ETHINYL ESTRADIOL

Fetal Risk Summary

Ethinyl estradiol is used frequently in combination with progestins for oral contraception (see Oral Contraceptives). The Collaborative Perinatal Project monitored 89 mother-child pairs who were exposed to ethinyl estradiol 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). In a smaller study, 12 mothers were exposed to ethinyl estradiol during the 1st trimester (4). No fetal abnormalities were observed. Ethinyl estradiol has also been used as a contraceptive when given within 72 hours of unprotected midcycle coitus (5). Use of estrogenic hormones during pregnancy is contraindicated.

Breast Feeding Summary

Estrogens are frequently used for suppression of postpartum lactation (6,7). Very small amounts are excreted in milk (7). When used in oral contraceptives, ethinyl estradiol has been associated with decreased milk production and decreased composition of nitrogen and protein content in human milk (8). Although the magnitude of these changes is low, the differences in milk production and composition may be of nutritional importance to nursing infants of malnourished mothers. If breast feeding is desired, the lowest dose of oral contraceptives should be chosen. Monitoring of infant weight gain and the possible need for nutritional supplementation should be considered (see Oral Contraceptives).

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, Kunstadler RH. Fetal effects of steroid therapy during pregnancy. Am J Dis Child 1963;106:586–90.
5. Dixon GW, Schlesselman JJ, Ory HW, Blye RP. Ethinyl estradiol and conjugated estrogens as postcoital contraceptives. JAMA 1980;244:1336–9.
6. Gilman AG, Goodman LS, Gilman A, eds. The Pharmacological Basis of Therapeutics. 6th ed. New York, NY:MacMillan Publishing Co, 1980:1431.
7. Klinger G, Claussen C, Schroder S. Excretion of ethinyloestradiol sulfonate in the human milk. Zentralbl Gynaekol 1981;103:91–5.
8. Lonnerdal B, Forsum E, Hambraeus L. Effect of oral contraceptives on composition and volume of breast milk. Am J Clin Nutr 1980;33:816–24.