Your questions answered: The impact of hormones, sex and gender on MS

As a follow up from my previous post on ‘Why is MS more common in women?‘ I thought I’d respond to some of your comments and questions…

As discussed in the previous post, MS is almost 3 times more common in women compared to men and we came to the conclusion that there is a hormonal link, but this may not be the whole reason for the difference between the sexes. It should be noted that sex-differences which could affect MS lie not only in the hormones but also genetics (women have an increased immune response to infection, believed to be the reason for a higher incidence of autoimmune disorders), chemical messengers (e.g. higher levels of the IL-33 cytokine in men, which limits the development of a destructive immune response), and the microbiome (which we all know is a hot topic in MS at the moment).

X-chromosomes (women have XX, men have XY) carry many genes which code for immune-modulating receptors, cytokines, and proteins regulating transcription and translation (processes needed for the conversion of DNA in to proteins to be used in the body). The X-chromosome is also home to the MS associated retrovirus (MSRV) gene, which can affect susceptibility and severity of MS. Therefore, it makes sense that having a double dose of the X-chromosome would affect immunity and potential risk of MS in women.

Comments were made on the previous blog post referring to vitamin D and this topic. Indeed, there is an immune tolerance mechanism in females which requires the interaction of estrogen and vitamin D, which could further contribute to the sex bias. However, if genetics are largely to blame, then it is surprising that juvenile (pre-pubertal) MS shows no sex-preference. Interestingly, relapse rates tends to be higher during puberty than post-puberty.

Questions were also asked about oral contraceptives and whether the use of these is linked to the increased ratio of women:men affected by MS. However, studies have shown no direct impact of oral contraceptives on the incidence of MS. Some studies have actually suggested that MS symptoms were worse during the pill-free week for women on oral contraceptives.

Many people were interested in the impact of the menopause on MS, and it seems that the EDSS rate of progression post-menopause is worse than pre-menopause (whether a natural or surgical menopause). There is also a tendancy of conversion to SPMS around the age 45, which may be linked, or explain this inflection in EDSS scores. Progression of EDSS scores post-menopause may also be linked to the post-menopausal decrease in estrogen, which is neuroprotective. Interestingly, late onset MS (age 50+) shows far less sex difference than average onset. So do female hormones increase risk of developing MS but decrease rate of progression?

An association has also been found between MS and gender identity disorders in male-to-females, and men who became women showed a 7x higher risk of MS. These findings also suggest a role of low testosterone and/or feminising hormones in the onset of MS.

So, hormones, vitamin D and genetics may all play a role in the increased rate of MS in women compared to men. I hope this answers some of your questions and I’m sure it will also raise some more!

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Mouse doctor 3


    • An old study from 1992 suggested that post-menopausal women with MS mostly found that HRT was beneficial for their MS symptoms. However, a small 2015 study suggested that HRT made no difference to MS symptoms/progression. Generally, the current consensus appears to be that HRT has no significant effect on MS but larger studies are needed to say this for certain. If this is something you're thinking about, your best bet will be to speak to your neurologist 🙂

  • Thank you for your addressing this topic(s). I am one who at menopause converted from an overtly mild RRMS of 40 years, whose walking had been completely normal, to someone now always dependent on walking aides: cane, rollater or wheelchair, depending on distance. At menopause, I did not have anything remotely resembling the relapses previously experienced. Indeed, given my extended relapse-free period, I had been characterized as Stable. Once menopause arrived, though, my walking became impaired and has remained so. It is unclear whether it is now deteriorating at a mildly “progressive” pace.

    • Interesting. It sounds as though your MS may have 'switched' around the time of the menopause, fitting with the studies discussed here. Fingers crossed you could now be stable again, or at least progressing very slowly.

    • The role of oestrogen as a neuroprotectant, though well-reported in numerous experimental studies, is all too often forgotten when it declines due to the menopause. There is a study showing an improvement in quality of life in post-menopausal women with MS.
      We need more studies to determine whether this can have an impact on disease progression.

  • I really liked this post.

    I can't connect the causal components involved in childhood and juvenile MS. In addition, I questioned myself a great deal about the role of hormonal contraceptives in MS after this poster presented in the AAN 2014, which showed a possible increased risk of developing MS in women using hormonal contraceptives for at least 4 years in a row.

    • I have to say, I don't know anything about this off the top of my head but I did find a paper about gut microbiota, in which they found lower levels of several organisms in the gut microbiota of pwRRMS including Prevotella, Parabacteroides, and Adlercreutziamicrobes, all of which are associated with the metabolism of phytoestrogens so there may be something in this! (

  • Interestingly, the mean age of menopause is 53, the same age with the popular elephant post. Whatever that might mean.

  • I had a horrible six week episode of Trigeminal Neuralgia that coincided with my 50th birthday. It made my party a lot less fun than it would otherwise been but confirmed very strongly that I am still having relapses. If the average age for women to stop having relapses is 45, does anyone know what the upper bound is? Or am I being too literal, assuming that 'conversion to SPMS' means relapses cease?

  • I was diagnosed at 52 after lots of little-ish symptoms that were easy to attribute to something else (sound familiar?). Anyway, I was in the menopause wind-down, but not there yet. I've only had one relapse since dx, and that happened within 6 months. From there I've been stable, with only fatigue maybe? slowly increasing. The interesting part is I started Tamoxifen a year after my diagnosis (it's been an exciting few years for me) which sends your hormones further into the nether realms, yet have not experienced any new symptoms nor significant worsening of existing symptoms. So did sputtering estrogen set off the MS in a big way for all to see, but now that it's pretty effectively gone, is the lack contributing to the slowdown of new symptoms? Who knows. I just know no one has said I've transitioned to SPMS yet, and the RR seems pretty quiet. (Yes, I'm on Tec)

    • Interesting theory. Apparently in late-onset MS, approximately 50% of people have PPMS, meaning the other 50% presumably start with RRMS. I haven't found anything specific about conversion to SPMS in late-onset. Fingers crossed you're still in the RR category!

  • I thought Barts was trying to get away from the RRMS / PPMS / SPMS division.
    My own MS was progressive in a very mild way from pretty near the start. My headstands and other balance poses in yoga got worse over months of practice, rather than better (as my other yoga poses did). This was happening before I was diagnosed and years before I had my first recognisable relapse and recovery.
    I still have relapses with complete recovery from some symptoms and deterioration in other symptoms without relapses. So I seem to have had all three types of MS. Could it be that MS is just one disease?

    • Yes, as I'm sure you've seen, there is lots of evidence to suggest MS is one disease and this is a theory Barts MS supports. When these terms are used here, this is generally because we are referring to studies in which a particular 'category' of MS has been investigated, meaning that there were specific criteria for who was in the study. This has to be taken in to consideration regardless of whether or not we believe it is one disease because the criteria and/or categories will likely relate to how severe the disease progression is, or how early someone is in their disease course.

    • That is a problem with all these studies, though, isn't it? There is no agreed definition of SPMS and different doctors categorise patients at a similar stage of their disease in different ways. Your answer to my question about conversion to SPMS demonstrated this exactly. Did I convert when I started using one stick for longer distances, when I needed one stick full-time, when I needed two sticks, when I started using a walker or when I started needing a wheelchair? Or 30 years ago, when my yoga balance positions started getting worse?
      I think the dividing people into different categories of MS is so unhelpful that Barts and the MS Society should both be campaigning against it.

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