ESTROGENS, CONJUGATED

Fetal Risk Summary

Conjugated estrogens are a mixture of estrogenic substances (primarily estrone). The Collaborative Perinatal Project monitored 13 mother-child pairs who were exposed to conjugated estrogens during the 1st trimester (1, pp. 389, 391). An increased risk for malformations was found, although identification of the malformations was not provided. Estrogenic agents as a group were monitored in 614 mother-child pairs. An increase in the expected frequency of cardiovascular defects, eye and ear anomalies, and Down's syndrome was reported (1, p. 395). Reevaluation of these data in terms of timing of exposure, vaginal bleeding in early pregnancy, and previous maternal obstetric history, however, failed to support an association between estrogens and cardiac malformations (2).

An earlier study also failed to find any relationship with nongenital malformations (3). No adverse effects were observed in one infant exposed during the 1st trimester to conjugated estrogens (4). However, in an infant exposed during the 4th–7th weeks of gestation to conjugated estrogens, multiple anomalies were found: cleft palate, micrognathia, wormian bones, heart defect, dislocated hips, absent tibiae, bowed fibulae, polydactyly, and abnormal dermal patterns (5). Multiple other agents were also taken during this pregnancy, but only conjugated estrogens and prochlorperazine (see also Prochlorperazine) appeared to have been taken during the critical period for the malformations.

Conjugated estrogens have been used to induce ovulation in anovulatory women (6). They have also been used as partially successful contraceptives when given within 72 hours of unprotected, midcycle coitus (7). No fetal adverse effects were mentioned in either of these reports.

Breast Feeding Summary

No reports of adverse effects from conjugated estrogens in the nursing infant have been located. It is possible that decreased milk volume and decreased nitrogen and protein content could occur (see Mestranol, Ethinyl Estradiol).

References

1. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977.
2. Wiseman RA, Dodds-Smith IC. Cardiovascular birth defects and antenatal exposure to female sex hormones: a reevaluation of some base data. Teratology 1984;30:359–70.
3. Wilson JG, Brent RL. Are female sex hormones teratogenic? Am J Obstet Gynecol 1981;141:567–80.
4. Hagler S, Schultz A, Hankin H, Kunstadter RH. Fetal effects of steroid therapy during pregnancy. Am J Dis Child 1963;106:586–90.
5. Ho CK, Kaufman RL, McAlister WH. Congenital malformations. Cleft palate, congenital heart disease, absent tibiae, and polydactyly. Am J Dis Child 1975;129:714–6.
6. Price R. Pregnancies using conjugated oestrogen therapy. Med J Aust 1980;2:341–2.
7. Dixon GW, Schlesselman JJ, Ory HW, Blye RP. Ethinyl estradiol and conjugated estrogens as postcoital contraceptives. JAMA 1980;244:1336–9.