Wednesday, 3 January 2018

Why is MS more common in women?

Last month, I attended ‘MS At the Limits’, and the final talk by Dr Riley Bove (University of California, San Francisco) was truly fascinating. I know I am a bit delayed in posting this but I thought I would share some of the key points…




As most of us know, MS affects more women than men, but you might not know that women tend to have more relapses and that the ratio of men:women affected by MS is on the rise. The most obvious culprit here is hormones, but it is also possible that the higher prevalence/relapse rate in women is related to nutrition or behaviour. For example, women tend to attend the doctors far more frequently than men, so are they more likely to report relapses or symptoms?

When we look at the lifetime of humans, we are very unique in that we are the only species to have a period of puberty and a period of post-fertility (primates are the only other species to have a period of adolescence, and only two species of whale live post-menopause). These life phases are very much dictated by hormones, could it be coincidence that we are the only species to go through all these hormonal changes and the only species to develop MS?

Early puberty is a risk factor for women developing MS, and the earlier puberty occurs, the earlier they tend to develop MS. So surely, this is direct evidence of a hormonal cause? However, it could be that puberty and MS have common risk factors, such as genetic mutations or BMI (increased weight is associated with both increased risk of MS and earlier onset of puberty). Also, if hormones are the main culprit here, you would expect a correlation between disease onset/progression and oral contraceptives wouldn’t you? But studies so far suggest only a slight effect.

However, the more we look, the more links we see to hormonal influence, although most findings show weak correlations or slight effects.

Later age at birth of the first child may be linked with MS onset. So, having children earlier in life appears to be protective. Pregnancy also has a short-term protective effect, reducing relapses but increasing risk of relapse in the short-term, after birth. Breast-feeding appears to be protective, so may help reduce the short-term increased risk of relapse post-birth.

As for the menopause and MS, EDSS scores appear to progress faster post-menopause. Also, early menopause through surgery is linked with increased cognitive decline and dementia (not yet studies in pwMS specifically). Could this be linked to hormone replacement therapy (HRT), which women take after surgical menopause? Further studies are required to find out.

Let’s not forget about the men…  lower testosterone in men has been found to correlate with higher EDSS scores in early MS, suggesting a faster rate of disease progression in early disease. So, could testosterone be protective in MS? Several studies have shown that it might be, but little attention has been paid to this topic in recent years.

So, can we blame hormones for the higher incidence of MS in women? Possibly, but proceed with caution! 

38 comments:

  1. The estriol trial was not very successful though :/

    Another theory:
    A new study suggests that when a process to balance out genes from the “extra” X chromosome found in females goes awry, dysfunction in the immune system can lead to autoreactive diseases.

    They build upon past findings that showed how the X chromosome inactivation process in female B and T cells often failed to reach completion. This was due to a long non-coding RNA (lncRNA) called Xist that failed to “initiate and maintain” the process. However, this failure was only before the immune cells were stimulated in response to an infection. The priming that takes place to prepare immune cells for the immune response, for whatever reason, caused Xist to (finally) show up in the right place.

    “B cells are the ones making antibodies and autoantibodies, so they're really crucial in both protective immune responses and autoimmunity," described senior author Montserrat C. Anguera. "A big question that remains is, why are these immune cells priming for this chromosome to be regulated differently and also, if these processes go awry, how does that lead to autoimmunity and loss of self-tolerance?"

    To answer these questions, the present study began to identify the factor that brings Xist RNA back during immune cell activation.

    http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007050

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  2. Another question is why is the rate of MS increasing in females compared to males over the past few decades?

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  3. Could it be increase in birth control pills use?

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    1. Certainly in Western countries it seems to be more recent than the widespread take-up of oral contraception.
      Vitamin D and lower levels thereof for a variety of reasons is most commonly implicated, indeed the data from Iran post-revolution is compelling.

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  4. I wonder if there is a correlation with the use of hormones in food production.

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    1. My money, pitiful though it is, is on pre-natal maternal Vitamin D levels as a significant factor.

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    2. Sorry, I think I must be missing something - how would that affect distribution of MS by gender? Do male foetuses take vit D from the mother to a greater extent than female foetuses? (That is a genuine question, and I won't follow it with some lazy gender stereotyping!)

      I think you're definitely on the money with pre-natal vit D as a significant factor, by the way, it fits with my case. (Obviously, I can't speak for anyone else)

      Isn't it also the case that the incidence of MS increased once they stopped adding vitamin D to common foods, such as bread?

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  5. This is a very interesting article. Thank you for this. Would you consider writing a post on prognosis and dmt effectiveness after menopause?

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    1. There's a study (free to view) on this subject here;
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824677/

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    2. Yes the paper MD2 cites looks very interesting and may answer your Qs. This topic seems very popular and is certainly an area of interest for me so I'm sure we can post some more on the subject :)

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  6. Another possible reason is, especially in Asian/African countries. A lot of woman stay out of the sun in pursuit of lighter skin tones. Could the rise in ms cases in woman be due to more woman in Asian and African continent being diagnosed with MS?

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    1. This is a very interesting Q. My understanding is that the ratio of men:women is increasing here in the UK, not just worldwide, but you could be on to something!

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    2. Thanks MD3. Glad it may lead to something. Always good idea to get feedback regardless of the audience.

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  7. I assumed higher BMI. It fits with lower vitamin D, woman having higher % body fat, and weight being a risk factor. It's a good line of best fit for other evidence.

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  8. And is there a correlation between the onset of SPMS and menopause? Not just oestrogen but cortisol, thyroid and insulin having an effect on MS?

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    1. Not that I can find with a quick look but I know Dr Bove has a lot of research ongoing in this area so there might be more info on this soon.

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  9. I really don't know if I'm posting in the right place, but I'm a 22 year old girl and i've just been diagnosed with PPMS - how lucky am I?! Could anyone point me in the direction of any research that at least looks promising? I'm feeling hopeless and really need some encouragement, I have no idea where to turn and I'm terribly frightened

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    1. I think the best place to start is with the MS society, they have a very nice website with lots of info to get you started https://www.mssociety.org.uk/what-is-ms
      There is a lot of info out there but also a lot of support and a community of people in a similar position. I hope this helps :)

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    2. Try here too
      https://www.mstrust.org.uk/

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    3. Another website is Shift.ms - a social network for people with MS. Keep checking back to this blog. We post lots of research updates and we are trying to make them less jargony. There are lots of people working really hard to find new treatments and to improve the lives of people with MS - you just have to know where to find all these amazing folk! Good luck and post here any time with a question :)

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  10. Sorry to interject here, but concerning the 2:1 prevalence of RRMS between genders, this is a slam dumk proof of the MSRV Retrovirus approach.

    The HERV-W polymorphism is located in chromosome X. Females: XX / Males: XY chromosomes. Hence 2:1 probability....

    http://www.ncbi.nlm.nih.gov/pubmed/24405691

    Your thoughts?

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    1. That's interesting Marc but from the latest data it appears that the ration of incidence of MS females:males appears to be increasing nearer to 3:1 than 2:1 and in Iran for example the ratio appears to be even higher.
      I'll have a look at the paper.

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  11. @Doginthehouseofcapulet - if you haven't done so already, get yourself on to shift.ms

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  12. There was a 'man flu is real' story was put just before Christmas.

    http://www.independent.co.uk/life-style/health-and-families/man-flu-colds-women-gender-scientists-immune-system-caveman-testosterone-a8105006.html

    I remember thinking at the time, could this be the reason for gender imbalance in MS.

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  13. This topic has always intrigued me, I already left several comments here on the blog about it.

    I didn't have an early puberty, as I was an athlete since I was a child, I was only 14 years old. I was not a fat kid or teenager, but I had IM and I took contraceptives for almost 07 years, just when I had the relapse that made me discover the disease.

    I always looked suspiciously at the oral contraceptives, hormones.

    And if the hormones really have any real implications in MS, what happens to women who use Testosterone (female bodybuilders, or women who change sex), are they more likely to develop MS, or not?!

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    1. it is converted to oestrogen inside the brain anyway. One of co-authors of the paper on oestrogen in ms suggested that testosterone is beneficial in ms and eae just because those oestrogen

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    2. So women using Testosterone would not have a problem with MS ?!

      But is the study, even led by a blog researcher, who showed that they have a 7x higher risk of developing MS who change sex and use female hormones?

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    3. I took the combined pill for many years and then came off it. I had my first MS relapse less than a year after coming off it, but this could all be coincidence?

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    4. Could be a coincidence but unfortunately there's no way of knowing. These are all good Qs but unfortunately the number of cases of transgender MS cases, bodybuilding women with MS etc will be very small, meaning a study of these groups would be very difficult. Lots of interesting potential areas of study though :)

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    5. Are there any neurologists who are collecting lifestyle data from their patients or is it only in studies with a small proportion of people? Me and my sister both have MS, BUT we are 100% unrelated genetically. Neither of us had early puberty, neither of us have ever been on hormone birth pills. I'm a summer baby, she is a winter baby, she's had MS for (probably) several decades and i've had it for just 5 years. We both had two boys and both breastfed, both of our eldest boys are autistic. We grew up in Cornwall in the fresh air and sunshine but i developed a sun allergy from the age of 14 which lasted a decade and we both had low D3 and Epstein Barr when tested at diagnosis...although i never had any obvious symptoms of EB growing up. I did have tons of antibiotics at a young age for undiagnosed kidney problems...did that impact something? I'd love to know what contributes....what i do know for sure is the hormonal cycle really influences my MS symptoms. I'm currently well managed on Lemtrada but during relapses all my symptoms both physical and cognitive were significantly worse during menstruation and i've often worried about menopause and the future because of this.

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    6. It's very intriguing that you and your sister shared so many experiences and are not genetically linked, yet both developed MS. Most neurologists will collect lifestyle data but this rarely goes further than your medical records. Collation of this data is very useful but also costly and will depend on which clinic you attend :)

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  14. But in fact, I am very, very white, and here in Brazil the risk of skin cancer is very high, so I always protected myself from the sun and I used sunscreen. Now after MS I take at least vitamin D3 every day.

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  15. Fascinating question, haven't formed an answer yet, but suspect XX genetics, and Vitamin D absorptions issues may intertwine nature + environment.

    For those who are concerned about increase in Iranian women and MS, the burqa was imposed after 1979 revolution.

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  16. How does this fit in with a girl who was diagnosed with MS at age 11 and who hit puberty at age 14+?

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    1. Hi puzzled. Good question which I'm afraid I can't answer! We're looking for potential links here and unfortunately one concept will never fit everyone's story. Also, it's worth bearing in mind that the research discussed here will not have included juvenile MS cases, for which the risk factors may be quite different. Again, another interesting area to be studied in future :)

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