Research: Sex and disease severity‑based analysis of steroid hormones in ME/CFS

“This is interesting new research but the findings have to be regarded as preliminary at the moment until they have been verified in further studies. They cannot be used to guide clinical decisions on aspects of management that involve the use of hormones. But this is information that can be brought to the attention of a doctor when hormonal treatment is being used or considered.”

Dr Charles Shepherd, Trustee and Hon. Medical Adviser to the ME Association.



Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease characterized by persistent fatigue and decreased daily activity following physical and/or cognitive exertion. While ME/CFS afects both sexes, there is a higher prevalence in women. However, studies evaluating this sex-related bias are limited.


Circulating steroid hormones, including mineralocorticoids (aldosterone), glucocorticoids (cortisol, corticosterone, 11-deoxycortisol, cortisone), androgens (androstenedione, testosterone), and progestins (progesterone, 17α-hydroxyprogesterone), were measured in plasma samples using ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS). Samples were obtained from mild/moderate (ME/CFSmm; females, n=20; males, n=8), severely afected patients (ME/CFSsa; females, n=24; males, n=6), and healthy controls (HC, females, n=12; males, n=17).


After correction for multiple testing, we observed that circulating levels of 11-deoxycortisol, 17α-hydroxyprogesterone in females, and progesterone in males were signifcantly diferent between HC, ME/CFSmm, and ME/CFSsa. Comparing two independent groups, we found that female ME/CFSsa had higher levels of 11-deoxycortisol (vs. HC and ME/CFSmm) and 17α-hydroxyprogesterone (vs. HC). In addition, female ME/CFSmm showed a signifcant increase in progesterone levels compared to HC.

In contrast, our study found that male ME/CFSmm had lower circulating levels of cortisol and corticosterone, while progesterone levels were elevated compared to HC. In addition to these univariate analyses, our correlational and multivariate approaches identifed diferential associations between our study groups. Also, using two-component partial least squares discriminant analysis (PLS-DA), we were able to discriminate ME/CFS from HC with an accuracy of 0.712 and 0.846 for females and males, respectively.


Our fndings suggest the potential value of including steroid hormones in future studies aimed at improving stratifcation in ME/CFS. Additionally, our results provide new perspectives to explore the clinical relevance of these diferences within specifc patient subgroups.

The UK ME/CFS Biobank

This new research study carried out by Francisco Westermeier et al at the University of Applied Sciences in Austria used blood samples from the UK ME/CFS Biobank to examine the role of steroid hormones, including cortisol, in ME/CFS. The ME Association Ramsay Research Fund pays for all the basic running costs (approx £80,000 per annum) of the ME/CFS Biobank. It forms part of the University College London Biobank at the Royal Free Hospital in London. Dr Charles Shepherd (Medical Adviser to the ME Association) chairs the Biobank Steering Group.

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