Perioperative Testosterone Supplementation Increases Lean Mass in Healthy Men Undergoing Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial

Brian Wu, Dan Lorezanza, Ido Badash, Max Berger, Christianne Lane, Jonathan C Sum, George F Hatch 3rd, E Todd Schroeder, Brian Wu, Dan Lorezanza, Ido Badash, Max Berger, Christianne Lane, Jonathan C Sum, George F Hatch 3rd, E Todd Schroeder

Abstract

Background: Rehabilitation after repair of the anterior cruciate ligament (ACL) is complicated by the loss of leg muscle mass and strength. Prior studies have shown that preoperative rehabilitation may improve muscle strength and postoperative outcomes. Testosterone supplementation may likewise counteract this muscle loss and potentially improve clinical outcomes.

Purpose: The purpose was to investigate the effect of perioperative testosterone administration on lean mass after ACL reconstruction in men and to examine the effects of testosterone on leg strength and clinical outcome scores. It was hypothesized that testosterone would increase lean mass and leg strength and improve clinical outcome scores relative to placebo.

Study design: Randomized controlled trial; Level of evidence, 1.

Methods: Male patients (N = 13) scheduled for ACL reconstruction were randomized into 2 groups: testosterone and placebo. Participants in the testosterone group received 200 mg of intramuscular testosterone weekly for 8 weeks beginning 2 weeks before surgery. Participants in the placebo group received saline following the same schedule. Both groups participated in a standard rehabilitation protocol. The primary outcome was the change in total lean body mass at 6 and 12 weeks. Secondary outcomes were extensor muscle strength, Tegner activity score, and Knee injury and Osteoarthritis Outcome Score.

Results: There was an increase in lean mass of a mean 2.7 ± 1.7 kg at 6 weeks postoperatively in the testosterone group compared with a decrease of a mean 0.1 ± 1.5 kg in the placebo group (P = .01). Extensor muscle strength of the uninjured leg also increased more from baseline in the testosterone group (+20.8 ± 25.6 Nm) compared with the placebo group (-21.4 ± 36.7 Nm) at 12 weeks (P = .04). There were no significant between-group differences in injured leg strength or clinical outcome scores. There were no negative side effects of testosterone noted.

Conclusion: Perioperative testosterone supplementation increased lean mass 6 weeks after ACL reconstruction, suggesting that this treatment may help minimize the effects of muscle atrophy associated with ACL injuries and repair. This study was not powered to detect differences in strength or clinical outcome scores to assess the incidence of testosterone-related adverse events.

Clinical relevance: Supraphysiological testosterone supplementation may be a useful adjunct therapy for counteracting muscle atrophy after ACL reconstruction. Further investigation is necessary to determine the safety profile and effects of perioperative testosterone administration on leg strength and clinical outcomes after surgery.

Registration: NCT01595581 (ClinicalTrials.gov).

Keywords: anterior cruciate ligament reconstruction; lean mass; randomized controlled trial; rehabilitation; testosterone.

Conflict of interest statement

One or more of the authors has declared the following potential conflict of interest or source of funding: This study was sponsored in part by a National Institutes of Health/Southern California Clinical and Translational Science Institute (SC CTSI) TL1 Pre-doctoral Training grant, an Intradepartmental Award for Interdisciplinary Work from the University of Southern California, the Division of Biokinesiology and Physical Therapy Funding Program at the SC CTSI, and a Sandy Kirkley Clinical Outcome Research Grant from the AOSSM.

Figures

Figure 1.
Figure 1.
CONSORT (Consolidated Standards of Reporting Trials) diagram showing the flow of participants during the study.
Figure 2.
Figure 2.
Serum testosterone levels by week. Line plot of testosterone levels at 2 weeks before surgery; 1 day before surgery; and 2, 6, 12, and 24 weeks after surgery. Data shown are the means ± standard errors of serum testosterone (ng/dL) as measured by blood analysis. An asterisk (*) indicates a significant between-group difference.
Figure 3.
Figure 3.
Effect of testosterone on the change in lean mass from baseline. Line plot of the change in lean mass from baseline at 1 day before surgery and 6, 12, and 24 weeks after surgery. Baseline lean mass was measured at 2 weeks before surgery and normalized to 0. Data shown are the means ± standard errors of the change in lean mass (kg). An asterisk (*) indicates a significant between-group difference.
Figure 4.
Figure 4.
Effect of testosterone on the change in strength of the uninjured leg from baseline. Line plot of the change in peak extension torque of the uninjured leg from baseline to 1 day before surgery and 6, 12, and 24 weeks after surgery. Baseline extension torque was measured at 2 weeks before surgery and normalized to 0. Data shown are the means ± standard errors of the change in peak extension torque (Nm). An asterisk (*) indicates a significant between-group difference.
Figure 5.
Figure 5.
Effect of testosterone on the change in strength of the injured leg from baseline. Line plot of the change in peak extension torque of the injured leg from baseline to 1 day before surgery and 6, 12, and 24 weeks after surgery. Baseline extension torque was measured at 2 weeks before surgery and normalized to 0. Data shown are the means ± standard errors of the change in peak extension torque (Nm). An asterisk (*) indicates a significant between-group difference.

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