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Objective  Ultra-sensitive hormone assays have detected slight sex differences in blood estradiol (E 2 ) levels in young children before adrenarche. However, the origin of circulating E 2  in these individuals remains unknown. This study aimed to clarify how E 2  is produced in young girls before adrenarche.    Design  This is a satellite project of the Japan Environment and Children’s Study organized by the National Institute for Environmental Studies.    Methods  We collected blood samples from healthy 6-year-old Japanese children (79 boys and 71 girls). Hormone measurements and data analysis were performed in the National Institute for Environmental Studies and the Medical Support Center of the Japan Environment and Children’s Study, respectively.    Results  E 2  and follicle stimulating hormone (FSH) levels were significantly higher in girls than in boys, while dehydroepiandrosterone sulfate (DHEA-S) and testosterone levels were comparable between the two groups. Girls showed significantly higher E 2 /testosterone ratios than boys. In children of both sexes, a correlation was observed between E 2  and testosterone levels and between testosterone and DHEA-S levels. Moreover, E 2  levels were correlated with FSH levels only in girls.    Conclusions  The results indicate that in 6-year-old girls, circulating E 2  is produced primarily in the ovary from adrenal steroids through FSH-induced aromatase upregulation. This study provides evidence that female-dominant E 2  production starts several months or years before adrenarche. The biological significance of E 2  biosynthesis in these young children needs to be clarified in future studies.

Female-dominant estrogen production in healthy children before adrenarche