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Soy formula associated with estrogenic response in infant girls

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March 12, 2018

Margaret Adgent
Margaret A. Adgent

Infant girls fed soy formula from birth had a higher vaginal cell maturation index and lower uterine volume involution over the first 9 months of infancy vs. infant girls fed cow’s milk formula during the same period, according to findings from an observational study.

Several epidemiologic studies suggest an association between use of soy formula and adult reproductive health, Margaret A. Adgent, MSPH, PhD, a research assistant and professor with Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues from the Children’s Hospital of Philadelphia and the National Institute of Environmental Health Sciences of the NIH, wrote in the study background. However, little is known about reproductive system changes that occur during infancy.

“Modern soy formula has been used safely for decades,” Adgent told Endocrine Today. “However, soy formula contains plant-based compounds, such as genistein, which demonstrate estrogenic activity in experimental rodent studies. In our observational study, when compared to infants who were fed cow’s milk formula, infants who were fed soy formula exclusively since birth demonstrated differences in uterine volume and urogenital epithelial cell characteristics over the first 7 to 9 months of life, consistent with an estrogen response. The long-term clinical consequences of these changes are unknown.”

Adgent and colleagues analyzed data from 283 mother-child dyads participating in the Infant Feeding and Early Development study, which assessed estrogen-responsive tissues and organs longitudinally during the postnatal period. Mothers were recruited from eight Philadelphia regional hospitals between August 2010 and November 2013. Participating infants were exclusively fed soy formula (n = 102), cow’s milk formula (n = 111) or breastmilk (n = 70). Mothers submitted feeding-history questionnaires at each follow-up visit, completed at 2 and 4 weeks and then monthly through week 36 for girls and week 28 for boys. Researchers measured serum estradiol, maturation index in vaginal and urethral epithelial cells and uterine volume and breast-bud diameter via ultrasound. Follicle-stimulating hormone levels were also measured in girls. Researchers used mixed-effects regression splines to estimate maturation index, organ growth and hormone level trajectories by feeding method.

Researchers observed a difference in maturation index trajectory between girls fed soy formula and cow’s milk formula (P = .01) and between girls fed soy milk formula and breast-fed infants (P = .01); however, no maturation index differences were observed for boys by feeding choice.

In examining trajectories of relative uterine volume, girls fed soy formula experienced slower involution vs. girls fed cow’s milk (P = .01) or breast milk (P < .01).

Researchers also observed a difference in estradiol trajectories between girls fed breastmilk and soy formula (P = .02); however, there were no differences in estradiol trajectories observed between girls fed soy formula and cow’s milk formula (P = .44) or between girls fed cow’s milk formula and breastmilk (P = .17). There were no between-group differences observed in follicle-stimulating hormone or breast-bud diameter for girls, whereas boys fed breastmilk experienced a larger decrease in breast-bud diameter vs. boys fed soy formula (P = .02) or cow’s milk formula (P = .05).

“Our findings are consistent with the animal literature, in that we detected several developmental perturbations of estrogen-responsive tissue,” the researchers wrote. “Our methods targeting subclinical metrics of tissue growth and response may be useful tools for identifying early responses to suspected estrogenic agents.”

Adgent said it remains unclear whether the subtle differences observed in estrogen-responsive tissues are associated with any future health consequences. Long-term follow-up of soy-fed infants, perhaps into adolescence, will be useful in determining whether soy formula exposure in infancy is associated with subsequent reproductive health, development and other health outcomes. – by Regina Schaffer

For more information:

Margaret A. Adgent , MSPH, PhD, can be reached at Vanderbilt University Medical Center, 1313 21st Ave., 313 Oxford House, Nashville, TN 37232-4313; email:

Disclosures: The authors report no relevant financial disclosures.