MS Speaks

Multiple sclerosis is more severe after menopause in a longitudinally followed clinical cohort   

R Bove1, BC Healy1, A Musallam2, B Glanz1, PL De Jager1, T Chitnis1

1Harvard Medical School, Brookline, MA, United States, 2Brigham and Women's Hospital, Neurology, Boston, MA, United States

Background:

Almost half of women living with multiple sclerosis (MS) are post-menopausal. While puberty and pregnancy represent key modulatory periods for MS, little is known about menopause. We have previously described worsening of MS severity after menopause in an online research platform, but now focused on a well-phenotyped clinical cohort.

Objectives:

To determine the effect of menopause on MS course in a well detailed clinical cohort.

Methods:

We linked reproductive survey data with prospectively collected disease severity measures for women with MS in CLIMB, a deeply phenotyped large Northeastern US MS clinic cohort. Disease severity was measured by the Expanded Disability Status Scale (EDSS). Menopausal status was the primary exposure.

Results:

Over half the 455 respondents were postmenopausal. Median age at natural menopause was 51.5 years. Women with surgically induced menopause reported earlier menopausal age (p< 0.001) and more hormone replacement therapy (HRT, p=0.02) use than natural menopause.

In our primary analysis of 87 women followed longitudinally through their menopausal transition, we detected an inflection point in EDSS changes at menopause. [AM1] The estimated increase in the average yearly change was 0.14 units per year (95% CI: 0.047, 0.23, p=0.003 in this linear spline mixed effects model. Similar results were noted in both natural and surgical menopause.

In a secondary model examining 275 women whose entire follow up was either during their pre- or post-menopausal period, there was a significant worsening of EDSS after menopause, adjusting for age and disease duration; the difference between the groups was 0.088 EDSS points per year (95% CI: 0.021, 0.16; p=0.011).

No differences in relapse rate and no effects of HRT use were noted, but numbers for these exploratory analyses were small.

Conclusions:

We observed a worsening of MS severity after menopause, consistent with our prior reports from an online research platform. Larger studies are required to explore a potential role for HRT.


Assigned speakers:
Riley Bove, Harvard Medical School , Brookline , US