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

Ada S. Cheung, Christopher Cunningham, Dong Kyoon Daniel Ko, Vivian Ly, Hans Gray, Rudolf Hoermann, Boyd J.G. Strauss, Ebrahim Bani Hassan, Gustavo Duque, Peter Ebeling, Marcus G. Pandy, Jeffrey D. Zajac, Mathis Grossmann

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)2229-2238
Number of pages10
JournalJournal of Clinical Endocrinology and Metablism
Volume104
Issue number6
DOIs
Publication statusPublished - 1 Jun 2019

Cite this

Cheung, A. S., Cunningham, C., Ko, D. K. D., Ly, V., Gray, H., Hoermann, R., ... Grossmann, M. (2019). Selective Loss of Levator Ani and Leg Muscle Volumes in Men Undergoing Androgen Deprivation Therapy. Journal of Clinical Endocrinology and Metablism, 104(6), 2229-2238. https://doi.org/10.1210/jc.2018-01954