How effective are 5-ARIs for the treatment of benign prostatic hyperplasia (BPH)?

Updated: Feb 19, 2021
  • Author: Levi A Deters, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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Answer

Inhibition of 5-alpha-reductase type 2 blocks the conversion of testosterone to DHT, resulting in lower intraprostatic levels of DHT. This leads to inhibition of prostatic growth, apoptosis, and involution. The exact role of 5-alpha-reductase type 1 in normal and abnormal prostatic development is undefined.

Finasteride, a 4-aza-steroid, has demonstrated 5-alpha type II–blocking activity, resulting in the inhibition of DHT-receptor complex formation. This effect causes a profound decrease in the concentration of DHT intraprostatically, resulting in a consistent decrease in prostate size. One third of men treated with this agent exhibit improvements in urine flow and symptoms.

In the Proscar Long-Term Efficacy and Safety Study (PLESS), patients treated with finasteride (5 mg/d) were at a significantly lower risk of developing acute urinary retention or needing surgery. [19]  This was a multicenter, 4-year, double-blind, placebo-controlled study of 3,040 patients. Men with PSA levels of more than 10 ng/mL and those with prostate cancer were excluded.

Dutasteride has an affinity for both type 1 and type 2 5-alpha-reductase receptors. The significance of blockage of type 1 receptors is currently unknown.

Both finasteride and dutasteride actively reduce DHT levels by more than 80%, improve symptoms, reduce the incidence of urinary retention, and decrease the likelihood of surgery for BPH. Adverse effects are primarily sexual in nature (decreased libido, erectile dysfunction, ejaculation disorder).

Both finasteride and dutasteride may reduce serum PSA values by as much as 50%. The decrease in PSA is typically maximally achieved when the maximal decrease in prostatic volume is noted (6 months). This effect must be taken into account when using PSA to screen for prostate cancer.

A prospective, randomized, double-blind study, the Enlarged Prostate International Comparator Study (EPICS), was conducted to compare the efficacy of dutasteride with that of finasteride in men with symptomatic BPH. Although this study was conducted over the course of only 1 year, the data suggest that both drugs were similarly effective in reducing prostate volume and improving maximum urinary flow rate (Qmax) and LUTS for this population. The long-term outcomes are yet to be investigated. [20]


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