Progestin-induced virilization

Maternal use of androgens or high doses of certain weakly androgenic synthetic progestogens (progestins) structurally related to testosterone can masculinize (virilize) the vulva of a female fetus during susceptible times in pregnancy.

Some degree of fusion of the labioscrotal folds and urogenital folds and clitoral enlargement can occur if exposure occurs from the 8th through the 12th week of gestation, but only clitoral enlargement can occur if exposure occurs after the 12th week. This can in some cases result in ambiguous genitalia.

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.

Fetal masculinization of the vulva due to maternal use of androgenic steroids is generally less advanced than that due to CAH, and unlike CAH, does not cause progressive virilization.

Affected females mature normally with normal fertility, there is almost total regression of the genital anomaly in cases of simple clitoral enlargement, and in even the most severe cases, surgical correction of labioscrotal fusion is relatively simple.

The incidence of fetal masculinization of the vulva varies with the drug and dosage.

The only sex steroid currently utilized in women that can cause virilization of female fetuses when administered in usually administered doses is the androgen danazol, a derivative of ethisterone (ethinyltestosterone).

Fetal masculinization of the vulva has resulted from doses of danazol as low as 200 mg/day, whereas 800 mg/day is the usual initial dose when danazol is used to treat severe endometriosis.