Misoprostol, a synthetic prostaglandin E1, was administered to CD-1 mice daily by gavage for 21 months in a safety study. Hyperostosis of the marrow cavity in the sternum and femur was found predominantly in female mice of the medium (1,600 mcg/kg/day) and high dosage (16,000 mcg/kg/day) groups. Many of the mice with hyperostosis also had cystic ovaries and cystic endometrial hyperplasia indicative of hyperestrinism. It is postulated that the hyperostosis was the result not only of the effects of misoprostol but also of endogenous estrogen. Since misoprostol did not cause hyperostosis in either rats or dogs, it is probable that this effect in mice is unique.
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