Impaired body weight and tail length gain and altered bone quality after treatment with the aromatase inhibitor exemestane in male rats.
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.
van Gool
Sandy A
SA
Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands. s.van_gool @ lumc.nl
Wit
Jan M
JM
De Schutter
Tineke
T
De Clerck
Nora
N
Postnov
Andreï A
AA
Kremer Hovinga
Sandra
S
van Doorn
Jaap
J
Veiga
Sergio J
SJ
Garcia-Segura
Luis Miguel
LM
Karperien
Marcel
M
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
D000730:Androstadienes; D047072:Aromatase Inhibitors; C056516:exemestane