Stress hormone imbalances

We all need stress hormones to survive. Cortisol, the key stress hormone drives our flight or fight mechanism. When we perceive a situation to be ‘stressful’ our stress hormones respond by:

• Increasing our blood sugar
  • To send glucose to our muscles, and inhibit glucose uptake in the peripheral regions of the body such as skeletal muscles which are less useful when fighting or fleeing Marik, P. E. and Bellomo, R. Stress hyperglycemia: an essential survival response!. [online] Critical Care, 17 (2), p. 305. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672537/ [accessed 10 Oct. 2017].
• Increasing our heart rate
  • To pump more blood into our system to fight or flee
• Slowing down our digestion
  • And reducing blood flow to the digestive system since it is nonessential to survival when faced with an immediate threat Ogoh, S., Sato, K., Okazaki, K., Miyamoto, T., Hirasawa, A., Morimoto, K. and Shibasaki, M. (2013). Blood flow distribution during heat stress: cerebral and systemic blood flow. [online] Journal of Cerebral Blood Flow & Metabolism, 33 (12), pp. 1915-20. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851900/ [accessed 10 Oct. 2017].
• Influencing our immune system
  • Short-term stress (lasting for minutes to hours) can activate and enhance the immune system
  • Long-term stress however can suppress the immune system Dhabhar, F. S. (2014). Effects of stress on immune function: the good, the bad, and the beautiful. [online] Immunologic Research, 58 (2-3), pp. 193-210. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24798553 [accessed 10 Oct. 2017].

McEwen, B. S. and Stellar, E. (1993). Stress and the individual. Mechanisms leading to disease. [online] Archives of International Medicine, 153 (18), pp. 2093-101. Available at: https://www.ncbi.nlm.nih.gov/pubmed/8379800/ [accessed 11 Oct. 2017].

The HPA (hypothalamic-pituitary-adrenal) axis is part of the limbic system of the brain.

The limbic system is the part of the brain involved with processing smell, as well as emotions such as fear, rage, sexual behaviour, addiction, motivation and memory. RajMohan V, Mohandas E. The limbic system. Indian J Psychiatry [serial online] 2007 [cited 2018 Feb 13];49:132-9. Available from: http://www.indianjpsychiatry.org/text.asp?2007/49/2/132/33264

The HPA axis coordinates the response to stress within the body.

Any stressor either externally in the form of fear or anxiety, or internally caused by infection or low blood sugar, for instance, is processed by the HPA axis.

Stress activates the HPA axis through the secretion of corticotropin-releasing factor (CRF) from the hypothalamus.

This, in turn, stimulates adrenocorticotropic hormone (ACTH) from the pituitary gland, which in turn leads to the release of the major stress hormone – cortisol – from the adrenal glands. Carabotti, M., Scirocco, A., Maselli, M. A., & Severi, C. (2015). The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Annals of Gastroenterology : Quarterly Publication of the Hellenic Society of Gastroenterology, 28(2), 203–209.

Dysregulation of the HPA axis or a hyper-sensitive HPA axis has been observed in people with IBS, CFS and fibromyalgia. Mayer, S.E. et al. (2017) The psychology of HPA axis activation: Examining subjective emotional distress and control in a phobic fear exposure model. Psychoneuroendocrinology , Volume 82 , 189 – 198

One of the most damaging effects of chronically high stress hormones is HPA axis dysregulation. Indeed, chronically elevated stress hormones can lead to a disruption of the HPA axis which regulates our perception of, and resilience to, stress and can cause mental health symptoms such as depression, anxiety, panic, exhaustion, mood swings, irritability, cognitive impairment and memory issues.

Chronic emotional stress is only a part of what can disrupt our HPA axis. Even if people don’t feel stressed, biochemical stressors could still be causing stress hormone imbalances.

Indeed, perceived stress may be low, but if you have a disrupted gut microbiome or chronic lack of sleep, this can cause low grade inflammation which then affects our HPA axis negatively, which in turn can increase inflammation.

According to Chris Kresser, there are four key factors which can disrupt the HPA axis:

• Perceived stress
  • What each of us will experience as stressful according to our own unique personality and life circumstances
• Blood sugar imbalances
  • Fluctuating blood sugar can increase stress hormones, so even if you’re not feeling stressed, your body can be releasing stress hormones with its cascade of biochemical consequences
• Circadian disruptions
  • We evolved in a 24hr light/dark cycle, and our physiology is adapted to that natural rhythm
  • When this is disrupted due to exposure to too much artificial light from screens; jet lag; night shifts or not getting enough exposure to bright light during the day, this can cause the release of stress hormones
  • Without feeling stressed, our bodies can still experience the effects of increased stress hormones
• Inflammation
  • Any kind of inflammation caused by injury, disease, gut dysbiosis, sleep deprivation (even mild), excessive exercise, etc. can act as a stressor to the HPA axis and can throw our bodies and hormonal systems out of balance, especially when the situation happens repeatedly or lasts a long time

The health of the HPA system, often referred to as “adrenal health”, is considered essential for preventing and healing mental health issues, and is often the first area of investigation by integrative and functional doctors.

HPA axis dysregulation is often misdiagnosed and can go untreated for a long time. Its symptoms are varied and wide ranging, often paralleling those of depression and other common mental health disorders, as well as other common medical complaints such as fatigue. Therefore, it is often overlooked or misdiagnosed in conventional medicine, as well as in alternative medicine.Gottfried, S. (2013). The Hormone Cure. New York: Scribner, p. 12, p. 76.

Mental health symptoms of HPA axis dysregulation

The key cause of HPA axis dysregulation is usually chronically high stress hormone levels. Therefore the mental health symptoms of high stress hormones and HPA axis dysregulation are similar. Furthermore, the symptoms of HPA axis dysregulation mirror symptoms of depression, so it is not surprising that conventional doctors often prescribe anti-depressants, anti-anxiety and sleeping pills, rather than treating the HPA axis system.

• Depression
  • Excessive cortisol can affect dopamine and serotonin levels, the neurotransmitters for pleasure, motivation and mood Talbott, S M. (2007). The Cortisol Connection. 2^nd ed. Alameda, CA: Hunter House, p. 81. Amen, D. (2013). Unleash the Power of The Female Brain. New York: Harmony Books, p. 130.
  • Depressed patients show higher than average cortisol levels Gottfried, S. (2013). The Hormone Cure. New York: Scribner, p. 86.
• Anxiety
  • Panic
  • Often in the middle of the night or early morning, sometimes waking with a pounding heart Chris Kresser webinar
  • Excessive cortisol can block the production of progesterone, the calming hormone, leading to anxiety Gottfried, S. (2013). The Hormone Cure. New York: Scribner, p. 129.
  • Excessive cortisol can interfere with your production of serotonin, causing anxiety and nervousness Amen, D. (2013). Unleash the Power of The Female Brain. New York: Harmony Books, p. 130.
  • PTSD
  • OCD Chris Kresser webinar
• Fatigue
  • Often unresolved by a good night sleep; lack of stamina Chris Kresser webinar
  • Partly caused by the fact that chronically high cortisol depletes DHEA, which is necessary for feeling energetic Amen, D. (2013). Unleash the Power of The Female Brain. New York: Harmony Books, p. 130.
  • Can also be due to cortisol resistance, when cells become numb to the effects of cortisol
• Sleep issues
  • Difficulty falling asleep or waking in the middle of the night and difficulty getting back to sleep Chris Kresser webinar
  • There is a correlation between high cortisol and insomnia
    • 24 hour cortisol levels have been shown to be higher in people with insomnia Gottfried, S. (2013). The Hormone Cure. New York: Scribner, p. 87.
• Feeling overwhelmed
• Decreased resilience to stress Amen, D. (2013). Unleash the Power of The Female Brain. New York: Harmony Books, p. 131.
• Low libido
• Anhedonia – inability to experience joy
• Increased susceptibility to PMS
• Poor concentration and attention Chris Kresser webinar, Talbott, S M. (2007). The Cortisol Connection. 2^nd ed. Alameda, CA: Hunter House, p. 47, p. 59, pp. 81-2, p. 128. Gottfried, S. (2013). The Hormone Cure. New York: Scribner, p. 80, pp. 86-7.
• Poor memory Talbott, S M. (2007). The Cortisol Connection. 2^nd ed. Alameda, CA: Hunter House, p. 47, p. 59, pp. 81-2, p. 128. Gottfried, S. (2013). The Hormone Cure. New York: Scribner, p. 80, pp. 86-7.
  • There are a large number of cortisol receptors in the hippocampus, the part of the brain responsible for memory, and chronically high cortisol kills cells in the hippocampus, affecting memory Amen, D. (2013). Unleash the Power of The Female Brain. New York: Harmony Books, p. 130.
  • Chronically high cortisol levels are also linked with Alzheimer’s, Holford, P. (2007). Optimum Nutrition for the Mind. London: Piatkus, p. 85. as well as with MS Gottfried, S. (2013). The Hormone Cure. New York: Scribner, pp. 86-7.
• Irritability
• Decreased productivity
• Addiction
• PMS

Physical symptoms of HPA axis dysregulation

• Susceptibility to repeated infections
• Difficulty recovering from illness, injury or trauma
• Cravings, especially for sweet and salty foods
• Muscle and joint aches
• Cold hands and feet
  • This can also be a symptom of hypothyroidism
  • The autonomic nervous system regulates blood flow and body temperature. During the stress response, certain arteries constrict while others expand so that blood is flowing to the parts of the body that need it for fight or flight. Therefore chronic stress leads to decreased circulation in the extremities (hands, feet, brain and sex organs) Chris Kresser webinar
• Blood sugar issues
  • Extreme hunger
  • Difficulty regulating blood sugar and reactive hypoglycemia Chris Kresser webinar
• Dizziness from standing up too quickly
• High blood pressure and rapid heartbeat
• Abdominal fat (tire around the middle)
• Weight gain or weight loss
• Premature ageing
• Skin problems
• Gut issues
• Hypo and hyperthyroidism

Amen, D. (2013). Unleash the Power of The Female Brain. New York: Harmony Books, p. 131.

Many of the above symptoms are caused by the fact that imbalances in the HPA system and chronically high stress hormones will throw other hormonal systems out of whack causing further hormonal imbalances in sex, thyroid and metabolic hormones.Amen, D. (2013). Unleash the Power of The Female Brain. New York: Harmony Books, p. 94.

Over time, chronically elevated levels of stress and accompanying cortisol can damage the body by:

• Impairing overall hormonal balance
• Influencing brain chemistry
  • Elevated cortisol levels can damage brain cells and impact neurotransmitter balance
• Contributing to anxiety, depression, brain fog and insomnia, and
• Resulting in atrophy of certain brain regions Bremner, D. J. (2006). Stress and Brain Atrophy. [online] CNS & Neurological Disorders Drug Targets, 5 (5), pp. 503–12. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269810/ [accessed 10 Oct. 2017].

Stress hormones are often produced at the expense of hormones which keep you feeling healthy, happy, calm and energetic.

This is linked to “pregnenolone steal” when pregnenolone is used to manufacture cortisol, at the expense of important hormones and brain chemicals, though this theory has recently been thrown into doubt and needs further research.

Chronically high stress hormones can negatively impact levels of:

• Sex hormones such as progesterone (calming), estrogen (mood boosting) and testosterone (confidence-boosting)
• Steroid hormones such as DHEA (energy-boosting, but also low levels of DHEA have been linked to psychosis) Lake, J. (2009). Integrative Mental Health Care. New York: W.W. Norton & Co., p. 238.
• Thyroid hormones
  • An increase in cortisol and adrenaline impact the hypothalamus and pituitary glands, causing the thyroid to produce less thyroid hormone, which can cause symptoms of hypothyroidism Gottfried, S. (2013). The Hormone Cure. New York: Scribner, p. 52, p. 247.
  • Both high and low cortisol can impair thyroid function Gottfried, S. (2013). The Hormone Cure. New York: Scribner, p. 279.
  • Strong link between the HPA and the HPT axis (hypothalamic-pituitary-thyroid) Gottfried, S. (2013). The Hormone Cure. New York: Scribner, pp. 279-81.
  • Mental illness, such as major depression, is associated with disordered function and impaired interaction between the HPA and HPT axis Mokrani, M-C, Duval, F., Erb, A., Gonzalez, F. and Paris, V. (2016). Impaired interactions between circadian activity of the HPA and HPT axes in depression. [online] Psychoneuroendocrinology, 71 (Suppl), p. 29. Available at: http://www.psyneuen-journal.com/article/S0306-4530(16)30304-3/abstract [accessed 10 Oct. 2017].
• Growth hormone
• Melatonin
• Insulin
  • Chronically high cortisol can cause insulin levels to rise and stay high, causing insulin resistance and low grade inflammation of the brain, thereby negatively impacting mental health Amen, D. (2013). Unleash the Power of The Female Brain. New York: Harmony Books, p. 129.

Chronically elevated cortisol can have a negative impact on brain regeneration and BDNF:

• BDNF is a brain chemical which encourages the growth of nerve cells and brain regeneration especially in the areas of the brain associated with higher thinking, learning and long term memory Gottfried, S. (2013). The Hormone Cure. New York: Scribner, p. 63.
• BDNF levels, trafficking and signalling are disrupted in early neurodegeneration Almeida, M. F., Chaves, R. S., Silva, C. M., Chaves, J., Melo, K. P. and Ferrari, M. (2016). BDNF trafficking and signalling impairment during early neurodegeneration is prevented by moderate physical activity. [online] IBRO Reports, 1, pp.19-31. Available at: http://www.sciencedirect.com/science/article/pii/S2451830116300036 [accessed 10 Oct. 2017]. and can impact neurotransmitter synthesis.
• Chronically high cortisol can cause vasoconstriction in the brain, physical atrophy of brain cells, and neurodegeneration Furtado, M. and Katzman, M. A. (2015). Examining the role of neuroinflammation in major depression. [online] Psychiatry Research, 229 (1-2), pp. 27-36. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26187338 [accessed 10 Oct. 2017].
• Chronically high cortisol is associated with increased nerve firing, which can be damaging to the brain, and also neuronal atrophy (diminished neurons in the brain and the connections between them) Nagaraja, A. S., Sadaoui, N. C., Dorniak, P. L., Lutgendorf, S. K. and Sood, A. K. (2016). SnapShot: Stress and Disease. [online] Cell Metabolism, 23 (2), p. 388. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26863488 [accessed 10 Oct. 2017].
• Low levels of BDNF are associated with cognitive decline, including Huntington’s, Parkinson’s and Alzheimer’s disease Liou, S. (2010). Brain-derived neurotrophic factor (BDNF). [online] HOPES: Huntington’s Outreach Project for Education, at Stanford. Available at: http://web.stanford.edu/group/hopes/cgi-bin/hopes_test/brain-derived-neurotrophic-factor-bdnf/ [accessed 19 Nov. 2018].

Gottfried, S. (2013). The Hormone Cure. New York: Scribner, p. 46, p. 126, p. 281. Talbott, S M. (2007). The Cortisol Connection. 2^nd ed. Alameda, CA: Hunter House, p. 83. Amen, D. (2013). Unleash the Power of The Female Brain. New York: Harmony Books, pp. 129-30.

Imbalances in stress hormones can cause and/or exacerbate mental health issues due to their impact on our nutritional status. Indeed, chronically high stress hormones will reduce the digestion and absorption of nutrients, in part because the stress response takes priority over other bodily functions such as digestion. Indeed “fight or flight” is the alternative to “rest and digest”.

• Blood is diverted from the stomach to the muscles
• The production of digestive enzymes and saliva are slowed
• Intestinal contractions and absorption of nutrients are stopped Talbott, S M. (2007). The Cortisol Connection. 2^nd ed. Alameda, CA: Hunter House, p. 120.
• Certain key nutrients essential for our resilience to stress get depleted
  • Vitamins B1, B5, B6, B12 and CB-1 which are important for stress tolerance Behrendt, I., Schneider, I., Schuchardt, J. P., Bitterlich, N. and Hahn, A. (2016). Effect of an herbal extract of Sideritis scardica and B-vitamins on cognitive performance under stress: a pilot study. [online] International Journal of Phytomedicine, 8 (1), pp. 95-103. Available at: http://www.arjournals.org/index.php/ijpm/article/view/1736 [accessed 10 Oct. 2017].
  • The amino acid Tyrosine
  • Magnesium Gottfried, S. (2013). The Hormone Cure. New York: Scribner, p. 100.

The extreme pathology of high cortisol is Cushing’s disease, characterised by:

• Extremely high cortisol levels
• Large amounts of abdominal fat and severe loss of muscle in the arms and legs Talbott, S M. (2007). The Cortisol Connection. 2^nd ed. Alameda, CA: Hunter House, p. 85.
• This condition is relatively rare. However, if you suffer from many of the symptoms of excessive cortisol (LINK) you may want to rule out Cushing’s
• Cushing’s disease is one end of the spectrum, however you don’t have to have Cushing’s to suffer from the symptoms of chronically high cortisol levels and the associated mental health effects

Chronic emotional stress can be caused by:

• Psychological and physical trauma
• Difficult life circumstances
• Relationship difficulties
• Negative thought patterns and beliefs
• Overworking, and/or working in high intensity, competitive environments
•  Commuting
• 24/7 connectivity and activity

• Due to skipping meals for instance
• “Cognitive dietary restraint” (defined as “a perceived ongoing effort to limit dietary intake to manage body weight”, or simply dieting) increases cortisol Talbott, S M. (2007). The Cortisol Connection. 2^nd ed. Alameda, CA: Hunter House, p. 147.

Chronic inflammation can be caused by:

• Gut issues
• Lack of sleep and disruption of circadian rhythms
• Nutritional imbalances
• Maladaptive exercise (too much or too little)
• Repeated illness or injury

Estrogen replacement therapy can increase cortisol levels.Edwards, K. M., & Mills, P. J. (2008). Effects of estrogen versus estrogen and progesterone on cortisol and interleukin-6. Maturitas, 61(4), 330–333. http://doi.org/10.1016/j.maturitas.2008.09.024

Chronic dehydration can cause chronically raised cortisol levels.Talbott, S M. (2007). The Cortisol Connection. 2^nd ed. Alameda, CA: Hunter House, p. 251.

Extremes of cold or heat for prolonged periods of time can cause chronically high stress hormones.

Repeated use of stimulants such as caffeine (2 or 3 cups per day) can raise cortisol, and ephedra (used for weight loss) can cause chronically high cortisol levels.Talbott, S M. (2007). The Cortisol Connection. 2^nd ed. Alameda, CA: Hunter House, pp. 45-6.

High BMI and obesity can cause chronically high cortisol levels.Talbott, S M. (2007). The Cortisol Connection. 2^nd ed. Alameda, CA: Hunter House, p. 58.

• As we age, cortisol levels increase in relation to other hormones (such as sex hormones, DHEA) which decline Heaney, J. L., Phillips, A. C. and Carroll, D. (2012). Ageing, physical function, and the diurnal rhythms of cortisol and dehydroepiandrosterone. [online] Psychoneuroendocrinology, 37 (3), pp. 341-9. Available at: https://www.ncbi.nlm.nih.gov/pubmed/21802858 [accessed 10 Oct. 2017]. Gottfried, S. (2013). The Hormone Cure. New York: Scribner, p. 79.
• As we age we often react to stressors (such as illness, trauma, exercise, etc.) with a more acute stress response, therefore causing higher cortisol levels, and we recover less quickly from these stressors, which causes cortisol levels to stay high for longer periods of time Talbott, S M. (2007). The Cortisol Connection. 2^nd ed. Alameda, CA: Hunter House, p. 126.

As we age, our cells can become more resistant to cortisol.

We feel tired because our cells are not responding as well to cortisol and yet we feel wired because we have high cortisol levels in our blood.

As with ageing, chronic stress can cause cellular resistance to cortisol, meaning that our tissues and brain are less sensitive to the effects of cortisol. Chris Kresser webinar

Taking synthetic glucocorticoid hormones for a long period of time (such as prednisone and other corticoids such as asthma inhalers) can reduce the body’s own cortisol production. This is because the hypothalamus and pituitary constantly monitor hormone levels in the body, and if there is an excess of a certain hormone, such as cortisol, they will reduce the production of cortisol. Chris Kresser webinar