Researchers at the Cleveland Clinic and University of California, San Diego, are launching two studies funded by the National MS Society to investigate how the midlife transition—specifically perimenopause and menopause—accelerates disability in women with multiple sclerosis (MS). By analyzing biological markers of ovarian aging alongside longitudinal patient outcomes, investigators aim to determine if hormonal shifts serve as independent drivers of neurodegeneration, potentially opening new windows for personalized therapeutic interventions.
Why is midlife a critical turning point for women with MS?
For many women, the onset of progressive forms of MS, such as secondary and primary progressive disease, occurs near the median age of 45, according to data from the Cleveland Clinic. This period often coincides with the hormonal fluctuations of perimenopause and menopause. While chronological age has long been a standard clinical metric, researchers suggest it may not fully capture the biological reality of how the body ages in the presence of MS.
How do biological markers track reproductive and somatic aging?
A study led by Dr. Le Hua and Dr. Jennifer Graves is moving away from self-reported menopause data, which has historically produced inconsistent results. Instead, the team is using objective biological markers to distinguish between reproductive and somatic aging in 400 women with MS and 100 healthy controls.
- Anti-Müllerian Hormone (AMH): Used as a validated biomarker for ovarian reserve to identify “fast” versus “slow” reproductive agers.
- Leukocyte Telomere Length (LTL): Serves as a marker for somatic aging, reflecting cumulative oxidative stress and immune system senescence.
According to Dr. Hua, the research team aims to determine if these two processes contribute independently to MS severity. By integrating serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (GFAP) measurements, the researchers hope to see if ovarian aging specifically drives neurodegeneration more aggressively in MS patients than in healthy individuals.
What is the impact of menopause on MS symptom burden?
A separate project led by Dr. Amber Salter of UT Southwestern and Dr. Robert Fox of the Cleveland Clinic is examining how the menopause transition influences long-term disease outcomes. Using the North American Research Committee on Multiple Sclerosis (NARCOMS) registry, the team is linking decades of patient data with new survey results to assess the efficacy of menopausal hormone therapy.
“Menopause is the most common health issue that women with MS encounter, yet many of its symptoms overlap those of MS, complicating clinical management,” Dr. Fox states. The study uses an interrupted time series analysis, which allows participants to serve as their own controls, to compare disability trajectories and quality of life scores before, during, and after the menopausal transition.
Frequently Asked Questions
- Does menopause make MS worse?
- Research is currently underway to determine if the biological transition of menopause independently drives MS disability. Some evidence suggests that hormonal shifts may exacerbate neurodegeneration.
- What is the role of AMH in MS research?
- AMH is an objective biomarker used to measure ovarian reserve. Researchers are using it to see if women who experience “fast” reproductive aging also experience faster MS disease progression.
- Can hormone therapy help women with MS during menopause?
- While early trials suggest potential benefits for hot flashes and quality of life, current evidence regarding long-term MS disease outcomes remains limited. Studies like the one led by Dr. Fox aim to provide clearer guidance for clinicians.
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