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.
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.
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.