Circadian Rhythm of Salivary Cortisol, 17α-Hydroxyprogesterone, and Progesterone in Healthy Children
Abstract
Very few reference intervals for salivary steroids in children have been established to date (1). Even the manufacturers of salivary steroid assays do not provide sufficient reference data for their products. This lack of information is surprising because the measurement of salivary steroids has been accepted as being noninvasive and stress-free (2)(3). In particular, psychiatric and neuro-endocrinologic experiments are frequently designed with saliva as the medium of choice for steroid analysis (4)(5)(6). A large variety of stressors can rapidly affect the adrenal cortex, causing increased adrenal steroid concentrations. For example, hypoglycemia (7) or physical exercise (8) are potent physiologic stressors, whereas fear (9), feelings of inferiority (10)(11), or experiences at school (12)(13) can affect the adrenal cortex activity as psychologic stressors. The taking of blood can also influence adrenal steroid concentrations in children; saliva collection, however, is almost stress-free (14). The use of saliva for steroid analysis in children is therefore an excellent alternative to blood.
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The paper found weak correlation or partial positive correlation for hormone circadian oscillations between glucocorticoids and gonadal hormones.
“As stated above, we found weak correlation or partial positive correlation for hormone circadian oscillations; see e.g. [114–116].”
From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [116]
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“, 2001) between 2:00-4:30pm to avoid post-awakening increases in hormones (Groschl et al., 2003) in 5 ml polypropylene vials (PGC Scientifics Corporation, MD).”
BackgroundMethodDeveloping physiologic stress profiles for school-age children who stutter
Ortega, A. Y., & Ambrose, N. G. (2011) · Journal of Fluency Disorders · doi:10.1016/j.jfludis.2011.04.007 · Cited by 25 · see citing works
“Cortisol reference measures were based on those developed by Gröschl, Rauh, and Dörr (2003).”
MethodHuman Sexual Differences in the Use of Social Ostracism as a Competitive Tactic
Benenson, J. F., Hodgson, L., Heath, S., & Welch, P. J. (2008) · International Journal of Primatology · doi:10.1007/s10764-008-9283-4 · Cited by 25 · see citing works
“The mean levels of salivary cortisol for the preplay (x= 5.92 pmo/L, SD=1.51) and postplay (x=4.57 pmo/L, SD=1.28) samples were within the range of established norms for children 11–13 yr of age at noon time (x= 6.00 pmo/L, ±3.30) (Groschl et al. 2003).”
BackgroundInfluentialUrlacher, S., Kim, E. Y., Luan, T., Young, L. J., & Adjetey, B. (2022) · American Journal of Human Biology · doi:10.1002/ajhb.23811 · Cited by 21 · see citing works
“First, cortisol has a strong pulsatile and diurnal pattern of secretion among humans and likely most other primates (Adam & Kumari, 2009; Gröschl et al., 2003).”
BackgroundSubstitution therapy in adult patients with congenital adrenal hyperplasia
Reisch, N. (2014) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2014.11.002 · Cited by 23 · see citing works
The effects of audiovisual distraction on children's pain during laceration repair
Ha, Y. O., & Kim, H. S. (2013) · International Journal of Nursing Practice · doi:10.1111/ijn.12165 · Cited by 22 · see citing works
Hadwin, J. A., Lee, E. J., Kumsta, R., Cortese, S., & Kovshoff, H. (2019) · Evidence-Based Mental Health · doi:10.1136/ebmental-2019-300098 · Cited by 22 · see citing works
Özdoğan, H., Çetinalp, S., Kuran, G., Tuğal, Ö., Tahiroglu, M., HERDEM, Ü. E., & Haytoğlu, S. (2017) · Journal of Clinical Anesthesia · doi:10.1016/j.jclinane.2017.03.001 · Cited by 21 · see citing works
Kara, D., Bayrak, N. A., Volkan, B., Uçar, C., Cevizci, M. N., & Yıldız, S. (2018) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0000000000002142 · Cited by 21 · see citing works
Schröder, M. A. M., van Herwaarden, A. E., Span, P. N., van den Akker, E. L. T., Bocca, G., Hannema, S. E., van der Kamp, H. J., Kort, S. W. K. D., Mooij, C. F., Schott, D. A., et al. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab826 · Cited by 20 · see citing works
Volkan, B., Bayrak, N. A., Uçar, C., Kara, D., & Yıldız, S. (2019) · Saudi Journal of Gastroenterology · doi:10.4103/sjg.sjg_493_18 · Cited by 19 · see citing works
“[15] A previous study reported s‐cortisol concentrations >28 nmol/L to indicate a high stress response in children.[16] In our study, some patients in both groups had higher s‐cortisol levels in different stages of the saliva sampling.”
Durán‐Carabali, L. E., Henao-Pacheco, M. L., Clavijo, A. ́. G., & Dueñas, Z. (2020) · Research in Developmental Disabilities · doi:10.1016/j.ridd.2020.103807 · Cited by 19 · see citing works
Dispatches from the Interface of Salivary Bioscience and Neonatal Research
Voegtline, K., & Granger, D. A. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00025 · Cited by 19 · see citing works
Progesterone and estrogen responsiveness to father‐toddler interaction
Gettler, L. T., McDade, T. W., Agustin, S. S., & Kuzawa, C. W. (2013) · American Journal of Human Biology · doi:10.1002/ajhb.22396 · Cited by 18 · see citing works
“…of other downstream steroid hormones, particularly CORT, and, relatedly, P4 might also decline during this afternoon study period due to circadian biology (Gr€oschl et al., 2003; Kage et al., 1982; Wirth et al., 2007), whereas E2 regulation is potentially tightly linked to its precursor, T.”
BackgroundAdriaansen, B. P. H., Kamphuis, J. S., Schröder, M. A. M., Olthaar, A. J., Bock, C., Brandt, A. M., Stikkelbroeck, N. M. M. L., Lentjes, E. G. W. M., Span, P. N., Sweep, F. C. G. J., et al. (2022) · Clinical Endocrinology · doi:10.1111/cen.14690 · Cited by 16 · see citing works
“In the early morning, A4 and 17‐OHP are at their highest levels and decrease during the day, which is consistent with a diurnal rhythm seen in previous studies.(8,9,20) This rhythm emphasises the importance of time‐controlled sample collection and time‐specific reference values for monitoring CAH patients during the d…”
BackgroundMcHale, T. S., Zava, D. T., Hales, D., & Gray, P. B. (2015) · Adaptive Human Behavior and Physiology · doi:10.1007/s40750-015-0030-8 · Cited by 18 · see citing works
“To address circadian rhythms and nutrition-related factors (Groschl et al. 2003), efforts were made to standardize times of practices and games.”
BackgroundHeritability of Cortisol Regulation in Children
Gustafsson, P. A., Gustafsson, P. E., Anckarsäter, H. S., Lichtenstein, P., Ljung, T., Nelson, N., & Larsson, H. (2011) · Twin Research and Human Genetics · doi:10.1375/twin.14.6.553 · Cited by 17 · see citing works
“However, the impact of sex on CAR is said to be rather small (Pruessner et al., 1997; Wüst et al., 2000a), and several studies have reported similar cortisol levels in boys and girls (Gröschl et al., 2003, Kiess et al., 1995, Knutsson et al., 1997).”
BackgroundFraser, R., Gower, D. B., Honour, J. W., Ingram, M. C., Kicman, A. T., Makin, H. L. J., & Stewart, P. M. (2010) · Springer eBooks · doi:10.1023/b135931_5 · Cited by 17 · see citing works
Salivary biomarkers may measure stress responses in critically ill children
Tzira, D., Prezerakou, A., Papadatos, I., Vintila, A., Bartzeliotou, Α., Apostolakou, F., Papassotiriou, I., & Papaevangelou, V. (2018) · SAGE Open Medicine · doi:10.1177/2050312118802452 · Cited by 17 · see citing works
“PRISM More than 8(29) Up to 8(36) Mechanical ventilation Yes (46) No (19) Total days in PICU More than 3(43) Up to 3(22) Vasoactive drugs Yes (9) No (56)”
BackgroundTaking the Lab to the Field: Monitoring Reproductive Hormones in Population Research
Valeggia, C. R. (2007) · Population and Development Review · doi:10.1111/j.1728-4457.2007.00183.x · Cited by 16 · see citing works
Klentrou, P., Giannopoulou, A., McKinlay, B. J., Wallace, P. J., Muir, C., Falk, B., & Mack, D. E. (2016) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2015-0668 · Cited by 16 · see citing works
Mall, C., Schmidt, S., Neuberger, E. W. I., Kirsch, P., Simon, P. D., & Dettweiler, U. (2019) · Frontiers in Public Health · doi:10.3389/fpubh.2019.00026 · Cited by 16 · see citing works
Evaluation of adrenal function in critically ill children
Balbão, V. D. M. P., Costa, M. M. A., de Castro, M., & Carlotti, A. P. D. C. P. (2014) · Clinical Endocrinology · doi:10.1111/cen.12444 · Cited by 14 · see citing works
Fibromyalgia pathogenesis explained by a neuroendocrine multistable model
Demori, I., Losacco, S., Giordano, G., Mucci, V., Blanchini, F., & Burlando, B. (2024) · PLOS ONE · doi:10.1371/journal.pone.0303573 · Cited by 14 · see citing works
The Impact of Asthma Control on Salivary Cortisol Level in Adult Asthmatics
Shin, Y. S., Liu, J. N., Kim, J., Nam, Y., Choi, G., Park, H., & Premier Researchers Aiming New Era in Asthma and Allergic Diseases (PRANA) Study Group (2014) · Allergy Asthma and Immunology Research · doi:10.4168/aair.2014.6.5.463 · Cited by 14 · see citing works
“This discordance between children and adult patients might be explained by age of study population, because cortisol levels depend on age.(9) Salivary cortisol levels vary greatly between individuals and confounding factors such as smoking and adherence to the saliva collection protocol may change the results.”
BackgroundUrlacher, S., Liebert, M., & Konečná, M. (2018) · Stress · doi:10.1080/10253890.2017.1414798 · Cited by 15 · see citing works
Cortisol daily rhythm in saliva of healthy school children
Tzortzi, C., Proff, P., Redlich, M., Aframian, D., Palmon, A., Golan, I., Muessig, D., Wichelhaus, A., & Baumert, U. (2009) · International Dental Journal · doi:10.1016/s0020-6539(20)33798-9 · Cited by 13 · see citing works
Condon, E. M. (2016) · Research in Nursing and Health · doi:10.1002/nur.21744 · Cited by 12 · see citing works
“The authors reported that this not only led to infant stress but posed a major safety concern due to risk of swallowing the swab (Groschl et al., 2003).”
BackgroundBedtime Salivary Cortisol as a Screening Test for Cushing Syndrome in Children
Ueland, G. Å., Kellmann, R., Jørstad Davidsen, M., Viste, K., Husebye, E. S., Almås, B., Storr, H. L., Sagen, J. V., Mellgren, G., Júlíusson, P. B., et al. (2021) · Journal of the Endocrine Society · doi:10.1210/jendso/bvab033 · Cited by 12 · see citing works
“There are a few studies that report on expected normal levels of salivary cortisol in children [15-17], but none of these use highly specific analytical methods such as liquid chromatography tandem mass spectometry (LC-MS/MS).”
BackgroundMethodKervezee, L., Romijn, M., van de Weijer, K. N. G., Chen, B. S. J., Burchell, G. L., Tollenaar, M. S., Tamayo‐Ortiz, M., Philbrook, L. E., de Weerth, C., Cao, Y., et al. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae590 · Cited by 12 · see citing works
Han, Z. R., Zhang, X., Davis, M., & Suveg, C. M. (2019) · Family Process · doi:10.1111/famp.12438 · Cited by 10 · see citing works
Yao, Y., & Silver, R. (2022) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2022.877256 · Cited by 11 · see citing works
Tegethoff, M., Knierzinger, N., Meyer, A. H., & Meinlschmidt, G. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.08.002 · Cited by 11 · see citing works
“The well-documented circadian rhythm of cortisol emerges within the first months postpartum (Price et al., 1983; Santiago et al., 1996; Antonini et al., 2000; Groschl et al., 2003).”
BackgroundLandscape of Aeroallergen Sensitization in Asia
Yin, X., Zhang, X., Xu, F., Xiao, H., Meng, J., & Li, P. H. (2025) · Clinical & Experimental Allergy · doi:10.1111/cea.70137 · Cited by 10 · see citing works
“Sex hormones likely modulate immune responses through receptor-mediated effects on cytokine production and lymphocyte activity [124, 125].”
Exploring Psychophysiological Markers of Vulnerability to Somatic Illnesses in Females
Hipwell, A. E., Keenan, K. E., & Marsland, A. L. (2009) · Journal of Pediatric Psychology · doi:10.1093/jpepsy/jsp010 · Cited by 10 · see citing works
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Salivary Markers as Potential Stress Descriptors for Pediatric Dental Patients: A Literature Review
Main, S., Carrilho, M., Alessandri‐Bonetti, A., Sawicki, C. M., Rao, J., Hall, S., & Sangalli, L. (2025) · Children · doi:10.3390/children12040500 · Cited by 11 · see citing works
Sajaniemi, N. K., Suhonen, E., Hotulainen, R., Törmänen, M. R. K., Alijoki, A., Nislin, M. A., & Kontu, E. K. (2013) · European Early Childhood Education Research Journal · doi:10.1080/1350293x.2013.783303 · Cited by 8 · see citing works
“On the other hand, some studies have pointed out that time-specific range for the normal salivary cortisol levels in older children have not yet been well established (Gröschl, Rauh, and Dörr 2003).”
BackgroundGlucocorticoid response to naturalistic interactions between children and dogs
Gnanadesikan, G. E., Carranza, E., King, K. M., Flyer, A. C., Ossello, G., Smith, P. G., Steklis, N. G., Steklis, H. D., Connelly, J. J., Barnett, M. A., et al. (2024) · Hormones and Behavior · doi:10.1016/j.yhbeh.2024.105523 · Cited by 7 · see citing works
The psychological impact of an adenoidectomy and adenotonsillectomy on young children
Broekman, B. F. P., Olff, M., Tan, F. M. L., Schreuder, B. J. N., Fokkens, W. J., & Boer, F. (2009) · International Journal of Pediatric Otorhinolaryngology · doi:10.1016/j.ijporl.2009.10.005 · Cited by 7 · see citing works
Nyberg, C. H. (2012) · Springer eBooks · doi:10.1007/978-1-4614-4060-4_6 · Cited by 5 · see citing works
Coalitional Physical Competition
McHale, T. S., Chee, W., Chan, K.-C., Zava, D. T., & Gray, P. B. (2018) · Human Nature · doi:10.1007/s12110-018-9321-7 · Cited by 6 · see citing works
- Authors
- Gröschl, M., Rauh, M., & Dörr, H.-G.
- Affiliations
- Klinik mit Poliklinik für Kinder und Jugendliche, Friedrich-Alexander-University Erlangen-Nürnberg, Loschgestrasse 15, 91054 Erlangen; Germany
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- ORCID
- Rauh, Manfred
- Venue
- Clinical Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-10-01
- Volume
- 49
- Issue
- 10
- Pages
- 1688-1691
- ISSN
- 0009-9147 (ISSN-L)
- 1530-8561
- OpenAlex
- W2126406667
- Cited by
- 145
- References
- 34
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 9 · 2016: 6 · 2015: 8 · 2014: 9 · 2013: 14 · 2012: 9
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Keywords
- salivary cortisol, 17-hydroxyprogesterone, salivary progesterone, circadian rhythm, children, reference values, salivary steroids, adrenal steroid secretion, psychological stress, non-invasive hormone measurement
- MeSH terms
- Adolescent, Age Factors, Child, Child, Preschool, Circadian Rhythm, Female, Humans, Hydrocortisone, Infant, Infant, Newborn, Male, Progesterone, Reference Values, Regression Analysis, Saliva, 17-alpha-Hydroxyprogesterone
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