5-α-Reductase inhibitors for prostate cancer chemoprevention: an updated Cochrane systematic review.
OBJECTIVE
• To estimate the benefits and harms of 5-α-reductase inhibitors (5-α-RIs) in preventing prostate cancer.


METHODS
• We searched MEDLINE and the Cochrane Collaboration Library through June 2010 to identify randomized trials. • We included articles if they examined 5-α-RI vs control, were ≥ 1 year in duration and provided clinical outcomes. • Our primary outcome was prostate cancer period-prevalence 'for-cause'.


RESULTS
• Eight studies met inclusion criteria but only the Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events were designed to assess the impact of 5-α-RIs on prostate cancer period-prevalence. The mean age of enrolees was 64 years, 92% were White, and mean PSA level was 3.1 ng/mL. For-cause prostate cancers comprised 54% of all cancers detected in placebo-controlled studies. • Compared with placebo, 5-α-RI resulted in a 25% relative risk (RR) reduction in prostate cancers detected for-cause [RR 0.75, 95% confidence interval (CI) 0.67-0.83; 1.4% absolute risk reduction (3.5% vs 4.9%)]. One BPH trial reported that the risk of prostate cancers detected for-cause was significantly reduced with dutasteride and combined dutasteride plus tamsulosin compared with tamsulosin monotherapy. • Six trials vs placebo assessed prostate cancers detected overall. There was a 26% RR reduction favouring 5-α-RI [RR 0.74, 95% CI 0.55-1.00; 2.9% absolute risk reduction (6.3% vs 9.2%)]. There were reductions across categories of age, race and family history of prostate cancer. • One placebo-controlled trial of men that investigators considered at greater risk for prostate cancer (based on age, elevated PSA level and having a previous suspicion of prostate cancer leading to a prostate biopsy) reported that dutasteride did not reduce prostate cancers detected for-cause based on needle-biopsy but did reduce risk of overall incident prostate cancer detected by biopsy by 23%[RR 0.77, 95% CI 0.70-0.85; absolute reduction 16.1% vs 20.8%]. There were reductions across age, family history of prostate cancer, PSA level, and prostate volume subgroups. • Incidences of erectile dysfunction, ejaculate volume, decreased libido, and gynaecomastia were greater with 5-α-RI vs placebo.


CONCLUSIONS
• 5-α-RIs reduce the risk of being diagnosed with prostate cancer among men who are screened regularly for prostate cancer. • Information is inadequate to assess the effect of 5-α-RIs on prostate cancer or all-cause mortality. • 5-α-RIs increase sexual and erectile dysfunction.
Wilt
Timothy J
TJ
Minneapolis VA Center for Chronic Disease Outcomes Research, Minneapolis, MN 55417, USA. tim.wilt@va.gov
Macdonald
Roderick
R
Hagerty
Karen
K
Schellhammer
Paul
P
Tacklind
James
J
Somerfield
Mark R
MR
Kramer
Barnett S
BS
D058891:5-alpha Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D016588:Anticarcinogenic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001378:Azasteroids / Q000627:therapeutic use; D000068538:Dutasteride; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000401:mortality / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic
D058891:5-alpha Reductase Inhibitors; D016588:Anticarcinogenic Agents; D001378:Azasteroids; D000068538:Dutasteride