CONTINUING EDUCATION Therapeutic Options FOCUS ON BENIGN PROSTATIC HYPERPLASIA Benign prostatic hyperplasia (BPH) is a urinary tract symptoms (LUTS).3 LUTS.6 A formal assessment of symptoms, histologic diagnosis referring to smooth including their impact on quality of life, is muscle and epithelial cell proliferation SYMPTOMATOLOGY & also recommended as part of the initial within the transition zone of the prostate.1 COMPLICATIONS diagnostic workup, as well as to monitor BPH can technically only be diagnosed An enlarged prostate gland has been symptom evolution and evaluate response after the prostate is biopsied and the proposed to contribute to male LUTS via to treatment.3,6 Such an assessment can be specimen examined under a microscope.2 In two primary mechanisms: (1) direct bladder done using the International Prostate contrast, benign prostatic enlargement is a outlet obstruction (static component), and Symptom Score (IPSS) or American clinical diagnosis that can be made on (2) increased smooth muscle tone and digital rectal examination.2 resistance (dynamic component).1 Based on Box 1 – Classification of male The prevalence of BPH increases these mechanisms, male LUTS are LUTS2,4 significantly with age. Greater than 50 per commonly classified as either cent of men will have BPH at 60 years of obstructive/voiding symptoms or Obstructive/voiding symptoms age, whereas approximately 90 per cent of storage/irritative symptoms1,2,4 (see Box 1). • Hesitancy men will have BPH by age 85.2 Fortunately, Potential complications of chronic • Weak urine flow not everyone with BPH will be bladder outlet obstruction secondary to • Intermittent urine flow symptomatic; bothersome symptoms are BPH include renal insufficiency, urinary • Straining estimated to affect about 30 per cent of retention, recurrent urinary tract infections, • Incomplete emptying men.2 For those affected, however, impact and bladder stones.1,5 on quality of life can be significant.1 As Storage/irritative symptoms symptom severity does not correlate well ASSESSMENT & DIAGNOSIS • Frequency with the degree of hyperplasia, and because According to recent Canadian guidelines • Urgency other conditions can cause similar for the management of BPH, assessment of • Urge urinary incontinence symptoms, the clinical syndrome associated symptom severity and bother is essential in • Nocturia with BPH is often referred to as male lower the initial evaluation of a man presenting with Drug Information and Research Centre JANUARY/375 UniversityFEBRUARY/MARCH Avenue, Suite2012 800, Toronto, Ontario M5G 2J5 THERAPEUTIC OPTIONS i Phone: 1-800-268-8058 Fax: (416) 385-2442 www.dirc-canada.org JANUARY/FEBRUARY/MARCH 2012 C.E. INSERT 1 Continuing Education – Therapeutic Options Focus on Benign Prostatic Hyperplasia Urological Association Symptom Index Box 2 – Some medications that can contribute to LUTS3,9 (AUA-SI).6 Both tools use the same seven questions (available online at Androgens Antihistamines Opiates http://www.usrf.org/questionnaires/ • Testosterone • Brompheniramine • Codeine AUA_SymptomScore.html) to assess the • Chlorpheniramine • Hydromorphone frequency of storage and voiding symptoms Anticholinergics • Cyproheptadine • Meperidine on a six-point scale (from 0 to 5, with • Atropine • Hydroxyzine • Methadone higher numbers indicating increased • Benztropine • Dimenhydrinate • Morphine frequency); based on the sum of the scores • Flavoxate • Diphenhydramine • Oxycodone for each question, BPH severity is classified • Hyoscine as follows: • Oxybutynin Antipsychotics Sympathomimetics • 0–7 = mild; • Scopolamine • Fluphenazine • Ephedrine • 8–19 = moderate; and • Loxapine • Phenylephrine • 20–35 = severe.3,7 Antidepressants • Pseudoephedrine For purposes of assessing treatment • Amitriptyline Muscle relaxants • Terbutaline response, a three-point improvement in • Doxepin • Baclofen total score is considered meaningful.8 • Nortriptyline • Cyclobenzaprine Further to the seven questions regarding • Trimipramine symptom frequency, the IPSS also asks a single quality of life question to assess the degree of bother associated with LUTS: “If (IPSS/AUA-SI ≤7) secondary to BPH. anticholinergics.10,12 As onset of effect is you were to spend the rest of your life with Watchful waiting is also appropriate for slower for 5ARIs, first follow-up is your urinary condition just the way it is those with moderate or severe BPH-related recommended after three to six months.10,12 now, how would you feel about that?”8 LUTS (IPSS/AUA-SI ≥8) who are not All patients should continue to be evaluated In addition to symptom assessment, a bothered by their symptoms and have no every six to 12 months.12 focused physical examination including a complications of bladder outlet digital rectal exam is considered a obstruction.1,8 Surgery mandatory part of the diagnostic workup Various lifestyle changes (see Box 3) Surgical approaches are warranted when for BPH.6 Urinalysis is required to rule out may also be suggested in combination with bothersome symptoms have not responded non-BPH diagnoses that may cause LUTS, watchful waiting, although not all are to conservative management and drug therapy, and other tests may also be required (refer supported by high quality evidence.6 or when complications of BPH are present.1,10,12 to the online version of the Canadian A detailed discussion of the various guidelines6 for details [see References, Pharmacotherapy surgical approaches to BPH, including below, for URL]). Pharmacological approaches are generally minimally invasive procedures, is beyond It is notable that a variety of medications reserved for men with moderate or severe the scope of this review. Readers interested can cause or exacerbate LUTS (see Box 2), (IPSS/AUA-SI ≥8), bothersome LUTS.6,12 in further information on surgical therapies and this should be kept in mind during The primary place in therapy of the various patient assessment. treatment alternatives, as well as other Box 3 – Lifestyle changes for pertinent information about the LUTS6,8,9 MANAGEMENT medications, is summarized in Table 1. It is The primary goals of BPH treatment are to notable that the comments in Table 1 do not • Modification or restriction of fluid improve symptoms and quality of life and generally discuss adverse effects of the intake (particularly prior to bedtime) lower the risk of disease progression.10 The treatment options; however, such • Avoidance of excessive intake of main treatment strategies include watchful information is provided in the U.S.1,8 and caffeinated/alcoholic beverages or waiting (with or without lifestyle European5 guidelines (see References, spicy foods modification), pharmacological therapies, below, for URLs). • Adjustment/avoidance/monitoring and surgical therapies.2,6,11 Information Presently, the main medical treatment of some drugs* (e.g., diuretics) regarding these approaches is presented options are the alpha-1 adrenoreceptor • Timed or organized voiding below. antagonists (alpha-blockers) and the 5-alpha (bladder retraining) reductase inhibitors (5ARIs).2 It is notable • Pelvic floor exercises Watchful waiting & lifestyle that these agents and others offer • Avoidance or treatment of modification symptomatic relief only and are not curative; constipation Current Canadian6 and U.S.1,8 guidelines therefore, therapy may be life-long.2 • Increased exercise recommend a “watchful waiting” approach Treatment response and adverse effects (i.e., active surveillance, but no active should be assessed after four to six weeks * See Box 2 treatment) for patients with mild LUTS in patients treated with alpha-blockers or ii THERAPEUTIC OPTIONS 2 JANUARY/FEBRUARY/MARCH 2012 C.E. INSERT Therapeutic Options Focus on Benign Prostatic Hyperplasia – Continuing Education TABLE 1 – SOME MEDICATIONS USED TO TREAT MALE LUTS1,5,6,10,12-14 Treatment Usual Daily Primary Place in Comments Option/Drug Dose* Therapy Alpha-blockers First-line treatment for • All agents in class appear to be equally effective in appropriate • Alfuzosin 10 mg moderate-to-severe BPH- doses † • Doxazosin 2–8 mg related LUTS • Typically reduce IPSS by ~35–40% and increase Qmax by ~20– • Tamsulosin 0.4 mg 25%; efficacy does not depend on prostate size • Terazosin 5–10 mg • Improvements may be noted in hours to days; full effects apparent within a few weeks; duration of efficacy appears to be maintained over at least 4 years • Clinical impact of formulation (e.g., immediate vs. sustained release, etc.) is modest • Do not alter the natural progression of disease • Doxazosin and terazosin require dose titration and blood pressure monitoring 5-α reductase Appropriate treatment for • Both agents in class appear to be equally effective inhibitors moderate-to-severe BPH- • Typically reduce IPSS by ~15–30%, decrease prostate volume by • Dutasteride 0.5 mg related LUTS associated ~18–28%, and increase Qmax by ~1.5–2 mL/s after 2–4 years of • Finasteride 5 mg with prostate enlargement treatment; efficacy depends on prostate size‡ • Improvements generally seen after a minimum treatment duration of 6–12 months • May alter the natural progression of disease through a reduction in risk of acute urinary retention and need for surgery • Should not be used for BPH-related LUTS without prostate enlargement • Result in decreased PSA levels,§ which needs to be considered for prostate cancer screening Anticholinergics|| Appropriate for moderate- • Efficacy data from RCTs are limited for men with LUTS; although • Darifenacin 7.5–15 mg to-severe BPH-related storage symptoms