EP.139/ Tired All The Time? HPA Axis Dysfunction and Endo
Okay so today I’m talking about hypothalamic pituitary adrenal dysfunction. A mouthful, I know and for ease, it’s called HPA axis dysfunction.
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If you haven’t heard of HPA axis dysfunction, you may be more familiar with the term ‘adrenal fatigue’. And yes, if you’re thinking adrenal fatigue was sort of debunked as not being real, you’d be correct, but HPA axis dysfunction is very, very real and there is a huge wealth of research and evidence behind it. Adrenal fatigue was essentially an attempt to describe what is happening with HPA axis dysfunction but it oversimplified the process and made it seem like the adrenals sort of ‘ran out’ of energy, which isn’t the what happens and misses a big part of the story. I imagine, originally, when the term was coined, it did come with the full explanation of HPA axis dysfunction, but eventually through the spread of social media, it perhaps lost that meaning.
But anyway, the bottom line is HPA axis dysfunction is real, and it’s incredibly prevalent within the endometriosis and chronic pain community - and it may be the root cause behind your fatigue. So if you’re finding yourself exhausted all the time and overwhelmed by life, I really encourage you to keep listening.
So in order to understand HPA axis dysfunction, we need to break down the system behind it.
The hypothalamic pituitary adrenal axis is a system consisting of the:
· The hypothalamus (a part of the brain, found at the base of the brain)
· Pituitary gland (a gland found at the base of the brain)
· Adrenal glands (found above the kidneys)
This system works together to regulate our stress response and to also regulate our circadian rhythm, which is like the internal body clock that governs our sleep/wake cycle.
Let’s begin first by understanding how the HPA axis controls our stress response.
First, our hypothalamus alerts the pituitary gland of a stressor, and then the pituitary gland sends a signal to the adrenal glands to go about making stress hormones, and neurotransmitters, to power us through the situation.
The brain and adrenals respond by first releasing adrenaline, which is released quickly but also subsides quickly and then 15 minutes later, cortisol and DHEA are released, and these guys hang around for several hours.
Adrenaline and cortisol increase blood flow to organs like the heart, brain and muscles; reduce blood flow from non-essential organs like the digestive tract and reproductive system and trigger the release of stored glucose and fat, so you have the energy to fight or run. And DHEA acts as a buffer to counteract some of the damaging effects that cortisol can cause.
An important difference to note between adrenaline and cortisol, in terms of pain, is that adrenaline is inflammatory. That initial stress response triggers inflammation because the body is anticipating that there may be an injury or infection that needs to be addressed. So for example, if the stressor was that we cut ourselves, the inflammatory white blood cells would help to heal the area and fight off any bacteria that may have entered the wound. However, long-term that inflammation would become damaging, so 15 minutes later, cortisol is released, which is actually anti-inflammatory in the short term to bring down inflammation to healthy levels.
I’m going to dive into the link between chronic cortisol output and pain in future episodes, but just keep in mind that in the right levels, cortisol is anti-inflammatory. I think this can sometimes be confusing as you hear people talk about stress being inflammatory, so to clear that up, the acute initial response is inflammatory, for about 15 minutes, then it becomes anti-inflammatory when cortisol is released and these events are totally normal. It becomes a problem when cortisol remains elevated or keeps being triggered, that’s when stress becomes inflammatory, when the stress is chronic.
So, adrenaline eventually lowers back down, but cortisol is left remaining in the system until the stressor passes and should reduce after a few hours. Adrenaline is basically the hormone that gets us through the acute moment of stress, where cortisol carries us through the aftermath so to speak. So, for example, when we had that crazy flood in our flat, it was adrenaline that got me through getting out our most valuable belongings, trying to turn the mains off, calling plumbers in the middle of the night, that kind of thing. But it was cortisol that stayed with me, that kept me awake on the drive to my mum’s at 5am. That got me up the next day so I could work, despite feeling super stressed out. That stayed with me when we moved into a temporary Airbnb and navigated all the stressors of trying to work in a new home without all my stuff, with dodgy internet and a drowned laptop charger that now needed replacing.
And this is actually where the problem occurs. Originally, this stress response was designed to get us out of acute moments of danger alive. So back in cavemen days, this system helped us to outrun a wild animal that was hunting us, or to fight another tribe that was threatening ours and the stakes were high, but the outcomes were usually pretty black and white. We either died, or we survived. If we got away from the wild animal, and found our way back to the safety of our tribe, our stress response would have lowered and we would moved out of the flight or fight response and into rest and digest mode, which is the part of our nervous system responsible for digestion, repair, etc.
But in modern society, the stakes aren’t that high, but the situations aren’t as simple either. We’re now bombarded by stressors every day. Emails from colleagues who make us anxious, constant sensational headlines and 24-hour news cycles, traffic jams, struggling to balance our work and family or social lives, endless to do lists. You get the picture, I’m sure! And equally, it’s not just emotional stressors, but physical stressors that appear to the body as a threat or danger. So chronic inflammation, a low-lying infection or condition like SIBO, blue light exposure, late nights, physical pain, etc.
And these stressors, to the brain, are no different to the wild animal hunting us. The brain sees it as the same – a threat to our lives - and the stress response goes off. This means that we’re potentially operating in a state of flight or fight the majority of the time, which means we’re experiencing elevated levels of cortisol on a regular basis. And cortisol is our survival hormone, it’s great in small doses to keep us alive when we need to it, but it’s not great for long-term exposure at high levels.
Long-term exposure to cortisol can damage the gut, causing leaky gut and negative shifts in our gut microbiome, and it can also cause chronic inflammation, a suppressed immune system, increased blood sugar (because remember, part of cortisol’s job is to raise energy levels so we can fight or run, and it does this by releasing glucose from our cells into our blood stream, elevating blood sugar levels), and it can cause low progesterone (which results in oestrogen dominance), lowered thyroid function, and lack of ovulation. This episode isn’t about the effects of stress directly on our sex hormones and cycle health, but if you’re interested to learn more about this then I discuss it with Nicole Jardim in one of our podcast episodes, which I’ve linked to in the show notes, and I cover this process in detail in my course, Live and Thrive with Endo, which you can get on the waiting list for now. Again, the link is in the show notes.
So in short, the body knows this is a problem, and eventually adapts to protect itself. Firstly, the body has a sort of internal cortisol shutdown mode. The high levels of cortisol in the body trigger a feedback loop in the brain which encourages the brain to actually lower cortisol output, so the adrenals stop producing as much. Another possibility is that the adrenals may also become resistant to the signals from the brain to make more cortisol, so they lower cortisol production in that way. A third possibility is that the cortisol receptors, known as glucocorticoid receptors, become resistant, so cortisol may be being released, but it’s not actually doing its job. There are multiple different avenues for cortisol to become dysfunctional or lowered, but these are some of the main ones.
So this may seem like a good thing, as cortisol is now lowered and is no longer damaging the body, but the issue now is that the HPA axis regulation of the circadian rhythm is dysregulated.
So, I’m now going to walk you through what that means.
Cortisol isn’t just your stress hormone. It’s your wake hormone. It’s the hormone that gets you up in the morning and powers you through your day. At night, cortisol lowers and our sleep hormone melatonin rises, to allow us to drift off.
If you looked at your cortisol pattens on a graph, it would look like a roller coaster. It starts to elevate before we wake up, and it reaches its peak height about an hour after waking, so this is when we should feel our most awake (which isn’t the case for many of us with endo, right?!). After that, it begins to decline fairly sharply throughout the morning until about 12pm (so this is why many people find themselves needing an extra caffeine boost at 11am), and at midday the decline continues but is less dramatic. Your levels hit another drop at about 3pm, which again, is why people tend to get that afternoon slump and then they peter out as the afternoon and evening continues. This is to allow melatonin to rise, as cortisol actually suppresses it.
Now what can happen with HPA axis dysregulation, is that if you’re chronically stressed, you may have high levels of cortisol at first. These may be at their highest in the morning, so you wake up feeling stressed and tense straight away, maybe you find your sleep is disturbed in the early hours of the morning, but your levels can also be high at night, which suppresses your melatonin, so you find yourself exhausted but wired and unable to switch off when you go to bed. You may also be gaining weight around your middle, have trouble stabilising your blood sugar levels and be experiencing fertility issues or hormonal imbalances. These are classic signs of high cortisol.
Then over time the cortisol levels lower, and this really depends on the individual as to when this happens, but it can be quickly, over the space of weeks in some cases, but I’ve seen it take much longer. And the cortisol pattern also varies from person to person. For some people, they have lower levels than usual at certain points in the day so they tend to feel like they have dramatic crashes in energy, or they have low levels all day long but high cortisol levels at night (which is really when you have those exhausted feelings yet you’re just wide awake or struggling to stay asleep), or they have low levels constantly, and that’s when we’re really fatigued.
Now these scenarios manifest a little differently depending on the pattern of cortisol dysfunction you have, but the tell-tale symptoms include:
· Chronic fatigue
· Brain fog
· Waking up tired (no matter how much sleep you get!)
· Feeling unable to cope with everyday stressors and bigger stressors like COVID, etc.
· Continuous feelings of overwhelm as the body struggles to respond adequately to stress
· Anxiety
· Depression
· Blood sugar dysregulation
· Exercise intolerance (you find it hard to do much exercise, or find it difficult to recover afterwards)
· Get ill easily
· Dizziness, especially when going from seated to standing
· Frequent energy crashes, especially mid-morning and mid-afternoon as cortisol begins to fall
· Insomnia, disturbed sleep or feeling suddenly energised at night (this would of course be more likely if your cortisol was creeping up at night)
And if this resonates with you, I wouldn’t be surprised.
Low cortisol output is associated with nearly all chronic pain conditions, especially pelvic pain conditions, endometriosis and fibromyalgia.
In one study of 92 women with endo and 82 ‘healthy’ volunteers, they found that the women with endo and chronic pelvic pain had low levels of cortisol despite reporting higher stress levels and a low cortisol awakening response, which is that rising cortisol level we need to be able to wake in the morning.
Because pain is a stressor to the body, at first, when we first experience this pain, the cortisol output is likely to be normal for the situation or high, but overtime, if we become anxious, stressed, worried or scared of our pain, which is of course, a totally natural response to endometriosis, then over time, our HPA axis becomes dysregulated and our cortisol levels deplete because they have been high for so long as response to this pain-fear cycle. In fact, the high cortisol type of HPA axis dysfunction from chronic stress (whether the stress is from pain or not) has been shown to trigger the onset of some chronic pain conditions and worsen existing chronic pain. Then cortisol becomes depleted, and the pain continues, because the protective anti-inflammatory properties of cortisol are now lowered. So essentially, high levels of cortisol contribute to inflammation and pain, but so does low cortisol. We want the healthy level of cortisol for optimal pain regulation.
So the stress of the pain doesn’t go away, but our body is now less able to deal with it. Remember, cortisol provides us with the energy to deal with stress, it literally gets the glucose and resources we need to power our body through a stressful situation and without it, we may feel unable to cope with the demands of every day stressors or bigger events. Usually, with depleted cortisol levels, our body begins to rely more heavily on adrenaline, so when we’re stressed, we may find that we experience symptoms of high adrenaline, like shaking, an increased heart rate, feeling jittery and wired, but yet we feel unable to cope with the situation because we don’t have enough cortisol to power us through.
So now you understand what HPA axis dysfunction is, what can we do about it?
The good news is, HPA axis dysfunction can be repaired and the are very key, often simple steps to repairing it. And for us, for those of us with endo specifically, it’s about giving our body reliable patterns in the day to normalise our circadian rhythm, and changing our response to stress and pain. So in a future episode, which will be out very soon, I’ll provide you with some of the initial key steps for repairing your HPA axis and alleviating your fatigue. I am also going to do another episode that dives deeper into the pain, cortisol and inflammation connection, because it’s fairly complex and deserves an episode to itself!
I really hope this information has been useful for you. I know for many of my clients, when they learn about this and we see their low cortisol levels on their test, it makes total sense to them. So I hope this has given you some answers.
If you want to test your cortisol levels, you can order what is known as a CAR test, which is a Cortisol Awakening Response. This measures your levels of cortisol from the morning into the night, and I have provided you with a couple of test options in the show notes.
Show Notes
Studies
https://academic.oup.com/humrep/article/33/9/1657/5055017
https://www.hoajonline.com/reproduction/2054-0841/3/2
https://www.tandfonline.com/doi/full/10.1080/10253890701840610
https://www.sciencedirect.com/science/article/abs/pii/S1521693418300324?via%3Dihub
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263906/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476783/
https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-020-01752-1#Sec21
https://journals.lww.com/psychosomaticmedicine/Abstract/1998/05000/Abuse_Related_Posttraumatic_Stress_Disorder_and.17.aspx
CAR tests
https://regeneruslabs.com/products/cortisol-awakening-response
https://www.letsgetchecked.com/gb/en/home-cortisol-test/
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