Friday, 16 October 2015

ResearchSpeak: worsening disability after the menopause

Menopause and worsening disability in MS. #ResearchSpeak #MSBlog #MSResearch

"There is a debate raging in the field of medical philosophy about whether or not to classify ageing as a disease or a natural process. The same can be said about the menopause. Is the natural failure of one's ovaries a disease or a normal physiological process? When I was in medical school I was taught that 40 was the magic number; if you had your menopause before the age of 40 it was considered premature and if older than 40 it was normal. Why is this important? The studies below shows that in women with MS menopause is associated with worsening disability. The average change in disability is very small, but significant. The results however suggest the observation has a biological basis and can therefore be manipulated to treat MS. Could these observations simply be due to age, or is the effect due to a loss of the neurotrophic effects of oestrogen on the brain and nervous system?"

"The first study did not find any impact of HRT on disability, but too few women were on HRT to be able to see a reliable effect on outcome. We know from the dementia field that HRT is likely to delay the onset of dementia, therefore I would not be surprised if HRT had an impact on brain health in MS. Do you think we should do a study of HRT in women with progressive MS? Or should we simply offer women with MS the option of starting HRT? The latter may be difficult in view of some of the negative effects of HRT, i.e. an increased incidence of cardiovascular events, breast cancer and deep vein thrombosis. What do you think?"


Study 1: CLIMB Study

Bove et al. Exploration of changes in disability after menopause in a longitudinal multiple sclerosis cohort.Mult Scler. 2015. pii: 1352458515606211.

BACKGROUND: Onset of multiple sclerosis (MS) is typically in early adulthood. The impact, if any, of menopause on the MS course is unknown.

OBJECTIVE: Our objective was to determine whether menopause is associated with changes in MS severity in a longitudinal clinical cohort.

METHODS: Responses from an ongoing reproductive questionnaire deployed in all active female. CLIMB observational study participants with a diagnosis of clinically isolated syndrome (CIS) or MS were analyzed when the response rate was 60%. Reproductive data were linked with clinical severity measures that were prospectively collected every six months, including our primary measure, the Expanded Disability Status Scale (EDSS).

RESULTS: Over one-half of the respondents (368 of 724 women) were post-menopausal. Median age at natural menopause was 51.5 years. In our primary analysis of 124 women who were followed longitudinally (mean duration 10.4 years) through their menopausal transition (natural or surgical), menopause represented an inflection point in their EDSS changes (difference of 0.076 units; 95% CI 0.010-0.14; p = 0.024). These findings were not explained by vitamin D levels, nor changes in treatment or smoking status over this period. There was no effect of hormone replacement therapy (HRT) exposure, but HRT use was low.

CONCLUSIONS: We observed a possible worsening of MS disability after menopause. Larger cohorts are required to assess any HRT effects.

Study 2: PatientsLikeMe

Bove et al. Patients report worse MS symptoms after menopause: findings from an online cohort. Mult Scler Relat Disord. 2015 Jan;4(1):18-24.

BACKGROUND: Many women with multiple sclerosis (MS) are postmenopausal, yet the impact of menopause on MS symptoms is unknown.

OBJECTIVE: To investigate patient-reported impact of menopause in a large online research platform, PatientsLikeMe (PLM).

METHODS: A detailed reproductive history survey was deployed to PLM members, and responses were linked to PLM׳s prospectively collected patient-reported severity score (MS Rating Scale, MSRS). The MSRS has previously shown good correlation with physician-derived EDSS scores.

RESULTS: Of the 513 respondents, 55% were postmenopausal; 54% of these reported induced menopause. Median age at natural menopause was 51. Surgical menopause occurred at an earlier age (p<0.001) and was associated with more hormone replacement therapy use (p=0.02) than naturalmenopause. Postmenopausal status, surgical menopause, and earlier age at menopause were all associated with worse MSRS scores (p≤0.01) in regressions adjusting for age, disease type and duration.

CONCLUSION: Postmenopausal patients in this study reported worse MS disease severity. Further, this study highlights a utility for online research platforms, which allow for rapid generation of hypotheses that then require validation in clinical settings.

11 comments:

  1. I think this is an area worthy of further research. With the benefit of hindsight I now know that my MS appears to have kicked off round about the time when menopausal symptoms became stronger - back in around 2006/2007. No relapses evident, just gradual deterioration of functioning, and was only diagnosed with MS two years ago (and now birthday number 57 is looming.......)

    There must be enough data lurking around for someone to crunch the numbers on women who are not diagnosed until after 50yo+ - could possibly be some interesting threads emerge.

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    1. All the evidence I'm aware of definitely poits to oestrogen being a neuroprotectant. I've been wondering whether outcomes worsen post menopause indicating potential increased neurodegeneration for some time. This study seems to indicate just that and is definitely worth following up but as Prof G states, HRT comes with its own potential downsides.

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  2. If oestrogen is a neuroprotectant how is it that MS is more common in women? Are there any countries or latitudes that do not see this pattern?

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    1. Just because something is neuroprotective doesn't mean it's anti-inflammatory. Autoimmune disease in general is 3 times more likely in women than men.

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  3. Are you sure about HRT and dementia? There was an epiodemiologist on Radio 4 this morning who stated that there was an increased risk of breast cancer, stroke and dementia with HRT, and that was why you are only suggested to be on it for a short time?

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    1. Probably multi-infarct dementia and not Alzheimer's disease. There is data on HRT in a critical window and before AZD sets in; once you have the disease it is too late.

      However, we are waiting for the definitive study to be done, but the data looks promising from small studies.

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  4. Interesting question. I spent a lot of timing looking at this and talking with both my neurologist and gynecologist. The bottom line was, it isn't clear and my gyno discussed the challenges of doing good studies postmenopausal; im part due to the "is it menopause, or is it age" question"

    As for me. I was on HRT for a short while, then breast cancer was diagnosed (not causal) and am now on hormone therapy so I'm totally "estrogen free". Again I talked with my doctors, now including an oncologist. The commentary: there is not clear indicator that it impacts my MS. My oncologist checks in with me about my MS and follows any changes, it since beginning hormone therapy.
    I've had no exacerbation post cancer treatment, though I do have a couple of increased existing symptoms. Cognition is just fine.

    This is definitely an area for further investigation.

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  5. "a possible worsening of MS disability" , "worse MS disease severity" are both very vague.

    "The average change in disability is very small, but significant" is a little more informative but not at an individual level

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  6. How I came to have an MRI is a long story, but I might have had MS/MS lesions for most of my life, without any reason to suspect any problem. Though in retrospect I can think of many things that fit in with MS.
    Post menopause some symptoms have appeared, so mild that it doesn't seem worthwhile to bother about them.
    My dilemma now is whether to consider myself a MSer and think of treatment etc. Or carry on as before, as I I never had any MRIs. Doctor thinks I'm past the age for MS

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  7. I pretty much just feel the symptoms of MS in menstrual period (since my neurologist suspended contraceptive that I used when I began treatment for MS, and I do not know for what reason she did it), certainly we women should feel very more symptoms and the progression of MS when we entered the menopause ... I think yes valid the idea of ​​a study to the topic...

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  8. A high plant based diet is apparently supposed to help menopause symptoms in the general population. Plant oestrogens act in a similar way to oestrogens which may keep hormones a bit more balanced. Populations that have a high plant based diet experience less menopause symptoms.
    I would be interested to see research of MSers on a high plant based diet. Seeds are a good source of plant oestrogens.

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