Links between menopause and MS progression explored in new studies

Two new research projects are looking at whether the hormonal and biological changes that happen around menopause play a role in how multiple sclerosis (MS) progresses in women, which could help doctors better predict the course of the disease and time treatments more effectively.

‘By better understanding the biological drivers of MS progression in women at midlife, we can move closer to a personalised medicine approach that respects the unique physiological transitions of the female lifespan,’ said Le Hua, MD, of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas.

She is co-leading one of the projects and reported her findings in a press release from the Cleveland Clinic.

MS is a disease in which the immune system mistakenly attacks the myelin sheath, the protective coating around nerve fibre that plays a key role in electrical signal transmission between nerve cells.

Around 45 years old, many women enter menopause, with hormones such as oestrogen declining rapidly, while also facing a higher risk of developing a progressive form of MS.

The two projects being funded by the National Multiple Sclerosis Society aim to better understand how women with MS navigate menopause and whether the hormonal and biological changes they experience play a role in how MS progresses. Although the projects use different approaches, both seek to help doctors provide personalised care during midlife.

Co-led by Hua and Jennifer Graves, MD, PhD, of the University of California, San Diego, the first project focuses on biological markers.

Previous research often relied on women recalling when their last menstrual period occurred, which can be inaccurate. Instead, researchers are measuring anti-Müllerian hormone (AMH), which reflects ovarian reserve, or the number of eggs remaining in the ovaries that have the potential to be fertilized.

Lower AMH indicates more advanced reproductive aging. Earlier research found that women with MS who had lower AMH experienced faster disability accumulation and greater loss of gray matter, the brain tissue that contains nerve cell bodies and is important for processing information and movement. This link appeared to be independent of age and disease duration.

‘We suspect we may identify a sex-specific vulnerability in midlife women with MS that can perhaps be targeted therapeutically. If ovarian aging is confirmed to be an important driver of neurodegeneration, it could justify the use of more-aggressive disease-modifying therapies or hormonal interventions during perimenopause,’ Hua said. Perimenopause is the time before menopause.

The project will also examine leukocyte telomere length, a marker of aging. Telomeres are protective structures located at the ends of chromosomes that naturally become shorter as cells age. This phenomenon is influenced by oxidative stress, which is cellular damage caused by harmful oxygen-containing molecules. Shorter telomeres have previously been linked to greater disability and more brain shrinkage in MS.

Researchers believe reproductive aging and biological aging may each contribute separately to MS progression and disability. To test this idea, they will analyse data from 400 women with MS, ages 20 to 60, and 100 healthy women of similar ages. Blood samples and DNA will be used to measure AMH levels and telomere length using highly sensitive laboratory techniques.

The researchers will also study neurofilament light chain, a protein released when nerve fibres are damaged, and glial fibrillary acidic protein, which reflects activation of astrocytes – cells that support nerve cells in central nervous system (brain and spinal cord) – and noninflammatory neurodegeneration.

MRI scans will be used to measure brain volume. Loss of volume is considered a sign of progression in MS.

The second project aims to study menopause from a different perspective. Co-led by Amber Salter, PhD, of the University of Texas Southwestern Medical Center and Robert Fox, MD, of the Cleveland Clinic’s Mellen Center, it will focus on symptoms, disability, and quality of life over time.

Researchers will use data from the North American Research Committee on Multiple Sclerosis Registry, a large database that has followed patients diagnosed with MS for more than two decades. Using detailed menopause questionnaires and long-term health records, researchers will compare women’s health before, during, and after menopause.

‘The findings are intended to directly support shared decision-making with patients,’ Fox said. ‘By understanding the typical trajectory of MS during menopause, clinicians can better counsel patients on which symptoms to expect and whether menopausal hormone therapy or lifestyle modifications might mitigate the impact of some menopausal changes.’

Together, these projects represent a shift toward sex-specific and age-specific care in MS. By identifying biological markers of reproductive aging and understanding how menopause affects symptoms, researchers hope to find the best times to treat patients during midlife.

Read more about how MS and menopause in our helpful Choices booklet