Human Experiences Related to Adverse Drug Reactions to the Fetus or Neonate from Some Maternally Administered Drugs

Lower Genital Tract Disease in Children and Adolescents—A review

“…This can be due to adrenogenital syndrome (congenital adrenal hyperplasia, or CAH), placental aromatase defect, which can lead to both maternal and fetal masculinization, maternal ingestion of progestins, 27 androgens, or a maternal virilizing tumor. Female pseudohermaphrodites show varying degrees of clitoral enlargement, and may have labioscrotal fusion.…”

“Natural” progesterone: information on fetal effects

“…Certain abnormalities of the external genitalia (e.g., clitoral hypertrophy) of newborn girls indicative of virilization are seen primarily in connection with the congenital adrenal hyperplasia syndrome. Shortly after introduction of nor-testosterone agents as progestagens in clinical practice in the 1950s, virilization began to be reported in newborns without associated congenital adrenal hyperplasia and was soon attributed to the use of progestagens (Kupperman, 1961;Hayles and Nolan, 1957;Jones and Wilkins, 1960;Wilkins, 1959;Wilkins et al, 1958;Burstein and Wasserman, 1964;Grumbach et al, 1959;Hillman, 1959;Shirkey, 1972). More than 400 girls are estimated to have been virilized in this manner.…”

“…A report described by Shirkey (1972), described enhanced virilization in five male fetuses whose mothers received 100 mg/week to 300 mg/week of progesterone by i.m. injection from the end of the 2nd to the 9th week of gestation.…”

Contributions of androgen and estrogen to fetal programming of ovarian dysfunction

“…For example, fetal androgen excess induces female uro-genital virilization along with masculinized behavior, and neural anatomy and function [ 4 ], while fetal estrogen excess results in female reproductive tract abnormalities, including clear cell adenocarcinoma of the vagina and cervix, as well as increased risk of breast cancer [ 5 ]. Less is known, however, about fetal progestin excess which can mimic androgen excess in its fetal programming outcomes [ 6 , 7 ]. Steroid hormones mediate their classical or genomic actions by binding to nuclear receptors and engaging a variety of molecular chaperones permitting ultimate binding of the entire complex to steroid response elements on promoters of target genes [ 8 ].…”