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5 alpha-reductase-inhibitors and prostate cancer

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

Finasteride reduces PSA by an unknown, possibly nonlinear factor that is 50% or more (1,2)

Finasteride and risk of prostate cancer:

  • there is evidence (3) that, in healthy men, finasteride reduced the incidence of prostate cancer
  • however the reduction in prostate cancers was accompanied by an absolute increase increase in incidence of high grade prostate cancers (i.e. more aggressive) in the finasteride treated group as well as increased incidence of sexual side effects
  • study authors concluded that "finasteride prevents or delays the appearance of prostate cancer, but this possible benefit and a reduced risk of urinary problems must be weighed against sexual side effects and the increased risk of high-grade prostate cancer."

In the Prostate Cancer Prevention Trial (PCPT), men receiving finasteride had a 24.8% lower risk of prostate cancer than men receiving placebo but a higher risk of high-grade cancer (4):

  • PSA had statistically significantly better sensitivity and for detecting prostate cancer in the finasteride arm of the PCPT than in the placebo arm. This bias would be expected to contribute to greater detection of all grades of prostate cancer with finasteride
  • found that finasteride introduces detection bias for both prostate cancer and for high-grade (i.e., Gleason grade 7–10) prostate cancer by increasing the sensitivity of PSA for these endpoints
  • authors theorised finasteride treatment of men with elevated PSA levels would cause the greatest fall in PSA level in men with benign conditions such as benign prostatic hyperplasia, whereas men with persistently elevated PSA levels would have a higher probability of cancer
    • men with higher PSA levels in the group receiving finasteride would therefore be more likely to have cancer than men not taking finasteride who also had higher PSA levels.
    • suggested that the increased risk of high-grade disease with finasteride in the PCPT was due, at least in part, to improved detection (i.e., increased sensitivity of PSA) rather than solely to true induction of high-grade disease by finasteride

Systematic review has been undertaken (5):

  • Eight studies were identified, including 54,335 cases of patients that used finasteride and 9197 patients who served as placebo controls. Our results illustrate that there is a significant correlation between finasteride use and prostate cancer with combined ORs of 0.70 [0.51, 0.96]. A significant correlation between finasteride use and high-grade prostate cancer was also observed with combined ORs of 2.10 [1.85, 2.38]
  • concluded that study that finasteride significantly reduced the risk of prostate cancer; however, the malignant degree of prostate cancer was increased. Studies with larger sample sizes are needed to better clarify the correlation between finasteride use and prostate cancer

A more recent cohort study to evaluate the association of treatment with 5 alpha reducatase inhibitors with prostate cancer mortality in men without a prior diagnosis of prostate cancer has concluded (6):

  • was no association between treatment with 5-alpha reductase inhibitors (5-ARI) and increased prostate cancer mortality (PCM) in a large population-based cohort of men without a previous a previous prostate cancer diagnosis
    • systematic review and meta-analysis that included 138,477 users of 5-ARI and 3,105,098 nonusers, no statistically significant association between 5-ARI use and prostate cancer morality was found (adjusted hazard ratio, 1.04; 95% CI 0.80-1.35; P=0.79).
  • additionally, a time-dependent association was seen with decreased risk of PCM with longer 5 alpha reductase inhibitors treatment
  • further research is needed to determine whether the differences are because of intrinsic drug effects or prostate cancer testing differences

Reference:


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