Sex and disease severity-based analysis of steroid hormones in ME/CFS, 2023, Westermeier et al

Link to the published paper
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Sex and disease severity-based analysis of steroid hormones in ME/CFS

Preprint Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease characterized by decreased daily activity and persistent fatigue after physical and/or cognitive exertion. Although ME/CFS affects both sexes, there is a higher preponderance of cases in women. However, endocrinological studies focused on evaluating this sex-related disparity are limited.

In this scenario, the aim of this study was to measure 9 circulating steroid hormones (SHs) divided into mineralocorticoids (aldosterone), glucocorticoids (cortisol, corticosterone, 11-deoxycortisol, cortisone), androgens (androstenedione, testosterone), and progestins (progesterone, 17α-hydroxyprogesterone) in plasma samples from mild/moderate (ME/CFSmm; females, n=20; males, n=8), severely affected patients (ME/CFSsa; females, n=24; males, n=6), and healthy controls (HC, females, n=12; males, n=17) using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).

After correction for multiple testing, we observed that circulating levels of 11-deoxycortisol, 17α-hydroxyprogesterone in females, and progesterone in males were significantly different 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 significant increase in progesterone levels relative to HC. In contrast, we observed 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 identified differential 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.

In conclusion, our findings not only suggest the potential value of including SHs in future studies aimed at improving stratification in ME/CFS, but also provide new perspectives to explore the clinical relevance of these SH-related differences within specific patient subgroups.

https://www.researchsquare.com/article/rs-3428946/v1

 

There has been a bit of discussion about Iwasaki's paper here and what lower cortisol could be indicative of. The sample sizes here are a lot smaller, but could still be able to add something to that discussion with lower cortisol levels only being noticeable in the mild/moderate female (edit: as @Hutan says, this should of course say males) patients in this study. Is there possibly a lower bound for reduced cortisol levels caused by decreased activity, after which these increase again or is everything too noisy to deduce anything?

 

Yeah, I appreciate I am likely in the minority, but the title here, imo, should have the word "Gender" in place of "Sex". Mitigates ambiguity for title surfers.

But I'm one of those who still believes the word "none" must always be singular, so likely just another generational ship sailing away.

 

Now published:
https://link.springer.com/article/10.1007/s40618-024-02334-1

Sex and disease severity-based analysis of steroid hormones in ME/CFS

• Original Article
• Open access
• Published: 10 May 2024

• (2024)

Journal of Endocrinological InvestigationAims and scopeSubmit manuscript

• Cornelia Pipper,
• Linda Bliem,
• Luis E. León,
• Daniela Mennickent,
• Claudia Bodner,
• Enrique Guzmán‑Gutiérrez,
• Michael Stingl,
• Eva Untersmayr,
• Bernhard Wagner,
• Romina Bertinat,
• Nuno Sepúlveda &
• Francisco Westermeier

Abstract
Purpose
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 affects both sexes, there is a higher prevalence in women. However, studies evaluating this sex-related bias are limited.

Methods
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 affected patients (ME/CFSsa; females, n=24; males, n=6), and healthy controls (HC, females, n=12; males, n=17).

Results
After correction for multiple testing, we observed that circulating levels of 11-deoxycortisol, 17α-hydroxyprogesterone in females, and progesterone in males were significantly different 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 significant 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 identified differential 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.

Conclusion
Our findings suggest the potential value of including steroid hormones in future studies aimed at improving stratification in ME/CFS. Additionally, our results provide new perspectives to explore the clinical relevance of these differences within specific patient subgroups.

 

Twitter thread by corresponding author on preprint:

 

Hutan I very much agree with your post above except the quoted sentences. Of course the definitions of levels of severity are soft, and vary according to clinicians. But if my level of severity for physical dimension was lower, as in able to go out and do things, but more severe for the cognitive and social dimension, which prevents me from interacting with people or even think too hard. I suspect I would still be classified as mild or moderate.

The idea I have of a severe or very severe patients is that they cannot tolerate much in terms of social activities, or even having visitors in their home, as it would trigger relapses, some of which very prolonged, therefore not sustainable.

I believe that the same weight should be attributed to physical and cognitive functioning when assessing severity.


I hope I am making sense…

 

That would be the case if it weren't for the huge number of cases that develop each year. Most of us who are ill for the long term eventually give up, but those who are ill for less than a year will be going through the usual rounds, sometimes seeing 10+ MDs in the process in a completely dysfunctional and incoherent process, since no one is managing it and everything is basically set up to make this the only option.

So it really is putting a huge burden on health care systems, specifically because it's so disjointed. You can have several different MDs doing mostly the same tests, because there is no coherent process, they don't talk to one another or coordinate anything. It's basically the most inefficient way of doing anything imaginable. Like a kitchen that does every single meal to order from scratch, with no preparation or prior cooking.

And most of those will be relatively mild, since being worse than mild early on means far less ability to try any of this. Looking at numbers from LC, there is a huge number of people who are ill for less than 3-6 months. Most of them will have seen multiple MDs by this point, because anyone being ill for more than 2 weeks will do that, depending on the severity of their illness. It's just too disruptive.

Going back to the early days of LC, it was pretty much that 2-3 weeks point that people started emphasizing. In France the main organization is called "After day 20" for that reason. People don't wait 6 months to do this, just because MDs expect that to happen is not how any of this works, but it's precisely because health care systems refuse to take charge of any of this that everything is disjointed and massively redundant.

More expensive testing is unlikely to happen before about the 6 month mark, like MRIs and such, while specialists usually have waiting periods longer than this, if they even agree to see the patients, but patients don't give up, if they can they'll see 20, 30 MDs if they have to. All invisible, by choice. All definitely a significant burden, by choice.

So, ironically, it's not us, the long term ill, who are the most expensive in terms of medical care. It's the short-termers, because of the sheer number of them, far more than us, and for some more than once in a lifetime. And that doesn't even take into account how many tertiary resources are wasted, like therapists and mental health programs.

 

ME Research UK

Francisco Westermeier and colleagues have recently published the results of a study investigating steroid hormone levels in people with ME/CFS, in which they also subgrouped participants by sex and disease severity.

Read more: https://www.meresearch.org.uk/steroid-hormone-changes-in-me-cfs