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
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.