Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway…, 2014, Bakken+

[Peter T]

One thing I think can be said at this point is that although it looks as if the second peak for men was partly an artefact there are also good reasons to think it is still there. It would be easy enough to link two peaks to changes in female hormone levels but if the male peak is real that doesn't work.

I was wondering that, as a male with a sudden onset in my mid thirties associated with an acute EBV infection I had no obvious reasons to suspect any hormonal issues at that point in my life. Also anecdotally the men I know about with adult onset also had their onset in their thirties. I wonder, given the smaller number of males in the various studies, if larger sample sizes would make a second male peak a more robust phenomenon.

I did have lots of viral infections in my twenties, but that was when I was working on a group of islands into some twenty schools and three hospitals. However they were usually mild and short lived and after several years I suspect I adapted to the local virus population, then having brief mild infections only when I visited the mainland. However my health was then pretty stable once I had settled in back into living in England, that is until I got the triggering glandular fever (mono).

Has any one compared levels of sex hormones in both male and female patients with appropriate controls?

 

[Amw66]

We'd have to rule out sex hormones as a critical driver, wouldn't we, if it is real? Both female peaks align roughly with changes in hormone levels, but they don't in males. And the second female peak would be more persuasive if it occurred between 40 and 50 instead of 30 and 40.

Presumably it would be quite helpful to be able to rule that out, though I suppose it's difficult to do so entirely.

Stopped for lunch before a meeting and reading this thread . Random thoughts which may not be relevant.

Hormones . Ratios rather than absolutes may be important.
Whilst focus tends to be on estrogen , it could equally be testosterone.
Taking it back further the basic block is cholesterol which factors in lipids

 

[Jonathan Edwards]

So if the second male peak is real, would we have to argue that the second peak being stronger for females is because of differences between the sexes' immune systems as they encounter infections, perhaps from children?

I don't think it need have much to do with encountering infections. We have to assume that some pathway in women is easier to subvert. It is likely to be "immune" but if involves an innate immune signals like TLR7 it might impact on susceptibility of brain cells without involving immune responses elsewhere to specific antigens. There may be an infection trigger step but it is what happens after that we need to understand.

The second male peak may get lost for technical reasons but it is relatively small cmpared to the first male peak in comparison to women. That raises an interesting issue. If female susceptibility is due to incomplete X chromosome inactivation it ought to operate at age 15 as well as 35. Unless of course the incomplete inactivation is oestrogen dependent.

 

[BrightCandle]

There is also a possibility that the second male peak is being impacted by diagnosis rates. We know that men are less likely to get a diagnosis, its possible the older men are dismissed more than the male children. Because this is gathered from a public health registry its quite likely its impacted by the medical systems own biases and there is a lot of that and Norway has been one of the more problematic places for this over the years and this study is from well before they started to accept ME/CFS wasn't psychosomatic.

 

[Evergreen]

We'd have to rule out sex hormones as a critical driver, wouldn't we, if it is real? Both female peaks align roughly with changes in hormone levels, but they don't in males. And the second female peak would be more persuasive if it occurred between 40 and 50 instead of 30 and 40.

Presumably it would be quite helpful to be able to rule that out, though I suppose it's difficult to do so entirely.

My post followed on from Jonathan's:

It would be easy enough to link two peaks to changes in female hormone levels but if the male peak is real that doesn't work.

My understanding is that if the second peak in males is real rather than an artefact, then we can rule out changes in hormones as a critical driver, because males don't have dramatic changes in hormones at that age in the way that women do.

So if the second male peak is real, we need another explanation. Or one explanation for females and a different one for males.

 

[bobbler]

We'd have to rule out sex hormones as a critical driver, wouldn't we, if it is real? Both female peaks align roughly with changes in hormone levels, but they don't in males. And the second female peak would be more persuasive if it occurred between 40 and 50 instead of 30 and 40.

Presumably it would be quite helpful to be able to rule that out, though I suppose it's difficult to do so entirely.

The age of menarche has got younger over the decades for the general population in industrialized countries (so if it’s linked to industrialization then countries who have become or parts of it have become affected in this way ie have become more industrialized later over the years would show the same trend with a time lag)

No idea re menopause (and I guess that’s been complicated by record keeping and ‘diagnosis’ changes related to medical developments and attitudes) and as you say the peak is 30-40 which could fit to other things

It would be a fearsome calculation fraught with other factors , and would require data on me/cfs that probably doesn’t exist across countries over long time periods

But theoretically I guess it could give clues if it did existed as to how much is ‘explained by directly/indirectly linked with’ those points of hormone change if there were any shifts that correlate with those same trends of menarche age in a country/population ?

 

[Mij]

I was wondering that, as a male with a sudden onset in my mid thirties associated with an acute EBV infection I had no obvious reasons to suspect any hormonal issues at that point in my life. Also anecdotally the men I know about with adult onset also had their onset in their thirties. I wonder, given the smaller number of males in the various studies, if larger sample sizes would make a second male peak a more robust phenomenon.

I had no obvious reason to suspect hormones in my case. I had sudden viral onset at age 29 PVFS that developed into ME in my mid 30s.. The ME specialist I saw in the 90s told me that my age group for ME was the most common he had seen in his 20 years experience.

 

[Evergreen]

If female susceptibility is due to incomplete X chromosome inactivation it ought to operate at age 15 as well as 35. Unless of course the incomplete inactivation is oestrogen dependent.

Speaking of oestrogen, it does rise in males as well as females during puberty, though not nearly as much, and then stays steady for males, while jumping around a lot for females. That's if this preprint is robust "Estrogen Hormone Is an Essential Sex Factor Inhibiting Inflammation and Immune Response in COVID-19":

 

[Trish]

I assume the suggestion of female hormones playing a role is as a possible predisposing factor for some, though it clearly can't be a necessary factor, since men and post menopausal women can get ME/CFS. And it can't be a key perpetuating factor either, as the menopause is not, as far as I know, a staging post for either worsening or recovery in those whose ME/CFS started before the menopause.

 

[Jonathan Edwards]

I assume the suggestion of female hormones playing a role is as a possible predisposing factor

Yes, it would be a statistical weighting factor, along with some other genes, as per DecodeME and age etc.. For any given set up there will be a risk level and it will be a matter of chance - 1 in 100 or 1 in 40 or 1 in 500, whether you get disease.

 

[OrganicChilli]

I assume the suggestion of female hormones playing a role is as a possible predisposing factor for some, though it clearly can't be a necessary factor

What about pregnancy? I remember a thread where some members reported remission during pregnancy.

 

[Midnattsol]

What about pregnancy? I remember a thread where some members reported remission during pregnancy.

Pregnancy can influence many of the things that are proposed to be part of the ME/CFS puzzle, like blood flow, in addition to hormones and the immune system.

On the peaks - the ages also coincide with times in life where you might have less time to rest and have more activities in your life that’s not necessarily for you to control. Time where what was up until then a manageable «I need more rest» situation into rolling PEM and eventually not being able to take part in things anymore.

For children:
In Norway, you have different times in childcare. Ages 1-2/3 will have opportunities to rest during the day, but this diminishes as the child becomes older and has to follow along with the group where most don’t need a daily nap. It has become increasingly common to have extracurricular activities even for ages 2+ in addition to childcare.

Starting school is obviously also a big change in a child’s life, and there are yet more extracurricular activities.

Moving from the younger classes to the older ones (we have a split between 1-4, 5-7 and 8-10, which for some may require a change in school environment. For me it meant going from a 10 min walk to school to a 30+min busdrive with all the noise that follows being in a bus full of children going to school). The older ages sometimes have more homework, but this can differ a lot between schools.

Schoolyears 11-13 are voluntary, but in practice required. Recently more focus has been put on attendance (I would bot have been able to finish school with todays rules).

Adults:
University years in Norway can allow for being sick for years without getting a diagnosis. We have student loans that you can have for years (you need something from a doctor to not be told you’re lagging too far behind to continue, but it is still a time where it can be possible to muddle along with illness pretty well. A sad joke in my disability community is that many master student’s over here really ought to be on disability instead of getting student loans…)

After university (or in stead of university) you might be working and have various possibilities to rest. But if you become a parent (currently this typically happens in early 30s in Norway), that doesn’t hold anymore. Your typical child in Norway starts in childcare around ~1 year old, and from then on is believed to bring home 5-10 infections a year during childcare for the parents to deal with.

It can just be too much even without any additional hormonal issues.

Time of diagnosis/time of symptom onset may also be very difficult to assess properly. I’ve thought I developed ME after I outgrew my migraines as a child, but with covid causing migraines - was my migraines actually post viral and then it for some reason changed into ME? My migraine triggers are now my PEM triggers so to me it doesn’t feel too far fetched.

 

[Jonathan Edwards]

It may be worth waiting until we can see the new analyses before plunging into this again. Things look to me very precise and to do with endogenous biology.