Advantages of Hair Cortisol (HC) Analysis

Motherisk Int J 2020;1;27


Mohamed Mari, Gideon Koren

school of Medicine

Ariel University



Although stress is not necessarily associated with adverse effects, high or continuous levels of stress or poor coping resources can make it a trigger for physical and mental health disorders which can negatively affect the quality of life. Consequently, in recent years, there has been a growing interest in quantifying stress levels. ‎1

The normal human response to stress is modulated by several complementary systems, including the autonomic nervous system and the hypothalamic-pituitary-adrenal axis (HPAA)‎ 2. ACTH, upon release into the general circulation, binds to high-affinity membrane receptors on cells in the zona fasciculate of the adrenal cortex, is rapidly inducing the production and release of the glucocorticoid, cortisol. After adrenocortical stimulation, ACTH acts on the hypothalamus to decrease the production of CRH, ultimately suppressing its production in negative feedback. Cortisol has been well studied in many populations as it is an important measure of the biological reactivity to stress and both excessive and deficient cortisol responses have been associated with dysregulation of the HPA axis 3‎,4.

Biomarkers of acute stress have been focused and measured by catecholamine release 5. However, finding a ‘‘gold standard’’ biomarker for chronic stress has been challenging due to its complex etiology and highly individual manifestations ‎6.

In humans, non-human primates and many larger mammals’ cortisol is the most common glucocorticoid, while in other vertebrates including rodents, corticosterone is the primary stress hormone and there are only very few studies on corticosterone in hair ‎6.

During times when an organism undergoes physiologic duress, cortisol acts to mobilize energy stores and modulate the immune system. Despite its well-recognized role in stress in both animals and humans, the ability of cortisol to reflect stress levels over long periods has been limited. This is largely due to the nature of the traditional matrices in which cortisol has been sampled. To date, the majority of studies have investigated cortisol responses using samples of serum, saliva, or urine. The most commonly used assays to detect cortisol in these samples are radio-immunoassays (RIAs), liquid chromatography-mass spectrometry (LC-MS/ MS), and enzyme-linked immunosorbent assays (ELISA) ‎7.

Both saliva and serum samples provide a measurement of the cortisol concentration at a single point in time. They can, therefore, be used to test acute changes, but are subject to major physiological daily fluctuations, making the assessment of overall long-term systemic cortisol exposure difficult if not impossible. In healthy individuals, plasma cortisol levels peak in the early morning, and gradually decrease thereafter. Hence, a single measurement cannot reflect the integration of systemic exposure. To help overcome this challenge, most contemporary studies obtain multiple salivary samples from the time of waking until sleep, but this is experimentally complex, the adherence of individual participants with the sampling schedule may vary ‎8, and this methodology is difficult to apply to large populations. Besides, measuring cortisol in serum samples assesses total serum cortisol that includes both protein-bound and bioactive (free) cortisol. However, total serum cortisol is affected by changes in levels of cortisol-binding globulin (e.g., by birth control pills or pregnancy) that can result in increases in total cortisol concentration measured, even though there is no increase in stress or free cortisol concentrations. Besides, the procedure of obtaining a sample via venipuncture could by itself be a source of stress and increased cortisol ‎9. Salivary cortisol concentrations correlate well with serum concentrations ‎9‎,10. In contrast to serum cortisol, salivary cortisol reflects free (unbound) cortisol and is collected by a less-invasive method. Yet, salivary cortisol concentrations still fluctuate significantly throughout the day. A similar strategy is employed when urine is used; 24-h urine collections provide an integration of the free cortisol concentrations through the day, thus overcoming the issue of its diurnal rhythm ‎11. However, the collection is labor-intensive for participants, and cannot be used in cases of chronic renal failure or dialysis ‎6.


Advantages of Hair Cortisol (HC) Analysis

Fifteen years ago, our laboratories at the University of Toronto and Western Ontario pioneered the use of hair cortisol as a biomarker of chronic stress ‎6. There are various advantages to using cortisol in hair as a biomarker of chronic stress. Hair has a fairly predictable growth rate of approximately 1 cm/month. Hence, the most proximal 1 cm segment to the scalp approximates the last month’s cortisol production, the second most proximal 1 cm segment approximates the production during the month before that, and so on ‎12. This phenomenon enables researchers to retrospectively examine cortisol production at the times when a stressor was most salient, without needing to take a sample right at that time. Alternatively, it can provide a baseline cortisol assessment for a time period during which the stress had not yet occurred. This was demonstrated in a study in rhesus macaques in which hair samples for cortisol were obtained both at baseline and after a major stressful event (relocation to a new habitat) ‎13. The sample could be collected noninvasively by simply cutting a 1 cm diameter sample of hair at the base of the vertex posterior of the head. This eliminates the risk that the sampling itself may impact cortisol production. Furthermore, as each centimeter sample represents approximately 1 months’ worth of cortisol production, the issue of intra- and inter-day cortisol fluctuations is mitigated. Finally, unlike the bodily fluids that require special storage conditions before analysis, hair samples are easily transported and stored in envelopes or vials at room temperature ‎14. A summary of the different properties of existing matrices for cortisol measurement is presented in Table 16.

Table 1: A comparison of properties of the various matrices for cortisol measurement.
Property Serum Saliva Urine Hair
Subjective level of invasiveness associated with sample collection High Low Moderate Low
Cortisol affected by stress of sampling procedure? Possibly Possibly Possibly No
Storage requirements Spinning and refrigeration

followed by freezing


or freezing


or freezing

Room temperature;

stable for years

Periods of cortisol

production represented

Single point measure


Single point measure 12—24 h; integral

of exposure

Months to years;

integral of exposure

Affected by changes in

cortisol binding globulin?

Yes; total cortisol


No; only free

cortisol measured

No; only free

cortisol measured

No; only free

cortisol measured

Clinically relevant reference

ranges established?

Yes Yes Yes No


Another matrix that may be capable of providing cumulative cortisol exposure is fingernails. Recently a pilot study was performed to determine whether cortisol and dehydroepiandrosterone (DHEA) could be detected in fingernails 15. Using a methanol extraction and ELISA, both cortisol and DHEA were detected in fingernails from 33 university students. During times of exam stress, the ratio of cortisol over DHEA was found to be significantly increased compared to baseline levels obtained at the beginning of the school year. One of the limitations identified by the authors was how fingernail growth is known to change depending on environmental factors (e.g., seasonal changes) and differences in personal behavior (e.g., nail-biting habits). Thus, controlling for such variables would be important for fingernail cortisol concentrations to accurately reflect the time of periods of interest. Another study used an extraction and ultra-performance mass spectrometry analysis to investigate whether cortisol, cortisone, and DHEA could be detected in fingernails ‎16. Further studies are required to validate fingernails as a reliable matrix, but they may present an alternative for cumulative cortisol measurement when hair analysis is not possible, such as in cases of balding or cultural objections against hair sample collection ‎6.


Hair Cortisol Analysis

Overall, the methods used for the measurement of cortisol in the hair are very similar, with some variations in procedures amongst laboratories. Briefly, to extract cortisol from hair, the sample is carefully sectioned into segment lengths that will approximate the time of period of interest (e.g., the most proximal 3 cm for the last 3 months of cortisol production). Then, the hair is finely minced with scissors or ground with a ball mill, and incubated in a solvent such as methanol. The resulting solution is evaporated to dryness and then reconstituted in a solution such as phosphate-buffered saline ‎17. Following the extraction, ELISA, RIA, or LC-MS/MS have all been used for cortisol quantification ‎14. Presently, there can be significant intraassay variability in the commercially available immunoassays. The immediate implication is that researchers in this field must try to perform all tests of a particular protocol using the same batch of cortisol immunoassay, using internal positive controls as standards, and preferably ‎6.


Mechanism of Cortisol Incorporation into Hair

From its inception as a tool to monitor stress and cortisol concentrations, there have been some persistent questions about the nature of hair cortisol analysis and the underlying pathophysiology. A frequently raised question is the mechanism by which cortisol enters the hair. Several mechanisms have been proposed (see Fig. 1). ‎6

The most commonly suggested hypothesis is based upon the complex multi-compartment model ‎18. Cortisol is thought to enter hair primarily at the level of the medulla of the hair shaft via passive diffusion from the blood. In this scenario, hair cortisol would be hypothesized to reflect the integrated free cortisol fraction rather than the total cortisol concentration in serum. Because growing hair is in contact with sweat and sebum excreted by the skin, one needs to consider also the possibility that chemicals may also be deposited externally to the hair shaft. This mechanism is important in the disposition of ethanol in hair. It is not yet known how cortisol enters the hair shaft. It is assumed that cortisol enters the hair shaft through passive diffusion, and therefore represents cumulative free circulating cortisol levels. This is further supported by the circumstantial evidence that oral contraception, which is known to increase total cortisol levels due to the effect of estrogens on corticosteroid-binding globulin levels ‎19, does not seem to have a major influence on hair cortisol concentration (HCC). However, the active transport of steroids from the bloodstream to the hair follicle cannot be excluded. Apart from incorporation from blood, sebum and sweat could also contribute to HCC ‎20,‎21. Cortisol has been demonstrated in human sweat, and it has been suggested that increased sweating may increase HCC, which may acutely influence HCC and therefore undermine the validity of HCC as a marker of long-term cortisol exposure ‎22. However, Stalder et al. recently showed that two sweat-inducing interventions (exercise and sauna bathing) do not seem to acutely influence the HCC ‎23‎,24.

Factors Affecting hair cortisol concentration (HCC)

In addition to clinical states and stressors, several other factors can potentially affect HCC. In large published studies, HCC has been shown to increase with age ‎25‎,26. In contrast, children have been found to have significantly lower HCC than adults ‎27. While several published studies have reported higher HCC in males than among females ‎25‎, 28‎, 29, in other studies no sex differences were observed ‎20‎, 26‎, 30. In two studies carried out in older adults, men had higher HCC, indicating that the sex difference in HCC becomes more pronounced later in life ‎25‎, 28. The associations between ethnicity and HCC have largely been unexplored, and need further study ‎23.

Multiple studies have confirmed a hair growth rate close to 10 mm/month ‎31. Slight differences in hair growth rate between ethnic groups have been reported, with African hair growing slower than Caucasian hair, which in turn grows more slowly than East Asian hair ‎32. Small variations in growth rate are not expected to have a large impact on studies using single measurements of long-term cortisol but should be considered when creating longer retrospective timelines ‎23.

Hair treatments such as hair dying, permanent curling, or straightening have been reported to decrease HCC ‎26‎, 30‎, 33, although other studies have not found such effects ‎20‎, 34‎, 35‎, 36‎, 37. In the largest published HCC study thus far, in which hair glucocorticoids were measured in 1258 individuals using LC-MS/MS, cortisol and cortisone were lower in hair that was colored, permanently curled, or straightened. Furthermore, the amount of cortisone decreased with higher hair washing frequency in this study ‎26. Another hair-specific limitation is the phenomenon of a wash-out, which means that hair cortisol is lower more distally in the hair, for instance, due to wear and tear, subsequent hair washings, or exposure to ultraviolet light. Another study found that HCC was stable in subsequent hair segments in 28 women over a hair length of 18 cm measured using an immunoassay ‎30, but the authors observed a decrease in cortisol levels along the hair shaft in LC-MS/MS-based method ‎38. Others have described a washout effect in HCC as well ‎19‎, 34. Therefore, wash-out of hair steroids is an important consideration, especially in studies involving retrospective timelines using segmental hair analysis ‎23.

Multiple studies have measured both cortisol and cortisone in scalp hair using LC-MS/MS ‎26‎, 38. In a study by Stalder et al ‎26. HCC correlated stronger with cardiovascular risk factors than hair cortisol did. This suggests that HCC offers valuable information about systemic glucocorticoid exposure. Furthermore, the determination of both cortisol and cortisone in hair may provide information about the activity of 11b hydroxysteroid dehydrogenase (11b-HSD) enzymes, which convert the active cortisol into cortisone and vice versa. However, 11b-HSD enzymes are expressed in the skin as well ‎39, and may, therefore, impact the ratio between cortisol and cortisol in hair locally, potentially limiting the value of this ratio as a marker of systemic 11b-HSD activity ‎23.

Medication use is known to influence different types of cortisol measurements, but until now this does not seem to be a major limiting factor in HCC measurements ‎19. It is important, however, to consider the use of topical steroids which may contaminate hair samples, and falsely increase HCC through cross-reactivity with the immunoassay. In general, topical or inhalation corticosteroids may also exert some systemic effects, and thereby decrease HCC. One study described that corticosteroid use, which was not further specified, increased HCC‎33. LC-MS/MS is not limited by cross-reactivity, but false increases may still occur with synthetic corticosteroids that are structurally similar to cortisol ‎23.





Sample Collection

Collecting head hair is less intrusive and causes less embarrassment than observed urine collection, and hair does not require refrigeration and can be stored indefinitely as cortisol is relatively stable in hair, and as such a second representative hair sample can be collected and analyzed months later.

Because hair grows at an average rate of 1 cm per month and a sample cut from the posterior scalp, it is preferred as this region of the scalp is associated with the least variation in growth rates. The root of the hair follicle itself must not be included in the analysis as it was found that hair follicles are capable of producing cortisol in response to corticotropin-releasing hormone stimulation and thus may skew the results. The amount of hair required for analysis is around 50 mg, corresponding to a pencil thickness of hair. It is important to collect sufficient hair to carry out a repeat analysis or confirmation test when needed ‎40.

Recommendations for sample collection: ‎40

  • The collection of hair samples should be undertaken by a competent individual within a secure contamination-free facility with access restrictions in place.
  • A hair collection kit with clear instructions for collection should be provided and the collector must observe a chain of custody procedures and wear gloves when handling hair.
  • The collection kit should include:
  • Chain of custody form
  • Foil and collection envelope
  • Security seal
  • Evidence bag
  • Transportation envelope
  • Instructions for the collection of a hair sample
  • The color, length, site of collection, and any obvious cosmetic treatments should be recorded.
  • The head hair sample should be aligned with the root end of the sample identified and secured, e.g., with foil.
  • Hair samples must be stored in a dry, dark environment at room temperature, away from direct sunlight. Hair samples should not be stored in the refrigerator or freezer, since swelling may occur and drugs may be lost.
  • Hair samples that are wet on a submission must be dried before storage and analysis.


Sample Preparation

The preparation of hair samples involves several steps including washing, segmentation (optional), and obtaining a representative sample from the material available ‎‎40.



Washing of hair samples before analysis has two main purposes. First, to remove hair care products, sweat, sebum, or surface material (e.g., skin cells, head lice, body fluids, etc.) that may interfere with the analysis or that may reduce extraction recovery. Second, to remove potential external cortisol. Several approaches have been described to discriminate between external contamination and cortisol. It is generally accepted that organic solvent such as isopropanol will remove only surface contamination whereas aqueous solutions or methanol will swell the hair and extract cortisol from within the hair matrix ‎40.

Incubation and Extraction

Method efficiency significantly depends on the use of a suitable extraction procedure that targets specifically cortisol. The hair sample and 1– 1.5 mL of methanol (MeOH) are incubated for 16 h at 50 OC for steroid extraction. Subsequently, the methanol is removed and dried under a gentle stream of nitrogen gas at 50 OC. The remaining residue is reconstituted with 250 mL of phosphate-buffered saline solution (PBS).

Screening Technique

Screening for a range of drugs in hair is achieved through immunological or chromatographic methodologies. Immunoassays commonly used for rapid screening of cortisol in biological fluids are also available for hair. The sample is vortexed and analyzed in duplicate using a commercially available high sensitivity salivary cortisol enzyme immunoassay kit from Salimetrics. We will describe their instructions, and both positive and negative controls are used to ensure accuracy ‎40.



Higher-stressed mothers exhibit significantly lower HCC compared to lower-stressed mothers, consistent with other research showing that chronic stress leads to blunted HPA axis activity over time. Furthermore, HCC in daughters was significantly and positively associated with previously assessed salivary cortisol stress reactivity. Finally, mother-daughter HCC associations were significantly moderated by negative parenting styles, such that associations became stronger as the quality of parenting decreased. ‎41


The Elderly

People at older ages are at increased risk for developing stress-related diseases associated with chronically elevated cortisol secretion. However, the main factors contributing to such endocrine alterations in this age group are still largely unknown.

Kirschbaum et al have found HCC to increase with participants’ age and higher in men compared to women. HCC also showed positive associations with waist-to-hip ratio, waist circumference, smoking, prevalent type 2 diabetes mellitus, mental health, daytime sleeping, and being unemployed or retired–—as well as a negative association with diastolic blood pressure. After full mutual adjustment, only age and smoking remained independent predictors of HCC. The association between prevalent type 2 diabetes mellitus and HCC was attenuated but persisted independently in women. Similarly, a positive relationship between HCC and alcohol consumption was found in women. These results confirm previous evidence of positive associations of HCC with age, sex, alcohol consumption, and type 2 diabetes mellitus and add new knowledge on factors such as smoking–—that may contribute to elevated cortisol levels in people at older ages. ‎25

Alme la et al Have shown that lower HCC was consistently related to worse working memory, learning, short-and long-term verbal memory. In contrast, higher mean levels and higher diurnal area under the curve of diurnal salivary cortisol were related to worse attention and short-term verbal memory, respectively. Interestingly, a higher ratio of mean levels of diurnal salivary cortisol over HCC was related to worse performance on working memory and short-term verbal memory. ‎42



Several factors are known to contribute to HCC in adults. However, there is less research on the determinants of HCC in children and adolescents. In a systematic review ‎43, 36 eligible pediatric studies were identified and selected for qualitative synthesis. Higher HCC was associated with male sex and anthropometry, particularly increased body mass index and waist circumference. There was preliminary evidence to suggest that socioeconomic status is inversely related to child HCC, particularly concerning caregiver education and income. Of note, most of the studies analyzing socio-economic variables were performed in relatively equal societies. Hair wash frequency and use of hair products and treatments did not affect HCC when proximal segments of hair were used. There is conflicting evidence regarding the relationship between HCC and age in children and adolescents. Further investigation is required to better delineate if and how the following are associated with HCC in children: hair color, hair type, exposure to trauma and stressors, psychiatric illness, atopic illness, steroid use (including topical and inhaled steroids), and perinatal variables.

Relatively few studies have examined hair cortisol as a marker for chronic stress in pediatric patients ‎44. The first reported HCC in newborns receiving neonatal intensive care has shown that those requiring mechanical ventilation had higher HCC than nonventilated term infants. Palmer et al ‎45 found significantly higher hair HCC in African American infants compared with white infants at 1 year of age, correlated with measures of prenatal adversity, maternal postpartum depression, parenting stress, and the child’s socio-emotional development at age 1 year. Among preschool children, HCC was negatively correlated with the parent’s educational level, but not parental income ‎46.  Longitudinal studies found a natural decrease in HCC with increasing age from 1 to 8 years ‎47. Groneveld et al ‎48 reported that HCC increased in children after starting school, with greater increases among the children who were fearful before starting school.




Koren and coworkers did not find any significant association between any of the stressors or psychological distress measures and spontaneous preterm birth. They found that spontaneous preterm birth was consistently and independently associated only with pregnancy-related anxiety, among a large number of the stressor and psychological distress measures they studied.

In the subgroup of participants with a sufficient maternal hair sample, hair cortisol was positively associated with gestational age. Neither maternal plasma CRH, hair cortisol, nor placental histopathologic features of infection/inflammation, infarction, or maternal vasculopathy was significantly associated with pregnancy-related anxiety or any other stress or distress measure. ‎49

Yamada, and co-workers have detected no significant differences between the hair HCC of term infants compared to preterm infants in the neonatal intensive care unit (NICU). When compared to a group of healthy term infants, hospitalized infants had significantly higher HCC. A subgroup analysis of the term NICU infants showed a statistically significant association between the total number of ventilator days and HCC. For every extra day on the ventilator, HCC increased on average by 0.2 nmol/g. 21% of the variance in HCC was explained by the total number of days on the ventilator. ‎44



Koren et al have detected a positive correlation between HCC and perceived chronic stress in healthy pregnant women. ‎50

Terrya et al concluded that there are a few associations between stress and HCC observed from preconception to the 3rd trimester. Observed differences in HCC based on educational attainment and anxiety were generally restricted to the preconception and 1st trimester when circulating cortisol concentrations are at their lowest compared to later in pregnancy. ‎51

Koren and his group found among a large number of stress and distress measures studied, only pregnancy-related anxiety was consistently and independently associated with spontaneous preterm birth. They did not find any significant relationships between any of the stressors or psychological distress measures and spontaneous preterm birth. Nor did they observe any associations between the stressors or measures of psychological distress and maternal plasma CRH or HCC. hair cortisol was positively associated with gestational age. Neither maternal plasma CRH, hair cortisol, nor placental histopathologic features of infection/inflammation, infarction, or maternal vasculopathy was significantly associated with pregnancy-related anxiety or any other stress or distress measure. ‎49



Karlen et al found in a sample of healthy students, that elevated HCC was found in participants who reported serious life events (e.g., death of a close relative, serious illness, etc.) during the months that were represented in the hair samples compared to participants without such an event. ‎52



Schmid et al study studied participants in five institutions employing Trauma-informed care (TIC) practices (intervention group).  and found significantly lower HCC at T4and occurrences of client physical aggression were assessed at four annual measurement time points (T1 to T4). They compared HCC between trained staff vs. staff members from institutions who did not receive training in TIC (control groups).  There were reduced physiological stress levels and HCC at T4, such that the intervention group reported significantly less physical aggression than the control group and lower HCC. ‎53


Culture and Environment

Marca et al had investigated the effect of 10-week basic military training (BMT) on HCC and found that military training increased perceived stress from the first to the second examination but did not affect HCC. In line with this, there was no correlation between HCC and perceived stress ratings. This could be interpreted as a lack of effect of mainly physical stress (e.g., exercise) on HCC. In contrast, significant correlations were found between HCC and ambient temperature, humidity, and education. ‎37


Henley et al. found no difference in HCC between volunteers from the slum settlements in Naivasha living adjacent to large floriculture farms and volunteers from Mogotio, who lived in slum settlements well-removed from large floriculture operations. Of some interest, HCC in individuals living in these settlements was higher than in Canadian of European descent. Also, they found no difference in the HCC of the 9 members of the Kenyan clinical team and the Canadians sampled.

Henley et al. reported that participants who were female, divorced, feeling unsafe using sanitation facilities, and (or) collecting water, and making less than the minimum wage in Kenya, have significantly higher HCC than their comparative controls.

After conducting a multiple linear regression with mutual adjustment for all factors, income remained the significant determinant of HCC. Individuals from these settlement communities who self-identified with the marital break-up, low income, and (or) fear, have elevated HCC. ‎54


Turbine Noise

People residing near wind turbines claim higher levels of stress and disease. In a large Canadian study, Michaud et al. concluded that there was no evidence that self-reported or objectively measured stress reactions are significantly influenced by exposure to increasing levels of wind turbine noise (WTN) up to 46 dB. ‎55



Goldberg et al. found HCC to be significantly decreased from baseline to one month after the quit smoking attempt in the entire sample. They concluded that smoking cessation intervention is associated with decreased HCC and that reduced hair cortisol may be specifically associated with mindfulness training and smoking abstinence. ‎56



Chan J et al found there was no difference in perceived stress (PSS) between non-obese and obese subjects. HCC was significantly correlated with weight and systolic blood pressure, while the correlation with BMI did not reach statistical significance. HCC did not correlate with age or urinary cortisol. There was a negative correlation between hair testosterone and age and BMI. The correlation between hair testosterone and free androgen index (FAI) did not reach statistical significance. The ratio of hair cortisol over hair testosterone (C/T) was higher in the obese group than in the young non-obese group. The C/T ratio correlated positively with age, waist circumference, and BMI, while the correlation between the C/T ratio and FAI did not reach statistical significance. ‎57

In 2017 Jackson et al examined associations between long-term cortisol levels, as assessed in hair, and adiposity in a large population-based sample. In cross-sectional analyses, HCC was positively correlated with body weight, BMI, and waist circumference and was significantly elevated in participants with obesity and raised waist circumference. ‎58

In 2018, the same group found obesity, BMI, and perceived weight discrimination were independently associated with elevated HCC. Perceived weight discrimination significantly mediated associations between obesity and hair cortisol. ‎59


Medical stress

Medical conditions can lead to medical stress, with a lot of factors generating stress in patients. We will provide 2 pieces of evidence that medical health can lead to medical stress and been measured by hair cortisol.

Russel and coworkers reported that HCC was significantly associated with the use of antidepressants, hazardous drinking, smoking, and disability after adjusting for sub-study and potential confounders (sex, body-mass index, use of glucocorticoids, and hair dyed). Besides, preliminary analyses suggest a significant curvilinear relationship between HCC and perceived stress; specifically, HCC increased with higher perceived stress but decreased at the highest level of stress. Overall, HCC was associated with mental health-related variables mainly reflecting substance use or experiencing a disability. ‎33

Abelson et al have found hair cortisol and depressive responses increased with stress, but they were decoupled, following distinct trajectories that likely reflected different aspects of stress reactivity. While depressive symptoms correlated with stressor demands and stress perceptions, the longitudinal pattern of hair cortisol suggested that it responded to contextual features related to anticipation, novelty/familiarity, and social evaluative threat. ‎60



A study by Van Uum et al demonstrated that HCC is significantly elevated in patients with severe chronic non-malignant pain syndromes as compared to non-obese control subjects. ‎61



Higher attention has been dedicated to the role of psychosocial stress in cardiovascular disease (CVD) as a result of increasing knowledge of its adverse physiological consequences for both mental and physical health.

We summarize here the cardiovascular consequences of HCC and provide an overview of recent studies investigating the relationship of HCC with CVD. The clinical implications and limitations of the evidence are discussed.

Hair cortisol may be a reliable biomarker of chronic stress since its present quantification of total cortisol secreted into the hair over several weeks to months. A growing body of evidence proposes that elevated HCC is associated with CVD. Moreover, increased HCC has been related to established cardiometabolic risk factors for CVD including high blood pressure, diabetes, and adiposity.

A systematic review of all published studies up to November 2020 revealed 14 studies examining the association of HCC with the incidence of recovery from CVD (Table 2)89. Four case-control studies found evidence for higher HCC in patients with acute coronary syndrome (ACS)‎ 62, myocardial infarction (MI) ‎63, coronary heart disease (CHD) ‎64, and aneurysmal subarachnoid hemorrhage ‎65 compared with control participants. Furthermore, a population-based study revealed that higher HCC was associated with an increased incidence of coronary heart disease, stroke, and peripheral arterial disease ‎28. In contrast, coronary heart disease diagnosis or the experience of a stroke was unrelated to HCC in a large observational cohort ‎66. However, HCC was positively associated with other CVD risk factors (i.e., BMI, diabetes) and CVD medication in this study and the authors suggest that HCC might be more predictive of CVD risk than being an actual marker of CVD.




Table 2: Association of hair cortisol with the incidence and prognosis of CVD
Factors Significant association Sample Size Duration Refs
CVD incidence


Acute coronary syndrome Yes 166 Cross-sectional 62
Acute myocardial infarction Yes 112 Cross-sectional 63
Aneurysmal subarachnoid hemorrhage Yes 32 Cross-sectional 65
Coronary heart disease Yes 598 Cross-sectional 64
Coronary heart disease/stroke/peripheral arterial disease Yes 283 Cross-sectional 28
Coronary heart disease/stroke No 3675 Cross-sectional 66
CVD prognosis
Condition Outcome/predictor
Chronic heart failure Symptom severity Yes 44 Prospective 67
Coronary artery disease Recovery Yes 56 Prospective 68
Stroke Recovery Yes 65 Prospective 69
Acute coronary syndrome Psychological distress No 121 Cross-sectional 36
Aneurysmal subarachnoid hemorrhage Psychological distress Yes 32 Cross-sectional 65
Structural heart disease Psychological distress Yes 261 Prospective 70
Structural heart disease Physical health status Yes 261 Cross-sectional 70


HCC has also been investigated as a prognostic factor in CVD. One of the studies revealed a positive relationship between HCC and the severity of symptoms in a sample of patients with chronic heart failure ‎67. Over a 1-year follow-up, there was also a positive albeit non-significant trend towards higher HCC in patients who had CVD-related hospitalizations compared with non-hospitalized patients. Elevated HCC predicted poorer memory improvement in a sample of patients with coronary artery disease attending a 1-year cardiac rehabilitation intervention ‎68, while another study demonstrated that higher HCC was associated with larger lesion volume and worse cognitive results 6-, 12- and 24-months following stroke ‎69. Elevated HCC has also been associated with greater psychological distress in patients with aneurysmal subarachnoid hemorrhage ‎65. Another study found that higher HCC was related to worse subjective physical health status in patients with structural heart disease (cardiomyopathy, congenital heart disease, or coronary heart disease), while a more favorable mental health status predicted a decline in cortisol levels at 12- week follow-up ‎70. By contrast, another study of patients with acute coronary syndrome found no evidence supporting the link between HCC and depressive symptoms.36





Verhamme et al showed that children with asthma have a significantly lower HCC than children without asthma after adjustment for age, sex, and BMI, but the HCC range completely overlapped between asthmatic and non-asthmatic subjects. Besides, they observed a nonsignificant trend of decreasing HCC with higher dosages of inhaled corticosteroids. ‎71

Smy and co-workers have tested pregnant women with asthma and found hair cortisol showed the expected change in cortisol over the course of pregnancy which hair cortisol may be a useful biomarker of HPA axis function during pregnancy and sensitive enough to detect the effects of asthma, both with and without inhaled corticosteroid treatment, on systemic cortisol levels.‎72

Carleton et al suggested that HCC may be a potential biomarker for detecting chronic adrenal suppression due to inhaled corticosteroid use in children with asthma since 5.6% of inhaled corticosteroid-treated children had HCC <2.0 ng/g compared to none in the control groups. ‎73

Koren and Carleton found that during ICS therapy, median HCC were twofold lower compared with the period of no ICS use, leading them to suggest hair cortisol is an effective biomarker of the HPA suppression associated with ICS therapy and can be a sensitive tool for determining systemic effects of ICS use and monitoring adherence. ‎74


Psychosocial Long-term Stress

Hair cortisol has the potential of providing insight into young children's long‐term stress response to social adversity. Psychosocial exposures are increasingly recognized as being critical to health throughout life. A possible mechanism could be physiologic dysregulation due to stress. Cortisol in hair is a new biomarker assessing long-term hypothalamic-pituitary-adrenal axis activity

Children born into families fraught with multiple adverse psychosocial exposures seem to have increased long-term HPA axis activity and are more likely to be affected by common childhood diseases in a dose-response manner. ‎75




Steudte et al studied hair cortisol and generalized anxiety disorder (GAD), which is characterized by long-lasting anxiety that is not specific to one situation or object, but rather is related to excessive worry and being overly concerned with everyday matters for six or more months, impairing daily functioning. The researchers found 50—60% lower HCC in GAD patients than in matched healthy controls. ‎76


Bipolar Depression

Manenschijn and colleagues found that HCC was not statistically different in bipolar disorder (BD) patients compared to healthy controls and were not associated with the disease state at the moment of sample collection. ‎77

In contrast, Coello et al. found a higher HCC in 181 patients with newly diagnosed or first episode BD compared with 101 healthy individuals. ‎78

Streit et al. found that perceived stress was higher in BD patients compared to controls, and was lower in outpatients in remission compared to inpatients on admission. In BD patients’ manic symptoms were correlated with HCC. In BD inpatients, perceived stress decreased over the 6 - month study period, while HCC did not change significantly over that period. Moreover, in controls, but not in the patient groups, the genetic risk score for BD was associated with HCC. ‎79

Staufenbiel et al found an association between the number of negative life events and increased HCC, in particular in patients with BD subtype I or in those who had an age of onset before 30 years. ‎80



Dowlati et al and colleagues inspected the relationship between HCC and depression in patients with coronary artery disease and found no association between cortisol concentration and the diagnosis of depression or between cortisol levels and the severity of depressive symptoms. ‎36

Dettenborn and colleagues conducted an analysis of hair cortisol in unipolar depressed medicated patients and showed that these patients had slightly higher HCC than healthy controls. ‎81

Rietschel et al showed moderate but significant associations between HCC and depressive symptoms. ‎82


Cushing Syndrome

Van Rossum showed that Cushing Syndrome (CS) patients had higher HCC than patient controls and healthy controls. Analysis of hair cortisol offers diagnostic accuracy for CS similar to currently used first-line tests and can be used to investigate cortisol exposure in CS patients months to years back in time, enabling estimation of disease onset. ‎83

Stratakis et al conducted the first study to evaluate segmental hair cortisol in patients with Cushing syndrome and compared it to urine and serum cortisol evaluation. Proximal hair contained the HCC and had the most significant relationship between serum and urine cortisol measurements. ‎84

Stratakis has concluded that hair cortisol can detect months’ worth of exposure to elevated cortisol levels and has been shown to stratify patients with and without Cushing syndrome. Recent evidence suggests increased sensitivity and specificity of hair cortisol in detecting Cushing syndrome. ‎85

                Thomson et al have conducted a major initial study comparing hair cortisol in healthy subjects and six patients with Cushing syndrome. They found that HCC was significantly higher in patients with CS than in healthy control subjects and that the levels decreased following successful therapy. Segmental hair analysis provided information for up to 18 months before the time of sampling. HCC appeared to vary per the clinical course. ‎86



Won Hann has found that the mean HCC in chronic hepatitis B (CHB) patients to be lower than other studies of adults over 50 years of age whose mean of hair cortisol ranged from 21.0 to 40.5 pg/mg. It suggests long-term suppression of hair cortisol production in the course of HBV infection and antiviral therapy. Low hair cortisol might indicate a specific pathogenic mechanism with cortisol production. This may explain the low HCC observed in CHB patients who are allegedly under chronic stress while suffering from CHB for years, most of them infected with HBV since birth. The rate of cortisol metabolism is decreased in liver disease. ‎87



In this study, HCC was significantly higher in patients with sarcoidosis than in general population controls. No differences were found in hair cortisol and testosterone levels between fatigued and non-fatigued sarcoidosis patients. Hair cortisol of sarcoidosis patients correlated significantly with psychological distress (anxiety, depression, and Short Form 36 (SF-36) Survey mental domain), but not with fatigue. The study suggested that hair cortisol is a promising non-invasive biomarker for psychological distress in patients with sarcoidosis. ‎88






  1. Prado-Gascó V, de la Barrera U, Sancho-Castillo S, de la Rubia-Ortí JE, Montoya-Castilla I. Perceived stress and reference ranges of hair cortisol in healthy adolescents. PLoS One. 2019 Apr 4;14(4):e0214856. doi: 10.1371/journal.pone.0214856.
  2. Heinrichs SC, Koob GF. Corticotropin-releasing factor in brain: a role in activation, arousal, and affect regulation. J Pharmacol Exp Ther. 2004 Nov;311(2):427-40. doi: 10.1124/jpet.103.052092.
  3. Gunnar MR, Donzella B. Social regulation of the cortisol levels in early human development. Psychoneuroendocrinology. 2002 Jan-Feb;27(1-2):199-220. doi: 10.1016/s0306-4530(01)00045-2.
  4. Gillespie CF, Phifer J, Bradley B, Ressler KJ. Risk and resilience: genetic and environmental influences on development of the stress response. Depress Anxiety. 2009;26(11):984-92. doi: 10.1002/da.20605.
  5. Goldstein DS. Clinical assessment of sympathetic responses to stress. Ann N Y Acad Sci. 1995 Dec 29;771:570-93. doi: 10.1111/j.1749-6632.1995.tb44711.x.
  6. Russell E, Koren G, Rieder M, Van Uum S. Hair cortisol as a biological marker of chronic stress: current status, future directions and unanswered questions. Psychoneuroendocrinology. 2012 May;37(5):589-601. doi: 10.1016/j.psyneuen.2011.09.009.
  7. Gatti R, Antonelli G, Prearo M, Spinella P, Cappellin E, De Palo EF. Cortisol assays and diagnostic laboratory procedures in human biological fluids. Clin Biochem. 2009 Aug;42(12):1205-17. doi: 10.1016/j.clinbiochem.2009.04.011.
  8. Yehuda R, Halligan SL, Golier JA, Grossman R, Bierer LM. Effects of trauma exposure on the cortisol response to dexamethasone administration in PTSD and major depressive disorder. Psychoneuroendocrinology. 2004 Apr;29(3):389-404. doi: 10.1016/s0306-4530(03)00052-0.
  9. Vining RF, McGinley RA, Maksvytis JJ, Ho KY. Salivary cortisol: a better measure of adrenal cortical function than serum cortisol. Ann Clin Biochem. 1983 Nov;20 (Pt 6):329-35. doi: 10.1177/000456328302000601.
  10. Aardal E, Holm AC. Cortisol in saliva--reference ranges and relation to cortisol in serum. Eur J Clin Chem Clin Biochem. 1995 Dec;33(12):927-32. doi: 10.1515/cclm.1995.33.12.927.
  11. Burch WM. Urine free-cortisol determination. A useful tool in the management of chronic hypoadrenal states. JAMA. 1982 Apr 9;247(14):2002-4. doi: 10.1001/jama.247.14.2002.
  12. Wennig R. Potential problems with the interpretation of hair analysis results. Forensic Sci Int. 2000 Jan 10;107(1-3):5-12. doi: 10.1016/s0379-0738(99)00146-2.
  13. Davenport MD, Tiefenbacher S, Lutz CK, Novak MA, Meyer JS. Analysis of endogenous cortisol concentrations in the hair of rhesus macaques. Gen Comp Endocrinol. 2006 Jul;147(3):255-61. doi: 10.1016/j.ygcen.2006.01.005.
  14. Gow R, Thomson S, Rieder M, Van Uum S, Koren G. An assessment of cortisol analysis in hair and its clinical applications. Forensic Sci Int. 2010 Mar 20;196(1-3):32-7. doi: 10.1016/j.forsciint.2009.12.040.
  15. Warnock F, McElwee K, Seo RJ, McIsaac S, Seim D, Ramirez-Aponte T, Macritchie KA, Young AH. Measuring cortisol and DHEA in fingernails: a pilot study. Neuropsychiatr Dis Treat. 2010 Feb 3;6:1-7.
  16. Ben Khelil M, Tegethoff M, Meinlschmidt G, Jamey C, Ludes B, Raul JS. Simultaneous measurement of endogenous cortisol, cortisone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate in nails by use of UPLC-MS-MS. Anal Bioanal Chem. 2011 Sep;401(4):1153-62. doi: 10.1007/s00216-011-5172-3.
  17. Sauvé B, Koren G, Walsh G, Tokmakejian S, Van Uum SH. Measurement of cortisol in human hair as a biomarker of systemic exposure. Clin Invest Med. 2007;30(5):E183-91. doi: 10.25011/cim.v30i5.2894.
  18. Boumba VA, Ziavrou KS, Vougiouklakis T. Hair as a biological indicator of drug use, drug abuse or chronic exposure to environmental toxicants. Int J Toxicol. 2006 May-Jun;25(3):143-63. doi: 10.1080/10915810600683028.
  19. Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM. The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008 May;93(5):1526-40. doi: 10.1210/jc.2008-0125.
  20. Stalder T, Steudte S, Alexander N, Miller R, Gao W, Dettenborn L, Kirschbaum C. Cortisol in hair, body mass index and stress-related measures. Biol Psychol. 2012 Jul;90(3):218-23. doi: 10.1016/j.biopsycho.2012.03.010.
  21. Stalder T, Steudte S, Miller R, Skoluda N, Dettenborn L, Kirschbaum C. Intraindividual stability of hair cortisol concentrations. Psychoneuroendocrinology. 2012 May;37(5):602-10. doi: 10.1016/j.psyneuen.2011.08.007.
  22. Russell E, Koren G, Rieder M, Van Uum SH. The detection of cortisol in human sweat: implications for measurement of cortisol in hair. Ther Drug Monit. 2014 Feb;36(1):30-4. doi: 10.1097/FTD.0b013e31829daa0a.
  23. Wester VL, van Rossum EF. Clinical applications of cortisol measurements in hair. Eur J Endocrinol. 2015 Oct;173(4):M1-10. doi: 10.1530/EJE-15-0313.
  24. Grass J, Kirschbaum C, Miller R, Gao W, Steudte-Schmiedgen S, Stalder T. Sweat-inducing physiological challenges do not result in acute changes in hair cortisol concentrations. Psychoneuroendocrinology. 2015 Mar;53:108-16. doi: 10.1016/j.psyneuen.2014.12.023.
  25. Feller S, Vigl M, Bergmann MM, Boeing H, Kirschbaum C, Stalder T. Predictors of hair cortisol concentrations in older adults. Psychoneuroendocrinology. 2014 Jan;39:132-140. doi: 10.1016/j.psyneuen.2013.10.007.
  26. Stalder T, Kirschbaum C, Alexander N, Bornstein SR, Gao W, Miller R, Stark S, Bosch JA, Fischer JE. Cortisol in hair and the metabolic syndrome. J Clin Endocrinol Metab. 2013 Jun;98(6):2573-80. doi: 10.1210/jc.2013-1056.
  27. Noppe G, Van Rossum EF, Koper JW, Manenschijn L, Bruining GJ, de Rijke YB, van den Akker EL. Validation and reference ranges of hair cortisol measurement in healthy children. Horm Res Paediatr. 2014;82(2):97-102. doi: 10.1159/000362519.
  28. Manenschijn L, Schaap L, van Schoor NM, van der Pas S, Peeters GM, Lips P, Koper JW, van Rossum EF. High long-term cortisol levels, measured in scalp hair, are associated with a history of cardiovascular disease. J Clin Endocrinol Metab. 2013 May;98(5):2078-83. doi: 10.1210/jc.2012-3663.
  29. Dettenborn L, Tietze A, Kirschbaum C, Stalder T. The assessment of cortisol in human hair: associations with sociodemographic variables and potential confounders. Stress. 2012 Nov;15(6):578-88. doi: 10.3109/10253890.2012.654479.
  30. Manenschijn L, Koper JW, Lamberts SW, van Rossum EF. Evaluation of a method to measure long term cortisol levels. Steroids. 2011 Sep-Oct;76(10-11):1032-6. doi: 10.1016/j.steroids.2011.04.005.
  31. Schu¨tz H, Ahrens B, Erdmann F & Rochholz G. Nachweis von Arzneiund anderen Fremdstoffen in Haaren. Pharmazie in unserer Zeit 1993 22 65–78.
  32. Loussouarn G, El Rawadi C & Genain G. Diversity of hair growth profiles. International Journal of Dermatology 2005 44 (Suppl 1) 6–9. (doi:10.1111/j.1365-4632.2005.02800.x)
  33. Wells S, Tremblay PF, Flynn A, Russell E, Kennedy J, Rehm J, Van Uum S, Koren G, Graham K. Associations of hair cortisol concentration with self-reported measures of stress and mental health-related factors in a pooled database of diverse community samples. Stress. 2014 Jul;17(4):334-42. doi: 10.3109/10253890.2014.930432.
  34. Kirschbaum C, Tietze A, Skoluda N, Dettenborn L. Hair as a retrospective calendar of cortisol production-Increased cortisol incorporation into hair in the third trimester of pregnancy. Psychoneuroendocrinology. 2009 Jan;34(1):32-7. doi: 10.1016/j.psyneuen.2008.08.024.
  35. Skoluda N, Dettenborn L, Stalder T, Kirschbaum C. Elevated hair cortisol concentrations in endurance athletes. Psychoneuroendocrinology. 2012 May;37(5):611-7. doi: 10.1016/j.psyneuen.2011.09.001.
  36. Dowlati Y, Herrmann N, Swardfager W, Thomson S, Oh PI, Van Uum S, Koren G, Lanctôt KL. Relationship between hair cortisol concentrations and depressive symptoms in patients with coronary artery disease. Neuropsychiatr Dis Treat. 2010 Sep 7;6:393-400.
  37. Boesch M, Sefidan S, Annen H, Ehlert U, Roos L, Van Uum S, Russell E, Koren G, La Marca R. Hair cortisol concentration is unaffected by basic military training, but related to sociodemographic and environmental factors. Stress. 2015 Jan;18(1):35-41. doi: 10.3109/10253890.2014.974028.
  38. Noppe G, de Rijke YB, Dorst K, van den Akker EL, van Rossum EF. LC-MS/MS-based method for long-term steroid profiling in human scalp hair. Clin Endocrinol (Oxf). 2015 Aug;83(2):162-6. doi: 10.1111/cen.12781.
  39. Tiganescu A, Walker EA, Hardy RS, Mayes AE, Stewart PM. Localization, age- and site-dependent expression, and regulation of 11β-hydroxysteroid dehydrogenase type 1 in skin. J Invest Dermatol. 2011 Jan;131(1):30-6. doi: 10.1038/jid.2010.257.
  40. Cooper GA, Kronstrand R, Kintz P; Society of Hair Testing. Society of Hair Testing guidelines for drug testing in hair. Forensic Sci Int. 2012 May 10;218(1-3):20-4. doi: 10.1016/j.forsciint.2011.10.024.
  41. Ouellette SJ, Russell E, Kryski KR, Sheikh HI, Singh SM, Koren G, Hayden EP. Hair cortisol concentrations in higher- and lower-stress mother-daughter dyads: A pilot study of associations and moderators. Dev Psychobiol. 2015 Jul;57(5):519-34. doi: 10.1002/dev.21302.
  42. Pulopulos MM, Hidalgo V, Almela M, Puig-Perez S, Villada C, Salvador A. Hair cortisol and cognitive performance in healthy older people. Psychoneuroendocrinology. 2014 Jun;44:100-11. doi: 10.1016/j.psyneuen.2014.03.002.
  43. Gray NA, Dhana A, Van Der Vyver L, Van Wyk J, Khumalo NP, Stein DJ. Determinants of hair cortisol concentration in children: A systematic review. Psychoneuroendocrinology. 2018 Jan;87:204-214. doi: 10.1016/j.psyneuen.2017.10.022.
  44. Yamada J, Stevens B, de Silva N, Gibbins S, Beyene J, Taddio A, Newman C, Koren G. Hair cortisol as a potential biologic marker of chronic stress in hospitalized neonates. Neonatology. 2007;92(1):42-9. doi: 10.1159/000100085.
  45. Palmer FB, Anand KJ, Graff JC, Murphy LE, Qu Y, Völgyi E, Rovnaghi CR, Moore A, Tran QT, Tylavsky FA. Early adversity, socioemotional development, and stress in urban 1-year-old children. J Pediatr. 2013 Dec;163(6):1733-1739.e1. doi: 10.1016/j.jpeds.2013.08.030.
  46. Vaghri Z, Guhn M, Weinberg J, Grunau RE, Yu W, Hertzman C. Hair cortisol reflects socio-economic factors and hair zinc in preschoolers. Psychoneuroendocrinology. 2013 Mar;38(3):331-40. doi: 10.1016/j.psyneuen.2012.06.009. Epub 2012 Jul 17.
  47. Karlén J, Frostell A, Theodorsson E, Faresjö T, Ludvigsson J. Maternal influence on child HPA axis: a prospective study of cortisol levels in hair. Pediatrics. 2013 Nov;132(5):e1333-40. doi: 10.1542/peds.2013-1178.
  48. Groeneveld MG, Vermeer HJ, Linting M, Noppe G, van Rossum EF, van IJzendoorn MH. Children's hair cortisol as a biomarker of stress at school entry. Stress. 2013 Nov;16(6):711-5. doi: 10.3109/10253890.2013.817553.
  49. Kramer MS, Lydon J, Séguin L, Goulet L, Kahn SR, McNamara H, Genest J, Dassa C, Chen MF, Sharma S, Meaney MJ, Thomson S, Van Uum S, Koren G, Dahhou M, Lamoureux J, Platt RW. Stress pathways to spontaneous preterm birth: the role of stressors, psychological distress, and stress hormones. Am J Epidemiol. 2009 Jun 1;169(11):1319-26. doi: 10.1093/aje/kwp061.
  50. Kalra S, Einarson A, Karaskov T, Van Uum S, Koren G. The relationship between stress and hair cortisol in healthy pregnant women. Clin Invest Med. 2007;30(2):E103-7. doi: 10.25011/cim.v30i2.986.
  51. Orta OR, Tworoger SS, Terry KL, Coull BA, Gelaye B, Kirschbaum C, Sanchez SE, Williams MA. Stress and hair cortisol concentrations from preconception to the third trimester. Stress. 2019 Jan;22(1):60-69. doi: 10.1080/10253890.2018.1504917.
  52. Karlén J, Ludvigsson J, Frostell A, Theodorsson E, Faresjö T. Cortisol in hair measured in young adults - a biomarker of major life stressors? BMC Clin Pathol. 2011 Oct 25;11:12. doi: 10.1186/1472-6890-11-12.
  53. Schmid M, Lüdtke J, Dolitzsch C, Fischer S, Eckert A, Fegert JM. Effect of trauma-informed care on hair cortisol concentration in youth welfare staff and client physical aggression towards staff: results of a longitudinal study. BMC Public Health. 2020 Jan 7;20(1):21. doi: 10.1186/s12889-019-8077-2.
  54. Henley P, Lowthers M, Koren G, Fedha PT, Russell E, VanUum S, Arya S, Darnell R, Creed IF, Trick CG, Bend JR. Cultural and socio-economic conditions as factors contributing to chronic stress in sub-Saharan African communities. Can J Physiol Pharmacol. 2014 Sep;92(9):725-32. doi: 10.1139/cjpp-2014-0035.
  55. Michaud DS, Feder K, Keith SE, Voicescu SA, Marro L, Than J, Guay M, Denning A, Bower T, Villeneuve PJ, Russell E, Koren G, van den Berg F. Self-reported and measured stress related responses associated with exposure to wind turbine noise. J Acoust Soc Am. 2016 Mar;139(3):1467-79. doi: 10.1121/1.4942402.
  56. Goldberg SB, Manley AR, Smith SS, Greeson JM, Russell E, Van Uum S, Koren G, Davis JM. Hair cortisol as a biomarker of stress in mindfulness training for smokers. J Altern Complement Med. 2014 Aug;20(8):630-4. doi: 10.1089/acm.2014.0080. Epub 2014 Jun 25.
  57. Chan J, Sauvé B, Tokmakejian S, Koren G, Van Uum S. Measurement of cortisol and testosterone in hair of obese and non-obese human subjects. Exp Clin Endocrinol Diabetes. 2014 Jun;122(6):356-62. doi: 10.1055/s-0034-1374609.
  58. Jackson SE, Kirschbaum C, Steptoe A. Hair cortisol and adiposity in a population-based sample of 2,527 men and women aged 54 to 87 years. Obesity (Silver Spring). 2017 Mar;25(3):539-544. doi: 10.1002/oby.21733.
  59. Jackson SE, Steptoe A. Obesity, perceived weight discrimination, and hair cortisol: a population-based study. Psychoneuroendocrinology. 2018 Dec;98:67-73. doi: 10.1016/j.psyneuen.2018.08.018.
  60. Mayer SE, Lopez-Duran NL, Sen S, Abelson JL. Chronic stress, hair cortisol and depression: A prospective and longitudinal study of medical internship. Psychoneuroendocrinology. 2018 Jun;92:57-65. doi: 10.1016/j.psyneuen.2018.03.020.
  61. Van Uum SH, Sauvé B, Fraser LA, Morley-Forster P, Paul TL, Koren G. Elevated content of cortisol in hair of patients with severe chronic pain: a novel biomarker for stress. Stress. 2008 Nov;11(6):483-8. doi: 10.1080/10253890801887388.
  62. Izawa S, Miki K, Tsuchiya M, Yamada H, Nagayama M. Hair and fingernail cortisol and the onset of acute coronary syndrome in the middle-aged and elderly men. Psychoneuroendocrinology. 2019 Mar;101:240-245. doi: 10.1016/j.psyneuen.2018.11.021.
  63. Pereg D, Gow R, Mosseri M, Lishner M, Rieder M, Van Uum S, Koren G. Hair cortisol and the risk for acute myocardial infarction in adult men. Stress. 2011 Jan;14(1):73-81. doi: 10.3109/10253890.2010.511352.
  64. Bossé S, Stalder T, DʼAntono B. Childhood Trauma, Perceived Stress, and Hair Cortisol in Adults With and Without Cardiovascular Disease. Psychosom Med. 2018 May;80(4):393-402. doi: 10.1097/PSY.0000000000000569.
  65. Colledge F, Brand S, Zimmerer S, Pühse U, Holsboer-Trachsler E, Gerber M. In Individuals Following Aneurysmal Subarachnoid Haemorrhage, Hair Cortisol Concentrations Are Higher and More Strongly Associated with Psychological Functioning and Sleep Complaints than in Healthy Controls. Neuropsychobiology. 2017;75(1):12-20. doi: 10.1159/000477966.
  66. Abell JG, Stalder T, Ferrie JE, Shipley MJ, Kirschbaum C, Kivimäki M, Kumari M. Assessing cortisol from hair samples in a large observational cohort: The Whitehall II study. Psychoneuroendocrinology. 2016 Nov;73:148-156. doi: 10.1016/j.psyneuen.2016.07.214.
  67. Pereg D, Chan J, Russell E, Berlin T, Mosseri M, Seabrook JA, Koren G, Van Uum S. Cortisol and testosterone in hair as biological markers of systolic heart failure. Psychoneuroendocrinology. 2013 Dec;38(12):2875-82. doi: 10.1016/j.psyneuen.2013.07.015.
  68. Saleem M, Herrmann N, Swardfager W, Oh PI, Shammi P, Koren G, Van Uum S, Kiss A, Lanctôt KL. Higher cortisol predicts less improvement in verbal memory performance after cardiac rehabilitation in patients with coronary artery disease. Cardiovasc Psychiatry Neurol. 2013;2013:340342. doi: 10.1155/2013/340342.
  69. Ben Assayag E, Tene O, Korczyn AD, Shopin L, Auriel E, Molad J, Hallevi H, Kirschbaum C, Bornstein NM, Shenhar-Tsarfaty S, Kliper E, Stalder T. High hair cortisol concentrations predict worse cognitive outcome after stroke: Results from the TABASCO prospective cohort study. Psychoneuroendocrinology. 2017 Aug;82:133-139. doi: 10.1016/j.psyneuen.2017.05.013.
  70. Younge JO, Wester VL, van Rossum EF, Gotink RA, Wery MF, Utens EM, Hunink MG, Roos-Hesselink JW. Cortisol levels in scalp hair of patients with structural heart disease. Int J Cardiol. 2015 Apr 1;184:71-8. doi: 10.1016/j.ijcard.2015.02.005.
  71. Baan EJ, van den Akker ELT, Engelkes M, de Rijke YB, de Jongste JC, Sturkenboom MCJM, Verhamme KM, Janssens HM. Hair cortisol and inhaled corticosteroid use in asthmatic children. Pediatr Pulmonol. 2020 Feb;55(2):316-321. doi: 10.1002/ppul.24551.
  72. Smy L, Shaw K, Amstutz U, Smith A, Berger H, Carleton B, Koren G. Hair cortisol as a hypothalamic-pituitary-adrenal axis biomarker in pregnant women with asthma: a retrospective observational study. BMC Pregnancy Childbirth. 2016 Jul 20;16(1):176. doi: 10.1186/s12884-016-0962-4.
  73. Smy L, Shaw K, Amstutz U, Staub M, Chaudhry S, Smith A, Carleton B, Koren G. Assessment of hair cortisol as a potential biomarker for possible adrenal suppression due to inhaled corticosteroid use in children with asthma: A retrospective observational study. Clin Biochem. 2018 Jun;56:26-32. doi: 10.1016/j.clinbiochem.2018.04.006.
  74. Smy L, Shaw K, Smith A, Russell E, Van Uum S, Rieder M, Carleton B, Koren G. Hair cortisol as a novel biomarker of HPA suppression by inhaled corticosteroids in children. Pediatr Res. 2015 Jul;78(1):44-7. doi: 10.1038/pr.2015.60.
  75. Karlén J, Ludvigsson J, Hedmark M, Faresjö Å, Theodorsson E, Faresjö T. Early psychosocial exposures, hair cortisol levels, and disease risk. Pediatrics. 2015 Jun;135(6):e1450-7. doi: 10.1542/peds.2014-2561.
  76. Steudte-Schmiedgen S, Wichmann S, Stalder T, Hilbert K, Muehlhan M, Lueken U, Beesdo-Baum K. Hair cortisol concentrations and cortisol stress reactivity in generalized anxiety disorder, major depression and their comorbidity. J Psychiatr Res. 2017 Jan;84:184-190. doi: 10.1016/j.jpsychires.2016.09.024.
  77. Manenschijn L, Spijker AT, Koper JW, Jetten AM, Giltay EJ, Haffmans J, Hoencamp E, van Rossum EF. Long-term cortisol in bipolar disorder: associations with age of onset and psychiatric co-morbidity. Psychoneuroendocrinology. 2012 Dec;37(12):1960-8. doi: 10.1016/j.psyneuen.2012.04.010.
  78. Coello K, Munkholm K, Nielsen F, Vinberg M, Kessing LV. Hair cortisol in newly diagnosed bipolar disorder and unaffected first-degree relatives. Psychoneuroendocrinology. 2019 Jan;99:183-190. doi: 10.1016/j.psyneuen.2018.09.020.
  79. Streit F, Memic A, Hasandedić L, Rietschel L, Frank J, Lang M, Witt SH, Forstner AJ, Degenhardt F, Wüst S, Nöthen MM, Kirschbaum C, Strohmaier J, Oruc L, Rietschel M. Perceived stress and hair cortisol: Differences in bipolar disorder and schizophrenia. Psychoneuroendocrinology. 2016 Jul;69:26-34. doi: 10.1016/j.psyneuen.2016.03.010.
  80. Staufenbiel SM, Koenders MA, Giltay EJ, Elzinga BM, Manenschijn L, Hoencamp E, van Rossum EF, Spijker AT. Recent negative life events increase hair cortisol concentrations in patients with bipolar disorder. Stress. 2014 Dec;17(6):451-9. doi: 10.3109/10253890.2014.968549.
  81. Dettenborn L, Muhtz C, Skoluda N, Stalder T, Steudte S, Hinkelmann K, Kirschbaum C, Otte C. Introducing a novel method to assess cumulative steroid concentrations: increased hair cortisol concentrations over 6 months in medicated patients with depression. Stress. 2012 May;15(3):348-53. doi: 10.3109/10253890.2011.619239.
  82. Rietschel L, Streit F, Zhu G, McAloney K, Kirschbaum C, Frank J, Hansell NK, Wright MJ, McGrath JJ, Witt SH, Rietschel M, Martin NG. Hair Cortisol and Its Association With Psychological Risk Factors for Psychiatric Disorders: A Pilot Study in Adolescent Twins. Twin Res Hum Genet. 2016 Oct;19(5):438-46. doi: 10.1017/thg.2016.50.
  83. Wester VL, Reincke M, Koper JW, van den Akker ELT, Manenschijn L, Berr CM, Fazel J, de Rijke YB, Feelders RA, van Rossum EFC. Scalp hair cortisol for diagnosis of Cushing's syndrome. Eur J Endocrinol. 2017 Jun;176(6):695-703. doi: 10.1530/EJE-16-0873.
  84. Hodes A, Lodish MB, Tirosh A, Meyer J, Belyavskaya E, Lyssikatos C, Rosenberg K, Demidowich A, Swan J, Jonas N, Stratakis CA, Zilbermint M. Hair cortisol in the evaluation of Cushing syndrome. Endocrine. 2017 Apr;56(1):164-174. doi: 10.1007/s12020-017-1231-7.
  85. Hodes A, Meyer J, Lodish MB, Stratakis CA, Zilbermint M. Mini-review of hair cortisol concentration for evaluation of Cushing syndrome. Expert Rev Endocrinol Metab. 2018 Sep;13(5):225-231. doi: 10.1080/17446651.2018.1517043.
  86. Thomson S, Koren G, Fraser LA, Rieder M, Friedman TC, Van Uum SH. Hair analysis provides a historical record of cortisol levels in Cushing's syndrome. Exp Clin Endocrinol Diabetes. 2010 Feb;118(2):133-8. doi: 10.1055/s-0029-1220771.
  87. Hann, Hie-Won & Meyer, Jerrold & Park, Grace & Block, Peter & Juon, Hee-Soon. Hair cortisol and chronic stress exposure in chronic Hepatitis B patients. Clin. Invest. (Lond.). 2019 Nov 15; 9(4), 121-127.
  88. van Manen MJG, Wester VL, van Rossum EFC, van den Toorn LM, Dorst KY, de Rijke YB, Wijsenbeek MS. Scalp hair cortisol and testosterone levels in patients with sarcoidosis. PLoS One. 2019 Jun 14;14(6):e0215763. doi: 10.1371/journal.pone.0215763.
  89. Iob E, Steptoe A. Cardiovascular Disease and Hair Cortisol: a Novel Biomarker of Chronic Stress. Curr Cardiol Rep. 2019 Aug 30;21(10):116. doi: 10.1007/s11886-019-1208-7.