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Possible Causes

Hormonal Fatigue in Fibromyalgia

Photo of what a fibromyalgia patient looks like with adrenal fatigue.

There’s nothing like a little bit of adrenaline from your adrenal glands to jumpstart your day. Cortisol is another hormone secreted by the adrenals that can also be alerting. It’s an anti-inflammatory steroid to help your tissues heal under all sorts of stressful situations. Ordinarily, your morning adrenaline and cortisol levels are much higher than in the evening. Otherwise, they would keep you awake at bedtime. But in people with fibromyalgia, hormonal disruption leads to a state of adrenal fatigue.

With fibromyalgia, your body is not fully energized, and your brain has trouble falling asleep. This leaves you in a state of limbo. You seldom feel like you have enough get-up-and-go in the morning, yet you are wired-but-tired in the evening. Part of the reason for this chronic out of sync feeling is due to an alteration of the normal secretion pattern for cortisol and adrenaline. But that is not all. Your immune and metabolic responses to stress are also partly to blame.

Stress Responses

Trauma, infections, starvation, overexertion, and lack of sleep are all stressful to your body. These situations rapidly trigger your immune system into action to contain tissue damage. Insulin is a hormone secreted from the pancreas to help your cells draw in glucose from the bloodstream. It’s a process that enables you to bounce back quickly from short-term stressors.

To prevent your immune system from going overboard, two other processes keep your body functions in check. One is your hypothalamic-pituitary-adrenal (HPA) system that releases a series of hormones, ending with the secretion of cortisol from the adrenal glands. Not only does cortisol improve morning alertness, but it also counters the effects of inflammatory cytokines that increase pain and fatigue.

Diagram showing how impaired hormonal function in fibromyalgia leads to adrenal fatigue.

Pain is a stressor that activates your entire HPA system. It responds by pouring out elevated amounts of hormones, but the process seems disrupted in people with fibromyalgia. Although the corticotrophin-releasing hormone (CRH) from the hypothalamus is doubled in the spinal fluid of fibromyalgia patients, the pituitary responds with surprisingly normal levels of ACTH. Worse yet, the cortisol level needed for morning alertness is lower in people with fibromyalgia, according to a study by Roberto Riva, Ph.D., of Sweden.1

The second process responding to stress is the sympathetic branch of your nervous system. Studies in fibromyalgia patients show the noradrenaline-transmitting nerves of the sympathetic system are dominant. As you can see from the diagram, noradrenaline works to get the adrenal glands to kick in. However, adrenaline secretion from the adrenals is lower than normal in fibromyalgia patients.2

While your body’s two main stress response systems show signs of being hyperactive (elevated CRH and increased sympathetic drive), the result is an underactive adrenal response. In turn, the adrenal gland contributes to your fibromyalgia fatigue.

Adrenal Hormones

Why would people with fibromyalgia produce low cortisol levels despite normal ACTH production from the pituitary? “A desensitization of the adrenal glands to ACTH might be possible,” says Riva. By desensitization, he means that the adrenals are not as responsive as they should be. Riva adds that the reduced cortisol production in fibromyalgia is commonly referred to as adrenal fatigue.

Riva looked to see if the low morning cortisol levels were simply a result of chronic pain or if they might be related specifically to fibromyalgia. He found people with regional pains in the neck and shoulder area produced ample amounts of cortisol, more so than the healthy controls. This finding implies that pain by itself doesn’t necessarily impede the HPA system from working properly. However, prolonged elevations in cortisol are not healthy, so time could be another factor. Maybe your HPA system undergoes changes over time and this contributes to your symptoms.

Another study measured cortisol levels in fibromyalgia patients with varying disease durations.3 Cortisol production for patients with a recent onset of symptoms was roughly the same as that of the healthy control group. Conversely, patients with 10-20 years of painful fibromyalgia showed a significant drop in cortisol, confirming Riva’s suspicions.

Even your sympathetic system, which is super-charged and disrupting your sleep, can’t get your adrenal glands to secrete enough adrenaline. When fibromyalgia patients are put through a stressful challenge of exhaustive exercise, their adrenals produce dramatically less adrenaline than healthy control subjects.4

Low adrenaline is another sign your adrenal glands are exhausted, and your body is ill-equipped to handle stressful challenges. But poor adrenal function is just part of your problem. Your immune response to cortisol and your body’s metabolic reaction to stress are also not working properly.

Immune Reaction

The quick response of your immune system to resolve any type of threat (such as injury or infection) is necessary for survival. During this process, your immune system pumps out all types of cytokine chemicals. One is interleukin-6 (IL-6). This cytokine is known for its ability to increase the availability of nutrients to the tissues to promote healing. IL-6 accomplishes this by activating the release of insulin to break down fat stores and increase blood glucose.

Injection of IL-6 in healthy subjects leads to activation of the HPA system, increased cortisol production, breakdown of fat stores, and greater energy expenditure. It is a favorable response to any short-term challenge to the body. But what happens when the threat outlives its usefulness and becomes chronic in nature, such as the pain of fibromyalgia?

Although fibromyalgia patients may not have elevated levels of cortisol, their bodies respond to this hormone with an overproduction of IL-6, according to Andrea Geiss, Ph.D., and her team in Germany.5 Geiss subjected fibromyalgia patients and healthy subjects to a brief pain stimulus to look at cortisol and IL-6 production. For each molecule of cortisol produced by the adrenals, twice the amount of IL-6 was produced by the fibromyalgia group. In addition, the IL-6 levels remained elevated in the fibromyalgia patients for more than nine hours.

“Reduced cortisol levels are associated with increased pain and fatigue ratings in fibromyalgia patients,” says Geiss. She adds, these symptoms are made worse by an enhanced production of IL-6 in response to pain. “Although the fibromyalgia patient’s adrenaline levels remained low before and after pressure pain stimulation,” Geiss says noradrenaline was higher at both test points. As you can see from the diagram above, noradrenaline overstimulates the adrenals and contributes to hypertension.

Daily Activity

A variety of situations make cortisol, noradrenaline and adrenaline levels fluctuate throughout the day. Measuring these substances at one point in time doesn’t explain what happens in fibromyalgia patients day after day. A German team followed a group of fibromyalgia patients for two weeks.6 Their goal was to explore the link between cortisol levels, sympathetic system activity, physical activity, and measures of fatigue.

Lower morning cortisol levels corresponded to feeling more physically fatigued. Measures of sympathetic activity did not correlate with fatigue. So, cortisol appears to be the adrenal hormone with the greatest influence on your degree of fibromyalgia-related fatigue. When looking at activity levels, days with greater physical activity predicted higher exhaustion ratings the next day.

“Our findings underline the fact that patients with fibromyalgia might find it hard to begin and adhere to exercise programs,” write the study authors. They point out patients likely benefit from such programs, but being physically drained will impede one’s ability to exercise.

Treatment

Treating the physical fatigue of fibromyalgia is not easy. You can’t simply take cortisol, nor can you take glucocorticoids because they suppress immune functions. See our article on Fatigue in Fibromyalgia for advice from three treatment experts. In addition, various supplements may help (see Diet & Nutrition), but probably not as much as you would like.7  Here are two possibilities:
• Coenzyme Q10 (300-400 mg/day)
• Acetyl L-Carnitine (500 mg – 3/day)

Improving the balance of friendly bacteria living in the gut may be another option, but more research is needed. Fibromyalgia patients have an imbalance in the number of unfriendly bacteria that reside in their gut. These bacteria can prompt the release of immune cytokines (like IL-6) entering the bloodstream. Studies investigating the role of gut bacteria in fibromyalgia and potential treatments are ongoing. For more details, see the articles on Gut Influences and Targeting the Gut.

Staying in Rhythm

Photo of exhausted man falling asleep sitting up because sleep-wake cycles are out of sync. Most of the systems in your body operate on a cyclic pattern; it’s called a circadian rhythm. Take your sleep-wake cycle as an example. The body is used to sleeping during the nighttime and being awake during the day. The pineal gland in the brain secretes melatonin at the same time each night, which sets your body’s internal clock. Cortisol and other hormones operate in a rhythmic fashion, which is strongly influenced by this internal clock.

If melatonin secretion is off kilter, this will cause a domino effect on the timing of other hormones, such as cortisol. As it turns out, your pattern of melatonin secretion is slightly abnormal.8 Not enough is secreted at bedtime, while the levels of melatonin are slightly elevated in the morning and throughout the day. This might explain why you have trouble falling asleep, yet you can’t quite get fully awake during the day. In addition, this altered melatonin pattern your HPA system and negatively impact cortisol levels.

Many fibromyalgia patients say adhering to a sleep-wake schedule helps them fall asleep at night and function better during the day. You might also increase your nighttime melatonin levels by supplementing with this hormone at bedtime. One study shows that 10 mg of melatonin at bedtime significantly reduces fibromyalgia pain and improves overall symptoms.9 Unfortunately, the impact of fatigue was not assessed. Yet, feeling jetlagged is a well-documented phenomenon that occurs when one’s melatonin cycle is out of sync. So, if you keep a rigid sleep schedule and take melatonin, this could increase morning cortisol and reduce daytime fatigue.

Summing Up Fatigue

There are many sources of your fatigue. Your brain’s hypothalamus and your sympathetic system are both urging your adrenals to pour out cortisol and adrenaline. Yet your adrenal glands are insensitive to these demands, leading to hormonal fatigue in fibromyalgia. Even when you exercise, your body does not produce as much adrenaline as it should (which may explain why exercise is less invigorating for you). Worse yet, your immune system over-reacts to your body’s cortisol by pumping out IL-6. This cytokine chemical has the potential to disrupt sleep and enhance pain. But this is just half the picture because there are also metabolic consequences (see the article on Altered Metabolism).

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What else could be causing your symptoms? Read our section on the Central Nervous System.  Or, if you are curious about alternative therapies, see Nondrug Treatments.

References on Hormonal Fatigue in Fibro

  1. Riva R, et al. Psychoneuroendocrinology 37(2):299-306, 2012. Abstract
  2. Adler GK, et al. Am J Med 106:534-43, 1999. Abstract
  3. Reyes del Paso GA, et al. Eur J Pain 28:821-830, 2023. Free Report
  4. Giske L, et al. Eur J Pain 12:351-60, 2008. Abstract
  5. Geiss A, et al. Psychoneuroendocrinology 37(5):671-84, 2012. Abstract
  6. Doerr JM, et al. J Psychosom Res 93:55-61, 2017. Free Report
  7. Barnish M, et al. Nutrients 15:2154, 2023. Free Report
  8. Caumo W, et al. J Pain Res 12:545-556, 2018. Free Report
  9. de Zanette SA, et al. BMC Pharmacol Toxicol 15:40, 2014. Free Report