Association Between Hair Cortisol,Dehydroepiandrosterone and Perceived Stress in Chronic Stress-related Conditions: A Systematic Review and Meta-analysis

Abstract

Background:

Hair concentrations of cortisol and dehydroepiandrosterone (DHEA) are increasingly recognized as non-invasive, retrospective biomarkers of hypothalamic–pituitary–adrenal axis function. The ratio of these hormones may reflect the balance between catabolic and anabolic activity, potentially serving as a composite marker of chronic stress. Despite its theoretical relevance, the clinical utility of the hair cortisol: DHEA ratio remains unclear. This PROSPERO-registered systematic review, done according to PRISMA guidelines, aimed to evaluate the association between the hair cortisol: DHEA ratio and perceived stress in adults with chronic stress exposure.

Methods:

A comprehensive search of five electronic databases and grey literature was conducted up to March 5, 2025. Studies were eligible if they included adults (≥18 years) with at least 4 weeks of documented chronic stress exposure and reported both hair cortisol and DHEA concentrations alongside validated perceived stress measures. Meta-analyses were performed for correlation coefficients and group comparisons. Risk of bias was assessed using a modified Downs and Black checklist.

Results:

Eight studies (five cross-sectional, three cohort; n = 60–210) met inclusion criteria. A meta-analysis of two studies using validated stress scales showed no significant association between the hair cortisol/DHEA ratio and perceived stress (ρ = 0.09; 95% CI: −0.07 to 0.26; I² = 0%). However, a separate analysis of three studies comparing high- versus low-stress groups revealed a moderate, statistically significant pooled effect (Hedges’ g = 0.69; 95% CI: 0.14–1.24; p = .01) with substantial heterogeneity (I² = 77.17%). Risk of bias ranged from moderate to low, but the overall certainty of evidence was rated very low due to small sample sizes and inconsistent findings.

Conclusion:

The hair cortisol: DHEA ratio has biological plausibility as a marker of chronic stress, but current evidence is insufficient to support its clinical application. Further standardized, longitudinal studies are needed to establish its diagnostic and prognostic value.

PROSPERO Registration:

CRD420251003364.

Keywords

Hair cortisol dehydroepiandrosterone (DHEA)cortisol: DHEA ratio chronic stress biomarker HPA axis systematic review meta-analysis

Key Messages

A registered systematic review and meta-analysis was conducted to investigate the association between the hair cortisol: DHEA ratio and perceived stress in adults experiencing chronic stress.

Eight eligible studies were included in the analysis, and no statistically significant correlation between the hair cortisol: DHEA ratio and perceived stress was identified.

Based on the limited number of available studies, this review did not find the hair cortisol: DHEA ratio to be a reliable biomarker of chronic stress.

The hypothalamo–pituitary–adrenal (HPA) axis is central to the body’s adaptation to psychological and physiological stress, orchestrating neuroendocrine responses through the secretion of cortisol and dehydroepiandrosterone sulfate (DHEA-S).¹ Cortisol, the primary glucocorticoid in humans, facilitates catabolic and immunosuppressive processes during acute and chronic stress, whereas DHEA exerts anabolic, neuroprotective and anti-glucocorticoid effects, providing a counter-regulatory influence.² The ratio of cortisol to DHEA is thus increasingly recognized as a sensitive composite marker of HPA axis function and allostatic load, capturing the balance between catabolic and anabolic activity under stress adaptation or dysregulation.³

Biological plausibility for using the cortisol: DHEA ratio as a marker of chronic stress is supported by both experimental and animal studies. Chronic or repeated stress exposures are known to induce persistent HPA axis activation, leading to sustained elevations in cortisol and a relative decline in DHEA, which results in an increased cortisol: DHEA ratio and reflects cumulative allostatic burden and potential neurotoxicity.⁴ Experimental models in rodents have demonstrated that chronic stress reduces hippocampal DHEA and enhances corticosterone (the rodent analog of cortisol). That supplementation with DHEA can mitigate some neurotoxic effects of excessive glucocorticoids.⁵

In humans, accumulating evidence links a higher cortisol: DHEA ratio with adverse physical and mental health outcomes, such as depression, anxiety, cognitive impairment and metabolic syndrome.⁶ Recent clinical research demonstrates that these hormone levels can be robustly assessed in hair samples, which, unlike serum or saliva, provide an integrated measure of hormone secretion over weeks to months, minimizing confounding by diurnal or short-term fluctuations. Meta-analytic studies have established that hair cortisol is elevated under chronic stress conditions. Initial evidence suggests that a higher hair cortisol: DHEA ratio is observed in individuals facing significant or long-standing stressors, further supporting the biological plausibility of this marker.

Given these findings, systematic evaluation of the hair cortisol: DHEA ratio may offer valuable insights into the biology of chronic stress and serve as a non-invasive biomarker for stress-related health outcomes. The present review aims to synthesize current evidence on the association between the hair cortisol: DHEA ratio and chronic stress and to examine its potential clinical and research applications.

Methods

Study Registration and Protocol

The study protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) on March 5, 2025 (Registration ID: CRD420251003364), prior to the commencement of the review, and no amendments were made thereafter. The systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The PRISMA 2020 checklist is provided in Supplementary Table S1.

Eligibility Criteria

Inclusion Criteria

The study population included adults aged 18 years and above who had experienced chronic stress-related conditions such as occupational stress, post-traumatic stress disorder (PTSD), depression, anxiety disorders, caregiving stress, pregnancy stress and chronic medical conditions for more than 4 weeks. Studies that measured the level of stress based on standardized, validated instruments or clinical response-based information, as well as studies that provided data on hair cortisol and DHEA levels measured using validated assays, were included. If the study mentioned a particular condition or illness to represent stress, it has been included. The types of studies included in this review are non-randomized study designs, namely cohort, case-control and cross-sectional studies, with or without a comparator group, including studies that compared with healthy human controls.

Exclusion Criteria

Studies without quantitative hair cortisol or hair DHEA data, studies using serum/salivary cortisol instead of hair samples, animal studies and studies in languages other than English were excluded. As the rate of hair growth is about 1 cm per month, studies that analyzed less than 1 cm of hair segment were excluded. The rationale is that hair typically grows at an approximate rate of 1 cm per month; therefore, segments shorter than 1 cm may not reliably represent at least 1 month of hormone accumulation, which is essential for the retrospective evaluation of chronic stress.

Outcome Measures

The primary outcome of this review was the correlation coefficient between the hair cortisol: DHEA ratio and perceived stress scores. This ratio was examined as a potential indicator of individual stress adaptation, given its biological plausibility as a composite marker of HPA axis function. While elevated DHEA levels have been associated with psychological resilience in some studies, there remains insufficient evidence to support the cortisol: DHEA ratio as a validated biomarker of resilience. Correlation coefficients were extracted directly from the included studies; where not reported, they were calculated using data provided by the authors upon request, or it was made available as a supplement.

Search Strategy

Databases, namely PubMed, Ovid MEDLINE, ProQuest, Scopus and BASE (Bielefeld Academic Search Engine; grey literature) from the inception till March 5, 2025, were searched. Grey literature was searched for unpublished work that may have been missed in other databases. The studies were searched using the MeSH terms (where available) and keywords—‘hair cortisol’, dehydroepiandrosterone, DHEA*, along with appropriate Boolean operators in the title and abstract. A detailed search string is provided in Supplementary File S1. Additionally, a citation search of the included studies was conducted using CitationChaser software.⁷ Both forward and backwards chasing techniques were used, and all relevant articles were included as per the eligibility criteria. All the studies detected were downloaded from the databases and then exported to COVIDENCE^→ software.⁸

Data Extraction

Three authors worked on the screening and the eligibility assessment stage. Two authors initially selected studies independently by screening the title and abstract (SB, VH) and then screened the full-text articles based on the explicit eligibility criteria (RH, VH). The discrepancies between the two authors in both stages were resolved by a third author (RRK); reference lists were hand-searched, as well as using citation chaser software for potential studies (RH). The quality of studies was independently assessed by two authors (RH, VH) for risk of bias evaluation, and disagreements were resolved by a third author (RRK) to reach a consensus about the risk of bias.

Data extraction was carried out using a standardized Microsoft Excel^→ spreadsheet. Reviewers independently extracted relevant data items from the included studies, including study characteristics, that is, design, sample size, population, stress assessment, hair cortisol and hair DHEA concentrations; it was calculated from the raw values provided. When essential data were missing or unclear, attempts were made to contact the corresponding authors of included articles for clarification, data sharing or additional information. Additionally, supplementary materials of included studies were examined, and data were retrieved from appendices or supporting files when available. This multi-step process ensured completeness and accuracy in the dataset used for synthesis. Any discrepancies between the reviewers during extraction were resolved through consensus or consultation with a third author.

Risk of Bias Assessment

Modified Downs and Black Checklist for assessing the risk of bias of the included studies. This checklist, developed by Sara H. Downs and Nick Black in 1998, is based on epidemiological principles, reviews and existing checklists for both randomized and non-randomized studies. This checklist consists of 27 items, divided into five subscales: reporting, external validity, internal validity (bias; confounding) and power, with a maximum score of 32. The internal consistency of the quality index is high (KR-20:0.89), and the test–retest reliability of the quality index is high (r = 0.88). The inter-rater reliability is good, the quality index score is high, and raters take around 20 minutes to rate a study. The checklist was modified to include relevant questions to assess the study designs of our included studies, with a maximum score of 18 for cross-sectional studies and 21 for cohort studies. The findings were grouped under the headings of reporting, external validity, internal validity and power, and the ratio was calculated.⁹

Statistical Analysis

A meta-analysis was performed using STATA (v17.0), focusing on two studies that reported Spearman’s correlation coefficients between hair cortisol: DHEA ratio and perceived stress scores. The pooled correlation coefficient was calculated. A secondary meta-analysis examining group differences in hair cortisol: DHEA ratios between stress-exposed and comparison groups across three studies employed a random-effects model using restricted maximum likelihood (REML) estimation. The funnel plot was created. Certainty of evidence was assessed using the GRADE framework (VH, RRK).

Results

Study Selection Data

Eight studies were included in the review, comprising diverse populations such as individuals living with HIV, post-partum mothers, foster caregivers and pregnant women. The selection process is summarized in the PRISMA style flow diagram (Figure 1).

Figure 1.

PRISMA Flowchart.

Excluded Studies

A total of 11 studies were excluded during title, abstract and full-text screening based on predefined eligibility criteria. Although the meta-analysis synthesized correlation coefficients between hair cortisol: DHEA ratios and perceived stress scores, studies were excluded if they lacked sufficient quantitative data to compute or extract valid correlations. Common reasons included are absence of hair-based hormone measurements, non-human subjects, lack of validated stress assessments (e.g., no Perceived Stress Scale [PSS] or equivalent) or failure to stratify hormone data by stress levels. Several studies reported biomarker values without corresponding psychological measures or omitted necessary statistical parameters (e.g., standard deviations, sample size or paired data) needed to compute correlations. A list of excluded studies and reasons is provided in Supplementary Material Table S2.

Included Studies

All eight studies included in the qualitative synthesis investigated hair cortisol and hair DHEA concentrations in adult populations exposed to various forms of chronic stress. The study populations were diverse, including individuals living with HIV in China, post-partum mothers in Pakistan¹⁰ and middle-aged men with vital exhaustion in Germany.¹¹ Additional studies explored chronic stress within the contexts of maternal childhood maltreatment.¹² Caregiving among foster and biological mothers, and psychosocial adversity among female refugees and immigrants.¹³ Two studies focused on maternal and prenatal health outcomes: one examining cardiovascular risk in apparently healthy middle-aged women and another assessing maternal fetal developmental signalling.^14,15

Most studies analyzed proximal hair segments of ~3 cm, representing an estimated 3-month retrospective window of hormone accumulation. Assay methods varied; studies that utilized either liquid chromatography-tandem mass spectrometry (LC-MS/MS), considered the gold standard for steroid hormone quantification, or enzyme-linked immunosorbent assay (ELISA) for measuring hair cortisol and DHEA were included. While LC-MS/MS was the preferred approach in studies such as those by Qiao et al. and Mazgelytė et al. other studies did not specify the analytical technique. They likely employed ELISA. Notably, six of the eight studies explicitly examined the cortisol: DHEA or DHEA: cortisol ratio, underscoring growing interest in this emerging biomarker of HPA axis regulation. However, only a subset of studies, such as those by Qiao et al. and Reindl et al. conducted group comparisons based on standardized stress scales, which limits direct comparability across studies.^16,17

The characteristics of the included studies are summarized in Table 1. These studies differed in design (cross-sectional vs. cohort), population demographics and the type of chronic stress exposure assessed. Most employed validated instruments for measuring stress, such as the PSS or equivalent structured interviews. Hormone assays were conducted using either LC-MS/MS or ELISA, though detailed assay parameters were not consistently reported. A methodological quality appraisal was conducted using the modified Downs and Black checklist, with results presented in Table 2. Overall, study quality ranged from fair to good, with commonly observed limitations including small sample sizes, heterogeneous populations and inadequate reporting of assay reliability. This variation in measurement tools reflects differing conceptualizations of chronic stress and may contribute to heterogeneity.

Table 1.

Characteristics of Included Studies (N = 8).

Author Year	Country	Population	Sample Size	Stress Measure	Hair Segment (cm)	Assay Method	Outcomes Reported
Qiao 2017¹⁶	China	People living with HIV	60	Clinical interview grouping (high vs. low stress)	3	LC-APCI-MS/MS	Yes (DHEA/Cortisol ratio) The high-stress group had higher perceived stress (mean ± SD), higher stressful events, higher hair cortisol and lower DHEA: cortisol ratio.
Schury 2017¹⁸	Germany	Mothers with childhood maltreatment	94	Childhood Trauma Questionnaire (CTQ)	Not specified	Not specified	Yes (cortisol and DHEA in mothers and infants) Higher CTQ scores correlated with higher maternal hair DHEA; no significant association with hair cortisol.
Noser 2018²³	Germany	Middle-aged men with vital exhaustion	121	Vital exhaustion scale	Not specified	Not specified	Yes (analyzed DHEA only) Highest biological stress index is in those with both chronic stress and low social support; DHEA is highest in men with substantial exhaustion; no significant group differences in hair cortisol/DHEA ratio.
Buchmuller 2020¹³	Germany	Female refugees and immigrants	89	PTSD symptoms, perceived stress	6	Not specified (likely ELISA or LC-MS/MS)	No (only cortisol) PTSD symptoms and perceived stress scores highest in IDPs; both scores positively correlated with hair cortisol.
Ruiz 2021¹⁰	Pakistan	Post-partum mothers (maternal behavior and child development)	90	Self-reported perceived stress	Not specified	Not specified	Yes (Cortisol, DHEA analyzed) Maternal stress biomarkers (hair cortisol, cortisone, DHEA, testosterone) correlated with different parenting behaviors.
Mazgelyte 2022²⁰	Lithuania	Apparently healthy middle-aged women	145	SCORE2 CVD risk score	3	UHPLC-MS/MS	Yes Higher hair cortisol and cortisone are associated with higher SCORE2 risk and with chronic stress/anxiety.
Bailey 2024¹⁴	USA	Pregnant women (maternal HPA axis and infant outcomes)	124	Infant emotional reactivity	3	Not specified	Yes (analyzed interaction) Higher maternal DHEA (late gestation) ® greater infant positive reactivity; higher maternal cortisol ® greater infant negative reactivity.
Reindl 2024¹⁷	Germany	Foster and biological mothers	210	Parenting stress index	3	Not specified	Yes (Cortisol/DHEA) No significant association between maternal hair cortisol/DHEA and parenting stress; higher dyadic coping was related to lower parenting stress.

LC-APCI-MS/MS: Liquid chromatography–atmospheric pressure chemical ionization–tandem mass spectrometry, UHPLC-MS/MS: Ultra-high-performance liquid chromatography–tandem mass spectrometry, PTSD: Post-traumatic stress disorder, CVD: Cardiovascular disease, SCORE2: Systematic coronary risk estimation 2 tool, HPA: Hypothalamic–pituitary–adrenal axis.

Quality Assessment

Risk of bias assessment was done using the modified Downs and Black checklist,⁹ independently rated by two authors (RH, VH) for the reporting, external validity, internal validity and power of the study. The ratios for quality of the studies were calculated and ranged between 0.61 and 0.83. Two cross-sectional studies and one cohort study had a ratio of 0.8 and above, suggesting the least risk of bias (Table 2).

Table 2.

Risk of Bias Assessment.

Author Year	Reporting	External Validity	Internal Validity—Bias	Internal Validity—Confounding	Power	Score/Total*	Ratio	Risk of Bias
Qiao 2017¹⁶	7	0	3	2	0	12/18	0.67	!
Schury 2017¹⁸	7	2	3	2	1	15/18	0.83	–
Noser 2018²³	7	2	3	3	0	15/18	0.83	–
Buchmüller 2020¹³	7	0	3	1	0	11/18	0.61	!
Ruiz CM 2021¹⁰	7	2	4	3	0	16/21	0.76	−
Mazgelytė 2022²⁰	7	0	3	1	1	12/18	0.67	!
Bailey 2024¹⁴	8	0	4	3	0	15/21	0.71	!
Reindl 2024¹⁷	8	1	4	4	0	17/21	0.81	−

*Cross-sectional studies were scored out of 18 and cohort studies out of 21 (− = Low risk of bias; ! = Some concerns; + = High risk of bias).

Meta-analysis

Meta-analysis was conducted on two studies (Qiao et al., 2017 and Schury et al., 2017)^16,18 that reported Spearman’s rank-correlation coefficients between hair cortisol/DHEA ratios and perceived stress scores. A Random-effects REML model was applied (I² = 0%, τ² = 0.00). The pooled correlation was small and statistically non-significant (ρ = 0.09; 95% CI: −0.07 to 0.26), indicating a weak and inconclusive association between perceived stress and the cortisol: DHEA ratio (Figure 2) and the DoI plot for these studies is presented in Supplementary Figure 4.

Notably, six studies were excluded from meta-analysis due to the absence of reported correlation statistics, lack of PSS usage, incomplete hormone data or methodological incompatibilities (e.g., use of non-hair matrices). These limitations highlight the need for standardized study designs and reporting practices in future research on hair-based stress biomarkers.

Sub-group Analysis

In a separate analysis comparing hair cortisol: DHEA ratios between high-stress and lower-stress groups (three studies), the pooled effect size using a random-effects REML model yielded a statistically significant Hedges’ g of 0.69 (95% CI: 0.14–1.24, p = .01). However, substantial heterogeneity was present (I² = 77.17%, τ² = 0.12) (Supplementary Figure 2), likely due to differences in population characteristics, stress measurement tools, assay methods and hair segment lengths.

Figure 2.

Forest Plot of Spearman’s Correlation Between Hair Cortisol/DHEA Ratio and Perceived Stress Scores.

This forest plot illustrates the results of a random-effects meta-analysis evaluating the association between perceived stress (measured using the Perceived Stress Scale) and the hair cortisol/DHEA ratio across two studies (Qiao, 2017¹⁶ and Schury, 2017¹⁸). Both studies reported Spearman’s rank correlation coefficients. The pooled correlation coefficient was ρ = 0.09 with a 95% confidence interval of [−0.07, 0.26], indicating a small, statistically nonsignificant positive relationship. Heterogeneity was minimal (I² = 0%, τ² = 0.00), suggesting consistent results across studies. Study weights were derived based on the inverse variance of Fisher’s z-transformed correlation estimates.

Sensitivity Analysis

A leave-one-out sensitivity analysis revealed that the pooled effect size was particularly influenced by Qiao et al. (2017)¹⁶; omitting this study reduced the effect to a non-significant level (Hedges’ g = 0.43, 95% CI: −0.07 to 0.94, p = .093) (Supplementary Figure 3). Exclusion of the other studies did not materially alter the results, supporting the relative robustness of the overall finding.

Heterogeneity

Substantial heterogeneity was observed across the included studies, reflecting variation at multiple levels, including population characteristics, definitions of chronic stress and methodological approaches. The populations examined ranged from people living with HIV, post-partum and pregnant women, to caregivers and foster mothers, each representing distinct psychosocial stressors and physiological states. Chronic stress was operationalized inconsistently, encompassing validated instruments such as the PSS, as well as role-based proxies and trauma-related indices, thereby introducing conceptual variability in exposure measurement. Methodological divergence was further evident in the hormonal assays employed in some studies, which measured cortisol and DHEA directly, while others quantified DHEA-S; additionally, hair segment lengths ranged from 1 to 6 cm, affecting the retrospective time window of hormonal integration.

Publication Bias

Visual inspection of the funnel plot (Supplementary Figure 1) did not reveal significant asymmetry, suggesting a lower likelihood of reporting bias. However, interpretation remains limited due to the small number of studies (N = 8). Despite detailed searching for unpublished or grey literature and citation chasing, only two studies were eligible for inclusion in the meta-analysis. Interpretation of potential reporting bias was approached with caution, given this as a limitation.

GRADE Assessment (Certainty of Evidence)

Certainty of the evidence for the pooled outcome was assessed using the GRADE approach and was judged to be low due to imprecision and inconsistency. While the biological rationale for the cortisol: DHEA ratio as a chronic stress biomarker is strong, the current body of evidence does not conclusively support its consistent clinical utility across diverse populations and settings (Table 3).

Table 3.

GRADE Assessment.

Certainty Assessment							Effect		Certainty	Importance
No. of Studies	Study Design	Risk of Bias	Inconsistency	Indirectness	Imprecision	Other Considerations	Correlation Coefficient (95% CI)	Absolute (95% CI)	Certainty	Importance
2	Non-randomized studies	Not serious	Not serious	Not serious	Serious^a	None	0.09 (−0.07 to 0.26)	NA	⨁ Very low^a	Important

CI: confidence interval.

^aAll studies CI Crossed the null effect and true effect line.

Discussion

This review is the first to systematically assess the hair cortisol: DHEA ratio as a biomarker of chronic stress. The overall impression from the eight studies was that the association between the ratio and perceived stress was weak and non-significant. Meta-analysis of two studies showed a non-significant correlation (ρ = 0.09; 95% CI: −0.07 to 0.26). The overall evidence was rated very low due to small sample sizes and inconsistent outcomes. Hence, current findings do not support the cortisol: DHEA ratio as a reliable indicator of chronic stress.

The included studies were of moderate methodological quality, with Downs and Black scores ranging from 60% to 80%. Most were cross-sectional, and study populations were diverse, including individuals with HIV, post-partum mothers and caregivers, increasing heterogeneity. Although most studies analyzed 3 cm hair segments, there was variability in hormone assay methods, with some using LC-MS/MS and others likely using ELISA—differences in stress definitions, assay protocols, and incomplete reporting limited data pooling and prevented subgroup analysis. Few studies adjusted for confounders such as age, sex, BMI, medication or hair treatments, all of which influence hormone levels. Due to the small number of studies, formal assessment of publication bias was unreliable.

Recent research shows mixed findings regarding the cortisol: DHEA ratio. Studies such as Pividori et al.¹⁹ reported elevated ratios in COVID-19 patients compared with healthcare workers, indicating stress-related dysregulation. Others, such as Mazgelytė et al.²⁰ linked high ratios to biological ageing markers. However, studies in trauma-exposed or diverse populations, including de Graaff et al.²¹ found no significant correlation with perceived stress. Some studies observed hormone-specific associations with stress symptoms rather than with the ratio itself. This inconsistency mirrors the present findings and suggests that the clinical value of the ratio may vary by context and population characteristics.

Several factors may explain the inconsistent results. Biological differences in hair hormone incorporation, influenced by age, sex, hair type, and cosmetic practices, can reduce measurement precision.²² The HPA axis also responds differently across individuals; some may show elevated cortisol, others higher DHEA or both may remain stable, leading to varying ratios. Methodological variations in stress assessment tools, hair segment lengths and assay types further contributed to heterogeneity. Incomplete reporting and lack of confounder adjustment in several studies made interpretation difficult. Despite these challenges, the cortisol: DHEA ratio remains biologically plausible as a marker of HPA axis function, reflecting the balance between catabolic and anabolic responses.

Strengths and Limitations

The review followed rigorous methodology, including broad database searches, citation chasing and standardized risk-of-bias assessment. Duplicate screening and data extraction enhanced reliability. Inclusion of varied populations improves external validity. A key strength is the combined assessment of cortisol and DHEA, offering a more comprehensive view of HPA axis activity. Limitations include a small number of eligible studies, most with modest sample sizes and cross-sectional designs. Variability in definitions, hormone assays and outcome measures restricted comparability. Confounding was variably addressed across primary studies; for example, several included studies reported adjusting for factors such as age, gender, body mass index, medication use or hair treatment.

Clinical Implications and Future Directions

Although not yet suitable for routine clinical use, the hair cortisol: DHEA ratio and its utility need further exploration. It may help differentiate between adaptive and maladaptive stress responses. In the future, this ratio could aid in identifying individuals at risk of stress-related disorders in occupational and mental health settings. To improve clinical applicability, future studies should use standardized protocols such as consistent hair segment lengths, validated assays and controlled pre-analytical conditions. Longitudinal research is essential to observe how the ratio responds to stress over time and following interventions. Trials evaluating changes in the ratio after mindfulness, psychotherapy or DHEA supplementation would help validate its clinical relevance. Additionally, factors such as sex, stress duration and genetic influences on steroid metabolism should be considered. Integrating the cortisol/DHEA ratio into broader biomarker panels, including inflammatory markers and telomere length, could improve the precision of stress assessment and provide a holistic understanding of chronic stress physiology.²²

Conclusion

The hair cortisol-to-DHEA ratio represents a biologically meaningful marker of HPA axis function; however, current evidence does not support its use as a reliable standalone biomarker for chronic stress in clinical settings. While elevated ratios have been observed in some high-stress groups, findings remain inconsistent due to methodological differences and individual variability. A higher ratio may reflect HPA axis dysregulation, whereas stable or increased DHEA levels could indicate resilience. Given these uncertainties, the ratio should currently be used only as a supplementary marker. Future studies must adopt standardized methods, use longitudinal designs and evaluate their role within broader biomarker panels to better define their clinical relevance.

Supplemental Material

Supplemental material for this article available online.

Supplemental Material

Supplemental material for this article available online.

Footnotes

Acknowledgements

The authors thank the Indian Psychiatric Society Karnataka Chapter and the Department of Psychiatry, NIMHANS, for their support in mentoring for Systematic Reviews.

Availability of Data and Materials

All data extraction forms, datasets used for synthesis, and supplementary materials (including the search strategy, excluded studies list, and quality appraisal scores) are available in the supplementary files accompanying this manuscript. Additional analytic data or SPSS/STATA syntax used in the meta-analysis are available from the corresponding author upon reasonable request.

Data Sharing Statement

This is secondary research. All additional data are made available in the supplementary material.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Disclosure of Use of Generative AI

None used.

Ethical Approval

Not applicable as this is secondary analysis of previously published data and did not involve the collection of new human or animal data.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Patient Consent

Not applicable. No individual patient data were collected, used, or reported.

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Supplementary Material

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