MESTRANOL

Fetal Risk Summary

Mestranol is the 3-methyl ester of ethinyl estradiol. Mestranol is used frequently in combination with progestins for oral contraception (see Oral Contraceptives). Congenital malformations attributed to the use of mestranol alone have not been reported.

The Collaborative Perinatal Project monitored 614 mother-child pairs with 1st trimester exposure to estrogenic agents (including 179 with exposure to mestranol) (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 mestranol (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). The use of estrogenic hormones during pregnancy is contraindicated.

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 190 newborns had been exposed to mestranol during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 13 (6.8%) major birth defects were observed (8 expected). Specific data were available for six defect categories, including (observed/expected) 1/2 cardiovascular defects, 1/0.5 oral clefts, 0/0 spina bifida, 0/0.5 polydactyly, 1/0.5 limb reduction defects, and 0/0.5 hypospadias.

Breast Feeding Summary

Estrogens are frequently used for suppression of postpartum lactation (4). Doses of 100–150 µg of ethinyl estradiol (equivalent to 160–240 µg of mestranol) for 5–7 days are used (4). Mestranol, when used in oral contraceptives with doses of 30–80 µg, has been associated with decreased milk production, lower infant weight gain, and decreased composition of nitrogen and protein content of human milk (5,6 and 7). The magnitude of these changes is low. However, the changes in milk production and composition may be of nutritional importance in 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. Gilman AG, Goodman LS, Gilman A. The Pharmacological Basis of Therapeutics. New York, NY: MacMillan, 1980:1431.
5. Kora SJ. Effect of oral contraceptives on lactation. Fertil Steril 1969;20:419–23.
6. Miller GH, Hughs LR. Lactation and genital involution effects of a new low-dose oral contraceptive on breast-feeding mothers and their infants. Obstet Gynecol 1970;35:44–50.
7. 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.