Modulation of the hypothalamic–pituitary–adrenal (HPA) axis by plants and phytonutrients: a systematic review of human trials

Objective:The mechanisms involved in the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, especially in the functioning of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) in depressed patients, are not well elucidated. The objective of this study was to conduct a systematic review of articles that assess the HPA axis activity from GR and MR in depressed patients and healthy controls with or without early life stress.Methods:We conducted a systematic review of articles in PubMed, SCOPUS and SciELO published between 2000 and 2011, using the following search terms:child abuse,depression,HPA axis,dexamethasone,prednisolone,fludrocortisoneandspironolactone. Thirty-four papers were selected for this review.Results:Most studies identified in this review used the dexamethasone/corticotropin-releasing hormone test and dexamethasone suppression test. In these studies, hypercortisolaemia was associated with depression. We identified three studies with the Prednisolone suppression test, only one study with the use of fludrocortisone and one with spironolactone. This review found nine studies that evaluated the HPA axis in individuals with early life stress.Conclusions:The majority of the studies assessed in this review show that early life stress leads to permanent changes in the HPA axis and may lead to development of depression in adults. The most consistent findings in the literature show increased activity of the HPA axis in depression associated with hypercortisolaemia and reduced inhibitory feedback. These findings suggest that this dysregulation of the HPA axis is partially attributable to an imbalance between GR and MR. Evidences have consistently showed that GR function is impaired in major depression, but few studies have assessed the activity of MR in depression and early life stress.

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Endocrinal Association of Hypothalamic-Pituitary-Adrenal (HPA) Axis with Obesity

THE JOURNAL OF MICROBIOLOGY AND MOLECULAR GENETICS ◽

10.52700/jmmg.v1i2.16 ◽

2020 ◽

Vol 1 (2) ◽

pp. 32-43

Author(s):

Kaynaat Sohail ◽

Umm E Aiman ◽

Sidra Younis ◽

Farah Deeba

Keyword(s):

Systematic Review ◽

Body Weight ◽

Hpa Axis ◽

Arcuate Nucleus ◽

Health Condition ◽

Stress Exposure ◽

Contributing Factors ◽

Hypothalamic Pituitary Adrenal ◽

Relationship Of ◽

The Relationship

Obesity is a serious health condition that has been affecting individuals of all ages worldwide.Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis and chronic stress exposure are implicated as main contributing factors for obesity development. This study is a systematic review of the research, based on all possible pathways that are involved in obesity involving HPA. The arcuate nucleus (ARC) and paraventricular nucleus (PVN) are involved in the interaction of HPA activity and energy intake. Neuropeptide Y and corticotrophin-releasing hormone (CRH) regulate the feeding behavior. Insulin and leptin levels also affect the HPA axis through different pathways and play a significant role in the pathogenesis of obesity. This review shows the relationship of the HPA axis with obesity. By decreasing the activation or by inhibition of different pathways the causes of obesity can be controlled. Recent therapies are being developed to decrease food intake and body weight regulations.

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A systematic review and meta-analysis of Synacthen tests for assessing hypothalamic-pituitary-adrenal insufficiency in children

Archives of Disease in Childhood ◽

10.1136/archdischild-2015-308925 ◽

2016 ◽

Vol 101 (9) ◽

pp. 847-853 ◽

Cited By ~ 15

Author(s):

Sze May Ng ◽

Juliana Chizo Agwu ◽

Kerry Dwan

Keyword(s):

Systematic Review ◽

Adrenal Insufficiency ◽

Hpa Axis ◽

Standard Dose ◽

Controlled Trial ◽

Meta Analysis ◽

Characteristic Curve ◽

Positive Likelihood Ratio ◽

Hypothalamic Pituitary Adrenal ◽

Synacthen Test

BackgroundThe diagnostic value of tests used in assessing hypothalamic-pituitary-adrenal axis (HPA) in children remains controversial.DesignA systematic review and meta-analysis with receiver-operated-characteristic curve was undertaken to assess the diagnostic values of conventional standard dose 250 μg tetracosactrin (ACTH), short Synacthen test (SSST) and/or low-dose Synacthen test (LDSST) in the assessment of HPA insufficiency in children. Studies eligible for inclusion were any study that compared the use of the LDSST and/or SSST in the assessment of central adrenal insufficiency in children compared with reference standard test.ResultsThere were no randomised trials found. SSST resulted in higher specificity and positive likelihood ratio than LDSST. The LDSST had a higher sensitivity (86% vs 61%) but a lower specificity (88% vs 99%) than the SSST, but there was high heterogeneity from the LDSST studies with various doses of Synacthen used.ConclusionsLack of standardisation of assays and protocols with regard to timing, frequency and dose has resulted in diagnostic inaccuracies. There is no clear evidence to indicate that LDSST is superior to SSST in the assessment of HPA axis in children. The choice of either SSST or LDSST should be individualised based on clinical judgement for each patient. This systematic review has identified the need for a well-designed, adequately powered, randomised controlled trial on the use of diagnostic tests used in assessing HPA axis in children.

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Sex differences in early-life programming of the hypothalamic–pituitary–adrenal axis in humans suggest increased vulnerability in females: a systematic review

Journal of Developmental Origins of Health and Disease ◽

10.1017/s204017441600074x ◽

2017 ◽

Vol 8 (2) ◽

pp. 244-255 ◽

Cited By ~ 70

Author(s):

T. Carpenter ◽

S. M. Grecian ◽

R. M. Reynolds

Keyword(s):

Systematic Review ◽

Sex Differences ◽

Birth Weight ◽

Low Birth Weight ◽

Hpa Axis ◽

Early Life ◽

Meta Analysis ◽

Later Life ◽

Cortisol Secretion ◽

Hypothalamic Pituitary Adrenal

Fetal glucocorticoid overexposure is a key mechanism linking early development with later-life disease. In humans, low birth weight associates with increased fasting cortisol, hypothalamic–pituitary–adrenal (HPA) axis reactivity, and with cardiovascular risk and cognitive decline. As there are sex differences in these adult diseases, we hypothesized that there may be sex differences in programming of the HPA axis in response to prenatal stressors. We conducted a systematic review following Meta-Analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analysis. We searched Embase, MEDLINE and Web of Science from inception to 31 October 2016. We included studies related to sex differences, prenatal exposures and HPA axis. We excluded studies investigating specific disease states. The 23 included studies investigated the consequences of low birth weight, preterm birth and maternal stressors of asthma, psychosocial stress and glucocorticoid medications on HPA axis outcomes of placental glucocorticoid biology and offspring HPA axis function in early life and later life. Female offspring exposed to stressors had increased HPA axis reactivity compared with males. Furthermore, the female placenta increased its permeability to maternal glucocorticoids following maternal stress with changes in the expression of 11β-hydroxysteroid dehydrogenase enzymes in response to maternal glucocorticoid exposure or asthma. Among males there was some evidence of altered diurnal cortisol secretion. We conclude that although there is some evidence of male vulnerability leading to altered diurnal cortisol secretion, the female HPA axis is more vulnerable to programming, particularly in terms of its reactivity; this suggests a mechanism underlying sex differences in later-life diseases.

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