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Medical treatment of benign prostatic hyperplasia

Medical treatment of benign prostatic hyperplasia
Author:
Kevin T McVary, MD, FACS
Section Editor:
Michael P O'Leary, MD, MPH
Deputy Editor:
Karen Law, MD, FACP
Literature review current through: Apr 2025. | This topic last updated: Oct 04, 2024.

INTRODUCTION — 

Lower urinary tract symptoms related to benign prostatic hyperplasia (LUTS/BPH) increase in prevalence with age. Urinary symptoms include increased frequency of urination, nocturia, hesitancy, urgency, and weak urinary stream. Treatment includes medical and surgical options. While BPH alone does not require treatment, it is often associated with LUTS and significant prostate enlargement, which may require treatment.

This topic reviews the medical management of patients with BPH. The epidemiology, pathophysiology, and diagnosis of BPH are discussed separately. The initial evaluation of LUTS and treatment of LUTS in men due to etiologies other than BPH are also discussed separately.

●(See "Epidemiology and pathophysiology of benign prostatic hyperplasia".)

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

●(See "Lower urinary tract symptoms in males".)

●(See "Lower urinary tract symptoms in males", section on 'Further management by etiology'.)

Surgical and other invasive therapies of BPH may be offered for selected patients following a detailed discussion of risks and benefits. These are also discussed separately. (See "Surgical treatment of benign prostatic hyperplasia (BPH)".)

PRETREATMENT CONSIDERATIONS — 

The treatment approach for BPH requires several pretreatment considerations and evaluations:

Confirm the diagnosis

●Confirm the presence of LUTS – When symptomatic, BPH presents with lower urinary tract symptoms (LUTS), including storage symptoms (urinary frequency, urgency, nocturia, and incontinence) and voiding symptoms (straining to void, urinary hesitancy, slow urinary stream, and dribbling) [1]. (See "Lower urinary tract symptoms in males", section on 'Patient evaluation'.)

●Confirm LUTS are due to BPH – While the majority of LUTS are attributed to BPH, other causes should be ruled out, including overactive bladder, urethral stricture, and prostate cancer (algorithm 1). (See "Lower urinary tract symptoms in males", section on 'Etiologies of LUTS'.)

The diagnosis of LUTS due to BPH is established by the presence of storage, voiding, and/or irritative urinary symptoms in the absence of findings on evaluation suggestive of a non-BPH cause. (See "Clinical manifestations and diagnostic evaluation of benign prostatic hyperplasia", section on 'Evaluation'.)

Review iatrogenic causes — Several commonly prescribed medications, including diuretics, antidepressants, antihistamines, and bronchodilators, may worsen LUTS by interfering with detrusor muscle and urinary sphincter function (table 1) [2-4]. Potential alternative medications should be reviewed with the patient prior to adding additional medical therapy for LUTS/BPH.

TREATMENT APPROACH — 

For most patients, the treatment of lower urinary tract symptoms (LUTS) due to BPH involves lifestyle modifications and behavioral therapy, followed by the addition of medications for persistent symptoms and/or enlarged prostate volume (algorithm 2).

Lifestyle modifications and behavioral interventions for all patients — Lifestyle modifications and behavioral interventions lessen the symptoms of LUTS due to BPH (table 2) [5]. These lifestyle changes should continue throughout BPH management, even if medical therapy is added. Further details on lifestyle and behavioral interventions are discussed in detail separately. (See "Lower urinary tract symptoms in males", section on 'Lifestyle and behavioral therapy for all patients'.)

Assess symptom severity and prostate size — These factors help inform the choice of therapy.

●Assessment of symptom severity – Symptom severity is assessed using the American Urological Association urinary symptom score/International Prostate Symptom Score (table 3) [6]. The urinary symptom score is a validated scoring system used to identify LUTS due to BPH, guide management, and monitor response to treatment (calculator 1). The combination of the patient's urinary symptom score and their perception of the impact of their symptoms on quality of life are used to classify patients into mild/minimal bother, moderate, and severe categories. Patients with moderate-to-severe, bothersome symptoms despite lifestyle modifications are candidates for additional medical and surgical therapy. (See 'Approach to medical therapy' below and 'Medications for symptom management' below.)

●Assessment of prostate size – Prostate size estimated to be >30 g is classified as "enlarged," and treatment with a 5-alpha-reductase inhibitor (5-ARI) is indicated. (See 'Additional treatment for enlarged prostate size (5-ARI's)' below.)

There are several methods to estimate prostate size, each with its own advantages and limitations, reviewed below and in detail in the table (table 4). Markers of an enlarged prostate gland include any of the following:

•Prostate-specific antigen (PSA) ≥1.5 ng/mL, measured prior to treatment with 5-ARIs

•Enlarged gland on digital rectal examination (DRE) (see "Clinical manifestations and diagnostic evaluation of benign prostatic hyperplasia", section on 'Physical examination')

•Prostate volume ≥30 g on transrectal ultrasonography, magnetic resonance imaging, or computed tomography of the pelvis

Most patients will have a DRE and PSA as part of their initial evaluation; in many cases, the results are sufficient to guide the decision to treat for prostate enlargement (see 'Additional treatment for enlarged prostate size (5-ARI's)' below). If results are uninformative or ambiguous (eg, PSA is borderline or DRE is equivocal, for example), we recommend referral to urology for further evaluation.

While imaging provides the most accurate estimate of prostate size, we discourage ordering imaging solely to determine medical therapy. Rather, previous imaging results from the last two years or imaging for other indications (eg, surgical planning, evaluation for malignancy) may be repurposed to estimate prostate size. (See "Clinical manifestations and diagnostic evaluation of benign prostatic hyperplasia", section on 'Prostate imaging'.)

Symptoms warranting specialist evaluation — Patients with any of the following conditions should be referred for prompt urologic evaluation, regardless of the severity of LUTS:

●PSA ≥4 ng/mL

●History of prostate cancer

●Recurrent urinary tract infection

●Bladder stone

●Hydronephrosis

●Refractory urinary retention

●Gross hematuria

●Progressive kidney function impairment

●Refractory LUTS/BPH despite medical therapy

In such patients, the urologist may arrange for urodynamic studies, additional imaging, and prompt initiation of medical or surgical therapy.

Approach to medical therapy — In patients without features that warrant early evaluation by a specialist (see 'Symptoms warranting specialist evaluation' above), the treatment of LUTS due to BPH involves lifestyle modifications and behavioral therapy, followed by the addition of medications for persistent symptoms and/or enlarged prostate.

Primary care clinicians often institute initial medical therapy. Symptom severity and prostate size guide the choice of monotherapy versus combination therapy for LUTS/BPH treatment (algorithm 2). (See 'Assess symptom severity and prostate size' above.)

●Mild, minimally bothersome LUTS/BPH – Patients with mild, minimally bothersome lower urinary tract symptoms (LUTS)/BPH are typically managed with lifestyle modifications and behavioral interventions alone (table 2) [7]. In such patients, further evaluation or treatment is generally not indicated, as symptoms cause minimal interference with daily activity.

In the rare circumstance of significant prostate enlargement without LUTS (eg, patient with elevated PSA, negative prostate cancer evaluation, and an incidental finding of enlarged prostate gland on imaging), the author of this topic has used 5-ARI monotherapy to reduce prostate size in patients who are poor surgical candidates to decrease the likelihood of needing surgery in the future.

●Moderate-to-severe, bothersome LUTS/BPH, no evidence of enlarged prostate – We use monotherapy with an alpha-1 adrenergic blocker in patients with persistent, bothersome LUTS/BPH when there is no evidence of an enlarged prostate. In selected patients, phosphodiesterase 5 (PDE-5) inhibitors, antimuscarinics, and/or beta-3 adrenergic agonists may also have a role as initial monotherapy. (See 'Medications for symptom management' below.)

●Moderate-to-severe, bothersome LUTS/BPH, with evidence of enlarged prostate – If the prostate is enlarged, we use combination therapy with a 5-ARI and an alpha-adrenergic blocker. While 5-ARIs may also improve LUTS/BPH symptoms, treatment effects may take several months, and therefore, they are not suitable as monotherapy for patients with moderate-to-severe, bothersome symptoms or in patients experiencing acute urinary retention from BPH [8,9]. The treatment effects of alpha-adrenergic blockers are seen within days; as above, they are the first-line treatment for bothersome LUTS/BPH for this reason. (See 'Medications for symptom management' below and 'Additional treatment for enlarged prostate size (5-ARI's)' below.)

We do not recommend adding 5-ARIs to treatment regimens with PDE-5 inhibitors or using combination 5-ARI/PDE-5 pills, as there is no evidence of additional benefit (see 'Erectile dysfunction (PDE-5 inhibitors)' below). We also do not use 5-ARIs with either beta-3 agonists or antimuscarinics due to lack of evidence.

For patients who prefer not to use long-term medications, surgical therapy is a reasonable alternative, as discussed below. (See 'Surgery as an alternative approach' below.)

Surgery as an alternative approach — Surgery should be offered as a reasonable alternative to medical therapy in patients with contraindications to medications and in patients who prefer not to take medications [5]. The choice of initial treatment with medical therapy or surgery is made using shared decision-making, considering the patient's comorbidities and potential risks and benefits of both strategies. Surgery is also an important second-line treatment for patients whose LUTS/BPH symptoms are refractory to medical therapy. (See "Surgical treatment of benign prostatic hyperplasia (BPH)".)

MEDICATIONS FOR SYMPTOM MANAGEMENT — 

Patients with persistent, bothersome symptoms despite lifestyle modifications warrant additional medical therapy (algorithm 2). Urinary symptom scores in these patients are generally moderate-to-severe (table 3).

Alpha-adrenergic receptor blockers for most patients

Selection and dosing — We use alpha-adrenergic receptor blockers as initial pharmacologic agents in most patients with lower urinary tract symptoms (LUTS)/BPH (table 5). They effectively reduce symptoms within days and are well tolerated. Phosphodiesterase 5 (PDE-5) inhibitors, beta-3 adrenergic agonists, or antimuscarinics (anticholinergics) are reasonable alternatives in patients with concomitant erectile dysfunction or overactive bladder (OAB) symptoms. Additional exceptions and prescribing considerations are discussed below. (See 'Special considerations in selected patients' below.)

We prefer selective alpha-1 adrenergic receptor antagonists (eg, alfuzosin, silodosin, tamsulosin, doxazosin, terazosin) over nonselective alpha-1 antagonists (eg, phenoxybenzamine, phentolamine), as they are better tolerated with fewer adverse effects [10]. Nonselective alpha-1 antagonists are a reasonable alternative in patients with other indications for these medications and in patients for whom cost and accessibility are issues. The most common treatment regimens for the selective alpha-adrenergic receptor blockers approved in the United States are shown in the table (table 5). A controlled-release tamsulosin tablet is also available in some markets but has not been well studied for the treatment of BPH.

Blood pressure should be monitored in patients who are started on alpha-adrenergic receptor blockers due to the risk of hypotension. Doses are titrated over several weeks. Terazosin and doxazosin carry a higher risk of hypotension; for these medications, bedtime dosing may reduce the impact of postural lightheadedness.

Alpha-1 antagonists may be used as monotherapy or in combination with other medications for BPH in the following scenarios:

●Beta-3 adrenergic agonists and antimuscarinics may be added to alpha-1 antagonists for persistent LUTS, especially when OAB symptoms predominate. (See 'Overactive bladder (beta-3 agonists and antimuscarinics)' below.)

●5-alpha-reductase inhibitors (5-ARIs) are added to alpha-1 antagonist therapy in patients with enlarged prostate size. (See 'Additional treatment for enlarged prostate size (5-ARI's)' below.)

●In patients with erectile dysfunction who develop LUTS/BPH, alpha-1 antagonists may be added to treatment with PDE-5 inhibitors, though this combination may cause significant hypotension in some patients. We do not use PDE-5 inhibitors and alpha-1 antagonists for the purposes of combination therapy in patients with isolated LUTS without erectile dysfunction, due to lack of additional efficacy. (See 'Erectile dysfunction (PDE-5 inhibitors)' below.)

While alpha-1 antagonists are effective for LUTS, they do not prevent BPH progression. Therefore, monotherapy with alpha-1 antagonists should continue indefinitely, as symptoms are likely to recur with discontinuation unless surgery is pursued [11].

Side effects and interactions

●Hypotension – Hypotension is an important potential side effect. Blood pressure should be monitored on initiation and with dose adjustment, as above. (See 'Selection and dosing' above.)

●Intraoperative floppy iris syndrome – Alpha-1 antagonists, particularly tamsulosin, have been associated with intraoperative floppy iris syndrome (IFIS) with cataract surgery. This association is discussed in further detail below. (See 'Future cataract surgery' below.)

●Cardiovascular risk – An association between alpha-1 adrenergic receptor antagonists and adverse cardiovascular events has been reported. This association is discussed in further detail below. (See 'Cardiovascular risk' below.)

●Ejaculatory dysfunction – The selective alpha-1 antagonists tamsulosin and silodosin have fewer systemic adverse effects but are associated with a higher frequency of retrograde or anejaculation (8 to 28 percent) compared with older, "conventional" drugs in this class (eg, terazosin, doxazosin) (table 5) [12-14].

Efficacy — Multiple randomized trials and meta-analyses have demonstrated the efficacy and tolerability of alpha-1 blockers for the treatment of LUTS/BPH [13-18]. In a meta-analysis of trials of alfuzosin, terazosin, doxazosin, or tamsulosin, when compared with placebo, the alpha-1 antagonists were associated with a 30 percent improvement in urinary symptom scores and 15 to 25 percent improvement in peak urinary flow (Qmax) [15]. In a newer network meta-analysis of 33 randomized trials including nearly 10,000 patients, alpha-1 blockers improved urinary symptom scores by 2.1 to 3.7 points compared with placebo and by 5.5 to 7.1 points compared with baseline, on a 35-point scale [18]. Although there have been few direct comparisons, all selective alpha-1 blockers appear to be similarly effective [13-18].

Bladder outlet obstruction is primarily mediated by alpha-1 adrenergic receptors located on prostatic smooth muscle [19], which are upregulated in the stromal glandular hyperplasia seen in BPH. Blocking signaling through the alpha-adrenergic receptors leads to smooth muscle relaxation of the bladder neck and prostatic urethra.

Special considerations in selected patients

Future cataract surgery — In patients with planned cataract surgery, we delay the initiation of alpha-1 antagonists until after surgery is completed. Alpha-1 antagonists, particularly tamsulosin, have been associated with IFIS [20-23]. IFIS is a surgical condition associated with cataract operations, characterized by a triad of findings: intraoperative miosis despite preoperative dilation; iris prolapse; and a billowing, flaccid iris [24]. Although a causal relation between the use of alpha-1 adrenergic blockers and IFIS remains controversial, IFIS is associated with increased rates of iris trauma and posterior capsular rupture during cataract surgery [25].

The American Urological Association guidelines recommend that patients with LUTS/BPH for whom alpha-1 antagonist therapy is offered should be asked about planned cataract surgery [7]. Patients with planned cataract surgery should avoid the initiation of alpha-1 antagonists until their cataract surgery is completed. In patients already on alpha-1 antagonists, there are insufficient data to recommend withholding or discontinuing the medication if the need for cataract surgery arises. In such patients, preoperative alpha-1 antagonist use should be discussed in advance with the ophthalmologist, as perioperative precautions may be taken to reduce the risk of IFIS complications. (See "Cataract in adults", section on 'Limiting risk of intraoperative floppy iris syndrome'.)

Cardiovascular risk — While we still consider selective alpha-1 antagonists first-line treatment, in patients with known cardiovascular disease, it is reasonable to consider alternative medications (eg, PDE-5 inhibitors, 5-ARIs, or beta-3 agonists) due to a potential association between alpha-1 adrenergic receptor antagonists and adverse cardiovascular events (table 5 and table 6). Following the landmark Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), in which patients receiving doxazosin had a 25 percent increased risk of cardiovascular events [26], guidelines no longer recommend alpha-1 adrenergic blockers as initial therapy for hypertension. The optimal use of these agents in patients with BPH is less clear, as the data on cardiovascular risk with the alpha-1 adrenergic blockers typically used for BPH are mixed [27-31]. In the largest cohort study to date of over 180,000 patients, initiation of alpha-1 adrenergic antagonists for BPH was associated with an increased risk of heart failure and other major cardiovascular events when compared with 5-ARIs [28]. The one-year risk of a major adverse cardiac event among treated versus untreated patients was 8.95 versus 8.32 percent, risk ratio 1.08 (95% CI 1.02-1.13), risk difference per 1000 individuals = 6.26 (95% CI 2.15-10.37), number needed to harm = 160 individuals (95% CI 97-466 individuals). The increased risk of adverse cardiovascular outcomes was sustained between both selective and nonselective alpha-1 adrenergic receptor antagonist subgroups.

Erectile dysfunction (PDE-5 inhibitors) — We use phosphodiesterase 5 (PDE-5) inhibitors as monotherapy in patients with erectile dysfunction and LUTS from BPH. Options and doses are listed in the table (table 6). PDE-5 inhibitors have been shown in several randomized trials to improve symptom scores in patients with LUTS/BPH, although no significant changes in urine flow rates have been demonstrated [32-36]. When used for BPH treatment, PDE-5 inhibitors are given daily, whereas when used for erectile dysfunction, these medications are used as needed. Reported adverse effects with PDE-5 inhibitors are relatively rare, with the more commonly reported effects consisting of headache, flushing, dyspepsia, nasal congestion, back pain, myalgias, and sinusitis.

For patients already on an alpha-1 blocker or 5-ARI for BPH treatment, the addition of a PDE-5 inhibitor is not recommended, as there is no evidence of additional benefit for LUTS/BPH symptoms [36,37]. For patients on alpha-1 blockers in whom a PDE-5 inhibitor is added for erectile dysfunction, caution is advised with concomitant use, as the combination may exacerbate symptomatic hypotension. Guidance for managing this drug interaction is discussed in further detail separately. (See "Treatment of male sexual dysfunction", section on 'Drug interactions'.)

Overactive bladder (beta-3 agonists and antimuscarinics) — In patients with mostly OAB symptoms (eg, frequency, urgency, and incontinence), beta-3 adrenergic agonists and antimuscarinics may be used as initial monotherapy (table 6) [38]. Beta-3 adrenergic agonists and antimuscarinics may also be added to alpha-1 blocker therapy for patients with persistent storage symptoms. The management of OAB is discussed in further detail separately. (See "Lower urinary tract symptoms in males", section on 'OAB with normal PVR'.)

Numerous clinical studies have demonstrated that antimuscarinics are effective and generally well-tolerated treatments for patients with OAB and that they successfully reduce the storage symptoms of frequency, urgency, and nocturia, both alone and when combined with alpha-1 blockers [39-45]. In a randomized trial evaluating the beta-3 agonist mirabegron as an add-on therapy to alpha-1 blocker treatment for men with BPH and ongoing OAB symptoms, tamsulosin and mirabegron were superior to tamsulosin and placebo in reducing the mean number of micturitions/day and urgency episodes/day and total urgency and frequency score [46].

Refractory symptoms — Patients with persistent symptoms despite monotherapy with an alpha-1 blocker may derive additional benefit from the addition of an antimuscarinic or beta-3 agonist for OAB symptoms, if present. (See 'Overactive bladder (beta-3 agonists and antimuscarinics)' above.)

If enlarged prostate volume is present, additional therapy with a 5-ARI is warranted. (See 'Additional treatment for enlarged prostate size (5-ARI's)' below.)

Consultation with a urologic specialist is appropriate to discuss additional medication therapy and surgical options. (See 'Symptoms warranting specialist evaluation' above.)

ADDITIONAL TREATMENT FOR ENLARGED PROSTATE SIZE (5-ARI'S)

5-ARI selection and dosing — For patients with an estimated prostate volume above 30 g (table 4), we use a 5-alpha-reductase inhibitor (5-ARI) to reduce stimulation of the prostate [47,48] (see 'Assess symptom severity and prostate size' above). Options and doses are provided in the table (table 6). 5-ARI treatment results in long-term reduction in prostatic volume, decreased BPH progression, and reduced need for prostate surgery [11,47,49]. We recommend the following approach for initiating 5-ARIs:

●Measure pretreatment PSA – 5-ARIs suppress serum prostate-specific antigen (PSA) levels by approximately 50 percent. Therefore, a baseline serum PSA should be checked prior to 5-ARI initiation. (See 'Suppression of serum PSA levels' below.)

●Select 5-ARI agent – Finasteride and dutasteride are the two 5-ARIs available in the United States and Europe (table 6). The choice between them depends on cost and availability. Though they differ slightly in the 5-alpha-reductase isozymes they inhibit, they are of similar efficacy for treating lower urinary tract symptoms (LUTS) due to BPH. In a head-to-head, randomized trial of patients with BPH, both drugs achieved similar reductions in prostate volume and improvement in symptom scores and urine flow rates [50]. 5-ARI treatment is continued indefinitely to ensure sustained prostatic volume reduction.

Side effects and concerns

Suppression of serum PSA levels — Because 5-ARIs suppress serum PSA levels by up to 50 percent, serum PSA should be checked prior to 5-ARI initiation. The baseline level is used as a proxy for prostate volume, which determines the likelihood of efficacy; the pretreatment PSA is also important for trend monitoring during subsequent follow-up. In patients receiving long-term (>3 months of continuous treatment) 5-ARI therapy, experts recommend multiplying the PSA value by two. Adjustment calculations for serum PSA are discussed in further detail separately. (See "Measurement of prostate-specific antigen", section on 'Medications'.)

Concerns regarding prostate cancer — Treatment with 5-ARIs has been associated with both a reduced overall risk of prostate cancer and a possible increased risk of high-grade prostate cancer. Two randomized trials, the Prostate Cancer Prevention Trial (PCPT; using finasteride) and the Reduction by Dutasteride of Prostate Cancer Events trial (REDUCE; using dutasteride), reported a reduced risk of prostate cancer compared with placebo, though no survival benefit with 5-ARIs was observed in either trial [51,52]. Importantly, however, both also raised concerns about a possible increased risk of high-grade prostate cancer with 5-ARI treatment. A subsequent analysis of the data from the PCPT suggests the apparent increase in the incidence of high-grade cancer may be due to detection bias; however, concerns regarding cancer risk remain [53]. These findings led the US Food and Drug Administration to recommend evaluation for other urologic conditions, including prostate cancer, in patients with BPH being considered for treatment with a 5-ARI. This is discussed in detail separately. (See "Chemoprevention strategies in prostate cancer", section on '5-Alpha reductase inhibitors'.)

Sexual dysfunction — Sexual dysfunction, including erectile dysfunction, ejaculatory dysfunction, or decreased libido, concurrent with 5-ARIs is common [54,55]. A subset of patients who experience sexual dysfunction with 5-ARIs prescribed for either BPH or androgenetic alopecia report continued, debilitating symptoms even when the medication is discontinued, sometimes termed "post-finasteride syndrome" (PFS) [56]. Most studies evaluating PFS are small, low-quality trials with methodologic issues [57-59]. Larger, high-quality, population-based studies have not replicated the incidence of PFS [60,61]. Understanding the persistent sexual dysfunction reported with PFS remains an area requiring further study.

Teratogenic effect in females — 5-ARIs may impact fetal development if ingested during pregnancy. Pregnant patients should be advised to avoid contact with crushed or broken tablets.

Efficacy — Both finasteride and dutasteride have shown a long-term reduction in prostatic volume, reduced BPH progression, improved LUTS, and reduced need for prostate surgery. In a randomized trial of 895 patients with LUTS/BPH, treatment with finasteride resulted in a 23 percent reduction in obstructive and 18 percent reduction in nonobstructive symptom scores, an increase in peak urinary flow rate, and a 19 percent reduction in mean prostatic volume compared with placebo [8]. Longer-term studies confirm sustained response [47,62-65]; in the Proscar Long-Term Efficacy and Safety Study (PLESS), patients taking finasteride had improvements in symptoms, urinary flow rates, and prostate volume that were durable over four years [64]. When compared with placebo, finasteride treatment reduced the risk of acute urinary retention and the need for surgical intervention by 57 percent and 55 percent, respectively (95% CI 40-69 percent for urinary retention and 95% CI 41-65 percent for surgical intervention) [47].

Dutasteride has also been shown to improve symptom scores and maximal urinary flow rates, decrease prostate volume, and reduce the risk of acute urinary retention and the need for surgical BPH intervention [66,67].

Combination therapy with alpha-1 blockers and 5-ARIs is associated with a greater reduction in symptomatic clinical progression and episodes of acute urinary retention, urinary tract infection, and urinary incontinence when compared with monotherapy with either agent [11,68,69]. In the largest randomized trial, which included 3047 patients with BPH, combination therapy reduced the risk of clinical progression (as measured by a combination of urinary symptom score, incontinence, and episodes of urinary retention and urinary tract infection) by 66 percent compared with placebo; monotherapy with either doxazosin or finasteride resulted in lower risk reductions (39 and 34 percent, respectively) [11]. A trial evaluating mono- and combination therapy with dutasteride and tamsulosin reported similar improved urinary symptoms with combination therapy [70].

NO ROLE FOR HERBAL REMEDIES — 

The use of plant/herb-based remedies, such as saw palmetto, for lower urinary tract symptoms/BPH is common, though evidence regarding their efficacy and safety is lacking. In a European survey, phytotherapy was the second most commonly utilized remedy behind alpha-adrenergic blocker monotherapy [71]. As these agents are not regulated by the US Food and Drug Administration's drug approval process, their production and safety are not rigorously monitored. Until additional studies are available, we do not use these agents for the treatment of BPH.

●Saw palmetto – Saw palmetto, derived from berries of the Serenoa repens (dwarf palm plant), has commonly been utilized as a phytotherapeutic for BPH, though studies to date have not shown clear evidence of benefit [72]. This is discussed in further detail separately. (See "Clinical use of saw palmetto", section on 'Benign prostatic hypertrophy'.)

●Hypoxis rooperi – South African star grass (Hypoxis rooperi) contains a beta-sitosterol that is believed to be its active ingredient. A meta-analysis noted that while studies of beta-sitosterol have reported improvements in urine flow rates and symptom scores, the problems of study design in these studies precluded strong inferences. Therefore, the long-term efficacy and safety of this product remain unclear [73].

●Pygeum africanum – African plum (Pygeum africanum) is believed by some to exert an anti-inflammatory effect by an inhibitory effect on neutrophils as well as on basic fibroblastic growth factor and epidermal growth factor-induced prostatic fibroblast proliferation. Proof of this postulated potential mechanism is lacking, and the efficacy of P. africanum remains uncertain.

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 email 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)")

●Beyond the Basics topics (see "Patient education: Benign prostatic hyperplasia (BPH) (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Discontinue medications associated with LUTS – Several commonly prescribed medications are known to cause or worsen lower urinary tract symptoms (LUTS). Potential alternative medications should be reviewed prior to adding medical therapy for LUTS/benign prostatic hyperplasia (BPH) (table 1). (See 'Review iatrogenic causes' above.)

●Implement lifestyle modifications and behavioral interventions – Lifestyle modifications and behavioral interventions lessen the symptoms of LUTS due to BPH (table 2). These lifestyle changes should continue throughout BPH management, even if medical therapy is added. (See 'Lifestyle modifications and behavioral interventions for all patients' above.)

●Assess symptom severity and prostate size – The severity of symptoms and the estimated size of the prostate determine indications for medical therapy (algorithm 2). Symptom severity is assessed using the American Urological Association urinary symptom score/International Prostate Symptom Score (table 3) (calculator 1). Several strategies may be used to estimate prostate size (table 4). (See 'Assess symptom severity and prostate size' above.)

●Symptoms warranting urology evaluation – Patients with any of the following conditions should be referred for prompt urologic evaluation, regardless of the severity of LUTS:

•Prostate-specific antigen ≥4 ng/mL

•History of prostate cancer

•Recurrent urinary tract infection

•Bladder stone

•Hydronephrosis

•Refractory urinary retention

•Gross hematuria

•Progressive kidney function impairment

•Refractory LUTS/BPH despite medical therapy

●Symptom management

•Mild, minimally bothersome symptoms – For most patients with minimally bothersome symptoms, lifestyle modifications and behavioral interventions are adequate for symptom management, and further evaluation and treatment are not indicated. (See 'Approach to medical therapy' above.)

•Moderate or severe, bothersome symptoms, no evidence of enlarged prostate – For patients with moderate or severe symptoms due to LUTS/BPH, we suggest selective alpha-1 antagonists as first-line therapy rather than other pharmacotherapies (algorithm 2) (Grade 2C). Although other classes are also effective, alpha-1 antagonists are well tolerated and fast-acting, and clinical experience with them is extensive. Options and doses are reviewed in the table (table 5). (See 'Alpha-adrenergic receptor blockers for most patients' above.)

Phosphodiesterase 5 inhibitors (table 6) are a reasonable alternative option for patients with concomitant erectile dysfunction. (See 'Erectile dysfunction (PDE-5 inhibitors)' above.)

Beta-3 adrenergic agonists or antimuscarinics (table 6) may be used for patients with predominant overactive bladder (OAB) symptoms. Symptoms of OAB include frequency, urgency, and incontinence with normal postvoid residual urine volumes. (See 'Overactive bladder (beta-3 agonists and antimuscarinics)' above and "Lower urinary tract symptoms in males", section on 'OAB with normal PVR'.)

●Additional treatment for enlarged prostate size – For patients with bothersome LUTS/BPH and enlarged prostate size >30 g (table 4), we recommend additional treatment with 5-alpha-reductase inhibitors (5-ARIs) (algorithm 2) (Grade 1B). 5-ARIs reduce prostate volume, prevent BPH progression, and reduce the need for surgery. Because treatment effects may take several months, 5-ARIs are not sufficient as monotherapy for LUTS due to BPH and instead should be combined with an alpha-adrenergic blocker or other pharmacotherapy for LUTS/BPH symptom management. (See 'Additional treatment for enlarged prostate size (5-ARI's)' above.)

●Surgery as an alternative approach – Surgery is a reasonable alternative to medical therapy in patients with contraindications to medications and in patients who prefer not to take medications. The choice of initial treatment with medical therapy or surgery is made using shared decision-making, taking into account the patient's comorbidities and potential risks and benefits of both strategies. Surgery is also an important second-line treatment for patients whose LUTS/BPH symptoms are refractory to medical therapy. (See 'Surgery as an alternative approach' above and "Surgical treatment of benign prostatic hyperplasia (BPH)".)

ACKNOWLEDGMENTS — 

The UpToDate editorial staff acknowledges Glenn Cunningham, MD, and Dov Kadmon, MD, who contributed to earlier versions of this topic review.

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  32. McVary KT, Monnig W, Camps JL Jr, et al. Sildenafil citrate improves erectile function and urinary symptoms in men with erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized, double-blind trial. J Urol 2007; 177:1071.
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  36. Pattanaik S, Mavuduru RS, Panda A, et al. Phosphodiesterase inhibitors for lower urinary tract symptoms consistent with benign prostatic hyperplasia. Cochrane Database Syst Rev 2018; 11:CD010060.
  37. Casabé A, Roehrborn CG, Da Pozzo LF, et al. Efficacy and safety of the coadministration of tadalafil once daily with finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia. J Urol 2014; 191:727.
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  40. Kaplan SA, Roehrborn CG, Dmochowski R, et al. Tolterodine extended release improves overactive bladder symptoms in men with overactive bladder and nocturia. Urology 2006; 68:328.
  41. Weiss JP, Jumadilova Z, Johnson TM 2nd, et al. Efficacy and safety of flexible dose fesoterodine in men and women with overactive bladder symptoms including nocturnal urinary urgency. J Urol 2013; 189:1396.
  42. van Kerrebroeck P, Chapple C, Drogendijk T, et al. Combination therapy with solifenacin and tamsulosin oral controlled absorption system in a single tablet for lower urinary tract symptoms in men: efficacy and safety results from the randomised controlled NEPTUNE trial. Eur Urol 2013; 64:1003.
  43. Chapple C, Herschorn S, Abrams P, et al. Tolterodine treatment improves storage symptoms suggestive of overactive bladder in men treated with alpha-blockers. Eur Urol 2009; 56:534.
  44. Kaplan SA, McCammon K, Fincher R, et al. Safety and tolerability of solifenacin add-on therapy to α-blocker treated men with residual urgency and frequency. J Urol 2013; 189:S129.
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  68. Lepor H, Williford WO, Barry MJ, et al. The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group. N Engl J Med 1996; 335:533.
  69. Kirby RS, Roehrborn C, Boyle P, et al. Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial. Urology 2003; 61:119.
  70. Montorsi F, Roehrborn C, Garcia-Penit J, et al. The effects of dutasteride or tamsulosin alone and in combination on storage and voiding symptoms in men with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH): 4-year data from the Combination of Avodart and Tamsulosin (CombAT) study. BJU Int 2011; 107:1426.
  71. Fourcade RO, Théret N, Taïeb C, BPH USAGE Study Group. Profile and management of patients treated for the first time for lower urinary tract symptoms/benign prostatic hyperplasia in four European countries. BJU Int 2008; 101:1111.
  72. Trivisonno LF, Sgarbossa N, Alvez GA, et al. Serenoa repens for the treatment of lower urinary tract symptoms due to benign prostatic enlargement: A systematic review and meta-analysis. Investig Clin Urol 2021; 62:520.
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Topic 6891 Version 82.0

References

1 : Analyzing Why Men Seek Treatment for Lower Urinary Tract Symptoms and Factors Associated With Nonimprovement.

2 : Contribution of common medications to lower urinary tract symptoms in men.

3 : Inhaled anticholinergic drugs and risk of acute urinary retention.

4 : Prescription rate of medications potentially contributing to lower urinary tract symptoms and detection of adverse reactions by prescription sequence symmetry analysis.

5 : Update on AUA guideline on the management of benign prostatic hyperplasia.

6 : The American Urological Association Symptom Index for Benign Prostatic Hyperplasia.

7 : Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: AUA GUIDELINE PART I-Initial Work-up and Medical Management.

8 : The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group.

9 : Finasteride for benign prostatic hyperplasia.

10 : Nonoperative management of benign prostatic hyperplasia.

11 : The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia.

12 : Phase III multicenter placebo-controlled study of tamsulosin in benign prostatic hyperplasia. Tamsulosin Investigator Group.

13 : Comparative Effectiveness of Newer Medications for Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: A Systematic Review and Meta-analysis.

14 : Silodosin for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia.

15 : A meta-analysis on the efficacy and tolerability of alpha1-adrenoceptor antagonists in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction.

16 : Doxazosin for treating lower urinary tract symptoms compatible with benign prostatic obstruction: a systematic review of efficacy and adverse effects.

17 : Alfuzosin for treatment of lower urinary tract symptoms compatible with benign prostatic hyperplasia: a systematic review of efficacy and adverse effects.

18 : Comparative Effectiveness and Safety of Monodrug Therapies for Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia: A Network Meta-analysis.

19 : The use of alpha-adrenergic blockers in benign prostatic obstruction.

20 : Prospective multicenter evaluation of cataract surgery in patients taking tamsulosin (Flomax).

21 : Intraoperative floppy iris syndrome associated with tamsulosin.

22 : Incidence of intraoperative floppy iris syndrome in patients on either systemic or topical alpha(1)-adrenoceptor antagonist.

23 : Association between tamsulosin and serious ophthalmic adverse events in older men following cataract surgery.

24 : Factors associated with intraoperative floppy iris syndrome.

25 : Risk factors for intraoperative floppy iris syndrome: a meta-analysis.

26 : Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). ALLHAT Collaborative Research Group.

27 : Study of the association between ischemic heart disease and use of alpha-blockers and finasteride indicated for the treatment of benign prostatic hyperplasia.

28 : Cardiovascular Outcomes ofα-Blockers vs 5-αReductase Inhibitors for Benign Prostatic Hyperplasia.

29 : Cardiac Failure Associated with Medical Therapy of Benign Prostatic Hyperplasia: A Population Based Study.

30 : Do adrenergic alpha-antagonists increase the risk of poor cardiovascular outcomes? A systematic review and meta-analysis.

31 : Efficacy and safety of adrenergic alpha-1 receptor antagonists in older adults: a systematic review and meta-analysis supporting the development of recommendations to reduce potentially inappropriate prescribing.

32 : Sildenafil citrate improves erectile function and urinary symptoms in men with erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized, double-blind trial.

33 : Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a dose finding study.

34 : Efficacy and safety of tadalafil once daily in the treatment of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: results of an international randomized, double-blind, placebo-controlled trial.

35 : Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international, randomised, parallel, placebo-controlled clinical trial.

36 : Phosphodiesterase inhibitors for lower urinary tract symptoms consistent with benign prostatic hyperplasia.

37 : Efficacy and safety of the coadministration of tadalafil once daily with finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia.

38 : Systematic review of therapy for men with overactive bladder.

39 : Efficacy of solifenacin in patients previously treated with tolterodine extended release 4 mg: results of a 12-week, multicenter, open-label, flexible-dose study.

40 : Tolterodine extended release improves overactive bladder symptoms in men with overactive bladder and nocturia.

41 : Efficacy and safety of flexible dose fesoterodine in men and women with overactive bladder symptoms including nocturnal urinary urgency.

42 : Combination therapy with solifenacin and tamsulosin oral controlled absorption system in a single tablet for lower urinary tract symptoms in men: efficacy and safety results from the randomised controlled NEPTUNE trial.

43 : Tolterodine treatment improves storage symptoms suggestive of overactive bladder in men treated with alpha-blockers.

44 : Safety and tolerability of solifenacin add-on therapy toα-blocker treated men with residual urgency and frequency.

45 : A randomized controlled study of the efficacy of tamsulosin monotherapy and its combination with mirabegron for overactive bladder induced by benign prostatic obstruction.

46 : Efficacy and Safety of Mirabegron versus Placebo Add-On Therapy in Men with Overactive Bladder Symptoms Receiving Tamsulosin for Underlying Benign Prostatic Hyperplasia: A Randomized, Phase 4 Study (PLUS).

47 : The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group.

48 : Natural history of prostatism: risk factors for acute urinary retention.

49 : Evidence for atrophy and apoptosis in the prostates of men given finasteride.

50 : Comparison of dutasteride and finasteride for treating benign prostatic hyperplasia: the Enlarged Prostate International Comparator Study (EPICS).

51 : The influence of finasteride on the development of prostate cancer.

52 : The effect of dutasteride on the usefulness of prostate specific antigen for the diagnosis of high grade and clinically relevant prostate cancer in men with a previous negative biopsy: results from the REDUCE study.

53 : Effect of finasteride on the sensitivity of PSA for detecting prostate cancer.

54 : Sexual dysfunction in subjects treated with inhibitors of 5α-reductase for benign prostatic hyperplasia: a comprehensive review and meta-analysis.

55 : Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients.

56 : The post-finasteride syndrome: possible etiological mechanisms and symptoms.

57 : THE ENVIRONMENT AND DISEASE: ASSOCIATION OR CAUSATION?

58 : A Review of the FAERS Data on 5-Alpha Reductase Inhibitors: Implications for Postfinasteride Syndrome.

59 : Finasteride 5 mg and sexual side effects: how many of these are related to a nocebo phenomenon?

60 : Long-term Consequences of Finasteride vs Placebo in the Prostate Cancer Prevention Trial.

61 : Risk of erectile dysfunction associated with use of 5-αreductase inhibitors for benign prostatic hyperplasia or alopecia: population based studies using the Clinical Practice Research Datalink.

62 : Efficacy of finasteride is maintained in patients with benign prostatic hyperplasia treated for 5 years. The North American Finasteride Study Group.

63 : Three-year safety and efficacy data on the use of finasteride in the treatment of benign prostatic hyperplasia.

64 : Urinary retention in patients with BPH treated with finasteride or placebo over 4 years. Characterization of patients and ultimate outcomes. The PLESS Study Group.

65 : A comparison of the efficacy of dutasteride on reducing lower urinary tract symptoms among patients with small versus large benign prostatic hyperplasia.

66 : Effect of dutasteride on clinical progression of benign prostatic hyperplasia in asymptomatic men with enlarged prostate: a post hoc analysis of the REDUCE study.

67 : Dutasteride on benign prostatic hyperplasia: a meta-analysis on randomized clinical trials in 6460 patients.

68 : The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group.

69 : Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial.

70 : The effects of dutasteride or tamsulosin alone and in combination on storage and voiding symptoms in men with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH): 4-year data from the Combination of Avodart and Tamsulosin (CombAT) study.

71 : Profile and management of patients treated for the first time for lower urinary tract symptoms/benign prostatic hyperplasia in four European countries.

72 : Serenoa repens for the treatment of lower urinary tract symptoms due to benign prostatic enlargement: A systematic review and meta-analysis.

73 : Beta-sitosterols for benign prostatic hyperplasia.