Randall H. Neal, MD

By age 60, more than half of men have histopathologic benign prostatic hyperplasia (BPH).¹ And, given the publicity BPH is receiving today, it’s quite possible that those who are experiencing symptoms will be less reticent to discuss it than before.

So what does the evidence tell us about how to best manage these patients? Specifically, do you know what the minimal assessment is for those who are experiencing symptoms? When might advanced testing methods be helpful?

Furthermore, among men who are now 50 years old, the expected lifetime incidence for any type of surgical intervention for BPH is approximately 35%.² What are the first-line treatments available to these patients? Who might be a candidate for combination drug therapy? Are herbal preparations worth considering? When might surgery be a first choice?

These questions underscore the importance of a proper primary care framework for evaluating and treating BPH, which we can develop based on a consensus guideline released by the American Urological Association (AUA)¹ and on more recent research.

Assessing symptoms: 2 tools can help

Symptoms of BPH can include urinary frequency, nocturia, urgency, hesitancy, weak or intermittent urine stream, straining to void, and a sensation of incomplete voiding.¹ Each patient experiences a unique constellation of these symptoms. Using a urinary symptom scoring system can help define the severity of BPH and be useful in monitoring the success of subsequent therapy. Available instruments for this purpose include the AUA’s 7-question Symptom Index for BPH (http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines.cfm?sub=bph) and the International Prostate Symptom Score, which adds an eighth question to the AUA list to gauge the extent to which symptoms bother a patient (http://www.usli.net/uro/Forms/ipss.pdf).^1-5 If the patient is unclear about the pattern of his symptoms, consider asking him to keep a voiding diary.

Ruling out other causes of BPH-like symptoms

TABLE 1 lists the differential diagnoses of obstructive urinary symptoms, otherwise known as lower urinary tract symptoms (LUTS).

Look for clues in the history. Ask the patient whether he uses medications known to cause obstructive urinary symptoms—tricyclic antidepressants, first-generation antihistamines, anticholinergic agents, diuretics, narcotics, and decongestants. Does he have any first-degree relatives with prostate cancer? If the answer is yes, how young was he when the cancer was diagnosed?

Focus your examination. Perform a digital rectal examination (DRE) to check prostate size and to detect palpable nodules, induration, or irregularities associated with malignancy or infection. An enlarged prostate is commonly found on rectal examination; however, the degree of hypertrophy does not necessarily correlate with the degree of obstruction or the severity of symptoms. Any irregularity suggestive of cancer requires that you talk to your patient about his preferences for further investigation.⁶

Conduct a neurologic exam to check mental status, gait, lower extremity strength, and anal sphincter tone to assess for conditions that could cause a neurogenic bladder.

TABLE 1
Lower urinary tract symptoms are also seen with these disorders³¹

Consider these tests. Urinary tract infection (UTI) or bladder cancer may produce symptoms similar to those of BPH. For any patient who has LUTS, perform a urinalysis to screen for infection or hematuria. If a UTI is found, treat it and re-evaluate the patient. If you detect microscopic hematuria, do a further work-up to rule out bladder cancer. If DRE findings are suggestive of prostate cancer, you’ll need an ultrasound-guided biopsy and histological examination to make the diagnosis.

Optional tests in the work-up of LUTS include urinary flow rate measurements, post-void residual urine measurements, and pressure flow studies. These tests may be informative if the diagnosis is unclear based on the history and physical exam or when patients do not respond to initial therapy. Ultrasonography, intravenous pyelography, filling cystometrography, and cystoscopy are not routinely recommended for the evaluation of suspected BPH. However, they may be helpful if a patient has a complex medical history (eg, neurologic disorder or other disease known to affect bladder function, or prior failure of BPH therapy), or if he wants to pursue invasive therapy.¹

Talk to your patient about the controversial PSA test. Measuring serum prostate-specific antigen (PSA) levels to screen for prostate cancer is controversial, even for patients with LUTS. Although PSA testing can effectively detect prostate cancer in its early pathologic stages, researchers continue to investigate whether early detection significantly improves outcomes. Quite recently, 2 studies demonstrated that the test saves few lives;^7,8 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent 1 death from prostate cancer.

A subset of detected cancers appears to be clinically significant, but many cancers will not progress during a patient’s lifetime.^3,5 The United States Preventive Services Task Force (USPSTF) has concluded that the evidence is insufficient to recommend for or against routine prostate cancer screening due to the uncertainty of the balance of potential benefits (reduction of prostate cancer morbidity and mortality) and risks (false-positive results, unnecessary biopsies, and possible complications) of treatment for early disease.^9-12 Furthermore, in its 2008 update, the USPSTF specifically recommended against screening for prostate cancer in men 75 years of age and older.

The American Cancer Society says that discouraging or not offering testing is inappropriate: Men who ask their physicians to make the decision on their behalf should be tested.⁹ A 2006 Cochrane review of this topic found only 2 eligible randomized trials, both of which had high risk of bias. They concluded that insufficient high-quality evidence exists to support or refute the use of any screening for prostate cancer in any patient population, including those with BPH.¹³

Given this conflicting advice, discuss the benefits and limitations of screening with your patient before deciding whether or not to test.

What is the optimal Approach to treatment?

Patients who are not bothered by their urinary symptoms—even those with moderate to severe symptom scores—can be managed with watchful waiting. Because of the cost and frequent side effects of medications for BPH, these patients generally will not benefit from drug therapy.^3,5,14,15 However, follow-up monitoring is important, because the severity of BPH can change even without treatment.

Even if patients with moderate or severe AUA symptom scores are not bothered by their symptoms, inform them of appropriate treatment options.³ When urinary obstruction symptoms from BPH significantly interfere with daily living and sleep activities, treatment is justified.¹

Medical management, yes, but which option?

Medical therapies are not as effective as surgical intervention,¹⁶ but they often provide adequate symptom relief and cause fewer, less severe, and less permanent adverse effects than surgery. Initiate treatment with medical therapy if (1) the patient is bothered by his symptoms, (2) no significant urinary obstruction exists, and (3) you have followed the patient’s preference for prostate cancer evaluation. TABLE 2 lists prescription medications for the treatment of BPH.

Nonselective α-adrenergic blockers, such as doxazosin and terazosin, reduce prostatic smooth muscle tone, thereby improving urinary flow. A Cochrane systematic review and a subsequent large randomized trial found terazosin to be superior to placebo in improving urinary flow and decreasing symptoms in men with BPH.^16,17

Selective α-adrenergic blockers, such as alfuzosin and tamsulosin, are highly selective α-1_A-adrenergic antagonists. They are believed to be as effective as the nonselective agents, and patients may experience fewer side effects than with nonselective agents.^1,18 However, these drugs are considerably more expensive than their nonselective counterparts.

5-α Reductase inhibitors, such as finasteride and dutasteride, are more effective than placebo for patients with LUTS associated with demonstrable prostate enlargement. In a Cochrane review and subsequent large randomized trial, finasteride proved inferior to terazosin.^16,17 However, finasteride reduces the progression to urinary obstruction and the need for invasive therapy; terazosin does not.¹⁷ Finasteride achieves this effect by reducing prostatic volume by about 20% over 3 to 6 months of treatment.

Finasteride decreases PSA levels by 40% to 50%. If you conduct PSA screening for prostate cancer in a patient taking finasteride, double the PSA level before comparing it with age-related norms. Handled this way, PSA screening will not lose its sensitivity or specificity for the diagnosis of prostate cancer.¹⁹

Though a 5-mg daily regimen of finasteride reduces the overall risk of prostate cancer from 24.4% to 18.4%, it increases the risk of high-grade disease associated with higher mortality from 5.1% to 6.4%. Warn patients of this risk.²⁰

Combining an α-adrenergic blocker and 5-α reductase inhibitor. Combination therapy is appropriate and effective for patients with LUTS associated with demonstrable prostate enlargement for whom monotherapy has failed.⁹ Taken together, a 5-α reductase inhibitor and a nonselective α-1_A-adrenergic blocker alleviate symptoms more effectively than either drug can do alone.^21,22 The incidence of most adverse drug reactions with the combination is similar to the baseline risk for each drug. However, ejaculatory abnormalities are reported in 7% of patients in the combination therapy group vs 2% or less in the monotherapy groups. Discontinuation rates for combination therapy are comparable to those in the nonselective α-adrenergic blocker group.²² The adverse effect profile of combining selective α-adrenergic blockers with 5-α reductase inhibitors has not been reported; however, the combination is often used in practice.

For patients to make an informed decision about treatment, discuss with them the common adverse reactions from these agents (TABLE 2) and the need for long-term daily therapy. Also give the patient a reasonable estimate of the risk of his retention symptoms progressing.

TABLE 2
BPH medications: How they compare

Complementary medicine: Information is still limited

Herbal or complementary medicines are used worldwide to treat BPH. These products are not regulated by the US Food and Drug Administration (FDA), and therefore no standardized formulation or dosing exists. Although a few substances appear to have some positive effects, high-quality clinical trials on clinical outcomes are lacking.

The AUA guideline does not recommend the use of phytotherapy.¹ Despite this, many patients—and any number of physicians—turn to phytotherapy to treat LUTS associated with BPH.

Some patients turn to phytotherapy without their physician’s knowledge, so it’s important to ask whether they are using any herbal preparations. Agents currently used include saw palmetto, African plum, South African star grass, and Cernilton.

Saw palmetto (Serenoa repens) has been used by more than 2 million men in the United States. In 2006, Bent et al conducted a rigorously designed double-blinded trial in which 225 men older than 49 years with moderate-to-severe symptoms of BPH were treated for 1 year with saw palmetto extract (160 mg twice a day) or placebo.²³ Saw palmetto did not ameliorate the symptoms of BPH. In contrast, a Cochrane systematic review last updated in 2002 asserted that this substance caused mild-to-moderate reductions in urologic symptoms and flow measures when given to men with symptomatic BPH.²⁴ Long-term efficacy and safety of this product are unknown. Given the efficacy of saw palmetto, it is a reasonable option for men who prefer a nonprescription product to treat symptoms of BPH.

African plum (Pygeum africanum) is more effective than placebo in reducing symptoms of BPH and has few side effects, based on poorly designed small studies.^25,26 Comparative data with finasteride or the α-adrenergic blockers are lacking.

South African star grass (Hypoxis rooperi and certain species of Pinus and Picea) contain beta-sitosterols and are sources for phytotherapeutic treatments for BPH. A systematic review analyzed the effects of beta-sitosterols in men and found improved urinary symptom scores and flow measures (n=519; 4 randomized, controlled, double-blind trials; duration, 4-26 weeks).²⁷ Their long-term effectiveness and safety are not known.

Cernilton, prepared from the ryegrass pollen Secale cereale, is marketed for the treatment of BPH. A Cochrane systematic review demonstrated that comparative trials lacked a proven active control. Available evidence suggests that short-term use of cernilton is well tolerated and modestly decreases overall urologic symptoms, including nocturia. Additional randomized placebo and active-controlled trials are needed to evaluate the long-term clinical effectiveness and safety of Cernilton.²⁸

Acupuncture was not effective in treating LUTS in men in randomized controlled (single-blinded) trials.²⁹

When patients don’t respond to medical treatment

Surgery is recommended for patients who have not responded to medical treatment, who have refractory retention with a failed attempt at catheter removal, or who experience recurrent UTIs, persistent hematuria, bladder stones, or renal insufficiency.³ In addition, surgery can be the initial treatment choice for patients with high AUA symptom scores who opt for this intervention and are good operative candidates.

The specific surgical approach (open or endoscopic; electrocautery or laser) are technical decisions based on the patient’s prostate size, the individual surgeon’s judgment, and the patient’s comorbidities.^1,30 For patients who are not surgical candidates, treatment with intermittent catheterization, an indwelling catheter, or a stent is recommended.

Acknowledgements

The authors thank Jen Creer, MA, of Edit Rx, LLC, for her assistance in the preparation of this manuscript. The University of Nebraska Medical Center, with which both authors were previously affiliated, funded this writing assistance.

Correspondence
Drew M. Keister, MD, Lehigh Valley Health Network, PO Box 7017, Allentown, PA 18105-7017; drew_m.keister@lvh.com

By age 60, more than half of men have histopathologic benign prostatic hyperplasia (BPH).¹ And, given the publicity BPH is receiving today, it’s quite possible that those who are experiencing symptoms will be less reticent to discuss it than before.

So what does the evidence tell us about how to best manage these patients? Specifically, do you know what the minimal assessment is for those who are experiencing symptoms? When might advanced testing methods be helpful?

Furthermore, among men who are now 50 years old, the expected lifetime incidence for any type of surgical intervention for BPH is approximately 35%.² What are the first-line treatments available to these patients? Who might be a candidate for combination drug therapy? Are herbal preparations worth considering? When might surgery be a first choice?

These questions underscore the importance of a proper primary care framework for evaluating and treating BPH, which we can develop based on a consensus guideline released by the American Urological Association (AUA)¹ and on more recent research.

Assessing symptoms: 2 tools can help

Symptoms of BPH can include urinary frequency, nocturia, urgency, hesitancy, weak or intermittent urine stream, straining to void, and a sensation of incomplete voiding.¹ Each patient experiences a unique constellation of these symptoms. Using a urinary symptom scoring system can help define the severity of BPH and be useful in monitoring the success of subsequent therapy. Available instruments for this purpose include the AUA’s 7-question Symptom Index for BPH (http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines.cfm?sub=bph) and the International Prostate Symptom Score, which adds an eighth question to the AUA list to gauge the extent to which symptoms bother a patient (http://www.usli.net/uro/Forms/ipss.pdf).^1-5 If the patient is unclear about the pattern of his symptoms, consider asking him to keep a voiding diary.

Ruling out other causes of BPH-like symptoms

TABLE 1 lists the differential diagnoses of obstructive urinary symptoms, otherwise known as lower urinary tract symptoms (LUTS).

Look for clues in the history. Ask the patient whether he uses medications known to cause obstructive urinary symptoms—tricyclic antidepressants, first-generation antihistamines, anticholinergic agents, diuretics, narcotics, and decongestants. Does he have any first-degree relatives with prostate cancer? If the answer is yes, how young was he when the cancer was diagnosed?

Focus your examination. Perform a digital rectal examination (DRE) to check prostate size and to detect palpable nodules, induration, or irregularities associated with malignancy or infection. An enlarged prostate is commonly found on rectal examination; however, the degree of hypertrophy does not necessarily correlate with the degree of obstruction or the severity of symptoms. Any irregularity suggestive of cancer requires that you talk to your patient about his preferences for further investigation.⁶

Conduct a neurologic exam to check mental status, gait, lower extremity strength, and anal sphincter tone to assess for conditions that could cause a neurogenic bladder.

TABLE 1
Lower urinary tract symptoms are also seen with these disorders³¹

Consider these tests. Urinary tract infection (UTI) or bladder cancer may produce symptoms similar to those of BPH. For any patient who has LUTS, perform a urinalysis to screen for infection or hematuria. If a UTI is found, treat it and re-evaluate the patient. If you detect microscopic hematuria, do a further work-up to rule out bladder cancer. If DRE findings are suggestive of prostate cancer, you’ll need an ultrasound-guided biopsy and histological examination to make the diagnosis.

Optional tests in the work-up of LUTS include urinary flow rate measurements, post-void residual urine measurements, and pressure flow studies. These tests may be informative if the diagnosis is unclear based on the history and physical exam or when patients do not respond to initial therapy. Ultrasonography, intravenous pyelography, filling cystometrography, and cystoscopy are not routinely recommended for the evaluation of suspected BPH. However, they may be helpful if a patient has a complex medical history (eg, neurologic disorder or other disease known to affect bladder function, or prior failure of BPH therapy), or if he wants to pursue invasive therapy.¹

Talk to your patient about the controversial PSA test. Measuring serum prostate-specific antigen (PSA) levels to screen for prostate cancer is controversial, even for patients with LUTS. Although PSA testing can effectively detect prostate cancer in its early pathologic stages, researchers continue to investigate whether early detection significantly improves outcomes. Quite recently, 2 studies demonstrated that the test saves few lives;^7,8 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent 1 death from prostate cancer.

A subset of detected cancers appears to be clinically significant, but many cancers will not progress during a patient’s lifetime.^3,5 The United States Preventive Services Task Force (USPSTF) has concluded that the evidence is insufficient to recommend for or against routine prostate cancer screening due to the uncertainty of the balance of potential benefits (reduction of prostate cancer morbidity and mortality) and risks (false-positive results, unnecessary biopsies, and possible complications) of treatment for early disease.^9-12 Furthermore, in its 2008 update, the USPSTF specifically recommended against screening for prostate cancer in men 75 years of age and older.

The American Cancer Society says that discouraging or not offering testing is inappropriate: Men who ask their physicians to make the decision on their behalf should be tested.⁹ A 2006 Cochrane review of this topic found only 2 eligible randomized trials, both of which had high risk of bias. They concluded that insufficient high-quality evidence exists to support or refute the use of any screening for prostate cancer in any patient population, including those with BPH.¹³

Given this conflicting advice, discuss the benefits and limitations of screening with your patient before deciding whether or not to test.

What is the optimal Approach to treatment?

Patients who are not bothered by their urinary symptoms—even those with moderate to severe symptom scores—can be managed with watchful waiting. Because of the cost and frequent side effects of medications for BPH, these patients generally will not benefit from drug therapy.^3,5,14,15 However, follow-up monitoring is important, because the severity of BPH can change even without treatment.

Even if patients with moderate or severe AUA symptom scores are not bothered by their symptoms, inform them of appropriate treatment options.³ When urinary obstruction symptoms from BPH significantly interfere with daily living and sleep activities, treatment is justified.¹

Medical management, yes, but which option?

Medical therapies are not as effective as surgical intervention,¹⁶ but they often provide adequate symptom relief and cause fewer, less severe, and less permanent adverse effects than surgery. Initiate treatment with medical therapy if (1) the patient is bothered by his symptoms, (2) no significant urinary obstruction exists, and (3) you have followed the patient’s preference for prostate cancer evaluation. TABLE 2 lists prescription medications for the treatment of BPH.

Nonselective α-adrenergic blockers, such as doxazosin and terazosin, reduce prostatic smooth muscle tone, thereby improving urinary flow. A Cochrane systematic review and a subsequent large randomized trial found terazosin to be superior to placebo in improving urinary flow and decreasing symptoms in men with BPH.^16,17

Selective α-adrenergic blockers, such as alfuzosin and tamsulosin, are highly selective α-1_A-adrenergic antagonists. They are believed to be as effective as the nonselective agents, and patients may experience fewer side effects than with nonselective agents.^1,18 However, these drugs are considerably more expensive than their nonselective counterparts.

5-α Reductase inhibitors, such as finasteride and dutasteride, are more effective than placebo for patients with LUTS associated with demonstrable prostate enlargement. In a Cochrane review and subsequent large randomized trial, finasteride proved inferior to terazosin.^16,17 However, finasteride reduces the progression to urinary obstruction and the need for invasive therapy; terazosin does not.¹⁷ Finasteride achieves this effect by reducing prostatic volume by about 20% over 3 to 6 months of treatment.

Finasteride decreases PSA levels by 40% to 50%. If you conduct PSA screening for prostate cancer in a patient taking finasteride, double the PSA level before comparing it with age-related norms. Handled this way, PSA screening will not lose its sensitivity or specificity for the diagnosis of prostate cancer.¹⁹

Though a 5-mg daily regimen of finasteride reduces the overall risk of prostate cancer from 24.4% to 18.4%, it increases the risk of high-grade disease associated with higher mortality from 5.1% to 6.4%. Warn patients of this risk.²⁰

Combining an α-adrenergic blocker and 5-α reductase inhibitor. Combination therapy is appropriate and effective for patients with LUTS associated with demonstrable prostate enlargement for whom monotherapy has failed.⁹ Taken together, a 5-α reductase inhibitor and a nonselective α-1_A-adrenergic blocker alleviate symptoms more effectively than either drug can do alone.^21,22 The incidence of most adverse drug reactions with the combination is similar to the baseline risk for each drug. However, ejaculatory abnormalities are reported in 7% of patients in the combination therapy group vs 2% or less in the monotherapy groups. Discontinuation rates for combination therapy are comparable to those in the nonselective α-adrenergic blocker group.²² The adverse effect profile of combining selective α-adrenergic blockers with 5-α reductase inhibitors has not been reported; however, the combination is often used in practice.

For patients to make an informed decision about treatment, discuss with them the common adverse reactions from these agents (TABLE 2) and the need for long-term daily therapy. Also give the patient a reasonable estimate of the risk of his retention symptoms progressing.

TABLE 2
BPH medications: How they compare

Complementary medicine: Information is still limited

Herbal or complementary medicines are used worldwide to treat BPH. These products are not regulated by the US Food and Drug Administration (FDA), and therefore no standardized formulation or dosing exists. Although a few substances appear to have some positive effects, high-quality clinical trials on clinical outcomes are lacking.

The AUA guideline does not recommend the use of phytotherapy.¹ Despite this, many patients—and any number of physicians—turn to phytotherapy to treat LUTS associated with BPH.

Some patients turn to phytotherapy without their physician’s knowledge, so it’s important to ask whether they are using any herbal preparations. Agents currently used include saw palmetto, African plum, South African star grass, and Cernilton.

Saw palmetto (Serenoa repens) has been used by more than 2 million men in the United States. In 2006, Bent et al conducted a rigorously designed double-blinded trial in which 225 men older than 49 years with moderate-to-severe symptoms of BPH were treated for 1 year with saw palmetto extract (160 mg twice a day) or placebo.²³ Saw palmetto did not ameliorate the symptoms of BPH. In contrast, a Cochrane systematic review last updated in 2002 asserted that this substance caused mild-to-moderate reductions in urologic symptoms and flow measures when given to men with symptomatic BPH.²⁴ Long-term efficacy and safety of this product are unknown. Given the efficacy of saw palmetto, it is a reasonable option for men who prefer a nonprescription product to treat symptoms of BPH.

African plum (Pygeum africanum) is more effective than placebo in reducing symptoms of BPH and has few side effects, based on poorly designed small studies.^25,26 Comparative data with finasteride or the α-adrenergic blockers are lacking.

South African star grass (Hypoxis rooperi and certain species of Pinus and Picea) contain beta-sitosterols and are sources for phytotherapeutic treatments for BPH. A systematic review analyzed the effects of beta-sitosterols in men and found improved urinary symptom scores and flow measures (n=519; 4 randomized, controlled, double-blind trials; duration, 4-26 weeks).²⁷ Their long-term effectiveness and safety are not known.

Cernilton, prepared from the ryegrass pollen Secale cereale, is marketed for the treatment of BPH. A Cochrane systematic review demonstrated that comparative trials lacked a proven active control. Available evidence suggests that short-term use of cernilton is well tolerated and modestly decreases overall urologic symptoms, including nocturia. Additional randomized placebo and active-controlled trials are needed to evaluate the long-term clinical effectiveness and safety of Cernilton.²⁸

Acupuncture was not effective in treating LUTS in men in randomized controlled (single-blinded) trials.²⁹

When patients don’t respond to medical treatment

Surgery is recommended for patients who have not responded to medical treatment, who have refractory retention with a failed attempt at catheter removal, or who experience recurrent UTIs, persistent hematuria, bladder stones, or renal insufficiency.³ In addition, surgery can be the initial treatment choice for patients with high AUA symptom scores who opt for this intervention and are good operative candidates.

The specific surgical approach (open or endoscopic; electrocautery or laser) are technical decisions based on the patient’s prostate size, the individual surgeon’s judgment, and the patient’s comorbidities.^1,30 For patients who are not surgical candidates, treatment with intermittent catheterization, an indwelling catheter, or a stent is recommended.

Acknowledgements

The authors thank Jen Creer, MA, of Edit Rx, LLC, for her assistance in the preparation of this manuscript. The University of Nebraska Medical Center, with which both authors were previously affiliated, funded this writing assistance.

Correspondence
Drew M. Keister, MD, Lehigh Valley Health Network, PO Box 7017, Allentown, PA 18105-7017; drew_m.keister@lvh.com

By age 60, more than half of men have histopathologic benign prostatic hyperplasia (BPH).¹ And, given the publicity BPH is receiving today, it’s quite possible that those who are experiencing symptoms will be less reticent to discuss it than before.

So what does the evidence tell us about how to best manage these patients? Specifically, do you know what the minimal assessment is for those who are experiencing symptoms? When might advanced testing methods be helpful?

Furthermore, among men who are now 50 years old, the expected lifetime incidence for any type of surgical intervention for BPH is approximately 35%.² What are the first-line treatments available to these patients? Who might be a candidate for combination drug therapy? Are herbal preparations worth considering? When might surgery be a first choice?

These questions underscore the importance of a proper primary care framework for evaluating and treating BPH, which we can develop based on a consensus guideline released by the American Urological Association (AUA)¹ and on more recent research.

Assessing symptoms: 2 tools can help

Symptoms of BPH can include urinary frequency, nocturia, urgency, hesitancy, weak or intermittent urine stream, straining to void, and a sensation of incomplete voiding.¹ Each patient experiences a unique constellation of these symptoms. Using a urinary symptom scoring system can help define the severity of BPH and be useful in monitoring the success of subsequent therapy. Available instruments for this purpose include the AUA’s 7-question Symptom Index for BPH (http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines.cfm?sub=bph) and the International Prostate Symptom Score, which adds an eighth question to the AUA list to gauge the extent to which symptoms bother a patient (http://www.usli.net/uro/Forms/ipss.pdf).^1-5 If the patient is unclear about the pattern of his symptoms, consider asking him to keep a voiding diary.

Ruling out other causes of BPH-like symptoms

TABLE 1 lists the differential diagnoses of obstructive urinary symptoms, otherwise known as lower urinary tract symptoms (LUTS).

Look for clues in the history. Ask the patient whether he uses medications known to cause obstructive urinary symptoms—tricyclic antidepressants, first-generation antihistamines, anticholinergic agents, diuretics, narcotics, and decongestants. Does he have any first-degree relatives with prostate cancer? If the answer is yes, how young was he when the cancer was diagnosed?

Focus your examination. Perform a digital rectal examination (DRE) to check prostate size and to detect palpable nodules, induration, or irregularities associated with malignancy or infection. An enlarged prostate is commonly found on rectal examination; however, the degree of hypertrophy does not necessarily correlate with the degree of obstruction or the severity of symptoms. Any irregularity suggestive of cancer requires that you talk to your patient about his preferences for further investigation.⁶

Conduct a neurologic exam to check mental status, gait, lower extremity strength, and anal sphincter tone to assess for conditions that could cause a neurogenic bladder.

TABLE 1
Lower urinary tract symptoms are also seen with these disorders³¹

Consider these tests. Urinary tract infection (UTI) or bladder cancer may produce symptoms similar to those of BPH. For any patient who has LUTS, perform a urinalysis to screen for infection or hematuria. If a UTI is found, treat it and re-evaluate the patient. If you detect microscopic hematuria, do a further work-up to rule out bladder cancer. If DRE findings are suggestive of prostate cancer, you’ll need an ultrasound-guided biopsy and histological examination to make the diagnosis.

Optional tests in the work-up of LUTS include urinary flow rate measurements, post-void residual urine measurements, and pressure flow studies. These tests may be informative if the diagnosis is unclear based on the history and physical exam or when patients do not respond to initial therapy. Ultrasonography, intravenous pyelography, filling cystometrography, and cystoscopy are not routinely recommended for the evaluation of suspected BPH. However, they may be helpful if a patient has a complex medical history (eg, neurologic disorder or other disease known to affect bladder function, or prior failure of BPH therapy), or if he wants to pursue invasive therapy.¹

Talk to your patient about the controversial PSA test. Measuring serum prostate-specific antigen (PSA) levels to screen for prostate cancer is controversial, even for patients with LUTS. Although PSA testing can effectively detect prostate cancer in its early pathologic stages, researchers continue to investigate whether early detection significantly improves outcomes. Quite recently, 2 studies demonstrated that the test saves few lives;^7,8 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent 1 death from prostate cancer.

A subset of detected cancers appears to be clinically significant, but many cancers will not progress during a patient’s lifetime.^3,5 The United States Preventive Services Task Force (USPSTF) has concluded that the evidence is insufficient to recommend for or against routine prostate cancer screening due to the uncertainty of the balance of potential benefits (reduction of prostate cancer morbidity and mortality) and risks (false-positive results, unnecessary biopsies, and possible complications) of treatment for early disease.^9-12 Furthermore, in its 2008 update, the USPSTF specifically recommended against screening for prostate cancer in men 75 years of age and older.

The American Cancer Society says that discouraging or not offering testing is inappropriate: Men who ask their physicians to make the decision on their behalf should be tested.⁹ A 2006 Cochrane review of this topic found only 2 eligible randomized trials, both of which had high risk of bias. They concluded that insufficient high-quality evidence exists to support or refute the use of any screening for prostate cancer in any patient population, including those with BPH.¹³

Given this conflicting advice, discuss the benefits and limitations of screening with your patient before deciding whether or not to test.

What is the optimal Approach to treatment?

Patients who are not bothered by their urinary symptoms—even those with moderate to severe symptom scores—can be managed with watchful waiting. Because of the cost and frequent side effects of medications for BPH, these patients generally will not benefit from drug therapy.^3,5,14,15 However, follow-up monitoring is important, because the severity of BPH can change even without treatment.

Even if patients with moderate or severe AUA symptom scores are not bothered by their symptoms, inform them of appropriate treatment options.³ When urinary obstruction symptoms from BPH significantly interfere with daily living and sleep activities, treatment is justified.¹

Medical management, yes, but which option?

Medical therapies are not as effective as surgical intervention,¹⁶ but they often provide adequate symptom relief and cause fewer, less severe, and less permanent adverse effects than surgery. Initiate treatment with medical therapy if (1) the patient is bothered by his symptoms, (2) no significant urinary obstruction exists, and (3) you have followed the patient’s preference for prostate cancer evaluation. TABLE 2 lists prescription medications for the treatment of BPH.

Nonselective α-adrenergic blockers, such as doxazosin and terazosin, reduce prostatic smooth muscle tone, thereby improving urinary flow. A Cochrane systematic review and a subsequent large randomized trial found terazosin to be superior to placebo in improving urinary flow and decreasing symptoms in men with BPH.^16,17

Selective α-adrenergic blockers, such as alfuzosin and tamsulosin, are highly selective α-1_A-adrenergic antagonists. They are believed to be as effective as the nonselective agents, and patients may experience fewer side effects than with nonselective agents.^1,18 However, these drugs are considerably more expensive than their nonselective counterparts.

5-α Reductase inhibitors, such as finasteride and dutasteride, are more effective than placebo for patients with LUTS associated with demonstrable prostate enlargement. In a Cochrane review and subsequent large randomized trial, finasteride proved inferior to terazosin.^16,17 However, finasteride reduces the progression to urinary obstruction and the need for invasive therapy; terazosin does not.¹⁷ Finasteride achieves this effect by reducing prostatic volume by about 20% over 3 to 6 months of treatment.

Finasteride decreases PSA levels by 40% to 50%. If you conduct PSA screening for prostate cancer in a patient taking finasteride, double the PSA level before comparing it with age-related norms. Handled this way, PSA screening will not lose its sensitivity or specificity for the diagnosis of prostate cancer.¹⁹

Though a 5-mg daily regimen of finasteride reduces the overall risk of prostate cancer from 24.4% to 18.4%, it increases the risk of high-grade disease associated with higher mortality from 5.1% to 6.4%. Warn patients of this risk.²⁰

Combining an α-adrenergic blocker and 5-α reductase inhibitor. Combination therapy is appropriate and effective for patients with LUTS associated with demonstrable prostate enlargement for whom monotherapy has failed.⁹ Taken together, a 5-α reductase inhibitor and a nonselective α-1_A-adrenergic blocker alleviate symptoms more effectively than either drug can do alone.^21,22 The incidence of most adverse drug reactions with the combination is similar to the baseline risk for each drug. However, ejaculatory abnormalities are reported in 7% of patients in the combination therapy group vs 2% or less in the monotherapy groups. Discontinuation rates for combination therapy are comparable to those in the nonselective α-adrenergic blocker group.²² The adverse effect profile of combining selective α-adrenergic blockers with 5-α reductase inhibitors has not been reported; however, the combination is often used in practice.

For patients to make an informed decision about treatment, discuss with them the common adverse reactions from these agents (TABLE 2) and the need for long-term daily therapy. Also give the patient a reasonable estimate of the risk of his retention symptoms progressing.

TABLE 2
BPH medications: How they compare

Complementary medicine: Information is still limited

Herbal or complementary medicines are used worldwide to treat BPH. These products are not regulated by the US Food and Drug Administration (FDA), and therefore no standardized formulation or dosing exists. Although a few substances appear to have some positive effects, high-quality clinical trials on clinical outcomes are lacking.

The AUA guideline does not recommend the use of phytotherapy.¹ Despite this, many patients—and any number of physicians—turn to phytotherapy to treat LUTS associated with BPH.

Some patients turn to phytotherapy without their physician’s knowledge, so it’s important to ask whether they are using any herbal preparations. Agents currently used include saw palmetto, African plum, South African star grass, and Cernilton.

Saw palmetto (Serenoa repens) has been used by more than 2 million men in the United States. In 2006, Bent et al conducted a rigorously designed double-blinded trial in which 225 men older than 49 years with moderate-to-severe symptoms of BPH were treated for 1 year with saw palmetto extract (160 mg twice a day) or placebo.²³ Saw palmetto did not ameliorate the symptoms of BPH. In contrast, a Cochrane systematic review last updated in 2002 asserted that this substance caused mild-to-moderate reductions in urologic symptoms and flow measures when given to men with symptomatic BPH.²⁴ Long-term efficacy and safety of this product are unknown. Given the efficacy of saw palmetto, it is a reasonable option for men who prefer a nonprescription product to treat symptoms of BPH.

African plum (Pygeum africanum) is more effective than placebo in reducing symptoms of BPH and has few side effects, based on poorly designed small studies.^25,26 Comparative data with finasteride or the α-adrenergic blockers are lacking.

South African star grass (Hypoxis rooperi and certain species of Pinus and Picea) contain beta-sitosterols and are sources for phytotherapeutic treatments for BPH. A systematic review analyzed the effects of beta-sitosterols in men and found improved urinary symptom scores and flow measures (n=519; 4 randomized, controlled, double-blind trials; duration, 4-26 weeks).²⁷ Their long-term effectiveness and safety are not known.

Cernilton, prepared from the ryegrass pollen Secale cereale, is marketed for the treatment of BPH. A Cochrane systematic review demonstrated that comparative trials lacked a proven active control. Available evidence suggests that short-term use of cernilton is well tolerated and modestly decreases overall urologic symptoms, including nocturia. Additional randomized placebo and active-controlled trials are needed to evaluate the long-term clinical effectiveness and safety of Cernilton.²⁸

Acupuncture was not effective in treating LUTS in men in randomized controlled (single-blinded) trials.²⁹

When patients don’t respond to medical treatment

Surgery is recommended for patients who have not responded to medical treatment, who have refractory retention with a failed attempt at catheter removal, or who experience recurrent UTIs, persistent hematuria, bladder stones, or renal insufficiency.³ In addition, surgery can be the initial treatment choice for patients with high AUA symptom scores who opt for this intervention and are good operative candidates.

The specific surgical approach (open or endoscopic; electrocautery or laser) are technical decisions based on the patient’s prostate size, the individual surgeon’s judgment, and the patient’s comorbidities.^1,30 For patients who are not surgical candidates, treatment with intermittent catheterization, an indwelling catheter, or a stent is recommended.

Acknowledgements

The authors thank Jen Creer, MA, of Edit Rx, LLC, for her assistance in the preparation of this manuscript. The University of Nebraska Medical Center, with which both authors were previously affiliated, funded this writing assistance.

Correspondence
Drew M. Keister, MD, Lehigh Valley Health Network, PO Box 7017, Allentown, PA 18105-7017; drew_m.keister@lvh.com