HPA Axis Dysfunction: Genes and Environment

Cortisol is a hormone produced by the adrenal glands in times of stress, and it also plays many roles in your normal bodily functions. It is a multi-purpose hormone that needs to be in the right amount (not too high, not too low) and at the right time. Your genes play a big role in how likely you are to have problems with cortisol.

HPA Axis Dysfunction:

The problems with cortisol come when levels are chronically elevated - or chronically low. There are two conditions of extreme cortisol dysregulation: Cushing's syndrome and Addison's disease. Cushing's is due to too much cortisol, either from glucocorticoid medications or too much cortisol produced by the adrenals due to a pituitary tumor. Symptoms of Cushing's include high blood pressure, abdominal weight gain, round face, stretch marks, thin skin, and, in women, facial hair, and menstrual irregularities. Addison's is due to too little cortisol production. Symptoms include weight loss, muscle weakness, nausea, and changes in mood.

Symptoms of HPA (hypothalamic–pituitary–adrenal) axis dysfunction

While Cushing's and Addison's show the extreme's of cortisol disorders, there are milder manifestations that plague many of us. HPA axis dysfunction can mean cortisol is chronically elevated and/or it doesn't respond appropriately to stress. It can also be due to a disrupted rhythm of cortisol production over the course of a day.

Chronically elevated cortisol can be due to repeated stress (physical or mental), genetic variants (below), and traumatic childhood events (epigenetic trigger).[ref Trusted Source: Peer Reviewed Journal]

Chronically elevated cortisol is linked to:

  • diabetes, insulin resistance[ref Trusted Source: Peer Reviewed Journal][ref Trusted Source: Peer Reviewed Journal]
  • immune dysfunction[ref Trusted Source: Peer Reviewed Journal]
  • depression and anxiety[ref Trusted Source: Peer Reviewed Journal][ref Trusted Source: Peer Reviewed Journal]
  • coronary artery disease[ref Trusted Source: Peer Reviewed Journal]
  • reproductive problems[ref Trusted Source: Peer Reviewed Journal]
  • weight gain[ref Trusted Source: Peer Reviewed Journal][ref Trusted Source: Peer Reviewed Journal]

Immune dysfunction:
One theory is that chronically elevated cortisol leads to glucocorticoid receptor resistance, which is a downregulation of the glucocorticoid receptor. When acute stress occurs, the body then cannot mount a normal stress response. This can lead to an increased susceptibility to infections, including colds.[ref Trusted Source: Peer Reviewed Journal]

Depression:
Reduced glucocorticoid receptor function along with altered cortisol circadian rhythm is found in women who have depression.[ref Trusted Source: Peer Reviewed Journal]

Several other studies show that higher basal levels of cortisol along with altered cortisol circadian rhythm is associated with major depressive disorder. This seems to be a two-way street -- treating depression can reduce elevated cortisol levels.[ref Trusted Source: Peer Reviewed Journal][ref Trusted Source: Peer Reviewed Journal]

Metabolic syndrome:
Hypertension, insulin resistance, and altered lipids add up to metabolic syndrome. And obesity goes hand-in-hand here...

So what does research show on obesity and cortisol? Hair cortisol levels, which give an average cortisol reading for the past few months, were tested in a group of British adults. The cortisol levels in hair were higher in those who were obese (BMI >30) and with larger waist circumferences. Higher hair cortisol levels also correlated to being overweight for a longer period of time (>4 years). [ref Trusted Source: Peer Reviewed Journal]

This doesn't mean that for everyone, weight gain is due to cortisol being high, but that for at least part of the population, higher cortisol correlates with higher weight.

Infertility:
Constant activation of the HPA axis can cause problems when trying to conceive. This is due to cortisol shifting the ratio of follicle stimulation hormone to luteinizing hormone (FSH:LH). The altered hormone ratio can cause decreased egg quality and an increased risk of infertility.[ref Trusted Source: Peer Reviewed Journal][ref Trusted Source: Peer Reviewed Journal] Read more details here.

Childhood trauma

I mentioned above that cortisol levels are controlled by three factors: genetics, chronic stress, and childhood trauma. There is quite a bit of scientific evidence showing childhood trauma can cause persistent changes in the HPA axis. One study describes it as the brain becoming sensitized, thus allowing episodes of depression to occur more frequently.[ref Trusted Source: Peer Reviewed Journal]

Childhood trauma can be mental or physical – from child abuse to a parent dying to having childhood leukemia.  Genetics interacts with this, and some people are more resilient to childhood trauma than others. Certain genetic variants cause a higher basal cortisol level with a blunted response to actual, acute stress. This increases the risk of depression, anxiety, and PTSD.[ref Trusted Source: Peer Reviewed Journal]

Adrenal fatigue: is it real?

Adrenal fatigue is an idea promulgated by alternative medicine practitioners. The idea is chronic stress causes the adrenals to wear out - become exhausted - and not be able to produce enough cortisol. This is thought to cause overall fatigue, depression, weight gain, brain fog, etc. Examples of alternative health sites writing about adrenal fatigue: Dr. Northrup's adrenal fatigue article, Dr. Wilson's adrenal fatigue website, Dave Asprey - Bulletproof - chiming in on the adrenal fatigue idea. This is just a handful of examples, and all the big alternative health websites used to be on the adrenal fatigue band-wagon.

Most endocrinologists don't think that adrenal fatigue is real. And research studies back up the idea that the adrenal glands aren't worn out, exhausted, or not producing enough cortisol.[ref Trusted Source: Peer Reviewed Journal][ref Trusted Source: Peer Reviewed Journal]  In fact, some alternative medicine practitioners seem to be re-vamping the way that they talk about adrenal fatigue and now are morphing their articles to talk about HPA axis dysfunction. [article][article]


Genetic Variants in the HPA Axis

 


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