Absence of estrogenic activity in some drugs commonly used during pregnancy.

Abstract

Treatment of pregnant women with estrogenic compounds such as diethylstilbestrol (DES) has been associated with genital tract abnormalities in their male and female offspring. Since these data suggest the developing fetus is highly susceptible to the tumorigenic and dysmorphogenic effects of estrogenic substances, knowledge of the estrogenic activity of some drugs commonly used during pregnancy is important. Based on structural similarities to other known estrogenic compounds and to the frequency of use among pregnant women, phenobarbital, saccharin and acetaminophen were assayed for estrogenic activity; DES was used as a positive control. Using a competitive receptor binding assay, these compounds did not show appreciable binding to a soluble uterine receptor preparation while DES showed strong binding interactions. Analysis of the compounds in an in vivo uterotropic bioassay using immature female mice showed that, over the dose range used (5 micrograms/kg-50 micrograms/kg), only DES had any estrogenic activity while the other compounds were negative. Therefore, phenobarbital, saccharin and acetaminophen did not display estrogenic activity under the conditions of test.