In utero DES has been associated with various reproductive abnormalities in women.50 In mice, prenatal administration of DES results in an earlier vaginal opening.27,28 We found an association of DES with very early menarche (≤10 years of age). Two studies based on documented prenatal DES exposure found no difference in mean age at menarche51 and no association with early or late age at menarche.52 However, these studies did not report on the frequency of very early menarche. Evaluating mean differences in age at menarche may not be sensitive to differences in the frequency of very early menarche because this group typically represents a small proportion of any population (7% in our study sample). Similar to our study findings, Hatch et al.53 reported an association with very early menarche in a cohort study of medically documented in utero DES exposure. Information on DES dose and timing during pregnancy was not available in our study.
