Propranolol for severe hemangiomas of infancy.

n engl j med 358;24 www.nejm.org june 12, 2008 2649 negative predictive value.1 It should be noted that plasma levels of imatinib in patients given high doses of the drug exceed those of the no­effect level in the study of rat fertility. We also disagree with the specific reservations expressed by the correspondents. The time relationship was rea­ sonable, with oligomenorrhea occurring a few months after the increase in the dose of imatinib. There were no other exposures, and no alterna­ tive causes were found on routine investigation of amenorrhea. Finally, the hypothesis of an etiolog­ ic link between imatinib and ovarian insufficiency is biologically plausible, since pathways involving kinases targeted by imatinib appear to play criti­ cal roles in the survival and maturation of folli­ cles and oocytes.2-4 Constantinos Christopoulos, M.D., Ph.D. Vasiliki Dimakopoulou, M.D. Evangelos Rotas, M.D.