Musculoskeletal and body composition response to high-dose testosterone with finasteride after chronic incomplete spinal cord injury—a randomized, double-blind, and placebo-controlled pilot study
BackgroundHigh-dose testosterone replacement therapy (TRT), paired with finasteride (type II 5α-reductase inhibitor), improves body composition, muscle strength, and bone mineral density (BMD) in older men, without inducing prostate enlargement—a side effect associated with TRT. Men with spinal cord...
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2024-12-01
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| author | Dana M. Otzel Dana M. Otzel Larissa Nichols Christine F. Conover Stephen A. Marangi Jayachandra R. Kura Dominic K. Iannaccone David J. Clark David J. Clark Chris M. Gregory Christopher F. Sonntag Anita Wokhlu Anita Wokhlu Hans K. Ghayee Michael J. McPhaul Charles E. Levy Charles A. Plumlee Charles A. Plumlee Robert B. Sammel Robert B. Sammel Kevin T. White Joshua F. Yarrow Joshua F. Yarrow Joshua F. Yarrow Joshua F. Yarrow |
| author_facet | Dana M. Otzel Dana M. Otzel Larissa Nichols Christine F. Conover Stephen A. Marangi Jayachandra R. Kura Dominic K. Iannaccone David J. Clark David J. Clark Chris M. Gregory Christopher F. Sonntag Anita Wokhlu Anita Wokhlu Hans K. Ghayee Michael J. McPhaul Charles E. Levy Charles A. Plumlee Charles A. Plumlee Robert B. Sammel Robert B. Sammel Kevin T. White Joshua F. Yarrow Joshua F. Yarrow Joshua F. Yarrow Joshua F. Yarrow |
| author_sort | Dana M. Otzel |
| collection | DOAJ |
| description | BackgroundHigh-dose testosterone replacement therapy (TRT), paired with finasteride (type II 5α-reductase inhibitor), improves body composition, muscle strength, and bone mineral density (BMD) in older men, without inducing prostate enlargement—a side effect associated with TRT. Men with spinal cord injury (SCI) exhibit neuromuscular impairment, muscle atrophy, bone loss, and increased central adiposity, along with low testosterone. However, sparse evidence supports TRT efficacy after SCI.MethodsThis parallel-group, double-blind, placebo-controlled, and randomized clinical trial (RCT) is a pilot study that enrolled men (N = 12) with low to low–normal testosterone and gait impairments after chronic motor-incomplete SCI. Participants received high-dose intramuscular TRT (testosterone-enanthate, 125 mg/week) with finasteride (5 mg/day) vs. vehicle+placebo for 12 months. Change relative to baseline was determined for body composition, musculoskeletal outcomes, and prostate size, with effect sizes calculated between groups using Hedges’ g. Adverse events and feasibility were assessed.ResultsTRT + finasteride consistently increased testosterone (g = 1.16–3.08) and estradiol (g = 0.43–3.48), while concomitantly reducing dihydrotestosterone (g = 0.31–2.27). Very large effect sizes at both 6 and 12 months suggest TRT + finasteride increased whole-body fat-free (lean) mass (+3–4% vs. baseline, g = 2.12–2.14) and knee extensor (KE) whole-muscle cross-sectional area (+8–11% vs. baseline, g = 2.06–2.53) more than vehicle+placebo. Moderate-to-large effect sizes suggest TRT + finasteride increased KE maximal voluntary isometric torque (+15–40% vs. baseline, g = 0.47–1.01) and femoral neck and distal femur BMD from 6 months onward (g = 0.51–1.13), compared with vehicle+placebo, and reduced fat mass 9–14% within the whole-body, trunk, and android (visceral) regions at 12 months (g = 0.77–1.27). TRT + finasteride also produced small effect sizes favoring lesser prostate growth than vehicle+placebo (g = 0.31–0.43). The participant retention, drug compliance, and incidence and severity of adverse events were similar among the groups.ConclusionThese data provide proof-of-concept and rationale for larger RCTs aimed at discerning the impact of TRT + finasteride on body composition, musculoskeletal health, and physical function in men with SCI, along with effect sizes and variance of responses to assist in planning subsequent trials.Clinical trial registrationClinicalTrials.gov, identifier NCT02248701. |
| format | Article |
| id | doaj-art-d22f66dd5bf64f0a9c7525b00e615faf |
| institution | OA Journals |
| issn | 1664-2295 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neurology |
| spelling | doaj-art-d22f66dd5bf64f0a9c7525b00e615faf2025-08-20T02:39:02ZengFrontiers Media S.A.Frontiers in Neurology1664-22952024-12-011510.3389/fneur.2024.14792641479264Musculoskeletal and body composition response to high-dose testosterone with finasteride after chronic incomplete spinal cord injury—a randomized, double-blind, and placebo-controlled pilot studyDana M. Otzel0Dana M. Otzel1Larissa Nichols2Christine F. Conover3Stephen A. Marangi4Jayachandra R. Kura5Dominic K. Iannaccone6David J. Clark7David J. Clark8Chris M. Gregory9Christopher F. Sonntag10Anita Wokhlu11Anita Wokhlu12Hans K. Ghayee13Michael J. McPhaul14Charles E. Levy15Charles A. Plumlee16Charles A. Plumlee17Robert B. Sammel18Robert B. Sammel19Kevin T. White20Joshua F. Yarrow21Joshua F. Yarrow22Joshua F. Yarrow23Joshua F. Yarrow24Brain Rehabilitation Research Center, Malcom Randall Department of Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, United StatesDepartment of Physiology & Aging, University of Florida College of Medicine, Gainesville, FL, United StatesBrain Rehabilitation Research Center, Malcom Randall Department of Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, United StatesBrain Rehabilitation Research Center, Malcom Randall Department of Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, United StatesBrain Rehabilitation Research Center, Malcom Randall Department of Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, United StatesBrain Rehabilitation Research Center, Malcom Randall Department of Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, United StatesBrain Rehabilitation Research Center, Malcom Randall Department of Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, United StatesBrain Rehabilitation Research Center, Malcom Randall Department of Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, United StatesDepartment of Neurology, University of Florida College of Medicine, Gainesville, FL, United StatesDepartment of Health Sciences and Research, Medical University of South Carolina, Charleston, SC, United StatesDiagnostic Imaging Service – Radiology, Malcom Randall Department of Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, United StatesMedical Specialties Service – Cardiology, Malcom Randall Department of Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, United StatesDivision of Cardiovascular Medicine, Department of Medicine, University of Florida College of Medicine, Gainesville, FL, United StatesDivision of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Florida College of Medicine, Gainesville, FL, United StatesQuest Diagnostics Nichols Institute, San Juan Capistrano, CA, United States0Physical Medicine and Rehabilitation Service, Malcom Randall Department of Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, United States0Physical Medicine and Rehabilitation Service, Malcom Randall Department of Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, United States1Spinal Cord Injury Service, Malcom Randall Department of Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, United States1Spinal Cord Injury Service, Malcom Randall Department of Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, United States2Geriatrics and Extended Care, South Texas Veterans Health Care System, Kerrville, TX, United States3Michael Bilirakis VA Spinal Cord Injury/Disorders Center, James A. Haley Department of Veterans Affairs Medical Center, Tampa, FL, United StatesBrain Rehabilitation Research Center, Malcom Randall Department of Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, United StatesDivision of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Florida College of Medicine, Gainesville, FL, United States4Eastern Colorado Geriatrics Research, Education, and Clinical Center, Rocky Mountain Regional Department of Veterans Affairs Medical Center, VA Eastern Colorado Health Care System, Aurora, CO, United States5Division of Geriatric Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesBackgroundHigh-dose testosterone replacement therapy (TRT), paired with finasteride (type II 5α-reductase inhibitor), improves body composition, muscle strength, and bone mineral density (BMD) in older men, without inducing prostate enlargement—a side effect associated with TRT. Men with spinal cord injury (SCI) exhibit neuromuscular impairment, muscle atrophy, bone loss, and increased central adiposity, along with low testosterone. However, sparse evidence supports TRT efficacy after SCI.MethodsThis parallel-group, double-blind, placebo-controlled, and randomized clinical trial (RCT) is a pilot study that enrolled men (N = 12) with low to low–normal testosterone and gait impairments after chronic motor-incomplete SCI. Participants received high-dose intramuscular TRT (testosterone-enanthate, 125 mg/week) with finasteride (5 mg/day) vs. vehicle+placebo for 12 months. Change relative to baseline was determined for body composition, musculoskeletal outcomes, and prostate size, with effect sizes calculated between groups using Hedges’ g. Adverse events and feasibility were assessed.ResultsTRT + finasteride consistently increased testosterone (g = 1.16–3.08) and estradiol (g = 0.43–3.48), while concomitantly reducing dihydrotestosterone (g = 0.31–2.27). Very large effect sizes at both 6 and 12 months suggest TRT + finasteride increased whole-body fat-free (lean) mass (+3–4% vs. baseline, g = 2.12–2.14) and knee extensor (KE) whole-muscle cross-sectional area (+8–11% vs. baseline, g = 2.06–2.53) more than vehicle+placebo. Moderate-to-large effect sizes suggest TRT + finasteride increased KE maximal voluntary isometric torque (+15–40% vs. baseline, g = 0.47–1.01) and femoral neck and distal femur BMD from 6 months onward (g = 0.51–1.13), compared with vehicle+placebo, and reduced fat mass 9–14% within the whole-body, trunk, and android (visceral) regions at 12 months (g = 0.77–1.27). TRT + finasteride also produced small effect sizes favoring lesser prostate growth than vehicle+placebo (g = 0.31–0.43). The participant retention, drug compliance, and incidence and severity of adverse events were similar among the groups.ConclusionThese data provide proof-of-concept and rationale for larger RCTs aimed at discerning the impact of TRT + finasteride on body composition, musculoskeletal health, and physical function in men with SCI, along with effect sizes and variance of responses to assist in planning subsequent trials.Clinical trial registrationClinicalTrials.gov, identifier NCT02248701.https://www.frontiersin.org/articles/10.3389/fneur.2024.1479264/fullandrogenestrogentestosterone replacementhypogonadismspinal cord injurymuscle |
| spellingShingle | Dana M. Otzel Dana M. Otzel Larissa Nichols Christine F. Conover Stephen A. Marangi Jayachandra R. Kura Dominic K. Iannaccone David J. Clark David J. Clark Chris M. Gregory Christopher F. Sonntag Anita Wokhlu Anita Wokhlu Hans K. Ghayee Michael J. McPhaul Charles E. Levy Charles A. Plumlee Charles A. Plumlee Robert B. Sammel Robert B. Sammel Kevin T. White Joshua F. Yarrow Joshua F. Yarrow Joshua F. Yarrow Joshua F. Yarrow Musculoskeletal and body composition response to high-dose testosterone with finasteride after chronic incomplete spinal cord injury—a randomized, double-blind, and placebo-controlled pilot study Frontiers in Neurology androgen estrogen testosterone replacement hypogonadism spinal cord injury muscle |
| title | Musculoskeletal and body composition response to high-dose testosterone with finasteride after chronic incomplete spinal cord injury—a randomized, double-blind, and placebo-controlled pilot study |
| title_full | Musculoskeletal and body composition response to high-dose testosterone with finasteride after chronic incomplete spinal cord injury—a randomized, double-blind, and placebo-controlled pilot study |
| title_fullStr | Musculoskeletal and body composition response to high-dose testosterone with finasteride after chronic incomplete spinal cord injury—a randomized, double-blind, and placebo-controlled pilot study |
| title_full_unstemmed | Musculoskeletal and body composition response to high-dose testosterone with finasteride after chronic incomplete spinal cord injury—a randomized, double-blind, and placebo-controlled pilot study |
| title_short | Musculoskeletal and body composition response to high-dose testosterone with finasteride after chronic incomplete spinal cord injury—a randomized, double-blind, and placebo-controlled pilot study |
| title_sort | musculoskeletal and body composition response to high dose testosterone with finasteride after chronic incomplete spinal cord injury a randomized double blind and placebo controlled pilot study |
| topic | androgen estrogen testosterone replacement hypogonadism spinal cord injury muscle |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2024.1479264/full |
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