Prostate Health Considerations: The Pharmacist's Role

Justin J. Sherman, PharmD
Published Online: Monday, August 1, 2005
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Prostate Health Considerations: The Pharmacist's Role Justin J. Sherman, PharmD 75

Behavioral Objectives

After completing this continuing education article, the pharmacist should be able to:

  1. Discuss the prevalence of prostate disorders and the general concerns of patients regarding their prostate health.
  2. Describe common lower urinary tract symptoms and treatment options for patients with benign prostatic hyperplasia (BPH).
  3. Recognize the presentation of a patient with one of the different types of prostatitis, and recommend treatment for each.
  4. Counsel patients with prostate cancer with regard to treatment options.
  5. Recommend medication treatment for BPH, prostatitis, and prostate cancer. Also, the pharmacist should be able to monitor the efficacy of medication treatment and adverse effects.
  6. Develop ways that management of prostate health and counseling can fit into the pharmacist's practice.

The prostate is a male accessory sex gland located below the urinary bladder and anterior to the rectum. This walnut-sized gland is heart-shaped, soft, and mobile on palpation, which is done manually through the rectal mucosa. The gland secretes an alkaline fluid that becomes part of the semen during ejaculation. The high concentration of zinc that is found in the fluid may provide an antibacterial effect.

Although the physiologic function of the prostate is minimal, its impact on the quality of life in elderly patients can be quite profound—regardless of whether the patient has benign prostatic hyperplasia (BPH), prostatitis, or prostate cancer.1-3 These disorders will be discussed, with an emphasis on available medication treatments and opportunities for pharmacists to use their unique, interventional skills for each disease state.

Presentation of the Patient with BPH

BPH is characterized by lower urinary tract symptoms (LUTS) that are bothersome and can be attributed to either prostate tissue hyperplasia or increased tone. Although the relationship between BPH and LUTS is complex and has not been completely elucidated, BPH may result from a variety of factors. In the adult, testosterone is converted into dihydrotestosterone (DHT) by the intraprostatic enzyme 5α-reductase. A growth spurt of the prostate tends to occur between the ages of 40 and 80, largely thought to be due to DHT. Many men experience prostate growth; however, in patients who present with LUTS, this growth spurt may result in hyperplasia of prostate tissue around the neck of the bladder. This is known as the static component of BPH. The dynamic component of BPH occurs because stimulation of α1-adrenergic receptors within prostate tissue leads to smooth muscle contraction and increased tone in the bladder neck, thus causing further obstruction. Current medications for this condition are targeted for relief of its static and dynamic components.1

Static and dynamic factors together result in the LUTS with which BPH patients present. Symptoms—including hesitancy, dribbling, incomplete emptying, weak stream, and straining to urinate—usually are obstructive in nature on initial presentation.1 During this phase of BPH, the prostate has enlarged substantially so as to interfere with bladder emptying. Prostate size is not necessarily proportional to the severity of LUTS, however, as symptoms depend primarily on the amount of urethral lumen and bladder neck obstruction. Patients with hesitancy may need to put pressure manually on their bladders to initiate voiding, and dribbling could cause the patient public embarrassment.

As BPH progresses, urinary frequency, urgency, and nocturia can develop. These irritative symptoms are consequences of long-standing bladder neck obstruction, whereby the muscles of the bladder neck enlarge in an attempt to compensate for the obstruction.4 This hypertrophy results in bladder decompensation, with a diminished capacity to store urine. Urinary frequency and urgency develop because the bladder becomes hypersensitive to the small amounts of urine that cannot be cleared through regular voiding. Patients may exhibit "toilet mapping," whereby the incessant need to urinate induces them to accommodate voiding into every activity of daily living. Furthermore, nocturia awakens patients every couple of hours throughout the night. Some patients even admit to keeping a bedpan or a makeshift urinal in their bedrooms.

Eventually, untreated BPH can lead to recurrent urinary tract infections (UTIs) due to the inability to void completely. Other complications include chronic renal impairment, bladder stones, incontinence, and hematuria.1 Thus, a patient presenting with longstanding, untreated BPH may require assessment for possible complications.

A patient presenting with LUTS represents only a probable case of BPH. Subsequent tests, such as the serum biochemical marker prostate-specific antigen (PSA) test and a digital rectal examination (DRE), must be done to rule out other causes of LUTS. Thus, the diagnosis of BPH is made primarily after other common causes, such as prostatitis and prostate cancer, are ruled out.5 For example, a current PSA level test can help rule out a potential diagnosis of prostate cancer. Whereas a PSA level of <4 ng/mL is considered normal, a level of >10 ng/mL can predict prostate cancer about 66% of the time. A PSA level between 4.1 ng/mL and 10 ng/mL may indicate BPH when other causes of LUTS are ruled out.6

The American Urological Association Symptom Score Index (AUASI) is the most widely used clinical assessment instrument for LUTS from BPH (Table 1). Because alleviation of symptoms is the main goal for patients with BPH, treatment is aimed at decreasing these symptom scores. The clinician records a baseline score when the patient is diagnosed with BPH, thus allowing recognition of a treatment effect once medication is started. Patients themselves generally recognize relief or worsening of LUTS when the AUASI decreases or increases by 3 points, respectively.5

figure

In addition to improving symptoms, the traditional goals of therapy include attenuating disease progression and preventing complications from either untreated or undertreated BPH. Because quality of life and symptom improvement are the main goals, the patient's concerns should take precedence in treatment considerations. An initial evaluation would include a detailed history of LUTS, a past medical history, a record of concomitant medications, and a baseline PSA and DRE. Next, the clinician would categorize the patient as having mild, moderate, or severe BPH, based on the AUASI (from a score of 0-7, 8-19, and 20-35, respectively). The subsequent treatment plan would depend upon this categorization.1 Whereas mild BPH usually is treated with watchful waiting, moderate BPH with bothersome symptoms can be managed with medications. Treatment options for severe BPH include surgical intervention with prostate resection or with minimally invasive treatments including transurethral needle ablasion, transurethral microwave heat treatment, and interstitial laser therapy.7

Role of Medications for Relief of LUTS

As stated above, moderate BPH usually is managed via medications, including α1-receptor inhibitors and 5α-reductase inhibitors. The α1-receptor inhibitors decrease smooth muscle tone in the prostate tissue, urethra, and bladder neck, thereby alleviating the dynamic component of LUTS. Their action of relieving LUTS is relatively quick, compared with that of 5α-reductase inhibitors. Thus, α-receptor blockers are considered first-line therapy when the patient needs significant and rapid symptom relief.8 They do not exert any appreciable effect on either prostate size or PSA levels, however.

The α1-receptor inhibitors can be stratified as first-, second-, or third-generation agents. Stratification depends upon several factors, including adverse effect profile, degree of receptor selectivity, and chronology of discovery of each medication. Stratification is not, however, related to efficacy since all α1-receptor blockers are equally efficacious. Phenoxybenzamine is the sole first-generation agent, but its nonselectivity and severe cardiovascular adverse effects make it an unpalatable choice for BPH. The second-generation agents include terazosin and doxazosin. Tamsulosin and alfuzosin comprise the third-generation agents.7

Terazosin and doxazosin are considered long-acting second-generation α1-receptor inhibitors.9 The once-daily starting doses for these medications are generally low (1 mg at bedtime [hs] for each), and they are titrated by doubling the dose every 2 weeks until either the patient has significant relief of LUTS or the maximum dose is achieved (10 mg hs and 8 mg hs for terazosin and doxazosin, respectively). Terazosin and doxazosin inhibit both subreceptors of α1 (α1A receptors and α1B receptors, which are found mainly in the prostate and the vascular epithelium, respectively).9 Thus, the use of a low starting dose and nighttime administration attenuate the first-dose effects of orthostatic hypotension, which results from the inhibition of α1B receptors. Other adverse side effects include syncope, malaise, dizziness, and somnolence.9 Prazosin, another α1-receptor inhibitor, is not approved by the FDA for BPH, and its use generally is not feasible due to the need for 3-times-daily dosing.

The third-generation α1-receptor inhibitors, tamsulosin and alfuzosin, are known as uroselective blockers because of their selective action on prostate tissue without a concomitant reduction in blood pressure. Tamsulosin, available as a 0.4-and a 0.8-mg/day dose, exhibits a 10 to 12 times greater affinity for α1A receptors, which results in clinically insignificant orthostatic changes and first-dose effects.10 Although dosing is once daily, administration at bedtime is not necessary. Also, the onset of effect can occur within the first week of therapy, and dose titration usually is not needed. In fact, clinical trials revealed that the higher dose increased the onset of adverse effects without increasing the degree of symptom relief. Tamsulosin is generally well tolerated. Its adverse effects include rhinitis, dizziness, asthenia, and abnormal ejaculation.10

Although alfuzosin also exerts a selective action on prostate tissue without reducing blood pressure, this effect is not necessarily related to receptor specificity. Available as a 10-mg/day dose, it is similar to tamsulosin with respect to the clinically insignificant orthostatic hypotension and onset of effect. It shares the same mild adverse effects, with the exception of the ejaculatory dysfunction sometimes encountered with tamsulosin.11

The 5α-reductase inhibitors, finasteride (5 mg daily) and dutasteride (0.5 mg daily), decrease conversion of testosterone to DHT in the prostate. These medications also cause apoptosis of prostate cells, thus alleviating the static component of BPH, eventually shrinking the prostate tissue itself, and relieving LUTS.12-14 Daily administration results in symptom improvement after an average of 6 months. Also, patients with a significantly enlarged prostate (40 g) experience the greatest symptom improvement. Finally, patients taking this class of medications are less likely to have acute urinary retention or to need surgical intervention.

Two special concerns regarding the use of 5α-reductase inhibitors need to be discussed. These drugs are contraindicated in women when they are or may potentially be pregnant, because they can cause abnormalities in the male fetus. Also, women who are or may be pregnant should not handle crushed or broken tablets due to the potential for absorption of the medication through skin. Only crushed tablets are harmful, however, because a protective coating alleviates this concern with normal handling. Another concern regarding finasteride is that, since it causes an actual reduction in the size of the prostate—and prostate size is proportional to PSA—patients receiving finasteride may lose the sensitivity of the PSA in detecting prostate cancer. This sensitivity is not compromised, however, if the patient's PSA value is multiplied by a factor of 2 when finasteride has been taken for 6 months or longer.15 Adverse effects most prevalent with this class include erectile dysfunction, ejaculatory disorders, and gynecomastia.

The most widely used phytotherapeutic agent is Serenoa repens (saw palmetto). Patients who present with mild LUTS and are already taking herbal therapy should be monitored for disease progression. Actual studies regarding efficacy suffer from poor study design. Furthermore, phytotherapy should not be used for the relief of moderate or severe BPH because delaying proper treatment could lead to complications.16

Because α-receptor blockers and 5α-reductase inhibitors have different mechanisms of action, the presumption would be that efficacy increases when both types are used together. This hypothesis was confirmed in the Medical Therapy of Prostatic Symptoms (MTOPS) Study, the longest and largest trial conducted to date regarding combination therapy.17 This 5-year study revealed that combination therapy with doxazosin and finasteride versus either medication alone significantly reduced overall risk of disease progression and improved AUASI scores. Therefore, combination therapy is appropriate for men with an increased risk of disease progression or inadequate relief of symptoms with the maximum dose of monotherapy.

Prostatitis: Classification, Presentation, and Treatment

Prostatitis, an inflammation of the prostate gland, is a common condition diagnosed during 2 million physician visits yearly and affecting approximately 10% of all adult men.18 This common condition can range from a comparatively simple case of acute bacterial prostatitis to a more complex, chronic form that is still plagued by a poor understanding of the underlying pathophysiology and treatment.19 Indeed, both patients and physicians may become frustrated with the chronic, relapsing forms of prostatitis. Although a clinical diagnosis of prostatitis is based on the patient history and physical examination, no consensus exists with regard to the physical findings or a diagnostic laboratory test. In 1998, the National Institutes of Health developed a widely used classification system, which includes the following 4 categories: (I) acute bacterial prostatitis; (II) chronic bacterial prostatitis; (III) chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); and (IV) asymptomatic inflammatory prostatitis.2

Acute Bacterial Prostatitis (Category I)

Acute bacterial prostatitis presents with symptoms of a UTI, including increased urinary frequency, dysuria, urgency, and a varying degree of bladder outlet obstruction. Also, patients often experience malaise, fever, and myalgias, suggesting a more systemic infection.

Causative uropathogens usually are gram-negative, with the most common one being Escherichia coli. Klebsiella, Proteus, Enterococci, and Pseudomonas are other species that may be found upon culturing the urine. Initial antibiotics are customarily prescribed empirically, but they can be modified if the pathogen is later found to be susceptible to another regimen. Standard antibiotics used for acute infections include trimethoprim-sulfamethoxazole (TMP-SMX), tetracycline, or a quinolone. Although the proper duration of therapy has not been clearly defined, antibiotics can be continued for 3 or 4 weeks to prevent relapse if the patient continues to respond clinically. Compared with the other categories, acute bacterial prostatitis is easily recognized and treated.

Chronic Bacterial Prostatitis (Category II)

The same organism, usually E coli, often causes the recurrent episodes of UTI that occur with chronic bacterial prostatitis. Cultures of prostate-specific specimens such as expressed prostatic secretions (EPS) suggest that the prostate is the focal point of infection, although no single clinical finding is diagnostic. The symptoms can be quite variable, including irritative LUTS, fever, myalgias, and pain in the back, testes, or penis. Patients can be asymptomatic between remitting episodes, however, and the prostate is often normal on DRE.

The efficacy of antibiotic treatment depends upon penetration of the lipophilic antibiotic into the prostatic epithelium. Unfortunately, most of the antibiotics that achieve highest penetration are not effective for gram-negative uropathogens. Therefore, failure is thought to occur because of poor antibiotic penetration.2 Due to the expense of newer antibiotics and the need for prophylactic therapy for recurrent disease, 4-to 12-week therapy with TMP-SMX or fluoroquinolones is a reasonable initial choice.

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) (Category III)

While acute and chronic bacterial prostatitis (categories I and II) are the best understood forms, they are much less common than CP/CPPS. This condition, formerly called nonbacterial prostatitis, generally is diagnosed when chronic symptoms are accompanied by negative midstream urine cultures. In contrast with the other forms, CP/CPPS suffers from a limited understanding as to the underlying etiology. In fact, studies have suggested that the prostate may not even be the source of pain for this condition. Instead, pain may result from a complex interaction between psychological factors and dysfunction in the neurologic, immune, and endocrine systems.20 Therefore, other causes of pelvic pain must be excluded.

Traditionally, CP/CPPS has been subcategorized into 2 subtypes, based on whether patients have leukocytes in their EPS (IIIA. inflammatory) or no evidence of inflammation (IIIB. noninflammatory). Treatment strategies for CP/CPPS include antibiotics and α-blockers. Colonization of uropathogens and infection in the prostate can develop in patients with inflammatory CPPS, and studies suggest that up to 50% of patients in this subclass respond to antibiotic therapy when it is given for 2 to 4 weeks.18 Data are emerging, however, to indicate that antibiotics are not helpful for patients with noninflammatory CPPS.21 In this subclass of patients, α-blockers have been useful in pain relief when given for an extended period of time (14-24 weeks). Medications that have been studied include terazosin, alfuzosin, and finasteride 5 mg daily (useful for pain relief in one study).22-24 It is worth noting, however, that a recent trial comparing ciprofloxacin, tamsulosin, both, and placebo resulted in no significant differences in all groups studied.25

Until more research is completed regarding CP/CPPS, patients with this frustrating, painful form of prostatitis may continue to experience substantial morbidity. The following are 3 reasonable axioms to keep in mind for the treatment of CP/CPPS: (1) although antibiotics have been shown to relieve pain for patients in category IIIA, ongoing empiric administration in patients with long-standing CP/CPPS is not recommended19; (2) prolonged treatment with α-blockers appears to be necessary to yield pain relief21; and (3) patients with ongoing, refractory CP/CPPS may need combination therapy, although further studies in this area are needed.21

Asymptomatic Inflammatory Prostatitis (Category IV)

Patients are placed in this category when other urinary tract issues are being evaluated. Infection or inflammation of the prostate occurs in the absence of pain. No treatment is indicated unless the patient presents with an elevated PSA level or unless prophylaxis is needed prior to endoscopy or surgery.

Considerations for the Patient with Prostate Cancer

Accounting for 11% of the cancerrelated deaths in men, malignancy of the prostate is the second leading cause of cancer-related death—second only to lung cancer.26 Although the overall 5-year survival rate is quite encouraging (96%), survival rates are dependent upon the extent of disease progression at diagnosis. For example, the 5-year survival rates range from approximately 100% for those with localized cancer to 34% for those with disease metastasis. Survival rates do decrease over time, though, with overall survival decreasing to 75% and 54% after 10 years and 15 years, respectively.26

Prostate cancer is a disease of the elderly. Incidence correlates with age and varies with race and other risk factors. The average age of men at diagnosis is 72. Although Hispanics, Asians, and Native Americans all have a lower incidence of this malignancy than Caucasians, African Americans have a higher incidence. In addition to age and race as primary risk factors, a family history of a first-degree relative with prostate cancer increases the risk. Specifically, the risk doubles or triples if the patient's father or brother, respectively, has prostate cancer. Other possible risk factors include BPH, high-fat or low-fiber diets, or decreased consumption of soy protein or vitamin E.27

Because the 5-year survival statistics are relatively favorable, screening remains controversial, based on the fact that routine screening has not yet decreased mortality. The American Urological Association recommends screening with a DRE and a PSA assessment yearly when men reach 50 years of age and have at least a 10-year life expectancy. The American Cancer Society additionally recommends that screening should begin at age 45 for African Americans or when 2 or more first-degree relatives have had prostate cancer.26

Both the DRE and the PSA concentration are used to screen for prostate cancer, although both are fraught with uncertainties in detection. An enlarged, nodular prostate could suggest prostate cancer, but the DRE is limited by its variability with clinician observation. The PSA can be used to assist in the diagnosis of prostate cancer, and it also serves as a tool to monitor disease progression and efficacy of treatment. Yet, the PSA is a limited tool that is poorly predictive of cancer unless the PSA is >10 ng/mL (a 66% chance). Comparatively, there is a 25% chance of cancer when the PSA is in the "gray area" of 4 to 10 ng/mL.26 The goal for using the DRE and the PSA test is to target those patients most likely to need biopsy or expensive imaging procedures, thus avoiding aggressive screening and treatment of clinically insignificant disease.

Because prostate cancer is a slowly progressing disease, patients usually do not exhibit symptoms until it becomes locally advanced.27 Both obstructive and irritative symptoms can present at this time. Additionally, patients may have erectile dysfunction and painful ejaculation. Once the cancer progresses to an advanced metastatic form, it can spread to the abdominal and pelvic lymph nodes and the lumbar spine. Patients with these metastases often complain of pain in their lower back and pelvis. Prostate cancer also can metastasize to the liver, lungs, and adrenal glands.26

When the patient presents with LUTS and positive findings with the DRE or PSA test, a pathologist must make a confirmation via prostate biopsy. Cellular features and degree of differentiation determine the grading of the tissue sample, where tissue with more poorly differentiated disease is designated by a higher Gleason score. The Gleason score is the most common grading system and has prognostic significance (Table 2). The 10-year survival rates for cancer confined to the prostate, regional extension of the cancer, and metastases are 75%, 55%, and 15%, respectively.28

figure

Treatment Options for Prostate Cancer

The stage of the cancer can be determined by the tumor, node, and metastasis (TNM) system. As the name implies, the TNM system is based on tumor size, lymph node involvement, and whether the disease has metastasized. The TNM system can be used to classify prostate cancer further into stages I through IV, depending on tumor size and degree of disease spread. Thus, treatment strategies depend upon the Gleason score, initial stage of the disease, life expectancy, and presence of concomitant disease states. For example, patients would receive aggressive treatment if they presented with no comorbid conditions, a low Gleason score, and a life expectancy of >10 years. Conversely, those with the opposite conditions (ie, a high Gleason score, >70 years old, and a <10-year life expectancy) would be more likely candidates for watchful waiting, with treatment started upon symptom presentation.26

Viable options to treat early grades of cancer (Gleason scores 2-5) include radical prostatectomy and radiation therapy. The curative option of prostatectomy usually is reserved for men <70 years old with a life expectancy of >10 years and cancer that is confined to prostate tissue.29 Complications with this option, which are more prevalent than with any other treatment, include a significant risk for erectile dysfunction and—to a lesser extent—urinary incontinence.

Radiation therapy is a more frequent option for those >70 years old, who generally are considered poorer candidates for surgery. Similar to prostatectomy, it is also a curative treatment option and is used for patients with locally advanced disease. This option is most effective for patients with earlystage disease and Gleason scores of 2 to 4. Radiation also, however, can provide palliative treatment for metastasized cancer.26 Radiation therapy is implemented by either external beam radiation therapy (EBRT) or interstitial implantation (brachytherapy). EBRT, administered daily for 4 to 6 weeks, involves gamma rays excising affected prostate tissue through radiation. Brachytherapy, a more convenient therapy requiring only 1 outpatient treatment, involves radioactive capsules implanted into the prostate tissue. Radiation therapy can cause local inflammation, rectal irritation, LUTS, and some erectile dysfunction.30

Because hormone therapy can yield up to an 80% response for metastatic cancer, it usually is incorporated in the treatment of moderate-to-late-stage disease. Medications can be given in combination with radiation therapy for advanced disease, but they also can be initiated for localized cancer in patients who are not candidates for surgery or radiation. Although a variety of choices are available in the categories of estrogens, luteinizing hormone-releasing hormone (LHRH) agonists, and nonsteroidal antiandrogens (Table 3), an unfortunate fact of therapy at this point is that the cancer becomes refractory to hormones for most patients within 1 to 1 1/2 years.31

figure

The first hormonal therapy developed in the treatment of prostate cancer, diethylstilbesterol (DES), is no longer available. Testosterone release from the testes is inhibited because gonadotropin-releasing hormone is inhibited from the hypothalamus. Although it is not produced commercially due to its undesirable toxicities, DES can be obtained as a second-line agent from specialty compounding pharmacies. Conjugated estrogens and estradiol are used for chemical castration but are limited by potentially severe adverse effects (Table 3).31

Because LHRH agonists are as effective as bilateral orchiectomy to decrease testosterone levels, this class of medications often is used as first-line therapy.26 Leuprolide, triptorelin, and goserelin are the available choices in this class labeled for this indication. By down-regulation of receptors on the pituitary, they inhibit release of follicle-stimulating hormone and luteinizing hormone (LH). Ultimately, the production of testosterone is inhibited because of the reduction of available LH to the testes. The reduction in testosterone levels and the tumor response are comparable to those achieved with bilateral orchiectomy. A significant adverse effect known as a "tumor flare" or "testosterone flare" is associated with use of LHRH agonists for the first 1 to 2 weeks. During this time, the initial surge in testosterone (until eventual down-regulation occurs) can lead to tumor growth and is characterized by hot flashes, LUTS, lethargy, sexual dysfunction, and bone pain.31 The effects of the initial testosterone flare, however, can be greatly reduced by using concurrent estrogen or antiandrogen therapy during the first 2 weeks.26

Nonsteroidal antiandrogens include flutamide, bicalutamide, and nilutamide. Because monotherapy with these medications is less efficacious than bilateral orchiectomy, their place in therapy is mainly adjunctive with LHRH agonists.32 This strategy is known as combined androgen blockade (CAB), and the nonsteroidal antiandrogen generally is added to an LHRH agonist for 2 to 4 weeks. Although CAB is useful for advanced disease, it is not intended for long-term maintenance therapy.32

Finally, disease progression and relapse should be addressed. Clinical employment of a concept known as maximal androgen blockade has developed. Disease progression despite androgen suppression is thought to occur due to the small amount (5%-10%) of testosterone produced by the adrenal glands. Therefore, the nonspecific steroidogenesis inhibitors aminoglutethimide and ketoconazole sometimes are used—along with a corticosteroid to prevent adrenal insufficiency to block adrenal testosterone. Yet, evidence of superior efficacy versus other treatments has not yet materialized in several meta-analyses.33 Because prostate cancer eventually progresses in almost all patients despite hormone therapy, investigation currently is under way to address relapse. Once patients are not responding to hormonal therapy anymore, antiandrogen withdrawal sometimes is effective. Also, systemic chemotherapy is used when the cancer becomes androgenindependent, and a variety of chemotherapeutic agents are being investigated regarding end-stage therapy.34

The Pharmacist's Role in Prostate Health

Because periodic testing of PSA and DRE are such an integral part of diagnosing diseases of the prostate, the prudent pharmacist should empower patients of requisite age by explaining the importance of annual testing in this area—especially those with urinary tract symptoms or at risk for developing BPH, prostatitis, or prostate cancer. Disease-specific interventions that require pharmacist support will be discussed presently.

As stated earlier, the overriding goal of BPH management is enhancement of the patient's quality of life. Therefore, ample opportunity exists for pharmacist intervention and management. When considering a choice of medications, the pharmacist is guided by the patient's perspective. Namely, the severity of LUTS and the need for immediate alleviation of symptoms are addressed at symptom onset and with regular follow-up visits. The symptom score index provides assistance in this regard. Also, pharmacists can counsel on behavioral techniques, such as fluid restriction and caffeine avoidance after the evening meal. Diuretics should be given solely in the morning rather than close to bedtime. These simple changes often lead to considerable symptom improvement. Finally, patients can avoid other medications that tend to exacerbate LUTS, such as anticholinergics, sympathomimetics, anabolic steroids, and other steroid precursors.

Prostatitis can be a confusing landscape of different categories with inherent specificities in disease state management. The pharmacist can counsel about the disease state itself, the proper choice of medications for each category, and potential adverse effects. CP/CPPS can be a particularly frustrating disease for both the patient and the provider. Because research on medication therapy for this category is ongoing, the pharmacist can provide information when new medications become available.

Regarding prostate cancer, pharmacists can counsel on both prevention and palliative care for those undergoing treatment. Finasteride, traditionally a treatment for BPH, has been studied as a preventive agent for prostate cancer. The results of a recent clinical trial indicate that, although finasteride is associated with attenuation of the risk of developing prostate cancer, those patients who are diagnosed subsequent to finasteride prophylaxis could present with more advanced disease.35 Pharmacists also can counsel on a variety of issues, including adverse effects of medications, adherence to therapy, and palliative care. For example, patients with advanced cancer often not only suffer from LUTS, but they also may have pain control issues from local tumor-related pain and—eventually—bone metastasis. Pharmacists can guide pain management with recommendations of a step-care plan with nonsteroidals, combination analgesics, and opioid analgesics. Those receiving narcotics for pain management should take prophylactic measures for constipation.

The impact of all 3 disease states—BPH, prostatitis, and prostate cancer—on quality of life is enormous. Thus, these issues need to be addressed alongside the standard staples of pharmacist intervention, disease and drug monitoring. Furthermore, pharmacists should be vigilant about patients' propensity to develop anxiety and depression. Assistance should be provided both with initial intervention and follow-up care, which should be ongoing and progressive with each step of treatment. In this manner, the pharmacist will be able to truly provide comprehensive care for the patient with declining prostate health.

Justin J. Sherman, PharmD, Assistant Professor of Pharmacy Practice, University of Louisiana at Monroe, School of Pharmacy

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CE REVIEW QUESTIONS

(Based on the article starting on page 75) Choose the 1 most correct answer.

1. Which of the following statements is true regarding benign prostatic hyperplasia (BPH)?

  1. The static component of BPH occurs when growth of the prostate tissue begins to constrict the bladder neck.
  2. When α1-adrenergic receptors within prostate tissue are stimulated, this effect causes increased tone and is called the dynamic component of BPH.
  3. Medications for BPH are targeted toward relief of either the static or dynamic components.
  4. All of the above are true statements.

2. Symptoms of BPH present in a continuum, whereby irritative symptoms:

  1. Include hesitancy, dribbling, and incomplete emptying and are typically the first symptoms to present.
  2. Include urinary frequency and nocturia and are considered to be a result of long-standing, unresolved, obstructive symptoms.
  3. Are considered severe only when the prostate is considerably enlarged.
  4. Will ultimately lead to complications for most patients even with treatment.

3. A patient with BPH has a routine prostate-specific antigen (PSA) test done. Because he presents with lower urinary tract symptoms (LUTS), a symptom score index questionnaire is used. Which of the following results would most likely necessitate treatment of his BPH with medications?

  1. PSA 2 ng/mL; score of 4 on symptom score index
  2. PSA 6 ng/mL; score of 7 on symptom score index
  3. PSA 8 ng/mL; score of 12 on symptom score index
  4. PSA 15 ng/mL; score of 25 on symptom score index

4. Which of the following medications is FDA-approved as first-line therapy for BPH when rapid relief of symptoms is needed?

  1. Terazosin
  2. Finasteride
  3. Prazosin
  4. Tolterodine

5. Which of the following statements is true regarding tamsulosin?

  1. It is considered a second-generation α1-receptor inhibitor.
  2. It should be dosed at bedtime to avoid orthostatic changes.
  3. It should be dosed initially at the lowest dose and doubled each week until maximum effect is achieved.
  4. It is considered a uroselective medication because it exhibits a greater, more selective affinity for α1A receptors.

6. Which of the following statements is true regarding finasteride?

  1. This medication decreases the conversion of dihydrotestosterone to testosterone in the prostate tissue.
  2. Although this medication can decrease the size of prostate tissue, it may take up to 6 months to have a significant effect on symptoms.
  3. Patients who experience the greatest benefit from this medication have a problem with the dynamic component of BPH.
  4. Female pharmacists dispensing this medication should handle only crushed tablets.

7. According to the results of the MTOPS (Medical Therapy of Prostatic Symptoms) study, a patient who has not obtained significant relief of LUTS with a maximum dose of a second-or third-generation α1-receptor blocker:

  1. Should be switched to another second- or third-generation α1-receptor blocker.
  2. Should be offered surgical intervention for prostatectomy.
  3. Should be started on combination therapy with a 5α-reductase inhibitor.
  4. Should be given a "drug-free holiday" to enhance response when the medication is restarted.

8. The best candidates for receiving phytotherapy for BPH are those with:

  1. Mild symptoms.
  2. Moderate symptoms.
  3. Severe symptoms.
  4. Symptoms refractory to surgery.

9. This type of prostatitis usually is caused by a singular type of bacterial organism that initiates recurrent episodes of urinary tract infections.

  1. Acute bacterial prostatitis
  2. Chronic bacterial prostatitis
  3. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)
  4. Asymptomatic inflammatory prostatitis

10. In this type of prostatitis, pain may result from a variety of psychological, neurologic, or immunologic factors rather than arising directly from the prostate itself.

  1. Acute bacterial prostatitis
  2. Chronic bacterial prostatitis
  3. CP/CPPS
  4. Asymptomatic inflammatory prostatitis

11. Which of the following is a correct statement regarding prostatitis?

  1. The most common form is acute prostatitis.
  2. In chronic prostatitis, an enlarged, tender prostate on digital rectal examination (DRE) is diagnostic.
  3. Acute prostatitis requires antibiotics to be given for 3 continuous months to prevent relapse.
  4. Although antibiotic therapy can be beneficial for inflammatory. CP/CPPS, some data indicate that it is not helpful for the noninflammatory form.

12. Patients with this type of prostatitis present with urinary tract problems rather than pelvic or prostate pain.

  1. Acute bacterial prostatitis
  2. Chronic bacterial prostatitis
  3. CP/CPPS
  4. Asymptomatic inflammatory prostatitis

13. Which of the following are reasonable guidelines for the treatment of CP/CPPS?

  1. Prolonged treatment with α-blockers may be required.
  2. Empiric therapy with antibiotics may have to be continued for years.
  3. Combination therapy for refractory CP/CPPS has not been proven to be helpful.
  4. All of the above are true statements.

14. Which of the following people are at the highest risk for prostate cancer?

  1. An Asian American with a firstdegree relative with prostate cancer
  2. A Caucasian whose father has prostate cancer
  3. An African American whose brother has prostate cancer
  4. An African American whose father has prostate cancer

15. The American Urological Association recommends routine screening for prostate cancer with a DRE and PSA levels in:

  1. Men starting at age 50 with a 10-year life expectancy.
  2. Men starting at age 45 with a 10-year life expectancy.
  3. Men starting at age 45 if they have an uncle with prostate cancer.
  4. African American men starting at age 40.

16. Which of the following statements is true regarding the role of radiation treatment for prostate cancer?

  1. It is considered a curative treatment option.
  2. It can be an alternative treatment for those not able to undergo surgery.
  3. It provides palliation when patients have cancer that has metastasized.
  4. All of the above are considered roles for radiation treatment.

17. This therapy for prostate cancer consists of one outpatient treatment during which capsules are placed within the patient's prostate tissue.

  1. Prostatectomy
  2. Brachytherapy
  3. External beam radiation therapy
  4. Hormonal therapy

18. Which of the following is a true statement regarding hormonal treatment for prostate cancer?

  1. Hormonal treatment should be used for patients with a Gleason score of 2.
  2. Diethylstilbesterol is currently a common hormonal treatment for prostate cancer.
  3. Severe adverse effects such as cerebrovascular events are possible when using conjugated estrogen therapy in castration doses.
  4. Conjugated estrogen therapy should be used as first-line hormonal therapy.

19. When using hormonal therapy, what is a correct statement regarding "testosterone flare"?

  1. It is the brief reduction of testosterone in the body that occurs when using conjugated estrogens.
  2. It is caused by the brief inhibition of follicle-stimulating hormone (FSH), which is followed by stimulation of FSH.
  3. It is a 1-to 2-week period of hyperandrogenism that can result in adverse effects such as hot flashes and erectile dysfunction.
  4. It can be reduced after a period of 3 months by using concomitant antiandrogen therapy.

20. Which of the following is a true statement about the pharmacist's role in prostate health?

  1. The pharmacist could encourage patients of requisite age to have a complete physical examination, including a DRE and a PSA level test.
  2. A patient who has increasing LUTS but has just started furosemide twice daily could be encouraged to take the entire diuretic dose in the morning.
  3. Finasteride has been studied as a preventative agent for prostate cancer by select patients who are at higher risk.
  4. All of the above are true statements.

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