ESTRADIOL

Fetal Risk Summary

Estradiol and its salts (cypionate, valerate) are used for treatment of menopausal symptoms, female hypogonadism, and primary ovarian failure. The more potent synthetic derivative, ethinyl estradiol, has similar indications and is also used in oral contraceptives (see also Oral Contraceptives).

The Collaborative Perinatal Project monitored 614 mother-child pairs with 1st trimester exposure to estrogenic agents (including 48 with exposure to estradiol) (1, pp. 389, 391). An increase in the expected frequency of cardiovascular defects, eye and ear anomalies, and Down's syndrome was found for estrogens as a group but not for estradiol (1, pp. 389, 391, 395). Re-evaluation 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 surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 29 newborns had been exposed to ethinyl estradiol during the 1st trimester (F. Rosa, personal communication, FDA, 1993). Four (13.8%) major birth defects were observed (one expected), including (observed/expected) 1/0.3 cardiovascular defects, and 1/0 hypospadias. No anomalies were observed in four other categories of defects (oral clefts, spina bifida, polydactyly, and limb reduction defects) for which specific data were available. The number of exposures is too small for any conclusion.

Developmental changes in the psychosexual performance of boys have been attributed to in utero exposure to estradiol and progesterone (4). The mothers received an estrogen/progestogen regimen for their diabetes. Hormone-exposed males demonstrated a trend to have less heterosexual experience and fewer masculine interests than controls. Estradiol has been administered to women in labor in an attempt to potentiate the cervical ripening effects of prostaglandins (5). No detectable effect was observed. Use of estrogenic hormones during pregnancy is contraindicated.

Breast Feeding Summary

Estradiol is used to suppress postpartum breast engorgement in patients who do not desire to breast-feed. Following the administration of vaginal suppositories containing 50 or 100 mg of estradiol to six lactating women who wished to stop breast feeding, less than 10% of the dose appeared in breast milk (6). The American Academy of Pediatrics considers estradiol to be compatible with breast feeding (7).

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. Yalom ID, Green R, Fisk N. Prenatal exposure to female hormones. Effect of psychosexual development in boys. Arch Gen Psychiatry 1973;28:554–61.
5. Luther ER, Roux J, Popat R, Gardner A, Gray J, Soubiran E, Korcaz Y. The effect of estrogen priming on induction of labor with prostaglandins. Am J Obstet Gynecol 1980;137:351–7.
6. Nilsson S, Nygren KG, Johansson EDB. Transfer of estradiol to human milk. Am J Obstet Gynecol 1978;132:653–7.
7. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.