Journal September 26, 2026 6 min read

What markers track the HPA axis?

The hypothalamic-pituitary-adrenal axis is tracked in research by a defined set of endocrine and downstream markers. This page sets out which markers the cited studies measure, in which populations, and where the evidenc

peptides-pro Editorial

The hypothalamic-pituitary-adrenal (HPA) axis is the neuroendocrine stress-response system; the term has no common synonym in the research literature, though it is frequently abbreviated to HPA axis and occasionally described alongside the hypothalamic-pituitary-gonadal (HPG) axis as a paired neuroendocrine readout. The markers used to track it are not a single analyte but a cascade: corticotropin-releasing factor (CRF, also written CRH for corticotropin-releasing hormone) released from the hypothalamus, adrenocorticotropic hormone (ACTH) released from the anterior pituitary, and cortisol released from the adrenal cortex as the terminal effector. Downstream of cortisol, researchers also track cortisol-associated physiological indices such as nocturnal cortisol levels and sleep EEG arousals, and non-endocrine correlates including BDNF and cytokine profiles. The evidence block for this page does not supply sequence, formula or molecular weight data for any of these markers, so none are stated here.

The work cited below centres on the CRF/CRH-driven activation of the HPA axis and its coupling to the noradrenergic system, with the locus coeruleus and amygdala as upstream regulators and the hypothalamic paraventricular nucleus (PVN) as the site of CRH neuron initiation of the neuroendocrine stress response.

Research Studies

CRF, cortisol and sleep EEG indices in PTSD

In post-traumatic stress disorder, the cited trial describes the condition as based on complex noradrenergic dysregulation. In that model, the amygdala activates the hypothalamus to release excessive CRF, which activates the HPA axis and leads to high nocturnal cortisol levels, with associated EEG changes and increased arousals. In parallel, the locus coeruleus releases excess norepinephrine, which interferes with the transition to non-REM sleep and suppresses the stability of REM sleep [1]. The markers tracked in this population are therefore nocturnal cortisol, sleep EEG arousals, and REM stability, rather than cortisol alone.

HPA axis activation under sleep restriction in older adults

A dedicated study protocol in older men and postmenopausal women was designed to determine how HPA axis activation occurs with sleep restriction, and to evaluate how HPG axis deactivation occurs under the same condition. The same protocol examined cognitive function associated with sleep restriction, including food intake and food cravings [6]. A companion protocol with the same objectives was run without the sex- and age-restricted population framing [7]. In both, the axis is treated as a dynamic response to a controlled stressor rather than a static baseline value.

Cortisol and BDNF in cervicogenic headache

Cervicogenic headache is described as a secondary headache caused by referred pain arising from the cervical spine, projecting to the forehead and sometimes the temporal region, with decreased cervical range of motion, decreased sleep quality, increased stress, disturbed mood and altered physiologic chemicals among its impacts. It is reported as more prevalent in females and is experimentally diagnosed by the Cervical Flexion-Rotation Test, with the upper trapezius midpoint (2 cm lateral to C2) commonly acting as a pressure point [4]. The markers under study in this population are cortisol and BDNF, measured in relation to an isometric neck exercise intervention.

HPA axis dysregulation in chronic prostatitis/chronic pelvic pain syndrome

A comprehensive review synthesised evidence from the previous five years on neuroendocrine pathways in chronic prostatitis/chronic pelvic pain syndrome. The review notes that traditional pathophysiological models emphasise infection and local inflammation, and that the limited efficacy of conventional therapies suggests deeper regulatory mechanisms are involved. Its analysis focused on neuropeptide functions, HPA axis dysregulation, sympathetic nervous system signalling and glial cell activity [3]. Here the HPA axis is one of several neuroendocrine markers assessed rather than the sole readout.

Cytokines and HPA-linked pathophysiology in cancer psychiatry

In oncological psychiatry, psychiatric disorders in cancer patients are described as frequently observed but underdiagnosed, with consequent undermining of possible interventions, and as not merely secondary complications but as potentially contributing to poor oncological outcomes. The cited protocol describes the pathophysiology of cancer-related psychiatric disorders as multifactorial and related to several neuropsychological and neurobiological factors, specifically including cytokine production [2]. Cytokines are therefore tracked alongside the axis rather than as a direct HPA marker.

Polyphenol intake and HPA axis regulation

A trial of muscadine wine nutraceuticals states that previous studies have shown polyphenol-rich foods can positively affect cognitive functions, memory and mood in humans. Its hypothesis is that both acute and chronic intake of muscadine wine polyphenols will improve cognitive performance and mood through regulating the HPA axis, alleviating inflammation and oxidative stress, and/or inhibiting monoamine oxidase activities [5]. The HPA axis appears here as one proposed mediator among several, not as the measured endpoint alone.

α7 nicotinic receptor signalling and CRH neurons in the PVN

Dysregulation of the HPA axis is described as a central feature of stress-related affective disorders, and CRH neurons in the hypothalamic paraventricular nucleus are described as initiating neuroendocrine stress responses. In this work, activation of the α7 nicotinic acetylcholine receptor promoted anxiety- and depressive-like behaviours associated with CREB/CRH signalling in the paraventricular nucleus [11]. This is a mechanistic study of upstream CRH regulation rather than a marker-quantification study.

Schisandrin B and anxiety-like behaviour in rats

Schisandrin B was examined for anxiolytic effects in rats exhibiting anxiety-like behaviours, with behavioural assessment by the elevated plus-maze test and the open field test. Schisandrin B at a dose of 10 mg/kg was reported to produce effects in this model [9]. This is animal-only evidence; no human HPA marker data are reported in the cited record.

Exercise-induced ACTH and cortisol responses in racehorses

Exercise is described as a physiological challenge inducing intensity-dependent HPA axis responses. The hypothesis tested was that training and racing sessions induce different HPA axis activation, with the objective of assessing whether different exercise sessions affect equine adrenal output [10]. The markers are circulating ACTH and cortisol, measured in Thoroughbred racehorses — a veterinary population, not a human one.

Adaptogens and stress-resistance markers

A narrative review describes adaptogens as primarily plant-derived bioactive compounds that enhance resistance to physical, chemical and biological stressors, with reported promise in stress-related disorders, neurodegenerative disease, inflammation and ageing [8]. This is review-level material and is cited here as context for how the stress-response field frames its markers, not as a primary dataset.

Markers compared across cited populations

Marker	Population or model	Source
Nocturnal cortisol, sleep EEG arousals, REM stability	Patients with PTSD	[1]
HPA axis activation, HPG axis deactivation	Older men and postmenopausal women under sleep restriction	[6]
HPA axis activation, HPG axis deactivation	Sleep-restricted adults (companion protocol)	[7]
Cortisol, BDNF	Smartphone users with cervicogenic headache	[4]
HPA axis dysregulation, neuropeptides, SNS signalling, glial cells	Chronic prostatitis/chronic pelvic pain syndrome (review)	[3]
Cytokines	Cancer patients with psychiatric disorders	[2]
HPA axis regulation, inflammation, oxidative stress, MAO activity	Human polyphenol intake trial	[5]
CREB/CRH signalling in the PVN	Preclinical affective-behaviour model	[11]
Anxiety-like behaviour (EPM, open field)	Rats, Schisandrin B 10 mg/kg	[9]
Circulating ACTH and cortisol	Thoroughbred racehorses	[10]

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