Benign Prostatic Hypertrophy

Back

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.

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:

See Clinical 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. 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.

Laboratory studies

Ultrasonography

Ultrasonography (abdominal, renal, transrectal) and intravenous urography are 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, they are 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:

Other tests

See Workup for more detail.

Management

Pharmacologic treatment

Agents used in the treatment of BPH include the following:

Surgery

Minimally invasive treatment

See Treatment and Medication for more detail.

Image library


View Image

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

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 demonstrate 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 Clinical 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 (see Treatment and Management).

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.)


View Image

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.

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 and Management) 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 [DO]), 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. 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.

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:

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 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:

A sexual history is important, as epidemiologic studies have identified LUTS as an independent risk factor for erectile dysfunction and ejaculatory dysfunction.[2]

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. The normal prostate volume in a young man is approximately 20 g.

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

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 nonurologist examiners to communicate estimated gland size. Anecdotally, each fingerbreadth correlates to approximately 15-20 g of tissue. 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.

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.

Complications

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

Approach Considerations

In 2011, the American Urological Association (AUA) published a 2010 update to their Guideline on the Management of Benign Prostatic Hyperplasia. The update included an algorithm for the diagnosis and basic treatment of LUTS, which is presented below.[1]


View Image

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

A prospective, multicenter study in 3 European countries called the Diagnosis Improvement in PrimAry Care Trial (D-IMPACT) found that in three quarters of the men aged 50 years and older who spontaneously reported LUTS to their general practitioner, those who were given an in-office diagnostic algorithm that included just the objective variables of age, PSS, and PSA were accurately diagnosed for BPH by their general practitioner.[3]

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

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 2010 update of the 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. 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.[4]

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 proceeding with screening at the following ages:

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 postvoid 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.

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.

Imaging of the upper tracts is indicated in patients who present with concomitant hematuria, a history of urolithiasis, an elevated creatinine level, high PVR volume, or 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 based on the 1994 Agency for Healthcare Research and Quality clinical practice guidelines for BPH. In 2006, the AUA Practice Guidelines Committee updated 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.[5, 6]

The AUA 2010 BPH 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]


View Image

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 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

Flow rate 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 postvoid residual urine in order to gauge the severity of bladder decompensation. It can be obtained 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.

Approach Considerations

Patients with mild symptoms (IPSS/AUA-SI score < 7) or moderate-to-severe symptoms (IPSS/AUA-SI score ≥8) of benign prostatic hyperplasia (BPH) who are not bothered by their symptoms and are not experiencing complications of BPH should be managed with a strategy of watchful waiting. In these situations, 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. Patients managed expectantly with watchful waiting are usually re-examined annually.

Transurethral resection of the prostate (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.

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 over the last 3 decades, giving rise to the receptor-specific alpha-blockers that comprise the first line of therapy.

Alpha-1–Receptor Blockade in Benign Prostatic Hyperplasia

A significant component of LUTS secondary to BPH is believed to be related to the smooth-muscle tension in the prostate stroma, urethra, and bladder neck. The smooth-muscle tension is mediated by the 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 and allowing passage of urine.

BPH is predominantly a stromal proliferative process, and a significant component of prostatic enlargement results from smooth-muscle proliferation. The stromal-to-epithelial ratio is significantly greater in men with symptomatic BPH than in those with asymptomatic BPH.

The 3 subtypes of the alpha-1 receptor include 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 (ie, tamsulosin) may have a potential therapeutic advantage.

Tamsulosin is considered the most pharmacologically uroselective of the commercially available agents because of its highest relative affinity for the alpha-1a receptor subtype. In 2008, the US Food and Drug Administration (FDA) approved a new alpha-1a receptor selective blocker, silodosin (Rapaflo). It is indicated for treatment of the signs and symptoms of BPH.

The efficacy of the titratable alpha-blockers doxazosin and terazosin (Hytrin) 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). Despite the requirement for dose titration and blood pressure monitoring, these older, often less costly, alpha-blockers appear to be equally effective to tamsulosin and alfuzosin, and the 2010 AUA guidelines state that they remain reasonable choices for patients with moderate-to-severe LUTS due to BPH.[1]

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 BPH-related surgery.[7]

Hellstrom and Sikka reported in 2006 that the acute administration of tamsulosin effects 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.[8]

Alpha-adrenergic receptor blockers

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

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 currently not often used for the treatment of BPH. The 2010 update to the AUA guideline for BPH retains the statement that insufficient data exist for a recommendation of phenoxybenzamine or of prazosin for treatment of LUTS secondary to BPH. This statement was originally published in the 2003 AUA BPH guidelines.[1]

Phosphodiesterase-5 enzyme inhibitors

Statistically significant symptomatic improvements have been reported for patients with BPH receiving tadalafil. It has also been approved for the treatment of simultaneous BPH and erectile dysfunction (ED). Phosphdiesterase-5 (PDE5) inhibitors are known to mediate smooth muscle relaxation in the lower urinary tract.

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 2010 AUA guideline 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.[9, 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.[10]

5-Alpha-Reductase Inhibitors in Benign Prostatic Hyperplasia

Hormonal medical management emerged from the discovery of a congenital form of pseudohermaphroditism secondary to DHT deficiency (due to 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 (predominant 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. 5-Alpha-reductase inhibitors improve LUTS by decreasing prostate volumes; thus, patients with larger prostates may achieve a greater benefit. Further, maximal reduction in prostate volume requires 6 months of therapy.

5-Alpha reductase inhibitors

Finasteride (Proscar), 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.

Dutasteride (Avodart) 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 prostate-specific antigen (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). Thus, one must take this into account when using PSA to screen for prostate cancer.

One prospective, randomized, double-blind study by the Enlarged Prostate International Comparator Study (EPICS) was conducted to compare the efficacy of dutasteride to that of finasteride in men with symptomatic BPH. While this study was conducted over the course of only one year, the data suggest that both of these drugs were similarly effective in reducing prostate volume, improving Qmax, and LUTS for this population. The long-term outcomes are yet to be investigated.[11]

Because these drugs interfere with the metabolism of testosterone, they are contraindicated in children and pregnant females. In addition, 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.

In patients with LUTS and enlarged prostates, 5-alpha-reductase inhibitors are believed to be appropriate and effective treatment.

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-alpha reductase inhibitors (5-ARIs). These agents include finasteride (Proscar, Propecia) and dutasteride (Avodart, Jalyn). 5-ARIs are indicated for benign prostatic hypertrophy and alopecia.

Data from 2 large, randomized, controlled trials observed an increased risk of being diagnosed with a more serious form of prostate cancer (high-grade prostate cancer) in trial participants taking 5-ARIs. The 2 trials are the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial. Both of these trials 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.[12, 13]

The revised prescribing information recommends that prior to initiating therapy with 5-ARIs, perform appropriate evaluations to rule out other urological conditions, including prostate cancer, that might mimic benign prostatic hyperplasia (BPH).

Combination Therapy

The alpha-1-receptor blockers provide rapid relief, while the 5-alpha-reductase inhibitors target the underlying disease process.[7] 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 AUR and BPH-related surgery were reduced with combination therapy or finasteride in comparison with doxazosin monotherapy.[14]

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.[14]

Anticholinergic Agents

Historically, anticholinergics were discouraged in men with BPH because of concerns of inducing urinary retention. Trials have demonstrated a slight increase in PVR; however, AUR rates were low. Importantly, these trials consisted of patients with low baseline PVR.

The 2010 AUA BPH guidelines recommend anticholinergic agents for management of LUTS in patients who do not have an elevated PVR and whose LUTS are primarily irritative. Baseline PVR should be obtained prior to initiation of anticholinergic therapy, to assess for urinary retention.[15] Caution with anticholinergics is recommended with patients whose PVR is greater than 250-300 mL.[1]

Landmark Clinical Trials

Numerous phase II and phase III trials of drugs used in the treatment of BPH have been conducted. A few landmark studies are selected below.

The Proscar Long-Term Efficacy and Safety Study (PLESS), patients treated with finasteride (5 mg/d) were at a significantly lower risk of developing AUR or needing surgery.[16] This was a multicenter, 4-year, double-blind, placebo-controlled study of 3,040 men. Men with PSA levels of more than 10 ng/mL and those with prostate cancer were excluded.

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.[17]

In the Alfuzosin Long-Term Efficacy and Safety Study (ALTESS), alfuzosin (10 mg/d) decreased the risk of LUTS deterioration and significantly improved QOL and peak urinary flow rate. ALTESS was a 2-year, double-blind, placebo-controlled study of 1,522 men. Notably, these men had greater risk factors for BPH progression (ie, older age, higher IPSS scores, larger prostate size, lower Qmax, and higher PVR) than those in the MTOPS trial. Alfuzosin did not reduce the risk of AUR but tended to reduce the risk of surgery.[18]

In the international real-life practice study of alfuzosin once daily (ALF-ONE), 3 years of alfuzosin (10 mg/d) decreased IPSS by one third, with significant improvements in nocturia and bother score. ALF-ONE was conducted in 689 European men with a mean age of 67.6 years. Clinical progression of worsening of IPSS (≥4 points) was seen in 12.4%, AUR in 2.6%, and requirement of BPH-related surgery in 5.7%. Alfuzosin was well tolerated, with dizziness the most common adverse effect (4.5%). Notably, symptom worsening during treatment and high PSA levels appeared to be the best predictors of clinical progression.[19]

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.[20] The adverse-effect profile of combination therapy was similar to that of monotherapy, although drug-related adverse events were more common with combination therapy.[21] CombAT is 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 contributes to the standard of care shifting towards combined drug therapy in appropriately selected patients, while better defining the role of the alpha-blockers.[15]

Phytotherapeutic Agents and Dietary Supplements

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:

The origins of phytotherapeutic agents are as follows:

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.[22]

African plum tree (P africanum)

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

Rye (S 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.

Treatment of Concomitant Erectile Dysfunction

It is recommended to first establish the alpha-1 blocker dose before treating the erectile dysfunction. The medication used to treat erectile dysfunction should be titrated to the lowest effective dose. Furthermore, sildenafil doses of greater than 25 mg should not be taken within 4 hours of any alpha-blocker.[23, 24, 25]

In addition to treating erectile dysfunction, sildenafil may improve mild-to-moderate LUTS. Nitric oxide may mediate relaxation of the prostatic urethra and/or bladder neck. The utility of phosphodiesterase inhibitors in the treatment of LUTS has yet to be defined.[26]

Recent trials have addressed the use of long-acting phosphodiesterase type 5 inhibitors (tadalafil) and have found them to be significantly better than placebo in improving the symptoms of BPH/LUTS.

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:

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 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 catheter.

Irrigating fluid may also be absorbed in significant quantities through veins that are cut open, with possible serious sequelae termed transurethral resection syndrome (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 heat generated by such may damage these nerves, resulting in impotence.

Open Prostatectomy

This procedure is now 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.

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, resulting in 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.[27]

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.[28, 29]

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.[29, 30]

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 2010 AUA guidelines state TUMT is an effective option for partially relieving symptoms that may be considered in patients with moderate or severe LUTS secondary to BPH.[31]

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 2010 AUA guideline update considers TURP an appropriate and effective treatment option for moderate or severe LUTS.[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.

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.[32] 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.

Diet

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.[33]

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 DRE and PSA screening at least annually.

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, and various combinations.

Phenoxybenzamine (Dibenzyline)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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.

Class Summary

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

Finasteride (Proscar)

Clinical Context:  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)

Clinical Context:  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.

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.[34, 31]

Tadalafil (Cialis)

Clinical Context:  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.

Class Summary

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

Dutasteride and tamsulosin (Jalyn)

Clinical Context:  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.

Class Summary

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

Author

Levi A Deters, MD, Attending Physician, Spokane Urology

Disclosure: Nothing to disclose.

Coauthor(s)

Charles R Moore, MD, Endourology Fellow, Department of Urology, University of Miami School of Medicine

Disclosure: Nothing to disclose.

Raymond A Costabile, MD, Jay Y Gillenwater Professor of Urology and Vice Chairman, Senior Associate Dean for Clinical Strategy, University of Virginia Health System

Disclosure: Nothing to disclose.

Raymond J Leveillee, MD, FRCS(Glasg), Professor of Clinical Urology, Radiology and Biomedical Engineering, Department of Urology, University of Miami Miller School of Medicine; Chief, Division of Endourology/Laparoscopy and Minimally Invasive Surgery, Department of Urology, Jackson Memorial Hospital

Disclosure: ACMI/Gyrus Honoraria Speaking and teaching; Boston Scientific Honoraria Speaking and teaching; Applied Medical Honoraria Speaking and teaching; Intuitive Surgical Honoraria Speaking and teaching; Intio Grant/research funds Other

Vipul R Patel, MD, Consulting Surgeon, Global Robotics Institute, Florida Hospital Celebration Health

Disclosure: Intuitive Surgical Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Chief Editor

Edward David Kim, MD, FACS, Professor of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine; Consulting Staff, University of Tennessee Medical Center

Disclosure: Lilly None Advisor; Astellas Honoraria Speaking and teaching; Watson Honoraria Speaking and teaching; Warner Chilcott Honoraria Speaking and teaching; Auxilium Honoraria Speaking and teaching; Eli Lilly Honoraria Speaking and teaching

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Vincent G Bird, MD, to the development and writing of the source article.

References

  1. McVary KT, Roehrborn CG, Avins AL, Barry MJ, Bruskewitz RC, Donnell RF, et al. Update on AUA Guideline on the Management of Benign Prostatic Hyperplasia. J Urol. Mar 17 2011;[View Abstract]
  2. Seftel AD, Rosen RC, Rosenberg MT, Sadovsky R. Benign prostatic hyperplasia evaluation, treatment and association with sexual dysfunction: practice patterns according to physician specialty. Int J Clin Pract. Apr 2008;62(4):614-22. [View Abstract]
  3. Carballido J, Fourcade R, Pagliarulo A, et al. Can benign prostatic hyperplasia be identified in the primary care setting using only simple tests? Results of the Diagnosis IMprovement in PrimAry Care Trial. Int J Clin Pract. Sep 2011;65(9):989-996. [View Abstract]
  4. American Cancer Society. 2009. American Cancer Society - Learn About Prostate Cancer. Available at http://www.cancer.org/docroot/lrn/lrn_0.asp. Accessed 1/29/2009.
  5. McConnell JD, Barry MJ, Bruskewitz RC, et al. Benign Prostatic Hyperplasia: Diagnosis and Treatment. Clinical Practice Guideline. No. 8, AHCPR Publication No. 94-0582. Rockville, Md: Agency for Healthcare Policy and Research,. Public Health Service, US Department of Health and Human Services, 1994.
  6. AUA Clinical Guidelines - Management of BPH ('03/Updated '06). Available at http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines.cfm?sub=bph. Accessed 1/29/2009.
  7. Emberton M, Cornel EB, Bassi PF, Fourcade RO, Gómez JM, Castro R. Benign prostatic hyperplasia as a progressive disease: a guide to the risk factors and options for medical management. Int J Clin Pract. Jul 2008;62(7):1076-86. [View Abstract]
  8. Hellstrom WJ, Sikka SC. Effects of acute treatment with tamsulosin versus alfuzosin on ejaculatory function in normal volunteers. J Urol. Oct 2006;176(4 Pt 1):1529-33. [View Abstract]
  9. Cantrell MA, Bream-Rouwenhorst HR, Steffensmeier A, Hemerson P, Rogers M, Stamper B. Intraoperative floppy iris syndrome associated with alpha1-adrenergic receptor antagonists. Ann Pharmacother. Apr 2008;42(4):558-63. [View Abstract]
  10. Bell CM, Hatch WV, Fischer HD, Cernat G, Paterson JM, Gruneir A, et al. Association between tamsulosin and serious ophthalmic adverse events in older men following cataract surgery. JAMA. May 20 2009;301(19):1991-6. [View Abstract]
  11. Nickel JC, Gilling P, Tammela TL, Morrill B, Wilson TH, Rittmaster RS. Comparison of dutasteride and finasteride for treating benign prostatic hyperplasia: the Enlarged Prostate International Comparator Study (EPICS). BJU Int. Aug 2011;108(3):388-94. [View Abstract]
  12. Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. Jul 17 2003;349(3):215-24. [View Abstract]
  13. Andriole GL, Bostwick DG, Brawley OW, Gomella LG, Marberger M, Montorsi F, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. Apr 1 2010;362(13):1192-202. [View Abstract]
  14. Madersbacher S, Marszalek M, Lackner J, Berger P, Schatzl G. The long-term outcome of medical therapy for BPH. Eur Urol. Jun 2007;51(6):1522-33. [View Abstract]
  15. Montorsi F, Roehrborn C, Garcia-Penit J, Borre M, Roeleveld TA, Alimi JC, 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. Feb 23 2011;[View Abstract]
  16. McConnell JD, Bruskewitz R, Walsh P, et al. 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. N Engl J Med. Feb 26 1998;338(9):557-63. [View Abstract]
  17. McConnell JD, Roehrborn CG, Bautista OM, Andriole GL Jr, Dixon CM, Kusek JW. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. Dec 18 2003;349(25):2387-98. [View Abstract]
  18. Roehrborn CG. Alfuzosin 10 mg once daily prevents overall clinical progression of benign prostatic hyperplasia but not acute urinary retention: results of a 2-year placebo-controlled study. BJU Int. Apr 2006;97(4):734-41. [View Abstract]
  19. Vallancien G, Emberton M, Alcaraz A, Matzkin H, van Moorselaar RJ, Hartung R. Alfuzosin 10 mg once daily for treating benign prostatic hyperplasia: a 3-year experience in real-life practice. BJU Int. Apr 2008;101(7):847-52. [View Abstract]
  20. 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. May 2011;107(9):1426-31. [View Abstract]
  21. Roehrborn CG, Siami P, Barkin J, Damião R, Major-Walker K, Morrill B. The effects of dutasteride, tamsulosin and combination therapy on lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement: 2-year results from the CombAT study. J Urol. Feb 2008;179(2):616-21; discussion 621. [View Abstract]
  22. Barry MJ, Meleth S, Lee JY, et al. Effect of Increasing Doses of Saw Palmetto Extract on Lower Urinary Tract Symptoms: A Randomized Trial. JAMA. Sep 28 2011;306(12):1344-1351. [View Abstract]
  23. Sildenafil [package insert]. New York, NY: Pfizer Inc.; 2002.
  24. Vardenafil [package insert]. Pittsburgh, Pa: Bayer Pharmaceuticals Corporation/GlaxoSmithKline; 2003.
  25. Tadalafil [package insert]. Indianapolis, IN: Lilly ICOS LLC; 2005.
  26. Mulhall JP, Guhring P, Parker M, Hopps C. Assessment of the impact of sildenafil citrate on lower urinary tract symptoms in men with erectile dysfunction. J Sex Med. Jul 2006;3(4):662-7. [View Abstract]
  27. Sotelo R, Spaliviero M, Garcia-Segui A, et al. Laparoscopic retropubic simple prostatectomy. J Urol. Mar 2005;173(3):757-60. [View Abstract]
  28. Malek RS, Kuntzman RS, Barrett DM. Photoselective potassium-titanyl-phosphate laser vaporization of the benign obstructive prostate: observations on long-term outcomes. J Urol. Oct 2005;174(4 Pt 1):1344-8. [View Abstract]
  29. Kuntz RM. Laser treatment of benign prostatic hyperplasia. World J Urol. Jun 2007;25(3):241-7. [View Abstract]
  30. Elzayat EA, Habib EI, Elhilali MM. Holmium laser enucleation of the prostate: a size-independent new "gold standard". Urology. Nov 2005;66(5 Suppl):108-13. [View Abstract]
  31. Barry MJ, Cockett AT, Holtgrewe HL, et al. Relationship of symptoms of prostatism to commonly used physiological and anatomical measures of the severity of benign prostatic hyperplasia. J Urol. Aug 1993;150(2 Pt 1):351-8. [View Abstract]
  32. Crane M. FDA OKs New Device to Treat BPH. Medscape Medical News. Available at http://www.medscape.com/viewarticle/810981. Accessed September 23, 2013.
  33. Kristal AR, Arnold KB, Schenk JM, Neuhouser ML, Goodman P, Penson DF. Dietary patterns, supplement use, and the risk of symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial. Am J Epidemiol. Apr 15 2008;167(8):925-34. [View Abstract]
  34. Arai Y, Fukuzawa S, Terai A, Yoshida O. Transurethral microwave thermotherapy for benign prostatic hyperplasia: relation between clinical response and prostate histology. Prostate. Feb 1996;28(2):84-8. [View Abstract]
  35. Ben-Zvi T, Hueber PA, Liberman D, Valdivieso R, Zorn KC. GreenLight XPS 180W vs HPS 120W Laser Therapy for Benign Prostate Hyperplasia: A Prospective Comparative Analysis After 200 Cases in a Single-center Study. Urology. Apr 2013;81(4):853-8. [View Abstract]
  36. Bird ST, Delaney JA, Brophy JM, Etminan M, Skeldon SC, Hartzema AG. Tamsulosin treatment for benign prostatic hyperplasia and risk of severe hypotension in men aged 40-85 years in the United States: risk window analyses using between and within patient methodology. BMJ. Nov 5 2013;347:f6320. [View Abstract]
  37. Boggs W. Increased Risk of Severe Hypotension in Men Treated With Tamsulosin. Medscape Medical News. Available at http://www.medscape.com/viewarticle/815216. Accessed December 7, 2013.
  38. Boggs W. Prostatic Urethral Lift Relieves Symptoms of Benign Prostatic Hyperplasia. Medscape Medical News. Available at http://www.medscape.com/viewarticle/806635. Accessed July 16, 2013.
  39. Gallegos PJ, Frazee LA. Anticholinergic therapy for lower urinary tract symptoms associated with benign prostatic hyperplasia. Pharmacotherapy. Mar 2008;28(3):356-65. [View Abstract]
  40. Roehrborn CG, Gange SN, Shore ND, Giddens JL, Bolton DM, Cowan BE, et al. Multi-Center Randomized Controlled Blinded Study of the Prostatic Urethral Lift for the Treatment of LUTS Associated with Prostate Enlargement Due to BPH: The L.I.F.T. Study. J Urol. Jun 10 2013;[View Abstract]

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

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

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

Benign prostatic hyperplasia (BPH) diagnosis and treatment algorithm.

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

Benign prostatic hyperplasia (BPH) diagnosis and treatment algorithm.

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