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ME/CFS affects more women than men, in an approximate ratio of 4:1. In this respect, the disease is similar to other immuno-inflammatory conditions, such as lupus erythematosus systemic, multiple sclerosis, rheumatoid arthritis, Sjögren’s syndrome, etc, which are also more prevalent in women.

As very few studies have ever examined whether being female or male affects the course of ME/CFS, it would be premature to assume that both sexes undergo the same disease process; perhaps men and women constitute different clinical ‘phenotypes’ of ME/CFS? After all, we already suspect that patients whose illness began with an infection, or patients who have a high degree of autonomic symptoms (read more), or patients who are older (read more) represent distinct subtypes of the illness.

To explore the issue, researchers at Vall d’Hebron University Hospital in Barcelona decided to compare the characteristics of 1309 consecutive ME/CFS patients (Fukuda-defined), mostly referrals from primary care seen at their clinic between January 2008 and May 2011, to identify any sex-related differences that might have implications for the progress of the disease or its therapeutic management. Of the 1309 patients, 119 (9.1%) were men and 1190 (90.9%) were women. The researchers found a number of significant differences between the sexes in a variety of clinical and demographic factors:

  • The most common triggering factor amongst all patients was an infection, but more of the men reported an initial infectious process (26.9 versus 13.0%), while pregnancy-partum issues were initial precipitating factors in 11.3% of women.
  • Men had been diagnosed at a younger age than women (43.0 versus 47.9 years), and had become ill at an earlier age.
  • More of the men were single (31 versus 16%), and more were described as ‘skilled workers’ (32 versus 20%).
  • Overall, 27.9% of women had a family history of chronic pain compared with only 18.5% of men, although there was no difference in their family history of illnesses.
  • The incidence of ‘comorbid conditions’ (illnesses existing alongside ME/CFS) was higher in women than men, with highly significant differences in the rates of thyroid disorders (approx 20% in women versus <5% in men), fibromyalgia (58 versus 29%), shoulder tendinitis and regional myofascial pain (i.e. pain and inflammation in the muscle or connective tissues).
  • The major clinical differences between the sexes was in immune and muscular symptoms. Immune symptoms were less frequent in men than women: Raynaud’s phenomenon (19.3 versus 27.9%), generalized morning stiffness (76.5 versus 83.7%), migratory arthralgia (79 versus 86.4%), drug allergy (16 versus 24.8%), and allergy to metals (6.7 versus 17.1%). Muscular symptoms were less frequent in men: generalized pain (78.2 versus 90.9%), difficulty in fine movements because of pain (77.3 versus 86.1%), and muscle contractures (83.2 versus 89.6%).
  • Women had worse scores for physical function, physical role, and overall physical health on the MOS SF-36 questionnaire assessing quality of life.

The take-home message from this relatively simple investigation is that there are many measurable differences between women and men with ME/CFS, particularly as regards onset, co-existing conditions and symptoms. Whether these are evidence of distinct, clinically meaningful sex-based “phenotypes” remains to be seen, however, as differences in accessing healthcare or other social factors may also be involved. Nevertheless, the authors point out that ME/CFS is best thought of as a neuro-inflammatory process (triggered by a range of influences) causing a particular cluster of symptoms, including exercise intolerance and neurocognitive problems, in patients with a genetic susceptibility. As there are neuro-immune differences between the sexes, some of the discrepancies between male and female ME/CFS patients could well reflect differences in the disease and how it develops.

Further reading
Gender differences in chronic fatigue syndrome. Faro M, et al. Reumatol Clin, 2015 Jul 16. Read more (full text in Spanish).
Is chronic fatigue syndrome in older patients a different disease? A clinical cohort study. Lewis I, et al. European Journal of Clinical Investigation, 2013 March; 43(3): 302–8. An ME Research UK-funded investigation (read more).
Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome. Lewis I, et al. Journal of Internal Medicine, 2013 May; 273(5): 501–10. An ME Research UK-funded investigation (read more).

Picture credit
Mikael Häggström, Wikipedia commons