title: Dose-response effects of sex hormone concentrations on body composition and adipokines in medically castrated healthy men administered graded doses of testosterone gel.
abstract: OBJECTIVE
  Serum sex steroid concentrations may alter body composition and glucose homoeostasis in men in a dose-response manner. We evaluated these end-points in healthy men rendered medically castrate through use of a gonadotrophin-releasing hormone antagonist (acyline) with incremental doses of exogenous testosterone (T) gel.
  
  
  METHODS
  Subjects (n=6-9 per group) were randomly assigned to injections of acyline every 2 weeks plus transdermal T gel (1.25 g, 2.5 g, 5.0 g, 10 g or 15 g) daily or double placebo (injections and gel) for 12 weeks.
  
  
  METHODS
  Healthy men, ages 25-55 years, with normal serum total T concentrations.
  
  
  METHODS
  Serum T, dihydrotestosterone (DHT) and oestradiol (E2) were measured at baseline and every 2 weeks. Body composition was analysed by dual-energy X-ray absorptiometry at baseline and week 12. Fasting serum adiponectin, leptin, glucose and insulin concentrations were measured at baseline and week 10.
  
  
  RESULTS
  Forty-eight men completed the study. A significant treatment effect was observed for change in lean mass (ANOVAP=.01) but not fat mass (P=.14). Lean mass increased in the 15 g T group relative to all lower dose groups, except the 10 g T group. When all subjects were analysed together, changes in lean mass correlated directly and changes in fat mass correlated inversely with serum T, E2 and DHT. No changes were noted in serum glucose, insulin or adipokine levels.
  
  
  CONCLUSIONS
  In healthy men, higher serum concentrations of T, DHT and E2 were associated with greater increases in lean mass and decreases in fat mass but not with changes in serum glucose, insulin or adipokines.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Arthi
authors.identifier: http://orcid.org/0000-0003-1239-2614
authors.initials: A
authors.lastname: Thirumalai
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Katya B
authors.initials: KB
authors.lastname: Rubinow
authors.affiliation: Endocrinology, The Polyclinic, Seattle, WA, USA.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Cooper
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Amory
authors.affiliation: Geriatric Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA.
authors.forename: Brett T
authors.initials: BT
authors.lastname: Marck
authors.affiliation: Geriatric Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA.|Division of Gerontology & Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Alvin M
authors.initials: AM
authors.lastname: Matsumoto
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Page
mesh_terms: D054392:Adipokines / Q000097:blood*; D000328:Adult; D001786:Blood Glucose; D001823:Body Composition / Q000187:drug effects*; D013196:Dihydrotestosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D012739:Gonadal Steroid Hormones / Q000008:administration & dosage* / Q000097:blood; D064368:Healthy Volunteers; D006727:Hormone Antagonists; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage; D013739:Testosterone / Q000008:administration & dosage* / Q000097:blood
chemical_list: D054392:Adipokines; D001786:Blood Glucose; D012739:Gonadal Steroid Hormones; D006727:Hormone Antagonists; D007328:Insulin; D009842:Oligopeptides; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; C109238:acyline
keywords: Testosterone; adipokines; insulin resistance; oestradiol