[1] Fetal masculinization of the vulva is usually due to enzyme abnormalities involved in adrenal steroid biosynthesis, resulting in congenital adrenal hyperplasia (CAH); fetal masculinization of the vulva is much less frequently due to maternal use of androgenic steroids.

[5][7] On June 21, 1976, the FDA approved the androgen danazol (Danocrine), a derivative of ethisterone, for treatment of endometriosis, with a warning that its use in pregnancy is contraindicated because of the risk of masculinization of vulvas of female fetuses.

[8] The first case report of fetal masculinization of the vulva of a female infant born to a mother inadvertently treated in pregnancy with danazol was published in 1981.

[9] Between 1975 and 1990, the manufacturer of Danocrine, Winthrop Laboratories, received reports worldwide of 129 pregnant women exposed to danazol, with 94 completed pregnancies and the birth of 57 female infants – 23 (40%) of whom were virilized with a pattern of clitoromegaly, fused labia and urogenital sinus formation, with genital reconstructive surgery usually, but not always, required in childhood.

[14][15] In a March 1960 JAMA article, pediatric endocrinologist Lawson Wilkins at Johns Hopkins reported on 34 cases of fetal masculinization of vulvas of female infants born from 1950 to 1959 to mothers treated with high-dose (20–250 mg/day) ethisterone to prevent miscarriage, and 35 cases of fetal masculinization of vulvas of female infants born from 1957 to 1959 to mothers treated with high-dose (10–40 mg/day) norethisterone to prevent miscarriage.

[21][22][23][24][25][excessive citations] On January 12, 1989, after determining that progestogens did not cause non-genital birth defects, the FDA published a notice revising the black box warning on all progestogen drugs (except contraceptives) to warn against their use during the first four months of pregnancy because of past reports of genital birth defects (an increased risk of hypospadias in male fetuses and mild virilization of vulvas in female fetuses).