Risk Factor: XM
Class: Hormones/ Progestogens
Fetal Risk Summary
Norethynodrel is a progestogen derived from 19-nortestosterone. It is used in oral contraceptive agents and hormonal pregnancy tests (no longer available in the United States). Masculinization of the female infant has been associated with norethynodrel (1,2). The Collaborative Perinatal Project monitored 866 mother-child pairs with 1st trimester exposure to progestational agents (including 154 with exposure to norethynodrel) (3, pp. 389, 391). Fetuses exposed to norethynodrel were not at an increased risk for malformation. However, an increase in the expected frequency of cardiovascular defects and hypospadias was observed for progestational agents as a group (3, p. 394; 4). 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 female sex hormones and cardiac malformations (5). An earlier study also failed to find any relationship with nongenital malformations (1). One investigator observed three infants, exposed to norethynodrel and mestranol during the 1st trimester, who had congenital defects, including atrial and ventricular septal defects (one infant), hypospadias (one infant), and inguinal hernias (two infants) (6). The relationship between the anomalies and the exposure to the hormones is unknown.
Breast Feeding Summary
Norethynodrel exhibits a dose-dependent suppression of lactation (7). Lower infant weight gain, decreased milk production, and decreased composition of nitrogen and protein content of human milk have been associated with similar synthetic progestogens and estrogen products (see Norethindrone, Mestranol, Ethinyl Estradiol, Oral Contraceptives) (8,9 and 10). 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. The American Academy of Pediatrics considers norethynodrel to be compatible with breast feeding (11).
- Wilson JG, Brent RL. Are female sex hormones teratogenic? Am J Obstet Gynecol 1981;141:56780.
- Hagler S. Schultz A, Hankin H, Kunstadter RN. Fetal effects of steroid therapy during pregnancy. Am J Dis Child 1963;106:58690.
- Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977.
- Heinonen OP, Slone D, Monson RR, Hook EB, Shapiro S. Cardiovascular birth defects and antenatal exposure to female hormones. N Engl J Med 1977;296:6770.
- Wiseman RA, Dodds-Smith IC. Cardiovascular birth defects and antenatal exposure to female sex hormones: a reevaluation of some base data. Teratology 1984;30:35970.
- Dillon S. Congenital malformations and hormones in pregnancy. Br Med J 1976;2:1446.
- Guiloff E, Ibarra-Polo A, Zanartu J, Toscanini C, Mischler TW, Gomez-Rogers C. Effect of contraception on lactation. Am J Obstet Gynecol 1974;118:425.
- Kora SJ. Effect of oral contraceptives on lactation. Fertil Steril 1969;20:41923.
- Miller GH, Hughes LR. Lactation and genital involution effects of a new low-dose oral contraceptive on breast-feeding mothers and their infants. Obstet Gynecol 1970;35:4450.
- Lonnerdal B, Forsum E, Hambraeus L. Effect of oral contraceptives on composition and volume of breast milk. Am J Clin Nutr 1980;33:81624.
- Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.