title: Androgen deprivation causes selective deficits in the biomechanical leg muscle function of men during walking: a prospective case-control study.
abstract: BACKGROUND
  Although muscle mass declines with testosterone deficiency in men, previous studies of muscle function have not demonstrated consistent deficits, likely due to relatively insensitive methodology. Our objective was to determine the effects of testosterone deprivation on the biomechanical function of individual lower-limb muscles.
  
  
  METHODS
  We conducted a 12-month prospective, observational case-control study of 34 men newly commencing androgen deprivation treatment (ADT) for prostate cancer and 29 age-matched prostate cancer controls. Participants were assessed at 0, 6, and 12 months while walking in a biomechanics laboratory. We combined video-based motion capture and ground reaction force data with computerized musculoskeletal modelling to assess the following primary outcomes: (i) peak joint torques at the hip, knee and ankle, and corresponding individual muscle forces; (ii) individual muscle contributions to acceleration of the body's centre of mass; and (iii) walking speed, stride length, and step width. A linear mixed model was used to compare mean differences between groups.
  
  
  RESULTS
  Compared with controls over 12 months, men receiving ADT had a mean reduction in total testosterone level from 14.1 to 0.4 nmol/L, and demonstrated more marked decreases in peak hip flexor torque by 14% [mean difference -0.11 N/kg (-0.19, -0.03), P = 0.01] and peak knee extensor torque by 16% [-0.11 N/kg (-0.20, -0.02), P = 0.02] of the initial mean value. Correspondingly, iliopsoas force decreased by 14% (P = 0.006), and quadriceps force decreased by 11%, although this narrowly missed statistical significance (P = 0.07). Soleus decreased contribution to forward acceleration of the body's centre of mass by 17% [mean difference -0.17 m/s2(-0.29, -0.05), P < 0.01]. No significant changes between groups were observed in other joint torques or individual muscle contributions to acceleration of the body. Step width increased by 18% [mean adjusted difference 1.4 cm (0.6, 27.4), P = 0.042] in the ADT group compared with controls, with no change in stride length or walking speed.
  
  
  CONCLUSIONS
  Testosterone deprivation selectively decreases lower-limb muscle function, predominantly affecting muscles that support body weight, accelerate the body forwards during walking, and mediate balance. Future exercise and pro-myogenic interventional studies to mitigate ADT-associated sarcopenia should target these deficits.
authors.affiliation: Department of Medicine, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia.|Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Ada S
authors.initials: AS
authors.lastname: Cheung
authors.affiliation: Department of Mechanical Engineering, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Hans
authors.initials: H
authors.lastname: Gray
authors.affiliation: Department of Mechanical Engineering, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Schache
authors.affiliation: Department of Medicine, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Hoermann
authors.affiliation: Department of Radiation Oncology, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Daryl
authors.initials: D
authors.lastname: Lim Joon
authors.affiliation: Department of Medicine, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia.|Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Zajac
authors.affiliation: Department of Mechanical Engineering, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Marcus G
authors.initials: MG
authors.lastname: Pandy
authors.affiliation: Department of Medicine, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia.|Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Mathis
authors.initials: M
authors.lastname: Grossmann
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D006801:Humans; D007866:Leg / Q000502:physiology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy; D055948:Sarcopenia / Q000139:chemically induced* / Q000503:physiopathology; D016138:Walking / Q000502:physiology*
chemical_list: D000726:Androgen Antagonists
keywords: Androgen deprivation; Balance; Falls; Kinematics; Muscle function; Prostate cancer; Sarcopenia