Prostate Health Considerations: The Pharmacist's Role

Prostate Health Considerations: The Pharmacist's RoleJustin J. Sherman, PharmD75

Behavioral Objectives

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

• Discuss the prevalence of prostate disorders and the generalconcerns of patients regarding their prostate health.
• Describe common lower urinary tract symptoms and treatmentoptions for patients with benign prostatic hyperplasia(BPH).
• Recognize the presentation of a patient with one of thedifferent types of prostatitis, and recommend treatmentfor each.
• Counsel patients with prostate cancer with regard to treatmentoptions.
• Recommend medication treatment for BPH, prostatitis, andprostate cancer. Also, the pharmacist should be able to monitorthe efficacy of medication treatment and adverse effects.
• Develop ways that management of prostate health andcounseling can fit into the pharmacist's practice.

The prostate is a male accessorysex gland located below the urinarybladder and anterior to therectum. This walnut-sized gland isheart-shaped, soft, and mobile on palpation,which is done manuallythrough the rectal mucosa. The glandsecretes an alkaline fluid that becomespart of the semen during ejaculation.The high concentration of zinc that isfound in the fluid may provide an antibacterialeffect.

Although the physiologic functionof the prostate is minimal, its impacton the quality of life in elderly patientscan be quite profound—regardless ofwhether the patient has benign prostatichyperplasia (BPH), prostatitis, orprostate cancer.^1-3 These disorders willbe discussed, with an emphasis onavailable medication treatments andopportunities for pharmacists to usetheir unique, interventional skills foreach disease state.

Presentation of the Patientwith BPH

BPH is characterized by lower urinarytract symptoms (LUTS) that arebothersome and can be attributed toeither prostate tissue hyperplasia orincreased tone. Although the relationshipbetween BPH and LUTS is complexand has not been completely elucidated,BPH may result from a varietyof factors. In the adult, testosterone isconverted into dihydrotestosterone(DHT) by the intraprostatic enzyme5α-reductase. A growth spurt of theprostate tends to occur between theages of 40 and 80, largely thought to bedue to DHT. Many men experienceprostate growth; however, in patientswho present with LUTS, this growthspurt may result in hyperplasia ofprostate tissue around the neck of thebladder. This is known as the staticcomponent of BPH. The dynamic componentof BPH occurs because stimulationof α₁-adrenergic receptors withinprostate tissue leads to smooth musclecontraction and increased tone in thebladder neck, thus causing furtherobstruction. Current medications forthis condition are targeted for relief ofits static and dynamic components.¹

Static and dynamic factors togetherresult in the LUTS with which BPHpatients present. Symptoms—includinghesitancy, dribbling, incompleteemptying, weak stream, and strainingto urinate—usually are obstructive innature on initial presentation.¹ Duringthis phase of BPH, the prostate hasenlarged substantially so as to interferewith bladder emptying. Prostate size isnot necessarily proportional to theseverity of LUTS, however, as symptomsdepend primarily on the amountof urethral lumen and bladder neckobstruction. Patients with hesitancymay need to put pressure manually ontheir bladders to initiate voiding, anddribbling could cause the patient publicembarrassment.

As BPH progresses, urinary frequency,urgency, and nocturia can develop.These irritative symptoms are consequencesof long-standing bladder neckobstruction, whereby the muscles ofthe bladder neck enlarge in an attemptto compensate for the obstruction.⁴This hypertrophy results in bladderdecompensation, with a diminishedcapacity to store urine. Urinary frequencyand urgency develop becausethe bladder becomes hypersensitive tothe small amounts of urine that cannotbe cleared through regular voiding.Patients may exhibit "toilet mapping,"whereby the incessant need to urinateinduces them to accommodate voidinginto every activity of daily living.Furthermore, nocturia awakens patientsevery couple of hours throughoutthe night. Some patients evenadmit to keeping a bedpan or amakeshift urinal in their bedrooms.

Eventually, untreated BPH can leadto recurrent urinary tract infections(UTIs) due to the inability to void completely.Other complications includechronic renal impairment, bladderstones, incontinence, and hematuria.¹Thus, a patient presenting with longstanding,untreated BPH may requireassessment for possible complications.

A patient presenting with LUTS representsonly a probable case of BPH.Subsequent tests, such as the serumbiochemical marker prostate-specificantigen (PSA) test and a digital rectalexamination (DRE), must be done torule out other causes of LUTS. Thus,the diagnosis of BPH is made primarilyafter other common causes, such asprostatitis and prostate cancer, areruled out.⁵ For example, a current PSAlevel test can help rule out a potentialdiagnosis of prostate cancer. Whereas aPSA level of <4 ng/mL is considerednormal, a level of >10 ng/mL can predictprostate cancer about 66% of thetime. A PSA level between 4.1 ng/mLand 10 ng/mL may indicate BPH whenother causes of LUTS are ruled out.⁶

The American Urological AssociationSymptom Score Index (AUASI) is themost widely used clinical assessmentinstrument for LUTS from BPH (Table1). Because alleviation of symptoms isthe main goal for patients with BPH,treatment is aimed at decreasing thesesymptom scores. The clinician recordsa baseline score when the patient isdiagnosed with BPH, thus allowingrecognition of a treatment effect oncemedication is started. Patients themselvesgenerally recognize relief orworsening of LUTS when the AUASIdecreases or increases by 3 points,respectively.⁵

In addition to improving symptoms,the traditional goals of therapy includeattenuating disease progression andpreventing complications from eitheruntreated or undertreated BPH.Because quality of life and symptomimprovement are the main goals, thepatient's concerns should take precedencein treatment considerations. Aninitial evaluation would include adetailed history of LUTS, a past medicalhistory, a record of concomitant medications,and a baseline PSA and DRE.Next, the clinician would categorizethe 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 treatmentplan would depend upon thiscategorization.¹ Whereas mild BPHusually is treated with watchful waiting,moderate BPH with bothersomesymptoms can be managed with medications.Treatment options for severeBPH include surgical intervention withprostate resection or with minimallyinvasive treatments including transurethralneedle ablasion, transurethralmicrowave heat treatment, and interstitiallaser therapy.⁷

Role of Medications for Reliefof LUTS

As stated above, moderate BPH usuallyis managed via medications, includingα₁-receptor inhibitors and 5α-reductase inhibitors. The α₁-receptorinhibitors decrease smooth muscle tonein the prostate tissue, urethra, and bladderneck, thereby alleviating thedynamic component of LUTS. Theiraction of relieving LUTS is relativelyquick, compared with that of 5α-reductaseinhibitors. Thus, α-receptor blockersare considered first-line therapywhen the patient needs significant andrapid symptom relief.⁸ They do notexert any appreciable effect on eitherprostate size or PSA levels, however.

The α₁-receptor inhibitors can bestratified as first-, second-, or third-generationagents. Stratification dependsupon several factors, including adverseeffect profile, degree of receptor selectivity,and chronology of discovery ofeach medication. Stratification is not,however, related to efficacy since all α₁-receptor blockers are equally efficacious.Phenoxybenzamine is the solefirst-generation agent, but its nonselectivityand severe cardiovascular adverseeffects make it an unpalatable choicefor BPH. The second-generation agentsinclude terazosin and doxazosin. Tamsulosinand alfuzosin comprise the third-generationagents.⁷

Terazosin and doxazosin are consideredlong-acting second-generationα₁-receptor inhibitors.⁹ The once-dailystarting doses for these medications aregenerally low (1 mg at bedtime [hs] foreach), and they are titrated by doublingthe dose every 2 weeks untileither the patient has significant reliefof LUTS or the maximum dose isachieved (10 mg hs and 8 mg hs for terazosinand doxazosin, respectively).Terazosin and doxazosin inhibit bothsubreceptors of α1 (α₁A receptors andα₁B receptors, which are found mainlyin the prostate and the vascular epithelium,respectively).⁹ Thus, the use of alow starting dose and nighttime administrationattenuate the first-doseeffects of orthostatic hypotension,which results from the inhibition ofα₁B receptors. Other adverse sideeffects include syncope, malaise, dizziness,and somnolence.⁹ Prazosin,another α₁-receptor inhibitor, is notapproved by the FDA for BPH, and itsuse generally is not feasible due to theneed for 3-times-daily dosing.

The third-generation α₁-receptor inhibitors,tamsulosin and alfuzosin, areknown as uroselective blockers becauseof their selective action on prostate tissuewithout a concomitant reductionin blood pressure. Tamsulosin, availableas a 0.4-and a 0.8-mg/day dose,exhibits a 10 to 12 times greater affinityfor α₁A receptors, which results inclinically insignificant orthostaticchanges and first-dose effects.¹⁰ Althoughdosing is once daily, administrationat bedtime is not necessary.Also, the onset of effect can occur withinthe first week of therapy, and dosetitration usually is not needed. In fact,clinical trials revealed that the higherdose increased the onset of adverseeffects without increasing the degree ofsymptom relief. Tamsulosin is generallywell tolerated. Its adverse effectsinclude rhinitis, dizziness, asthenia,and abnormal ejaculation.¹⁰

Although alfuzosin also exerts aselective action on prostate tissue withoutreducing blood pressure, this effectis not necessarily related to receptorspecificity. Available as a 10-mg/daydose, it is similar to tamsulosin withrespect to the clinically insignificantorthostatic hypotension and onset ofeffect. It shares the same mild adverseeffects, with the exception of the ejaculatorydysfunction sometimes encounteredwith tamsulosin.¹¹

The 5α-reductase inhibitors, finasteride(5 mg daily) and dutasteride (0.5mg daily), decrease conversion oftestosterone to DHT in the prostate.These medications also cause apoptosisof prostate cells, thus alleviating thestatic component of BPH, eventuallyshrinking the prostate tissue itself, andrelieving LUTS.^12-14 Daily administrationresults in symptom improvement afteran average of 6 months. Also, patientswith a significantly enlarged prostate(&#8805;40 g) experience the greatest symptomimprovement. Finally, patients takingthis class of medications are lesslikely to have acute urinary retention orto need surgical intervention.

Two special concerns regarding theuse of 5α-reductase inhibitors need tobe discussed. These drugs are contraindicatedin women when they areor may potentially be pregnant,because they can cause abnormalitiesin the male fetus. Also, women who areor may be pregnant should not handlecrushed or broken tablets due to thepotential for absorption of the medicationthrough skin. Only crushed tabletsare harmful, however, because a protectivecoating alleviates this concernwith normal handling. Another concernregarding finasteride is that, sinceit causes an actual reduction in the sizeof the prostate—and prostate size isproportional to PSA—patients receivingfinasteride may lose the sensitivityof the PSA in detecting prostate cancer.This sensitivity is not compromised,however, if the patient's PSA value ismultiplied by a factor of 2 when finasteridehas been taken for 6 months orlonger.¹⁵ Adverse effects most prevalentwith this class include erectile dysfunction,ejaculatory disorders, and gynecomastia.

The most widely used phytotherapeuticagent is Serenoa repens (saw palmetto).Patients who present with mildLUTS and are already taking herbaltherapy should be monitored for diseaseprogression. Actual studies regardingefficacy suffer from poor studydesign. Furthermore, phytotherapyshould not be used for the relief ofmoderate or severe BPH because delayingproper treatment could lead tocomplications.¹⁶

Because α-receptor blockers and 5α-reductase inhibitors have differentmechanisms of action, the presumptionwould be that efficacy increaseswhen both types are used together.This hypothesis was confirmed in theMedical Therapy of Prostatic Symptoms(MTOPS) Study, the longest andlargest trial conducted to date regardingcombination therapy.¹⁷ This 5-yearstudy revealed that combination therapywith doxazosin and finasteride versuseither medication alone significantlyreduced overall risk of diseaseprogression and improved AUASIscores. Therefore, combination therapyis appropriate for men with an increasedrisk of disease progression orinadequate relief of symptoms with themaximum dose of monotherapy.

Prostatitis: Classification,Presentation, and Treatment

Prostatitis, an inflammation of theprostate gland, is a common conditiondiagnosed during 2 million physicianvisits yearly and affecting approximately10% of all adult men.¹⁸ This commoncondition can range from a comparativelysimple case of acute bacterialprostatitis to a more complex, chronicform that is still plagued by a poorunderstanding of the underlying pathophysiologyand treatment.¹⁹ Indeed,both patients and physicians maybecome frustrated with the chronic,relapsing forms of prostatitis. Althougha clinical diagnosis of prostatitis isbased on the patient history and physicalexamination, no consensus existswith regard to the physical findings ora diagnostic laboratory test. In 1998,the National Institutes of Health developeda widely used classification system,which includes the following 4categories: (I) acute bacterial prostatitis;(II) chronic bacterial prostatitis; (III)chronic prostatitis/chronic pelvic painsyndrome (CP/CPPS); and (IV) asymptomaticinflammatory prostatitis.²

Acute Bacterial Prostatitis(Category I)

Acute bacterial prostatitis presentswith symptoms of a UTI, includingincreased urinary frequency, dysuria,urgency, and a varying degree of bladderoutlet obstruction. Also, patientsoften experience malaise, fever, andmyalgias, suggesting a more systemicinfection.

Causative uropathogens usually aregram-negative, with the most commonone being Escherichia coli. Klebsiella,Proteus, Enterococci, and Pseudomonasare other species that may befound upon culturing the urine. Initialantibiotics are customarily prescribedempirically, but they can be modified ifthe pathogen is later found to be susceptibleto another regimen. Standardantibiotics used for acute infectionsinclude trimethoprim-sulfamethoxazole(TMP-SMX), tetracycline, or aquinolone. Although the proper durationof therapy has not been clearlydefined, antibiotics can be continuedfor 3 or 4 weeks to prevent relapse ifthe patient continues to respond clinically.Compared with the other categories,acute bacterial prostatitis is easilyrecognized and treated.

Chronic Bacterial Prostatitis(Category II)

The same organism, usually E coli,often causes the recurrent episodes ofUTI that occur with chronic bacterialprostatitis. Cultures of prostate-specificspecimens such as expressed prostaticsecretions (EPS) suggest that theprostate is the focal point of infection,although no single clinical finding isdiagnostic. The symptoms can be quitevariable, including irritative LUTS,fever, myalgias, and pain in the back,testes, or penis. Patients can be asymptomaticbetween remitting episodes,however, and the prostate is often normalon DRE.

The efficacy of antibiotic treatmentdepends upon penetration of thelipophilic antibiotic into the prostaticepithelium. Unfortunately, most of theantibiotics that achieve highest penetrationare not effective for gram-negativeuropathogens. Therefore, failure isthought to occur because of poorantibiotic penetration.² Due to theexpense of newer antibiotics and theneed for prophylactic therapy forrecurrent disease, 4-to 12-week therapywith TMP-SMX or fluoroquinolonesis a reasonable initial choice.

Chronic Prostatitis/Chronic Pelvic PainSyndrome (CP/CPPS) (Category III)

While acute and chronic bacterialprostatitis (categories I and II) are thebest understood forms, they are muchless common than CP/CPPS. This condition,formerly called nonbacterial prostatitis,generally is diagnosed whenchronic symptoms are accompanied bynegative midstream urine cultures. Incontrast with the other forms, CP/CPPS suffers from a limited understandingas to the underlying etiology.In fact, studies have suggested that theprostate may not even be the source ofpain for this condition. Instead, painmay result from a complex interactionbetween psychological factors and dysfunctionin the neurologic, immune,and endocrine systems.²⁰ Therefore,other causes of pelvic pain must beexcluded.

Traditionally, CP/CPPS has been subcategorizedinto 2 subtypes, based onwhether patients have leukocytes intheir EPS (IIIA. inflammatory) or noevidence of inflammation (IIIB. noninflammatory).Treatment strategies forCP/CPPS include antibiotics and α-blockers. Colonization of uropathogensand infection in the prostate candevelop in patients with inflammatoryCPPS, and studies suggest that up to50% of patients in this subclassrespond to antibiotic therapy when itis given for 2 to 4 weeks.¹⁸ Data areemerging, however, to indicate thatantibiotics are not helpful for patientswith noninflammatory CPPS.²¹ In thissubclass of patients, α-blockers havebeen useful in pain relief when givenfor an extended period of time (14-24weeks). Medications that have beenstudied include terazosin, alfuzosin,and finasteride 5 mg daily (useful forpain relief in one study).^22-24 It is worthnoting, however, that a recent trialcomparing ciprofloxacin, tamsulosin,both, and placebo resulted in no significantdifferences in all groups studied.²⁵

Until more research is completedregarding CP/CPPS, patients with thisfrustrating, painful form of prostatitismay continue to experience substantialmorbidity. The following are 3 reasonableaxioms to keep in mind for thetreatment of CP/CPPS: (1) althoughantibiotics have been shown to relievepain for patients in category IIIA, ongoingempiric administration in patientswith long-standing CP/CPPS is not recommended¹⁹;(2) prolonged treatmentwith α-blockers appears to be necessaryto yield pain relief²¹; and (3) patientswith ongoing, refractory CP/CPPS mayneed combination therapy, althoughfurther studies in this area are needed.²¹

Asymptomatic InflammatoryProstatitis (Category IV)

Patients are placed in this categorywhen other urinary tract issues arebeing evaluated. Infection or inflammationof the prostate occurs in theabsence of pain. No treatment is indicatedunless the patient presents withan elevated PSA level or unless prophylaxisis needed prior to endoscopy orsurgery.

Considerations for thePatient with Prostate Cancer

Accounting for 11% of the cancerrelateddeaths in men, malignancy ofthe prostate is the second leading causeof cancer-related death—second onlyto lung cancer.²⁶ Although the overall5-year survival rate is quite encouraging(96%), survival rates are dependentupon the extent of disease progressionat diagnosis. For example, the 5-yearsurvival rates range from approximately100% for those with localized cancerto 34% for those with disease metastasis.Survival rates do decrease overtime, though, with overall survivaldecreasing to 75% and 54% after 10years and 15 years, respectively.²⁶

Prostate cancer is a disease of the elderly.Incidence correlates with age andvaries with race and other risk factors.The average age of men at diagnosis is72. Although Hispanics, Asians, andNative Americans all have a lower incidenceof this malignancy than Caucasians,African Americans have ahigher incidence. In addition to ageand race as primary risk factors, a familyhistory of a first-degree relative withprostate cancer increases the risk.Specifically, the risk doubles or triples ifthe patient's father or brother, respectively,has prostate cancer. Other possiblerisk factors include BPH, high-fat orlow-fiber diets, or decreased consumptionof soy protein or vitamin E.²⁷

Because the 5-year survival statisticsare relatively favorable, screening remainscontroversial, based on the factthat routine screening has not yetdecreased mortality. The AmericanUrological Association recommendsscreening with a DRE and a PSA assessmentyearly when men reach 50 yearsof age and have at least a 10-year lifeexpectancy. The American CancerSociety additionally recommends thatscreening should begin at age 45 forAfrican Americans or when 2 or morefirst-degree relatives have had prostatecancer.²⁶

Both the DRE and the PSA concentrationare used to screen for prostatecancer, although both are fraught withuncertainties in detection. An enlarged,nodular prostate could suggestprostate cancer, but the DRE is limitedby its variability with clinician observation.The PSA can be used to assist inthe diagnosis of prostate cancer, and italso serves as a tool to monitor diseaseprogression and efficacy of treatment.Yet, the PSA is a limited tool that ispoorly predictive of cancer unless thePSA is >10 ng/mL (a 66% chance).Comparatively, there is a 25% chanceof cancer when the PSA is in the "grayarea" of 4 to 10 ng/mL.²⁶ The goal forusing the DRE and the PSA test is to targetthose patients most likely to needbiopsy or expensive imaging procedures,thus avoiding aggressive screeningand treatment of clinically insignificantdisease.

Because prostate cancer is a slowlyprogressing disease, patients usually donot exhibit symptoms until it becomeslocally advanced.²⁷ Both obstructiveand irritative symptoms can present atthis time. Additionally, patients mayhave erectile dysfunction and painfulejaculation. Once the cancer progressesto an advanced metastatic form, it canspread to the abdominal and pelviclymph nodes and the lumbar spine.Patients with these metastases oftencomplain of pain in their lower backand pelvis. Prostate cancer also canmetastasize to the liver, lungs, andadrenal glands.²⁶

When the patient presents withLUTS and positive findings with theDRE or PSA test, a pathologist mustmake a confirmation via prostate biopsy.Cellular features and degree of differentiationdetermine the grading ofthe tissue sample, where tissue withmore poorly differentiated disease isdesignated by a higher Gleason score.The Gleason score is the most commongrading system and has prognostic significance(Table 2). The 10-year survivalrates for cancer confined to theprostate, regional extension of the cancer,and metastases are 75%, 55%, and15%, respectively.²⁸

Treatment Options forProstate Cancer

The stage of the cancer can be determinedby the tumor, node, and metastasis(TNM) system. As the name implies,the TNM system is based ontumor size, lymph node involvement,and whether the disease has metastasized.The TNM system can be used toclassify prostate cancer further intostages I through IV, depending ontumor size and degree of diseasespread. Thus, treatment strategies dependupon the Gleason score, initialstage of the disease, life expectancy,and presence of concomitant diseasestates. For example, patients wouldreceive aggressive treatment if they presentedwith no comorbid conditions, alow Gleason score, and a life expectancyof >10 years. Conversely, those withthe opposite conditions (ie, a highGleason score, >70 years old, and a<10-year life expectancy) would bemore likely candidates for watchfulwaiting, with treatment started uponsymptom presentation.²⁶

Viable options to treat early grades ofcancer (Gleason scores 2-5) includeradical prostatectomy and radiationtherapy. The curative option of prostatectomyusually is reserved for men<70 years old with a life expectancy of>10 years and cancer that is confinedto prostate tissue.²⁹ Complications withthis option, which are more prevalentthan with any other treatment, includea significant risk for erectile dysfunctionand—to a lesser extent—urinaryincontinence.

Radiation therapy is a more frequentoption for those >70 years old, whogenerally are considered poorer candidatesfor surgery. Similar to prostatectomy,it is also a curative treatmentoption and is used for patients withlocally advanced disease. This option ismost effective for patients with earlystagedisease and Gleason scores of 2 to4. Radiation also, however, can providepalliative treatment for metastasizedcancer.²⁶ Radiation therapy is implementedby either external beam radiationtherapy (EBRT) or interstitialimplantation (brachytherapy). EBRT,administered daily for 4 to 6 weeks,involves gamma rays excising affectedprostate tissue through radiation.Brachytherapy, a more convenienttherapy requiring only 1 outpatienttreatment, involves radioactive capsulesimplanted into the prostate tissue.Radiation therapy can cause localinflammation, rectal irritation, LUTS,and some erectile dysfunction.³⁰

Because hormone therapy can yieldup to an 80% response for metastaticcancer, it usually is incorporated in thetreatment of moderate-to-late-stagedisease. Medications can be given incombination with radiation therapyfor advanced disease, but they also canbe initiated for localized cancer inpatients who are not candidates forsurgery or radiation. Although a varietyof choices are available in the categoriesof estrogens, luteinizing hormone-releasing hormone (LHRH) agonists,and nonsteroidal antiandrogens(Table 3), an unfortunate fact of therapyat this point is that the cancerbecomes refractory to hormones formost patients within 1 to 1 1/2 years.³¹

The first hormonal therapy developedin the treatment of prostate cancer,diethylstilbesterol (DES), is nolonger available. Testosterone releasefrom the testes is inhibited becausegonadotropin-releasing hormone isinhibited from the hypothalamus.Although it is not produced commerciallydue to its undesirable toxicities,DES can be obtained as a second-lineagent from specialty compoundingpharmacies. Conjugated estrogens andestradiol are used for chemical castrationbut are limited by potentiallysevere adverse effects (Table 3).³¹

Because LHRH agonists are as effectiveas bilateral orchiectomy to decreasetestosterone levels, this class ofmedications often is used as first-linetherapy.²⁶ Leuprolide, triptorelin, andgoserelin are the available choices inthis class labeled for this indication. Bydown-regulation of receptors on thepituitary, they inhibit release of follicle-stimulating hormone and luteinizinghormone (LH). Ultimately, the productionof testosterone is inhibitedbecause of the reduction of availableLH to the testes. The reduction intestosterone levels and the tumorresponse are comparable to thoseachieved with bilateral orchiectomy. Asignificant adverse effect known as a"tumor flare" or "testosterone flare" isassociated with use of LHRH agonistsfor the first 1 to 2 weeks. During thistime, the initial surge in testosterone(until eventual down-regulation occurs)can lead to tumor growth and ischaracterized by hot flashes, LUTS,lethargy, sexual dysfunction, and bonepain.³¹ The effects of the initial testosteroneflare, however, can be greatlyreduced by using concurrent estrogenor antiandrogen therapy during thefirst 2 weeks.²⁶

Nonsteroidal antiandrogens includeflutamide, bicalutamide, and nilutamide.Because monotherapy withthese medications is less efficaciousthan bilateral orchiectomy, their placein therapy is mainly adjunctive withLHRH agonists.³² This strategy isknown as combined androgen blockade(CAB), and the nonsteroidal antiandrogengenerally is added to anLHRH agonist for 2 to 4 weeks. AlthoughCAB is useful for advanced disease,it is not intended for long-termmaintenance therapy.³²

Finally, disease progression andrelapse should be addressed. Clinicalemployment of a concept known asmaximal androgen blockade has developed.Disease progression despite androgensuppression is thought to occurdue to the small amount (5%-10%) oftestosterone produced by the adrenalglands. Therefore, the nonspecificsteroidogenesis inhibitors aminoglutethimideand ketoconazole sometimesare used—along with a corticosteroidto prevent adrenal insufficiency toblock adrenal testosterone. Yet, evidenceof superior efficacy versus othertreatments has not yet materialized inseveral meta-analyses.³³ Because prostatecancer eventually progresses inalmost all patients despite hormonetherapy, investigation currently isunder way to address relapse. Oncepatients are not responding to hormonaltherapy anymore, antiandrogenwithdrawal sometimes is effective.Also, systemic chemotherapy is usedwhen the cancer becomes androgenindependent,and a variety of chemotherapeuticagents are being investigatedregarding end-stage therapy.³⁴

The Pharmacist's Role in Prostate Health

Because periodic testing of PSA andDRE are such an integral part of diagnosingdiseases of the prostate, the prudentpharmacist should empowerpatients of requisite age by explainingthe importance of annual testing inthis area—especially those with urinarytract symptoms or at risk for developingBPH, prostatitis, or prostate cancer.Disease-specific interventions thatrequire pharmacist support will be discussedpresently.

As stated earlier, the overriding goalof BPH management is enhancement ofthe patient's quality of life. Therefore,ample opportunity exists for pharmacistintervention and management.When considering a choice of medications,the pharmacist is guided by thepatient's perspective. Namely, the severityof LUTS and the need for immediatealleviation of symptoms are addressedat symptom onset and with regular follow-up visits. The symptom score indexprovides assistance in this regard. Also,pharmacists can counsel on behavioraltechniques, such as fluid restriction andcaffeine avoidance after the eveningmeal. Diuretics should be given solelyin the morning rather than close tobedtime. These simple changes oftenlead to considerable symptom improvement.Finally, patients can avoid othermedications that tend to exacerbateLUTS, such as anticholinergics, sympathomimetics,anabolic steroids, andother steroid precursors.

Prostatitis can be a confusing landscapeof different categories with inherentspecificities in disease state management.The pharmacist can counselabout the disease state itself, the properchoice of medications for each category,and potential adverse effects.CP/CPPS can be a particularly frustratingdisease for both the patient and theprovider. Because research on medicationtherapy for this category is ongoing,the pharmacist can provide informationwhen new medications becomeavailable.

Regarding prostate cancer, pharmacistscan counsel on both preventionand palliative care for those undergoingtreatment. Finasteride, traditionallya treatment for BPH, has been studiedas a preventive agent for prostatecancer. The results of a recent clinicaltrial indicate that, although finasterideis associated with attenuation of therisk of developing prostate cancer,those patients who are diagnosed subsequentto finasteride prophylaxiscould present with more advanced disease.³⁵ Pharmacists also can counsel ona variety of issues, including adverseeffects of medications, adherence totherapy, and palliative care. For example,patients with advanced canceroften not only suffer from LUTS, butthey also may have pain control issuesfrom local tumor-related pain and—eventually—bone metastasis. Pharmacistscan guide pain management withrecommendations of a step-care planwith nonsteroidals, combination analgesics,and opioid analgesics. Thosereceiving narcotics for pain managementshould take prophylactic measuresfor 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 addressedalongside the standard staples of pharmacistintervention, disease and drugmonitoring. Furthermore, pharmacistsshould be vigilant about patients'propensity to develop anxiety anddepression. Assistance should be providedboth with initial interventionand follow-up care, which should beongoing and progressive with eachstep of treatment. In this manner, thepharmacist will be able to truly providecomprehensive care for the patientwith 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 statementsis true regarding benign prostatichyperplasia (BPH)?

• The static component of BPHoccurs when growth of the prostatetissue begins to constrict thebladder neck.
• When α₁-adrenergic receptors withinprostate tissue are stimulated,this effect causes increased toneand is called the dynamiccomponent of BPH.
• Medications for BPH are targetedtoward relief of either the static ordynamic components.
• All of the above are true statements.

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

• Include hesitancy, dribbling, andincomplete emptying and are typicallythe first symptoms to present.
• Include urinary frequency andnocturia and are considered to be aresult of long-standing, unresolved,obstructive symptoms.
• Are considered severe only whenthe prostate is considerablyenlarged.
• Will ultimately lead to complicationsfor most patients even withtreatment.

3. A patient with BPH has a routineprostate-specific antigen (PSA) test done.Because he presents with lower urinarytract symptoms (LUTS), a symptom scoreindex questionnaire is used. Which ofthe following results would most likelynecessitate treatment of his BPH withmedications?

• PSA 2 ng/mL; score of 4 onsymptom score index
• PSA 6 ng/mL; score of 7 onsymptom score index
• PSA 8 ng/mL; score of 12 onsymptom score index
• PSA 15 ng/mL; score of 25 onsymptom score index

4. Which of the following medicationsis FDA-approved as first-line therapy forBPH when rapid relief of symptoms isneeded?

• Terazosin
• Finasteride
• Prazosin
• Tolterodine

5. Which of the following statements istrue regarding tamsulosin?

• It is considered a second-generationα₁-receptor inhibitor.
• It should be dosed at bedtime toavoid orthostatic changes.
• It should be dosed initially at thelowest dose and doubled each weekuntil maximum effect is achieved.
• It is considered a uroselective medicationbecause it exhibits a greater,more selective affinity for α₁Areceptors.

6. Which of the following statements istrue regarding finasteride?

• This medication decreases the conversionof dihydrotestosterone totestosterone in the prostate tissue.
• Although this medication candecrease the size of prostate tissue,it may take up to 6 months to havea significant effect on symptoms.
• Patients who experience the greatestbenefit from this medicationhave a problem with the dynamiccomponent of BPH.
• Female pharmacists dispensing thismedication should handle onlycrushed tablets.

7. According to the results of the MTOPS(Medical Therapy of Prostatic Symptoms)study, a patient who has not obtainedsignificant relief of LUTS with a maximumdose of a second-or third-generationα₁-receptor blocker:

• Should be switched to another second-or third-generation α₁-receptorblocker.
• Should be offered surgical interventionfor prostatectomy.
• Should be started on combinationtherapy with a 5α-reductaseinhibitor.
• Should be given a "drug-free holiday"to enhance response when themedication is restarted.

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

• Mild symptoms.
• Moderate symptoms.
• Severe symptoms.
• Symptoms refractory to surgery.

9. This type of prostatitis usually iscaused by a singular type of bacterialorganism that initiates recurrent episodesof urinary tract infections.

• Acute bacterial prostatitis
• Chronic bacterial prostatitis
• Chronic prostatitis/chronic pelvicpain syndrome (CP/CPPS)
• Asymptomatic inflammatory prostatitis

10. In this type of prostatitis, pain mayresult from a variety of psychological,neurologic, or immunologic factorsrather than arising directly from theprostate itself.

• Acute bacterial prostatitis
• Chronic bacterial prostatitis
• CP/CPPS
• Asymptomatic inflammatory prostatitis

11. Which of the following is a correctstatement regarding prostatitis?

• The most common form is acuteprostatitis.
• In chronic prostatitis, an enlarged,tender prostate on digital rectalexamination (DRE) is diagnostic.
• Acute prostatitis requires antibioticsto be given for 3 continuousmonths to prevent relapse.
• Although antibiotic therapy can bebeneficial for inflammatory.CP/CPPS, some data indicate that itis not helpful for the noninflammatoryform.

12. Patients with this type of prostatitispresent with urinary tract problemsrather than pelvic or prostate pain.

• Acute bacterial prostatitis
• Chronic bacterial prostatitis
• CP/CPPS
• Asymptomatic inflammatory prostatitis

13. Which of the following are reasonableguidelines for the treatment ofCP/CPPS?

• Prolonged treatment with α-blockersmay be required.
• Empiric therapy with antibioticsmay have to be continued for years.
• Combination therapy for refractoryCP/CPPS has not been proven to behelpful.
• All of the above are true statements.

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

• An Asian American with a firstdegreerelative with prostate cancer
• A Caucasian whose father hasprostate cancer
• An African American whose brotherhas prostate cancer
• An African American whose fatherhas prostate cancer

15. The American Urological Associationrecommends routine screening forprostate cancer with a DRE and PSA levels in:

• Men starting at age 50 with a 10-year life expectancy.
• Men starting at age 45 with a 10-year life expectancy.
• Men starting at age 45 if they havean uncle with prostate cancer.
• African American men starting at age 40.

16. Which of the following statements istrue regarding the role of radiation treatmentfor prostate cancer?

• It is considered a curative treatmentoption.
• It can be an alternative treatmentfor those not able to undergo surgery.
• It provides palliation when patientshave cancer that has metastasized.
• All of the above are consideredroles for radiation treatment.

17. This therapy for prostate cancer consistsof one outpatient treatment duringwhich capsules are placed within thepatient's prostate tissue.

• Prostatectomy
• Brachytherapy
• External beam radiation therapy
• Hormonal therapy

18. Which of the following is a truestatement regarding hormonal treatmentfor prostate cancer?

• Hormonal treatment should beused for patients with a Gleasonscore of 2.
• Diethylstilbesterol is currently acommon hormonal treatment forprostate cancer.
• Severe adverse effects such as cerebrovascularevents are possiblewhen using conjugated estrogentherapy in castration doses.
• Conjugated estrogen therapyshould be used as first-line hormonaltherapy.

19. When using hormonal therapy, whatis a correct statement regarding "testosteroneflare"?

• It is the brief reduction of testosteronein the body that occurswhen using conjugated estrogens.
• It is caused by the brief inhibitionof follicle-stimulating hormone(FSH), which is followed by stimulationof FSH.
• It is a 1-to 2-week period of hyperandrogenismthat can result inadverse effects such as hot flashesand erectile dysfunction.
• It can be reduced after a period of 3months by using concomitantantiandrogen therapy.

20. Which of the following is a truestatement about the pharmacist's role inprostate health?

• The pharmacist could encouragepatients of requisite age to have acomplete physical examination,including a DRE and a PSA leveltest.
• A patient who has increasing LUTSbut has just started furosemidetwice daily could be encouraged totake the entire diuretic dose in themorning.
• Finasteride has been studied as apreventative agent for prostate cancerby select patients who are athigher risk.
• All of the above are true statements.