Secondary Logo

Journal Logo

AAPA Members can view Full text articles for FREE. Not a Member? Join today!

Benign prostatic hyperplasia: A clinical review

Skinder, Danielle PA-C; Zacharia, Ilana PA-C; Studin, Jillian PA-C; Covino, Jean DHSc, MPA, PA-C

Journal of the American Academy of PAs: August 2016 - Volume 29 - Issue 8 - p 19–23
doi: 10.1097/01.JAA.0000488689.58176.0a
CME: Men's Health
Free
CME

ABSTRACT Benign prostatic hyperplasia (BPH) is an increasingly common diagnosis seen in men over age 50 years. Primary care providers must be aware of patient presentation, diagnostic tests, appropriate lifestyle modifications, treatment options, and potential complications in order to properly manage and educate patients with BPH. If left untreated, BPH can significantly decrease a man's quality of life; however, many pharmacologic and surgical treatments are available to control the symptoms.

At New York-Presbyterian/Columbia University Medical Center in New York City, Danielle Skinder practices interventional cardiology, Ilana Zacharia practices oncology, and Jillian Studin practices in the cardiothoracic ICU. Jean Covino is a clinical professor and director of didactic education at Pace University-Lenox Hill Hospital and practices at Medemerge Family Practice in Green Brook, N.J. The authors have disclosed no potential conflicts of interest, financial or otherwise.

Earn Category I CME Credit by reading both CME articles in this issue, reviewing the post-test, then taking the online test at http://cme.aapa.org. Successful completion is defined as a cumulative score of at least 70% correct. This material has been reviewed and is approved for 1 hour of clinical Category I (Preapproved) CME credit by the AAPA. The term of approval is for 1 year from the publication date of August 2016.

Figure

Figure

Box 1

Box 1

Benign prostatic hyperplasia (BPH) is one of the leading diagnoses affecting men of increasing age. By age 50 years, about 50% of men are diagnosed with BPH; by 80 years, 90% of men are diagnosed, and the greatest prevalence occurs among men ages 70 to 79 years.1,2 In BPH, a proliferation of prostatic cells leads to an increase in prostate size, urethral obstruction, and lower urinary tract symptoms.2,3 Men with BPH can experience great discomfort with urination and may develop complications including recurrent urinary tract infections (UTIs) and renal failure.2 Given the aging population, healthcare providers can expect an overall increase in the rates of BPH diagnoses, and must be able to recognize and treat the disorder.

Back to Top | Article Outline

PATHOPHYSIOLOGY

BPH occurs in the prostate's transitional zone, where stromal and epithelial cells interact. The growth of these cells is affected by sex hormones and cytokine responses.2

Back to Top | Article Outline

Dihydrotestosterone (DHT)

Within the prostate, testosterone is converted to DHT, the androgen thought to be the main mediator of prostatic hyperplasia. The clinical importance of DHT became clear when patients treated with orchiectomy and 5-alpha-reductase inhibitors (which stop conversion of testosterone to DHT) showed decreases in BPH symptomatology. The role of DHT was further demonstrated when men with BPH were found to have significantly higher DHT levels within prostate tissue compared with men whose prostates were of normal size.4

Box 2

Box 2

Back to Top | Article Outline

Age

Because plasma androgen levels decrease with age, more data are needed to specify why BPH occurs as men get older. Estrogens may play a role in BPH, targeting stromal cells through an estrogen receptor mechanism. The ratio of estrogens to androgens increases with age, and this may explain why BPH occurs among men as they get older; however, more evidence is needed to reach a definitive conclusion.4

Back to Top | Article Outline

Cytokines

Cytokines contribute to prostate enlargement by inciting an inflammatory response and by inducing epithelial growth factors. As the prostate enlarges due to hyperplasia, the portion of the urethra that passes through the prostate is compressed, ultimately compromising urinary outflow and leading to obstructive symptoms. The patient develops bladder hyperactivity, inflammation, and distension as bladder smooth muscle cells enlarge to maintain urine flow in response to resistance from prostatic obstruction. These changes cause oxidative stress and free radical formation, as well as alterations to the alpha-adrenergic nerves of the bladder, resulting in storage symptoms (Table 1). When bladder smooth muscle cells can no longer grow and thereby counteract this resistance, smooth muscle contractions become impaired and voiding symptoms dominate.2

TABLE 1

TABLE 1

Back to Top | Article Outline

RISK FACTORS

Common risk factors for BPH include increasing age, functioning testicles, metabolic syndrome, family history of BPH, obesity, history of diabetes, and black race.2,5

A patient's diet, smoking, and exercise can influence BPH progression.2,6,7 Patients who consume a diet rich in vegetables appear to have less severe BPH symptoms than those who do not, although the consumption of fruit has not been shown to have a similar significant relationship to BPH severity. A diet high in starches and meat has been linked to an increased risk of developing BPH. Studies have also shown that excessive alcohol intake can increase BPH risk and progression.2 Although smoking may be a risk factor for BPH, conflicting evidence precludes the establishment of such a relationship.7

Studies demonstrate that a sedentary lifestyle can increase the risk of developing BPH or intensify the severity of lower urinary tract symptoms in patients who already have the condition.6 Incorporating exercise and physical activity into the daily routine are important, because activity can help prevent BPH as well as metabolic syndrome, which is strongly linked to BPH. Being physically active is also more cost-effective than using pharmacologic or surgical interventions for treating BPH.6

Once a patient is diagnosed with BPH, clinicians and patients must be aware of factors associated with worsening disease progression, including increased age, severe lower urinary tract symptoms, increased prostate size, and high prostate-specific antigen (PSA) levels.5

Back to Top | Article Outline

CLINICAL MANIFESTATIONS

The symptoms of BPH can be grouped into two main categories: storage and voiding (Table 1). Men may have few of these symptoms initially, but with increasing age and disease progression, symptoms can become more prevalent.3 Patients with BPH often report that the symptoms are distressing and bothersome, and impair their quality of life.8

Back to Top | Article Outline

DIAGNOSIS

Practically speaking, BPH is a diagnosis of exclusion. When men over age 50 years complain of lower urinary tract symptoms, the following tests can be used to rule out all other possible causes before arriving at a BPH diagnosis.1

Back to Top | Article Outline

History

Healthcare providers must ask specific questions about storage and voiding symptoms, and should be aware of excessive water consumption or diuretic use that may account for a patient's symptoms.5 The American Urological Association Symptom Index (AUASI) and the International Prostate Symptom Score (IPSS) are subjective questionnaires that can be used to help evaluate lower urinary tract symptoms and their effect on patients suffering from BPH.3,5 These questionnaires have patients rate symptoms of incomplete bladder emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia on scales from 0 (not at all) to 5 (almost always). The scores are then tallied, and classified as mild (0-7), moderate (8-19), or severe (20-35).9 These rankings help to guide treatment decisions and responses.3 The IPSS contains identical questions to that of AUASI, but includes an additional quality of life measure, asking patients to classify their feelings if they had to live with their urinary symptoms for the rest of their lives on a scale of 0 (delighted) to 6 (terrible).9,10

TABLE 2

TABLE 2

Back to Top | Article Outline

Digital rectal examination (DRE)

Perform a DRE to assess the size, shape, and consistency of the prostate gland.3 An enlarged prostate often presents on examination as soft, smooth, boggy, mobile, and with an obscured sulcus. Note any nodules or indurations, which may suggest prostate cancer.

Back to Top | Article Outline

Prostate-specific antigen (PSA) level

Given the challenges of evaluating true prostate size in primary care offices by DRE, obtaining a PSA level makes it easier to diagnose BPH. PSA levels often correlate with prostate size; therefore, a PSA level of 1.5 ng/mL is often indicative of BPH.1 However, this value is highly variable and may fluctuate based on the patient's age, race, medications, or comorbid urinary conditions. Due to the nonspecific nature of PSA, a diagnosis of BPH cannot be made from PSA levels alone. Yet in the presence of other positive diagnostic outcomes, an elevated PSA level can help a primary care provider arrive at a BPH diagnosis.1

Back to Top | Article Outline

Urinalysis

Ordering a urinalysis is recommended as a primary step in order to exclude UTI, prostatitis, cystolithiasis, nephrolithiasis, renal cancer, and prostate cancer as causes of lower urinary tract symptoms.5

Back to Top | Article Outline

Voiding diaries

Documenting the time voided, volume voided, and associated activities (such as fluid intake) in a voiding diary may help in BPH diagnosis, especially in patients with urinary frequency. The primary care provider can differentiate if symptoms are BPH-related or due to polyuria, overactive bladder, or behavioral causes. Patients should keep a voiding diary for at least 24 hours, although many primary care providers suggest keeping it for 3 to 7 days so that they can evaluate trends.2,11 Voiding diaries also can be used to evaluate treatment efficacy.

Back to Top | Article Outline

Measuring postvoid residual volume

A postvoid residual volume measurement is recommended for patients with moderate or severe symptoms, defined by an AUASI/IPSS score of 8 or greater.11 Symptoms of BPH can be associated with urinary retention, and a large residual volume in combination with other tests may indicate BPH.5

Back to Top | Article Outline

Prostatic ultrasound

Transabdominal or transrectal prostatic ultrasound also may be considered to accurately evaluate the size, shape, anatomy, and potential pathology of the prostate in a minimally invasive, cost-effective, and reproducible way.2,12 A transabdominal ultrasound also can assess the bladder and postvoid residual urine, which may be contributing to a patient's symptoms.2

Back to Top | Article Outline

Blood urea nitrogen (BUN) and creatinine

Serum BUN and creatinine levels may be used in diagnosing and monitoring BPH, although the use of these levels in initial BPH assessment is controversial. The European Association of Urology (EAU) recommends obtaining baseline BUN and creatinine measurements and watching for potential renal failure complications associated with BPH.2 The American Urological Association (AUA) does not suggest obtaining these baseline levels because preliminary renal insufficiency tends to be equal among men of similar ages regardless of whether they have BPH.11 However, measuring the patient's BUN and creatinine levels may help evaluate progressive obstruction and impaired renal function.

Refer the patient to a urologist if his symptoms are too severe or complicated to evaluate and treat in a primary care setting.5 Increasing PSA levels, persistent hematuria, urinary retention, recurrent urinary tract infections, possible prostate cancer, renal failure, or inadequate pharmacologic treatment are indications for a urology consult.3

Back to Top | Article Outline

TREATMENT

Many pharmacologic (Table 3) and surgical interventions have been approved for treating BPH, with the goals of improving patient symptoms and quality of life while slowing disease progression and reducing complications.9 Treatment decisions are based on the severity of the condition.

Back to Top | Article Outline

Watchful waiting

For men with mild BPH symptoms (IPSS less than 8), watchful waiting is recommended. This includes yearly follow-up appointments with history and physical examination to determine the progression of the disorder and reevaluate treatment options.5 During this time period, various behavioral modifications, such as avoiding antihistamines, reducing fluid intake in the evening, and decreasing alcohol and caffeine consumption can provide symptom relief.11

Men suffering from moderate to severe symptoms (IPSS of 8 and greater) may consider lifestyle changes, but will likely require pharmacologic treatment or surgery if pharmacologic treatment fails.2,11 Patients on medication should be evaluated at least twice a year in the office to discuss the efficacy of the medication and potential dose adjustment. They also should undergo DRE and PSA screening at least annually.

Back to Top | Article Outline

Alpha-adrenergic receptor antagonists

The mainstay of BPH treatment, these medications inhibit sympathetic adrenergic receptors, causing prostatic and bladder smooth muscle cell relaxation.5 The resultant reduced urethral constriction and improved urinary flow lessen obstructive BPH symptoms.3

Alpha-adrenergic receptor antagonists are further subclassified according to their extent of selectivity for certain alpha-1 receptors. Doxazosin, terazosin, and alfuzosin are considered nonselective, blocking all alpha-1 receptors equally; silodosin and tamsulosin are selective for alpha-1A receptors that are mainly located in the urogenital tract.5 Selective agents are associated with fewer systemic adverse reactions (such as hypotension, dizziness, and fatigue) than nonselective agents.3,9 Clinicians should avoid prescribing nonselective alpha-blockers to older adults because these drugs can cause orthostatic hypotension and syncope.13 However, a patient with BPH and hypertension may be a candidate for a nonselective agent because it would treat both conditions.

Both types of alpha-adrenergic receptor antagonists cause clinically significant decreases in BPH symptoms after 1 week of therapy, as reflected by AUASI score decreases; however, 2 to 4 weeks of treatment is recommended to achieve the full effect of the medication.

Alpha-adrenergic receptor antagonists should not be prescribed to patients planning to have cataract surgery due to the risk of floppy iris syndrome.5 Because this class of medications does not reduce prostate size, patients are still at risk for urinary retention, associated complications, and disease progression.3

Back to Top | Article Outline

5-alpha-reductase inhibitors

Another first-line drug option is a 5-alpha-reductase inhibitor, which blocks the conversion of testosterone to DHT, inhibiting prostatic hyperplasia, reducing prostate size, and slowing disease progression. Treatment with a 5-alpha-reductase inhibitor reduces urinary retention and the need for future BPH surgeries, and should be started in patients with PSA levels greater than 1.5 ng/mL, as long as patients have no contraindications. Within 2 to 6 months, men taking 5-alpha-reductase inhibitors for BPH treatment should experience a 25% decrease in prostate size and an improvement in BPH symptoms.5 These drugs can be used as monotherapy or adjunct therapy to alpha-adrenergic receptor antagonists. Combination therapy is more successful than monotherapy but is associated with more adverse reactions.5

Back to Top | Article Outline

Tadalafil

This drug, mainly used to treat erectile dysfunction, is the phosphodiesterase-5 inhibitor approved for BPH treatment. Tadalafil causes smooth muscle relaxation of the detrusor muscle, prostate, and vascular cells of the urinary tract, and decreases prostatic and bladder hyperplasia.5 After 4 weeks of use, tadalafil improves lower urinary tract symptoms and quality of life, and is an option for men suffering from concomitant BPH and erectile dysfunction.5,8

Back to Top | Article Outline

Anticholinergic agents

This class of medication has been approved as add-on therapy when alpha-adrenergic antagonists fail to control BPH symptoms. Anticholinergics block muscarinic receptors on the detrusor muscle and improve storage symptoms after fewer than 12 weeks of therapy.5 However, anticholinergics may exacerbate constipation, cognitive impairment, and dementia in older adults, and should be avoided or closely monitored if used in these patients.13

Back to Top | Article Outline

Saw palmetto

This herb has been used to reduce lower urinary tract symptoms; however, recent data propose that symptom improvement may be solely a placebo effect.14

Back to Top | Article Outline

Surgery

Surgical treatment for BPH is indicated when medical treatment fails to elicit a sufficient response, when symptoms are severe, if there is concern for complications, or if the patient has renal failure, refractory gross hematuria, recurrent UTIs, or bladder stones.11 Recommended options include open surgery, transurethral resection of the prostate (TURP), and transurethral holmium laser enucleation of the prostate (HoLEP).2

Open surgery involves removing the prostatic adenoma from the adjacent prostate tissue. With the enlarged prostate no longer compressing the urethra, voiding symptoms improve postoperatively. This procedure carries the risk of several complications including wound infection, hemorrhage, UTI, and sepsis.

TURP is the gold standard for BPH treatment and is the most commonly performed procedure for men suffering from BPH.1,2 During TURP, an endoscope is inserted through the urethra and the prostatic adenoma is removed via loop electrode. TURP is effective for improving BPH symptoms but may cause complications such as hemorrhage, hyponatremia, and retrograde ejaculation.

Bipolar TURP uses bipolar current and is a minimally invasive procedure associated with fewer complications and a shorter hospital stay. Because 0.9% sodium chloride solution can be used for irrigation instead of nonconducting glycine as in monopolar TURP, the procedure can be longer and complications are reduced.

HoLEP, another minimally invasive procedure, involves removal of the prostate adenoma by laser irradiation, and can be considered in men who do not qualify for TURP due to prostate size. Although HoLEP is a longer surgical procedure than TURP, it is less commonly associated with complications and requires a shorter hospital stay.2,9

Temporary and permanent urethral stents are also used to treat BPH in high-risk patients who are unable to undergo invasive surgery. The minimally invasive procedure involves endoscopic stent placement into the prostatic urethra, improving BPH symptoms and minimizing complications because of the smaller incision and reduced trauma to the surrounding tissue.2

Botulinum toxin is another potential treatment option that has been explored but is not approved. Injecting the toxin into the prostate inhibits acetylcholine release, resulting in smooth muscle paralysis and tissue atrophy.2 Acute inflammation is followed by scarring and shrinkage of the prostate.

Back to Top | Article Outline

COMPLICATIONS

Recurring urinary retention is a common complication of BPH. Men at greater risk for urinary retention are those with PSA levels above 1.6 ng/mL or prostate volumes over 31 mL. Other complications include bladder calculi as a result of urinary stasis and UTIs from increased postvoid residual urine. Macroscopic hematuria and renal failure have also been observed.2

Patients also may develop sexual dysfunction as a result of pharmacologic or surgical interventions. Erectile dysfunction has been reported in patients taking 5-alpha-reductase inhibitors, and men taking these medications or alpha-adrenergic antagonists have reported ejaculatory dysfunction. Ejaculatory dysfunction also is a complication in 80% of men undergoing open surgery and 65% to 80% of men undergoing TURP.2

Back to Top | Article Outline

PATIENT EDUCATION

Patients with BPH or at risk for the condition should be told about the symptoms, preventive measures that can be integrated into daily life, diagnostic tests, treatments, possible complications, and when to schedule follow-up appointments with their primary care providers.

Clinicians should encourage patient lifestyle modifications to decrease the risk of developing BPH or to help control preexisting symptoms. Such lifestyle modifications include diet and exercise to maintain a healthful weight, limiting excessive water intake, limiting or avoiding coffee and alcoholic beverages, and bladder training (including urinating at least once every 3 hours).2

Patients also should be aware of the symptoms of BPH complications so they can seek adequate medical attention if necessary. Encourage patients to return to the primary care office if their symptoms worsen or they develop dysuria, pelvic pain, urinary retention, or hematuria.

Patients with mild symptoms who are otherwise healthy should see their primary care provider annually. Those taking alpha-adrenergic receptor antagonists should follow up every 2 to 4 weeks for the first year of therapy and then yearly thereafter if symptoms are controlled. Patients taking a 5-alpha-reductase inhibitor should see their primary care provider every 3 months during the first year of therapy, and then annually.11 Patients who have had TURP should follow up with their providers on an individual basis.

Back to Top | Article Outline

CONCLUSION

As the US population ages, the prevalence of BPH is bound to increase. Primary care providers must be well-versed on the definition, pathophysiology, associated risk factors, evaluation, diagnosis, treatment, prevention, and complications of BPH. Providers must ask patients about lower urinary tract symptoms when taking a health history of older men, so they can manage patients optimally and refer them to a specialist when indicated.

Back to Top | Article Outline

REFERENCES

1. Sausville J, Naslund M. Benign prostatic hyperplasia and prostate cancer: an overview for primary care physicians. Int J Clin Pract. 2010;64(13):1740–1745.
2. Homma Y, Gotoh M, Yokoyama O, et al. Outline of JUA clinical guidelines for benign prostatic hyperplasia. Int J Urol. 2011;18(11):741–756.
3. Kapoor A. Benign prostatic hyperplasia (BPH) management in the primary care setting. Can J Urol. 2012;19(suppl 1):10–17.
4. Ho CK, Habib FK. Estrogen and androgen signaling in the pathogenesis of BPH. Nat Rev Urol. 2011;8(1):29–41.
5. Sarma AV, Wei JT. Clinical practice. Benign prostatic hyperplasia and lower urinary tract symptoms. N Engl J Med. 2012;367(3):248–257.
6. Lee HW, Kim SA, Nam JW, et al. The study about physical activity for subjects with prevention of benign prostate hyperplasia. Int Neurourol J. 2014;18(3):155–162.
7. Parsons JK. Benign prostatic hyperplasia and male lower urinary tract symptoms: epidemiology and risk factors. Curr Bladder Dysfunct Rep. 2010;5(4):212–218.
8. Dong Y, Hao L, Shi Z, et al. Efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a meta-analysis. Urol Int. 2013;91(1):10–18.
9. Djavan B, Dianat SS, Kazzazi A. Effect of combination treatment on patient-related outcome measures in benign prostatic hyperplasia: clinical utility of dutasteride and tamsulosin. Patient Relat Outcome Meas. 2011;2:71–79.
10. Barry MJ, Fowler FJ Jr, O'Leary MP, et al. The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association. J Urol. 1992;148:1549–1557.
11. McVary KT, Roehrborn CG, Avins AL, et al.AUA Practice Guidelines Committee. AUA guideline on management of benign prostatic hyperplasia. Chapter 1: guideline on the management of benign prostatic hyperplasia (BPH). https://www.auanet.org/education/guidelines/benign-prostatic-hyperplasia.cfm. Accessed April 12, 2016.
12. Kim SB, Cho IC, Min SK. Prostate volume measurement by transrectal ultrasonography: comparison of height obtained by use of transaxial and midsagittal scanning. Korean J Urol. 2014;55(7):470–474.
13. American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American geriatrics society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2012;60(4):616–631.
14. Barry MJ, Meleth S, Lee JY, et al. Complementary and Alternative Medicine for Urological Symptoms (CAMUS) Study Group. Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: a randomized trial. JAMA. 2011;306(12):1344–1351.
Keywords:

benign prostatic hyperplasia; alpha-adrenergic antagonists; 5-alpha-reductase inhibitors; transurethral resection of the prostate; TURP; urinary retention

Copyright © 2016 American Academy of Physician Assistants