Reproductive Hormone Concentrations and Associated Anatomical Responses: Does Soy Formula Affect Minipuberty in Boys?

Abstract

Context Soy formula feeding is common in infancy and is a source of high exposure to phytoestrogens, documented to influence vaginal cytology in female infants. Its influence on minipuberty in males has not been established. Objective To assess the association between infant feeding practice and longitudinally measured reproductive hormones and hormone-responsive tissues in infant boys. Design The Infant Feeding and Early Development study was a prospective cohort of maternal-infant dyads requiring exclusive soy formula, cow-milk formula, or breastmilk feeding during study follow-up. Reproductive hormone concentrations and male anatomical measurements were longitudinally assessed from birth to 28 weeks. Setting Clinic-based cohort Participants 147 mother-infant boy pairs Interventions not applicable Main outcome measure Serum testosterone and luteinizing hormone (LH) concentrations, stretched penile length, anogenital distance, and testis volume. Results Median serum testosterone was at pubertal levels at 2 weeks [176 ng/dL (quartiles:124, 232)] and remained in this range until 12 weeks, in all feeding groups. We did not observe differences in trajectories of hormone concentrations or anatomical measures between boys fed soy formula (n=55) and boys fed cow-milk formula (n=54). Compared with breastfed boys (n=38), soy-formula-fed boys had a more rapid increase in penile length (p=0.004) and slower initial lengthening of AGD (p=0.03), but no differences in hormone trajectories. Conclusions Reproductive hormone concentrations and anatomical responses followed similar trajectories in soy and cow-milk formula-fed infant boys. Our findings suggest that these measures of early male reproductive development do not respond to phytoestrogen exposure during infancy.

Effects of Soy Protein Isolate on Fragile X Phenotypes in Mice

“…Feeding marmosets soy infant formula increases testis weight 14% at 120–138 weeks of age [ 106 ], but there is no difference at 35–45 days old [ 107 ]. The National Institute of Environmental Health Sciences Infant Feeding and Early Development (IFED) Study of a prospective cohort of maternal-infant dyads exclusively fed soy formula, cow milk formula, or breast milk did not find statistical differences in trajectories of hormone concentrations or anatomical measures between boys fed soy formula and cow milk formula; however, compared with breastfed, soy formula-fed boys had a more rapid increase in penile length and slower initial lengthening of AGD with data adjusted for weight-for-length z-scores [ 35 , 36 , 108 ]. Despite lack of statistical significance with N = 38–55 infants per cohort, the trajectories show trends for the highest penile length in the soy cohort followed by cow milk formula and then breast milk.…”

Phytoestrogens and Health Effects

“…When differences were observed in human subjects consuming soy-based infant formula, it was generally in comparison to breastfeeding, not to cow-milk formula [ 227 ]. Likewise, in [ 228 ] it was shown that the neonatal use of soy-based infant formula reduced the testes diameter in four-month-old-babies.…”

“…When such an issue was studied in humans it essentially dealt with a high neonatal exposure to soy phytoestrogens through soy-based infant formula. Finally, the results are unclear, with cases showing anti-androgenic effects [ 228 ], cases showing androgenic effects [ 227 ] and cases where no effect could be reported on androgenic biomarkers [ 270 ]. In adult men, the over-consumption of soybeans and isoflavones decreases sperm production via a dramatic drop in LH and testosterone [ 214 ].…”

“…However, it is known that aromatase, which is able to convert testosterone into estradiol as well as GPER and Erβ, for which isoflavones have a great affinity are all involved in the male-genital-tract development in humans [ 272 ]. Therefore, although the effect of isoflavones on the increased penis length in infants fed soy-based formula, as reported in [ 227 ], is not explained so far, the interaction of phytoestrogens with the androgen axis in male humans requires attention. Moreover, early heavy phytoestrogen exposure through infant formulas can definitively have an endocrine effect in male and female babies.…”

Sexual Dimorphism in Kisspeptin Signaling

“…The NTS is partially responsible for establishing sexually dimorphic brain function that controls male reproductive physiology [ 136 , 137 ]. NTS also plays an important role in the development of male reproductive organs and reproductive function [ 138 , 139 , 140 , 141 , 142 ]. Remarkably, there is no equivalent neonatal estradiol or testosterone surge in females [ 143 ].…”