What Do Cortisol Curves Tell Us About Health?

Young Black girl meditating on her couch with headphones on, a functional medicine therapy which helps her cortisol curves balance.
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The adrenal hormone cortisol impacts nearly all of the body’s systems. Cortisol levels fluctuate throughout the day, normally peaking in the morning hours and bottoming out at night. Deviations from this diurnal pattern have been associated with signs and symptoms of adrenal dysfunction. One such dysfunctional pattern is a flat cortisol curve, in which the amount of cortisol secreted (high or low) shifts very little throughout the day. In both healthy and clinical populations, flatter diurnal cortisol slopes have been associated with risk of a shorter lifespan and with negative physical and mental health outcomes.1-4

Mortality Risk & Cardiovascular Implications

Research continues to elucidate the health consequences of flattened or dysregulated cortisol slopes. Results of one observational study suggested that the flattening of the cortisol curve predicted early death from lung cancer and was associated with low T-cell lymphocyte counts.5 In an older cohort study of healthy individuals (n=4,047 adults, average age of 61 years), flattened cortisol curves correlated with mortality from all causes, including cardiovascular deaths.1

Most recently, a 2022 German cohort study that included a random representative sample from the general population (n=1,090 adults) assessed salivary cortisol and cardiovascular morbidity and mortality.3 Reported results indicated that a greater diurnal cortisol peak-to-bedtime ratio at baseline predicted a decreased risk of cardiovascular mortality (HR: 0.50; CI: 0.34-0.73) and a decreased risk of stroke (HR: 0.71; CI: 0.55-0.92).3 In addition, an increased level of late-night salivary cortisol that reflected a dysregulated diurnal cortisol pattern was associated with a higher risk of cardiovascular mortality (HR: 1.49; CI: 1.13-1.97) and an increased risk of stroke (HR: 1.24; 1.01-1.52).3

In addition to the potential heart and health impacts of increased late-night cortisol levels, studies have also suggested that elevated morning plasma cortisol levels may be a risk factor for cardiovascular disease.6

Diabetes and Depression

A blunted cortisol curve may also be correlated with diabetes and higher HbA1c in individuals with diabetes.7,8 Due to potential differences among diurnal cortisol profiles in different race populations9 and age groups, the 2021 CARDIA study examined the longitudinal association of diurnal cortisol curve patterns with incident diabetes over a 10-year period among African American adults (n=376) and middle-aged individuals (n=333 white adults, median age 40 years).10 Results indicated that a robust cortisol awakening response was associated with lower odds of incident diabetes among middle-aged white participants while a flatter late decline slope was associated with increased odds of incident diabetes among middle-aged white participants; however, the study’s analysis did not indicate a relationship between the measured diurnal cortisol curve features and the development of diabetes in African Americans.10

Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been implicated in the development of major depressive disorder (MDD) in adults. A 2020 systematic review and meta-analysis analyzed several prospective biomarkers of MDD and found that only cortisol was identified as a potential predictor of onset, relapse, and recurrence of MDD.11 A 2022 systematic review and meta-analysis evaluated the relationship between cortisol and MDD in adolescents.12 From the 14 studies included in the meta-analysis, elevated morning cortisol levels were found to precede depression in the younger population.12

Chronic Stressors & Populations

Measuring cortisol over the course of a day may help predict health outcomes both for patients with diseases and for seemingly healthy individuals. And understanding the factors that affect cortisol secretion can inform appropriate treatment interventions. Recurrent exposure to multiple social, physical, or environmental stressors not only impacts a patient’s quality of life and wellness but may compound negative health effects and disease burden.13 A 2019 US-based observational study (N=1,793 adults, median age of 65) evaluated exposure to traffic-related air pollution and salivary cortisol levels.14 A moderate association was reported. Specifically, higher morning cortisol levels were seen among those participants who were exposed to higher NO2 levels, and among all participants in the cross-sectional analysis, the features of the cortisol curve became flatter over five years.14 Sustained psychosocial stress may also contribute to cortisol dysregulation. A small 2022 study examined the relationship between racial discrimination and stress responses among healthy Black adults (n=12).15 Researchers found that the previous day’s racial discrimination exposure was significantly associated with the next day’s waking cortisol level and diurnal slope.15 In addition, experiencing microaggressions was significantly associated with the diurnal cortisol slope in the same day. Investigators further explained that on the days when participants reported more microaggressions, a flatter diurnal slope of cortisol was observed.15

Posttraumatic stress disorder (PTSD), a severe form of psychological stress that affects 3.5% of US adults, also affects 8% of pregnant women.16 Cortisol is an important biomarker for perinatal and developmental research; in utero elevations in hypothalamic-pituitary-adrenal (HPA) axis hormones have been associated with adverse perinatal outcomes, including preterm birth and early morbidity and mortality. An interesting 2018 study suggested that pregnant women with the dissociative subtype of PTSD, a complex form associated with a history of childhood maltreatment, may be experiencing toxic levels of cortisol.16 Studies on childhood maltreatment (and other adverse childhood experiences) and toxic stress continue to evolve, as some research suggests that these experiences may be linked with disease across the lifespan.17


Results from the 2022 Stress in America survey indicated that nearly three-quarters of adults experienced health impacts due to stress in the prior month, including headache, fatigue, feeling nervous or anxious, and feeling depressed or sad.18 Key areas of stress included health care, inflation, violence and safety, and both the racial and political climates.18

The importance of addressing chronic stress is growing, as more and more studies continue to link stress to disease across the lifespan. How can clinicians screen for high levels of emotional and psychological stress in their patients? What can be done to mitigate the effects of toxic stress? The functional medicine model shows clinicians how to identify the sources of stress in each patient and best practices for measuring cortisol levels and implementing the most appropriate personalized treatment plans. Read more about modifiable lifestyle factors that impact cortisol levels in IFM’s article Lifestyle Changes for Shifting Cortisol Levels.

Determining the underlying cause of a hormonal imbalance or dysfunction may be challenging, depending on
the individual patient and presentation. The functional medicine approach helps identify points of leverage where physicians can apply individualized interventions to help restore cortisol patterns and overall hormonal balance. Learn more at IFM’s upcoming Hormone Advanced Practice Module (APM).


Related Articles

Lifestyle Changes for Shifting Cortisol Levels

How do stress and inflammation contribute to chronic disease?

Chronic stress and hormone disruption


  1. Kumari M, Shipley M, Stafford M, Kivimaki M. Association of diurnal patterns in salivary cortisol with all-cause and cardiovascular mortality: findings from the Whitehall II study. J Clin Endocrinol Metab. 2011;96(5):1478-1485. doi:1210/jc.2010-2137
  2. Imami L, Jiang Y, Murdock KW, Zilioli S. Links between socioeconomic status, daily depressive affect, diurnal cortisol patterns, and all-cause mortality. Psychosom Med. 2022;84(1):29-39. doi:1097/PSY.0000000000001004
  3. Karl S, Johar H, Ladwig KH, Peters A, Lederbogen F. Dysregulated diurnal cortisol patterns are associated with cardiovascular mortality: findings from the KORA-F3 study. Psychoneuroendocrinology. 2022;141:105753. doi:1016/j.psyneuen.2022.105753
  4. Adam EK, Quinn ME, Tavernier R, McQuillan MT, Dahlke KA, Gilbert KE. Diurnal cortisol slopes and mental and physical health outcomes: a systematic review and meta-analysis. Psychoneuroendocrinology. 2017;83:25-41. doi:1016/j.psyneuen.2017.05.018
  5. Sephton SE, Lush E, Dedert EA, et al. Diurnal cortisol rhythm as a predictor of lung cancer survival. Brain Behav Immun. 2013;30(Suppl):S163-S170. doi:1016/j.bbi.2012.07.019
  6. Crawford AA, Soderberg S, Kirschbaum C, et al. Morning plasma cortisol as a cardiovascular risk factor: findings from prospective cohort and Mendelian randomization studies. Eur J Endocrinol. 2019;181(4):429-438. doi:1530/EJE-19-0161
  7. Joseph JJ, Golden SH. Cortisol dysregulation: the bidirectional link between stress, depression, and type 2 diabetes mellitus. Ann N Y Acad Sci. 2017;1391(1):20-34. doi:1111/nyas.13217
  8. Panagiotou C, Lambadiari V, Maratou E, et al. Insufficient glucocorticoid receptor signaling and flattened salivary cortisol profile are associated with metabolic and inflammatory indices in type 2 diabetes. J Endocrinol Invest. 2021;44(1):37-48. doi:1007/s40618-020-01260-2
  9. Boileau K, Barbeau K, Sharma R, Bielajew C. Ethnic differences in diurnal cortisol profiles in healthy adults: a meta-analysis. Br J Health Psychol. 2019;24(4):806-827. doi:1111/bjhp.12380
  10.  Kluwe B, Ortiz R, Odei JB, et al. The association of cortisol curve features with incident diabetes among whites and African Americans: the CARDIA study. Psychoneuroendocrinology. 2021;123:105041. doi:1016/j.psyneuen.2020.105041
  11.  Kennis M, Gerritsen L, van Dalen M, Williams A, Cuijpers P, Bockting C. Prospective biomarkers of major depressive disorder: a systematic review and meta-analysis. Mol Psychiatry. 2020;25(2):321-338. doi:1038/s41380-019-0585-z
  12.  Zajkowska Z, Gullett N, Walsh A, et al. Cortisol and development of depression in adolescence and young adulthood – a systematic review and meta-analysis. Psychoneuroendocrinology. 2022;136:105625. doi:1016/j.psyneuen.2021.10562510
  13.  Guidi J, Lucente M, Sonino N, Fava GA. Allostatic load and its impact on health: a systematic review. Psychother Psychosom. 2021;90(1):11-27. doi:1159/000510696
  14.  Hajat A, Hazlehurst MF, Golden SH, et al. The cross-sectional and longitudinal association between air pollution and salivary cortisol: evidence from the Multi-Ethnic Study of Atherosclerosis. Environ Int. 2019;131:105062. doi:1016/j.envint.2019.105062
  15.  Nam S, Jeon S, Lee SJ, Ash G, Nelson LE, Granger DA. Real-time racial discrimination, affective states, salivary cortisol and alpha-amylase in Black adults. PLoS One. 2022;17(9):e0273081. doi:1371/journal.pone.0273081
  16.  Seng JS, Li Y, Yang JJ, et al. Gestational and postnatal cortisol profiles of women with posttraumatic stress disorder and the dissociative subtype. J Obstet Gynecol Neonatal Nurs. 2018;47(1):12-22. doi:1016/j.jogn.2017.10.008
  17.  Kuras YI, Assaf N, Thoma MV, et al. Blunted diurnal cortisol activity in healthy adults with childhood adversity. Front Hum Neurosci. 2017;11:574. doi:3389/fnhum.2017.00574
  18.  American Psychological Association. Stress in America 2022: concerned for the future, beset by inflation. Published October 2022. Accessed March 21, 2023.

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