What Causes Chronic Fatigue Syndrome? - Part IV: Hormones

Note: This is the fourth article in an ongoing series. Make sure to check out the following articles once you’re finished with this one!

What Causes Chronic Fatigue Syndrome? – Part I: Understanding Fatigue
What Causes Chronic Fatigue Syndrome? – Part II: The Epstein-Barr Virus & Other Infections
What Causes Chronic Fatigue Syndrome? – Part III: Genetics
What Causes Chronic Fatigue Syndrome? – Part V: A Functional Medicine Approach

For years, chronic fatigue syndrome was thought to be a mental or psychiatric illness. New research is finally starting to paint a picture of hormone imbalances playing a key role in the development of chronic fatigue syndrome.

What is a hormone?

Hormones are small molecules that are transported throughout the body to distant organs/glands that then regulate the behaviour or function of said organ. One way to think of hormones is as the language your body uses to communicate with different areas of itself. How can your brain tell your kidneys to lower your blood pressure? Through hormones like aldosterone which help to ensure your blood pressure stays balanced. Hormones bind to what are called receptor sites on your cells. This binding process will alter the way in which a particular cell behaves.

Hormones are typically classified into three groups:

Eicosanoids
1. These hormones are made from healthy fats called polyunsaturated fatty acids (PUFAs). This is why it’s so important to consume healthy fats – they’re the building blocks to some of your hormones!
2. They help your immune system to mount inflammatory responses, fevers, allergies. Eicosanoids even help your body perceive pain and regulate the growth of new cells.
Steroids
1. When you think of steroids, bodybuilding likely comes to mind. But there are many other steroids hormones in your body. Cortisol, for example, is a steroid used to help your body regulate blood sugar and stress.
2. Steroids either alter the cell membrane or, activate changes in cells by binding to steroid receptor sites on cells.
Amino acids or protein derivatives
1. The amino acid-derived hormones are relatively small molecules derived from the amino acids tyrosine and tryptophan. If a hormone is amino acid-derived, its chemical name will end in “-ine”.
2. Epinephrine is one example of an amino acid or protein-derived hormone.

When are hormones released?

Hormones get released in response to specific triggers within your body. Think about the last meal you ate. After eating, your blood sugar increased in response to the food being digested into glucose (sugar). Gauges within your body monitor your blood sugar regularly. When they identify an increase in blood sugar, they signal for the hormone insulin to be released. Insulin helps to transport sugar from your blood (where it’s dangerous) to the inside of your muscle, fat, or liver cells (where it’s safe). Once your blood sugar has returned to a safe or normal level, insulin secretion stops and the remaining hormone in circulation is broken down.

But before a hormone is ready to be released, it has to go through a series of steps. First, your body has to synthesize the particular hormone in a particular tissue. For example, testosterone is synthesized in the testes of men and ovaries of women. Once your body has created the hormone, the next step is secretion of the hormone to target cells.

Once a hormone arrives at its target cells, there is a recognition process. This ensures that the hormone binds only to the correct cell(s). Once a hormone has bound to a cell, its effects are then exerted upon the cell. Once testosterone binds to muscle cells it causes the cell to go through something called protein synthesis, or, cell growth. This is why those who take testosterone steroids develop large muscles. After a hormone has exerted its effect on a cell, the body then breaks down any excess. Testosterone is broken down and metabolized by the liver. Any excess testosterone is eliminated from the body via urination.

What hormones are associated with chronic fatigue syndrome?

When it comes to fatigue, the hormone most commonly associated is the thyroid hormone. Low levels of thyroid hormones (T3 and T4) result in a condition called hypothyroidism. The most common symptom associated with hypothyroidism is fatigue. If you suffer from chronic fatigue syndrome, you’ve likely had your thyroid examined thoroughly. If not, make sure that is the next thing you do!

But there are many more hormones that can affect your energy levels than just thyroid. Below, I’ll explain some of the most common culprits.

Thyroid hormones

I know, I just said this was related to hypothyroidism, not chronic fatigue syndrome. But a new study done in 2018 found that those with chronic fatigue syndrome had normal levels of TSH (thyroid stimulating hormone) but low levels of T3 and T4. You see, doctors will typically start by running only TSH. If that comes back within normal ranges, no further investigation of your thyroid is done. Yet this studied showed that in those with chronic fatigue syndrome, their TSH was normal but they had low levels of both T3 and T4. (2) If you have only had your TSH analyzed, make sure you push your doctor to also test for T3 and T4 thyroid hormones.

Another phenomenon that can occur in your thyroid gland is an autoimmune condition. This occurs when your immune system creates antibodies against its own tissue(s). The autoimmune forms of thyroid illness include Hashimoto’s (low thyroid) and Graves disease (high thyroid). In Hashimoto’s, your immune system attacks the T3 hormone as though it was a foreign invader. This results in low levels of thyroid hormone and symptoms like fatigue. In Graves disease, antibodies are developed to TSH (thyroid stimulating hormone) receptors. This causes an excess of thyroid hormones T3 and T4.

Your body will produce antibodies to thyroid tissue well before you develop hypothyroidism. Your lab tests will show normal TSH levels. But thyroid antibodies (thyroid peroxidase and/or thyroglobulin antibodies) will be elevated. This is the very early stage of an autoimmune condition. Often, the only symptom is fatigue. If you’re suffering from chronic fatigue syndrome, make sure you rule in/out autoimmune thyroid conditions! Ask your doctor to run the following thyroid lab tests:

TSH
Free T3
Free T4
Total T3
Total T4
Reverse T3
Thyroid peroxidase antibodies
Thyroglobulin antibodies

Cortisol

Cortisol is more popular in the adrenal fatigue circles. However, it can be a common culprit for those with chronic fatigue as well. Cortisol is a hormone within the network called the hypothalamic-pituitary-adrenal axis (HPA axis). Your HPA axis is responsible for a number of physical and emotional functions. Including:

Sleep
Response(s) to stress
Digestion

Exploration of the HPA axis and its effect on chronic fatigue syndrome is a relatively new area of research. To make matters worse, most conventionally trained physicians do not take the HPA axis into consideration. Fortunately, functionally trained physicians are likely well versed in the proper treatment of HPA axis disorders.

In those with chronic fatigue syndrome, the following hormonal abnormalities can be present: (4, 5, 6, 7)

Interrupted circadian rhythm
- The HPA axis helps to regulate your sleep-wake cycle through the use of hormones such as melatonin and cortisol.
- Sleep issues (which are incredibly common in chronic fatigue syndrome) often involve the suppression of cortisol during the morning.
  - To best combat, this, try exposing yourself to 10-minutes of sunlight immediately after waking.
Cortisol deficiency
- Also called hypocortisolism or adrenal fatigue. It occurs when your body is unable to produce enough cortisol.
- Low levels of cortisol can cause fatigue, low blood pressure, an intolerance to stresses, and a suppressed immune system.
Cortisol excess
- Also called hypercortisolism; high levels of cortisol occur when your body is actively undergoing a stress.
- High levels of cortisol can cause fatigue, anxiety, high blood pressure, and weight gain.

At the time of this writing, researchers have not identified specific genes that predispose one to develop cortisol or HPA axis imbalances. There is, however, evidence of a heritable component to both cortisol imbalance(s) and HPA axis dysfunction. (8) Around 50% of those with chronic fatigue syndrome report at least one childhood trauma. (9, 10). It has been estimated that childhood trauma increases the risk of CFS between 6- and 8-fold. (11, 12) The more intense the trauma, the higher the risk of developing chronic fatigue syndrome. Trauma aside, other childhood illness(es), disease(s), or infection(s) will also exert an effect on the HPA axis. Should the effect on the HPA axis be severe enough, it is possible that this will set you up for cortisol, HPA axis, and/or fatigue issues as an adult.

In animal models, it has been shown that early life stress(es) create changes in cortisol and the HPA axis which persist (or become evident) in adulthood. (13). It is hypothesized that the HPA axis in humans will respond in a similar manner. Early life stress(es) may alter the way your genes express themselves which in turn can increase (or decrease) the amount of cortisol excreted by your body. For more info on how your genetics affect chronic fatigue syndrome, check out this post.

This is not to say that if you experienced a severe illness or trauma as a child you’re stuck with chronic fatigue syndrome for life. Instead, I present this information as a way of helping you understand why CFS developed in you. With proper understanding comes proper treatment. Cortisol imbalances and HPA axis dysregulation are very treatable.

Sex hormones

Sex hormones are those that affect your reproduction or sexual development. Common examples include estrogen, progesterone, and testosterone. The effect these hormones have on chronic fatigue syndrome has yet to be explored thoroughly. In the research is currently available, it was found that 76% of menopausal women with CFS in reported having had a hysterectomy. This high prevalence of hysterectomies may explain the early onset of menopause that is commonly found in CFS patients. Hysterectomies and/or early onset of menopause will cause a decrease in sex hormones. (14) While sex hormones don’t seem to be causal in their relationship with chronic fatigue syndrome, there is a strong correlation and a lot more research needs to be done in this area!

Ok, now you know about the hormones most commonly associated with chronic fatigue syndrome.

Do you need help improving your fatigue?

For a deeper dive into other possible causes of chronic fatigue syndrome, check out the below links: