Benign Prostatic Hyperplasia (BPH) 

Updated: Jan 15, 2019
Author: Levi A Deters, MD; Chief Editor: Edward David Kim, MD, FACS 

Overview

Practice Essentials

Benign prostatic hyperplasia (BPH), also known as benign prostatic hypertrophy, is a histologic diagnosis characterized by proliferation of the cellular elements of the prostate. Chronic bladder outlet obstruction (BOO) secondary to BPH may lead to urinary retention, renal insufficiency, recurrent urinary tract infections, gross hematuria, and bladder calculi. The image below illustrates normal prostate anatomy.

Normal prostate anatomy. The prostate is located a Normal prostate anatomy. The prostate is located at the apex of the bladder and surrounds the proximal urethra.

Signs and symptoms

When the prostate enlarges, it may constrict the flow of urine. Nerves within the prostate and bladder may also play a role in causing the following common symptoms:

  • Urinary frequency

  • Urinary urgency

  • Nocturia- Needing to get up frequently at night to urinate

  • Hesitancy - Difficulty initiating the urinary stream; interrupted, weak stream

  • Incomplete bladder emptying - The feeling of persistent residual urine, regardless of the frequency of urination

  • Straining - The need strain or push (Valsalva maneuver) to initiate and maintain urination in order to more fully empty the bladder

  • Decreased force of stream - The subjective loss of force of the urinary stream over time

  • Dribbling - The loss of small amounts of urine due to a poor urinary stream as well as weak urinary stream

See Presentation for more detail.

Diagnosis

Digital rectal examination

The digital rectal examination (DRE) is an integral part of the evaluation in men with presumed BPH. With the DRE, the examiner can assess prostate size and contour, evaluate for nodules, and detect areas suggestive of malignancy.

Laboratory studies

  • Urinalysis - Examine the urine using dipstick methods and/or via centrifuged sediment evaluation to assess for the presence of blood, leukocytes, bacteria, protein, or glucose

  • Urine culture - This may be useful to exclude infectious causes of irritative voiding and is usually performed if the initial urinalysis findings indicate an abnormality

  • Prostate-specific antigen (PSA) - Although BPH does not cause prostate cancer, men at risk for BPH are also at risk for this disease and should be screened accordingly (although screening for prostate cancer remains controversial)

  • Electrolytes, blood urea nitrogen (BUN), and creatinine - These evaluations are useful screening tools for chronic renal insufficiency in patients who have high postvoid residual (PVR) urine volumes; however, a routine serum creatinine measurement is not indicated in the initial evaluation of men with lower urinary tract symptoms (LUTS) secondary to BPH[1]

Ultrasonography

Ultrasonography (abdominal, renal, transrectal) is useful for helping to determine bladder and prostate size and the degree of hydronephrosis (if any) in patients with urinary retention or signs of renal insufficiency. Generally, it is not indicated for the initial evaluation of uncomplicated LUTS.

Endoscopy of the lower urinary tract

Cystoscopy may be indicated in patients scheduled for invasive treatment or in whom a foreign body or malignancy is suspected. In addition, endoscopy may be indicated in patients with a history of sexually transmitted disease (eg, gonococcal urethritis), prolonged catheterization, or trauma.

IPSS/AUA-SI

The severity of BPH can be determined with the International Prostate Symptom Score (IPSS)/American Urological Association Symptom Index (AUA-SI) plus a disease-specific quality of life (QOL) question. Questions on the AUA-SI for BPH concern the following:

  • Incomplete emptying
  • Frequency
  • Intermittency
  • Urgency
  • Weak stream
  • Straining
  • Nocturia

Other tests

  • Flow rate - Useful in the initial assessment and to help determine the patient’s response to treatment

  • PVR urine volume - Used to gauge the severity of bladder decompensation; it can be obtained invasively with a catheter or noninvasively with a transabdominal ultrasonic scanner

  • Pressure-flow studies - Findings may prove useful for evaluating for BOO

  • Urodynamic studies - To help distinguish poor bladder contraction ability (detrusor underactivity) from BOO

  • Cytologic examination of the urine - May be considered in patients with predominantly irritative voiding symptoms

See Workup for more detail.

Management

Pharmacologic treatment

Agents used in the treatment of BPH include the following:

  • Alpha-adrenergic receptor blockers

  • 5-alpha reductase inhibitors

  • Phosphodiesterase-5 enzyme inhibitors

  • Anticholinergic agents

Surgery

  • Transurethral resection of the prostate (TURP) - The criterion standard for relieving BOO secondary to BPH

  • Open prostatectomy - Reserved for patients with very large prostates (>75 g), patients with concomitant bladder stones or bladder diverticula, and patients who cannot be positioned for transurethral surgery

Minimally invasive treatment

  • Transurethral incision of the prostate (TUIP)

  • Laser treatment - Used to cut or destroy prostate tissue; multiple laser types are available, including green light, holmium, and thulium, and each has its own strengths and weaknesses

  • Transurethral microwave therapy (TUMT) - Generates heat that causes cell death in the prostate, leading to prostatic contraction and volume reduction

  • Transurethral needle ablation of the prostate (TUNA)

  • High-intensity ultrasonographic energy therapy - Currently in the clinical trial stage

  • Prostatic stents - Flexible devices that expand when put in place to improve the flow of urine past the prostate

  • Laparoscopic prostatectomy

  • Implanted devices to relieve prostatic obstruction (eg, UroLift)

  • Prostate artery embolization - Performed by a radiologist; this technique has yet to become established as a standard-of-care therapeutic option

See Treatment and Medication for more detail.

Background

Benign prostatic hyperplasia (BPH), also known as benign prostatic hypertrophy, is a histologic diagnosis characterized by proliferation of the cellular elements of the prostate. Cellular accumulation and gland enlargement may result from epithelial and stromal proliferation, impaired preprogrammed cell death (apoptosis), or both.

BPH involves the stromal and epithelial elements of the prostate arising in the periurethral and transition zones of the gland (see Pathophysiology). The hyperplasia presumably results in enlargement of the prostate that may restrict the flow of urine from the bladder.

BPH is considered a normal part of the aging process in men and is hormonally dependent on testosterone and dihydrotestosterone (DHT) production. An estimated 50% of men demonstrate histopathologic BPH by age 60 years. This number increases to 90% by age 85 years.

The voiding dysfunction that results from prostate gland enlargement and bladder outlet obstruction (BOO) is termed lower urinary tract symptoms (LUTS). It has also been commonly referred to as prostatism, although this term has decreased in popularity. These entities overlap; not all men with BPH have LUTS, and likewise, not all men with LUTS have BPH. Approximately half of men diagnosed with histopathologic BPH report moderate-to-severe LUTS.

Clinical manifestations of LUTS include urinary frequency, urgency, nocturia (awakening at night to urinate), decreased or intermittent force of stream, or a sensation of incomplete emptying. Complications occur less commonly but may include acute urinary retention (AUR), impaired bladder emptying, the need for corrective surgery, renal failure, recurrent urinary tract infections, bladder stones, or gross hematuria. (See Presentation.)

Prostate volume may increase over time in men with BPH. In addition, peak urinary flow, voided volume, and symptoms may worsen over time in men with untreated BPH (see Workup). The risk of AUR and the need for corrective surgery increases with age.

Patients who are not bothered by their symptoms and are not experiencing complications of BPH should be managed with a strategy of watchful waiting. Patients with mild LUTS can be treated initially with medical therapy. Transurethral resection of the prostate (TURP) is considered the criterion standard for relieving bladder outlet obstruction (BOO) secondary to BPH. However, there is considerable interest in the development of minimally invasive therapies to accomplish the goal of TURP while avoiding its adverse effects[2] (see Treatment).

Anatomy

The prostate is a walnut-sized gland that forms part of the male reproductive system. It is located anterior to the rectum and just distal to the urinary bladder. It is in continuum with the urinary tract and connects directly with the penile urethra. It is therefore a conduit between the bladder and the urethra. (See the image below.)

Normal prostate anatomy. The prostate is located a Normal prostate anatomy. The prostate is located at the apex of the bladder and surrounds the proximal urethra.

The gland is composed of several zones or lobes that are enclosed by an outer layer of tissue (capsule). These include the peripheral, central, anterior fibromuscular stroma, and transition zones. BPH originates in the transition zone, which surrounds the urethra.

Pathophysiology

Prostatic enlargement depends on the potent androgen dihydrotestosterone (DHT). In the prostate gland, type II 5-alpha-reductase metabolizes circulating testosterone into DHT, which works locally, not systemically. DHT binds to androgen receptors in the cell nuclei, potentially resulting in BPH.

However, the fact that serum testosterone levels decrease with age, yet the development of BPH increases, suggests that other agents play an etiologic role. Possible factors include the metabolic syndrome, hyperinsulinemia, norepinephrine, angiotensin II, and insulin-like growth factors.[3]

In vitro studies have shown that large numbers of alpha-1-adrenergic receptors are located in the smooth muscle of the stroma and capsule of the prostate, as well as in the bladder neck. Stimulation of these receptors causes an increase in smooth-muscle tone, which can worsen LUTS. Conversely, blockade of these receptors (see Treatment) can reversibly relax these muscles, with subsequent relief of LUTS.

Microscopically, BPH is characterized as a hyperplastic process. The hyperplasia results in enlargement of the prostate that may restrict the flow of urine from the bladder, resulting in clinical manifestations of BPH. The prostate enlarges with age in a hormonally dependent manner. Notably, castrated males (ie, who are unable to make testosterone) do not develop BPH.

The traditional theory behind BPH is that, as the prostate enlarges, the surrounding capsule prevents it from radially expanding, potentially resulting in urethral compression. However, obstruction-induced bladder dysfunction contributes significantly to LUTS. The bladder wall becomes thickened, trabeculated, and irritable when it is forced to hypertrophy and increase its own contractile force.

This increased sensitivity (detrusor overactivity), even with small volumes of urine in the bladder, is believed to contribute to urinary frequency and LUTS. The bladder may gradually weaken and lose the ability to empty completely, leading to increased residual urine volume and, possibly, acute or chronic urinary retention.

In the bladder, obstruction leads to smooth-muscle-cell hypertrophy. Biopsy specimens of trabeculated bladders demonstrate evidence of scarce smooth-muscle fibers with an increase in collagen. The collagen fibers limit compliance, leading to higher bladder pressures upon filling. In addition, their presence limits shortening of adjacent smooth muscle cells, leading to impaired emptying and the development of residual urine.

The main function of the prostate gland is to secrete an alkaline fluid that comprises approximately 70% of the seminal volume. The secretions produce lubrication and nutrition for the sperm. The alkaline fluid in the ejaculate results in liquefaction of the seminal plug and helps to neutralize the acidic vaginal environment.

The prostatic urethra is a conduit for semen and prevents retrograde ejaculation (ie, ejaculation resulting in semen being forced backwards into the bladder) by closing off the bladder neck during sexual climax. Ejaculation involves a coordinated contraction of many different components, including the smooth muscles of the seminal vesicles, vasa deferentia, ejaculatory ducts, and the ischiocavernosus and bulbocavernosus muscles.

Epidemiology

BPH is a common problem that affects the quality of life in approximately one third of men older than 50 years. BPH is histologically evident in up to 90% of men by age 85 years. As many as 14 million men in the United States have symptoms of BPH.[4] Worldwide, approximately 30 million men have symptoms related to BPH.

The prevalence of BPH in white and African-American men is similar. However, BPH tends to be more severe and progressive in African-American men, possibly because of the higher testosterone levels, 5-alpha-reductase activity, androgen receptor expression, and growth factor activity in this population. The increased activity leads to an increased rate of prostatic hyperplasia and subsequent enlargement and its sequelae.

Prognosis

In the past, chronic end-stage BOO often led to renal failure and uremia. Although this complication has become much less common, chronic BOO secondary to BPH may lead to urinary retention, renal insufficiency, recurrent urinary tract infections, gross hematuria, and bladder calculi.

Patient Education

For patient education information, see the Prostate Health Center and Kidneys and Urinary System Center, as well as Enlarged Prostate, Bladder Control Problems, and Inability to Urinate.

 

Presentation

History

The diagnosis of benign prostatic hyperplasia (BPH) can often be suggested on the basis of the history alone. Special attention to the following features is essential to making the correct diagnosis and recommending treatment choices:

  • Onset and duration of symptoms

  • General health issues (including sexual history)

  • Fitness for any possible surgical interventions

  • Severity of symptoms and how they are affecting quality of life

  • Medications

  • Previously attempted treatments

Symptoms often attributed to BPH can be caused by other disease processes, and a history and physical examination are essential in ruling out other etiologies of (lower urinary tract symptoms (LUTS) (see DDx/Diagnostic Considerations).

When the prostate enlarges, it may act like a "clamp on a hose," constricting the flow of urine. Nerves within the prostate and bladder may also play a role in causing the following common symptoms:

  • Urinary frequency - The need to urinate frequently during the day or night (nocturia), usually voiding only small amounts of urine with each episode

  • Urinary urgency - The sudden, urgent need to urinate, owing to the sensation of imminent loss of urine without control

  • Hesitancy - Difficulty initiating the urinary stream; interrupted, weak stream

  • Incomplete bladder emptying - The feeling of persistent residual urine, regardless of the frequency of urination

  • Straining - The need strain or push (Valsalva maneuver) to initiate and maintain urination in order to more fully evacuate the bladder

  • Decreased force of stream - The subjective loss of force of the urinary stream over time

  • Dribbling - The loss of small amounts of urine due to a poor urinary stream

A sexual history is important, as epidemiologic studies have identified LUTS as an independent risk factor for erectile dysfunction and ejaculatory dysfunction.[5]

Physical Examination

Conduct a focused physical examination to assess the suprapubic area for signs of bladder distention and a neurological examination for sensory and motor deficits.

The digital rectal examination (DRE) is an integral part of the evaluation in men with presumed BPH. During this portion of the examination, prostate size and contour can be assessed, nodules can be evaluated, and areas suggestive of malignancy can be detected. 

Decreased anal sphincter tone or the lack of a bulbocavernosus muscle reflex may indicate an underlying neurological disorder.

The prostate is examined using the index finger of the dominant hand. The finger is placed through the anus after relaxation of the anal sphincter, and the prostate is palpated circumferentially (analogous to a windshield wiper movement).

In general, an estimation of the number of index finger pads that one can sweep over the rectal surface of the prostate during DRE is a useful way for non-urologist examiners to communicate estimated gland size. For example, one can report the prostate size as "2-3 fingerbreadths wide" when charting in the medical record or communicating with a colleague. Most asymptomatic men have glands of 2 fingerbreadths or less.  Anecdotally, each fingerbreadth correlates to approximately 15-20 g of tissue. The normal prostate volume in a young man is approximately 20 g.

In addition, pelvic floor tone, the presence or absence of fluctuance (ie, prostate abscess), and pain sensitivity of the gland (prostatodynia/prostatitis) can be assessed.

A more precise volumetric determination can be made using transrectal ultrasonography (TRUS) of the prostate.

Complications

Complications related to bladder outlet obstruction (BOO) secondary to BPH include the following:

  • Urinary retention
  • Renal insufficiency
  • Recurrent urinary tract infections
  • Gross hematuria
  • Bladder calculi
  • Renal failure or uremia (rare in current practice)
 

DDx

Diagnostic Considerations

Symptoms often attributed to benign prostatic hyperplasia (BPH) can be caused by any of the following conditions:

  • Cystitis

  • Prostatitis

  • Prostatodynia

  • Prostatic abscess

  • Overactive bladder (OAB)

  • Carcinoma of the bladder

  • Foreign bodies in the bladder (stones or retained stents)

  • Urethral stricture due to trauma or a sexually transmitted disease

  • Prostate cancer

  • Neurogenic bladder

  • Pelvic floor dysfunction

Excluding these entities based on findings from a thorough history and appropriately directed diagnostic studies is essential.

Differential Diagnoses

 

Workup

Approach Considerations

The American Urological Association (AUA) has issued a guideline on the management of benign prostatic hyperplasia (BPH), which the AUA validated in 2014. The guideline includes an algorithm for the diagnosis and basic treatment of lower urinary tract symptoms (LUTS), which is presented below.[1]

Basic management of lower urinary tract symptoms ( Basic management of lower urinary tract symptoms (LUTS) in men

The Diagnosis Improvement in PrimAry Care Trial (D-IMPACT), a prospective, multicenter study in three European countries, identified simple tests for primary care practitioners to diagnose BPH in men who present with LUTS. D-IMPACT found that a diagnostic algorithm including only the objective variables of age, International Prostate Symptom Score (IPSS) and prostate-specific antigen level (PSA), allows accurate diagnosis of BPH in approximately three-quarters of patients who report LUTS.[6]

Urinalysis and Urine Culture

Examine the urine using dipstick methods and/or via centrifuged sediment evaluation to assess for the presence of blood, leukocytes, bacteria, protein, or glucose.

A urine culture may be useful to exclude infectious causes of irritative voiding. It is usually performed if the initial urinalysis findings indicate an abnormality.

Prostate-Specific Antigen

Although BPH does not cause prostate cancer, men at risk for BPH are also at risk for prostate cancer and should be screened accordingly. Screening for prostate cancer remains controversial and should done after an informed discussion between the physician and patient.

The current American Cancer Society (ACS) guideline for early detection of prostate cancer stresses the importance of involving men in the decision whether to test for prostate cancer.[7] The ACS notes that PSA testing may reduce the likelihood of dying from prostate cancer but poses serious risks, particularly of treatment of prostate cancer that would not have caused ill effects if left undetected.

The ACS recommends that men receive information about the uncertainties, risks, and potential benefits associated with prostate cancer screening. After this discussion, if the patient wishes to proceed with screening (ie, prostate-specific antigen [PSA] testing and digital rectal examination [DRE] for prostate cancer), the ACS recommends that screening start at the following ages:

  • Age 50 years in men at average risk for prostate cancer who are expected to live at least 10 more years

  • Age 45 years in men at high risk for prostate cancer (African Americans and men with a first-degree relative diagnosed with prostate cancer before age 65)

  • Age 40 years in men at very high risk (those with more than one first-degree relative who had prostate cancer at an early age).

A physician should discuss the risks and benefits of PSA screening with the patient. Notably, men with larger prostates may have slightly higher PSA levels.

Electrolytes, BUN, and Creatinine

These evaluations are useful screening tools for chronic renal insufficiency in patients who have high post-void residual (PVR) urine volumes. A routine serum creatinine measurement is not indicated in the initial evaluation of men with lower urinary tract symptoms (LUTS) secondary to BPH.[1]

Ultrasonography

Ultrasonography (abdominal, renal, transrectal) and intravenous urography are useful for helping determine bladder and prostate size and the degree of hydronephrosis (if any) in patients with urinary retention or signs of renal insufficiency. Generally, they are not indicated for the initial evaluation of uncomplicated LUTS.

A systematic review concluded that patients with suspected large post-void residual volumes should undergo a bladder scan for urine volume to assess for bladder outlet obstruction. Urine volumes measured by bladder scanning correlated highly with urine volumes measured by bladder catheterization.  Symptoms alone proved insufficient for diagnosis, although an International Prostate Symptom Score of 20 or greater increased the likelihood of bladder outlet obstruction.[8]

Transrectal ultrasonography (TRUS) of the prostate is recommended in selected patients, to determine the dimensions and volume of the prostate gland. The success of certain minimally invasive treatments may depend on the anatomical characteristics of the gland. In patients with elevated PSA levels, TRUS-guided biopsy may be indicated to assess for prostate cancer.

Imaging of the upper tracts is indicated in patients who present with any of the following:

  • Concomitant hematuria
  • A history of urolithiasis
  • An elevated creatinine level
  • High PVR volume
  • History of upper urinary tract infection

Other imaging studies, such as CT scanning and MRI, have no role in the evaluation and treatment of uncomplicated BPH.

American Urological Association Guidelines

The American Urological Association (AUA) has developed rigorous clinical practice guidelines for BPH.[1] The AUA guidelines were based on the 1994 evidence-based guidelines for the diagnosis and treatment of BPH originally created under the auspices of the United States Department of Health and Human Services Agency for Health Care Policy and Research.[9] The AUA updated its guidelines in 2006 and 2010, and reviewed and confirmed their validity in 2014.[1]

The AUA 2010 guideline update lowered the age of the Index Patient from age 50 years or older to age 45 years or older. Two algorithms were published: the algorithm for diagnosis and basic management of LUTS in the Approach section above, and an algorithm for detailed management of bothersome LUTS that persists after basic management, shown below.[1]

Benign prostatic hyperplasia (BPH) diagnosis and t Benign prostatic hyperplasia (BPH) diagnosis and treatment algorithm.

These panels have established the following categories to classify diagnostic tests and studies. A recommended test is one that should be performed on every patient, whereas an optional test is of proven value in selected patients.

Recommended tests

A medical history should be taken to qualify and quantify voiding dysfunction. Identification of other causes of voiding dysfunction and medical comorbidities are essential to properly assess the condition and to determine conditions that may complicate treatment.

The physical examination consists of a focused physical examination and a neurologic examination. The physical examination includes a DRE to measure prostate size and to assess for abnormalities. The neurological examination is geared toward lower-extremity neurologic and muscular function, as well as anal sphincter tone. Examination of the phallus and foreskin occasionally reveals meatal stenosis, unretractable foreskin, penile ulcers, or foreign bodies such as warts.

PSA testing should be offered to any patient with a 10-year life expectancy in whom the diagnosis of prostate cancer would change management.

The severity of BPH can be determined with the International Prostate Symptom Score (IPSS)/American Urological Association Symptom Index (AUA-SI) plus a disease-specific quality of life (QOL) question. The AUA-SI for BPH is a set of 7 questions that has been adopted worldwide and yields reproducible and quantifiable information regarding symptoms and response to treatment. Questions concern incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia.

The IPSS uses the same 7 questions as the AUA-SI, with the addition of an eighth question, known as the bother score, which is designed to assess perceived disease-specific QOL. The International Prostate Symptom Score">AUA-SI/IPSS questionnaire is available online. Based on the sum of the score for all 8 questions, patients are classified as 0-7 (mildly symptomatic), 8-19 (moderately symptomatic), or 20-35 (severely symptomatic).

Optional tests

Urine flow rate measurement is useful in the initial assessment and to help determine the response to treatment. It may be performed prior to embarking on any active treatments, including medical treatment.

A maximal flow rate (Qmax) is the single best measurement, but a low Qmax does not help differentiate between obstruction and poor bladder contractility. For more detailed analysis, a pressure-flow study (urodynamic testing) is required. A Qmax value of greater than 15 mL/s is considered by many to be normal. A value of less than 7 mL/s is widely accepted as low.

The results of flow rate measurements are somewhat effort- and volume-dependent. Therefore, the best plan to make a reasonable determination of significance is to obtain at least 2 tracings with at least 150 mL of voided volume each time.

Obtain post-void residual (PVR) urine volume in order to gauge the severity of bladder decompensation. PVR can be determined invasively with a catheter or noninvasively with a transabdominal ultrasonic scanner. A high PVR (ie, 350 mL) may indicate bladder dysfunction and/or bladder outlet obstruction and may predict a poor response to treatment.

Although pressure-flow studies are somewhat invasive, requiring catheterization of the urethra and placement of a transrectal pressure transducer, the findings may prove useful for evaluating for bladder outlet obstruction (BOO).

Urodynamic studies are the only way to help distinguish poor bladder contraction ability (detrusor underactivity) from outlet obstruction. BOO is characterized by high intravesical voiding pressures (>60 cm water) accompanied by low urine flow rates (Qmax < 15 mL/s).

Cytologic examination of the urine may be considered in patients with predominantly irritative voiding symptoms. Risk factors for bladder cancer (smoking, previous bladder cancer) should alert the physician to consider this noninvasive test.

Tests that are not recommended

Routine measurement of serum creatinine is not indicated in the initial evaluation of men with LUTS secondary to BPH.

Endoscopy of the Lower Urinary Tract

Cystoscopy may be indicated in patients scheduled for invasive treatment or in whom a foreign body or malignancy is suspected. In addition, endoscopy may be indicated in patients with a history of sexually transmitted disease (eg, gonococcal urethritis), prolonged catheterization, or trauma. Findings may suggest urethral stricture as the cause of BOO, instead of BPH.

Flexible cystoscopy can be easily performed in several minutes in an office-based setting using topical gel-based intraurethral anesthesia without sedation. The appearance of the gland alone on cystoscopy cannot make the diagnosis of obstruction but can help the clinician decide on treatment modalities if intervention is warranted.

Histologic Findings

BPH is characterized by a varying combination of epithelial and stromal hyperplasia in the prostate. Some cases demonstrate an almost pure smooth-muscle proliferation, although most demonstrate a fibroadenomyomatous pattern of hyperplasia.

In the bladder, obstruction leads to smooth-muscle-cell hypertrophy. Biopsy specimens of trabeculated bladders demonstrate evidence of scarce smooth-muscle fibers with an increase in collagen.

 

Treatment

Approach Considerations

[10] Therapeutic options for benign prostatic hyperplasia (BPH) include the following[1] :

  • Watchful waiting
  • Drug therapy (eg, alpha-blockers, 5-alpha-reductase inhibitors)  – For patients with bothersome, moderate-to-severe lower urinary tract symptoms (LUTS) from BPH 
  • Interventional therapy  (eg,  transurethral resection of the prostate [ TURP])  – For patients with moderate-to-severe LUTS and those who have developed acute urinary retention, or other complications of BPH

Watchful waiting is the recommended strategy for patients with BPH who have mild symptoms (International Prostate Symptom Score/American Urological Association Symptom Index [IPSS/AUA-SI] score ≤7) and for those with moderate-to-severe symptoms (IPSS/AUA-SI score ≥8) who are not bothered by their symptoms and are not experiencing complications of BPH. In those patients, medical therapy is not likely to improve their symptoms and/or quality of life (QOL).

In addition, the risks of treatment may outweigh any benefits in such cases. Patients managed expectantly with watchful waiting are usually re-examined annually.

Metabolic syndrome is associated with a higher prevalence and severity of BPH.[11, 10, 12]  Thus, it may be possible to  postpone the progression of BPH by lowering blood glucose, improving insulin resistance, and reducing inflammation through a healthy lifestyle and clinical treatment.[12]

The era of medical therapy for BPH dawned in the mid 1970s with the use of nonselective alpha-blockers such as phenoxybenzamine. The medical therapeutic options for BPH have evolved significantly since then, with the development of receptor-specific alpha-blockers that comprise current first-line therapy, as well as the approval of 5-alpha-reductase inhibitors.

TURP has long been accepted as the criterion standard for relieving bladder outlet obstruction (BOO) secondary to BPH. In current clinical practice, most patients with BPH do not present with obvious surgical indications; instead, they often have milder lower urinary tract symptoms (LUTS) and, therefore, are initially treated with medical therapy. Several minimally invasive treatments for BOO are also available.

A guideline from the American Urological Association outlines clinical scenarios in which surgery is recommended for LUTS/BPH. The AUA guideline also suggests interventional techniques that can be used as alternatives to TURP (see Guidelines).[1]

Alpha-Blockers

Smooth-muscle tension in the prostate stroma, urethra, and bladder neck is thought to be a significant component of  LUTS secondary to BPH. The smooth-muscle tension is mediated by alpha-1-adrenergic receptors; therefore, alpha-adrenergic receptor–blocking agents should theoretically decrease resistance along the bladder neck, prostate, and urethra by relaxing the smooth muscle, thus allowing easier passage of urine.

An approximately 4- to 6-point improvement is expected in IPSS/AUA-SI scores when alpha-blockers are used. Interestingly, alpha-blocker therapy has not been shown to reduce the overall long-term risk for acute urinary retention (AUR) or need for BPH-related surgery.[13]

The alpha-blocking agents studied in BPH can be subgrouped according to receptor subtype selectivity and the duration of serum elimination half-lives, as follows:

  • Nonselective alpha-blockers - Phenoxybenzamine

  • Selective short-acting alpha-1 blockers - Prazosin, alfuzosin, indoramin

  • Selective long-acting alpha-1 blockers -  Terazosin, doxazosin, slow-release (SR) alfuzosin.

  • Partially subtype (alpha-1a)–selective agents – Tamsulosin (Flomax), silodosin (Rapaflo)

Nonselective alpha-blockers

Phenoxybenzamine was the first alpha-blocker studied for BPH. It is nonselective, antagonizing both the alpha 1- and alpha 2-adrenergic receptors, which results in a higher incidence of adverse effects. Because of the availability of more alpha-1-receptor–specific agents, phenoxybenzamine is no longer often used for the treatment of BPH. The current American Urological Association (AUA) guideline for BPH retains the statement from the 2003 guideline that insufficient data exist for a recommendation of phenoxybenzamine or of prazosin for treatment of LUTS secondary to BPH.[1]

Selective alpha-blockers

The AUA considers alfuzosin, doxazosin, tamsulosin, and terazosin to be appropriate and effective options for treatment of patients with bothersome, moderate-to-severe LUTS secondary to BPH (AUA-SI score ≥8). Although doxazosin and terazosin are older alpha-blockers that require dose titration and blood pressure monitoring, the AUA considers them reasonable choices, as they are inexpensive, are dosed once daily, and appear to be as effective as tamsulosin and alfuzosin.[1]

The efficacy of doxazosin and terazosin is dose-dependent. Maximum tolerable doses have not been defined for any alpha-blocker; however, the higher the dose, the more likely the adverse events (orthostatic hypotension, dizziness, fatigue, ejaculatory disorder, nasal congestion).

Three subtypes of the alpha-1 receptor have been identified: 1a, 1b, and 1c. Of these, the alpha-1a receptor is most specifically concentrated in the bladder neck and prostate. Provided that the alpha-1a subtype is predominant in the prostate, bladder neck, and urethra, but not in other tissues, drugs that are selective for this receptor may offer a potential therapeutic advantage.

Two alpha-1a receptor–selective blockers are currently available for symptomatic treatment of BPH: tamsulosin and silodosin. The AUA guidelines do not include recommendations regarding silodosin, as no relevant studies had yet been published in the peer-reviewed literature at the time of its review.[1]  A more recent Cochrane systematic review, while noting limitations in the available evidence, concluded that the efficacy of silodosin appears similar to that of tamsulosin, naftopidil, and alfuzosin, but the rate of sexual side effects is likely higher.[14]  

Hellstrom and Sikka reported that the acute administration of tamsulosin affects ejaculatory function and ejaculate volume. Nearly 90% of study subjects experienced decreased ejaculate volume, and approximately 35% experienced anejaculation. In their study, subjects treated with alfuzosin or placebo did not experience anejaculation.[15]  A randomized controlled trial by Pande et al that compared silodosin with tamsulosin in 53 men with BPH found that the two drugs have comparable efficacy; however, retrograde ejaculation was encountered only with silodosin and postural hypotension only with tamsulosin.[16]

Intraoperative floppy iris syndrome

Intraoperative floppy iris syndrome (IFIS) is characterized by miosis, iris billowing, and prolapse in patients undergoing cataract surgery who have taken or currently take alpha-1-blockers. It is particularly prevalent among patients taking tamsulosin. The AUA recommends that clinicians ask patients about planned cataract surgery when offering alpha-blocker therapy for LUTS due to BPH. Alpha-blockers should not be initiated until cataract surgery is completed.[1]  Patients currently on alpha-blocker therapy must disclose this to their ophthalmologist prior to cataract surgery so that the appropriate preoperative and intraoperative precautions can be taken. Experienced ophthalmologists can thereby reduce the risk of complications from IFIS.[17, 1]

In a review by Bell et al, exposure to tamsulosin within 14 days of cataract surgery was significantly associated with serious postoperative ophthalmic adverse events, specifically IFIS and its complications (ie, retinal detachment, lost lens or fragments, endophthalmitis). No significant associations were noted with exposure to other alpha-blocker medications or to previous exposure to tamsulosin or other alpha-blockers.[18]

5-Alpha-Reductase Inhibitors

Two 5-alpha-reductase inhibitors (5-ARIs) are approved for use in BPH: finasteride (Proscar) and dutasteride (Avodart). American Urological Association (AUA) guidelines advise that in men with lower urinary tract symptoms (LUTS) and enlarged prostates, 5-ARIs may help prevent progression of LUTS secondary to BPH and reduce the risk of urinary retention and future prostate-related surgery. The AUA notes that prostatic enlargement can be determined by volume measurement, prostate-specific antigen (PSA) l level as a proxy for volume, and/or digital rectal examination.[1]

Unlike alpha-blockers, which work by reducing smooth muscle tone, 5-ARIs improve LUTS by reducing prostate volume. Thus, patients with larger prostates may achieve a greater benefit. Maximal reduction in prostate volume requires 6 months of therapy.

The role of 5-ARIs in medical management of BPH emerged from the discovery of a congenital form of pseudohermaphroditism secondary to dihydrotestosterone (DHT) deficiency, which results from a lack of 5-alpha-reductase activity. This deficiency produced a hypoplastic prostate. The two types of 5-alpha-reductase include type 1 (predominantly located in extraprostatic tissues, such as skin and liver) and type 2 (predominantly prostatic reductase).

Inhibition of 5-alpha-reductase type 2 blocks the conversion of testosterone to DHT, resulting in lower intraprostatic levels of DHT. This leads to inhibition of prostatic growth, apoptosis, and involution. The exact role of 5-alpha-reductase type 1 in normal and abnormal prostatic development is undefined.

Finasteride, a 4-aza-steroid, has demonstrated 5-alpha type II–blocking activity, resulting in the inhibition of DHT-receptor complex formation. This effect causes a profound decrease in the concentration of DHT intraprostatically, resulting in a consistent decrease in prostate size. One third of men treated with this agent exhibit improvements in urine flow and symptoms.

In the Proscar Long-Term Efficacy and Safety Study (PLESS), patients treated with finasteride (5 mg/d) were at a significantly lower risk of developing acute urinary retention or needing surgery.[19]  This was a multicenter, 4-year, double-blind, placebo-controlled study of 3,040 patients. Men with PSA levels of more than 10 ng/mL and those with prostate cancer were excluded.

Dutasteride has an affinity for both type 1 and type 2 5-alpha-reductase receptors. The significance of blockage of type 1 receptors is currently unknown.

Both finasteride and dutasteride actively reduce DHT levels by more than 80%, improve symptoms, reduce the incidence of urinary retention, and decrease the likelihood of surgery for BPH. Adverse effects are primarily sexual in nature (decreased libido, erectile dysfunction, ejaculation disorder).

Both finasteride and dutasteride may reduce serum PSA values by as much as 50%. The decrease in PSA is typically maximally achieved when the maximal decrease in prostatic volume is noted (6 months). This effect must be taken into account when using PSA to screen for prostate cancer.

A prospective, randomized, double-blind study, the Enlarged Prostate International Comparator Study (EPICS), was conducted to compare the efficacy of dutasteride with that of finasteride in men with symptomatic BPH. Although this study was conducted over the course of only 1 year, the data suggest that both drugs were similarly effective in reducing prostate volume and improving maximum urinary flow rate (Qmax) and LUTS for this population. The long-term outcomes are yet to be investigated.[20]

Because 5-ARIs interfere with the metabolism of testosterone, pregnant females or those who are considering conception should not handle crushed or broken tablets because of the potential for absorption and subsequent potential risk to a male fetus.

5-alpha reductase inhibitors and prostate cancer

On June 9, 2011, the US Food and Drug Administration (FDA) announced revisions to the prescribing information for 5-ARIs. The FDA advised that prior to initiating therapy with 5-ARIs, clinicians should perform appropriate evaluations to rule out other urological conditions, including prostate cancer, that might mimic BPH.

The FDA's action was based on findings from 2 large, randomized, controlled trials of 5-ARIs for prostate cancer prevention, which reported that trial participants taking 5-ARIs had an increased risk of being diagnosed with a more serious form of prostate cancer (high-grade prostate cancer). Both trials—the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial—observed a decreased incidence of prostate cancer overall when preventive treatment included 5-ARIs, but an increased incidence of high-grade prostate cancer in men taking dutasteride or finasteride compared with placebo.[21, 22]

In contrast, a 2015 retrospective cohort study conducted in 13,892 men with a new diagnosis of prostate cancer found that use of 5-ARIs before prostate cancer diagnosis was not associated with an increased risk of prostate cancer-specific mortality (adjusted hazard ratio, [aHR] 0.86) or all-cause mortality (aHR, 0.87). The researchers cite the need for additional studies to replicate these findings.[23]

Combination Therapy

American Urological Association (AUA) guidelines advise that combination therapy with an alpha-blocker and a 5-alpha-reductase inhibitor can be appropriate and effective for patients with lower urinary tract symtpoms (LUTS) who have enlarged prostates.[1] The alpha-1-receptor blocker provides rapid relief, while the 5-alpha-reductase inhibitor targets the underlying disease process.[13, 24]  A fixed-dose combination capsule of tamsulosin 0.4 mg and dutasteride 0.5 mg (Jalyn) is approved by the US Food and Drug Administration (FDA) in 2010 for treatment of symptomatic BPH in men with an enlarged prostate.

Landmark clinical trials

The Medical Therapy of Prostatic Symptoms (MTOPS) trial demonstrated that combination therapy reduced the risk of progression and produced a greater improvement in IPSS than therapy with finasteride or doxazosin alone. The risks of acute urinary retention (AUR) and BPH-related surgery were reduced with combination therapy or finasteride in comparison with doxazosin monotherapy.[25]

The Symptom Management After Reducing Therapy (SMART-1) trial demonstrated that after 6 months of combination therapy, discontinuation of the alpha-1-blocker is possible in men with moderate LUTS. However, those with severe LUTS may require longer combination therapy.[25]

The Medical Therapy of Prostatic Symptoms (MTOPS) trial demonstrated that combination therapy with doxazosin and finasteride was well tolerated, and was superior to placebo and monotherapy with either agent. The primary endpoints of the study were reduction in AUA-SI score, AUR, recurrent infections, renal insufficiency, incontinence, changes in flow, and PSA level and a lower rate of invasive treatments. MTOPS was a multicenter, 4- to 6-year, double-blind, randomized, placebo-controlled trial of 3,047 men with symptomatic BPH.[26]

Four-year results in the Combination of Avodart and Tamsulosin (CombAT) study revealed that for men with prostate volumes of 30-58 mL, combination therapy with dutasteride (dual 5-alpha-reductase inhibitor) and tamsulosin (alpha-1-blocker) improved symptoms, urinary flow, and QOL better than monotherapy with either drug, although not in men who had a prostate volume of 58 mL or more.[27] The adverse-effect profile of combination therapy was similar to that of monotherapy, although drug-related adverse events were more common with combination therapy.[28]  

CombAT was a 4-year, multicenter, randomized, double-blind, parallel group study of 4,844 men aged 50 years or older with moderate-to-severe BPH symptoms (IPSS ≥12), prostate volume of 30 mL or greater, and a PSA level of 1.5-10 ng/mL. This study contributed to the standard of care shifting towards combined drug therapy in appropriately selected patients, while better defining the role of the alpha-blockers.[29]

Phosphodiesterase-5 Enzyme Inhibitors

Phosphodiesterase-5 (PDE5) inhibitors are known to mediate smooth muscle relaxation in the lower urinary tract. The long-acting PDE5 inhibitor tadalafil (Cialis) has been shown to be significantly better than placebo in improving the symptoms of BPH/LUTS.[30, 31]  Tadalafil is approved for treatment of the signs and symptoms of BPH, used alone or with finasteride (tadalafil 5 mg plus finasteride 5 mg orally, once daily for 26 weeks or less. Tadalifil is also approved for daily use in patients with both BPH and erectile dysfunction (ED).

In patients with BPH who also have ED, the alpha-1 blocker dose should be established first, before treating the ED. The medication used to treat ED should be titrated to the lowest effective dose. If sildenafil is used, doses of greater than 25 mg should not be taken within 4 hours of any alpha-blocker.[32, 33, 34]

 

 

Anticholinergic Agents

Historically, anticholinergics were discouraged in men with BPH because of concerns of inducing urinary retention. Trials in patients with BPH have demonstrated a slight increase in post-void residual (PVR) urine volume with the use of anticholinergics; however, acute urinary retention rates were low. Importantly, these trials consisted of patients with low baseline PVR.

The American Urological Association BPH guidelines recommend anticholinergic agents for management of LUTS in patients who do not have an elevated PVR volume and whose LUTS are primarily irritative. Baseline PVR should be measured prior to initiation of anticholinergic therapy, to assess for urinary retention.[29]  Caution with anticholinergics is recommended with patients whose PVR is greater than 250-300 mL.[1]

Phytotherapeutic Agents and Dietary Supplements

A number of  herbal formulations and plant-derived compounds have gained popularity worldwide for the management of BPH.[35] Phytotherapeutic agents and dietary supplements are considered emerging therapy by the AUA Guidelines panel and are not recommended for the treatment of BPH because of the lack of evidence at this time.

Pharmaceuticals derived from plant extracts are widely used throughout the world for the treatment of various medical ailments. In 1998, Americans spent a total of $3.65 billion on all herbal remedies. In France and Germany, plant extracts have a market share of up to 50% of all drugs prescribed for symptomatic BPH. In the United States, these agents are also popular and readily available.

The attraction to phytotherapeutic agents appears to be related to the perception of therapeutic healing powers of natural herbs, the ready availability, and the lack of adverse effects.

Most of the phytotherapeutic agents used in the treatment of LUTS secondary to BPH are extracted from the roots, seeds, bark, or fruits of plants listed below. Some suggested active components include phytosterols, fatty acids, lectins, flavonoids, plant oils, and polysaccharides. Some preparations derive from a single plant; others contain extracts from 2 or more sources.

Each agent has one or more proposed modes of action. The following modes of action are suggested:

  • Antiandrogenic effect

  • Antiestrogenic effect

  • Inhibition of 5-alpha-reductase

  • Blockage of alpha receptors

  • Antiedematous effect

  • Anti-inflammatory effect

  • Inhibition of prostatic cell proliferation

  • Interference with prostaglandin metabolism

  • Protection and strengthening of detrusor

The origins of phytotherapeutic agents are as follows:

  • Saw palmetto, (American dwarf palm; Serenoa repens, Sabal serrulata) fruit

  • South African star grass (Hypoxis rooperi) roots

  • African plum tree (Pygeum africanum) bark

  • Stinging nettle (Urtica dioica) roots

  • Rye (Secale cereale) pollen

  • Pumpkin (Cucurbita pepo) seeds

Saw palmetto (American dwarf palm)

Extracts of saw palmetto berries are the most popular botanical products for BPH. The active components are believed to be a mixture of fatty acids, phytosterols, and alcohols. The proposed mechanisms of action are antiandrogenic effects, 5-alpha-reductase inhibition, and anti-inflammatory effects.

The recommended dosage is 160 mg orally twice daily. Studies show significant subjective improvement in symptoms without objective improvements in urodynamic parameters. Minimal adverse effects include occasional GI discomfort.

The 2010 AUA guidelines, based on more recent studies, do not detect a clinically meaningful effect of saw palmetto on LUTS. Further clinical trials are underway.[1] In fact, in a double-blind, multicenter, placebo-controlled randomized trial at 11 North American clinical sites, saw palmetto extract was studied at up to 3 times the standard dose on lower urinary tract symptoms attributed to BPH. Saw palmetto extract was no more effective than placebo on the American Urological Association Symptom Index. No clearly attributable adverse effects were identified. Similar to the Saw Palmetto Treatment for Enlarged Prostates (STEP) study, saw palmetto was not found to be beneficial for the treatment of LUTS in men.[36]

African plum tree (Pygeum africanum)

Suggested mechanisms of action include inhibition of fibroblast proliferation and anti-inflammatory and antiestrogenic effects. This extract is not well studied.

Rye (Secale cereale)

This extract is made from pollen taken from rye plants growing in southern Sweden. Suggested mechanisms of action involve alpha-blockade, prostatic zinc level increase, and 5-alpha-reductase activity inhibition. Significant symptomatic improvement versus placebo has been reported.

Pumpkin seeds (Cucurbita pepo)

Observational studies, retrospective surveys, and randomized controlled trials have provided evidence that pumpkin seeds may reduce urinary urgency and frequency in men with LUTS related to BPH. Adverse effects are mild. Suggested mechanisms of action include increased prostaglandin synthesis, due to their high amounts of linoleic acid, and anti-inflammatory effects from gamma-tocopherol and nitric acid precursors.[37]

 

Transurethral Resection of the Prostate

TURP is considered the criterion standard for relieving BOO secondary to BPH. The indications to proceed with a surgical intervention include the following:

  • Acute urinary retention
  • Failed voiding trials
  • Recurrent gross hematuria
  • Urinary tract infection
  • Renal insufficiency secondary to obstruction

Additional indications for surgical intervention include failure of medical therapy, a desire to terminate medical therapy, and/or financial constraints associated with medical therapy. However, TURP carries a significant risk of morbidity (18%) and a slight mortality risk (0.23%).

TURP is performed with regional or general anesthesia and involves the placement of a working sheath in the urethra through which a hand-held device with an attached wire loop is placed. High-energy electrical cutting current is run through the loop so that the loop can be used to shave away prostatic tissue. The entire device is usually attached to a video camera to provide vision for the surgeon.

Although TURP is often successful, it has some drawbacks. When prostatic tissue is cut away, significant bleeding may occur, possibly resulting in termination of the procedure, blood transfusion, and a prolonged hospital stay. Patients are usually monitored overnight and discharged the following morning, with or without a  urinary catheter.

Irrigating fluid may also be absorbed in significant quantities through veins that are cut open, with possible serious sequelae termed transurethral resection (TUR) syndrome. However, this is very rare and does not occur with saline irrigation used in bipolar devices. A urinary catheter must be left in place until the bleeding has mostly cleared.

The large working sheath combined with the use of electrical energy may also result in stricturing of the urethra.

The cutting of the prostate may also result in a partial resection of the urinary sphincteric mechanism, causing the muscle along the bladder outlet to become weak or incompetent. As a result, when the patient ejaculates, this sphincteric mechanism cannot keep the bladder adequately closed. The ejaculate consequently goes backwards into the bladder (ie, retrograde ejaculation), rather than out the penis. Additionally, if the urinary sphincter is damaged, urinary incontinence may result.

The nerves associated with erection run along the outer rim of the prostate, and the high-energy current and/or the heat it generates may damage these nerves, resulting in impotence.

Minimally Invasive Treatment

There is considerable interest in the development of other therapies to decrease the amount of obstructing prostate tissue while avoiding the above-mentioned adverse effects associated with TURP. These therapies are collectively called minimally invasive therapies.

Most minimally invasive therapies rely on heat to destroy prostatic tissue. This heat is delivered in a limited and controlled fashion, in the hope of avoiding the complications associated with TURP. They also allow for the use of milder forms of anesthesia, which translates into less anesthetic risk for the patient.

Heat may be delivered in the form of laser energy, microwaves, radiofrequency energy, high-intensity ultrasound waves, and high-voltage electrical energy. As in TURP, delivery devices are usually passed through a working sheath placed in the urethra, although they are usually of a smaller size than that needed for TURP. Devices may also simply be attached or incorporated into a urinary catheter or passed through the rectum, from which the prostate may also be accessed.

Keep in mind that many of these minimally invasive therapies are undergoing constant improvements and refinements, resulting in increased efficacy and safety. Ask urologists about the specifics of the minimally invasive therapies that they use and what results they have experienced.

Transurethral Incision of the Prostate

Transurethral incision of the prostate (TUIP) has been in use for many years and, for a long time, was the only alternative to TURP. It may be performed with local anesthesia and sedation. TUIP is suitable for patients with small prostates and for patients unlikely to tolerate TURP well because of other medical conditions. TUIP is associated with less bleeding and fluid absorption than TURP. It is also associated with a lower incidence of retrograde ejaculation and impotence than TURP.

Lasers

Lasers deliver heat to the prostate in various ways. Lasers heat prostate tissue, causing tissue death by coagulative necrosis, with subsequent tissue contraction; however, laser coagulation of the prostate in this specific sense has met with limited results.

Lasers have also been used to directly evaporate, or to melt away, prostate tissue, which is more effective than laser coagulation. Photoselective vaporization of the prostate produces a beam that does not directly come into contact with the prostate; rather, it delivers heat energy into the prostate, resulting in destruction/ablation of the prostate tissue.

Potassium-titanyl-phosphate (KTP) and holmium lasers are used to cut and/or enucleate the prostate, similar to the TURP technique. These are widely used laser techniques.

Transurethral vaporization/ablation with the KTP or holmium laser can be performed with general or spinal anesthesia and can be performed in an outpatient setting. Catheter time usually lasts less than 24 hours. Studies suggest that photoselective vaporization of the prostate can significantly improve and sustain symptomatic and urodynamic outcomes.

This procedure has been quite useful in patients who require anticoagulation for various medical conditions, since anticoagulation does not need to be interrupted for this procedure, thus further decreasing patient risk.[38, 39]

Lasers may be used in a knifelike fashion to directly cut away prostate tissue (ie, holmium laser enucleation of the prostate), similar to a TURP procedure. The holmium laser allows for simultaneous cutting and coagulation, making it quite useful for prostate resection. Laser enucleation of the prostate has proved to be safe and effective for treatment of symptomatic BPH, regardless of prostate size, with low morbidity and short hospital stay.

TUR syndrome is not seen with this technique, because iso-osmotic saline is used for irrigation. Additionally, removed prostatic tissue is available for histologic evaluation, whereas vaporization/ablation technique does not provide tissue for evaluation. Holmium laser enucleation of the prostate may prove to be the new criterion standard for surgical management of BPH.[39, 40]

Laser treatment usually results in decreased bleeding, fluid absorption, and length of hospital stay, as well as decreased incidence of impotence and retrograde ejaculation when compared with standard TURP. However, healing from laser treatment does not occur until after a period when dead cells slough; thus, patients may experience urinary urgency or irritation, resulting in frequent or uncomfortable urination for a few weeks.

The results of laser therapy vary from one another because not all wavelengths yield the same tissue effects. For example, interstitial lasers (eg, indigo lasers) are designed to heat tissue within the confines of the prostate gland and spread radiant energy at relatively low energy levels. They do not directly involve the urethral portion; thus, irritative symptoms following the procedure are potentially reduced.

Contact lasers such as KTP or holmium, on the other hand, are designed to cut and vaporize at extremely high temperatures They usually bring about more relief of urinary symptoms than treatment with medicines, but not always as much as is provided with TURP. However, KTP laser vaporization and holmium laser enucleation yield results that rival those of TURP.

Transurethral Microwave Therapy

The use of microwave energy, termed transurethral microwave therapy (TUMT), delivers heat to the prostate via a urethral catheter or a transrectal route. The surface closest to the probe (the rectal or urethral surface) is cooled to prevent injury. The heat causes cell death, with subsequent tissue contraction, thereby decreasing prostatic volume.

TUMT can be performed in the outpatient setting with local anesthesia. Microwave treatment appears to be associated with significant prostatic swelling; a considerable number of patients require a urinary catheter until the swelling subsides. In terms of efficacy, TUMT places between medical therapy and TURP. The 2018 AUA guideline states that TUMT may be offered, but patients should be informed that surgical retreatment rates are higher with TUMT than with TURP.[1]

Transurethral Needle Ablation of the Prostate

Transurethral needle ablation of the prostate (TUNA) involves using high-frequency radio waves to produce heat, resulting in a similar process of thermal injury to the prostate as previously described. A specially designed transurethral device with needles is used to deliver the energy.

TUNA can be performed under local anesthesia, allowing the patient to go home the same day. Similar to microwave treatment, radiofrequency treatment is quite popular, and a number of urologists have experience with its use. Radiofrequency treatment appears to reliably result in significant relief of symptoms and better urine flow, although not quite to the extent achieved with TURP. The 2018 AUA guideline does not recommend TUNA for the treatment of BPH.[1]

High-Intensity Ultrasound Energy Therapy

High-intensity ultrasound energy therapy delivers heat to prostate tissue, with the subsequent process of thermal injury. High-intensity ultrasound waves may be delivered rectally or extracorporeally and can be used with the patient on intravenous sedation. Urinary retention appears to be common with its use.

High-intensity ultrasound energy also produces moderate results in terms of improvement of the urinary flow rate and urinary symptoms, although its use is now relatively limited compared with the more popular TUNA and TUMT.

High-intensity ultrasound is considered investigational at this time and should not be offered outside of clinical trials.

Radiofrequency-generated Water Thermotherapy

The Rezum system (NxThera, Inc, Maple Grove MN) uses radiofrequency energy to turn sterile water into vapor or steam, which is convectively delivered directly into the obstructive prostate tissue.[41] The Rezum procedure has been approved by the FDA for treatment of BPH, and the AUA considers the procedure a viable treatment for BPH (ie, neither investigational nor experimental).

Mechanical Approaches

Mechanical approaches are used less commonly and are usually reserved for patients who cannot have a formal surgical procedure. Mechanical approaches do not involve the use of energy to treat the prostate.

Prostatic stents are flexible devices that can expand when put in place to improve the flow of urine past the prostate. Complications associated with their use include encrustation, pain, incontinence, and overgrowth of tissue through the stent, possibly making their removal quite difficult.

In September 2013, the FDA authorized the marketing of the first permanent implant to relieve low or blocked urine flow in men aged 50 years and older with an enlarged prostate. The UroLift system (NeoTract Inc) relieves urine flow by pulling back prostate tissue that is pressing on the urethra. Approval was based on 2 studies of 274 men with BPH implanted with 2 or more UroLift sutures.[42] The UroLift was successfully inserted in 98% of participants, and a 30% increase in urine flow and a steady amount of residual urine in the bladder was observed. Patients reported fewer symptoms and improved quality of life in the 2 years following device implantation.

Prostatic Artery Embolization

The incidental discovery that the use of selective prostatic arty embolization (PAE) to control bleeding secondary to BPH resulted in improved LUTS led to investigation of its direct use in the relief of LUTS in patients with BPH. Although a growing body of evidence supports its safety and efficacy, PAE has yet to be established as a standard-of-care treatment option.[43, 44] A systematic review that included 16 studies concluded that PAE should still be considered experimental.[45]

Open Prostatectomy

Open prostatectomy is now reserved for patients with any of the following:

  • A very large prostate (>75 g)
  • Concomitant bladder stones or bladder diverticula
  • INability to be positioned for transurethral surgery.

Open prostatectomy requires hospitalization and involves the use of general/regional anesthesia and a lower abdominal incision. The inner core of the prostate (adenoma), which represents the transition zone, is shelled out, thus leaving the peripheral zone behind. This procedure may involve significant blood loss, necessitating transfusion. Open prostatectomy usually has an excellent outcome in terms of improvement of urinary flow and urinary symptoms.

More recently, laparoscopic simple prostatectomy has been performed at a number of institutions and appears to be feasible. However, prostatectomy performed in this fashion still appears to be associated with risk for significant blood loss. Experience to date with this procedure is limited.[46]

Long-term Monitoring

Patients with BPH who have symptoms significant enough to be placed on medication should be evaluated during office visits to discuss the efficacy of the medication and potential dose adjustment. These visits should take place at least biannually. Patients should undergo prostate cancer screening at least annually.

Prevention

Data from the Prostate Cancer Prevention Trial revealed that a diet low in fat and red meat and high in protein and vegetables may reduce the risk of symptomatic BPH. Additionally, regular alcohol consumption was associated with a reduced risk of symptomatic BPH, but this is to be interpreted cautiously, given the untoward effects of excessive alcohol consumption.[47]

 

Guidelines

Guidelines Summary

The American Urological Association (AUA) updated its guideline on  surgical management of lower urinary tract symptoms (LUTS) attributed to benign prostatic hyperplasia iBPH) in 2018. Recommendations are listed below; unless otherwise specified, recommendations are based on clinical principles.[1]

Evaluation and Preoperative Testing

The initial evaluation of patients presenting with bothersome LUTS possibly attributed to BPH should include the following:

  • Medical history, utilizing the AUA-Symptom Index (AUA-SI)
  • Urinalysis
  • Select patients may also require post-void residual (PVR), uroflowmetry, or pressure flow studies.

Prior to surgical intervention for LUTS attributed to BPH, clinicians should do the following:

  • Consider assessment of prostate size and shape via abdominal or transrectal ultrasound, or cystoscopy, or by preexisting cross-sectional imaging (ie, magnetic resonance imaging [MRI]/ computed tomography [CT])
  • Perform a PVR assessment 
  • Consider uroflowmetry
  • Consider pressure flow studies, when diagnostic uncertainty exists. (Expert Opinion)

Surgical Therapy

Surgery is recommended for patients with any of the following resulting from BPH:

  • Renal insufficiency
  • Refractory urinary retention
  • Recurrent urinary tract infections (UTIs)
  • Recurrent bladder stones or gross hematuria
  • LUTS, in patients unresponsive to, or unwilling to use, other therapies

Clinicians should not perform surgery solely for an asymptomatic bladder diverticulum. However, evaluation for bladder outlet obstruction should be considered. 

Surgical approaches for men with LUTS attributed to BPH are listed below.

Transurethral resection of the prostate (TURP):

  • Offer TURP as a treatment option. (Moderate Recommendation; Evidence Level: Grade B)
  • Use a monopolar or bipolar approach to TURP, depending on clinician expertise with these techniques. (Expert Opinion)

Simple prostatectomy:

  • In patients with large prostates, consider open, laparoscopic or robotic assisted prostatectomy, depending on clinician expertise with these techniques (Moderate Recommendation; Evidence Level: Grade C)

Transurethral incision of the prostate (TUIP):

  • Offer TUIP as an option for patients with prostates ≤30 g. (Moderate Recommendation; Evidence Level: Grade B)

Transurethral vaporization of the prostate (TUVP):

  • Bipolar TUVP may be offered. (Conditional Recommendation; Evidence Level: Grade B)

Photoselective vaporization of the prostate (PVP):

  • Consider PVP as an option using 120W or 180W platforms. (Moderate Recommendation; Evidence Level: Grade B)

Prostatic urethral  lift (PUL):

  • Clonsider PUL as an option in patients with prostate volume < 80 g and verified absence of an obstructive middle lobe; however, patients should be informed that symptom reduction and flow rate improvement is less significant than with TURP. (Moderate Recommendation; Evidence Level: Grade C)
  • PUL may be offered to eligible patients concerned with erectile and ejaculatory function. (Conditional Recommendation; Evidence Level: Grade C)

Transurethral microwave therapy (TUMT):

  • TUMT may be offered, but patients should be informed that surgical retreatment rates are higher with TUMT than with TURP. (Conditional Recommendation; Evidence Level: Grade C)

Water vapor thermal therapy:

  • Water vapor thermal therapy may be offered if prostate volume is < 80 g; however, patients should be informed that evidence of efficacy, including longer-term retreatment rates, remains limited. (Conditional Recommendation; Evidence Level: Grade C)
  • Water vapor thermal therapy may be offered to eligible patients who desire preservation of erectile and ejaculatory function. (Conditional Recommendation; Evidence Level: Grade C)

Transurethral needle ablation (TUNA):

  • TUNA is not recommended. (Expert Opinion)

Laser enucleation:

  • Consider holmium laser enucleation of the prostate (HoLEP) or thulium laser enucleation of the prostate (ThuLEP), depending on clinician expertise with either technique, as prostate size–independent treatment options . (Moderate Recommendation; Evidence Level: Grade B)

Prostate artery embolization (PAE):

  • PAE is not recommended outside the context of a clinical trial. (Expert Opinion)

Medically Complicated Patients

HoLEP, PVP, and ThuLEP should be considered in patients who are at higher risk of bleeding, such as those on anticoagulant drugs. (Expert Opinion)

 

Medication

Medication Summary

The goals of pharmacotherapy for benign prostatic hypertrophy (BPH) are to reduce morbidity and to prevent complications. The agents used include alpha-adrenergic blockers, 5-alpha-reductase inhibitors, phosphodiesterase-5 enzyme inhibitors, and various combinations.

Alpha-Adrenergic Blockers

Class Summary

These agents block effects of postganglionic synapses at the smooth muscle and exocrine glands.

Phenoxybenzamine (Dibenzyline)

Phenoxybenzamine is a nonselective alpha-adrenergic receptor blocker that antagonizes both alpha-1 and alpha-2 receptors. This nonselectivity leads to a higher incidence of adverse effects, which has led to decreased use of this agent in clinical settings. Phenoxybenzamine induces subjective improvement in urinary flow rates when compared with placebo. It may improve daytime and nighttime urinary frequency. Symptoms improve in 75% of patients.

Prazosin (Minipress)

Prazosin is currently approved for the treatment of hypertension. Prazosin improves urine flow rates by relaxing smooth muscle. Relaxation is produced by blocking alpha-1 adrenoreceptors in the bladder neck and prostate. The advantage of prazosin over nonselective alpha-adrenergic blockers includes a lower incidence of adverse effects. Because of availability of longer-acting, once-daily selective agents, however, the clinical utility of prazosin for BPH has been reduced.

Prazosin improves urinary flow rate and frequency of micturition. Subjective improvement is observed in 82% of patients treated. When increasing dosages, administer the first dose of each increment at bedtime to reduce syncopal episodes. Although doses above 20 mg/d do not usually increase efficacy, some patients may benefit from up to 40 mg/d.

Alfuzosin (UroXatral)

Alfuzosin is indicated for the treatment of the signs and symptoms of BPH. Alfuzosin is an alpha-1 blocker of adrenoreceptors in the prostate. Blockade of adrenoreceptors may cause smooth muscles in the bladder neck and prostate to relax, resulting in improvement in urine flow rate and reduction in symptoms of BPH.

Indoramin

This agent is not available in the United States. Indoramin improves urine flow rates by blocking alpha-1 adrenoreceptors in the bladder neck and prostate, thus relaxing smooth muscle in those sites. Indoramin also reduces the frequency of micturition.

The advantage of indoramin over nonselective alpha-adrenergic blockers includes lower incidence of adverse effects. Because of availability of longer-acting, once-daily selective agents, clinical utility of this agent for BPH has been reduced.

Terazosin (Hytrin)

Terazosin is a quinazoline compound that counteracts alpha1-induced adrenergic contractions of bladder neck, facilitating urinary flow in the presence of BPH. It is indicated for the treatment of symptomatic BPH and hypertension. Its effect on voiding symptoms and flow rates is dose-dependent. It improves irritative and obstructive voiding symptoms. Improvement in flow rate is objective. A Hytrin starter pack is available for easy dosing progression to 5 mg.

Doxazosin (Cardura, Cardura XL)

Doxazosin is indicated for the treatment of urinary outflow obstruction and irritative symptoms associated with BPH and hypertension. It inhibits postsynaptic alpha-adrenergic receptors, resulting in vasodilation of veins and arterioles and a decrease in total peripheral resistance and blood pressure. It is a long-acting alpha1-blocking agent with a profile similar to that of terazosin. Doxazosin improves irritative and obstructive voiding symptoms.

Tamsulosin (Flomax)

Tamsulosin is indicated for the treatment of the signs and symptoms of BPH. It is an alpha-adrenergic blocker specifically targeted to alpha-1 receptors. Tamsulosin has the advantage of producing relatively less orthostatic hypotension; it requires no gradual up-titration from the initial dosage. It inhibits postsynaptic alpha-adrenergic receptors, resulting in vasodilation of veins and arterioles and a decrease in total peripheral resistance and blood pressure. It improves irritative and obstructive voiding symptoms.

Silodosin (Rapaflo)

Silodosin is indicated for the treatment of the signs and symptoms of BPH. Silodosin selectively antagonizes postsynaptic alpha1-adrenergic receptors in the prostate, bladder base, prostatic capsule, and prostatic urethra. This action induces smooth muscle relaxation and improves urine flow.

5-Alpha-Reductase Inhibitors

Class Summary

These agents are used to treat symptomatic BPH in men with an enlarged prostate. They inhibit the conversion of testosterone to DHT, causing DHT levels to drop, which, in turn, may decrease prostate size.[48, 49]

Finasteride (Proscar)

Finasteride is indicated for the treatment of symptomatic BPH in men with an enlarged prostate. When combined with doxazosin, it can also reduce the risk of symptomatic progression of BPH. Finasteride inhibits conversion of testosterone to DHT, causing serum DHT levels to decrease. It is beneficial in men with prostates larger than 40 g and can improve symptoms and reduce prostatic size by 20-30%. Reduction in prostate size is sustained for 5 years following treatment. Finasteride improves urinary flow rate by 2 mL/s.

Dutasteride (Avodart)

Dutasteride is indicated for the treatment of BPH as monotherapy or in combination with tamsulosin. Dutasteride improves symptoms, reduces urinary retention, and may decrease the need for BPH-related surgery. It inhibits 5alpha-reductase isoenzymes types I and II. This agent suppresses conversion of testosterone to DHT by more than 95%, causing serum DHT levels to decrease.

Phosphodiesterase-5 Enzyme Inhibitors

Class Summary

These agents mediate smooth muscle relaxation in the lower urinary tract, thus improving the symptoms of BPH.

Tadalafil (Cialis)

PDE5 selective inhibitor. Inhibition of PDE5 increases cGMP activity, which increases vasodilatory effects of nitric oxide. Sexual stimulation is necessary to activate response. Tadalafil has been approved by the FDA for the treatment of BPH signs and symptoms.

PDE5 inhibition has been shown to induce smooth muscle relaxation in the lower urinary tract. It has also been approved for the treatment of simultaneous BPH and ED.

Increased sensitivity for erections may last 36 h with intermittent dosing. Low-dose daily dosing may be recommended for more frequent sexual activity (ie, twice weekly); men can attempt sexual activity at anytime between daily doses.

Combination Products

Class Summary

Various combination products are emerging on the market to improve patient compliance and symptoms.

Dutasteride and tamsulosin (Jalyn)

The combination of dutasteride, a 5-alpha-reductase inhibitor, and tamsulosin, an alpha-adrenergic antagonist is indicated for benign prostatic hypertrophy in men with an enlarged prostate. Each cap contains dutasteride 0.5 mg and tamsulosin 0.4 mg.

 

Questions & Answers

Overview

What is benign prostatic hyperplasia (BPH)?

What are the symptoms of benign prostatic hyperplasia (BPH)?

What is the role of digital rectal exam (DRE) in the diagnosis of benign prostatic hyperplasia (BPH)?

Which lab studies are indicated in the workup of benign prostatic hyperplasia (BPH)?

What is the role of ultrasonography in the workup of benign prostatic hyperplasia (BPH)?

Which procedures are indicated in the workup of benign prostatic hyperplasia (BPH)?

How is the severity of benign prostatic hyperplasia (BPH) determined?

What other tests are used in the diagnosis of benign prostatic hyperplasia (BPH)?

Which drugs are used in the treatment of benign prostatic hyperplasia (BPH)?

Which surgical procedures are used in the treatment of benign prostatic hyperplasia (BPH)?

What minimally invasive treatment is available for benign prostatic hyperplasia (BPH)?

What is benign prostatic hyperplasia/hypertrophy (BPH)?

What are the voiding symptoms of benign prostatic hyperplasia (BPH)?

How is benign prostatic hyperplasia (BPH) managed?

What is the anatomy of the prostate in benign prostatic hyperplasia (BPH)?

What is the role of hormones in the pathophysiology of benign prostatic hyperplasia (BPH)?

How is benign prostatic hyperplasia (BPH) characterized microscopically?

How does benign prostatic hyperplasia (BPH) contribute to bladder dysfunction?

What is the main function of the prostate gland?

How common is benign prostatic hyperplasia (BPH)?

What is the prognosis of benign prostatic hyperplasia (BPH)?

What is the patient education for benign prostatic hyperplasia (BPH)?

Presentation

Which features of the patient history are relevant to the diagnosis and treatment of benign prostatic hyperplasia (BPH)?

What symptoms are associated with benign prostatic hyperplasia (BPH)?

What is involved in the physical exam for benign prostatic hyperplasia (BPH)?

What are the complications of bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH)?

DDX

What other conditions cause symptoms associated with benign prostatic hyperplasia (BPH)?

What are the differential diagnoses for Benign Prostatic Hyperplasia (BPH)?

Workup

What are the guidelines for the workup of benign prostatic hyperplasia (BPH)?

When are urinalysis and urine culture indicated in the workup of benign prostatic hyperplasia (BPH)?

When is prostate-specific antigen testing indicated in the workup of benign prostatic hyperplasia (BPH)?

What are the recommendations for prostate cancer screening in patients with benign prostatic hyperplasia (BPH)?

When are electrolytes, blood urea nitrogen (BUN), and creatinine evaluations indicated in the workup of benign prostatic hyperplasia (BPH)?

What are the benefits of ultrasonography in the workup of benign prostatic hyperplasia (BPH)?

When is imaging of the upper urinary tract indicated in the workup of benign prostatic hyperplasia (BPH)?

What are the AUA guidelines for the workup and treatment of benign prostatic hyperplasia (BPH)?

What are the AUA guidelines on the assessment and workup of benign prostatic hyperplasia (BPH)?

Which tests for the workup of benign prostatic hyperplasia (BPH) are optional according to the AUA guidelines?

Which tests are not indicated in the workup of benign prostatic hyperplasia (BPH) according to the AUA guidelines?

When is cystoscopy indicated in the workup of benign prostatic hyperplasia (BPH)?

How are the histologic findings of benign prostatic hyperplasia (BPH) characterized?

Treatment

What are the therapeutic options for benign prostatic hyperplasia (BPH)?

What are the approach considerations for the treatment of benign prostatic hyperplasia (BPH)?

What is the role of alpha-blockers in the treatment of benign prostatic hyperplasia (BPH)?

Which alpha-blocking drugs are used in the treatment of benign prostatic hyperplasia (BPH)?

What is the role of phenoxybenzamine in the treatment of benign prostatic hyperplasia (BPH)?

What is the role of selective alpha-blockers in the treatment of benign prostatic hyperplasia (BPH)?

What are the potential adverse effects of alpha blockers in the treatment of benign prostatic hyperplasia (BPH)?

What is the role of 5-alpha-reductase inhibitors (5-ARIs) in the treatment of benign prostatic hyperplasia (BPH)?

How effective are 5-ARIs for the treatment of benign prostatic hyperplasia (BPH)?

What precautions are indicated for 5-ARIsin the treatment of benign prostatic hyperplasia (BPH)?

Do 5-ARIs prevent prostate cancer in patients with benign prostatic hyperplasia (BPH)?

What are the AUA guidelines on the use of combination therapy for the treatment of benign prostatic hyperplasia (BPH)?

What clinical trials have been conducted on combination therapy for the treatment of benign prostatic hyperplasia (BPH)?

How effective are phosphodiesterase-5 (PDE5) inhibitors in the treatment of benign prostatic hyperplasia (BPH)?

What are the UAU guidelines on anticholinergic drugs for the management of benign prostatic hyperplasia (BPH)?

What is involved in long-term monitoring of benign prostatic hyperplasia (BPH)?

What is the role of phytotherapeutic agents and dietary supplements in the treatment of benign prostatic hyperplasia (BPH)?

What is the origin of phytotherapeutic agents used in the treatment of benign prostatic hyperplasia (BPH)?

Is saw palmetto an effective treatment for benign prostatic hyperplasia (BPH)?

Is African plum tree an effective treatment for benign prostatic hyperplasia (BPH)?

Is rye (Secale cereale) an effective treatment for benign prostatic hyperplasia (BPH)?

Are pumpkin seeds (Cucurbita pepo) an effective treatment for benign prostatic hyperplasia (BPH)?

What are the indications for transurethral resection of the prostate (TURP) in the treatment of benign prostatic hyperplasia (BPH)?

How is TURP performed in the treatment of benign prostatic hyperplasia (BPH)?

What are the drawbacks of TURP in the treatment of benign prostatic hyperplasia (BPH)?

What are the options for minimally invasive therapy for the treatment of benign prostatic hyperplasia (BPH)?

When is transurethral incision of the prostate (TUIP) indicated in the treatment of benign prostatic hyperplasia (BPH)?

How are lasers used in the treatment of benign prostatic hyperplasia (BPH)?

How effective is laser treatment for benign prostatic hyperplasia (BPH)?

When is transurethral microwave therapy (TUMT) indicated for the treatment of benign prostatic hyperplasia (BPH)?

When is transurethral needle ablation of the prostate (TUNA) indicated for the treatment of benign prostatic hyperplasia (BPH)?

When is high-intensity ultrasound energy therapy indicated for the treatment of benign prostatic hyperplasia (BPH)?

What is the Rezum system for the treatment of benign prostatic hyperplasia (BPH)?

What mechanical approaches are used to treat benign prostatic hyperplasia (BPH)?

How is prostatic artery embolization (PAE) used in the treatment of benign prostatic hyperplasia (BPH)?

When is open prostatectomy indicated for the treatment of benign prostatic hyperplasia (BPH)?

What is involved in open prostatectomy for the treatment of benign prostatic hyperplasia (BPH)?

How can benign prostatic hyperplasia (BPH) be prevented?

Medications

What are the goals of drug treatment for benign prostatic hyperplasia (BPH)?

Which medications in the drug class Combination Products are used in the treatment of Benign Prostatic Hyperplasia (BPH)?

Which medications in the drug class Phosphodiesterase-5 Enzyme Inhibitors are used in the treatment of Benign Prostatic Hyperplasia (BPH)?

Which medications in the drug class 5-Alpha-Reductase Inhibitors are used in the treatment of Benign Prostatic Hyperplasia (BPH)?

Which medications in the drug class Alpha-Adrenergic Blockers are used in the treatment of Benign Prostatic Hyperplasia (BPH)?