Generic Aygestin (Norethindrone acetate 5mg)
NORETHINDRONE
(Micronor, Norlutin, Nor-Q.D.)
Norethindrone is a synthetic progestin that is used as an oral contraceptive (when formulated with an estrogenic compound) and in treatment of menstrual disorders. The dose used to treat endometriosis (up to 15 mg/d) is much greater than that currently used in oral contraceptives (0.4-2.5 mg/d).
Teratogenic Risk
Magnitude of teratogenic risk to child born after exposure during gestation:
Non-genital congenital anomalies: None.
Virilization of female fetus with large doses (used to treat endometriosis): Small.
Virilization of female fetus with small doses (used in oral contraceptives): None.
Quality and quantity of data on which risk estimate is based:
Non-genital congenital anomalies: Fair.
Virilization of female fetus with large doses (used to treat endometriosis): Fair.
Virilization of female fetus with small doses (used in oral contraceptives): Fair.
Maternal use of large doses of norethindrone during pregnancy has associated with the occurrence of masculinization of the external Italia in female infants. The genital anomalies observed include various degrees of clitoral hypertrophy with or without labioscrotal fusion. Internal genitalia and pubertal development are not affected. Labioscrotal fusion is associated with exposure between the seventh and thirteenth week of gestation, but clitoral hypertrophy can develop with exposure at this time or later in pregnancy. The frequency of genital virilization among daughters of women who took norethindrone during pregnancy in doses similar to or greater than those used to treat endometriosis was 13% and 19% in clinical series of 39 and 82 female infants, respectively.
The overall frequency of congenital anomalies was not significantly greater than expected among the children of 132 women who took norethindrone during the first four lunar months of pregnancy or of 148 women who took this drag anytime in pregnancy in a large epidemiological study. In another study, maternal use of norethindrone during pregnancy was not significantly increased among 171 children with various congenital anomalies. Similarly, the frequency of hormonal pregnancy tests using norethindrone and ethinyl estradiol (an estrogenic agent) during the second month of pregnancy was not increased among the mothers of 194 infants with major malformations or 551 infants with minor congenital anomalies.
Masculinization of the genitalia of female offspring can be induced in several species of experimental animals by treatment of the mother with norethindrone in high doses during pregnancy.
Studies in nonhuman primates, mice, and rabbits suggest that treatment of pregnant women with norethindrone in usual therapeutic or contraceptive doses is unlikely to increase the children's risk of non-genital congenital anomalies greatly.
Risk Related to Breast-feeding
Norethindrone is excreted in breast milk. The amount of norethindrone that the nursing infant would be expected to ingest is
Norethindrone concentrations ranging from 0.07-0.42 ng/mL were measured in the serum of 15 breast-fed infants whose mothers took an oral contraceptive containing norethindrone. These levels of norethindrone were between 4-25% of those found in the maternal serum. In another study, no norethindrone was found in the serum of breast-fed infants whose mothers had been given an intramuscular injection of norethindrone.
Maternal use of norethindrone as a contraceptive during lactation had no adverse effects on growth or development of infants followed up to one year of age.
WOMEN’S HEALTH
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