Effects of the aromatase inhibitor letrozole on in utero development in rats.
BACKGROUND
The aromatase inhibitor letrozole has recently been identified as a promising ovulation-inducing agent. As information regarding possible adverse effects on gestation outcome is limited, the present study was undertaken to evaluate the developmental toxicity potential of letrozole in the rat.


METHODS
Pregnant Sprague-Dawley rats were exposed via drinking water to letrozole at 0 (control group), 0.01, 0.02, or 0.04 mg/kg during the period of organogenesis. Developmental endpoints, including intrauterine mortality, fetal growth and incidence of structural abnormalities, were evaluated near the end of gestation.


RESULTS
Major treatment-related effects included: (i) a dose-dependent increase in post-implantation loss, which reached 47.2% following exposure to 0.04 mg/kg letrozole; (ii) minor vertebral anomalies affecting 32.2, 29.3 and 42.2% of fetuses exposed to 0.01, 0.02 and 0.04 mg/kg, respectively.


CONCLUSIONS
Gestational exposure to doses of letrozole that are equal to or lower than the daily recommended human dose has toxic effects on prenatal development in rats.
Tiboni
G M
GM
Dipartimento di Medicina e Scienze dell'Invecchiamento, Facoltà di Medicina e Chirurgia, Università G. d'Annunzio, Chieti-Pescara, Ospedale Clinicizzato SS. Annunziata, Via dei Vestini, 66013 Chieti, Italy. tiboni@unich.it
Marotta
F
F
Rossi
C
C
Giampietro
F
F
D000818:Animals; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D020567:Fetal Weight / Q000187:drug effects; D000077289:Letrozole; D018811:Maternal Exposure; D009570:Nitriles / Q000494:pharmacology*; D038081:Organogenesis / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013131:Spine / Q000002:abnormalities / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology*
D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole