[58] Benign Prostatic Hypertrophy – An update on drug therapy

Benign Prostatic Hypertrophy – An update on drug therapy

[58] Benign Prostatic Hypertrophy – An update on drug therapy

Benign Prostatic Hypertrophy – An update on drug therapyBenign prostatic hypertrophy (BPH) is relatively common and potentially bothersome to aging men. See Therapeutics Letter #19 (May/June 1997) for background information.1 This Letter updates the evidence of benefit and harm from alpha blockers and 5-α-reductase inhibitors.

The goals of drug therapy are symptom relief and prevention of complications. Symptoms are classified as irritative (frequency, nocturia, burning, urgency, or urge incontinence) or obstructive (hesitancy, weak stream, dribbling, incomplete voiding, or retention).

Many trials use the 35-point American Urological Association (AUA) symptom scale.1 When AUA scores were compared with patient perceptions, men who felt ‘slightly improved’ averaged a 3-pt reduction; those ‘not improved’ averaged a 0.7-pt reduction.8 Over 4 years, mean AUA scores fell by 5 points on placebo.5

Complications of BPH include infection, acute urinary retention (AUR) requiring catheterization, and urinary obstruction requiring surgery (partial or complete prostatectomy).

Alpha blockers

Five alpha blockers are available in Canada: alfuzosin, doxazosin, prazosin, tamsulosin, and terazosin.

Alpha blockers provide modest symptomatic benefit. Compared with placebo, on average terazosin reduced AUA score by 3 points,4 tamsulosin by 3 points,5 doxazosin by 3 points at 1 year6 and 2 points at 4 years,2 alfuzosin by 2 points short-term7 and 1 point at 2 years.3 Comparable data are not available for prazosin. Alpha blockers do not prevent BPH complications. Doxazosin was tested over 4 years vs. placebo (n=1493).2 Incidence of AUR (doxazosin 1%, placebo 2%) and surgery (doxazosin 3%, placebo 5%) did not differ. A 2-year trial of alfuzosin vs. placebo (n=1506) also found no difference in AUR or surgery.3

Only one trial longer than a year reports on serious adverse events (SAEs): alfuzosin 12%, placebo 11%.3 In the ALLHAT hypertension trial (no placebo arm), doxazosin increased congestive heart failure, angina and stroke vs. chlorthalidone. (see Therapeutics Letter 36)

The most frequent adverse effects of alpha blockers are dizziness, asthenia and postural hypotension. Tamsulosin’s efficacy increases slightly with higher doses, but adverse effects are dose-related: dizziness 17% at 0.8mg, 9% at 0.4mg and 3% at 0.2mg.5 Average absolute risk increases for alpha blockers versus placebo are: dizziness 3-8%, postural hypotension 3-5%, and asthenia 5-6%, number needed to harm (NNH) 13-33.4, 5, 7, 9

No consistent evidence exists for a therapeutic advantage of one alpha blocker over another.

5-α-reductase inhibitors

Two 5-α-reductase inhibitors are available in Canada: finasteride and dutasteride.


Finasteride did not significantly reduce symptom scores vs. placebo in one 4-year trial.2 In a second 4-year trial, scores fell by a mean of 1.6 points.11

We meta-analyzed 16 randomized controlled trials (RCTs) (n=17,456; max 4 years) with at least one clinically important health outcome (Table 1).2, 6, 10-23 Since finasteride reduces AUR and surgery it is surprising that total SAEs are not also reduced. Published reports provide insufficient detail to assess rates of other SAEs.

During a 4-year trial, 4/1554 (0.3%) men on finasteride developed breast cancer (~ 200 times expected rate).2, 24 In a 7-year prostate cancer prevention trial (n=18,882) fewer men on finasteride vs. placebo developed tumours, 18.4% vs. 24.4%, but more men on finasteride had high-grade tumours with a worse prognosis: 6.4% vs. 5.1%. Mortality did not differ.25

Table 1: Benefits and Harms of Finasteride vs Placebo

Outcome N* Finasteride Placebo RR
(95% CI)
Mortality 2,358 1.2% 0.7% 1.7
Total SAEs 9,180 11.0% 11.4% 0.9
Prostate Surgery 15,398 2.1% 4.8% 0.6
2.7% 37
Acute Urinary Retention 14,329 1.1% 3.1% 0.4
2.0% 50
Ejaculation Abnormality 14,396 2.7% 0.7% 3.6
2.0% 50
Erectile Dysfunction 15,839 8.1% 4.8% 1.8
3.3% 30
Decreased Libido 14,626 5.3% 3.4% 1.7
1.9% 53

*N = number of patients in trials with this outcome
RR = relative risk
CI = confidence interval
ARR = absolute risk reduction
ARI = absolute risk increase
NNT = number needed to treat to prevent one event
NNH = number needed to treat to cause one harmful event

Finasteride versus alpha blockers

Five RCTs (0.5 – 4 yrs) compared finasteride with an alpha blocker.2, 6, 10, 26, 27 Mortality,6, 10 SAEs 26, 27 and withdrawals due to adverse effects 6, 10, 26, 27 did not differ. Finasteride increased sexual dysfunction; alpha blockers increased dizziness, postural hypotension and asthenia. Surgery rates did not differ: finasteride 1.6%, doxazosin or terazosin 2.2%.2, 6, 10 In 4 studies alpha blockers reduced AUA symptom scores by 1-3 points more than finasteride.2, 6, 10, 27 Alfuzosin affected scores similarly to finasteride.26

Adding finasteride to an alpha blocker

Adding finasteride did not reduce mean symptom score as compared with an alpha-blocker alone in 0.5 – 1 year trials: difference = 0.3 points.6, 10, 26 In one 4-year RCT the mean symptom score fell by 0.8 points.2

Adding an alpha blocker to finasteride

Combination therapy reduced a combined outcome (“clinical progression”) largely driven by symptom scores vs. finasteride alone,2 but did not reduce AUR (0.4% vs. 0.7%)2, 6, 26 or surgery (1.0% vs. 1.6%).2, 6, 10


Dutasteride has been tested less extensively. In 3 double-blind trials (combined n=4325), dutasteride reduced AUA scores by 1.3 points vs. placebo at 1 year. Dutasteride reduced AUR (1.8% vs. 4.2%) and need for surgery (2.2% vs. 4.1%), but increased impotence (7.3% vs. 4.0%), ejaculation disorder, gynecomastia and lowered libido.28 Mortality and SAE rates did not differ.29 A 6-month trial (n=399)30 and an unpublished 1-year trial (n=1630) vs. finasteride found no difference in efficacy or adverse events. Total SAEs and mortality were not reported.31-33

Table 2: Usual dose range, half-life and cost of drugs for BPH

Drug Brand name Dose range Half-life Daily cost
alfuzosin Xatral® 10 mg/d 5-10 hrs $1.14^
doxazosin Cardura®, generic 1-8 mg/d 22 hrs $0.35 – $1.09*
prazosin generic 1-5 mg BID 2-3 hrs $0.32 – $0.62*
tamsulosin Flomax® 0.4-0.8 mg/d 5-7 hrs $1.04 – $2.08*
terazosin Hytrin®, generic 1-10 mg/d 12 hrs $0.36 – $0.90*
dutasteride Avodart® 0.5 mg/d 5 weeks $1.96^
finasteride Proscar® 5 mg/d 6 hrs $1.78*

* = Average daily cost for the lowest priced formulation, calculated using 2005 BC PharmaCare data.
^ = Average price at local pharmacy in Vancouver, BC.


  • Alpha blockers improve symptoms on average by 2-3 points more than placebo (35 point AUAscale), a difference patients perceive as ‘slight benefit’. Alpha blockers do not reduce complications, but increase dizziness, postural hypotension and asthenia (ARI 3-8%, NNH 13-33).
  • 5-a-reductase inhibitors reduce acute urinary retention (ARR 2%, NNT 50), and BPH surgery (ARR 2-3%, NNT 33-50), but impair sexual function (ARI 3%, NNH 33).
  • There is insufficient evidence that combining the two drug classes provides additional benefit.
  • Most BPH trials do not report total serious adverse events and mortality. This prevents an assessment of the overall clinical impact of drug treatment.

Clinical implications

Men with bothersome symptoms who wish a trial of alpha blocker therapy should set their own treatment goals and weigh the benefits (e.g. symptom relief) against side effects (e.g. postural hypotension, asthenia). Since all alpha blockers have relatively short half-lives (see Table 2), maximum concentrations and effect will occur within 4 days. A reasonable approach is to start with a low dose and assess for symptoms during a series of 1-week therapeutic trials at several doses. Neither finasteride nor dutasteride provide symptomatic benefit for most men. Patients considering long-term therapy to prevent complications should be informed of the magnitude of potential benefits and harms, as outlined above.

Addendum: saw palmetto extract
Letter #19 discussed saw palmetto (S.repens), a commonly used herbal treatment. A Cochrane review suggested a short term modest reduction in symptoms with saw palmetto.34 A new 1-year RCT comparing standardized doses (160 mg BID) with placebo showed no differences in symptom scores, urinary flow rates, quality of life measures, adverse effects or SAEs.35

The draft of this Therapeutics Letter was submitted for review to 40 experts and primary care physicians in order to correct any inaccuracies and to ensure that the information is concise and relevant to clinicians.


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