Effects of Indomethacin on Corpus Luteum Function and Pregnancy in Rhesus Monkeys

Abstract

Indomethacin was administered during the luteal phase of the menstrual cycle and during late pregnancy in rhesus monkeys. The plasma indomethacin concentrations achieved were within the ranges effective in inhibiting the microsomal prostaglandin synthetase, even when allowances were made for 90% binding to plasma proteins. There were no significant differences in duration of the luteal phase of menses or in luteal phase progesterone concentrations with indomethacin treatment. Our findings do not support the hypothesis that endogenous prostaglandins are important luteolysins in primates. They provide indirect evidence that administration of prostaglandin synthetase inhibitors would have no therapeutic benefit in treatment of the "short luteal phase" syndrome in women. Indomethacin administration in late pregnancy had a significant effect in prolonging gestation. Uteri of treated animals remained flaccid and distended after fundal hysterotomy and removal of fetuses. Maternal plasma concentrations of unconjugated estradiol, estrone, and progesterone during indomethacin treatment were within the expected ranges for late pregnancy in rhesus monkey, although in two animals we found transient, unexplained, high concentrations of estrone in maternal plasma. Chronic indomethacin administration was associated with continuing fetal and placental growth, a 50% fetal mortality rate, oligohydramnios, and meconium staining, and maternal anemia but normal bleeding times. Severe oligohydramnios was noted in preterm as well as post-term fetuses, indicating that indomethacin per se alters regulation of amniotic fluid volume.