Menopause linked with lower MS relapse rate, increased disability

Women with multiple sclerosis (MS) have significantly lower relapse rates after entering menopause, but disability levels increase significantly in that period, according to a pooled analysis of studies.

The findings are consistent with a decrease in immune activity with age and loss of estrogen, leading to fewer disease-related relapses, researchers said. In turn, estrogen is known to be neuroprotective and its reduction could contribute to more pronounced nerve cell loss and disability.

The study, “Impact of menopause on relapse rate and disability level in patients with multiple sclerosis (MS): a systematic review and meta-analysis,” was published in the journal BMC Neurology.

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MS is a neurodegenerative disease in which an overactive immune response causes damage to nerve cells in the brain and spinal cord, leading to a wide range of symptoms. In most cases, patients experience acute episodes, called relapses, in which new symptoms appear or old ones worsen suddenly, followed by periods of partial or complete recovery known as remissions.

The autoimmune condition affects about three times more women than men, which is believed to be related partly to hormonal differences. MS activity is reduced during pregnancy, especially during the third trimester, due to changes in hormone levels that affect immune T-cell activity. Then, immediately after delivery, relapses may occur more often than before pregnancy.

A recent literature review by a team of researchers in Iran showed that women who were older at the time of their first menstrual cycle had a significantly lower risk of developing MS. This is likely because having a first menstrual cycle at earlier ages results in estrogen imbalances that predispose people to MS.

In this report, the same team conducted a follow-up literature review and pooled analysis to estimate the impact of menopause on relapse rates and disability progression in women with MS.

A combined review of four studies

Following a detailed search of several medical literature databases, four studies, published between 2017 and 2020, were selected. Researchers conducted a meta-analysis, meaning they statistically combined, or pooled, the results from the independent studies to create a stronger analysis on the effects of menopause in MS.

Two studies were conducted in Italy, one in Spain, and one in Portugal. Each enrolled from 37 to 148 MS patients, with mean ages of 47-50 years. None of the studies provided information on the use of disease-modifying therapies.

Across studies, researchers estimate the strength of the relationship between menopause and disease outcomes using a statistical method called standardized mean difference (SMD). An SMD value of 0 means no relationship, 0.2-0.5 is considered weak, 0.5-0.8 is medium, and values greater than 0.8 reflect strong associations.

In the four studies, the SMD of the mean annual relapse rate ranged between -1.04 and -0.29, with negative values indicating a lower relapse rate after menopause than before. The pooled SMD across all studies was -0.52, showing that “after menopause, women with MS experience less disease-related relapses compared to reproductive time,” the researchers wrote.

Meanwhile, mean disability scores, assessed with the Expanded Disability Status Scale (EDSS), ranged between 1.5 and 2 before menopause, indicating most patients had either no disability with minimal symptoms, or minimal disability. After menopause, mean EDSS scores went to 2 to 3.1, indicating moderate disability. From these data, the SMD of EDSS ranged between 0.46 and 0.71 across studies, with a pooled value of 0.56.

Disease-related disability increased significantly

“Alternatively, we found that disease-related disability which was measured by EDSS, increased significantly,” the team wrote, indicating a “negative effect of menopause on disease course in women.”

“The result of this systematic review and meta-analysis show that menopause can be associated with relapse rate reduction,” they added.

The team noted that relapses tend to reduce with age due to a less active immune system, while disability can increase significantly with increasing age. In menopause, this may be exacerbated by a reduction in estrogen, which has neuroprotective effects.

“The increase in disease-related disability after menopause could be due to decreased [estrogen] level, and lack of its neuroprotective effects,” they wrote. “Both human, and animal studies showed that oestrogen has neuroprotective effects, leading to better neural survival.”