Commentary

In the US, fibromyalgia is one of the most common reasons for referral to a rheumatologist.12 For several centuries, muscle pains have been known as rheumatism and subsequently as muscular rheumatism.13 Fibromyalgia is now a recognized clinical entity causing chronic and disabling pain. The classification, causation mechanisms, clinical course and outcomes, and management strategies of fibromyalgia are controversial. Because no defined pathology or specific etiology has been found, fibromyalgia may be considered a dysfunctional disorder.14

Many hypotheses have been advanced in the medical community concerning the etiology of fibromyalgia. Theories involving the central and peripheral nervous system, and the immunological system, are frequently aired. Current research is investigating whether alterations in the regulation of neurotransmitters—particularly serotonin, norepinephrine, and substance-P—may play a role in fibromyalgia. Other researchers are examining the relationship of immune function, sleep physiology, and hormonal regulation with fibromyalgia. A defective neural feedback loop mechanism or other abnormal neurophysiology may underlie the pathophysiology of fibromyalgia. The hypothalamic-pituitary-adrenal (HPA) axis appears to play an important role in fibromyalgia. Both hyperactivity and hypoactivity of the HPA axis have been reported in patients with fibromyalgia.15,16 There may also be altered autonomic nervous system function in patients with fibromyalgia.17

Some scientists have hypothesized that fibromyalgia is caused by an irreversible disturbance of the neuroimmunoendocrinological system.18 We partially support this hypothesis and believe that fibromyalgia patients have a dysfunction of the autonomic nervous system as a result of hormonal deficiency associated with a loss of sensitivity of cell membranes to hormonal impulses. We do not agree, however, that this condition is “irreversible,” because fibromyalgia symptoms have disappeared quite often in patients treated with hormone-restorative therapy. Our hypothesis as to what causes fibromyalgia is that fibromyalgia is a result of a loss of neurohormonal and metabolic integrity. Hormone-restorativetherapy may play a key role in “resetting” the various endocrine loops.

Our own experience and the following studies and observations provide clues as to the nature of fibromyalgia:

• The greater prevalence of fibromyalgia in women, particularly those in their reproductive years, suggests an association between fibromyalgia and sex hormones. Fibromyalgia has been associated with delayed menarche (beginning of menstruation) and reduced fertility, which may be signs of hormonal imbalance.1
• Fibromyalgia is characterized by symptoms such as chronic and widespread musculoskeletal pain, fatigue, poor sleep, gastrointestinal complaints, and psychological problems. These symptoms are similar to those experienced by patients with hormonal deficiencies.17
• A variety of disorders—including migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder—frequently are concurrent with fibromyalgia, suggesting that these various disorders may share a common physiologic abnormality.19 Migraine, fibromyalgia, irritable bowel syndrome, and related conditions display common clinical, biochemical, and pathophysiological patterns.6,20-22
• Chronic stress has been linked with the subsequent development of fibromyalgia. One or more abnormalities in neuroendocrine function may explain this connection.23
• Fibromyalgia and chronic fatigue syndrome may belong to the same clinical entity and may be considered “psycho-neuro-endocrinological autoimmune diseases.”24 Many features of fibromyalgia and associated disorders, such as widespread pain and fatigue, may be related to observed neuroendocrine perturbations.25 Because fibromyalgia and chronic fatigue syndrome share symptoms, we suspect they share a similar etiology and pathogenesis. Neuroendrocrine abnormalities have been observed in both disorders, including dysregulation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes.
• Patients with fibromyalgia have been noted to have an impaired ability to activate the hypothalamic-pituitary portion of the hypothalamic-pituitary-adrenal axis as well as the sympathoadrenal system.16
• Hyperactivity of the sympathetic nervous system may be a common denominator for low levels of DHEA-S in inflammatory and non-inflammatory diseases (for example, in patients with heart failure, fibromyalgia, or cancer cachexia).26
• Animal experiments suggest hyperexcitability of the central nervous system as a possible cause of fibromyalgia.27
• Fibromyalgia-like symptoms are quite typical for patients who suffer adverse effects from cholesterol-reducing statin drugs. The most common complaints from statin drug users include abdominal and chest pain, dizziness, fatigue, fibromyalgia, headache, insomnia, and upper respiratory tract infection.28 The similarities between fibromyalgia symptoms and statin drug side effects suggest a possible common pathophysiological mechanism. We hypothesize that statin drugs may produce fibromyalgia-like symptoms by lowering levels of the hormone precursor cholesterol, which could lead to decreases or imbalances in hormone levels.
• Fibromyalgia symptoms such as fatigue, cognitive dysfunction, headache, irritable bowel syndrome, musculoskeletal aches, and others have been significantly improved following treatment with an anti-fungal medication.29
• Fibromyalgia is associated with impaired deep sleep30 and non-restorative sleep.31
• Low melatonin levels have been observed in women with fibromyalgia. Melatonin supplementation reduced pain, sleeping disorders, and depression in patients with fibromyalgia.32

Treatment of fibromyalgia has traditionally met with limited success, most likely because many practitioners attempt only to manage the symptoms of the condition rather than to uncover and address its underlying cause. The interaction of hormonal, metabolic, and lifestyle factors likely plays an important role in the development and progression of fibromyalgia. Fibromyalgia’s prevalence in women, particularly those between the ages of 30 and 60, suggests that alterations between reproductive hormone levels may be involved in fibromyalgia’s etiopathology.

Because fibromyalgia and migraine often occur together, it follows that effective migraine therapies might also benefit fibromyalgia sufferers.33 A multimodal approach that includes restoration of neurohormonal and metabolic integrity has been successfully applied in migraine patients.33 We found that a similar strategy of hormone restoration greatly benefited this patient with fibromyalgia.

The patient described in this case report had a combination of symptoms from fibromyalgia. Analysis of the medical literature and clinical experience suggests that fibromyalgia patients have a combination of neuroendocrinological and metabolic disorders, with an imbalance of the hormonal axes. This is why the first step of our program was to test hormone levels in the patient and then use bioidentical hormones to balance and restore youthful levels of her hormones. We have frequently noted a pattern of “male dominance” in patients with chronic conditions such as fibromyalgia. Endocrine disorders often lead to a wide spectrum of symptoms that may be reversible using hormone restoration. Because melatonin has been reported to improve sleep and reduce pain in fibromyalgia patients,32 melatonin was a crucial component of this patient’s treatment plan.

Integrative practitioners often find that restoring gastrointestinal health is an integral part of a comprehensive treatment plan. We suspected that the patient’s history of prescription drug use might have altered her gastrointestinal flora and function. This was the rationale for using therapeutics to relieve her constipation and restore optimal levels of gut microflora. We found that addressing the patient’s gastrointestinal health improved her overall well-being.

Further clarification of the role of neuroendocrine and metabolic abnormalities in fibromyalgia is necessary to evaluate the effectiveness of an integrated therapeutic strategy that includes hormone restoration.

Sergey A. Dzugan, MD, PhD, was formerly chief of cardiovascular surgery at the Donetsk Regional Medical Center in Donetsk, Ukraine. Dr. Dzugan’s current primary interests are anti-aging, biological therapy for cancer, cholesterol, and hormonal disorders.