#ACTRIMS2022 – Hormone Therapies May Benefit Menopausal MS Patients

Hormonal changes over time — and especially those around menopause — are often associated with disability worsening in multiple sclerosis (MS) patients, which suggests that sex-specific hormone therapies may be useful in MS treatment.

Burcu Zeydan, MD, assistant professor of neurology and radiology at Mayo Clinic, provided an overview of the current state of research into hormones and aging in her talk, “The Interactions of Sex, Hormones and Age in MS Prognosis,” during the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022.

Biological sex is a critical factor affecting the development of MS, which is roughly three times more common in females than males. Females also develop the disease earlier than males, but males tend to have a faster rate of disability progression in the early stages of the disease.

Sex-related hormones — mainly estrogen in females and testosterone in males — are thought to be the key reason for these differences, as they can modulate the activity of the immune system and how well the nervous system is able to repair damage, according to Zeydan.

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Several lines of evidence support the importance of sex hormones in affecting MS risk. For example, pediatric MS affects children of all sexes equally, and the sex-based difference in disease risk does not become evident until around puberty, when hormone levels spike. Additionally, transgender women on hormone therapy — who are chromosomally XY, but have hormone levels similar to those assigned female at birth — have a similar MS risk as cisgender women (whose identity and gender corresponds with their birth sex).

Most patients are initially diagnosed with relapsing-remitting MS and eventually enter a progressive phase, where disability accumulates over time. In addition to MS risk, sex-specific differences also seem to affect the course of the disease itself.

During the relapsing phase, females tend to have more frequent relapses and those relapses more often cause sensory problems. By contrast, relapses are less frequent in males, but are more likely to cause motor issues. Males also tend to have poorer recovery from relapses than females.

In large part due to this tendency towards poorer recovery, males tend to experience a faster rate of disability progression during the relapsing phase of MS. However, later on in the progressive phase, the reverse pattern is seen.

“In a way, [women] kind of catch up with men” in the progressive phase, Zeydan said.

Pregnancy and its associated hormone changes also have a profound effect on the progression of MS. Among patients, relapse rates usually decrease substantially during pregnancy itself, but there is usually “a substantial rebound in the immediate postpartum period,” Zeydan said.

Pregnancy also has been associated with a reduced risk of developing the neurodegenerative disorder, a slower accumulation of disability, and a later onset to progressive disease.

Menopause is another hormone-altering life event that may affect the course of MS. It tends to happen for women in their 50s, which is around the age that most patients advance to progressive MS. Age at menopause and onset of progressive MS are “tightly correlated,” according to Zeydan.

“The transition from the relapsing phase to the progressive phase usually happens during the fifth decade,” she said. “The same fifth decade marks the perimenopausal [near-to-menopause] transition. So the question is, does MS impact menopause, or vice versa?”

Among patients who develop MS symptoms before age 50, disability accumulation and brain atrophy occur faster in males than females, but these sex-specific differences are not apparent among older patients.

“Could hormonal aging, specifically menopause, play a role in these changes?” Zeydan said.

Available evidence indicates that MS itself does not influence the onset of natural menopause as it occurs around the same timeframe, regardless of disease. However, non-natural menopause (e.g., surgical removal of the ovaries and/or uterus) is disproportionately common among MS patients, and these patients tend to exhibit faster cognitive decline and early atrophy in the brain.

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Collectively, the data suggest that “menopause seems to impact many prognostic metrics negatively,” Zeydan said.

Given this association, researchers speculate that therapies designed to minimize menopause-related hormone changes may benefit some women with MS. This idea is being studied in some small trials, and early results have suggested that this type of therapy can prevent MS-related brain damage, lower relapse rates, and improve cognition. Other studies are ongoing.

“The findings so far are promising … but of course, we need more trials and data,” Zeydan said.

Editor’s note: The Multiple Sclerosis News Today team is providing in-depth coverage of the ACTRIMS Forum 2022 Feb. 24–26. Go here to see the latest stories from the conference.