11 July, 2019
Commentary on "Impact of natural menopause on multiple sclerosis: a multicentre study" by Baroncini D, et al.
In their recent paper, Baroncini et al  evaluated changes in relapse rate and clinical disability, as measured by the Expanded Disability Status Scale (EDSS) score, associated with menopause in women with multiple sclerosis (MS). They asked 148 women from the Lombardia region of Italy about their menopausal history, and then collected their relevant clinical information from medical records. Most of the women were on self-injectable MS treatments and, at the time of menopause, the group overall had mild-moderate disability (mean EDSS was 2.3, and the range was 0-7.5). Only 3% of women used hormone replacement therapies after menopause. The primary finding was that annualized relapse rate (average number of relapses in one year) decreased from 0.21 relapses a year on average before menopause, to 0.13 relapses a year after menopause. This represented a 38% decrease in relapses. However, this finding was no longer considered statistically significant when the investigators controlled for possible confounding factors, like age and MS duration. The second finding was that after menopause, increases in EDSS score were steeper, i.e there was more rapid worsening of disability. This more rapid progression of disability remained statistically significant after adjusting for confounding factors.
This manuscript is a much-needed contribution to the field, as very few studies have evaluated the effect of menopause on objective markers of MS or disability progression. Here, the most robust findings was the acceleration in disability progression after menopause. This finding appears to replicate an initial evaluation of MS progression at menopause . In a cohort of 124 women prospectively followed through their menopausal transition, EDSS worsening accelerated after the final menstrual period. In the current paper , the annualized relapse rate did not appear to decrease after menopause once the investigators accounted for confounders. In a smaller recent study, Ladeira et al  reported a significant decline in annualized relapse rate after menopause, but statistical adjustment for confounders might have varied. There are several important caveats to this research. First, the investigators focused on the EDSS examination as a measure of neurologic worsening. However, it is possible that the EDSS score itself reflects worsening in menopause-related factors (such as fatigue, sleep or bladder impairment), rather than in neurological function per se. As the authors note, MRI studies would be beneficial to confirm that neurological changes drive their observations about EDSS. Second, the investigators excluded some groups of women from the study, such as women with poor recall of the timing of their menopause, as well as women not on MS treatments. This could have selected for a sample with milder MS course overall. This study has several important implications. From a counselling perspective, women who are approaching menopause might be counselled to consider a number of interventions to stabilize their MS course, such as MS treatments, exercise and rehabilitation, smoking cessation, and once available, neuroprotective treatments. From a research perspective, more research is needed regarding mechanisms underlying the worsening of MS disability after menopause, and about possible protective mechanisms. Further, it remains to be determined whether hormone replacement therapies might alleviate either menopausal symptoms or disablility progression in women with MS .
Director, Program for Gender-Based Care. Assistant Professor in Neurology UCSF Center for Multiple Sclerosis and Neuroinflammation University of California, San Francisco
- Baroncini D, Annovazzi PO, De Rossi N, Mallucci G, Torri Clerici V, Tonietti S, Mantero V, Ferrò MT, Messina MJ, Barcella V, La Mantia L, Ronzoni M, Barrilà C, Clerici R, Susani EL, Fusco ML, Chiveri L, Abate L, Ferraro O, Capra R, Colombo E, Confalonieri P, Zaffaroni M. Impact of natural menopause on multiple sclerosis: a multicentre study. J Neurol Neurosurg Psychiatry. 2019 Jun 12.
- Bove R, Healy BC, Musallam A, Glanz BI, De Jager PL, Chitnis T. Exploration of changes in disability after menopause in a longitudinal multiple sclerosis cohort. Mult Scler. 2016 Jun;22(7):935-43
- Ladeira F, Salavisa M, Caetano A, Barbosa R, Sá F, Correia AS. The Influence of Menopause in Multiple Sclerosis Course: A Longitudinal Cohort Study. Eur Neurol. 2018;80(3-4):223-227
- Bove R, White CC, Fitzgerald KC, Chitnis T, Chibnik L, Ascherio A, Munger KL. Hormone therapy use and physical quality of life in postmenopausal women with multiple sclerosis. Neurology. 2016 Oct 4;87(14):1457-1463.