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

• Published in: The journal of clinical endocrinology and metabolism 2019-06, Vol.104 (6), p.2229-2238
• Main Authors: Cheung, Ada S, Cunningham, Christopher, Ko, Dong-Kyoon Daniel, Ly, Vivian, Gray, Hans, Hoermann, Rudolf, Strauss, Boyd J G, Bani Hassan, Ebrahim, Duque, Gustavo, Ebeling, Peter, Pandy, Marcus G, Zajac, Jeffrey D, Grossmann, Mathis
• Format: Article
• Language: English
• Subjects: Aged; Analysis; Androgen Antagonists - adverse effects; Androgens; Animal models; Body Composition - drug effects; Body weight; Humans; Leg; Male; Middle Aged; Muscle, Skeletal - drug effects; Muscle, Skeletal - pathology; Muscles; Prospective Studies; Prostate cancer; Quadriceps muscle; Sarcopenia; Sarcopenia - chemically induced; Sexual disorders; Sexual Dysfunction, Physiological - chemically induced; Testosterone; Walking
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2018-01954

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. 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. Prospective longitudinal case-control study. Tertiary referral hospital. Thirty-four men newly beginning ADT and 29 age-matched controls with PCa. The muscle volumes in liters of the levator ani and primary muscles involved in walking (iliopsoas, quadriceps, gluteus maximus, gluteus medius, calf). 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. 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.