title: Impact of acute biochemical castration on insulin sensitivity in healthy adult men.
abstract: BACKGROUND
  Evidence supports an inverse relationship between serum testosterone (T) and insulin resistance in men. However, data with respect to causality are limited. The aim of this study was to explore the impact of acute biochemical castration on insulin sensitivity in healthy adult men.
  
  
  METHODS
  Ten healthy, adult males (mean age 41.0 +/- 3.9 yr) were studied. Subjects were studied at baseline and after 2 and 4 weeks of biochemical castration. Outpatient hospital research setting. Body composition (dual-energy x-ray absorptiometry), energy expenditure (indirect calorimetry), abdominal and visceral adiposity (MRI), skeletal muscle intramyocellular lipid content ([IMCL] (1)H-MR spectroscopy), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) were assessed before and after 2 and 4 weeks of biochemical castration induced by a GnRH antagonist (acyline 300 mug/kg subcutaneous every 10-14 days). Serum T, insulin and glucose levels, body composition, abdominal visceral fat, IMCL, and glucose disposal rate (M) were measured.
  
  
  CONCLUSIONS
  Acyline administration suppressed serum T to frankly hypogonadal levels in all subjects for the duration of the study (P <0.009). No significant changes in body composition, energy expenditure, or M were observed at either 2 or 4 weeks of castration. Acyline is an effective GnRH antagonist inducing acute castration in all subjects. ii) Four weeks of biochemical castration has no impact on insulin sensitivity in healthy men likely due to unchanged body composition variables. iii) Insulin resistance associated with chronic low T levels may be largely driven by decreased fat free mass, increased percent body fat, and/or other metabolic regulatory factors.
authors.affiliation: Department of Surgery and Department of Medicine, Johns Hopkins Medical School, Baltimore, Maryland, USA.
authors.forename: Atoosa
authors.initials: A
authors.lastname: Rabiee
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Dwyer
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Caronia
authors.forename: Frances J
authors.initials: FJ
authors.lastname: Hayes
authors.forename: Maria A
authors.initials: MA
authors.lastname: Yialamas
authors.forename: Dana K
authors.initials: DK
authors.lastname: Andersen
authors.forename: Bijoy
authors.initials: B
authors.lastname: Thomas
authors.forename: Martin
authors.initials: M
authors.lastname: Torriani
authors.forename: Dariush
authors.initials: D
authors.lastname: Elahi
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000502:physiology; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D050152:Intra-Abdominal Fat / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage; D009919:Orchiectomy; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism; D013739:Testosterone / Q000097:blood*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D009842:Oligopeptides; D012738:Sex Hormone-Binding Globulin; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C109238:acyline