Menopause in MS

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Regardless of from whence you hail, if you’re a woman you are twice as likely to be diagnosed with MS than a man. It is probably one of the most constant and persistent risk factor in MS.

Hidden beneath this risk is the effect of hormones on the immune system. For instance, until the age of puberty, the frequency of MS is similar in both boys and girls. The cases start to become female predominant after puberty. Whilst during pregnancy, especially during third trimester, there is a sense of protection against MS activity, with rebound in the post-partum period.

Oestrogen is felt play a crucial role in the wider scheme of things, and as a hormone has been mainly demonstrated to be anti-inflammatory and protective against demyelination and neuronal loss.

The effect of oestrogen during menopause is less well studied – wherein there is a stable reduction in oestrogens. What does this mean in terms of MS disease activity?

Here Baroncini et al. look at exactly this, and found eventhough there was a reduction in relapse rates with menopause, there was also an increased occurrence of disease progression. The EDSS score increased by 0.2±0.6 points before menopause and by 0.4±0.7 points after menopause (see figure below). This suggests that the accumulation of disability is not secondary to greater inflammatory activity, but most likely neurodegenerative processes. 

Figure: Analisys of variance of annual EDSS score (mean±SD) in the 3 years before and after menopause (total 6 years, 108 patients), with post-hoc pairwise comparisons. MP, menopause; y, year

Moreover, they found that women who smoked had a faster rate of disease progression, suggesting an influence of an environmental factor on genetic make up – nature vs nuture.

ABSTRACT

Impact of natural menopause on multiple sclerosis: a multicentre study.

D Baroncini, P O Annovazzi, N D Rossi, G Mallucci, V T Clerici,  S Tonietti, V Mantero, M T Ferrò, M J Messina, V Barcella, L La Mantia, M Ronzoni, C Barrilà, R Clerici, E La Susani, M L Fusco, L Chiveri, L Abate, O Ferraro, R Capra, E Colombo, P Confalonieri, M Zaffaroni

Objective: To study the effect of natural menopause on multiple sclerosis clinical course.

Methods: This was an observational, retrospective, multicentre, cohort study. Menopause onset was defined by the final menstrual period (FMP) beyond which no menses occurred for 12 months. We included multiple sclerosis (MS) patients with FMP occurred after 2005 and a recorded follow-up of at least 2 years pre-FMP and post-FMP. We excluded patients with primary progressive course, iatrogenic menopause and with other confounders that could mask menopause onset. We compared relapse-rate and expanded disability status scale (EDSS) scores pre-FMP and post-FMP, searching for possible interactions with age, disease duration, cigarette smoking and nulliparity status.

Results: 148 patients were included (mean observation: 3.5 years pre-FMP and post-FMP). Most patients (92%) received disease-modifying therapies, mainly first-lines. After menopause the annualised relapse rate (ARR) significantly decreased (from 0.21±0.31 to 0.13± 0.24; p=0.005), while disability worsened (increase of mean 0.4 vs 0.2 points after menopause; p<0.001). Older age and long-lasting disease were associated with ARR reduction (p=0.013), but not with disability worsening. Cigarette smokers showed a trend to a higher disability accumulation after menopause (p=0.059).

Conclusion: Natural menopause seems to be a turning point to a more progressive phase of MS. Relapse rate is also reduced after menopause, but this effect could be driven most by ageing and shifting to progressive phase in patients with long-lasting disease. Cigarette smoking could speed up disability progression after menopause.

About the author

Neuro Doc Gnanapavan

11 comments

    • This would definitely need to be looked at. It would be good if the authors went back and looked at the PPMS group in their cohort.

    • HRT isn’t a long term strategy because of an increased risk of blood clots and some cancers. I wonder, however, if this effect though only 0.5+ rise in EDSS from peri menopause is time dependent, similar to what happens to MS relapse risk in pregnancy?

      • Two of the three studies mentioned in the review don’t have results posted. Of the phase II that does have results, it demonstrates significant benefit from 8 mg oral estriol daily on relapse rates and grey matter volume in combination with GA vs placebo plus GA. The HRT use in MouseDoctor’s study is laughably low- 8 ever-used HRT in the natural menopause and 5 ever-used within 3 years. 2 ever-used in the surgical menopause group, so honestly that study has no predictive value on HRT use and its effects on MS disability progression at all. The placebo controlled phase II study is far more valuable with 82 vs 76 drug vs placebo, and would strongly suggest more research is needed- if people feel that clemastine in its Phase II study warrants more investigation as a neuroprotectant, then so does estriol based on this phase II study.

  • This sentence freaks me out: Natural menopause seems to be a turning point to a more progressive phase of MS.

    After seeing Prof G’s article about menopause I went to the GP to see if I could get it…The GP sent me for blood tests when I said I thought the menopause was near (def in perimenopause) they said the levels were ok and said no to HRT

    Should us women with MS be on HRT as standard when we get to, say, mid 40’s?

    • HRT is offered currently for menopausal symptoms, there is a lot to consider on an individual based on their medical risks. It is therefore unlikely to be offered as standard. It may change for MS if an impact on disability is demonstrated by a large randomised blinded (for the doctor and the person taking the treatment) study.

      • Thanks for pointing out it should be based on medical risks. I asked my breast surgeon at 51 years old would my MS be affected by taking medication for oestrogen blockers. It made absolutely no difference to my MS. Had a surgical menopause at the age of 54. So people considering going on HRT in their early 40s seems a bit risky to me. This is a very small sample of women used in this research.

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