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.

Keywords: Androgen deprivation; Balance; Falls; Kinematics; Muscle function; Prostate cancer; Sarcopenia.

Figure 1

Representative participant in the Biomotion Laboratory. Anterior view of subject fitted with 45 reflective markers standing on one of the three ground reaction force plates embedded in the laboratory floor. Nine cameras were positioned circumferentially around the laboratory. Subject photographed has provided full consent for publication of image.

Figure 2

The gait cycle. Depicted is one gait cycle, with the right leg dominant, beginning at right heel strike and ending at the next right heel strike. HS, heel strike; CTO, contralateral toe off the ground; CHS, contralateral heel strike; TO, toe off. The stance phase is defined as the time the dominant (right) foot is on the ground, which is 62% of one gait cycle. The swing phase is the time the dominant foot is off the ground and comprises 38% of one gait cycle. Muscle activation varies for each individual muscle as a function of time during the gait cycle. The gluteus maximus, gluteus medius, hamstrings, and quadriceps are active during early stance (from right heel strike to just after contralateral toe‐off) to generate support whereas the iliopsoas, gastrocnemius, soleus, and plantarflexor invertors are active during mid‐late stance to accelerate the body forward in preparation for the subsequent swing phase.

Figure 3

Muscle‐tendon actuators in a musculoskeletal model. Muscle‐tendon actuators shown in red used in the computerized musculoskeletal model representing lower‐limb and torso muscles of a subject during stance phase beginning with right heel strike through to right toe‐off.

Figure 4

Temporal‐spatial parameters. Mean difference refers to the difference in the change in the mean of the ADT group over change in the mean of the control group over 12 months and is presented with (95% confidence interval) and P value. ^# P < 0.05 represents a significant difference in the change in the mean of the ADT group compared with the change in the control group over 12 months (main outcome). ^* P < 0.05 represents a significant difference between the mean 12‐month value and mean baseline value within the same group. No significant interactions were observed from 0 to 6 months. Box plots demonstrate median, interquartile range, and range. The diamond represents the mean and the 95% confidence interval of the mean.