ESPE Yearbook of Paediatric Endocrinology

Clin Endocrinol (Oxf). 2025 Jun;102(6):656-663. doi: 10.1111/cen.15215. PMID: 39930933.

Brief summary: This prospective study reports a positive correlation between urinary estrone levels during late puberty and both adiposity and metabolic risk in 321 Chilean girls. This association was absent in girls with premature adrenarche, suggesting the involvement of alternative pathways in their metabolic risk.

Premature adrenarche has been linked to increased metabolic risk throughout puberty (1, 2). However, it remains unclear whether these effects are driven by androgens, estrogens, or a combination of both. This study evaluated the association between urinary estrogen levels (estradiol and estrone) and metabolic risk during late puberty, and determined whether this relationship differs between girls with and without premature adrenarche.

Multilevel analysis revealed a positive correlation between urinary estrone levels and body mass index, waist circumference, and body fat percentage at Tanner stage 4, one year post-menarche, and 4 years post-menarche. In contrast, urinary estradiol levels showed no such association. Similarly, estrone concentrations were positively correlated with the metabolic syndrome score (MetS score), whereas estradiol concentrations were not. In girls with premature adrenarche (defined by elevated DHEA-S levels at age 7), neither estrone nor estradiol levels were correlated with the MetS score.

These findings suggest that, in adolescent girls, metabolic risk may be mediated in part by estrogens, particularly estrone, highlighting its potential role as a biomarker of metabolic risk. Moreover, the lack of association between urinary estrogens and MetS score in girls with premature adrenarche suggests the potential role of androgens in their metabolic disturbances.

Taken together, these results support the existence of distinct biological pathways underlying metabolic risk during puberty in girls with and without premature adrenarche.

References: 1. Corvalán C, Uauy R, Mericq V. Obesity is positively associated with dehydroepiandrosterone sulfate concentrations at 7 y in Chilean children of normal birth weight. Am J Clin Nutr. 2013 Feb;97(2):318-25.2. Pereira A, Merino PM, Santos JL, Iñiguez G, Cutler GB Jr, Corvalan C, Mericq V. High DHEAS in girls and metabolic features throughout pubertal maturation. Clin Endocrinol (Oxf). 2022 Mar;96(3):419-427.