Soy-Based Infant Feeding Is Associated with Estrogenized Urogenital Epithelium in Girls at 24 Weeks of Age

Abstract

Soy-based infant formulas contain isoflavone compounds that are estrogenic. Infants exclusively fed soy formula experience high exposure to these compounds, but it is not known if infants respond to such exposures as they would to estradiol. Cytological evaluation of urogenital epithelial cells for relative proportions of cell types, a classic marker of estrogen response in adult women, can be used to characterize estrogen response in infants (PLoS ONE 8(10): e77061 (2013)). Here, we apply this method in a study of soy formula fed infants. Methods: We analyzed urogenital epithelial cells from 212 infants. All were fed either breast milk (n=70), formula based on cow milk (CMF) (n=100), or soy formula (n=42) since birth. Cell samples were obtained from swabs of the vaginal introitus or urethral meatus at age 24 weeks, and the percentage of superficial (S) and intermediate (I) cell types was determined. A summary maturation index (MI), where higher scores suggest more estrogenization, was calculated as %S + (%I/2). Mean MI for feeding group and sex was evaluated. Results: A significant feeding group*sex interaction was observed (p<0.01). For girls, MI was higher among the soy fed (n=18, MI=56, 95% Confidence Interval (CI): 52, 61), as compared to both CMF fed (n=53, MI=49, 95%CI: 46, 51; p=0.002) and breast fed (n=32, MI=48, 95%CI: 46, 50; p=0.002). No differences were observed between breast and CMF fed girls (p=0.62). For boys, breast (MI=57, 95%CI: 54, 59), soy (MI=54, 95%CI: 52, 56), and CMF (MI=57, 95%CI: 54, 59) were not different (all p> 0.24). Conclusion: Soy formula is associated with elevated MI in the vaginal, but not male urethral, epithelium at 24 weeks. Infancy is a period of low endogenous estrogen production; these vaginal cell changes suggest that an exclusive soy diet is associated with a response in young girls that is consistent with physiologically active estrogen exposure, i.e., endocrine disruption. A similar response was not seen in boys.