Study Suggests Hormones, Autoimmunity and/or Viruses at Work in ME/CFS

Age Patterns Provide Pointer

A Norwegian study of ME/CFS patient records that found two age peaks in Chronic Fatigue Syndrome, one starting from ages 10-19, the other from 30-39, could tell us something about the disorder.Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008–2012   Inger Johanne Bakken1*, Kari Tveito2, Nina Gunnes1, Sara Ghaderi1, Camilla Stoltenberg1,3, Lill Trogstad1, Siri Eldevik Håberg1 and Per Magnus1 Bakken et al. BMC Medicine 2014, 12:167It wasn’t as if people of other ages didn’t come down with Chronic Fatigue Syndrome – many people in other age groups did - but the numbers of ME/CFS cases spiked in these age groups.The least likely times to come down with ME/CFS were at the two ends of the age spectrum: from 5-9 and after the age of 55.Just 121 cases were reported from ages 5-9, but after the age of nine the incidence of ME/CFS spiked up sharply with almost 700 cases reported from ages 10-14 and 15-19. From 20-29 it dropped about 30% with about 500 cases reported, and then zoomed up again to about 700 cases from ages 30-39. From ages 40-44, 45-49, 50-54 declined until at ages 55+ the incidence was very low indeed.That’s in contrast to many disorders which get more prevalent as we age.As in other surveys, young female and adult women in their most productive years were much more likely (75%) to come down with ME/CFS than men.What does it all mean?

Females Dominate

The high rate of females with ME/CFS combined with the unusual pattern of incidence points a finger directly at female hormones.   Three periods of major hormonal fluctuations occur in women; during puberty, during pregnancy and during menopause. Spikes in ME/CFS incidence occurred during two of these; puberty and when women often get pregnant, but not during menopause.

Sex Hormones, ME/CFS and IBS

A CDC study indicating women with ME/CFS have greatly increased rates of gynecological disorders also suggested that sex hormones could play a major role in the disorder. Despite the female predominance in ME/CFS and FM sex hormones have not been well studied in either disorder, but they have been better studied in another female dominated disorder  that often co-occurrswith ME/CFS and Fibromyalgia - irritable bowel syndrome.The same pattern of disease development over time is found in IBS. The incidence of IBS peaks in women from their teens to about their mid-forties and then declines over time. By the time women reach their seventies their incidence of IBS drops to that found in men.

Estrogen

Estrogen is the major female  hormone produced. Its many effects on the body and its widely varying production had made it difficult to  study, but Broderick’s ME/CFS model suggests that estrogen triggered dysregulation of the HPA axis may play a key role the development of Chronic Fatigue Syndrome in females.That’s Low Estrogen – If estrogen plays a role it’s probably low not high estrogen levels that are the problem. Estrogen effects neurotransmitter production and activity and electrical excitability, and has a neuroprotective effect on central nervous system functioning.Pain Connection - Some evidence suggests low estrogen level may play a role in chronic pain.  The greater degree of emotional arousal women with IBS display in response to pain could reflect reduced estrogen levels. The association of high estrogen levels with increased opioid receptors suggests higher estrogen levels may reduce pain.Gut Connection - Female hormones not only influence gut motility – a key feature of IBS - but also gut secretions, gut contractions, immune functioning and pain sensitivity. The fact that about a third of women with IBS issues have them only during menstruation again suggests reduced sex hormone levels could play a role.  Reduced hormone levels during menstruation have been linked to abdominal pain and bloating.Overall, the evidence suggests that estrogen probably plays a protective role in IBS, multiple sclerosis, pain disorders and possibly chronic fatigue syndrome.  However, the lower incidence of ME/CFS during menopause - when estrogen levels tend to be low - suggests that more than estrogen is  involved.

A Positive Role for Male Hormones

In contrast to women, age appears to play little role in the development of IBS in men:  they experience no significant changes in IBS incidence throughout their lifespan.Male hormones often get a bad rap :) but the lower rates of incidence and the lack of a discernible pattern of incidence in men suggests they may have a protective function. Broderick’s modeling studies suggest that male hormones such as testosterone are protective in ME/CFS and some evidence suggests the same may be true in IBS.Testosterone also appears to have pain reducing properties that provide protection against the development of pain disorders.  Low testosterone levels in men, for instance, have been associated with increased sensitivity to rectal pain.  Some men with ME/CFS have find testosterone supplementation helpful.Hormones, or the lack of them, may very well be a contributing  factor to getting ME/CFS, but the spikes in incidence also point a finger at two other factors: viruses and autoimmune disorders.

The Viral Connection - Epstein Barr Virus

Spike in Adolescence  - The increasingly late exposure to the Epstein-Barr virus found in the Western world could contribute to the spike in ME/CFS prevalence in adolescence.Exposure to EBV in infancy, when cytotoxic T-cell levels are at their highest, is usually hardly noticed, but a first exposure to EBV in adolescence often results in a severe illness such as infectious mononucleosis/glandular fever  -  which appears to trigger ME/CFS in about ten percent  of patients.Spike in Middle Adulthood - Attributing the spike in ME/CFS prevalence in from 30-39 to EBV activation is a bit more difficult. Pregnancy in combination with the stress of child rearing could help explain it, however.EBV reactivation in response to stress is well documented, but EBV reactivation also commonly occurs during pregnancy. One study found EBV reactivation in 35% of pregnant women by the second trimester and reactivation rates may be as high as 50% in pregnant women experiencing depression or high rates of stress.Dramatic changes in estrogen,  progesterone and interestingly enough, cortisol - given Broderick's model of ME/CFS - also occur during pregnancy.Pregnancy is  also  associated with an increased risk of autoimmune disorders and the incidence of  MS increases in the first six  months after pregnancy.Reductions in symptoms that often also occur in existing cases of ME/CFS and multiple sclerosis during pregnancy are believed to reflect spikes in estrogen.  (Anti-inflammatory cytokines that spike during pregnancy could play a role as well.)  Coming up shortly we’ll explore an estrogen targeting drug for MS that could possibly spell good news for people with ME/CFS and FM.Set to Up to Fail? - Studies indicating that infectious mononucleosis increases the risk of coming down with multiple sclerosis later in life two-threefold raises the question whether a similar pattern might exist in chronic fatigue syndrome. Could a severe case of mononucleosis as a teenager set you up for getting ME/CFS several decades later?

Autoimmune Disorders

A similar age-related  incidence pattern is also found in some autoimmune disorders. Lupus is most commonly diagnosed between the ages of 15-35. Multiple sclerosis (MS) is most commonly diagnosed in people between the ages of 20 and 50 years.  Sjogren's  Syndrome typically begins in the same "middle adult" years  that ME/CFS spikes are seen in.

Conclusion 

The age spikes  found in this study  suggests chronic  fatigue syndrome shares  features with several other disorders.  Similar patterns of incidence in IBS, multiple  sclerosis, lupus and Sjogren's Syndrome, and high rates of female predominance also occur in some autoimmune disorders (systemic lupus erythematosus (SLE; females:males - 91), autoimmune thyroid disease (81), scleroderma (51), rheumatoid arthritis (41) and multiple sclerosis (31)).Determining what the spikes mean will  take time and much in the very complex interactions involving hormones and the immune system. The evidence suggests that a constellation of factors, perhaps involving hormones, immune activation, central nervous system excitation, and in some cases viruses play a role in producing ME/CFS.  This study highlights "danger points" when women may be particularly vulnerable.The reduced incidence of ME/CFS and autoimmune and pain disorders in men, on the other hand, may reflect the protective effects male hormones provide.Next Up - a possible breakthrough multiple sclerosis drug that affects estrogen activity. Could it have potential for ME/CFS?