Multiple Sclerosis and being a woman

M

MS is commoner in women than men. In fact the incidence of MS is increasing all over the world but this seems to be preferentially in women. Now this new publication looking at cases and controls (through a process of enrichment from a large group of women with MS) is suggesting that there are marginal differences in non-natural menopause in MS females, with more cases observed in MS. Moreover, the onset of progressive MS was shorter in those with early/premature menopause (see Figures below). There were no differences with the age of onset of menarche in the study, however.

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(A) Age at menarche in multiple sclerosis and controls. Menarche age did not differ between females with multiple sclerosis and control females. (B) Age at menopause in multiple sclerosis and controls. Age at natural menopause did not differ between females with multiple sclerosis and control females. Age at non-natural menopause was older in multiple sclerosis than control females. 
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Graphical representation of study findings

They also found an association between the number of pregnancies and the age of onset of progressive disease, with greater number of pregnancies having a protective effect (see Figure below).

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The association between number of pregnancies and age at progressive multiple sclerosis onset. Higher number of pregnancies was associated with older age at progressive multiple sclerosis onset (mean ± SD) with a dose-dependent effect: nulliparous females (para 0) had the youngest age at progressive multiple sclerosis onset, females with para 1–3 had an intermediate age at progressive multiple sclerosis onset and females with para ≥4 had the oldest age at progressive multiple sclerosis onset

The study raises some interesting points that require further investigation especially from other natural history cohorts. The major problem with case-control studies is the potential for recall bias:

Recall bias in a case-control study is the increased likelihood that those with the outcome will recall and report exposures compared to those without the outcome.

Abstract

Brain Commun. 2020; 2(2): fcaa185.Published online 2020 Nov 17. doi: 10.1093/braincomms/fcaa185PMCID: PMC7772117PMID: 33409489

Reproductive history and progressive multiple sclerosis risk in women

Burcu Zeydan,Elizabeth J Atkinson,Delana M Weis,Carin Y Smith,Liliana Gazzuola Rocca,Walter A Rocca,Brian Mark Keegan,Brian G Weinshenker,Kejal Kantarci, and Orhun H Kantarci

Being a woman is one of the strongest risk factors for multiple sclerosis. The natural reproductive period from menarche to natural menopause corresponds to the active inflammatory disease period in multiple sclerosis. The fifth decade marks both the peri-menopausal transition in the reproductive aging and a transition from the relapsing-remitting to the progressive phase in multiple sclerosis. A short reproductive period with premature/early menopause and/or low number of pregnancies may be associated with an earlier onset of the progressive multiple sclerosis phase. A cross-sectional study of survey-based reproductive history in a multiple sclerosis clinical series enriched for patients with progressive disease, and a case–control study of multiple sclerosis and age/sex matched controls from a population-based cohort were conducted. Menarche age, number of complete/incomplete pregnancies, menopause type and menopause age were compared between 137 cases and 396 control females. Onset of relapsing-remitting phase of multiple sclerosis, progressive disease onset and reaching severe disability (expanded disability status scale 6) were studied as multiple sclerosis-related outcomes (n = 233). Menarche age was similar between multiple sclerosis and control females (P = 0.306). Females with multiple sclerosis had fewer full-term pregnancies than the controls (P < 0.001). Non-natural menopause was more common in multiple sclerosis (40.7%) than in controls (30.1%) (P = 0.030). Age at natural menopause was similar between multiple sclerosis (median, interquartile range: 50 years, 48–52) and controls (median, interquartile range: 51 years, 49–53) (P = 0.476). Nulliparous females had earlier age at progressive multiple sclerosis onset (mean ± standard deviation: 41.9 ± 12.5 years) than females with ≥1 full-term pregnancies (mean ± standard deviation: 47.1 ± 9.7 years) (P = 0.069) with a pregnancy-dose effect [para 0 (mean ± standard deviation: 41.9 ± 12.5 years), para 1–3 (mean ± standard deviation: 46.4 ± 9.2 years), para ≥4 (mean ± standard deviation: 52.6 ± 12.9 years) (P = 0.005)]. Menopause age was associated with progressive multiple sclerosis onset age (R2 = 0.359, P < 0.001). Duration from onset of relapses to onset of progressive multiple sclerosis was shorter for females with premature/early menopause (n = 26; mean ± standard deviation: 12.9 ± 9.0 years) than for females with normal menopause age (n = 39; mean ± standard deviation: 17.8 ± 10.3 years) but was longer than for males (mean  ±standard deviation: 10.0 ± 9.4 years) (P = 0.005). There was a pregnancy-dose effect of age at expanded disability status scale 6 (para 0: 43.0 ± 13.2 years, para 1–3: 51.7 ± 11.3 years, para ≥4: 53.5 ± 4.9 years) (P = 0.013). Age at menopause was associated with age at expanded disability status scale 6 (R2 = 0.229, P < 0.003). Premature/early menopause or nulliparity was associated with earlier onset of progressive multiple sclerosis with a ‘dose effect’ of pregnancies on delaying progressive multiple sclerosis and severe disability. Although causality remains uncertain, our results suggest a beneficial impact of oestrogen in delaying progressive multiple sclerosis. If confirmed in prospective studies, our findings have implications for counselling women with multiple sclerosis about pregnancy, surgical menopause and menopausal hormone therapy.

About the author

Neuro Doc Gnanapavan

12 comments

  • Yes, a study involving both mensuration and MS!!! Is it too much to hope the study looked at breastfeeding duration? Since Breastfeeding delays return of period post birth. Is it way too much to hope they gathered dats on use of birth control pills, number of years of use, and type of formulation too? (Sure lots of variables but metadata has way to see something at 20,000 feet) . I ask this because A wise gyn advised me to stay with natural estradiol formulations instead of synthetic ethinylestradiol because she felt it impacted MS less. But subsequent Gyns would shrug and even offer continuous birth control pills. Who needs monthly periods, right??? My joke. Well, glad scientists started looking at this connection, a bit any how.

  • I was diagnosed and crashed straight into the menopause at the same time. I don’t know if the shock of diagnosis caused the menopause, but I did not know which symptoms were caused by which. I had to teach my male neurologist that when a fifty year old woman can’t sleep at night because she is bathed in sweat, it might be the menopause. HRT patches allowed me to regain temperature control and start planning DMT. It is am issue that neurologist treating older women need to consider.

  • So, having gone through menopause, or if still in peri menopause should we be insisting on oestrogen treatments?

    In my experience it’s like getting blood out of a stone getting help with meno related issues – but if it helps with keeping progression away ?!!

      • Re.Oestrogen treatments and if they keep progression away…
        Should we be researching into a eating a diet full of Phytoestrogens and MS?

        ‘Phytoestrogens are plant derived compounds found in a wide variety of foods, most notably soy. A litany of health benefits including a lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms, are frequently attributed to phytoestrogens but many are also considered endocrine disruptors, indicating that they have the potential to cause adverse health effects as well.’
        (The pros and cons of phytoestrogens
        https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074428)

      • Thanks for link! Informative and lays out risks well. I’m going to share it with my doctors. Amazing how little it is discussed when it will happen to every woman with MS at some point.

    • menopausesupport.co.uk provides useful advice on accessing NHS Menopause clinics.

      To his credit it was my GP who offered to refer me when I approached him about a change to my HRT prescription.

      The Brigham and Women’s Hospital have an interesting video on YouTube about the benefits of oestrogen to women with MS.

  • No conclusive evidence for or against soy and BTW, soy bean farms destroy rainforest and soy products are usually only available as UPF i.e., ultra processed foods. Not a good idea.

  • There’s definitely sexism in NHS healthcare, that women’s health issues are (sometimes/often) assumed caused by menopause, early menopause or time of the month and dismissed as something more serious.
    Men seem to get taken more seriously by HCP’s and get referrals to hospital departments quicker than women.
    It’s a very sad observation.

  • I wouldn’t eat a diet high in soya or take so called natural supplements.
    I would prefer to eat a healthy diet containing good amounts of green vegetables, peaches, flax seeds and dried fruits which contain high amounts of phytoestrogen.

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