Marginal growth increase, altered bone quality and polycystic ovaries in female prepubertal rats after treatment with the aromatase inhibitor exemestane.
BACKGROUND
Aromatase inhibition has been proposed as a potential approach for growth enhancement in children with short stature, but detailed animal studies are lacking.


OBJECTIVE
To assess the effect and potential adverse effects of aromatase inhibition on growth in female rats.


METHODS
Prepubertal Wistar 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) for 3 weeks. A control group was ovariectomized (OVX). Weight and length gain, tibia and femur length, growth plate width, organ weights, insulin-like growth factor I (IGF-I) levels, and histology of the ovaries, uterus and brain were analyzed. X-ray microtomography of femora was performed.


RESULTS
E100 significantly increased weight gain and growth plate width, but less prominently than OVX. Trabecular number and thickness were decreased in E100 and OVX in the metaphysis and epiphysis. E100 significantly decreased ovarian weight and multiple cysts were seen upon histological evaluation. No significant effects were found on IGF-I levels and brain morphology in E100. E10 and E30 had no effects on growth.


CONCLUSIONS
A high dose of exemestane marginally increases axial and appendicular growth in female rats, at the expense of osteopenia and polycystic ovaries.
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 / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D015519:Bone Density / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D005260:Female; D048788:Growth and Development / Q000187:drug effects*; D007273:Injections, Intramuscular; D010048:Ovarian Cysts / Q000139:chemically induced* / Q000503:physiopathology; D010919:Placebos; D011786:Quality Control; D051381:Rats; D017208:Rats, Wistar; D012741:Sexual Maturation / Q000187:drug effects* / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects; D055114:X-Ray Microtomography
D000730:Androstadienes; D047072:Aromatase Inhibitors; D010919:Placebos; C056516:exemestane