Background: Specific measurement of low serum / plasma concentrations of 17β-estradiol (E2) is important in pre-pubertal and pubertal children in routine paediatric endocrinology. However, there is still a gap in available reference intervals (RIs) for E2 in paediatrics. The study was partially funded by the German Ministry of Health, grant number 2519FSB503.
Objective: First, we technically developed a highly sensitive LC-MS/MS method for E2. We then measured left-over control samples of 454 boys and 963 girls for calculation of RIs. Secondly, we performed a systematic review of published E2 RIs in children and adolescents. This was conducted by PubMed and Google scholar. Selection criteria were: a cohort size >700 and an age range covering the complete pediatric age range in both sexes.
Results: 157 initial literature hits were documented and screened. Only four publications fulfilled our selection criteria. We then compared the RIs of the four selected studies and of our own study. Two publication used an immunoassay-based method (Elmlinger et al.1 and Konforte et al.2) and three used an LC/MS-MS based method (Frederiksen et al.3, Bae et al.4, and our own study). The LODs ranged from 3 to 37 pmol/l and age groups were separated under different conditions, e.g. statistical reasons or fixed age groups. Although measurement and statistical methods were different, we found a similar trend in all studies. Mini-puberty with an increase of E2 was clearly visible in four of the five studies in both sexes. Until start of puberty, there was no significant sex difference. In girls, E2 then increased markedly up to 1000 pmol/l at the age of 16 years. Interestingly, in boys, we also found considerable increase of E2 up to 300 pmol/l at the age of 14 years. Therefore, pubertal E2 levels in boys overlapped considerably with levels found in girls in both, the literature studies and our own study.
Conclusion: Our study provides a comprehensive analysis of RIs of E2 in children and adolescents of both sexes covering the complete pediatric age range. Interestingly, boys may show pubertal E2 levels comparable with girls even though boys usually do not show breast development. Therefore, regional differences in the pubertal regulation and cellular action of estrogens and androgens must exist in breast tissue. Our data will help to get more insights into the role and the variability of E2 during development from infancy to early adulthood in both sexes.
15 Sep 2022 - 17 Sep 2022