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.