ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Journal of clinical endocrinology and metabolism vol. 105,3 (2020):754–768. doi: https://academic.oup.com/jcem/article/105/3/754/5624050

The authors used state-of-the-art liquid chromatography tandem mass spectrometry to establish sex-specific reference ranges for estrone (E1) and estradiol (E2) throughout life and evaluate sex-differences.

Evaluating circulating estrogens is necessary in several clinical conditions in girls and women throughout life, as well as in specific situations in boys and adult men. This requires highly specific and sensitive standardized assays and liquid chromatography tandem mass spectrometry (LC–MS/MS) is now considered as the reference method (1). However, most reference values still rely on immunoasssays which lack sensitivity for very low ranges such as found in infants, prepubertal children or adolescent boys.

In this study, serum samples from 1838 healthy subjects (772 boys and men/1066 girls and women; selected from 5 different cohorts) were analyzed for estrogen concentrations. E2 was detectable in 96% and 63% of all female and male serum samples, respectively. E1 was detectable in 89% in both sexes. From infancy until puberty onset, E2 was detectable in 68% and 22% of the female and male samples, respectively, while E1 was detectable in 88% (female) and 74% (male). E3 was detectable in only very few samples. In infant girls, both E1 and E2 concentrations were significantly higher around 3 months of age than concentrations at other prepubertal ages, confirming the rise associated with mini-puberty (2,3). The authors found clear sex differences, as E2 levels in infant boys were mostly undetectable. E1 and E2 concentrations increased with age and pubertal stage both in boys and girls. The highest E2 concentration in prepubertal girls aged <7 years was 20 pmol/l, while older prepubertal girls (>7 years) had slightly higher E2 concentrations. Prepubertal girls had significantly higher levels of E2 than prepubertal boys. Almost all girls with breast stage B2 or more had levels >10 pmol/l. In conclusion, this article provides much needed reference ranges for estrogen values throughout life.

References:

1. Wang Q, Rangiah K, Mesaros C, et al. (2015). Ultrasensitive quantification of serum estrogens in postmenopausal women and older men by liquid chromatography-tandem mass spectrometry. Steroids. 96:140–152.

2. Chellakooty M, Schmidt IM, Haavisto AM, et al. (2003). Inhibin A, inhibin B, follicle-stimulating hormone, luteinizing hormone, estradiol and sex hormone-binding globulin levels in 473 healthy infant girls. J Clin Endocrinol Metab. (2003); 88(8):3515–3520.

3. Johannsen TH, Main KM, Ljubicic ML, et al. (2018). Sex differences in reproductive hormones during mini-puberty in infants with normal and disordered sex development. J Clin Endocrinol and Metab 103(8):3028–3037.