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. 2017 Jul 11;8(1):23.
doi: 10.1186/s13293-017-0144-8.

Is HPA axis reactivity in childhood gender-specific? A systematic review

Jonneke J Hollanders #  1 , Bibian van der Voorn #  1 , Joost Rotteveel  1 , Martijn J J Finken  1
Affiliations

Is HPA axis reactivity in childhood gender-specific? A systematic review

Jonneke J Hollanders et al. Biol Sex Differ. .

Abstract

Background: In adults, hypothalamus-pituitary-adrenal (HPA) axis activity shows sexual dimorphism, and this is thought to be a mechanism underlying sex-specific disease incidence. Evidence is scarce on whether these sex differences are also present in childhood. In a meta-analysis, we recently found that basal (non-stimulated) cortisol in saliva and free cortisol in 24-h urine follow sex-specific patterns. We explored whether these findings could be extended with sex differences in HPA axis reactivity.

Methods: From inception to January 2016, PubMed and EMBASE.com were searched for studies that assessed HPA axis reactivity in healthy girls and boys aged ≤18 years. Articles were systematically assessed and reported in the categories: (1) diurnal rhythm, (2) cortisol awakening response (CAR), (3) protocolled social stress tests similar or equal to the Trier Social Stress Test for children (TSST-C), (4) pharmacological (ACTH and CRH) stress tests, and (5) miscellaneous stress tests.

Results: Two independent assessors selected 109 out of 6158 records for full-text screening, of which 81 studies (with a total of 14,591 subjects) were included. Studies showed that girls had a tendency towards a more variable diurnal rhythm (12 out of 29 studies), a higher CAR (8 out of 18 studies), and a stronger cortisol response to social stress tests (9 out of 21 studies). We found no evidence for sex differences in cortisol response after a pharmacological challenge or to miscellaneous stress tests.

Discussion: Sex differences in HPA axis reactivity appear to be present in childhood, although evidence is not unequivocal. For a better evaluation of sex differences in HPA axis reactivity, standardization of protocols and reports of stress tests is warranted.

Keywords: Cortisol; Glucocorticoid; HPA axis; Infant; Pediatric; Sex characteristics; Stress hormone; Stress reaction; Stress response.

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The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
This flowchart presents the different phases of the systematic review and conforms to the PRISMA statement. (www.prisma-statement.org)
See this image and copyright information in PMC

References

    1. Hanson MA, Gluckman PD. Early developmental conditioning of later health and disease: physiology or pathophysiology? Physiol Rev. 2014;94:1027–1076. doi: 10.1152/physrev.00029.2013. - DOI - PMC - PubMed
    1. De Kloet ER, Vreugdenhil E, Oitzl MS, Joels M. Brain corticosteroid receptor balance in health and disease. Endocr Rev. 1998;19:269–301. - PubMed
    1. Slotkin TA, Seidler FJ, Wood CR, Lau C. Development of glucocorticoid receptor regulation in the rat forebrain: implications for adverse effects of glucocorticoids in preterm infants. Brain Res Bull. 2008;76:531–535. doi: 10.1016/j.brainresbull.2008.03.002. - DOI - PubMed
    1. Kudielka BM, Kirschbaum C. Sex differences in HPA axis responses to stress: a review. Biol Psychol. 2005;69:113–132. doi: 10.1016/j.biopsycho.2004.11.009. - DOI - PubMed
    1. Otte C, Hart S, Neylan TC, Marmar CR, Yaffe K, Mohr DC. A meta-analysis of cortisol response to challenge in human aging: importance of gender. Psychoneuroendocrinology. 2005;30:80–91. doi: 10.1016/j.psyneuen.2004.06.002. - DOI - PubMed

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