title: Decrease in lean body mass in men with prostate cancer receiving androgen deprivation therapy: mechanism and biomarkers.
abstract: OBJECTIVE
  To elucidate the mechanism of the androgen deprivation therapy (ADT)-related decrease in lean body mass (LBM).
  
  
  METHODS
  The LBM and blood samples were studied before and after 6 months of ADT in 72 patients with localized prostate cancer. The LBM was assessed using a foot-to-foot bioelectrical impedance analyzer.
  
  
  RESULTS
  Before ADT, the LBM correlated with none of the serum sex steroid levels; however, it correlated closely with serum 5α-androstane-3α,17β-diol glucuronide (Spearman's rank correlation coefficient = 0.409, P = .001) and insulin-like growth factor-1 (IGF-I, Spearman's rank correlation coefficient = 0.329, P = .005). After ADT, the LBM decreased by 0.9% (P = .036), and the serum testosterone and dihydrotestosterone had decreased by 96.8% and 94.3%, respectively (P <.001 for both), and the IGF-I had increased by 11.6% (from 19.9 to 22.2 nmol/L, P = .001). The serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D] levels decreased after ADT by 9.8% (from 66.2 to 59.7 pg/mL, P = .008), and the post-treatment LBM correlated inversely with 1,25(OH)2D (Spearman's rank correlation coefficient = -0.343, P = .003). The post-treatment LBM was dissociated with 5α-androstane-3α,17β-diol glucuronide and IGF-I. The pretreatment and post-treatment LBMs both correlated inversely with serum sex hormone-binding globulin (P = .024 and P = .016, respectively).
  
  
  CONCLUSIONS
  The deficiency in androgen levels was suggested to be a link to the ADT-related decrease in LBM; the androgen metabolite 5α-androstane-3α,17β-diol glucuronide has a potential value for assessing the LBM in untreated men. IGF-I also promotes muscle building and is positively regulated during ADT. Sex hormone-binding globulin possibly accelerates the ADT-related decrease in LBM. Although the mechanism for the decrease in 1,25(OH)2D and its inverse correlation with LBM during ADT is unclear, 1,25(OH)2D might be a biomarker reflecting the ADT-related decrease in LBM.
authors: Division of Urology, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. harasho@med.niigata-u.ac.jp
authors: Noboru
authors: N
authors: Hara
authors: Fumio
authors: F
authors: Ishizaki
authors: Toshihiro
authors: T
authors: Saito
authors: Tsutomu
authors: T
authors: Nishiyama
authors: Takashi
authors: T
authors: Kawasaki
authors: Kota
authors: K
authors: Takahashi
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D015113:Androstane-3,17-diol / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001823:Body Composition / Q000187:drug effects*; D015992:Body Mass Index; D002117:Calcitriol / Q000097:blood; D013196:Dihydrotestosterone / Q000097:blood; D017097:Electric Impedance; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000097:blood; D013851:Thinness / Q000209:etiology
chemical_list: D000726:Androgen Antagonists; D015415:Biomarkers; D012738:Sex Hormone-Binding Globulin; D013196:Dihydrotestosterone; D015113:Androstane-3,17-diol; C028895:androstane-3,17-diol glucuronide; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D002117:Calcitriol