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Study of Estrogen Activity and Development (SEAD) Soy Study

Epidemiology Branch

SEAD Soy Study

The Study(ies) of Estrogen Activity and Development (SEAD) are a series of cross-sectional pilot studies designed to establish methods for prospective studies on the effects of soy infant formula and other exogenous estrogens on the developing infant. The study examines in detail the response of the infant to maternal estrogen, which is at its peak at birth, and the waning of that effect over the first months of life. This allows us to test the hypothesis that any “endocrine disrupter” will prolong the effects of maternal estrogen in a cell or tissue that we have shown to be responsive.

Term newborns have anatomic and sonographic evidence of estrogen exposure in utero. Over the first six months to a year of life, as the influence of maternal hormone wanes, the effects of estrogen on the child recede. However, soy infant formula contains large amounts of isoflavones—daidzein and genistein—that can occupy estrogen receptors and act as estrogens in the laboratory. A food substance with estrogen activity might prolong the effect of maternal hormones, or interfere with hormonal homeostasis in the child.

To this end, Rogan and collaborators developed a series of three cross-sectional pilot studies to help establish methods for future studies of the effects of any exogenous estrogen, including soy infant formula, on the developing infant.

The Sonography study was designed to establish protocols for sonograms for organs not commonly measured in infants. The Physical Examination study was designed to assess gestational age based on the conditions of estrogen-responsive tissues. The Biochemistry study assessed hormonal and biochemical status of full-term infants, and established sampling methods for specimen collection for later studies. As part of the Biochemistry / specimen collection protocol, we also measured soy isoflavones in order to document that infants had high exposures, and tested several methods for analyzing endogenous hormones.

We evaluated ultrasonography for monitoring growth of multiple estrogen-responsive organs in healthy infants and developed organ-growth trajectories. We studied 38 boys (61 visits) from birth to age 6 months and 41 girls (96 visits) from birth to age 1 year using a partly cross-sectional, partly longitudinal design. We measured uterus and ovaries in girls, testes and prostate in boys, and kidneys, breasts, thymus, and thyroid in all children. We imaged all organs from the body surface in one session of < 1hour.

Uterine volume decreased from birth (P < 0.0001), whereas ovarian volume increased sharply until age 2 months and then decreased (P < 0.001). Testicular volume increased with age (P < 0.0001), but prostatic volume showed minimal age trend. Breast bud diameter showed no age trend in girls but declined from birth in boys (P = 0.03). These studies established that examination of multiple estrogen-responsive organs in infants in a single session is feasible in the US, and yields volume estimates useful for assessing potential endocrine disruptor effects on organ growth.


Principal Investigators

Walter J. Rogan, M.D.
Special Volunteer
Tel (919) 541-4578

Selected Publications

  1. Bernbaum JC, Umbach DM, Ragan NB, Ballard JL, Archer JI, Schmidt-Davis H, Rogan WJ. Pilot studies of estrogen-related physical findings in infants. Environmental Health Perspectives 116:416-420 (2008).
  2. Cao Y, Rao SD, Phillips TM, Umbach DM, Bernbaum JC, Archer JI, Rogan WJ. Are breast-fed infants more resilient? Feeding method and cortisol in infants. The Journal of pediatrics 154(3):452-454, 2009. [Abstract]
  3. Cao Y, Calafat AM, Doerge DR, Umbach DM, Bernbaum JC, Twaddle NC, Ye X, Rogan WJ. Isoflavones in urine, saliva and blood of infants - data from a pilot study on the estrogenic activity of soy formula. Journal of exposure science & environmental epidemiology 19(2):223-234, 2009. [Abstract]
  4. Cao Y, Blount BC, Valentin-Blasini L, Bernbaum JC, Phillips T, Rogan WJ. Goitrogenic anions, Thyrotropin, and Thyroid Hormone in Infants.  Environmental Health Perspectives 118:1332-1337, 2010
  5. Valentín-Blasini L, Blount BC, Otero-Santos S, Cao Y, Rogan W.  Perchlorate exposure and dose estimates in infants.  Environ Sci Technol 45:4127–4132, 2011
  6. Nguyen R, Umbach DM, Parad R, Stroehla B, Rogan WJ, Estroff J.  Ultrasonographic Assessment of Estrogen-responsive Organ Growth among Healthy Term Infants: The Soy Estrogen and Development Pilot Study. Pediatr Radiol 41:633-642, 2011

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