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.
Women are, generally, physically smaller than men and our hearts and lungs are much smaller in size. Yet our anatomy makes added room to carry a fetus in order to create new human life.
Our smaller heart, lungs, and organs still have to be able to do everything a human male does – pump oxygen, circulate blood, run fast, think fast, be awake 16 hours a day – and have the necessary fuel to carry a child to term. We have to do double duty, on half the machinery. Women can do so much more on less because we also have higher baseline levels of the hormone estrogen. Oestrogen acts as a kind of messenger, carrying information between groups of our cells. Say we are stressed, or catch a flu, or get a vaccine – estrogen helps women have a more robust immune response. This more robust immune response is also thanks to steroid hormones known as glucocorticoids (or GCs).l, which are produced by the adrenal gland and are anti-inflammatory. They help regulate inflammation. This heightened female immune response also means that when our immune system sets out to fight off any foreign invader, such as a virus or bacteria, as women we also produce more of what are called antibodies, or fighter immune cells. That’s good BUT it can also be a problem. As women, when we produce more antibody fighter cells, we also produce more autoantibodies. Autoantibodies are rogue fighter immune cells that can mistakenly attack the body’s own tissue or organs, in what we refer to as friendly fire/ #autoimmunedisease.
When girls repeatedly face #toxicstress during the developmental years, over time, their stress response begins to be dysregulated. Glucocorticoids, or GCs, become less able to properly regulate a healthy, appropriate immune response, which leads to more inflammation. Boys immune systems become dysregulated in response to #toxicstress too — e.g. boys who face #ACEs are more likely to show decreases in brain matter volume in the caudate region of the brain — related to impulse control and behavior), whereas for women risk of autoimmunity is increased 20% for every ace score. Women develop Hashimoto’s thyroiditis at a rate of 10:1 compared with men. In lupus, that rate is 9:1. In Sjögren’s syndrome, 9:1. #AutoimmuneDisease is one of the top ten leading causes of death in women under the age of sixty-five. Women are also twice as likely as men to have chronic pain syndromes. Women with an ACE score of 3 are significantly more likely to have chronic pain syndromes including headaches, back and neck problems. Both boys and girls who grow up with #toxicstress demonstrate, on brain scans, fewer neural connections between the pre-frontal cortex (the decision-making center of the brain) and the hippocampus (area of the brain that helps us to make sense of our emotions and experiences). But, in girls who grow up with #toxicstress and #ACEs, another area of neural connectivity is affected. It goes offline. Synaptic connections between an area of the brain known as the amygdala (fear-and-alert center of the brain) and the pre-frontal cortex are also weakened. the risk that growing up with #toxicstress and #adversechildhoodexperiences will lead to neuroinflammatory diseases such as depression and anxiety disorders is, as with autoimmune disease, 2x as high for women as it is for men. Having experienced 6 categories of childhood adversity can take 20 years off your lifespan. #toxicstress each ace is 20% increased fish for women but only 10% for men. And girls face more #ACEs growing up in general. In fact, girls are 50% more likely to have experienced 5 or more categories of childhood adversity.
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 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’
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.
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.
Here is a related segment on sex hormones in fibromyalgia.