Mark Helfand, MD, MPH, FACP

Staff Physician

Portland VA Medical Center

Portland, OR

Tara Muzyk, Pharm.D.

Clinical Pharmacist

VA Southern Nevada Healthcare System

Las Vegas, NV

Mark Garzotto, MD

Staff Physician, Urology Section 

Portland VA Medical Center

Portland, OR

Evidence Synthesis Pilot Program 

Benign Prostatic Hyperplasia (BPH) 

Management in Primary Care – 

Screening and Therapy

Comparative Effectiveness Review

Department of Veterans Affairs

Health Services Research & Development Service

Final Report

February 2007

The purpose of this report is to make available information regarding the comparative effectiveness and safety 

profiles of different drugs within pharmaceutical classes. 

Reports are not usage guidelines, nor should they be 

read as an endorsement of, or recommendation for, any 

particular drug, use or approach. 

Portland VA Medical Center does not recommend or 

endorse any guideline or recommendation developed by 

users of these reports.
EXECUTIVE SUMMARY 

Background 

Benign prostatic hyperplasia (BPH) causes urinary hesitancy and intermittency, weak urine 

stream, nocturia, frequency, urgency, and the sensation of incomplete bladder emptying. 

These symptoms, collectively called “lower urinary tract symptoms,” or LUTS, can 

significantly reduce quality of life. Men with no symptoms or mild symptoms (AUA 

Symptom Index [SI] score of <7 points), and those who tolerate moderate symptoms well, 

may be managed without pharmacotherapy (“watchful waiting”). For those who have 

moderate or severe symptoms, medical treatments include alpha-1-selective adrenergic 

receptor (a-1-AR) antagonists, 5-alpha-reductase inhibitors (5-aRIs), or a combination 

therapy with one drug from each of these classes. 

This report addresses the following questions about treatment for BPH: 

1. For patients with BPH, what are the comparative benefits, harms, and efficacy of 

combination therapy with a 5-alpha-reductase inhibitor plus an alpha blocker versus 

either treatment alone? 

2. What are the comparative efficacy and harms of alpha-1-adrenergic antagonists? 

3. Are there subgroups of patients based on demographics (age, racial groups), other 

medications, or co-morbidities for which one treatment is more effective or associated 

with fewer adverse events? 

Results 

Combination therapy versus an alpha blocker or 5-ARI alone. 

In the first year of treatment, alpha blockers are more effective than finasteride in improving 

symptoms. Combination therapy and an alpha blocker alone have similar effects on quality 

of life in the first year and a half of treatment. 

For men who have BPH and have a large prostate or a high PSA at baseline, combination 

therapy can prevent about 2 episodes of clinical progression per 100 men per year over 4 

years of treatment. There is no additional benefit within the first year of treatment. Most 

men who take combination therapy will have no additional benefit, and about 4 additional 

patients per 100 will become impotent who would not have taking an alpha blocker alone. 

Combination therapy can also be instituted after clinical progression occurs, but this strategy, 

while used widely, has not been studied. 

There is considerable uncertainty about how best to monitor PSA in whom to choose to take 

finasteride or combination therapy and who are otherwise candidates for PSA screening. 

Candidates for combination therapy—patients who have large prostates and at least moderate 

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Benign Prostatic Hyperplasia 3 
symptoms—tend to have higher PSA levels than other patients who have BPH. Finasteride 

reduces prostate size and PSA levels, making detection of prostate cancer more difficult. 

Alpha-blockers do not affect PSA levels. Expanding access to combination therapy as an 

initial option would require higher utilization of ultrasound and PSA testing in BPH patients 

to assess the risk of progression. The consequences of such a program in a primary care 

setting have not been studied. 

Choice of Alpha Blocker. 

Previous, good-quality systematic reviews found that the alpha blockers, including alfuzosin 

prolonged-release and doxazosin GITS, have similar efficacy in improving symptoms and 

urinary flow rate. Observational studies of doxazosin, terazosin, and tamsulosin in selected 

patients indicate that in most patients who respond to an alpha blocker and who tolerate it 

well initially, the drug continues to work and to be well-tolerated for many years. 

Head-to-head trials of alpha-blockers are few, small, and have serious limitations. They do 

not adequately test commonly held beliefs about differences in the side effect profiles of the 

alpha blockers. Specifically, they do not prove that, when used in practice, tamsulosin causes 

fewer cardiovascular adverse effects than other alpha-blockers because it does not reduce 

blood pressure. In placebo-controlled trials, tamsulosin caused higher rates of sexual 

ejaculation abnormalities than other alpha blockers. The placebo-controlled trials do not 

adequately test the hypothesis that use of tamsulosin as initial therapy reduces the risk of 

symptomatic hypotension. 

For combination therapy, doxazosin is the best-studied alpha blocker. 

Treatment of BPH in subgroups of patients. 

Long-term observational studies establish that BPH can be treated safely with alpha blockers 

in patients taking other medications for hypertension. Alpha blockers should not be used as 

initial treatment for patients with hypertension, even those with BPH, because they are 

associated with poorer long-term outcomes than other choices. Data on the safety of alpha 

blockers in patients taking erectile dysfunction drugs are sparse. 

Recently, the FDA issued a notice that intraoperative Floppy Iris Syndrome (IFIS) has been 

observed during phacoemulsification cataract surgery in some patients currently or recently 

treated with tamsulosin. 

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