Management of Persistent Storage Symptoms and Overactive Bladder in Men Diagnosed with Benign Prostatic Hyperplasia: A Narrative Review

Abstract

Benign prostatic hyperplasia (BPH) and overactive bladder (OAB) both cause lower urinary tract symptoms (LUTS) in men. Ongoing urgency, frequency, and nocturia despite effective BPH management may indicate coexistence of primary OAB in many individuals. A literature search was conducted to support a narrative review aimed at enhancing awareness that urinary symptoms in men should not be attributed solely to either BPH or OAB, as LUTS have numerous etiologies, and OAB and BPH are both prevalent among men. Owing to different etiologies of BPH and OAB, LUTS in men may not be adequately addressed with a single treatment. BPH medications primarily target voiding-related symptoms, and storage-related symptoms may persist. Storage-related symptoms (i.e., OAB) are generally the most bothersome and frequently reported element of LUTS, reducing quality of life, and studies suggest that OAB in men is inadequately addressed. Furthermore, men with both BPH and OAB seldom receive treatment for OAB after BPH management, if at all. Thus, men may benefit from clinicians prescribing OAB medication alongside those for BPH. This approach has been evaluated in clinical trials, some of which have shown improvements in OAB symptoms among men with BPH, without introducing additional safety concerns. Proactive discussions about symptoms, especially in the primary care setting, may help facilitate timely and effective treatment of this common issue. There are established OAB treatments that can be safely and successfully combined with BPH management to effectively address persistent storage symptoms and complex urinary symptoms in men.

Key Summary Points

Lower urinary tract symptoms (LUTS) in men are multifactorial; both benign prostatic hyperplasia (BPH) and overactive bladder (OAB) can cause lower urinary tract symptoms (LUTS) in men.

Coexisting OAB and BPH is common; however, OAB is inadequately addressed in men, and men with both BPH and OAB tend to only receive OAB treatment after BPH management does not adequately address their LUTS.

Given the diverse nature of LUTS, a single therapeutic may not adequately address the various symptoms associated with BPH and OAB, warranting the combined management of BPH and OAB with multiple medications (i.e., OAB treatments with α-blockers).

In primary care settings, proactive discussions about symptoms may better align patients with more timely and effective treatment appropriate for their symptoms and conditions.

There is a pressing need for enhanced awareness of OAB in men and the effectiveness of OAB medications (e.g., anticholinergic medication may be an appropriate treatment for OAB and β3-adrenergic receptor agonists such as vibegron are effective with a strong safety profile) in addressing the urinary symptoms OAB presents in men.

Introduction

Both benign prostatic hyperplasia (BPH) and overactive bladder (OAB) are significant contributors to lower urinary tract symptoms (LUTS) that are common among aging men [1, 2]. LUTS are categorized into symptoms related to voiding (such as hesitancy, weak stream, straining to void, and postvoid dribbling) or storage-related symptoms (such as frequency, nocturia, urgency, and incontinence) [3]. Voiding symptoms may result from prostatic enlargement or obstruction, as typically observed in BPH [2, 3]. Storage-related symptoms, on the other hand, are typically secondary to non-obstructive bladder-related conditions and may be more characteristic of OAB [3, 4]. Clinical symptoms often overlap at presentation, with many men having coexisting BPH and OAB [3], posing both a diagnostic and management challenge for clinicians.

This review aims to enhance the understanding that BPH is not the sole cause of urinary symptoms experienced by men, but instead, LUTS are multifactorial and can be driven by primary OAB or BPH, independently or simultaneously. Importantly, this review highlights factors related to the underdiagnosis and misdiagnosis of OAB in men, and the resultant undertreatment of such cases. The negative impact of storage symptoms on quality of life (QoL), as well as the role of primary care in screening for and managing these bothersome conditions is also addressed. Lastly, the article outlines the utility of medical therapy for OAB, including in men receiving BPH medication.

To support this narrative review, a targeted literature search was conducted using PubMed with key search terms: “OAB diagnoses/symptoms and treatments”; “BPH diagnoses/symptoms and treatments”; “OAB and BPH in men”; and “undertreatment of OAB in men”. Full search strings included BPH diagnoses AND symptoms AND treatments; OAB diagnoses AND symptoms AND treatments; OAB pathophysiology; BPH pathophysiology; undertreatment of OAB in men with BPH, men with BPH AND OAB. The last search date was January 5, 2026. Clinical study types include prospective studies, phase 3 and phase 4 clinical trials. Clinical trials focused on men receiving BPH treatment (i.e., α-blocker with or without 5α-reductase inhibitors) with persistent OAB symptoms. Key evidence was prioritized by emphasizing clinical data to support statements, followed by a literature review that provided an overview of the topic. The majority of the publications cited were from years 2000 to 2025. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

BPH and OAB Pathophysiology

BPH is a histologic diagnosis of nonmalignant cellular proliferation that may increase the volume (benign prostatic enlargement) and extent of obstruction of the prostate (benign prostatic obstruction) [2], but can be asymptomatic in many men [5]. BPH can increase smooth muscle tone, resistance to urinary flow within the obstructed, enlarged tissue, and induce bladder changes, which, collectively, cause symptoms [2] including frequency and urgency, impairment of the urinary stream, hesitancy, intermittency, and incomplete emptying [2, 3].

OAB is a clinical syndrome characterized by urinary urgency, with or without urgency incontinence, with increased daytime frequency and nocturia, in the absence of infection or another obvious pathologic cause [4, 6]. The etiology of OAB is complex, and storage symptoms are its hallmark [2]. OAB symptoms are suggestive of detrusor overactivity, which can be observed on cystometric (urodynamic) testing, and may arise spontaneously, be associated with vesicourethral dysfunction, or be driven by another comorbid condition [7, 8]. Structural or functional changes in the bladder leading to myogenic, neurogenic, and/or urothelial dysfunction can also contribute to OAB pathophysiology [9, 10].

Multiple medications can be used to treat LUTS, each with distinct targets. Treatments for BPH (i.e., α-blockers, 5α-reductase inhibitors, and phosphodiesterase 5 inhibitors) primarily address voiding-related symptoms [2, 11]. Whereas α-blockers reduce smooth muscle contraction in the prostate and bladder neck, 5α-reductase inhibitors can reduce prostate size by inhibiting androgen-driven growth of the gland through their interference with dihydrotestosterone production. Phosphodiesterase 5 inhibitors can relax muscles in the prostate, urethra, and bladder via nitric oxide-mediated effects [11]. BPH medication may also improve storage symptoms.

Tadalafil, a phosphodiesterase 5 inhibitor, can also improve storage symptoms (i.e., OAB) [12, 13], which may be owing to its ability to relax bladder tissue [14, 15]. Furthermore, a retrospective study of men with LUTS who were treated with either an α-blocker alone or an α-blocker in combination with 5α-reductase inhibitors demonstrated improvement in storage symptoms measured via the International Prostate Symptom Score (IPSS; storage score) in both groups [16]. However, there were no significant differences between the groups (α-blockers alone vs α-blockers with 5α-reductase inhibitors), indicating that the improvement was likely associated with the α-blockers, rather than the 5α-reductase inhibitors [16]. Treatments for OAB, including anticholinergics and β₃-adrenergic receptor agonists, address storage-related symptoms [4] by reducing detrusor muscle contraction [17, 18] and increasing bladder capacity [19, 20], albeit via different mechanisms. Given the diverse nature of LUTS, a single treatment approach may not adequately address the range of symptoms associated with BPH or OAB alone, warranting the combined management of BPH and OAB with multiple medications [2, 4].

Need for Improved Awareness and Treatment

Undertreatment of OAB Symptoms

Even when BPH and OAB coexist, there is a propensity to address BPH but overlook the management of OAB despite available treatment options. A retrospective analysis of the MarketScan Commercial and Medicare Supplemental databases from 2012 to 2017 assessed 462,000 men ≥ 40 years of age who were diagnosed or pharmacologically treated for BPH and/or OAB [21]. Of patients with a BPH only diagnosis, 64% received BPH medication, while of those diagnosed with solely OAB, only 14% were prescribed OAB medication [21]. Men diagnosed with both BPH and OAB more often received BPH medication only (55%) compared with OAB medications only (3%), while 11% received treatment for both OAB and BPH [21]. Collectively, this indicates that symptoms associated with OAB are likely addressed inadequately, despite studies showing OAB symptoms are prevalent, more bothersome to men than voiding symptoms [22–24], and persistent in many men receiving BPH medication [25].

The historical focus on BPH and BPH treatments that persists today may stem from a lack of comfort or expertise in treating OAB in men, which may result in prostate bias and the undertreatment of OAB symptoms [25]. In consideration of the role of obstructive prostates in contributing to OAB, it is common practice to treat the obstruction and to wait and see if the BPH treatment resolves OAB symptoms. Additionally, there may be bias toward procedural treatments targeting the prostate; in cases where α-blockers are ineffective, procedures to de-obstruct and/or reduce the prostate are often the next intervention.

A presumed concern for many clinicians in prescribing medications for OAB in men is the potential of acute urinary retention [4]. Anticholinergic medications are not approved for the treatment of BPH and should be administered with caution to patients with clinically significant bladder outlet obstruction (BOO) because of the risk of urinary retention [4]. In a systematic review, 17 studies reported an increased risk of urinary retention with anticholinergics vs placebo for the treatment of OAB (risk ratio 3.52; 95% CI 2.04–6.08; P < 0.00001) [26]. In contrast, β₃-adrenergic receptor agonists present lower risk of urinary retention [27, 28].

BPH and OAB Clinical and Humanistic Burden

Worsening urinary symptoms are a common indicator of BPH progression, which may result in more severe conditions such as acute urinary retention, and urinary tract infection, amongst others [29]. Acute urinary retention occurs most commonly among men aged 60–80 years, with BPH being the primary cause [30]. Over a 5-year period, approximately 10% of men > 70 years of age will experience acute urinary retention [31]. Other complications associated with BPH include deterioration of or damage to the bladder, bladder stones, incomplete emptying, and incontinence [32]. Complicated urinary tract infections are more likely in the setting of poor bladder emptying, which promotes bacterial colonization and persistence as well as the formation of urinary stones that further serve as a nidus of repeated infection [29]. To this end, emphasizing timely and appropriate treatment of BPH may reduce the potential of severe urinary tract conditions [32].

Symptoms of OAB are bothersome and significantly reduce individuals’ QoL [33, 34]. In the EPIC study, a large population-based survey, storage symptoms were reported more frequently than voiding symptoms [22]. Such OAB symptoms drive patients to report higher degrees of symptom-related distress, significantly diminished health-related QoL, and considerable work impairment compared with populations without OAB [34–36]. Sleep deprivation is a challenge faced by many individuals with OAB, often resulting in diminished daily functioning [33, 37]. Nocturia, experienced by nearly half of men with OAB [38], has been shown to significantly disrupt sleep [37].

Early Diagnosis and Management

Role of Primary Care in Management

While the prevalence of OAB is similar between men and women, men are less likely to be treated for the condition [39]. This likely stems from being less forthcoming in discussing OAB symptoms with their healthcare providers, as well as a lower likelihood of seeking (and thus receiving) treatment for OAB, perhaps owing to the common misconception that OAB symptoms are a normal part of aging [5, 40]. Considering its substantial impact on overall health, QoL, and economic well-being [3], there is significant opportunity to positively impact patients through the timely diagnosis and management of OAB in the primary care setting—including men who may or may not already be receiving BPH treatment.

Patient Evaluation

For patients experiencing bothersome LUTS, the American Urological Association (AUA) recommends a series of assessments, including a comprehensive medical history, physical examination, administration of the IPSS, and urinalysis to rule out other causes of symptoms, (e.g., infection, inflammation, or glucosuria) [2, 4]. The aim of an initial visit in which LUTS are evaluated is to rule out other medical conditions or treatments (e.g., congestive heart failure, diabetes mellitus, urinary tract infection, diuretics) that may cause LUTS and present in a similar manner, thus enabling subsequent evaluation and management to focus on BPH and OAB (Table 1) [5].

Table 1.

Known contributors to OAB symptoms

Risk factors	OAB	BPH	LUTS
Age	OAB prevalence increases with age [45]	BPH is a prevalent condition that affects older men [47] Men aged ≥ 62 years are at risk of BPH progression and worsening symptoms compared with men < 62 years [47]	LUTS prevalence increases with age [77]
Genetics			A genetic component to risk of high-moderate/severe LUTS [78]
Prostate size and obstruction		Men with total prostate volume ≥ 31 mL compared with < 31 mL had a greater risk of BPH progression [47] Greater risk of worsening symptoms, acute urinary retention, and a greater need for invasive surgical treatment [47]
PSA		Men with PSA values ≥ 1.6 ng/dL compared with values < 1.6 ng/dL had a greater risk of BPH progression [47]   Greater risk of worsening symptoms and acute urinary retention and a greater need for invasive surgical treatment [47]
Urinary flow		Men with urinary flow < 10.6 mL/s compared with value ≥ 10.6 mL/s had a greater risk of BPH progression [47]   Greater risk of worsening symptoms and a greater need for invasive surgical treatment [47]
PVR		Men with PVR values ≥ 39 mL compared with values < 39 mL had a greater risk of BPH progression [47]   Greater risk of worsening symptoms and a greater need for invasive surgical treatment [47]
Diet	Whole grain and high alcohol dietary patterns were positively associated with a risk of OAB [42]	Cereals, poultry, and egg consumption positively associated with BPH risk [41]	Higher prevalence of LUTS in men with poor diet quality (less protein and fewer food groups in the diet compared with an overall healthy diet) [79]
Caffeine	A high consumption of caffeine (> 300 mg caffeine a day) was associated with a higher proportion of individuals with severe OAB symptoms compared with patients who had < 300 mg caffeine a day [80]	Increased coffee consumption was associated with increased risk of BPH [81]	High coffee consumption (> 2 cups a day) in men was associated with an increased risk of developing LUTS, specifically storage symptoms [82]
Alcohol	A higher proportion of individuals with OAB were found in the high-frequency and low-frequency consumption groups (consuming alcohol > 10 drinks or 1–5 drinks per month, respectively) compared to the modest-consumption group [83]	High alcohol consumption increased rates of incontinence, obstruction, and LUTS, while modest consumption was associated with less severe symptoms compared to nondrinkers [84]	In men, high alcohol consumption was positively associated with increased risk of urgency [85]
Obesity	BMI was significantly higher in patients with OAB than in individuals without OAB [45]	Increased BMI is positively associated with increased prostate volume [44]	High BMI had a modest (non-significant) association with high-moderate to severe LUTS [44]
Diabetes	Duration of diabetes is a risk factor for OAB progression [43]	High levels of fasting plasma glucose and diabetes are associated with prostate enlargement [44]	High levels of fasting plasma glucose and diabetes are associated with high-moderate to severe LUTS [44] Empagliflozin, which is prescribed for the management of type 2 diabetes, may lead to increased urination, potentially resulting in polyuria

BMI body mass index, BPH benign prostatic hyperplasia, LUTS lower urinary tract symptoms, OAB overactive bladder, PSA prostate-specific antigen, PVR postvoid residual urine volume

Risk factors associated with BPH and OAB include older age, high body mass index (BMI), diet, metabolic disorders, and diabetes [41–44]. In a meta-analysis of studies on risk factors associated with OAB, 20 out of 28 articles included showed a positive relationship between age and OAB (Z = 5.37, P < 0.00001), while the overall analysis demonstrated that higher BMI was significantly associated with OAB (standardized mean difference [95% CI] 0.39 [0.24–0.53]) [45]. A cross-sectional study from a health and nutrition survey from 2013 to 2023 used principal component analysis to demonstrate whole grain (may include alcohol) dietary patterns were associated with a moderate increased risk of OAB (odds ratio [OR] > 1; P < 0.05) [42], whereas another survey study identified an increasing risk of BPH with greater consumption of cereal (OR range 1.12–1.60), bread (1.08–1.69), eggs (1.43–1.53), and poultry (1.03–1.52) [41]. Notably, the increased risk associated with cereal and bread may stem from refined or processed products.

A cross-sectional analysis of patients with type 2 diabetes and OAB from 2020 to 2024 determined that duration of diabetes is a risk factor for the progression of OAB (OR 1.94; 95% CI 0.53–2.23) [43], and another cross-sectional analysis of a cohort study found that men with elevated fasting blood glucose (vs normal fasting glucose) and/or diabetes (vs men without diabetes) were more likely to have an enlarged prostate (OR 2.98, 95% CI 1.70–5.23, and OR 2.25, 95% CI 1.23–4.11, respectively) [44]. An additional and increasingly common risk factor for LUTS is treatment with empagliflozin (or other SGLT2 inhibitors) for the management of type 2 diabetes and cardiovascular disease, which induces iatrogenic glucosuria that often results in increased urinary frequency, as well as bothersome urinary urgency [46].

As BPH and OAB symptoms are common and often overlapping, primary care providers can benefit from information on how to optimally identify and manage these bothersome conditions. In practice, differentiating between the diagnoses of BPH and OAB can best be done with a careful clinical history [3]. A detailed discussion of bothersome symptoms (which can be aided by voiding diaries and symptom questionnaires such as the IPSS) can facilitate the accurate diagnosis and initial treatment of BPH and OAB, particularly with regard to establishing baseline levels of bother and symptoms that are useful for assessing response to treatment [2, 4]. In refractory cases or when the diagnosis is unclear, further testing with postvoid residual (PVR) urine volume measurements, as well as noninvasive uroflowmetry, urodynamics, and/or cystoscopy may be warranted [2, 4].

Guidance in Early Management of BPH and OAB

The high prevalence of OAB in adults, coupled with the increasing incidence of BPH with age [45, 47], adds complexity in determining treatments, as comorbidities and polypharmacy are common in this patient population [48]. In men with OAB, including those with concurrent BPH, management often involves multiple modalities, comprising lifestyle changes, medications, procedural options, and traditional surgeries. Treating OAB is similarly multifaceted; previously, a stepwise approach was recommended, but contemporary guidelines now recommend shared decision-making in selecting across a range of therapies [2, 4]. This approach helps patients understand what to expect from specific treatments and allows for tailoring management options to the individual patient [2, 4].

OAB Treatments

Noninvasive Approaches

Noninvasive approaches include bladder hygiene or behavioral and dietary changes, for example, timed voiding, urgency suppression, fluid management, bladder irritant avoidance (i.e., caffeine, alcohol), and constipation control, as well as pelvic floor physical therapy, biofeedback, and transcutaneous tibial nerve stimulation [4].

Pharmacologic Therapies

In the AUA guidelines for BPH, in men with mixed OAB and BPH, the treatment of storage symptoms follows the AUA guidelines for OAB [2]. Specifically, in men with predominant OAB symptoms who also have BPH, the AUA OAB guidelines recommend pharmacotherapy for OAB (anticholinergics such as fesoterodine and solifenacin or β₃-adrenergic receptor agonists such as mirabegron and vibegron), as monotherapy or in combination with BPH treatment via α-blockers [4]. Multiple clinical trials have assessed the efficacy and safety of anticholinergics and β₃-adrenergic receptor agonists (Table 2).

Table 2.

Key clinical trials

Clinical trial	Length of trial/treatment	Population	BPH regimen or BOO/PVR criteria	Endpoints	AEs
Victor trial (NCT00771394) [51]	12-week, double-blind, placebo-controlled Treatment: 5 mg solifenacin + 0.4 mg tamsulosin or placebo + 0.4 mg tamsulosin once daily for 12 weeks	Men age ≥ 45 years Had residual OAB symptoms documented via bladder diary (mean ≥ 8 micturitions, ≥ 1 more urgency episodes per 24 h) after taking 0.4 mg tamsulosin once daily for ≥ 4 weeks Solifenacin + tamsulosin (n = 202) Placebo + tamsulosin (n = 195)	PVR volume ≤ 200 mL and peak flow rate ≥ 5 mL/s before randomization PSA ≤ 10 ng/mL	Solifenacin + tamsulosin vs placebo + tamsulosin showed reductions in frequency but were not statistically significant Statistically significant reductions in urgency with solifenacin + tamsulosin vs placebo + tamsulosin	Treatment-related TEAEs were more frequent in the solifenacin + tamsulosin vs placebo plus tamsulosin groups Solifenacin + tamsulosin group had 7 (3%) patients with urinary retention and 3 required catheterization; no patients on placebo + tamsulosin reported urinary retention
Prospective study [52]	June 2009 to April 2011 Patients treated for 1 week with 0.4 mg tamsulosin, and an additional 4-week period with tamsulosin or tamsulosin + fesoterodine combination	Men age ≥ 50 years Men with LUTS storage symptoms from OAB and BOO Tamsulosin (n = 23) Tamsulosin + fesoterodine (n = 24)	PVR volume < 200 mL Qmax > 10 mL/s Prostate volume < 60 cm3 PSA < 4 ng/mL	At the end of treatment period, there was no statistically significant difference in Qmax, and PVR between patients with tamsulosin + fesoterodine and patients treated only with tamsulosin After the second visit (after 1 week of treatment) and third visit (from baseline to week 6), men receiving fesoterodine + tamsulosin had significant improvement in storage and total IPSS scores vs tamsulosin alone	Overall, 4 (16.6%) patients reported dry mouth and 1 (4.1%) reported constipation 1 (4.1%) patient from the tamsulosin + fesoterodine treatment group reported increased voiding difficulties, but no patients required catheterization and no urinary retention was reported In the tamsulosin alone group, 1 patient reported dizziness
SATURN Trial (NCT00510406) [53]	12-week double-blind, parallel-group, placebo-controlled, multicenter, dose-ranging study Treatment: Placebo Tamsulosin 0.4 mg monotherapy Solifenacin 3, 6, or 9 mg + tamsulosin 0.4 mg Dose-matched solifenacin monotherapy	Men age ≥ 45 years Diagnosed with LUTS (both voiding and storage symptoms) Placebo (n = 92) Tamsulosin 0.4 mg (n = 177) Solifenacin 3 mg (n = 43) Solifenacin 6 mg (n = 43) Solifenacin 9 mg (n = 43) Solifenacin 3 mg + tamsulosin 0.4 mg (n = 179) Solifenacin 6 mg + tamsulosin 0.4 mg (n = 178) Solifenacin 9 mg + tamsulosin 0.4 mg (n = 175)	PVR volume ≤ 200 mL Qmax of 4.0–15.0 mL/s Volume voided during free flow ≥ 120 mL No minimum or maximum prostate size	In the total study population, IPSS subscores were not significantly different in patients receiving solifenacin and α-blocker compared with α-blocker alone In the total study population, there were significant improvements in micturition frequency, total urgency and frequency score, and voided volume with increasing solifenacin dose + tamsulosin vs tamsulosin alone In a subgroup of patients stratified by baseline storage symptom severity, there were statistically significant improvements in IPSS storage subscore, urgency episodes, micturition frequency, total urgency score, voided volume with solifenacin + tamsulosin vs tamsulosin alone	Treatment-related dry mouth was reported in 47 (8.8%) patients treated with solifenacin + tamsulosin vs 4 (2.3%) treated with tamsulosin alone PVR volume increase was not considered clinically relevant Acute urinary retention was low in both treatment groups   5 occurred within the first 32 days of treatment and 4 required catheterization (1 patient in group: solifenacin 9 mg, tamsulosin monotherapy, solifenacin 3 mg + tamsulosin, solifenacin 9 mg + tamsulosin)
MATCH Trial (NCT02656173) [63]	12-week double-blind placebo-controlled study Treatment: Tamsulosin 0.2 mg + mirabegron 50 mg Tamsulosin 0.2 mg + placebo	Men age ≥ 40 years Average of ≥ 2 episodes of urgency/day and average of ≥ 8 micturitions/day last 3 days before screening period Treatment with tamsulosin 0.2 mg for ≥ 4 weeks before screening period Tamsulosin + mirabegron (n = 283) Tamsulosin + placebo (n = 282)	PVR volume ≤ 100 mL Qmax ≥ 5 mL/s PSA < 4 ng/mL	Mirabegron combination therapy was statistically significant vs placebo in improving mean number of micturitions/day; and mean volume voided/micturition, OAB symptom score, and IPSS total	Treatment-related TEAEs were lower in the placebo group vs mirabegron group Incidences of urination-related events were 1.4% in mirabegron group and 0.4% in placebo group Increased residual urine volume was reported in 3 (1.1%) patients in mirabegron group and 1 (0.4%) patient in placebo group
Phase 4 PLUS Study (NCT02757768) [62]	12-week double-blind, multicenter study Treatment: Tamsulosin 0.4 mg + 25 mg mirabegron and at week 4 dose titrated to 50 mg Tamsulosin 0.4 mg + matched placebo	Men age ≥ 40 years Diagnosed with BPH-associated LUTS Received tamsulosin 0.4 mg daily for ≥ 2 months OAB symptoms (≥ 8 micturitions per day and ≥ 2 more urgency episodes per day) Tamsulosin + mirabegron (n = 337) Tamsulosin + placebo (n = 339)	PVR volume < 200 mL PSA > 4 ng/mL or 4 to < 10 ng/mL with a negative biopsy within 2 years Qmax ≥ 5.0 mL/s with a minimum volume voided of 125 mL Excluded if had clinically significant bladder outlet obstruction determined by investigator	Tamsulosin + mirabegron statistically significantly reduced the mean number of daily micturitions and urgency episodes compared with tamsulosin plus placebo; there were no significant differences between the total IPSS scores between groups Rates of UUI did not significantly differ between groups	Fewer TEAEs with tamsulosin + mirabegron vs tamsulosin + placebo Drug-related adverse events and urinary retention rates were higher in the tamsulosin + mirabegron vs tamsulosin + placebo group
COURAGE Trial (NCT03902080) [27]	24-week double-blind treatment period Treatment: Vibegron 75 mg + α-blocker with/without 5-ARI Placebo + α-blocker with/without 5-ARI	Men age ≥ 45 years Persistent OAB symptoms (≥ 8 micturitions and ≥ 3 urgency episodes per day) for ≥ 2 months Diagnosed with BPH and treated with α-blocker (initiated ≥ 3 months before screening) with/without 5-ARI (initiated ≥ 6 months before screening) Vibegron (n = 538) Placebo (n = 542)	Urodynamic assessment of BOO and detrusor dysfunction were not criteria for the study PVR < 100 mL Qmax  ≥ 5.0 mL/s required to have at baseline	Vibegron vs placebo was associated with significant reductions in daily micturitions, urgency episodes, nocturia episodes, UUI episodes, IPSS storage score, and volume voided vs placebo	Vibegron was well tolerated, with similar rates of TEAE in the vibegron group vs placebo group (9.9% vs 9.4%) Urinary retention AEs were slightly higher in the vibegron combination therapy vs BPH medication alone, but the rates were < 1% for both treatment groups
COURAGE Extension Trial (NCT04103450) [65]	Open-label extension trial consisting of a 28-week treatment period In the COURAGE trial, participants assigned to vibegron continued vibegron for an additional 28 weeks, defined as 52-week cohort; and those assigned to placebo, received vibegron for 28 weeks, defined as 28-week cohort	Same as COURAGE trial Participants who completed the 24-week COURAGE trial were eligible to enroll in the extension trial 52-week cohort (n = 142) 28-week cohort (n = 134)	Same as COURAGE trial	52-week cohort demonstrated sustained improvements in mean daily micturitions, urgency episodes, nightly nocturia episodes, and daily UUI episodes throughout the extension 28-week cohort demonstrated improvements from extension trial baseline (week 24) in mean daily micturitions, daily urgency episodes, and nocturia episodes	Rates of AEs with vibegron were similar to the double-blind treatment in the 24-week COURAGE trial There were 2 discontinuations of urinary retention, but not related to treatment No clinically relevant changes from baseline in mean PVR urine volume No participants had PVR urine volume ≥ 200 mL at ≥ 2 consecutive assessments
Bladder Function and Safety Analysis of the COURAGE Trial (NCT03902080) [66]	Same as COURAGE trial 24-week double-blind treatment period Additional safety was assessed in the safety analysis set, consisting of all participants who received ≥ 1 dose of double-blind study medication Urodynamic parameters were assessed in the urodynamic evaluable set, randomized participants in the urodynamic substudy who received ≥ 1 dose of double-blind study medication and had Qmax and PdetQmax measurements at baseline and at 12 weeks	Same as COURAGE trial Safety analysis set (vibegron, n = 553; placebo, n = 551) Urodynamic evaluable set (vibegron, n = 21; placebo, n = 22)	Same as COURAGE trial	In the safety analysis set:  Differences in PVR and Uroflow-Qmax between vibegron and placebo were minimal from baseline to week 12 and week 24  Change from baseline to week 24 in peak flow rate was similar between groups  Only 20 (3.7%) and 7 (1.3%) participants receiving vibegron and placebo, respectively, had PVR increases ≥ 100 mL at > 1 consecutive visit; no participants receiving vibegron had increases ≥ 200 mL at > 1 consecutive visit In the urodynamic evaluable set:  There are no negative effects of vibegron on urodynamic function and no change in detrusor contractility or obstruction in men with BPH	Urinary retention was reported as an AE for 5 (0.9%) in the vibegron group and 4 (0.7%) in the placebo group Residual urine volume increased in 1 (0.2%) and 3 (0.5%) participants receiving vibegron and placebo, respectively, at the level of protocol-defined AE (elevated PVR considered clinically significant by the investigator but not meeting the protocol definition of urinary retention)

5-ARI 5α-reductase inhibitors, AE adverse event, BPH benign prostatic hyperplasia, BOO bladder outlet obstruction, IPPS International Prostate Symptom Score, OAB overactive bladder, P_detQ_max detrusor pressure at peak flow rate, PSA prostate-specific antigen, PVR postvoid residual urine volume, Q_max peak flow rate, Uroflow-Q_max maximum urinary flow rate, TEAE treatment-emergent adverse event, UUI urge urinary incontinence

Anticholinergics

Anticholinergics have long been used to treat OAB [49, 50], with the effectiveness of these medications varying among individuals with concomitant BPH [51–53]. A prospective study of fesoterodine and tamsulosin in men with BPH and LUTS found significant improvement in storage and total IPSS scores with the medications combined compared with tamsulosin alone [52]. In a 12-week clinical trial, patients with OAB symptoms and BPH showed improvement in OAB-related symptoms, including reduced urinary urgency, when treated with a combination of solifenacin and α-blocker, compared to α-blocker monotherapy; however, there were no significant differences in the total IPSS score [51]. Similarly, in another 12-week trial, the overall population of patients receiving solifenacin and α-blocker compared with α-blocker alone showed improvement in micturitions and volume voided, whereas IPSS subscores, including IPSS-QoL scores were not significantly different; improvement in urgency, total IPSS subscores, and IPSS-QoL scores were observed in a subgroup of patients stratified by baseline storage symptom severity [53]. While treatment with anticholinergic medications can improve symptoms, undesirable side effects may occur, such as dry mouth, dry eyes, constipation [26], an increased risk of incident dementia [54], and an elevated risk of falls/fractures [55].

β₃-adrenergic Receptor Agonists

Owing to the risk of cognitive impairment and dementia with many OAB medications, Society of Urodynamics, Female Pelvic Medicine, and Urogenital Reconstruction recommends β₃-adrenergic receptor agonists over anticholinergic medications [56]. β₃-adrenergic receptor agonists represent a newer class of drugs approved for the treatment of OAB [57, 58]. Both medications in this group (vibegron and mirabegron) are effective for the treatment of OAB symptoms and lack anticholinergic activity [56, 59–61]; however, whether these medications have an effect on overall bladder structure and function with long-term use is not well characterized.

Mirabegron is a β₃-adrenergic receptor agonist approved in 2012 for the treatment of OAB symptoms including urge urinary incontinence, urinary urgency, and urinary frequency [57]. The efficacy and safety of mirabegron for the management of OAB symptoms in patients receiving tamsulosin for LUTS attributable to BPH was assessed in the 12-week phase 4 PLUS study [62]. Although tamsulosin plus mirabegron significantly reduced the mean number of daily micturitions and urgency episodes compared with tamsulosin plus placebo, there were no significant between-group differences observed in the total IPSS score and IPSS-QoL score [62]. Drug-related adverse events and urinary retention rates were more frequent in the tamsulosin plus mirabegron group compared with tamsulosin alone [62]. In two 12-week clinical trials, rates of urge urinary incontinence did not significantly differ with combination therapy vs tamsulosin alone [62, 63]. Some adverse effects of mirabegron are attributable, in part, to its role as a moderate inhibitor of the CYP2D6 enzyme, which can lead to increased systemic levels of concurrently used medications that are CYP2D6 substrates (e.g., metoprolol, tamsulosin, desipramine, etc.). Mirabegron has also been associated with increases in hypertension, warranting careful blood pressure monitoring and potential dosage adjustments in some patients [57].

Vibegron is a β₃-adrenergic receptor agonist approved by the US Food and Drug Administration (FDA) in 2020 for the treatment of OAB and has an FDA-approved indication for OAB symptoms of urge urinary incontinence, urinary urgency, and urinary frequency in men on BPH medication [58]. Compared with placebo, vibegron significantly reduced mean daily micturitions, urinary urgency, and nocturia, while being well tolerated [60, 64]. The most commonly reported adverse reactions (≥ 2%) reported with vibegron were headache, urinary tract infection, nasopharyngitis, diarrhea, nausea, and upper respiratory tract infection [58]. The vibegron label indicates a drug interaction with digoxin, and advises to monitor serum digoxin concentrations before initiating and during therapy with vibegron [58]. Monitoring of digoxin concentrations should be used to assist in appropriately titrating the digoxin dosage to obtain the desired clinical effect [58]. Vibegron is metabolized by CYP3A4 and a P-gp substrate; however, no clinically significant differences in vibegron pharmacokinetics were observed with moderate or strong P-gp or CYP3A4 inhibitors or inducers [58].

The efficacy of vibegron to treat OAB symptoms in men with BPH was specifically studied in the COURAGE trial. In the 24-week phase 3 COURAGE trial, men pharmacologically treated for BPH with persistent OAB symptoms demonstrated significant improvements in OAB symptoms following 12 weeks of treatment with vibegron (primary and key secondary endpoints) [27]. The safety profile was comparable with previously published results of vibegron [27, 60, 64]. Vibegron was well tolerated in men, with similar rates of treatment-related adverse events in the vibegron group compared with the placebo group (9.9% and 9.4%, respectively) [27]. In the phase 3 open-label COURAGE extension trial, participants who received vibegron in the primary study continued for a total of 52 weeks, and showed sustained improvement in OAB symptoms [65]. Of note, two discontinuations due to urinary retention were reported but were not related to vibegron [65]. Additional safety assessments and a urodynamics substudy within the COURAGE trial were conducted to further evaluate measures related to bladder function [66].

In the bladder function and safety analysis of the COURAGE trial, participants in the placebo and vibegron groups similarly experienced minimal differences in PVR and maximum urinary flow rate (Uroflow-Q_max) between groups at baseline, week 12 and 24 [66]. Vibegron also did not negatively impact urodynamic function in men with BPH, including detrusor contractility or obstruction in men with BPH [66]. Urinary retention was reported as an AE for 5 (0.9%) patients in the vibegron group and 4 (0.7%) in the placebo group [66]. Furthermore, a post hoc responder analysis of the COURAGE data showed that a greater percentage of participants treated with vibegron compared with placebo achieved clinically relevant symptom reductions and meaningful improvements in quality of life [67].

Invasive/Procedural Approaches

Invasive or procedural approaches for OAB management, which include same day procedures (e.g., botulinum toxin injection of bladder, sacral neuromodulation, percutaneous tibial nerve stimulation, acupuncture, and implantable tibial nerve stimulation) are now part of shared decision-making, whereas major surgeries (e.g., urinary diversion and bladder augmentation cystoplasty) are reserved for severe cases when other therapeutic options have failed [4].

Treatment Challenges and Special Considerations

Risk of Additive Side Effects in Combination Therapy

Although combination treatment may provide symptom relief for men with OAB and BPH, there may be an increased risk of additive side effects as more medications are combined. In a cross-sectional survey of patients with OAB, the primary reason for not trying combination therapy among patients on monotherapy was concern related to side effects [68]. In patients on combination therapy, side effects were ranked third among reasons for discontinuation [68]. Furthermore, in a meta-analysis evaluating the efficacy and safety of α-blockers and anticholinergics in men, there was an increase in PVR and decrease in Q_max, despite a lower rate of acute urinary retention (1.4% [2/2971] vs 0.4 [7/1704]) among those receiving combination therapy compared with α-blocker monotherapy [69]. In the COURAGE trial, urinary retention was slightly higher with vibegron combination therapy than BPH medication alone, albeit < 1% for both treatment groups [27]. β₃-adrenergic receptor agonists are generally better tolerated and impose fewer side effects than anticholinergics [70, 71]. Although the incidence of adverse events is low when treating OAB symptoms in combination with BPH therapy, polypharmacy may increase the risk of side effects that warrant recognition.

OAB Treatment Adherence and Persistence

Treatment persistence is a challenge in OAB management among men and women, and men are less likely than women to progress from lifestyle changes to medications or procedural treatments [72]. In a retrospective analysis of the MarketScan Commercial Claims and Encounters Database (2013–2014), OAB medications were prescribed to just 13.4% of the 26,100 men having OAB who were included in the study, with 29% of patients remaining on pharmacotherapy through 2 years, and only 1.4% moving to procedural management (botulinum toxin or neuromodulation) over the same time frame [73]. This study highlighted low persistence rates of initial pharmacotherapy, as well as an overall undermanagement of OAB in men, with most patients not pursuing further OAB treatment after medication discontinuation (i.e., less likely to seek care, obtain refills, or undergo procedures).

Overall, patients receiving pharmacologic treatment for OAB historically have shown low rates of treatment adherence [74], as well as a decrease in persistence with medication over time [75]. Common reasons for treatment discontinuation include limited symptom improvement and bothersome side effects, often associated with anticholinergic medications [75]. In a recent comparative retrospective claims study, patients treated with vibegron had significantly better adherence and longer persistence compared with those treated with mirabegron or anticholinergics [76]. Looking ahead, improved therapeutic options offering better symptom control and less bothersome side effects may lead to significant gains in QoL and OAB management for men through improved persistence and adherence with treatment.

Limitations

The nature of narrative reviews is non-systematic, which involves the selection of relevant articles when presenting overall evidence covering a range of studies. Because the review included only pertinent publications, it may be subject to selection bias. A narrative review provides an overall background of the topic; however, it does not include an in-depth evidence-based synthesis on a focused topic. Furthermore, the data presented in the narrative review are subject to the authors’ interpretations and therefore may be biased owing to personal opinions or experiences.

Conclusion

The overlap and coexistence of OAB and BPH are common. Often, OAB symptoms are undertreated in men, and may be associated with a significant burden to patients and health systems. Proactive discussions about symptoms, starting in the primary care setting, may help better align patients with appropriate and timely treatment. Improved familiarity with OAB medications for use in men with BPH is likely needed. Safe and effective treatments for OAB can be used in combination with BPH treatments to manage the complex presentation of urinary symptoms in men.

Author Contributions

Bradley C. Gill, Matt T. Rosenberg, Steven A. Kaplan, and Lori B. Lerner contributed to the study conception and design. All authors performed material preparation, data collection, and analysis. All authors wrote the first draft of the manuscript and commented on previous versions of the manuscript. All authors read and approved of the final manuscript.

Funding

This study and medical writing and editorial support for the preparation of this manuscript were supported by funding from Sumitomo Pharma America, Inc. The journal’s Rapid Service Fee and Open Access Fees were funded by Sumitomo Pharma America, Inc.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Declarations

Conflict of Interest

Bradley C. Gill is a consultant for Boston Scientific and Sumitomo Pharma America, and an investigator in research studies for Boston Scientific. Matt T. Rosenberg is an advisor to and meeting participant/lecturer for Astellas and Sumitomo Pharma America, Inc. He is a meeting participant/lecturer for Ferring. Steven A. Kaplan is a consultant for Boston Scientific. Lori B. Lerner is a consultant for Boston Scientific and Sumitomo Pharma America; on regulatory committees for Proverum and ALPFA; and an investigator in research studies funded by Boston Scientific, Teleflex, and Janssen.

Ethical Approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.