A novel tocolytic agent: effects of letrozole on gestational length and parturition time

The purpose of this study was to determine whether letrozole, a potent aromatase inhibitor, could prolong gestation and/or delay parturition in rats. Seventy-five rats were divided into five groups of 15 rats each. Group I and group II rats were administered letrozole orally at doses of 0.002 and 0.02 mg/kg/day from days 15 through 21 of pregnancy, respectively. Rats in group IA were administered a concomitant estradiol cyclopentylpropionate (ECP) injection on day 15 and 0.002 mg/kg letrozole in that same manner as for group I. Rats in group IIA were administered concomitant ECP on day 15 and 0.02 mg/kg letrozole in the same manner as for group II. The control group received sterile saline only. Study and control groups were compared with respect to gestational length, parturition time, fetal mortality rate, stillbirth rate, and fetal body weight. Oral administration of letrozole both at daily doses of 0.002 mg/kg/day (group I) and 0.02 mg/kg/day (group II) consistently prolonged gestation and parturition time. The values of stillbirth rate, fetal mortality rate, and fetal body weight of group I were similar to those in the control group; conversely, fetal mortality rate and stillbirth rate of group II were higher than those values in the control group, and fetal body weight of group II was lower than in the control group. It was observed that concomitant injection of ECP effectively reversed the deleterious effects of letrozole on gestational length, parturition time, fetal mortality rate, stillbirth rate, and fetal body weight. The results of this study indicate that the aromatase inhibitor letrozole can prolong gestation and delays parturition in rats. Its deleterious effects on parturition can be reversed by ECP injection.