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

Shalender Bhasin, Thomas G. Travison, Thomas W. Storer, Kishore Lakshman, Manas Kaushik, Norman A. Mazer, Ahn Hoa Ngyuen, Maithili N. Davda, Hernan Jara, Adam Aakil, Stephan Anderson, Philip E. Knapp, Samson Hanka, Nurahmed Mohammed, Pierre Daou, Renee Miciek, Jagadish Ulloor, Anqi Zhang, Brad Brooks, Katie OrwollLeife Hede-Brierley, Richard Eder, Ayan Elmi, Geeta Bhasin, Lauren Collins, Ravinder Jit Singh, Shehzad Basaria

Research output: Contribution to journalArticle

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Abstract

Context: 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). Design, Setting, and Patients: 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. Interventions: 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). Main Outcome Measures: 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. Conclusion: 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. Trial Registration: clinicaltrials.gov Identifier: NCT00493987.

Original languageEnglish (US)
Pages (from-to)931-939
Number of pages9
JournalJAMA - Journal of the American Medical Association
Volume307
Issue number9
DOIs
StatePublished - Feb 29 2012

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Testosterone
Oxidoreductases
Randomized Controlled Trials
Fats
Dihydrotestosterone
Placebos
Sebum
Muscle Strength
Hematocrit
Prostate
Lipids
Anabolic Agents
Muscles
Erythropoiesis
Alopecia
Prostatic Hyperplasia
Dutasteride
Androgens
Steroids
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Medicine(all)

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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. / Bhasin, Shalender; Travison, Thomas G.; Storer, Thomas W.; Lakshman, Kishore; Kaushik, Manas; Mazer, Norman A.; Ngyuen, Ahn Hoa; Davda, Maithili N.; Jara, Hernan; Aakil, Adam; Anderson, Stephan; Knapp, Philip E.; Hanka, Samson; Mohammed, Nurahmed; Daou, Pierre; Miciek, Renee; Ulloor, Jagadish; Zhang, Anqi; Brooks, Brad; Orwoll, Katie; Hede-Brierley, Leife; Eder, Richard; Elmi, Ayan; Bhasin, Geeta; Collins, Lauren; Singh, Ravinder Jit; Basaria, Shehzad.

In: JAMA - Journal of the American Medical Association, Vol. 307, No. 9, 29.02.2012, p. 931-939.

Research output: Contribution to journalArticle

Bhasin, S, Travison, TG, Storer, TW, Lakshman, K, Kaushik, M, Mazer, NA, Ngyuen, AH, Davda, MN, Jara, H, Aakil, A, Anderson, S, Knapp, PE, Hanka, S, Mohammed, N, Daou, P, Miciek, R, Ulloor, J, Zhang, A, Brooks, B, Orwoll, K, Hede-Brierley, L, Eder, R, Elmi, A, Bhasin, G, Collins, L, Singh, RJ & Basaria, S 2012, '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', JAMA - Journal of the American Medical Association, vol. 307, no. 9, pp. 931-939. https://doi.org/10.1001/jama.2012.227
Bhasin, Shalender ; Travison, Thomas G. ; Storer, Thomas W. ; Lakshman, Kishore ; Kaushik, Manas ; Mazer, Norman A. ; Ngyuen, Ahn Hoa ; Davda, Maithili N. ; Jara, Hernan ; Aakil, Adam ; Anderson, Stephan ; Knapp, Philip E. ; Hanka, Samson ; Mohammed, Nurahmed ; Daou, Pierre ; Miciek, Renee ; Ulloor, Jagadish ; Zhang, Anqi ; Brooks, Brad ; Orwoll, Katie ; Hede-Brierley, Leife ; Eder, Richard ; Elmi, Ayan ; Bhasin, Geeta ; Collins, Lauren ; Singh, Ravinder Jit ; Basaria, Shehzad. / 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. In: JAMA - Journal of the American Medical Association. 2012 ; Vol. 307, No. 9. pp. 931-939.
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abstract = "Context: 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). Design, Setting, and Patients: 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. Interventions: 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). Main Outcome Measures: 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. Conclusion: 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. Trial Registration: clinicaltrials.gov Identifier: NCT00493987.",
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TY - JOUR

T1 - Effect of testosterone supplementation with and without a dual 5α-reductase inhibitor on fat-free mass in men with suppressed testosterone production

T2 - A randomized controlled trial

AU - Bhasin, Shalender

AU - Travison, Thomas G.

AU - Storer, Thomas W.

AU - Lakshman, Kishore

AU - Kaushik, Manas

AU - Mazer, Norman A.

AU - Ngyuen, Ahn Hoa

AU - Davda, Maithili N.

AU - Jara, Hernan

AU - Aakil, Adam

AU - Anderson, Stephan

AU - Knapp, Philip E.

AU - Hanka, Samson

AU - Mohammed, Nurahmed

AU - Daou, Pierre

AU - Miciek, Renee

AU - Ulloor, Jagadish

AU - Zhang, Anqi

AU - Brooks, Brad

AU - Orwoll, Katie

AU - Hede-Brierley, Leife

AU - Eder, Richard

AU - Elmi, Ayan

AU - Bhasin, Geeta

AU - Collins, Lauren

AU - Singh, Ravinder Jit

AU - Basaria, Shehzad

PY - 2012/2/29

Y1 - 2012/2/29

N2 - Context: 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). Design, Setting, and Patients: 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. Interventions: 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). Main Outcome Measures: 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. Conclusion: 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. Trial Registration: clinicaltrials.gov Identifier: NCT00493987.

AB - Context: 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). Design, Setting, and Patients: 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. Interventions: 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). Main Outcome Measures: 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. Conclusion: 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. Trial Registration: clinicaltrials.gov Identifier: NCT00493987.

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