ME/CFS Epidemiology - sex ratios, female predominance

[Snow Leopard]

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Could you explain what you mean by this? The study said that "The sample population of the Lifelines study is broadly representative of the total Dutch population." Mean baseline age was 44.9 with a large standard deviation of 13.2. I think it includes all ages older than 18.

Unless they provide a histogram, and account for participation biases... There may still be a lack of sample size to make any conclusions about an earlier age peak too.

 

[DigitalDrifter]

Just found this: https://ourworldindata.org/gender-ratio#sex-ratio-at-birth

Boys are at higher risk of infectious diseases

Boys are also at higher risk of infectious diseases such as syphilis, malaria, respiratory infections, tetanus and diarrheal diseases. This is more generally true for a broad range of infections, spanning person-to-person, vector-borne, blood-borne, and food and water borne diseases.24 We see this clearly when we compare mortality rates for boys and girls in the earlier chart. But why are boys more susceptible to infection?

Overall, boys have weaker immune systems. There are two key hypotheses for why.

The Y-chromosome in boys increases their vulnerability. Biologically, males and females are differentiated by chromosomes: females have two X chromosomes (XX) and males one X and one Y chromosome (XY). Having two X chromosomes means that the newborn has a stronger immune system because X chromosomes contain a larger number of immune-related genes.25,26 This means that, since females have two X chromosomes, they have a stronger immune response; boys on the other hand, are more vulnerable to X-linked infections.27

This makes males more vulnerable to many infectious diseases. They are also more susceptible to specific genetic diseases where the defective genes are carried on either the X or Y chromosomes; this is because boys have only one X chromosome so a single recessive gene on that X chromosome results in the disease.

But the stronger immune response of females comes with a cost. It’s the reason why women are more susceptible to autoimmune disorders such as HIV/AIDS.28

Sex hormones may be another key reason for weaker immune systems in males. Males have much higher amounts of testosterone which seem to inhibit two major parts of the immune system – B and T-lymphocytes.29 Estrogen, on the other hand, acts as an effective regulator of this. Overall, male hormones weaken the immune system relative to females.

Interesting.

 

[Mithriel]

It may not be relevant to what they are saying here, but one x chromosome is switched off in every cell in a woman. this is the barr body (?) that they used in sport to determine if someone was female or not.

This switching off is one reason why one of identical twins can have a genetic disease while the other does not.

 

[Yvonne]

Does anyone know if the high female:male ratio is only in adults or in both adults and children?

 

[Saz94]

Does anyone know if the high female:male ratio is only in adults or in both adults and children?

I think both?

 

[Hutan]

Posts moved from:
Suppose you have €5-10 million for ME/CFS research, what would you spend it on?

Can you say how that would work? I've been tracking this in studies for decades and have never seen good evidence for anything much below 80%.

I haven't collected up all the evidence in one place, but my impression has been of an incidence of more like two thirds female, one third male. Regardless, here are some possible ideas of the top of my head as to why reported rates might not be accurate:

• Bias in exposure to ME/CFS triggers (or factors that make triggers more potent) in certain studies that aren't reflective of overall incidence. Cultural bias in what infections/triggers are regarded as causing ME/CFS. In the case of Q-fever fatigue syndrome (and possibly Ross River fever too), I think there might even be more males than females, because of the gender patterns in exposure to the pathogens. Some people discount QFFS as ME/CFS, saying that the people who get QFFS are 'made of different stuff' to those who get ME/CFS. There was a suggestion that more young females were exposed to the giardia outbreak in Norway due to them being more likely to drink lots of water. I think a lot of Gulf War Illness is in fact ME/CFS, but it doesn't get diagnosed as that.

• I believe, from observing young people with ME/CFS, that males are less likely to admit there is a problem if the disease is mild than females are. They may prefer to be viewed as lazy than labelled with a stigmatised 'it's all in your mind' disease. That might be why some people have concluded that the disease tends to be more severe in males - it's just the most affected who get the label. Also, I think culture has (at least in the past) tended to allow males with a mild ME/CFS disease to continue to function without a disease label - they may continue to work and then come home and slump in a chair. There hasn't been the same expectation that they will come home and get dinner on and look after the children. I think it's generally accepted that women are more likely to go to the doctor with a health issue than men - that may not be true and certainly won't apply across the board, but it is a prevailing stereotype that may have some basis in fact.

• Doctors may be more mindful of the stigma that goes with a CFS diagnosis when they have a male patient, and spend more time seeking alternative diagnoses, delaying or avoiding the CFS diagnosis. They may be less worried about that for females, in fact they may assume that CFS is a woman's disease, and so may tend to readily reach for a CFS diagnosis when a female patient sits in front of them complaining of fatigue.

• Males tend to have higher incidences (or at least diagnoses) of some other "serious" diseases, with biomarkers, that can cause fatigue, so ME/CFS symptoms may be attributed to those other diseases. Females may have lifestyles that are more likely to cause fatigue (working mother with inadequate help for housework, breastfeeding, anaemia due to blood loss) and so phone surveys supposedly screening for CFS that ask things like 'have you been fatigued for more than 6 months while not having a medical condition that explains the fatigue' may skew towards females.

• Further on the point that having the symptoms of ME/CFS may be harder to accept and less accepted in some cultures if you are a male: This may lead to higher rates of self-medication with alcohol and other drugs and perhaps even suicide in men than in women. I suspect that some of the people who end up homeless have undiagnosed ME/CFS - they just don't have the energy to do what is required to get themselves out of that situation, and family and friends have given up on them.

 

[Hoopoe]

I believe, from observing young people with ME/CFS, that males are less likely to admit there is a problem if the disease is mild than females are. They may prefer to be viewed as lazy than labelled with a stigmatised 'it's all in your mind' disease. That might be why some people have concluded that the disease tends to be more severe in males - it's just the most affected who get the label. Also, I think culture has (at least in the past) tended to allow males with a mild ME/CFS disease to continue to function without a disease label - they may continue to work and then come home and slump in a chair. There hasn't been the same expectation that they will come home and get dinner on and look after the children. I think it's generally accepted that women are more likely to go to the doctor with a health issue than men - that may not be true and certainly won't apply across the board, but it is a prevailing stereotype that may have some basis in fact.

The way it felt for me as male adolescent with (maybe) ME/CFS was that I wasn't allowed to be ill. There was a lot of pressure to go to school and my symptoms were reinterpreted to fit the belief system of the adults. I was not considered a credible witness to my own condition (and indeed, I was very confused by what was happening, but still not as confused as everyone else). I was expected to push through, and if that didn't work or I refused to do it, then that was a behavioural/psychological problem. A teacher convinced himseld that I had a secret drug addiction. These may reflect more the dysfunctional in my family and school environment than society's attitudes.

Even though I clearly was ill (in retrospect), I didn't see myself as having an illness but kept trying to make the aforementioned approach given to me by the adults work. Until at some point, after many crashes, each causing more demoralization and despair, I rebelled against it. Then I was no longer pressured as much, but instead abandoned, as a "bad person".

I see a lot of similarities between this dynamic I exerienced and the PACE trial author approach to ME/CFS.

 

[Dolphin]

I think it's more acceptable for a woman to not work full-time than for a man.

And indeed what I've seen in the ME community is very few men who can't work full-time ending up with a more serious relationship (as defined by a composite of starting to live together/getting engaged/getting married/having children) while it's not rare for women who can't work full-time to end up with a more serious relationship (as defined by a composite of starting to live together/getting engaged/getting married/having children).

Working full-time is very challenging with ME/CFS. I don't think it's easier than working part-time (or not at all) with some extra domestic chores.

 

[Hutan]

Posts copied from Replicated blood-based biomarkers for Myalgic Encephalomyelitis not explicable by inactivity, 2024, Beentjes, Ponting et al

It is a female-dominant disease, with females outnum- bering males by up to five-to-one; females also report more severe symptoms [13, 14].

(Sex ratio has been discussed elsewhere. I would be very interested to see any good papers showing a significantly lower sex ratio - the best would be from community studies, and they are based on tiny numbers of cases and the error margins on M and F prevalence are wide. But if there is new evidence, I'm keen to see it.)

Five to one is a very high ratio. Yes, it says 'up to five-to-one', which covers a lot of ground, but still. I don't think it gives an accurate representation of what we know.

You yourself (Simon) said this on the epidemiology thread, suggesting a ratio of 3 to 1 or 4 to 1.

The Nacul 2011 Prevalence study found around 80% female cases for ME/CFS (Table 4 https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-9-91). The huge Norwegian study gives an incidence ratio of 3.2 female cases for every male case (76% female). And just about every mecfs study ever done, covering many thousands of cases, have 75%-80% female cases (I always check).

The first meta analysis I found when searching the forum was this one of 8 studies in Korea and Japan, admittedly Fukuda criteria. It found a ratio of 2.2 to 1 in Korea and 1.2 to 1 in Japan.

Results: Of the eight studies (five in Korea, three in Japan) included, the total prevalence rate of Korean studies was 0.77% (95% CI 0.34–1.76), and 0.76% (95% CI 0.46–1.25) for the Japanese studies. The prevalence rate in females was approximately two-fold higher than males in Korean studies (1.31% female vs. 0.60% male), while the gender difference was less obvious in Japanese studies (0.76% female vs. 0.65% male).

My sense is that it would be more representative of the data to note that epidemiology is poor but suggests a ratio of three to one (75%:25%) - the Norwegian study would do for reference. And note that that is for diagnoses. It is often said that most people with ME/CFS aren't diagnosed, and so there's a lot we don't know. (There's also the issue of some diseases that seem to trigger ME/CFS tending to infect more men e.g. Q fever, Ross river fever. Indications are the gender ratios of the resulting ME/CFS are more even for those diseases.)

 

[Chris Ponting]

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Five to one is a very high ratio. Yes, it says 'up to five-to-one', which covers a lot of ground, but still. I don't think it gives an accurate representation of what we know.

You yourself (Simon) said this on the epidemiology thread, suggesting a ratio of 3 to 1 or 4 to 1.


The first meta analysis I found when searching the forum was this one of 8 studies in Korea and Japan, admittedly Fukuda criteria. It found a ratio of 2.2 to 1 in Korea and 1.2 to 1 in Japan.


My sense is that it would be more representative of the data to note that epidemiology is poor but suggest a ratio of three to one (75%:25%) - the Norwegian study would do for reference. And note that that is for diagnoses. It is often said that most people with ME/CFS aren't diagnosed, and so there's a lot we don't know. (There's also the issue of some diseases that seem to trigger ME/CFS tending to infect more men e.g. Q fever, Ross river fever. Indications are the gender ratios of the resulting ME/CFS are more even for those diseases.)

In DecodeME we see a female/male ratio of 5-to-1 (https://openresearch.nihr.ac.uk/articles/3-20), and across all ICD10 G93.3 codes in England we see a ratio of 4-to-1 (https://www.medrxiv.org/content/10.1101/2024.01.31.24302070v1). As these are for UK populations and count >17,000 cases, I do think personally that these are the most relevant and reliable estimates.

 

[Hutan]

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In DecodeME we see a female/male ratio of 5-to-1 (https://openresearch.nihr.ac.uk/articles/3-20),

But we can't assume that the voluntary response to a mail-in study is the same as population prevalences. See this study for example. Men might be less likely to be diagnosed with ME/CFS, less likely to network with others with the disease and so hear about the study, and less likely to participate in a study.
DecodeMe was a sample of 20,000 or so people out of a population of maybe 250,000? There's plenty of room for bias in the DecodeME cohort.

Here's another paper, a large study (50 million), that still doesn't account for a likely bias in diagnosis, that found a similar gender ratio to that of the Korean and Japanese meta-analysis.
Estimating Prevalence, Demographics, and Costs of ME/CFS Using Large Scale Medical Claims Data and Machine Learning, 2019
Discussed on the forum here

Techniques of data mining and machine learning were applied to a large database of medical and facility claims from commercially insured patients to determine the prevalence, gender demographics, and costs for individuals with provider-assigned diagnosis codes for myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS). The frequency of diagnosis was 519–1,038/100,000 with the relative risk of females being diagnosed with ME or CFS compared to males 1.238 and 1.178, respectively. While the percentage of women diagnosed with ME/CFS is higher than the percentage of men, ME/CFS is not a “women's disease.” Thirty-five to forty percent of diagnosed patients are men.

 

[Simon M]

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You yourself (Simon) said this on the epidemiology thread, suggesting a ratio of 3 to 1 or 4 to 1.

Bakken: this is the lowest of studies I trust. DecodeME is likely better as bigger and broader recruitment (doesn't need GP referral) at 83% female (Mail in rate sample return was VERY high, reducing bias risk.)

Japan/S Korea prevalence. As before, prevalence studies tend to have small samples, wide confidence intervals, so are unreliable for sex ratios. And most of the studies I've seen from these countries (not necessarily these ones) are of questionable quality.
Nacul: not ideal either: no doctor ME diagnosis for many cases (questionnaire only of cases selected by medical codes with a GP reviewing records only).

ere's another paper, a large study (50 million), that still doesn't account for a likely bias in diagnosis, that found a similar gender ratio to that of the Korean and Japanese meta-analysis.
Estimating Prevalence, Demographics, and Costs of ME/CFS Using Large Scale Medical Claims Data and Machine Learning, 2019

Insurance claim databases have a more than iffy record on diagnosis (including having the highest rates of incidence in those aged 65+, suggesting it is can be used as a bucket code).

It is possible the true ratio is as 3:1, still pretty high, but I think it could well be 5:1 (I think DecodeMe is 6:1). However, we are revisiting old ground and I will leave it there.

 

[Hutan]

From a discussion on another thread about a claimed sex ratio in ME/CFS of 5 to 1:

It is possible the true ratio is as 3:1, still pretty high, but I think it could well be 5:1 (I think DecodeMe is 6:1). However, we are revisiting old ground and I will leave it there.

In DecodeME we see a female/male ratio of 5-to-1 (https://openresearch.nihr.ac.uk/articles/3-20), and across all ICD10 G93.3 codes in England we see a ratio of 4-to-1 (https://www.medrxiv.org/content/10.1101/2024.01.31.24302070v1). As these are for UK populations and count >17,000 cases, I do think personally that these are the most relevant and reliable estimates.

Insurance claim databases have a more than iffy record on diagnosis (including having the highest rates of incidence in those aged 65+, suggesting it is can be used as a bucket code).

I know the issue of sex ratios issue isn't very important in a paper about biomarkers, but there are good reasons to try to get it as right as possible in published papers. I'm a bit surprised about the belief that the voluntary DecodeME participation rates is the best data on sex ratios around, resulting in the use of a 5 to 1 sex ratio. DecodeME required that people had had a medical diagnosis of ME/CFS, and then it is highly likely that there was some bias skewing towards female participation in the study overlaid on that. In almost any voluntary study open to both sexes that doesn't actively recruit for balanced representation, there is more female participation. I think the 5 to 1 sex ratio is out of step with the ratio reported in most literature I have seen, which tends to use a 3 to 1 ratio. A 3 to 1 ratio is in fact the 'old ground'; a claim of a 5 to 1 ratio is a departure that I think needs to be well-evidenced.

If the ICD10 G93.3 codes in England suggest a ratio of 4 to 1, wouldn't that be a more solid number to tie a claimed sex ratio to than the DecodeME participation rates? Arguably, the stigma of an ME/CFS diagnosis is particularly high in the UK, and that may affect male identification with, and participation in, the ME/CFS community. Ongoing claims that ME/CFS is a 'female disease' may actually exacerbate the stigma some men feel with the diagnosis, and also contribute to lower rates of diagnosis in men (in a similar way to past under-diagnosis of heart disease in females). Given that, I think the sex ratio of 4 has to be at the top end of the plausible range.

The US medical insurance paper had a catchment population of 50 million people, and it analysed medical diagnosis data separately for people given a diagnosis of CFS and of ME (with similar sex ratios found in each). It's a decent paper. The data is analysed in 10 year age bands, and in no age band does the sex ratio (females to males) exceed 2. So, it's possible to discount the data in the age bands above 70 years or even 60 years, and still conclude that the sex ratio in this population was not higher than 2. It's a valid data point, comparable to the English ICD code data in credibility.

Estimating Prevalence, Demographics, and Costs of ME/CFS Using Large Scale Medical Claims Data and Machine Learning, 2019
Discussed on the forum here

 

[Jonathan Edwards]

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I tend to agree with @Ravn about not needing a lot of background on ME/CFS, and also with @Hutan 's post (on the epidemiology thread) on sex ratio.

Just as a technical point. My main concern about internet recruitment originally was that the GWAS might pick up an allele linked to behaviour that included answering internet calls. The defence would be that we do not know of any such alleles and if they had a major influence they might have been picked up in other studies.

But we do have one genetic difference that is well known to be associated with behaviours relating to health care and that is the XX, XY difference. Rates of attending GPs and outpatients are confounded by female-related health issues in long adults, which is where differences are regularly reported. But we know that women are more likely to deliberately take up healthy diets (regardless of whether they stick to them!). My guess is that a call for volunteers for an ME/CFS study is likely, for a complicated combination of reasons, to be overweighted towards women responders by a factor of 1.5-1.7. I have no data but that means that for me the most likely interpretation of a 5:1 response is that it reflects a 3:1 prevalence.

Maybe, as Rain says, the safest thing, not to raise hares about methodology, is just not to quote a figure. It isn't relevant beyond there being a female predominance.

 

[Simon M]

The US medical insurance paper had a catchment population of 50 million people, and it analysed medical diagnosis data separately for people given a diagnosis of CFS and of ME (with similar sex ratios found in each). It's a decent paper. The data is analysed in 10 year age bands, and in no age band does the sex ratio (females to males) exceed 2. So, it's possible to discount the data in the age bands above 70 years or even 60 years, and still conclude that the sex ratio in this population was not higher than 2. It's a valid data point, comparable to the English ICD code data in credibility.

I've reread that paper. It's interesting and has some notable ME authors: Lucinda Bateman, Charles Lapp and Peter Rowe.

However, there are issues with the data that cast doubt on the accuracy of diagnosis and so the finding of 59% female (sex ratio 1.4) for ME codes as shown in Table 8.

The consensus on the discussion thread is that the CFS data isn't worth much because its codes includes chronic fatigue. The authors were unable to create a robust model using this data, which is why they looked separately at just ME using diagnostic codes G93.3, and ICDM-9 code 380.71, which was also when the data was collected.

The big anomaly about this ME data is the prevalence rate by age shown in fig 2. Prevalence should increase with age, with increases between age bands broadly reflecting age incidence. I've shown it below with added straight lines to help show where incidence increases:



What we see is fairly steady increases implying a steady rates of incidence - with a big increase over the age of 70 ) e.g for females prevalence increase from around 160/100k aged 50-59 to double that for ages 80-89.

Physicians normally say that diagnoses over age 60 are rare, not least because of the difficulty ruling out other potential causes.

For comparison, here is incidence (not prevalence, so you see peaks and troughs directly) for the recent 11k EMEA pan-european study that asked PwME about age of onset (Bakken/Hilland only have age at diagnosis). The pattern is similar to Bakkken/Hilland with a peak in adolescence (note, this is only seen in a few individual countries in the EMEA study) and a substantial increase midlife peaking in late 30s/early 40s. Then a sharp drop with very few new cases after age 60 (cropped by my screenshot but check the original)



And these studies are backed up by reports from people like Charles Shepherd and Tony Komaroff who have said that the most common age of onset is midlife. By contrast, the medical claims data has no midlife peak but a big geriatric surge. This suggests that the codes measured are not accurately picking up ME - or even a cohort that is mostly ME.

This might be because awareness/understanding of ME is poor among US doctors (e.g. the Jason prevalence study finding that a large majority of specialist-diagnosed cases it found had not already been diagnosed). The claims database covers both physician and hospital diagnoses (the split isn't given): physician diagnoses are usually less reliable, and I don't know how much specialist diagnosis there is in the US. Above all, I can't see a reason why we should assume this study is right, and many others are wrong.

I'm done for the day/this study

But when I have the energy, I will post on the big hospital-only G93.3 studies, which seem to offer the best sources for robust figures and hopefully an area where we can find agreement:
Bakken 2014
Hilland 2022 (an update of the Bakken findings)
Samms 2024 pre-print with 100k NHS hospital G93.3 cases.

 

[Hutan]

By contrast, the medical claims data has no midlife peak but a big geriatric surge. This suggests that the codes measured are not accurately picking up ME - or even a cohort that is mostly ME.

There is the interchangeability of the ME and CFS diagnoses, and the varying popularities of the two diagnoses over time. It seems likely to me that the higher prevalence of an ME diagnosis aged 80+ could be explained by those people receiving that diagnosis back in the 1980s, when they were in their 30s and 40s. Whereas the diagnosis of CFS became more common in the US (and indeed everywhere) after that time.

The first definition of CFS was published in 1988,

The data in the paper was for 2011-2016, and 2017. Note that some people had both CFS and ME diagnoses.

Also note, the paper is not about when a diagnosis was first made, so it's not about teh time of disease onset. It's about people who consulted a doctor and for whom the insurance claim for that consultation had attached an ME or CFS diagnostic code.

I think it might be possible to argue that the people diagnosed with ME in the US after the promotion of the name 'CFS' are actually more likely to have a disease with PEM than the people in those other databases.


More on the prevalence in the older age groups:
It's not inconceivable that ME/CFS is associated with longevity. There's the risk of suicide of course, but, as a group I expect we eat more healthily than most, smoke less, drink less alcohol. We probably mostly don't do risky activities, we drive less. Perhaps that is a small part of the reason why people with a diagnosis of ME made up a bigger proportion of the geriatric population than expected.

It's also not inconceivable that it is true, that the risk of having ME/CFS actually does increase as we get older. I think the illness is quite a bit like being old prematurely. Maybe almost all 90 year olds actually have ME/CFS! We have seen that repeat Covid-19 infections result in an additive risk of developing Long Covid. So, more infections means more rolls of the dice. With waning immune systems, an increasing burden of chronic infections and many older people collected together in retirement homes, perhaps the dice is being rolled more quickly in later years.

But, of course it's true that doctors may have trouble differentiating ME/CFS from old age, and so the prevalence figures in those older age groups can be questioned. However, as I noted, we can set the figures in those older age bands aside when looking for evidence of sex ratios. That data for older age groups does not invalidate the sex ratios found in younger age groups.

 

[Simon M]

Thanks to @Hutan for splitting off this thread on sex ratios/female predominance.

I was going to focus on the other big studies, but wanted to make a few points in response to yours above.

I'm glad we agree that the prevalence data (and implied incidence) looks wrong. The question is whether there are good explanations for it.

There is the interchangeability of the ME and CFS diagnoses, and the varying popularities of the two diagnoses over time. It seems likely to me that the higher prevalence of an ME diagnosis aged 80+ could be explained by those people receiving that diagnosis back in the 1980s, when they were in their 30s and 40s. Whereas the diagnosis of CFS became more common in the US (and indeed everywhere) after that time.

That's an interesting point. Even those 65 are quite likely to have got their diagnosis in the 1980s or earlier when ME was the only diagnosis available. That could boost relative rates for ME in the over 65 given that a significant proportion of younger people may well have got a CFS diagnoses instead.

The question mark over that is that any diagnosis was very hard to get back in the 80s and earlier. It certainly was in the UK, with only a few specialists known to be willing to make it, e.g. Peter Behan in Scotland. And the UK seemed to be well ahead of most places in ME diagnosis, with a few US exceptions like Dan Peterson. It's hard to see there being enough ME diagnoses back then to make a difference.

Also, we would still expect to see a jump in prevalence in midlife, when most people would be in the "CFS" era. The recent EMEA study - which recruited via social media and had few respondents over age 70 still saw strong midlife peaks in countries across Europe. (This is a similar age range to this study with the older cases removed.)

However, as I noted, we can set the figures in those older age bands aside when looking for evidence of sex ratios. That data for older age groups does not invalidate the sex ratios found in younger age groups.

I'm not sure that follows. If doctors are misusing codes for diagnosing older folk, I don't think we can conclude their diagnoses of younger folk are reliable.

It's not inconceivable that ME/CFS is associated with longevity.

It's also not inconceivable that it is true, that the risk of having ME/CFS actually does increase as we get older.

Many things are not inconceivable. The question here is are they and the findings of this study likely?

Let me summarise my concerns about this study:
1. The prevalence data is very different from what we would expect and it's not clear if this can be explained.
2. The US has poor reputation for diagnosing ME/CFS. There are the studies finding most community-recruited cases (eg Jason) had not been previously diagnosed. There seem to be very few specialist clinics. And #MEAction have campaigned hard in the US on the need to make diagnosis easier, at least when this data was gathered (different from the UK as I will post later).
3. As the paper notes, this data comes from many different medical providers and ther eis no way of knowing how the different organisations use the codes.
4. The data covers both phsysician codes (notoriously unreliable) and hospital ones. There seem to be very few specialist clinics in the US, so I don't know how good the hospital diagnoses are.

I will come back to these issues when looking at other relevant studies (which no doubt have their own weaknesses). But you may be pleased to hear I won't return to this study .

 

[Simon M]

NHS Hospital Episode Statistics Samms & Ponting preprint (thread)
80% Female/3.9:1, 100,000 cases diagnosed with the G93.3 code.

This is the biggest study for sex ratios using codes that do not include chronic fatigue.

Data quality/diagnosis
The dataset reaches back to 1989, but outpatient data is only available from 2004 (initially on a trial basis), and this will provide almost all the cases. There will be negligible numbers of A&E cases. And sadly very few inpatient admissions (many of which might be wrongly-coded as eating disorders et cetera).

There's likely to be some reasonable consistency of diagnosis in that almost all of them will be through the new CFS/ME clinics set up from the late 90s onwards (note that some of these are also fatigue cinics, but fatigue would not be included under a G 93.3 diagnosis). The clinics were primarily set up to offer CBT and graded exercise, but diagnosis is a substantial part of their work. They only consider cases referred from GPs, so are unlikely to include any mild cases. Although the clinics are independent, historically they have networked and the majority of the 43-odd clinics are members of BACME.

However, diagnosis will be far from perfect because CFS/ME clinics are underresourced and can't always get the exclusionary tests they want.

Results
The study found an overall diagnosis rate of 0.16% for people referred to hospital, with a sex ration of 3.9 (80% female).

It also found that diagnostic rates amongst white people were far higher than those for non-whites, even though that the slim evidence we have suggests that true rates are higher amongst black and ethnic minority groups (e.g Dinos 2009). This is a big diagnostic discrepancy by ethnicity than for other common illnesses.

There's also an almost tenfold difference in diagnostic rates amongst white people between the different ICB local health boards (e.g. 0086% to 0.82% for women). Again, nobody believes there is a true difference in prevalence by region, so this again points to an issue with diagnosis.

Cornwall and the Isles of Scilly has the highest diagnostic rate
The highest diagnostic rate by a long way is for Cornwall and the Isles of Scilly Isle at 0.6% for white people (based on over 3,000 diagnosed cases). This makes a lot of sense, because for a very long time, Cornwall has been particularly good for CFS/ME – at least at identifying it (while offering the same ineffective treatments). Now-retired consultant Professor Tony pinching championed the illness for years, not only for Cornwall but for neighbouring counties (which also have higher diagnostic rates). He played a big role in training doctors in the area, including as Dean of the Peninsula School of Medicine. Cornwall has also been amongst the best at patient engagement.

Sex ratio remains high when diagnostic rates are very high
One argument is that the sex ratio is biased because of diagnostic choices and are not representative of the wider patient population. The results for Cornwall (based on over 3,000 cases) indicate that even where diagnostic rates are very high, the sex ratio is much the same: Cornwall has a sex ratio of 3.9, the average for the study.

 

[bobbler]

Posts moved from:
Suppose you have €5-10 million for ME/CFS research, what would you spend it on?


I haven't collected up all the evidence in one place, but my impression has been of an incidence of more like two thirds female, one third male. Regardless, here are some possible ideas of the top of my head as to why reported rates might not be accurate:

• Bias in exposure to ME/CFS triggers (or factors that make triggers more potent) in certain studies that aren't reflective of overall incidence. Cultural bias in what infections/troggers are regarded as causing ME/CFS. In the case of Q-fever fatigue syndrome (and possibly Ross River fever too), I think there might even be more males than females, because of the gender patterns in exposure to the pathogens. Some people discount QFFS as ME/CFS, saying that the people who get QFFS are 'made of different stuff' to those who get ME/CFS. There was a suggestion that more young females were exposed to the giardia outbreak in Norway due to them being more likely to drink lots of water. I think a lot of Gulf War Illness is in fact ME/CFS, but it doesn't get diagnosed as that.

• I believe, from observing young people with ME/CFS, that males are less likely to admit there is a problem if the disease is mild than females are. They may prefer to be viewed as lazy than labelled with a stigmatised 'it's all in your mind' disease. That might be why some people have concluded that the disease tends to be more severe in males - it's just the most affected who get the label. Also, I think culture has (at least in the past) tended to allow males with a mild ME/CFS disease to continue to function without a disease label - they may continue to work and then come home and slump in a chair. There hasn't been the same expectation that they will come home and get dinner on and look after the children. I think it's generally accepted that women are more likely to go to the doctor with a health issue than men - that may not be true and certainly won't apply across the board, but it is a prevailing stereotype that may have some basis in fact.

• Doctors may be more mindful of the stigma that goes with a CFS diagnosis when they have a male patient, and spend more time seeking alternative diagnoses, delaying or avoiding the CFS diagnosis. They may be less worried about that for females, in fact they may assume that CFS is a woman's disease, and so may tend to readily reach for a CFS diagnosis when a female patient sits in front of them complaining of fatigue.

• Males tend to have higher incidences (or at least diagnoses) of some other "serious" diseases, with biomarkers, that can cause fatigue, so ME/CFS symptoms may be attributed to those other diseases. Females may have lifestyles that are more likely to cause fatigue (working mother with inadequate help for housework, breastfeeding, anaemia due to blood loss) and so phone surveys supposedly screening for CFS that ask things like 'have you been fatigued for more than 6 months while not having a medical condition that explains the fatigue' may skew towards females.

• Further on the point that having the symptoms of ME/CFS may be harder to accept and less accepted in some cultures if you are a male: This may lead to higher rates of self-medication with alcohol and other drugs and perhaps even suicide in men than in women. I suspect that some of the people who end up homeless have undiagnosed ME/CFS - they just don't have the energy to do what is required to get themselves out of that situation, and family and friends have given up on them.

I've often thought that the sex difference is a big assumption that we do really need to test before we use it as a clue to the level of using it to point to where to look for the mechanisms or checking 'fit' of any models.

due to all sorts of things that might be little to do with the pwme themselves ie cultural and about the people they may or may not see and their assumptions or as you say things like GWS or other alternative diagnoses, or just inappropriate dismissal or misdiagnoses.

and because of this, and because there are bodily differences between males and females, this leads to us needing to be aware of it being possible 'assumptions' on types and symptoms and prognoses/the way certain things affect other things in the illness (as well as common comorbidities people might have or that ME/CFS might make people more suscptible to) are possibly slightly red-herring things. Because that one is a chicken-and-egg - if you don't describe heart attacks as they appear for certain women then those take longer to pick up and vice versa.

I'd be pretty intrigued to have a thread of male experiences of these things, ie if there are a number of men here who might input directly too on this (so we can compare notes), to see if there are common themes/trapdoors that might make diagnosis take longer, need more luck or culmination of certain factors (like a good GP), different common 'other initial diagnoses' or assume its just behavioural/will go away, and so on

One example is I know as soon as I thought of it then realised how many I've had say it to me over the years that I've come across quite a lot of men who've had things described as 'had glandular fever once and since then I've never really been the same...' type thing. Only two of those were people I'd later met with ME (and were saying this retrospectively as a cause), so I wonder whether those people I came across always just described it as due to GF? or eventually recovered enough they just accepted it?

I also know I'm engaging a cliche by saying there is a suggestion that men apparently are less likely to chinwag about their lives than women - and from my experience with women there are a lot who just do smalltalk anyway or might hear 'fatigue' and think all the mis-assumptions. Plus men don't only have male friends and colleagues and family.

But if someone isn't getting medical support that knows ME/CFS but happens to know someone else who has it (not the classic 'my mate's mate who had it a year and recovered') be it a colleague, relative, friend or 'one or two removed' from this then that often is a helpful source of suggestion in the past at that stage where someone is stuck in the wilderness wondering what is happenning to them.

I'm curious is this any more or less likely to have happened for males too? If it is then I guess there is the roll-over effect because there are fewer men out there with it so fewer people to think to mention it.

 

[Jonathan Edwards]

It's also not inconceivable that it is true, that the risk of having ME/CFS actually does increase as we get older.

Trouble is, if I felt the way I do these days when I was forty I would be sure I had ME/CFS. But I am pretty sure it is just being over the hill and full of worn out joints, blunted nerves and wasting muscles. A diagnostic requirement of ME/CFS is that the symptoms are not explained by something known. Being 75 is something known!