title: Impaired body weight and tail length gain and altered bone quality after treatment with the aromatase inhibitor exemestane in male rats.
abstract: BACKGROUND
  Estrogen deficiency induced by aromatase inhibitors may be a novel treatment modality for growth enhancement in short children, but may have adverse effects on bone, brain and reproduction.
  
  
  OBJECTIVE
  To assess growth effects and potential adverse effects of aromatase inhibition in male rats.
  
  
  METHODS
  26-day-old prepubertal rats received intramuscular injections with placebo or the aromatase inhibitor exemestane at a dose of 10, 30 or 100 mg/kg/week [E10, E30, E100(6)] for 6 weeks, completely covering the sexual maturation phase, or with 3 weeks E100 followed by 3 weeks placebo [E100(3)]. Growth parameters and histology of the testis, seminal vesicle and brain were analyzed. Bone architecture was studied with X-ray microtomography.
  
  
  RESULTS
  Exemestane dose-dependently decreased body weight and tail length gain, as well as liver and seminal vesicle weights, but did not affect nose-anus length gain, growth plate width or radial growth. E100(6) decreased trabecular thickness (epiphysis and metaphysis) and number (metaphysis). Normal IGF-I levels and brain, testis and seminal vesicle morphology were observed. E100(3) resulted in decreased tail length gain only.
  
  
  CONCLUSIONS
  Exemestane treatment during sexual maturation did not augment linear growth in male rats, but caused impaired body weight and tail length gain and osteopenia.
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands. s.van_gool @ lumc.nl
authors.forename: Sandy A
authors.initials: SA
authors.lastname: van Gool
authors.forename: Jan M
authors.initials: JM
authors.lastname: Wit
authors.forename: Tineke
authors.initials: T
authors.lastname: De Schutter
authors.forename: Nora
authors.initials: N
authors.lastname: De Clerck
authors.forename: Andreï A
authors.initials: AA
authors.lastname: Postnov
authors.forename: Sandra
authors.initials: S
authors.lastname: Kremer Hovinga
authors.forename: Jaap
authors.initials: J
authors.lastname: van Doorn
authors.forename: Sergio J
authors.initials: SJ
authors.lastname: Veiga
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Garcia-Segura
authors.forename: Marcel
authors.initials: M
authors.lastname: Karperien
mesh_terms: D000730:Androstadienes / Q000009:adverse effects*; D000818:Animals; D047072:Aromatase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000139:chemically induced*; D001842:Bone and Bones / Q000187:drug effects*; D006132:Growth Plate / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013623:Tail / Q000187:drug effects / Q000254:growth & development*; D055114:X-Ray Microtomography
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; C056516:exemestane