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The HPA-axis and Hormone Balance

Contextualizing the neuroendocrine system is no easy feat, as there are hundreds of signals and factors that enable each organ to communicate sending positive and negative feedback signals. Imagine if you will, each organ is centered on a teeter-totter in the middle of many scattered across a playground, with strings connecting them all. The tension in the strings is constantly changing as each organ needs to stay balanced. When lifestyle, and environmental factors push any organ in one direction, the strings help the other organs compensate releasing more or less of a hormone- while we have developed impressive resilience to stressors over time the strength of the string falters and we can cause suppression or hyperstimulation of the entire network. While it may sound overwhelming this approach offers a number of benefits in terms of a) understanding disease pathophysiology and b) offering alternative treatment approaches.

The “MVP organs” of the endocrine system- our Hypothalamus (the “master gland” of the neuroendocrine system), Pituitary gland, Adrenal gland, Thyroid gland, and sex organs, are being investigated as a beautifully calibrated and responsive network rather than isolated organs. In shifting our exploration to complex interconnectedness of these organs as “endocrine axis” such as the HPA/HPT axis, we begin to understand intricate signaling and response pathways that get triggered with neurohormones and circulating serum hormones. Replacing concepts such as “adrenal fatigue” which only focuses on a single organ output, and instead focusing on the “hypothalamic-pituitary-adrenal axis dysfunction” as a systemic network with multiple influences helps us understand how the breakdowns in communication pathways result in complex endocrine disorders such as hypothyroidism, adrenal insufficiency, PCOS, Cushing’s with a spectrum of symptoms.

Physiology of “Normal” response:

Portions of the brain that are responsible for regulating hormone output, namely the hypothalamus and pituitary, directly tell the “primary gland” i.e. adrenal gland to produce cortisol during times of stress. When the body has enough cortisol to “cope” with stress or when the stressor is removed, it should tell the brain centers to turn off this loop. Ultimately, the HPA axis is responsible for regulating how our body reacts to stress by determining how much cortisol is needed. The HPT axis is a parallel network but relating to regulation of the production and release of thyroid hormone. But it doesn’t stop there, chronic stress can actually interrupt the HPT axis as well. These disruptions clinically manifest as depression, fatigue, insomnia, food cravings, weight gainto more insidious concerns such as tissue or organ damage, low libido, anxiety, increased blood pressure, immune dysregulation, chronic inflammation, and improper digestion. The reason we see such a strong link between stress and our digestive, sleep, immune, and reproductive systems is related to the changes that often occur “higher up” in this pathway. Like a dam, blockages upstream can have significant effects downstream, for example corticotropin-releasing-factor (CRF), released by the hypothalamus signals the pituitary to release ACTH but also increases anxiety-like behavior, abdominal pain, colon secretions, muscle contractions (motility) and increases bowel permeability. CRF also impacts immune cell in the gut. Suffice to say it is worth investigating and managing elevated stress levels from a deeper perspective!

Staging Hypothalamic-pituitary- adrenal dysfunction

Chronically in Alarm phase:

  • Response mechanisms are on high alert.
  • Highly elevated- BP/ serum, salivary, and urinary cortisol/ body temperature
  • “wired but tired”

Chronically in a Resistance phase:

  • Silent threat- seemingly returning to “normal” functioning however cortisol, blood pressure remain elevated
  • Un-able to wake up in the mornings with an increase in energy in evenings
  • “Like a duck- calm above water but frantically paddling below water”

Chronically in Exhaustion phase

  • Nutrients and cofactors have become depleted leading to a desensitization of the feedback looks in hypothalamus and pituitary causing an overall depression or exhaustion
  • Low BP, Blood sugar, cortisol curve
  • Poor digestion, weight fluctuations
  • Depressed mood and sleep dysfunction
  • The cortisol depression results in the removal of the immune suppression thus individuals are more susceptible to infection and slow to recover.

How to Reset a dysfunctional HPA axis:

The “stress response” to external stressors can occur in stages depending on the intensity, type, and duration of exposure to a stressor, from extreme temperature changes to bear attacks our body has to respond quickly and appropriately. When stressors persist, such as years of frantic deadlines and 60-hour work weeks, we can move through stages of the adrenal response. Where initially your endocrine system may be primed and ready to receive transmissions and respond appropriately, over time if the stressor has been removed, we either become desensitized to the stimulus, or no longer have the resources to mount an appropriate response. Therefore, management of HPA axis dysfunction is complicated and often requires a multipronged approach. Further complicated by the wide spectrum of non-specific symptoms that individuals can experience. Treatment largely depends on the appropriate identification of the stage of dysfunction in individual is in.


So, where do we start?

First, identify where stress is cropping up in your life and determine which are modifiable factors and which you cannot change given your circumstances. Perhaps it’s your living situation, relationships, a job or aspect of work. Begin to pay attention to physical symptoms that may accompany mental or emotional stressors. Don’t ignore the pounding headache or inability to sleep whenever you have to do a presentation at work. Bringing awareness does not remove the stressor however at least it gives you an opportunity to take stock of behaviours and environments that trigger your stress so you can begin to address them.

Second, seek support. Whether that’s social, professional, or physical support make sure you build a team that can help you. In fact, loneliness is a type of chronic stress and is related to increased cardiovascular risk. The idea is not to simply “get out more” rather to establish meaningful interactions and engagement with the world we live in. Experts suggest using social media not as a way to envy the lives of our friends and strangers but as a means to get back in contact and have meaningful dialogue but making sure to put the devices down and get physical interaction regularly. Further, professional support can help develop tangible tools whether these are therapeutic mental emotional tools, or physical dietary or lifestyle interventions that will mitigate the impacts of stress.

Third, move, eat, sleep repeat- wild, we know! Sometimes we forget to engage in the simplest and most basic restorative and nutritive activities. We won’t belabor the point (as we have lots of articles on sleep here) but good quality deep sleep is highly restorative on a physiological level. Movement and exercise also offset the physical damage that inflammation from stress can cause, while also improving mood and resilience to mental stress. While the complex relationship between our gut and brain (and thus stress response) has been well described. Restoring balance in the body requires the nutrients, cofactors, and energy we derive from our food. Further, dietary triggers of inflammation can also cause a stress response by overburdening tissues. Thus, we must get our digestive health in order for proper functioning of the HPA axis. Of course, for defined periods of time we may consider supplementation to support these systems. The overarching theme for botanical and nutrient actions is to restore homeostasis- in alarm phase this requires calming and “quenching”; in the resistance phase gentle support for both sleep and immune needs to be added; finally, in exhaustion phase treatment focuses on repleting depleted nutrients, stimulating and resetting feedback systems.

A well-rounded formula utilizes clinical research of active constituents in botanicals and nutrients to address current dysfunctions while also addressing the progression of symptoms. Meaning it can offer calming and relaxation without sedating, support immune function, act as a precursor to mediators in the HPA axis.

About The Author

Dr. NavNirat Nibber, ND is a graduate of the Canadian College of Naturopathic Medicine and a registered Naturopathic Doctor. She is a Co-Owner at Crescent Health Clinic, as well as a Senior Medical Advisor at Advanced Orthomolecular Research.

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