Therapeutic Options for FibromyalgiaJuly 2005
By Dr. Sergey A. Dzugan
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:
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.
1. Schochat T, Beckmann C. Sociodemographic characteristics, risk factors and reproductive history in subjects with fibromyalgia—results of a population-based case-control study. Z Rheumatol. 2003 Feb;62(1):46-59.
2. Yunus MB. The role of gender in fibromyalgia syndrome. Curr Rheumatol Rep. 2001 Apr;3(2):128-34.
3. Bennett RM. Fibromyalgia: the commonest cause of widespread pain. Compr Ther. 1995 Jun;21(6):269-75.
4. Ataoglu S, Ozcetin A, Yildiz O, Ataoglu A. Evaluation of dexamethasone suppression test in fibromyalgia patients with or without depression. Swiss Med Wkly. 2003 Apr 19;133(15-16):241-4.
5. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the multicenter criteria committee. Arthritis Rheum. 1990 Feb;33(2):160-72.
6. Matsumoto Y. Fibromyalgia syndrome. Nippon Rinsho. 1999 Feb;57(2):364-9.
7. Muller B, Muller W. Generalized tendomyopathy (fibromyalgia). Z Gesamte Inn Med. 1991 Aug;46(10-11):361-9.
8. Nampiaparampil DE, Shmerling RH.A review of fibromyalgia. Am J Manag Care. 2004 Nov;10(11 Pt 1):794-800.
9. Yunus M, Masi AT, Calabro JJ, Shah IK. Primary fibromyalgia. Am Fam Physician. 1982;25(5):115-21.
10. Samborski W, Lezanska-Szpera M, Rybakowski JK. Effects of antidepressant mirtazapine on fibromyalgia symptoms. Rocz Akad Med Bialymst. 2004;49:265-9.
11. Cathebras P, Lauwers A, Rousset H. Fibromyalgia. A critical review. Ann Med Interne (Paris). 1998;149(7):406-14.
12. Wallace DJ. The fibromyalgia syndrome. Ann Med. 1997 Feb;29(1):9-21.
13. Inanici F, Yunus MB. History of fibromyalgia: past to present. Curr Pain Headache Rep. 2004 Oct;8(5):369-78.
14. Masi AT. Concepts of illness in populations as applied to fibromyalgia syndromes: a biopsychosocial perspective. Z Rheumatol. 1998;57 Suppl 2:31-5.
15. Calis M, Gokce C, Ates F, et al. Investigation of the hypothalamo-pituitary-adrenal axis (HPA) by 1 microg ACTH test and metyrapone test in patients with primary fibromyalgia syndrome. J Endocrinol Invest. 2004 Jan;27(1):42-6.
16. Buskila D. Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome. Curr Opin Rheumatol. 2000 Mar;12(2):113-23.
17. Adler GK, Manfredsdottir VF, Creskoff KW. Neuroendocrine abnormalities in fibromyalgia. Curr Pain Headache Rep. 2002 Aug;6(4):289-98.
18. Olin R. Fibromyalgia. A neuro-immuno-endocrinologic syndrome? Lakartidningen. 1995 Feb 22;92(8):755-8.
19. Hudson JI, Goldenberg DL, Pope HG Jr, Keck PE Jr, Schlesinger L. Comorbidity of fibromyalgia with medical and psychiatric disorders. Am J Med. 1992 Apr;92(4):363-7.
20. Russo EB. Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinol Lett. 2004 Feb-Apr;25(1-2):31-9.
21. Nicolodi M, Sicuteri F. Fibromyalgia and migraine, two faces of the same mechanism. Serotonin as the common clue for pathogenesis and therapy. Adv Exp Med Biol. 1996;398:373-9.
22. Thompson D, Lettich L, Takeshita J. Fibromyalgia: an overview. Curr Psychiatry Rep. 2003 Jul;5(3):211-7.
23. Gupta A, Silman AJ. Psychological stress and fibromyalgia: a review of the evidence suggesting a neuroendocrine link. Arthritis Res Ther. 2004;6(3):98-106.
24. Klein R, Berg PA. High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders. Eur J Med Res. 1995 Oct 16;1(1):21-6.
25. Crofford LJ, Engleberg NC, Demitrack MA. Neurohormonal perturbations in fibromyalgia. Baillieres Clin Rheumatol. 1996 May;10(2):365-78.
26. Kizildere S, Gluck T, Zietz B, Scholmerich J, Straub RH. During a corticotropin-releasing hormone test in healthy subjects, administration of a beta-adrenergic antagonist induced secretion of cortisol and dehydroepiandrosterone sulfate and inhibited secretion of ACTH. Eur J Endocrinol. 2003 Jan;148(1):45-53.
27. Pongratz D, Spath M. Fibromyalgia. Fortschr Neurol Psychiatr. 2001 Apr;69(4):189-93.
28. Chung N, Cho SY, Choi DH, et al. STATT: a titrate-to-goal study of simvastatin in Asian patients with coronary heart disease. Simvastatin Treats Asians to Target. Clin Ther. 2001 Jun;23(6):858-70.
29. Santelmann H, Laerum E, Roennevig J, Fagertun HE. Effectiveness of nystatin in polysymptomatic patients. A randomized, double-blind trial with nystatin versus placebo in general practice. Fam Pract. 2001 Jun;18(3):258-65.
30. Hug C, Gerber NJ. Fibromyalgia syndrome, a frequently misdiagnosed entity. Schweiz Med Wochenschr. 1990 Mar 24;120(12):395-401.
31. Moldofsky H. Management of sleep disorders in fibromyalgia. Rheum Dis Clin North Am. 2002 May;28(2):353-65.
32. Rohr UD, Herold J. Melatonin deficiencies in women. Maturitas. 2002 Apr 15;41 Suppl 1:S85-104.
33. Dzugan SA, Smith RA. The simultaneous restoration of neurohormonal and metabolic integrity as a very promising method of migraine management. Bull Urg Rec Med. 2003;4(4):622-8.