Selective Loss of Levator Ani and Leg Muscle Volumes in Men Undergoing Androgen Deprivation Therapy

Context Androgen deprivation therapy (ADT) for prostate cancer (PCa) leads to a selective loss of leg muscle function during walking. Rodent models of ADT have demonstrated that the levator ani is exquisitely androgen sensitive. Objective To determine whether the high androgen responsiveness of the levator ani muscle documented in rodents is evolutionarily conserved and ADT is associated with a selective loss in leg muscle volume. Design Prospective longitudinal case-control study. Setting Tertiary referral hospital. Participants Thirty-four men newly beginning ADT and 29 age-matched controls with PCa. Main outcome measures The muscle volumes in liters of the levator ani and primary muscles involved in walking (iliopsoas, quadriceps, gluteus maximus, gluteus medius, calf). Results Compared with controls, during a 12-month period, men receiving ADT experienced a mean reduction in total testosterone from 14.1 to 0.4 nmol/L and demonstrated greater decreases in levator ani [mean adjusted difference (MAD), -0.005 L; 95% CI, -0.007 to -0.002; P = 0.002; -16% of initial median value], gluteus maximus (MAD, -0.032 L; 95% CI, -0.063 to -0.002; P = 0.017; -5% of initial median value), iliopsoas (MAD, -0.005 L; 95% CI, -0.001 to 0.000; P = 0.013; -5% of initial median value), and quadriceps (MAD, -0.050 L; 95% CI, -0.088 to -0.012; P = 0.031; -3% of initial median value). No substantial differences were observed in the gluteus medius and calf muscles. Conclusions The androgen responsiveness of the levator ani appears to be evolutionarily conserved in humans. ADT selectively decreases the volume of muscles that support body weight. Interventional strategies to reduce ADT-related sarcopenia and sexual dysfunction should assess whether targeting these muscle groups, including the pelvic floor, will improve clinical outcomes.