The role of estrogen in the maintenance of primate pregnancy

OBJECTIVE: The aim of this study was to determine the role of estrogen in pregnancy maintenance in baboons by suppressing estrogen synthesis through administration of a highly specific nonsteroidal aromatase inhibitor, CGS 20267. STUDY DESIGN: CGS 20267 was administered subcutaneously at maximal dosages of 2.0 mg/d to pregnant baboons (n = 24) daily beginning on either day 30 (n = 8), day 60 (n = 8), or day 100 (n = 8) of gestation (normal length of gestation is 184 days) until animals miscarried or were delivered abdominally on days 160 through 168 of gestation. CGS 20267 and estradiol (n = 9), each at maximal dosages of 2 mg/d, were administered at the same intervals of gestation. Twenty baboons served as untreated control animals. Serum estradiol and progesterone levels were determined by radioimmunoassay from serum samples obtained at 1- to 3-day intervals from a maternal peripheral vein. RESULTS: Within 1 to 3 days of the initiation of CGS 20267 administration, maternal serum estradiol concentration decreased to and remained at a level that was substantially lower (mean +/- SE, 0.096 +/- 0.003 ng/mL) than in the untreated control animals throughout gestation (0.35-4.0 ng/mL; P < .001). Although pregnancy was maintained in 19 of the 20 untreated control baboons (95%), only 12 of the 24 animals that received CGS 20267 (50%) maintained pregnancy. In contrast, all the baboons treated concomitantly with estradiol and CGS 20267 (9/9) maintained pregnancy. Thus estradiol alone prevented the high rate of miscarriage induced by the antiestrogenic agent CGS 20267. Serum progesterone concentrations were not significantly different throughout the experimental period between the CGS 20267-treated baboons that maintained pregnancy (12.9 +/- 1.4 ng/mL) and those that miscarried (13.6 +/- 1.6 ng/mL) and were not lower in antiestrogen-treated baboons than in untreated control baboons (10.6 +/- 0.8 ng/mL). CONCLUSION: Estrogen, acting directly, indirectly, or both through a factor or factors other than the level of progesterone, plays a critically important physiologic role in the maintenance of primate pregnancy.