title: Aromatase Inhibition Reduces Insulin Sensitivity in Healthy Men.
abstract: Deficiency of aromatase, the enzyme that catalyzes the conversion of androgens to estrogens, is associated with insulin resistance in humans and mice.
  
  
  
  We hypothesized that pharmacological aromatase inhibition results in peripheral insulin resistance in humans.
  
  
  
  This was a double-blind, randomized, controlled, crossover study.
  
  
  
  The study was conducted at a clinical research facility.
  
  
  
  Seventeen healthy male volunteers (18-50 y) participated in the study.
  
  
  
  The intervention included oral anastrozole (1 mg daily) and placebo, each for 6 weeks with a 2-week washout period.
  
  
  
  Glucose disposal and rates of lipolysis were measured during a stepwise hyperinsulinemic euglycemic clamp. Data are mean (SEM).
  
  
  
  Anastrozole therapy resulted in significant estradiol suppression (59.9 ± 3.6 vs 102.0 ± 5.7 pmol/L, P = < .001) and a more modest elevation of total T (25.8 ± 1.2 vs 21.4 ± 0.7 nmol/L, P = .003). Glucose infusion rate, during the low-dose insulin infusion, was lower after anastrozole administration (12.16 ± 1.33 vs 14.15 ± 1.55 μmol/kg·min, P = .024). No differences in hepatic glucose production or rate of lipolysis were observed.
  
  
  
  Aromatase inhibition reduces insulin sensitivity, with respect to peripheral glucose disposal, in healthy men. Local generation and action of estradiol, at the level of skeletal muscle, is likely to be an important determinant of insulin sensitivity.
authors.affiliation: British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom.
authors.forename: Fraser W
authors.initials: FW
authors.lastname: Gibb
authors.affiliation: British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom.
authors.forename: Natalie Z M
authors.initials: NZ
authors.lastname: Homer
authors.affiliation: British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom.
authors.forename: Abdullah M M
authors.initials: AM
authors.lastname: Faqehi
authors.affiliation: British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom.
authors.forename: Rita
authors.initials: R
authors.lastname: Upreti
authors.affiliation: British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom.
authors.forename: Dawn E
authors.initials: DE
authors.lastname: Livingstone
authors.affiliation: British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: McInnes
authors.affiliation: British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom.
authors.forename: Ruth
authors.initials: R
authors.lastname: Andrew
authors.affiliation: British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Walker
mesh_terms: D000293:Adolescent; D000328:Adult; D000077384:Anastrozole; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D064368:Healthy Volunteers; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008066:Lipolysis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology*; D013739:Testosterone / Q000097:blood; D014230:Triazoles / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D013739:Testosterone; D004958:Estradiol; D005947:Glucose