The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Selective loss of levator ani and leg muscle volumes in men undergoing androgen deprivation therapy (#100)

Ada S Cheung 1 2 , Vivian Ly 1 , Christopher Cunningham 1 , Daniel Ko 1 , Hans Gray 3 , Rudolf Hoermann 1 , Boyd JG Strauss 4 , Ebrahim Bani Hassan 5 , Gustavo Duque 5 , Marcus Pandy 3 , Jeffrey D Zajac 1 2 , Mathis Grossmann 1 2
  1. Trans Health Research Group, Department of Medicine, The University of Melbourne, Heidelberg, VIC, Australia
  2. Department of Endocrinology, Austin Health, Heidelberg, VIC, Australia
  3. Mechanical Engineering, The University of Melbourne, Melbourne, Victoria, Australia
  4. Department of Medicine, Monash University, Clayton, Vic, Australia
  5. Department of Medicine (Western Precinct) and Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne, St Albans, Vic, Australia

Background: Androgen deprivation therapy (ADT) for prostate cancer leads to adverse endocrine effects including a global loss of lean mass and sexual dysfunction. ADT leads to a selective loss of leg muscle function1, however individual muscle volumes have not been evaluated. We aimed to assess in men undergoing ADT, the muscle volumes of levator ani, a highly androgen-responsive muscle in mice2, and of lower-limb muscles.

Methods: We conducted a prospective case-control study involving 34 men newly commencing ADT and 29 age-matched prostate cancer controls. Levator ani and leg muscle volumes (litres) of primary muscles involved in walking (iliopsoas, quadriceps, gluteus maximus, gluteus medius, calf) were measured using MRI and quantitated using Slice-O-Matic software at 0, 6 and 12 months. Generalised linear models determined the mean adjusted difference (MAD) [95% confidence interval] between groups over time.

Results: Compared with controls over 12 months, men receiving ADT had a mean reduction in total testosterone level from 14.1 to 0.4nmol/L and demonstrated greater decreases in levator ani (MAD -0.005 litres [-0.007, -0.002], p=0.002, -16% of initial median value), gluteus maximus (MAD -0.032 litres [-0.063, -0.002], p=0.017, -5%), iliopsoas (MAD -0.005 litres [-0.001, 0.000], p=0.013, -5%) and quadriceps (MAD -0.050 litres [-0.088, -0.012], p=0.031, -3%). No significant differences were observed in gluteus medius and calf muscles.

Conclusion: Testosterone deprivation causes marked decreases in levator ani muscle, demonstrating that it’s androgen responsiveness is evolutionarily conserved across men and mice. Further studies are required to investigate whether loss of levator ani muscle mass contributes to the profound sexual dysfunction seen in men on ADT. Consistent with previously reported functional deficits1, ADT selectively decreases volume of muscles that support body weight. Future interventional studies aimed at reducing ADT-related sarcopenia and sexual dysfunction should evaluate the role of targeting these muscle groups, including the pelvic floor.

 

 

  1. Cheung AS, Gray H, Schache AG, et al. Androgen deprivation causes selective deficits in the biomechanical leg muscle function of men during walking: a prospective case-control study. Journal of cachexia, sarcopenia and muscle. 2017;8(1):102-112.
  2. Rana K, Lee NK, Zajac JD, MacLean HE. Expression of androgen receptor target genes in skeletal muscle. Asian journal of andrology. 2014;16(5):675-683.