Background and aims: Testosterone is important for maintaining muscle mass in ageing men, however it’s role in physical performance is unclear. We hypothesise that testosterone withdrawal causes differential deficits in leg muscle function. We aimed to assess effects of androgen deprivation therapy (ADT) for prostate cancer on functional mobility.
Methods: This prospective 12-month case-control study of men with localised prostate cancer included 29 cases (newly commencing ADT) and 24 controls (not receiving ADT), matched for age and radiotherapy. Video-based quantitative gait analyses (walking on level ground) was combined with computational musculoskeletal modelling to determine the following main outcome measures of interest in the lower limbs:
1) stride length, step width, walking speed
2) joint torques (hip, knee, ankle)
3) individual muscle contributions to the acceleration of the body’s centre of mass (COM) in three directions; vertically, forwards and sideways.
A linear mixed model was performed to assess between group differences over time.
Results: Compared with controls over 12 months, the ADT group had significantly
increased step width (mean adjusted difference (MAD) 1.4cm [0.6, 27.4], p=0.042) with no change in stride length or walking speed. Decreased peak joint torques for hip flexion (mediated by iliopsoas, MAD -0.11newtons/kg [-0.19, -0.028], p=0.01) and knee extension (mediated by quadriceps, MAD -0.11newtons/kg [-0.20, -0.02], p=0.02) were observed. There was also decreased contribution of soleus to forward acceleration of the body’s COM (MAD -0.17m/s2 [-0.29, -0.05], p<0.01). No significant interactions were noted in other muscles.
Conclusion: ADT may have effects on balance and causes differential effects on lower limb muscles, predominantly those involved in supporting body weight and forward propulsion of the body during walking (iliopsoas, quadriceps, soleus). This may be related to differential androgen sensitivity of individual muscles. These changes provide a rational basis to target exercise and promyogenic interventions to mitigate ADT-associated sarcopenia.