Reference intervals for plasma concentrations of adrenal steroids measured by LC-MS/MS: Impact of gender, age, oral contraceptives, body mass index and blood pressure status
Open accessAbstract
BACKGROUND: Mass spectrometric-based measurements of the steroid metabolome have been introduced to diagnose disorders featuring abnormal steroidogenesis. Defined reference intervals are important for interpreting such data. METHODS: Liquid chromatography-tandem mass spectrometry was used to establish reference intervals for 16 steroids (pregnenolone, progesterone, 11-deoxycorticosterone, corticosterone, aldosterone, 18-oxocortisol, 18-hydroxycortisol, 17-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, cortisol, cortisone, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androstenedione, testosterone) measured in plasma from 525 volunteers with (n=227) and without (n=298) hypertension, including 68 women on oral contraceptives. RESULTS: Women showed variable plasma concentrations of several steroids associated with menstrual cycle phase, menopause and oral contraceptive use. Progesterone was higher in females than males, but most other steroids were higher in males than females and almost all declined with advancing age. Using models that corrected for age and gender, body mass index showed weak negative relationships with corticosterone, 21-deoxycortisol, cortisol, cortisone, testosterone, progesterone, 17-hydroxyprogesterone and 11-deoxycorticosterone, but a positive relationship with 18-hydroxycortisol. Hypertensives and normotensives showed negligible differences in plasma concentrations of steroids. CONCLUSION: Age and gender are the most important variables for plasma steroid reference intervals, which have been established here according to those variables for a panel of 16 steroids primarily useful for diagnosis and subtyping of patients with endocrine hypertension.
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Several sensitive and robust LC-MS/MS methods for multiple steroids have been developed in recent years and many methods meet the requirements for clinical applications.
“Several sensitive and robust LC-MS/MS methods for multiple steroids have been developed in recent years and many methods meet the re quirements for clinical applications [5 -16].”
From Sex- and age-specific reference intervals of 16 steroid metabolites quantified simultaneously by LC-MS/MS in sera from 2458 healthy subjects aged 0 to 77 years (2024) · cites this paper as [8]
The Introduction (page not available) describes LC-MS/MS methods that measure multiple steroids and their increasing utility in investigating steroidogenesis disorders. It does not establish that many methods meet clinical requirements; the Discussion instead emphasizes the need for accuracy, harmonization, and reference intervals, and notes possible assay interferences. (LLM, conf=0.83)
Experimental — accuracy not yet measuredReference intervals have been published for five to nine adrenal and androgenic steroids in men and women.
“and five to nine adrenal and androgenic steroids in men and women [8,13,14,21]”
From Sex- and age-specific reference intervals of 16 steroid metabolites quantified simultaneously by LC-MS/MS in sera from 2458 healthy subjects aged 0 to 77 years (2024) · cites this paper as [8]
The Results (Reference intervals; page not available) say the study compiled reference intervals for all 16 steroids, accounting for sex and age where needed. This supports the publication of intervals for men and women, but not the attributed range of five to nine steroids. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn eumenorrheic women, protein catabolism is higher at rest and following aerobic endurance exercise in the luteal phase, when estrogen and progesterone are elevated, compared to the early follicular phase when estrogen and progesterone concentrations are low.
“In eumenorrheic women, evidence suggests protein catabolism is higher at rest and following aerobic endurance exercise in the luteal phase, when estrogen and progesterone are elevated, compared to the early follicular phase when estrogen and progesterone concentrations are low [81,164,223,224].”
From International society of sports nutrition position stand: nutritional concerns of the female athlete (2023) · cites this paper as [224]
Table 2 in Results (Menstrual cycle, menopause and oral contraceptive use; page not provided) shows higher median progesterone in luteal than follicular-phase women. The paper does not report estrogen concentrations or protein catabolism at rest or after aerobic endurance exercise, so it does not support the sentence's main finding. (LLM, conf=0.88)
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BackgroundSex differences in 11-oxygenated androgen patterns across adulthood
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- Authors
- Eisenhofer, G., Peitzsch, M., Kaden, D., Langton, K., Pamporaki, C., Masjkur, J., Tsatsaronis, G., Mangelis, A., Williams, T. A., Reincke, M., Lenders, J. W. M., & Bornstein, S. R.
- Affiliations
- University Hospital Carl Gustav Carus (DE)
- Elsevier BV (Netherlands) (NL)
- LMU Klinikum (DE)
- Radboud University Medical Center (NL)
- Corresponding author
- Eisenhofer, Graeme
- ORCID
- Venue
- Clinica Chimica Acta
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 470
- Pages
- 115-124
- ISSN
- 0009-8981 (ISSN-L)
- PMC
- PMC5504266
- OpenAlex
- W2610430925
- Cited by
- 171
- References
- 50
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 24 · 2023: 18 · 2022: 21 · 2021: 23 · 2020: 22 · 2019: 21 · 2018: 6 · 2017: 5
- FWCI
- 11.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Clinica Chimica Acta (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc-nd)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Deutsche Forschungsgemeinschaft (LE3660/1-2, KFO252)
- Horizon 2020 (633983-2)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Keywords
- adrenal steroids, steroid metabolome, sex differences, age effects, body mass index, oral contraceptives, hypertension, endocrine hypertension, cortisol, progesterone, aldosterone, 18-hydroxycortisol, 17-hydroxyprogesterone, 21-deoxycortisol, deoxycorticosterone, corticosterone, dehydroepiandrosterone, testosterone, menopause
- MeSH terms
- Adolescent, Adrenal Glands, Adult, Aged, Aged, 80 and over, Aging, Blood Chemical Analysis, Blood Pressure, Chromatography, Liquid, Contraceptives, Oral, Female, Humans, Male, Middle Aged, Reference Values, Sex Characteristics, Steroids, Body Mass Index, Tandem Mass Spectrometry, Young Adult
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