Avodart Bone Health and Density Impact: What the Evidence Says About Dutasteride

What the two 4-year trials measured

REDUCE randomized 8,231 men aged 50 to 75 with a PSA of 2.5 to 10 ng/mL and a negative prostate biopsy within the previous 6 months to dutasteride 0.5 mg daily or placebo for up to four years [1]. Among 6,729 men who had a biopsy or prostate surgery, cancer was detected in 659 of 3,305 men on dutasteride versus 858 of 3,424 on placebo, a 22.8% relative reduction (95% CI 15.2 to 29.8) [3]. During years 3 and 4 there were 12 Gleason 8 to 10 tumors on dutasteride versus 1 on placebo (P=0.003) [3]. Acute urinary retention was 1.6% versus 6.7% [3].

CombAT randomized 4,844 men aged 50 or older with BPH to dutasteride 0.5 mg, tamsulosin 0.4 mg, or both, once daily for four years [2]. Its reported outcomes were time to first acute urinary retention or BPH-related surgery, BPH clinical progression, symptom scores, maximum urinary flow rate, prostate volume and tolerability [2]. Combination therapy was better than tamsulosin alone but not better than dutasteride alone for acute urinary retention or BPH-related surgery, and better than either monotherapy for symptom scores and clinical progression [2].

What dutasteride does to DHT and testosterone

Dutasteride is a competitive inhibitor of both 5-alpha-reductase isoforms, forming a stable enzyme complex that dissociates extremely slowly, and it does not bind the androgen receptor [1]. Median serum DHT fell 85% after one week, 90% after two weeks, 94% at one year, 93% at two years and 95% at three and four years [1].

Median serum testosterone rose about 19% to 26% and stayed within the physiologic range [1]. Finasteride inhibits mainly type 2 and, at 1 mg, suppresses serum DHT by about 65% [1]. Dutasteride also clears far more slowly: its terminal half-life at steady state is about 5 weeks, compared with about 5 to 6 hours for finasteride [1].

What the Avodart label covers

The label says PSA falls about 50% within 3 to 6 months of starting. It calls for a new baseline at least 3 months in, doubling an isolated value in a treated man for comparison with normal ranges, and evaluating any confirmed rise from the lowest on-treatment value even if it is still within the normal range for untreated men [1].

The label warns of an increased risk of high-grade prostate cancer: Gleason 8 to 10 cancer was 1.0% on Avodart versus 0.5% on placebo in REDUCE [1]. It says women who are or may be pregnant should not handle the capsules because dutasteride can be absorbed through the skin, and that the contact area should be washed immediately with soap and water if a leaking capsule is touched [1]. It also says men being treated with Avodart should not donate blood until at least 6 months have passed since the last dose [1]. Over 52 weeks, total sperm count fell 23%, semen volume 26% and sperm motility 18% versus placebo, with mean values remaining within the normal range [1]. Bone density and fracture are not among these warnings [1].

Off-label use for hair loss

Dutasteride is FDA-approved only for symptomatic BPH; androgenetic alopecia is off-label [1]. A 24-week trial randomized 917 men aged 20 to 50 to dutasteride 0.02, 0.1 or 0.5 mg, finasteride 1 mg, or placebo [4]. Dutasteride 0.5 mg increased hair count more than finasteride (P=.003) and placebo (P<.001), with similar numbers and severity of adverse events across groups [4].

Bottom line

Dutasteride lowers serum DHT substantially and raises testosterone modestly within the normal range [1]. The Avodart label's warnings center on PSA interpretation, high-grade prostate cancer, pregnancy handling, blood donation and semen characteristics [1].