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Stress and Hormone Regulation

Stress is a natural part of our lives, and although it gets a bad reputation, stress isn’t necessarily a terrible thing. Stress helps us deal with new situations and threats. It keeps us alert and on our toes. It can even be considered healthy: the ability to adapt to stress can make the body (and mind) stronger – but only if there is a proper “recovery” period afterwards. Where we get into trouble health wise is in situations of chronic stress; when there isn’t enough recovery but a maintenance or resistance to stress for so long, followed by a phase of exhaustion.

When the brain perceives something as a threat, it connects that signal to the hypothalamic-pituitary-adrenal (HPA) axis. This pathway of the HPA axis is a cascade of hormones being released starting from within the brain and working their way down to the adrenal glands. Other hormone systems and the immune system can both be affected by these signals as well.

Hormones Cortisol and DHEA

What’s a normal response to acute stress? When something alarms us, two very important stress hormones, cortisol and DHEA, work together to mediate glucose metabolism and the immune system to prepare the body to handle the energy demands of that stress.  

Cortisol and DHEA are equally important because they regulate each other. DHEA actually helps reduce the potentially damaging effects of cortisol. When this balance is disrupted, we tend to see physical and mental health issues. For example, if specific immune responses aren’t suppressed, this can lead to increased levels of inflammation – an immune-related reaction.

DHEA is also important because in response to acute stress, it supports cognitive function. Therefore, DHEA might actually support a resilience to stress.1

Cortisol’s actions go beyond just reacting to acute stress. Cortisol release works in a daily cyclical fashion where levels are highest in the morning as you start your day, and trend downward, being the lowest at bedtime. This makes sense as we should be winding down at bedtime, not ramping up to deal with a stress trigger or threat.

Chronic stress: Resistance and Exhaustion

When dealing with prolonged stress (versus acute), we fall into a state of resistance. Cortisol levels will still be increased but DHEA levels actually decline. Without the protective effects of DHEA there’s a tendency to feel more stressed, with an increase in anxiety levels, mood changes and it can feel like you’re in a constant state of “fight or flight.” When this continues without any recovery we reach what is known as the exhaustion phase of stress and levels of both cortisol and DHEA remain low and less responsive.

If you were to conduct the four-point cortisol test on someone in the resistance state (either with blood draws, or as a saliva test), you would notice elevated levels of cortisol typically in the afternoon and/or before bed. This is one of the reasons why chronic stress can lead to sleep disturbances. In the exhaustion state, it’s more common to see a flatline effect whereby the normal morning elevation in cortisol is blunted, making individuals feel more lethargic, especially in the mornings.

Researchers have found that individuals who had greater lifetime stress exposure (number of stressful events, not the perceived severity of those stressors) had blunted cortisol in response to acute stress, but heightened DHEA responses.1 Interestingly, the association between cumulative stress and cortisol levels is strongest for “stressors occurring in adulthood and involving romantic relationships.”1

This same response (blunted cortisol and enhanced DHEA) has been seen more in those with posttraumatic stress disorder (PTSD).1 But how this affects overall and long-term health has yet to be established.

Stress and Sex Hormones

Increased levels of cortisol also affect sex hormones and reproduction. In particular, when cortisol levels increase to those associated with stress, it inhibits the release of gonadotropin-releasing hormone (GnRH), which then blunts the release in estrogen and luteinizing hormone (LH).2 In an animal (sheep) model of stress, increased concentrations of cortisol led to a delay in egg maturation and ovulation.2 In human studies, stress was associated with women having longer menstrual cycles (>35 days) and decreased pregnancy rates.2

This helps explain the effect of anovulation (a lack of ovulation and often times absent menstruation) in women experiencing high levels of stress and/or in those who over-train/over-exercise. This condition is known as hypothalamic amenorrhea: stress-induced loss of menstruation. This effect is typically reversible once cortisol levels have normalized.



  1. Lam JCW, et al. (2019). Greater lifetime stress exposure predicts blunted cortisol but heightened DHEA responses to acute stress. Stress Health. 35(1): 15-26
  2. Palomba S, et al. (2018). Lifestyle and fertility: the influence of stress and quality of life on female fertility. Reprod Biol Endocrinol. 16: 113



About The Author

Dr. Sarah Zadek is a licensed naturopathic doctor in Ontario with a clinical focus on women’s health, endocrinology and fertility. Sarah graduated from Nipissing University with an honours degree in biology after completing her thesis on genetics, oxidative stress and immune function. Her working background includes 14 years in pharmacy. Sarah is also an author and has written for multiple publications across North America including the NaturalPath, Naturopathic News and Review (NDNR), Naturopathic Currents, and Eco Parent Magazine online. Dr. Sarah Zadek is a naturopathic doctor with Conceive Health, practicing at Lakeridge Fertility in Whitby, and is a technical writer for Advanced Orthomolecular Research (AOR).

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