ON THE FETAL MASCULINIZING ACTION OF CERTAIN ORAL PROGESTINS*

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Abstract
Data are presented on 18 females with congenital masculinization of the external genitalia who were born of mothers treated with certain oral progestins during pregnancy. Nine of the mothers had received 19-nor-17α-ethynyltestosterone; 1, norethynodrel; and 8 others, 17α-ethynyltestosterone. The masculinizing effect on the female fetus of the first compound, and possibly the second, was comparable to that of known androgens. Labioscrotal fusion was exhibited only in those instances in which the oral progestin had been administered prior to the thirteenth week of gestation. Evidence is reviewed which suggests that these oral progestins have a direct masculinizing action on the female fetus. It is suggested that the discordance in androgenic activity exhibited by these compounds in the fetus as compared to the adult may be attributed to differences in the sensitivity of the end-organs and to delayed fetal disposal of steroid transferred across the placenta. The importance of distinguishing fetal masculinization due to administration of testosterone analogues with progestational activity from those rare instances of congenital masculinization of the female fetus in which a relationship to treatment during pregnancy with progesterone or its analogues or dicthylstilbestrol has been suspected but not established, is emphasized. The authors recommend that treatment of pregnant women with semi-synthetic oral progestins which exhibit masculinizing properties in the female fetus be abandoned.