Reproductive hormone concentrations and associated anatomical responses: does soy formula affect minipuberty in boys?

J Clin Endocrinol Metab. 2021 May 20;dgab354. doi: 10.1210/clinem/dgab354. Online ahead of print.

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.

Keywords: anogenital distance; luteinizing hormone; minipuberty; penile length; testicular volume; testosterone.