Study reports accelerated multiple sclerosis progression at menopause

Study reports accelerated multiple sclerosis progression at menopause | Image Credit: © saelim - © saelim - stock.adobe.com.

Multiple sclerosis (MS) progression may be accelerated by menopause, according to a recent study from UC San Francisco (UCSF).¹

Worsened Timed 25-Foot Walk scores were observed in participants after menopause. This provides a significant increase in data quality when compared to prior work focused on Expanded Disability Status Scale (EDSS), according to investigators.²

“We know that hormonal changes during puberty can trigger autoimmune diseases like MS,” said Riley Bove, MD, an associate professor of neurology at UCSF and corresponding author of the study.¹ “We see a lower rate of relapse during the third trimester of pregnancy, followed by a rebound postpartum.”¹

Seventy-five percent of MS patients are women, and this populations will often experience slowed walking and other fine motor changes during the postmenopausal period. The study was conducted to determine how hormone therapy (HT) may help 30% to 40% of perimenopausal and postmenopausal MS patients.²

The study included individuals diagnosed with MS or clinically isolated syndrome using International Panel Criteria.² Participants were cisgender women with postmenopausal status determined by a date of final period known within 1 year. A Gender-Inclusive EPIC Lifestyle Questionnaire was used to obtain reproductive data.

Reproductive variables included menopausal status, cause of menopause, and use of menopausal HT. Follicle stimulating hormone (FSH) levels were used to determine menopause status in women who received fertility-sparing hysterectomy.²

Administration of systemic estrogen within 5 years of menopause was reported to dichotomously determine HT use. Exclusion criteria included menopause caused by chemotherapy and amenorrheic status, surgical endometrial ablation, or ovary-sparing hysterectomy without date of menopause available through FSH measurements.²

The MS Functional Composite (MSFC), an empirical rating scale of participant performance, was reported as the primary functional outcome. MSFC domains include cognitive, fine motor, and walking. A change of 20% for the composite score indicated clinically significant worsening.²

Clinician-derived EDSS was reported as the secondary outcome. Functional symptoms assessed in the EDSS included cerebellar, pyramidal, bowel and bladder, brainstem, sensory, visual, and cerebral. Covariates included age at examination, body mass index, and tobacco use.²

There were 184 individuals included in the final analysis, 100 of whom were enrolled premenopausal, 70 postmenopausal, and 14 without postmenopausal data. Participants were aged a median 37 years at first MS symptom onset and 63 years at the most recent visit.²

Relapsing-remitting MS was reported in 69% of participants, and the median MS duration was 24 years. Natural menopause was reported in 85% of participants, vs surgical menopause in 15%. The median EDSS score was 2.5 years at menopause, and disease lasted for a median 13 years.²

Accelerated worsening of the MSFC was reported after menopause, with a slope difference of 0.08 after adjustment. This remained for all domains, with slope differences of 0.06 and −0.23 for cognitive and fine motor domains, respectively. A statistically significant worsening was reported for walking, with a slope difference of -0.46.²

EDSS scores indicated significant deceleration of worsening after menopause, with a slope difference of 0.05. Similar results were reported when adjusting for MS variables.²

As estrogen therapy was only taken by 17% of participants, investigators could not reach a conclusion about its benefits.¹ “We would need large, randomized trials that compare hormone treatment to a placebo before we can know the true effects of hormone therapy in a condition as complex as MS,” said Bove.

References

1. For women with MS, mobility takes step backward at menopause. University of California San Francisco. January 9, 2025. Accessed January 14, 2025. https://www.eurekalert.org/news-releases/1070023
2. Silverman HE, Bostrom A, Nylander AN, et al. Association of menopause with functional outcomes and disease biomarkers in women with multiple sclerosis. Neurology. 2025;104(2). doi:10.1212/WNL.0000000000210228