What Eun Dutasteride for AGA Actually Changes in Clinical Practice

The trial behind the claim

Eun and colleagues randomized 153 men aged 18 to 49 with male pattern hair loss to dutasteride 0.5 mg once daily or placebo for 6 months, double-blind, as a phase III study [1]. Efficacy was judged by change in hair counts, subject self-assessment, and photographic assessment by investigators and a panel [1]. That is the entire design: one active drug, one comparator, and 6 months of treatment [1].

What the results showed

Mean hair count from baseline to 6 months rose 12.2 per cm² in the dutasteride group and 4.7 per cm² in the placebo group, a statistically significant difference (P=.0319) [1]. Dutasteride also scored better than placebo on subject self-assessment and on investigator and panel photographic assessment [1]. The investigators reported no major difference in adverse events between the two groups and listed the 6-month duration as a limitation [1].

Pharmacology from the Avodart label (studied in men with BPH): dutasteride inhibits both type 1 and type 2 5-alpha-reductase, and the type 1 isoenzyme is also responsible for testosterone conversion in skin as well as liver [3]. Median serum DHT fell 85% after 1 week and 90% after 2 weeks on 0.5 mg daily, reaching 94% at 1 year [3]. Median serum testosterone rose about 19% to 26% but stayed within the physiologic range [3].

Where the finasteride comparison comes from

The head-to-head claim that dutasteride 0.5 mg beats finasteride 1 mg on hair count comes from a separate study: 917 men aged 20 to 50 randomized to dutasteride 0.02, 0.1 or 0.5 mg daily, finasteride 1 mg daily, or placebo for 24 weeks, in which dutasteride 0.5 mg increased hair count on a 2.54-cm diameter measurement and increased hair width versus finasteride (P=.003 and P=.004) and versus placebo (all P<.001), with similar number and severity of adverse events across groups [2].

An earlier dose-ranging trial of 416 men aged 21 to 45 compared dutasteride 0.05, 0.1, 0.5 and 2.5 mg with finasteride 5 mg and placebo for 24 weeks. Dutasteride raised target-area hair count versus placebo in a dose-dependent way, and dutasteride 2.5 mg was superior to finasteride 5 mg at 12 and 24 weeks [4]. The finasteride comparator in that trial was 5 mg [4], compared with 1 mg in the later head-to-head trial [2].

Dose and regulatory status

0.5 mg once daily is the dose Eun tested [1], the dose that beat finasteride 1 mg in the 2014 trial [2], and the dose on the BPH label [3]. The Avodart label lists 0.5 mg once daily and says to swallow the capsule whole, not chewed or opened, with or without food [3].

Avodart is indicated for symptomatic BPH in men with an enlarged prostate, alone or with tamsulosin, to improve symptoms and reduce the risk of acute urinary retention and BPH-related surgery [3]. The limitations section states it is not approved for prevention of prostate cancer [3].

Label facts that matter once a man is taking it

PSA. Dutasteride lowers serum PSA by about 50% within 3 to 6 months [3]. The label directs a new PSA baseline at least 3 months after starting with periodic monitoring, doubling of an isolated PSA value in a man treated 3 months or more when comparing against ranges for untreated men, and evaluation of any confirmed rise from the lowest on-treatment value even if it is still within the normal range [3]. Percent free PSA is unchanged, and combining with tamsulosin changes PSA the same as dutasteride alone [3]. Non-compliance can also affect results [3].

Time in the body. Terminal half-life is about 5 weeks at steady state, with serum levels above 0.1 ng/mL for up to 4 to 6 months after the last dose; the label says men being treated should not donate blood until at least 6 months after the last dose [3]. About 65% of steady state is reached after 1 month and about 90% after 3 months [3].

Semen and fertility. Over 52 weeks in healthy men, dutasteride reduced total sperm count by 23%, semen volume by 26% and sperm motility by 18% compared with placebo. Sperm concentration and morphology were unaffected and mean values for all semen parameters stayed within the normal range; total sperm count was still 23% below baseline after 24 weeks off drug [3]. The label states that the clinical significance for an individual patient's fertility is not known [3].

Sexual adverse effects. In pooled 2-year BPH trials (mean age 66), months 0 to 6: impotence 4.7% versus 1.7% on placebo, decreased libido 3.0% versus 1.4%, ejaculation disorders 1.4% versus 0.5%, and breast disorders 0.5% versus 0.2% [3]. The label notes these sexual reactions may persist after discontinuation and that the role of dutasteride in that persistence is unknown [3]. In hair-loss populations, a meta-analysis of 15 randomized placebo-controlled trials (4,495 men) found a 1.57-fold overall relative risk of sexual dysfunction with 5-alpha reductase inhibitors; for dutasteride 0.5 mg the relative risk was 1.37 (95% CI 0.81 to 2.32), not statistically significant, with few dutasteride trials available [5].

Mood. The Avodart label lists depressed mood among postmarketing reports [3]. In a Swedish register cohort of 2.2 million men aged 50 to 90, the 8,774 who started dutasteride had a depression hazard ratio of 1.68 (95% CI 1.43 to 1.96), with no association for suicide (HR 0.98, 95% CI 0.62 to 1.54); the group was mostly older men treated for BPH and the study was observational [6].

Prostate cancer. REDUCE, a 4-year trial in men 50 to 75 with a prior negative biopsy and PSA 2.5 to 10 ng/mL, found Gleason 8 to 10 cancer in 1.0% on dutasteride versus 0.5% on placebo, and the label warns that 5-alpha reductase inhibitors may increase the risk of high-grade prostate cancer [3]. Overall biopsy-detected cancer was lower on dutasteride: 659 of 3,305 men versus 858 of 3,424, a relative risk reduction of 22.8% (95% CI 15.2 to 29.8) [7].

Pregnancy handling. The label contraindicates dutasteride in pregnancy and says women who are pregnant or may be pregnant should not handle the capsules; it states dutasteride can be absorbed through the skin, and that if a pregnant woman touches a leaking capsule, the area should be washed immediately with soap and water [3]. The label also states Avodart is not indicated for use in women [3].

Bottom line

The Eun trial produced a clean, placebo-controlled result: dutasteride 0.5 mg grew more hair than placebo in men aged 18 to 49 with male pattern hair loss over 6 months, with no major difference in adverse events at that duration [1]. It provides 6-month evidence for a measurable hair-count benefit with 0.5 mg daily, but it does not establish long-term benefit, compare multiple doses, or compare dutasteride with finasteride [1].