Abstract
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. (Am J Obstet Gynecol 2000;182:432-8.)
Keywords
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Article Info
Publication History
Accepted:
September 22,
1999
Received in revised form:
June 23,
1999
Received:
April 8,
1999
Footnotes
☆Supported by National Institutes of Health research grant R01 HD-13294.
☆☆Reprint requests: Eugene D. Albrecht, PhD, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Bressler Research Laboratories 11-019, 655 W Baltimore St, Baltimore, MD 21201.
Identification
Copyright
© 2000 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
