Impaired body weight and tail length gain and altered bone quality after treatment with the aromatase inhibitor exemestane in male rats

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. Aim: 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.

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.

Exemestane treatment during sexual maturation did not augment linear growth in male rats, but caused impaired body weight and tail length gain and osteopenia.

S.A. van Gool, J.M. Wit, T. de Schutter, N. de Clerck, A.A. Postnov, S. Kremer Hovinga, J. van Doorn, S.J. Veiga, L.M. Garcia-Segura, M. Karperien
2010; 73 (5): 376-385
Published in: 
Hormone Research in Paediatrics
Date of publication: 
April, 2010
Status of the publication: