Reference intervals of nine steroid hormones over the life-span analyzed by LC-MS/MS: Effect of age, gender, puberty, and oral contraceptives
Abstract
New reference intervals need to be established for a new analytical method with improved sensitivity and specificity. We aimed to establish the new reference intervals from infancy to senescence of nine steroid hormones (cortisol, cortisone, progesterone, 17-hydroxyprogesterone (17-OHP), androstenedione, testosterone, estradiol, DHEAS, and aldosterone) for LC-MS/MS method. Serum samples from 4678 reference individuals (age range: 0.3-79 years) were measured with LC-MS/MS. Samples were collected between 7 a.m. and 10 a.m. Exclusion criteria were concomitant endocrine diseases and body mass index ≥ 33. Generalized additive model for location, scale and shape, the nonparametric or robust method was applied. We established the reference intervals of the nine steroid hormones by sex, age, and pubertal stage. Below the age of one, we observed the surge of androgen and estrogen which implied mini-puberty. At the same period of life, aldosterone and cortisone levels were very high reflecting physiological hyperaldosteronism. An increase of steroid hormones during the pubertal development and slow decrease towards senescence after the peak at early adulthood were observed. Due to the increase of CBG synthesis, cortisol levels were increased under oral contraceptives (OC) significantly (p < 0.0001), while OC suppressed progesterone, 17-OHP, androstenedione, and estradiol (p < 0.0001). Our results will facilitate the interpretation of patient data in routine diagnostics with the use of LC-MS/MS method. Since LC-MS/MS methods have shown good comparability among the different laboratories, our reference intervals can be further adopted in other laboratories equipped with LC-MS/MS, once the validation with a small number of reference samples is performed.
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In that study, nine steroids (PROG, DHEAS, 17-OHP, Adione, T, E2, ALDO, cortisone and cortisol) were measured in 4678 healthy subjects aged 0.3 to 79 years.
“In that study, nine steroids (PROG, DHEAS, 17-OHP, Adione, T, E2, ALDO, cortisone and cortisol) were measured in 4678 healthy subjects aged 0.3 to 79 years [23].”
Only one study reports a LC-MS/MS method and sex- and age-specific reference intervals encompassing the whole lifetime from birth to senescence.
“To our knowledge, only one study reports a LC-MS/MS method and sex- and age-specific reference intervals encompassing the whole lifetime from birth to senescence [23].”
Comparing our data to theirs, the reference intervals of all these steroid metabolites were in general very similar in the age range from 10 to 77 years.
“Comparing our data to theirs, the reference intervals of all these steroid metabolites were in general very similar in the age range from 10 to 77 years.”
During puberty, testes-derived testosterone levels increase 20-fold in males, but remain low in females, resulting in circulating testosterone concentrations at least 15 times higher in males than in females of any age.
“During puberty, testes-derived testosterone levels increase 20-fold in males, but remain low in females, resulting in circulating testosterone concentrations at least 15 times higher in males than in females of any age [4, 25].”
From Transgender Women in the Female Category of Sport: Perspectives on Testosterone Suppression and Performance Advantage (2021) · cites this paper as [25]
A large study (n = 4678) by Bae and coworkers presented sex- and age-specific reference intervals throughout life from 0.3 to 79 years of age for cortisol, cortisone, aldosterone, DHEAS, PROG, 17-OHP, androstenedione, T, and E2.
“A large study (n = 4678) by Bae and coworkers presented sex- and age-specific reference intervals throughout life from 0.3 to 79 years of age for cortisol, cortisone, aldosterone (ALDO), DHEAS, PROG, 17-hydroxyprogesterone (17-OHP), andro stenedione (Adione), T, and E2 [23].”
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.”
The reference ranges below 10 years differ partly for some metabolites.
“By contrast, the reference ranges below 10 years differs partly for some of the metabolites”
Similar differences between the two studies were observed for PROG, DHEAS, 17-OHP and Adione when comparing reference ranges for children.
“Similar differences between the two studies were observed for PROG, DHEAS, 17-OHP and Adione, when comparing the reference ranges for children.”
In the study by Bae, T was below LLOQ (0.035 nmol/L) in many samples from a few months to 10 years.
“where e.g. T in the study by Bae [23] was below LLOQ (0.035 nmol/L) in many samples in the range from few months to 10 years”
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References 33 · Cited by 123
- Authors
- Bae, Y. J., Zeidler, R., Baber, R., Vogel, M., Wirkner, K., Loeffler, M., Ceglarek, U., Kiess, W., Körner, A., Thiery, J., & Kratzsch, J.
- Affiliations
- Leipzig University (DE)
- University Hospital Leipzig (DE)
- Corresponding author
- Bae, Yoon Ju
- ORCID
- Venue
- The Journal of Steroid Biochemistry and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 193
- Pages
- 105409
- ISSN
- 0960-0760 (ISSN-L)
- OpenAlex
- W2949507904
- Cited by
- 123
- References
- 33
- Citations by year
- 2026: 13 · 2025: 18 · 2024: 18 · 2023: 25 · 2022: 21 · 2021: 14 · 2020: 12 · 2019: 2
- FWCI
- 9.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- LIFE – Leipzig Research Center
- University of Leipzig
- European Union
- European Social Fund (ESF)
- European Regional Development Fund (ERDF)
- Free State of Saxony
- Topics
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- reference values, steroid hormones, lifespan, puberty, oral contraceptives, cortisol, cortisone, progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, estradiol, dehydroepiandrosterone sulfate, aldosterone, sex hormone-binding globulin, minipuberty, sex differences, age differences
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Child, Child, Preschool, Chromatography, Liquid, Contraceptives, Oral, Female, Humans, Infant, Longevity, Male, Middle Aged, Puberty, Reference Values, Sex Characteristics, Steroids, Tandem Mass Spectrometry, Young Adult
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