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Effects of the aromatase inhibitor letrozole on in utero development in rats.

Research paper by G M GM Tiboni, F F Marotta, C C Rossi, F F Giampietro

Indexed on: 20 May '08Published on: 20 May '08Published in: Human reproduction (Oxford, England)



Abstract

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.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.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.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.