Sex, age, pubertal development and use of oral contraceptives in relation to serum concentrations of DHEA, DHEAS, 17α-hydroxyprogesterone, δ4-androstenedione, testosterone and their ratios in children, adolescents and young adults
Abstract
The influence of sex, age, pubertal development and oral contraceptives on dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), 17α-hydroxyprogesterone (17-OHP), Δ4-androstenedione (Adione), testosterone (T), calculated free testosterone (fT), free androgen index (FAI) and selected ratios in 1798 serum samples from healthy children, adolescents and young adults was evaluated. Samples were analyzed by Turboflow-LC-MS/MS. Sex hormone-binding globulin was analyzed by immunoassay. All steroid metabolite concentrations were positively associated with age and pubertal development in both sexes and generally higher in males than in females except for Adione. The pubertal rise in T in males was more pronounced compared to females, reflecting contribution from the testes. Ratios between steroid metabolites varied and depended on sex and age. All ratios were lower during infancy compared to later in life. Use of oral contraceptives significantly lowered serum concentrations of all steroid metabolites, fT, FAI, the 17-OHP/Adione, the Adione/T and the DHEA/Adione ratios, but not the DHEA/DHEAS ratio. We provide reference ranges for DHEA, DHEAS, 17-OHP, Adione, T, fT, FAI and selected ratios in relation to sex, age and pubertal development. Use of oral contraceptives strongly influences adrenal steroidogenesis and should be considered when diagnosing and monitoring treatment of patients with disorders of sex development.
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Reference intervals have been published for five androgen metabolites in prepubertal and pubertal children and adolescents.
“five androgen metabolites in prepubertal and pubertal children and adolescents [20]”
Reference intervals covering the whole life span for all metabolites in the steroid hormone biosynthesis quantified by sensitive and robust analytical methods are sparse or not existing.
“Background: Reference intervals covering the whole life span for all the metabolites in the steroid hormone biosynthesis quantified by sensitive and robust analytical methods are sparse or not existing.”
Multiple and simultaneously measured metabolites allow for calculation of substrate to product ratios that can provide information on specific enzyme activities and steroid pathway usage.
“Multiple and simultaneously measured metabolites allow for the calculation of substrate to product ratios that can provide information on specific enzyme activities and steroid pathway usage [20].”
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- Authors
- Søeborg, T., Frederiksen, H., Mouritsen, A., Johannsen, T. H., Main, K. M., Jørgensen, N., Petersen, J. H., Andersson, A.-M., & Juul, A.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Søeborg, Tue
- ORCID
- Venue
- Clinica Chimica Acta
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 437
- Pages
- 6-13
- ISSN
- 0009-8981 (ISSN-L)
- OpenAlex
- W1980312294
- Cited by
- 81
- References
- 32
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 6 · 2023: 11 · 2022: 9 · 2021: 10 · 2020: 7 · 2019: 5 · 2018: 4 · 2017: 4 · 2016: 7 · 2015: 1
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinica Chimica Acta (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Danish National Advanced Technology Foundation (14-2013-4)
- Danish Agency for Science, Technology and Innovation (09-067180)
- ReproSund consortium (EU InterRegIV (150879, 167158)
- ReproHigh consortium (EU InterReg IV
- Danish Ministry of Health, the Danish Environmental Protection Agency and the Danish Agency for Science, Technology and Innovation (271070678)
- Kirsten and Freddy Johansen Foundation
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- dehydroepiandrosterone, DHEA sulfate, 17-hydroxyprogesterone, Δ4-androstenedione, testosterone, free testosterone, free androgen index, oral contraceptives, puberty, sex differences, age-related changes, reference values, adrenal steroidogenesis, disorders of sex development, children and adolescents
- MeSH terms
- Adolescent, Adult, Age Factors, Androstenedione, Child, Child, Preschool, Contraceptives, Oral, Cross-Sectional Studies, Dehydroepiandrosterone, Female, Humans, Infant, Male, Progesterone, Puberty, Sex Factors, Testosterone, Cohort Studies, Biomarkers, Dehydroepiandrosterone Sulfate, Young Adult
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