title: Effect of testosterone supplementation with and without a dual 5α-reductase inhibitor on fat-free mass in men with suppressed testosterone production: a randomized controlled trial.
abstract: BACKGROUND
  Steroid 5α-reductase inhibitors are used to treat benign prostatic hyperplasia and androgenic alopecia, but the role of 5α-dihydrotestosterone (DHT) in mediating testosterone's effects on muscle, sexual function, erythropoiesis, and other androgen-dependent processes remains poorly understood.
  
  
  OBJECTIVE
  To determine whether testosterone's effects on muscle mass, strength, sexual function, hematocrit level, prostate volume, sebum production, and lipid levels are attenuated when its conversion to DHT is blocked by dutasteride (an inhibitor of 5α-reductase type 1 and 2).
  
  
  METHODS
  The 5α-Reductase Trial was a randomized controlled trial of healthy men aged 18 to 50 years comparing placebo plus testosterone enthanate with dutasteride plus testosterone enanthate from May 2005 through June 2010.
  
  
  METHODS
  Eight treatment groups received 50, 125, 300, or 600 mg/wk of testosterone enanthate for 20 weeks plus placebo (4 groups) or 2.5 mg/d of dutasteride (4 groups).
  
  
  METHODS
  The primary outcome was change in fat-free mass; secondary outcomes: changes in fat mass, muscle strength, sexual function, prostate volume, sebum production, and hematocrit and lipid levels.
  
  
  RESULTS
  A total of 139 men were randomized; 102 completed the 20-week intervention. Men assigned to dutasteride were similar at baseline to those assigned to placebo. The mean fat-free mass gained by the dutasteride groups was 0.6 kg (95% CI, -0.1 to 1.2 kg) when receiving 50 mg/wk of testosterone enanthate, 2.6 kg (95% CI, 0.9 to 4.3 kg) for 125 mg/wk, 5.8 kg (95% CI, 4.8 to 6.9 kg) for 300 mg/wk, and 7.1 kg (95% CI, 6.0 to 8.2 kg) for 600 mg/wk. The mean fat-free mass gained by the placebo groups was 0.8 kg (95% CI, -0.1 to 1.7 kg) when receiving 50 mg/wk of testosterone enanthate, 3.5 kg (95% CI, 2.1 to 4.8 kg) for 125 mg/wk, 5.7 kg (95% CI, 4.8 to 6.5 kg) for 300 mg/wk, and 8.1 kg (95% CI, 6.7 to 9.5 kg) for 600 mg/wk. The dose-adjusted differences between the dutasteride and placebo groups for fat-free mass were not significant (P = .18). Changes in fat mass, muscle strength, sexual function, prostate volume, sebum production, and hematocrit and lipid levels did not differ between groups.
  
  
  CONCLUSIONS
  Changes in fat-free mass in response to graded testosterone doses did not differ in men in whom DHT was suppressed by dutasteride from those treated with placebo, indicating that conversion of testosterone to DHT is not essential for mediating its anabolic effects on muscle.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00493987.
authors.affiliation: Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine and Boston Medical Center, 670 Albany St, Boston, MA 02118, USA. bhasin@bu.edu
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Travison
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Storer
authors.forename: Kishore
authors.initials: K
authors.lastname: Lakshman
authors.forename: Manas
authors.initials: M
authors.lastname: Kaushik
authors.forename: Norman A
authors.initials: NA
authors.lastname: Mazer
authors.forename: Ahn-Hoa
authors.initials: AH
authors.lastname: Ngyuen
authors.forename: Maithili N
authors.initials: MN
authors.lastname: Davda
authors.forename: Hernan
authors.initials: H
authors.lastname: Jara
authors.forename: Adam
authors.initials: A
authors.lastname: Aakil
authors.forename: Stephan
authors.initials: S
authors.lastname: Anderson
authors.forename: Philip E
authors.initials: PE
authors.lastname: Knapp
authors.forename: Samson
authors.initials: S
authors.lastname: Hanka
authors.forename: Nurahmed
authors.initials: N
authors.lastname: Mohammed
authors.forename: Pierre
authors.initials: P
authors.lastname: Daou
authors.forename: Renee
authors.initials: R
authors.lastname: Miciek
authors.forename: Jagadish
authors.initials: J
authors.lastname: Ulloor
authors.forename: Anqi
authors.initials: A
authors.lastname: Zhang
authors.forename: Brad
authors.initials: B
authors.lastname: Brooks
authors.forename: Katie
authors.initials: K
authors.lastname: Orwoll
authors.forename: Leife
authors.initials: L
authors.lastname: Hede-Brierley
authors.forename: Richard
authors.initials: R
authors.lastname: Eder
authors.forename: Ayan
authors.initials: A
authors.lastname: Elmi
authors.forename: Geeta
authors.initials: G
authors.lastname: Bhasin
authors.forename: Lauren
authors.initials: L
authors.lastname: Collins
authors.forename: Ravinder
authors.initials: R
authors.lastname: Singh
authors.forename: Shehzad
authors.initials: S
authors.lastname: Basaria
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors / Q000494:pharmacology*; D050154:Adiposity / Q000187:drug effects*; D000328:Adult; D001378:Azasteroids / Q000494:pharmacology*; D015992:Body Mass Index; D004311:Double-Blind Method; D000068538:Dutasteride; D006400:Hematocrit; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D053580:Muscle Strength / Q000187:drug effects*; D011467:Prostate / Q000033:anatomy & histology / Q000187:drug effects; D012098:Reproduction / Q000187:drug effects*; D012629:Sebum / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D008055:Lipids; D013739:Testosterone; C013915:boldenone; C004648:testosterone enanthate; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D000068538:Dutasteride