monotherapy showed an increase in the volume at first involuntary contraction [58]. Beta-3 agonists or antimuscarinics can be added if OAB symptoms persist. (See "Medical treatment of benign prostatic hyperplasia", section on 'Alpha-adrenergic receptor blockers for most patients' and 'Antimuscarinic agents' above.)

Surgical reduction of BOO is an acceptable treatment alternative for patients who do not respond to medical therapy. Up to 60 percent of men with BOO have evidence of detrusor overactivity. BOO reduction surgery results in resolution of detrusor overactivity in one-half of patients with detrusor overactivity preoperatively. Importantly, relieving the obstruction may prevent worsening of OAB.

BOO and OAB with high PVR – Patients with OAB who have evidence of BOO and elevated PVR should initially be treated for relief of their obstruction by either medical or surgical therapy. (See 'Isolated bladder outlet obstruction' above and "Strictures of the adult male urethra", section on 'Management'.)

This group is at high risk of urinary retention with anticholinergic monotherapy, and therapy for OAB symptoms should be delayed until obstruction is relieved. Following relief of obstruction, these patients can be managed with beta-3 adrenergic agonists or antimuscarinics similar to patients with isolated OAB if symptoms persist (algorithm 2). (See 'Isolated overactive bladder' above.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Benign prostatic hyperplasia".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Benign prostatic hyperplasia (enlarged prostate) (The Basics)" and "Patient education: Neurogenic bladder in adults (The Basics)")

Beyond the Basics topics (see "Patient education: Benign prostatic hyperplasia (BPH) (Beyond the Basics)" and "Patient education: Urinary incontinence in women (Beyond the Basics)" and "Patient education: Urinary incontinence treatments for women (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Symptoms – Lower urinary tract symptoms (LUTS) can be classified as storage symptoms (urgency, frequency, nocturia, urgency incontinence), voiding symptoms (hesitancy, weak stream, dysuria), or postmicturition symptoms (incomplete bladder emptying, postmicturition dribbling). (See 'Symptoms' above.)

Etiologies – Traditionally, LUTS in males have been primarily attributed to benign prostatic hyperplasia (BPH) and consequent bladder outlet obstruction (BOO). However, overactive bladder (OAB), characterized by involuntary contraction of the detrusor muscle, may be the principal cause or a contributory cause of LUTS in some patients. (See 'Etiologies of LUTS' above.)

Bladder outlet obstruction – LUTS are often attributed to BOO resulting from benign prostatic enlargement or BPH. Voiding symptoms are suggestive of BOO but are not diagnostic. (See 'Bladder outlet obstruction from BPH' above.)

Overactive bladder – OAB is related to detrusor overactivity and is most commonly associated with storage symptoms that are frequently more bothersome than voiding symptoms. The cause of OAB is often unknown. OAB may be neurogenic (eg, secondary to stroke or other neurologic condition) or may be caused by chronic obstruction. (See 'Overactive bladder' above.)

Evaluation – Male patients with LUTS should be evaluated initially with history; physical examination including prostate examination; and laboratory studies, which may include creatinine, glucose, prostate-specific antigen, urinalysis, and urine culture. Determining the International Prostate Symptom Score can be helpful in monitoring treatment response. (See 'Patient evaluation' above.)

Limited role for diagnostic studies – The role for urologic studies in evaluating LUTS is controversial. Postvoid residual (PVR) does not correlate with LUTS severity or provide diagnostic information regarding BOO or OAB. However, awareness of an elevated PVR may guide treatment with antimuscarinic medication as well as the need for closer follow-up. (See 'Diagnostic testing for persistent or complicated symptoms' above.)

Initial management

Lifestyle modifications – Lifestyle changes (eg, limiting fluid intake, avoiding bladder irritants, physical activity, weight loss) are the cornerstone of initial management. Data suggest that lifestyle modifications improve LUTS and reduce medication requirements compared with watchful waiting. Lifestyle modifications also have an additive effect when combined with medication therapy. (See 'Initial management' above and 'Lifestyle and behavioral therapy for all patients' above.)

Presumptive medical therapy – For patients with persistent, bothersome LUTS despite lifestyle modifications, we suggest presumptive therapy with an alpha blocker rather than other interventions or specialized diagnostic testing (Grade 2C). Alpha blockers improve the symptoms of BPH, the most common cause of LUTS, and can also improve some bladder irritability symptoms. The exception is patients with significant nocturia, for whom additional testing may be useful to determine optimal therapy. (See 'Additional therapy' above.)

Indications for urologic referral – Primary care clinicians can initiate this presumptive therapy in most cases. We refer patients who are less than 45 years old; have a prostate abnormality, hematuria in the absence of infection, incontinence, significant nocturia, or increasing PVR; or who do not respond to empiric therapy. (See 'Indications for specialist referral' above.)

Management based on LUTS etiology

Isolated bladder outlet obstruction – Isolated BOO is generally related to BPH. Details on medical and surgical management of BPH are discussed elsewhere. (See "Medical treatment of benign prostatic hyperplasia" and "Surgical treatment of benign prostatic hyperplasia (BPH)".)

Isolated overactive bladder – For patients with isolated OAB and persistent symptoms despite lifestyle modification, we suggest a beta-3 agonist rather than an antimuscarinic agent (Grade 2B). Although both are effective options, antimuscarinics are associated with more side effects, including a risk of dementia. Most of these patients will have already been trialed on an alpha-adrenergic receptor antagonist for general therapy of LUTS; in such cases, the beta-3 agonist or antimuscarinic agent is added. (See 'Antimuscarinic agents' above and 'Beta-3 adrenergic agonists' above.)

If the baseline PVR is elevated, additional bladder voiding strategies may be needed for full bladder emptying; ongoing PVR monitoring is also warranted. Beta-3 agonists are also preferred in these patients to avoid exacerbating urinary retention. (See 'OAB with high PVR' above.)

Sacral neuromodulation and botulinum therapy are options for refractory OAB symptoms. (See 'Isolated overactive bladder' above.)

Mixed OAB with BOO – This is the most common presentation in clinical practice. Bladder outlet obstruction (BOO) should be managed first, as above, prior to addressing overactive bladder (OAB) symptoms, due to the risk of exacerbating urinary retention. (See 'Mixed BOO and OAB' above.)

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References

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