Like autoimmune diseases and POTS, Women are affected by ME/CFS at much higher rates. Presumably the factors which lead to this may play a role in treatment response and recovery rates.

Recent metabolomics studies show a different pattern of disruption, with differences in the protein deficiencies and pathways affected between males and females. Similar to other autoimmune diseases like lupus, 80-90% of ME/CFS patients are women. Anecdotally, CFS recovery, especially through exercise, seems more common amongst men. Perhaps men are originally affected at similar rates to women (without being diagnosed) but recover. Testosterone may play a role, given the role of muscle wasting, as testosterone makes it easier to build muscle. It may also be anti-inflammatory (ref). Menstruation and inflammatory ostrogen may also play a maintaining role. 

2015 study on gender differences in CFS: Only 9.1% of patients were men. 

‘Widespread pain, muscle spasms, dizziness, sexual dysfunction, Raynaud’s phenomenon, morning stiffness, migratory arthralgias, drug and metals allergy, and facial oedema were less frequent in men. Fibromyalgia was present in 29% of men vs. 58% in women. The scores on physical function, physical role, and overall physical health of the SF-36 were higher in men. The sensory and affective dimensions of pain were lower in men.’
‘Men had less pain and less muscle and immune symptoms, fewer comorbid phenomena, and a better quality of life.’

‘More men reported an initial infectious process (26.9 versus 13.0%), while pregnancy-partum issues were precipitating factors in 11.3% of women.’

Ratios of male to female differ and differing case definitions confuse the issue even more so. A 2014 Norwegian study found the female to male incidence rate ratio of CFS/ME was 3.2 (75.4% women). 

Metabolic features of me/cfs Naviaux 2016 study showed distinct patterns for males versus females. This could theoretically explain higher incidence of me/cfs in females, the above lower quality of life for females, and potential differences in treatment response. 

Fluge and Mella found sex differences also: 

Analysis in 200 ME/CFS patients and 102 healthy individuals showed a specific reduction of amino acids that fuel oxidative metabolism via the TCA cycle, mainly in female ME/CFS patients. Serum 3-methylhistidine, a marker of endogenous protein catabolism, was significantly increased in male patients.

‘Sex appeared to be an important factor in interpretation of the results, with significant reductions of mean serum levels of category II and III amino acids evident in female ME/CFS patients’


Infections reveal inequality between the sexes

Hormones also play a part. Oestrogen can activate the cells involved in antiviral responses, and testosterone suppresses inflammation. Some vaccines have been more effective in girls (TB), others have killed girls (measles in 1992).

‘Genetic factors may also guide how the sexes deal with infection. Meyaard studies a protein called TLR7, which detects viruses and activates immune cells. Encoded by a gene on the X chromosome, the protein causes a stronger immune response in women than in men. Meyaard suspects that this is because it somehow circumvents the process whereby one of the two X chromosomes in women is shut down to avoid overexpression of proteins.’

This is particularly interesting in light of the protein deficiencies found in women but not men by naviaux (above).

As a result of these differences, many ME/CFS researchers (such as the Armstrong lab in Melbourne Australia and Nauvieux with his suramin research) are now using a female only cohort to reduce variability.

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There may also be a social dimension whereby men are more likely to be believed by doctors, family members and peers. See for example Women are dying because doctors treat us like men or the ABC podcast on the same topic. This article regarding the psychologisation of illness may also be of interest. 

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