ESPE Yearbook of Paediatric Endocrinology

regis.coutant@chu-angers.fr J Clin Endocrinol Metab. 2022 Mar 24;107(4):e1568–e1576. doi: 10.1210/clinem/dgab845https://pubmed.ncbi.nlm.nih.gov/34918072/

Brief Summary: This cross-sectional study describes how levels of Sertoli and Leydig cell hormones differ between 351 obese and overweight boys aged 5–19 years from a normative collective of 652 healthy, non-overweight, non-obese boys of similar age and Tanner stage from France.

The authors showed that from age 12–14 years or Tanner G1-2 onwards, overweight and obese (ow/ob) boys had lower levels of inhibin B, with 22% having levels <5th percentile. A significant difference in testosterone levels could be shown from the age of 14 or Tanner G4 onward, with 28% of the ow/ob boys having levels <5th percentile. There were no differences found in gonadotrophin levels. A higher estradiol level was found already before puberty from age 8 onward, showing excess aromatization of adrenal androgens. The lower inhibin B levels were highly correlated to estradiol levels and FSH, indicating a contribution of excess aromatization, as well as primary Sertoli cell impairment. The testosterone levels were inversely correlated to fat mass measured by DXA. AMH values did not differ, but there was a higher dispersion in ow/ob boys. Lower AMH levels were physiologically correlated to testosterone but also to fasting insulin, indicating an effect of insulin resistance on Sertoli cell function. The measured effects on inhibin B and testosterone levels confirmed previous data showing altered testicular growth and hormone production in obese boys [1,2]. The precise assessments of body composition and metabolism on large numbers of boys revealed potential underlying causes of these variations. Due to the cross-sectional design, it was not possible to evaluate whether these were persistent changes, but data on adult men suggest a lasting effect on sperm production [2,3].

While there are other positive nutritional drivers of sex hormone secretion [4] these data suggest a inhibitory effect of fat mass on testosterone in boys. This may explain why some boys with OW/OB present with delayed puberty [1]. Further longitudinal research will be needed to assess these questions and whether weight loss can reverse the observed alterations.

References: 1. Denzer C, Weibel A, Muche R, Karges B, Sorgo W, Wabitsch M. Pubertal development in obese children and adolescents. Int J Obes (Lond). 2007 Oct;31(10):1509–19. doi: 10.1038/sj.ijo.0803691. Epub 2007 Jul 24. PMID: 17653066. 2. Winters SJ, Wang C, Abdelrahaman E, Hadeed V, Dyky MA, Brufsky A. Inhibin-B levels in healthy young adult men and prepubertal boys: is obesity the cause for the contemporary decline in sperm count because of fewer Sertoli cells? J Androl. 2006 Jul–Aug;27(4):560–4. doi: 10.2164/jandrol.05193. Epub 2006 Apr 1. PMID: 16582411. 3. Andersen JM, Herning H, Aschim EL, Hjelmesæth J, Mala T, Hanevik HI, Bungum M, Haugen TB, Witczak O. Body Mass Index Is Associated with Impaired Semen Characteristics and Reduced Levels of Anti-Müllerian Hormone across a Wide Weight Range. PLoS One. 2015 Jun 12;10(6):e0130210. doi: 10.1371/journal.pone.0130210. PMID: 26067627; PMCID: PMC4466334. 4. Lam BYH, Williamson A, Finer S, Day FR, Tadross JA, Gonçalves Soares A, Wade K, Sweeney P, Bedenbaugh MN, Porter DT, Melvin A, Ellacott KLJ, Lippert RN, Buller S, Rosmaninho-Salgado J, Dowsett GKC, Ridley KE, Xu Z, Cimino I, Rimmington D, Rainbow K, Duckett K, Holmqvist S, Khan A, Dai X, Bochukova EG; Genes & Health Research Team, Trembath RC, Martin HC, Coll AP, Rowitch DH, Wareham NJ, van Heel DA, Timpson N, Simerly RB, Ong KK, Cone RD, Langenberg C, Perry JRB, Yeo GS, O’Rahilly S. MC3R links nutritional state to childhood growth and the timing of puberty. Nature. 2021 Nov;599(7885):436–441. doi: 10.1038/s41586-021-04088-9. Epub 2021 Nov 3. PMID: 34732894; PMCID: PMC8819628.