The underlying sex differences in neuroendocrine adaptations relevant to Myalgic Encephalomyelitis Chronic Fatigue Syndrome, 2022, Thomas et al

Abstract

Introduction
Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) is a complex multisystem disease characterised by severe and disabling new-onset symptoms of post-exertional malaise (PEM), fatigue, brain fog, and sleep dysfunction that lasts for at least six months. Accumulating evidence suggests that sex and endocrine events have a significant influence on symptom onset and moderation of ME/CFS, with female sex being one of the most consistent and credible predictive risk factors associated with diagnosis. Such sex differences suggest sex chromosomes and sex steroids may play a part in the development of the condition or moderation of symptoms, although this has yet to be explored in detail.

Methods/Aims
This narrative review outlines sex differences in ME/CFS in terms of vulnerability factors and clinical phenotype and explores the known sex differences in neuroendocrine systems affected in ME/CFS and how this may relate to disease risk, onset, pathophysiology, and potential treatment avenues.

Conclusions
There is clear evidence of a sex dimorphism with regards to prevalence (3:1 female preponderance), clinical phenotypes, and aetiological triggers prior to symptom onset of ME/CFS. Endocrinological events, particularly those throughout the female lifespan, are associated with ME/CFS and include reproductive menstrual cycle fluctuations, pregnancy, post-partum and perimenopause. Further, there is evidence for gonadal sex, adrenal stress and renal neuroendocrine systems as implicated in ME/CFS, including changes in estrogen, progesterone compounds, aldosterone, and cortisol levels, of which there are established sex differences. The broad effects of steroid hormones on the physiological systems may also speak to the diversity of ME/CFS symptomatology observed in patients. Further attention must be paid to sex, age, and steroid biology in ME/CFS.

Open access, https://www.sciencedirect.com/science/article/abs/pii/S0091302222000188

 

Until it becomes mandatory to have women in all research that isn't exclusively about men, and not only that but to split results along gender lines and report them separately in research papers, nobody is ever really going to appreciate what differences might exist between how men and women react to certain drugs or react to various ailments, or what differences there are in symptoms between women and men.

I remember being shocked that it was made mandatory to include women as research subject, but the results didn't have to be split by gender and reported separately. What was the point of that? And in many cases when this "include women" demand first started it was often ignored.

 

This is a good research avenue but it's not unique to ME and should be studied within the broader context of why chronic immune diseases affect women more (but not exclusively) than men, especially autoimmune diseases. Of course that requires accepting that the whole nonsense about dismissing all immunology as being relevant to chronic illness was a disastrous failure, which is a tiny bit embarrassing given the screaming matches and foaming at the mouth some very eminent egomaniacs did insisting this was false and that's final.

I doubt anything specific will come out of this looking only at ME. There is no question that the reproductive system has a huge bidirectional impact with the immune system, pregnancy is basically the balance of a body that wants to keep a small growing parasite with some foreign DNA, which, hey, sounds a bit familiar, a kind of standoff state between attack and defense when you can't do a full elimination. While also not foolishly limiting themselves to thinking exclusively of this affecting women, sadly an actual common failure.

It's a damn business cliché to say "think outside the box" but damn is it required in medical science, the lack of curiosity and ability to think differently than what is taught are infuriating, literally ideological taboos are holding back the progress and health of our species. It's like deliberately wearing the kind of blinders horses wear to avoid looking at anything threatening, while also wearing shades. It only leaves a very narrow field of view directly in front.