We thank Dr. Bougnères for his letter (1) and his interest in our recent publication (2). He raises several noteworthy issues; we respond to each in turn:
First, Bougnères highlights the potential for confounding by race to influence our result that soy-fed boys had slower penile growth compared with breastfed boys because 78% (not 80%) of the soy-fed infants were black in comparison to only 37% (not 17%) of the breastfed infants. In our study, penile length was similar at birth in white (mean 3.5 cm, SD 0.4) and black infants (mean 3.6 cm, SD 0.5). Growth differences by race may emerge, but we likely do not have the sample size to stratify analyses by race within feeding group. Also, we had no stated prior hypothesis about the breastfed infants; consequently, we regarded this difference as a description, not a conclusion.
Second, we do not present correlations between penile growth and circulating testosterone in our study. Boas et al examined penile growth from birth to age 3 years, a wider age range than our study, and while the Boas et. al study had a larger sample size, testosterone was measured once at age 3 months (3). A future analysis in our cohort will focus on examining the association between testosterone trajectories and penile growth, using ≥3 testosterone measurements between 2 weeks and 28 weeks and up to 10 measures of penile length from birth to 28 weeks.
Third, Bougnères raises an important point regarding the differences in demographic characteristics between the feeding groups in our study. Larger studies or pooling data across multiple studies of male minipuberty would help to address this concern. However, we believe demographic differences to be a problem mainly with comparisons involving breastfed infants.
Finally, we restricted the study population to term birth defined as 37 to 42 weeks gestation and birthweight between 2500 and 4500 grams. To address the possibility that the anatomical outcomes (penile length, testis volume, and anogenital distance) were related to age and, within age, to body size, we used the z-score of weight-for-length as an adjustment for possible confounding. Residual confounding remains a possibility.
Main et al reports interesting results regarding testis development (4), but interpreting these differences is difficult given the absence of information on the prenatal environment and fetal growth trajectories of the infants included.
We appreciate the attention Dr. Bougnères gave to our paper and echo his call for additional research focused on minipubertal development.
Acknowledgments
Financial Support: This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.
Contributor Information
Helen B Chin, Department of Global and Community Health, George Mason University, Fairfax, VA, USA.
Andrea Kelly, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Pediatrics, Division of Endocrinology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Margaret A Adgent, Department of Health Policy, Vanderbilt University Medical Center, Nashville, TN, USA.
Stacy A Patchel, Westat, Inc., Durham, NC, USA.
Kerry James, FHI 360, Durham, NC, USA.
Donald Walt Chandler, Endocrine Sciences, LabCorp, Calabasas Hills, CA, USA.
Babette S Zemel, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA.
Joan I Schall, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA.
Eileen G Ford, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA.
Kassa Darge, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Radiology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Virginia A Stallings, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA.
Donna D Baird, Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
Walter J Rogan, Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
David M Umbach, Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
Additional Information
Disclosures: The authors have nothing to disclose.
References
- 1. Bougnères P. Letter to the editor from Bougnères: “Reproductive hormone concentrations and associated anatomical responses: does soy formula affect minipuberty in boys?” J Clin Endocrinol Metab. Published online October 06, 2021. doi: 10.1210/clinem/dgab716 [DOI] [PubMed] [Google Scholar]
- 2. Chin HB, Kelly A, Adgent MA, et al. Reproductive hormone concentrations and associated anatomical responses: does soy formula affect minipuberty in boys? J Clin Endocrinol Metab 2021;106(9):2635-2645. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Boas M, Boisen KA, Virtanen HE, et al. Postnatal penile length and growth rate correlate to serum testosterone levels: a longitudinal study of 1962 normal boys. Eur J Endocrinol. 2006;154(1):125-129. [DOI] [PubMed] [Google Scholar]
- 4. Main KM, Toppari J, Suomi AM, et al. Larger testes and higher inhibin B levels in Finnish than in Danish newborn boys. J Clin Endocrinol Metab. 2006;91(7):2732-2737. [DOI] [PubMed] [Google Scholar]
