Although age at menarche does not completely capture pubertal development, our finding that soy formula consumption was associated with both early and late menarche is consistent with animal data suggesting that the dose of genistein influences whether puberty will be advanced or delayed. Mice administered a higher dose of genistein had a delayed vaginal opening (marker of puberty) while mice given a lower dose had an accelerated vaginal opening.26 Neonatal administration of genistein to mice has also produced other alterations in reproductive characteristics, including changes in estrous cycles, early reproductive senescence, and decreased fertility.43 Soy formula delivers a high dose of estrogenic isoflavones to infants per unit body weight44; high plasma and urinary concentrations of genistein have been reported in infants fed soy formula.44-46 There are inconsistent results from the two previous epidemiologic studies of soy versus cow milk formula during infancy: one reported no difference in age at menarche,47 and the other reported that those given soy formula early in life (≤4 months through ≥6 months of age) had earlier menarche.48 Soy formula composition changed in the early 1960s
