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Essential System 2 - HPA Axis & Stress

The second problem is HPA axis dysregulation, which is also referred to as adrenal fatigue syndrome. This and the gut, are probably the two biggest issues with hormone imbalance.

Pregnenolone is the mother of all hormones. It’s the precursor to all of the different adrenal and sex hormones that are produced in the body, and the enzyme that converts cholesterol into pregnenolone – so cholesterol is the precursor to pregnenolone, and that’s why cholesterol is so important in the body, and really low cholesterol can be a problem for hormones as cholesterol is the precursor to pregnenolone.

The enzyme that converts cholesterol to pregnenolone is limited, and it requires a lot of ATP, which is cellular energy. It’s an energy-intensive process. Thus, the amount of pregnenolone we can make in the body is limited, and there’s something called the pregnenolone steal which describes a process where the majority of the pregnenolone that we produce on a daily basis, is channeled into cortisol production, and this happens when we’re under a lot of stress because cortisol is one of the hormones that’s involved in the stress response.  

So if you’re not sleeping well, you’re not managing your stress, you’ve got a lot of stuff going on in your life, and/or you have gut infections or you’re eating a poor diet or you’re dealing with any kind of chronic illness/injury/pain problem, that’s going to create a stress response in the body, and that in turn will divert pregnenolone into that cortisol pathway, and it takes it away from the DHEA pathway.


The DHEA pathway is where oestrogen and testosterone are produced. So if you have low DHEA levels on a lab, that’s often a sign of pregnenolone steal, and getting back to the replacement model, if you just give that patient more pregnenolone, it can actually make things worse because it just channels more raw material into that cortisol pathway.

The solution, in this case, is that you have to decrease stress physiology, so you have to address the underlying causes of the stress, whether it’s a gut infection or poor diet or lack of sleep, or emotional/psychological factors.  

Blood sugar issues 

You have to also address blood sugar issues because that can be a stressor on the body. Insulin resistance can lead to elevated cortisol levels, and high cortisol levels can lead to insulin resistance.


And of course, you need to do all of the other things that we’ve talked about at length to manage stress, so making sure you’re getting enough sleep, doing some regular stress management, addressing any gut issues or any other chronic health issues that are causing a stress response in the body.

Dr. Maureen Allem: "Despite the fact that I’m keenly aware of how important it is and I take steps to manage it pretty regularly, it’s still something that I struggle with. But what I can tell you is- in doing a lot of testing and treating well over a thousand patients with these kinds of problems, almost every man or woman had a sex hormone issue". She adds, "women who either have low progesterone and estrogen dominance or excess testosterone and men with low testosterone; virtually every single one of these patients that I’ve treated had an underlying HPA axis issue. So I can’t emphasize this enough. You have to address the adrenal side because if your pregnenolone levels are low or they’re getting diverted into cortisol because of stress, you just will not have enough raw material to make the sex hormones, and that can lead to infertility, it can lead to menstrual cycle issues, mood imbalances, low libido – all the classic hormone symptoms".

The HPA axis is responsible for managing and adapting our stress response. When we are exposed to stressors, cortisol is released and our body is placed in a fight or flight response. When our bodies are functioning optimally, the body is supposed to return to homeostasis after a while as the hypothalamus and the pituitary gland situated in the brain release the necessary hormones to bring us back into balance. 

When we are however repeatedly or constantly exposed to certain stressors, we can over time adapt to the stressors resulting in sustained HPA axis activation resulting in ongoing states of alarm. If this continues, the brain becomes insensitive to the signals that help us return to homeostasis and so begins a cascade of responses that lead to inflammation & illness.

It is therefore imperative to manage stress, manage cortisol levels, so as to mitigate the negative effects of prolonged stress on the mind and the body.

The consequences of chronic stress can be devastating, therefore early detection and management are vital!

A chilling example is stress cardiomyopathy. This is a spontaneous weakening of the heart that predisposes victims to arrhythmia and even sudden cardiac death. Stress cardiomyopathy is not yet clearly understood, but it is thought that chronic stress-induced elevations in adrenaline can over-stimulate the cardiac muscle, which leads to altering its function and causing atrial remodelling.

Karoshi is another deadly consequence; this is how the Japanese refer to an overworked individual who dies as a result of it, identified post World War II. It was found that relatively young high-level executives suffered strokes and heart attacks at alarming rates due to being severely emotionally and physically stressed. Researchers discovered that the death of these otherwise healthy men was due to chronic, unremitting stress. The Japanese government estimates of 1990 put the number of men dying each year from Karoshi at over 10,000.

Prolonged stress has been linked with elevated circulating markers of inflammation, and increased intima-media thickness, a measure of atherosclerosis progression.

Chronic stress considerably increases the risk of anxiety and depression by causing structural and functional changes in the brain. It has also been found that individuals who do not learn to properly manage and adapt to chronic stress are more likely to be overweight and develop sexual dysfunction. 

Stress management 

Exercising at least three times a week for 30mins at a time goes a long way to helping the body and mind cope and combat stress.