MASOULINIZATION OF THE FEMALE FETUS ASSOCIATED WITH ADMINISTRATION OF ORAL AND INTRAMUSCULAR PROGESTINS DURING GESTATION: NON-ADRENAL FEMALE PSEUDOHERMAPHRODISM*
There are relatively few reports of female pseudohermaphrodism not associated with congenital adrenal hyperplasia. The writers report 21 cases of females born with partial masculinization of the external gcnitalia, consisting of an enlarged phallus, with or without varying degrees of fusion of the labioscrotal folds. The diagnosis was established by finding female chromatin patterns, low excretion of urinary 17-kctosteroids and absence of progressive virilization. Exploratory laparotomy revealed normal ovaries and a normal female genital tract, although in some cases the vagina and urethra opened into a common urogenital sinus. In 15 of the cases, the mother had been treated because of threatened or habitual abortion with an oral progestin, 17-cthinyltestosterone (anhydrohydroxyprogesterone or ethisterone), marketed undersuch trade names as Pranone, Progestoral and Lutocjlol. In 2 cases the mother had received intramuscular injections of progesterone. In 1 case both intramuscular progesterone and oral methyltcstosterone had been given. In 3 cases no steroids were administered during pregnancy. The progestinic medication was usually begun before the tenth week of gestation and in most instances between the fourth and sixth weeks. Reasons are discussed for believing that the oral and intramuscular administration of progestins induced the partial masculinization of the female fetus. It is believed that the female fetus is affected in only occasional mothers who receive these steroids, and that in such mothers there may be an abnormality of cither the metabolism of progestins or their transmission across the placenta. It is most important to diagnose the condition correctly at birth, and to rear the infant as a female. No treatment is required except surgical correction of the abnormalities of the external genitalia. Normal female development is certain.