Marked Suppression of Dihydrotestosterone in Men with Benign Prostatic Hyperplasia by Dutasteride, a Dual 5α-Reductase Inhibitor

Abstract

Dihydrotestosterone (DHT) is the primary metabolite of testosterone in the prostate and skin. Testosterone is converted to DHT by 5alpha-reductase, which exists in two isoenzyme forms (types 1 and 2). DHT is associated with development of benign prostatic hyperplasia (BPH), and reduction in its level with 5alpha-reductase inhibitors improves the symptoms associated with BPH and reduces the risk of acute urinary retention and prostate surgery. A selective inhibitor of the type 2 isoenzyme (finasteride) has been shown to decrease serum DHT by about 70%. We hypothesized that inhibition of both isoenzymes with the dual inhibitor dutasteride would more effectively suppress serum DHT levels than selective inhibition of only the type 2 isoenzyme. A total of 399 patients with BPH were randomized to receive once-daily dosing for 24 wk of dutasteride (0.01, 0.05, 0.5, 2.5, or 5.0 mg), 5 mg finasteride, or placebo. The mean percent decrease in DHT was 98.4 +/- 1.2% with 5.0 mg dutasteride and 94.7 +/- 3.3% with 0.5 mg dutasteride, significantly lower (P < 0.001) and with less variability than the 70.8 +/- 18.3% suppression observed with 5 mg finasteride. Mean testosterone levels increased but remained in the normal range for all treatment groups. Dutasteride appeared to be well tolerated with an adverse event profile similar to placebo.

Testosterone and Erectile Function: From Basic Research to a New Clinical Paradigm for Managing Men with Androgen Insufficiency and Erectile Dysfunction

“…Subphysiologic levels of DHT may occur with the medical treatment for lower urinary tract symptoms (LUTS) that engages clinical use of 5-alpha reductase inhibitors and lowers the circulating level of DHT by as much as 80% [112]. The 5-alpha reductase inhibitors finasteride and dutasteride are reportedly associated with a greater risk of ED, ejaculatory dysfunction, and decreased libido compared with placebo [113,114].…”

Androgens and male aging: current evidence of safety and efficacy

“…By contrast, a variety of studies, using various designs and testosterone formulations, over periods ranging from several months to 15 years, in men with a wide range of ages, have not revealed an increased risk of prostate cancer [139][140][141][142][143][144][145][146][147][148][149][150][151][152][153][154]. A meta-analysis found that testosterone treatment in older men compared to placebo was not associated with a significantly higher risk of detection of prostate cancer [131], although the frequency of prostate biopsies was much higher in the testosterone-treated group than in the placebo group [131].…”

Prostate cancer prevention: concepts and clinical recommendations

“…10,[33][34][35] As dutasteride inhibits both isoforms, it results in greater reductions in serum and intraprostatic DHT levels than finasteride. [36][37][38][39] REDUCE was a 4-year, multi-institutional, RCT of 0.5 mg daily oral dutasteride versus placebo in 8000 men. Inclusion criteria included PSA 2.5-10 ng ml -1 for men 50-60 years or 3.0-10 ng ml -1 for men 60-75 years; prostate volume o80 ml; American Urologic Association symptom score o25; and a prostate biopsy negative for cancer, high-grade prostatic intraepithelial neoplasia (HGPIN), and atypical small acinar proliferation within the earlier 6 months.…”