- Women are around three times more likely than men to develop MS, but researchers are still investigating why this difference exists.
- Research suggests that hormones can influence both the risk of developing MS and how the disease behaves throughout life.
- Understanding why women are more susceptible to MS could help identify new opportunities for prevention, earlier diagnosis and more personalised treatments.
Multiple sclerosis (MS) affects women more than men. In Australia, women are around three times more likely than men to be diagnosed with MS, a pattern that has also been seen around the world.
While researchers have known about this difference for decades, understanding exactly why women are more susceptible to MS remains one of the biggest questions in MS research.
Researchers are also discovering that biological sex may influence not only the risk of developing MS, but also how the disease behaves throughout life, including during puberty, pregnancy and menopause.
Today, researchers believe there is no single explanation. Instead, MS appears to develop through a complex interaction between genetics, the immune system, hormones and environmental factors. Recent discoveries are helping researchers piece together this puzzle and, importantly, may provide new opportunities to prevent MS in the future.
Biological differences may help explain the gap
MS is an immune-mediated disease where the body’s immune system mistakenly attacks the protective covering of nerve fibres in the brain, spinal cord and optic nerve.
Women are generally more likely than men to develop autoimmune conditions. Researchers believe this may be partly due to differences in how the immune system functions. While a stronger immune response can help fight infections, it may also increase the likelihood of the immune system targeting the body’s own tissues. Recent studies have identified sex-specific differences in the activity of immune-related genes, providing new clues about why autoimmune diseases are more common in women.
Researchers are also increasingly recognising that sex hormones do more than influence MS risk. Hormonal changes throughout life may influence inflammation and disease activity, helping explain some of the differences observed between women and men with MS.
To better understand these differences, researchers are investigating the role of sex hormones such as oestrogen and progesterone, as well as genes carried on the X chromosome. Because women have two X chromosomes, researchers are exploring whether differences in the way certain immune-related genes are regulated could contribute to the higher risk of autoimmune diseases, including MS.
Researchers have also examined the role of puberty in MS susceptibility. The higher prevalence of MS among women is not observed before puberty, suggesting that hormonal changes during adolescence may contribute to later disease risk. Some studies have linked earlier puberty with an increased risk of developing MS and an earlier age of disease onset.
Environmental risk factors may affect women differently
Over the past decade, researchers have identified a number of factors that increase the risk of developing MS, including:
- Low vitamin D levels
- Limited sun exposure
- Smoking
- Obesity, particularly during childhood and adolescence
- Epstein-Barr virus infection
Researchers increasingly recognise that MS risk factors may affect people differently. Differences in hormones, immune function and genetics may influence how the body responds to factors such as smoking, obesity, low vitamin D and Epstein-Barr virus (EBV) infection. Biological sex may also influence how these risk factors affect both susceptibility to MS and disease activity. For example, studies suggest that smoking may influence MS risk differently in women and men, although the reasons for these differences are still being investigated. Understanding these complex interactions may help explain why women are more likely to develop MS than men.
The Epstein-Barr virus breakthrough
One of the most significant developments in MS research in recent years has been the growing evidence linking EBV to the development of MS.
EBV is an extremely common virus, with most people becoming infected at some point during their lives. For many years, researchers suspected that EBV played a role in MS. More recently, large studies have provided compelling evidence that infection with EBV is a key step in the development of the disease.
Importantly, not everyone who is infected with EBV develops MS. Australian researchers have shown that oestrogen can influence the expression of MS risk genes in EBV-infected B cells (a type of immune cell), suggesting that biological sex may affect how the body responds to the virus. Researchers are exploring whether these sex-specific responses to EBV contribute to the higher risk of MS in women.
This work is helping to transform our understanding of how MS develops and may eventually lead to new strategies to prevent the disease.
What about pregnancy?
Researchers have long recognised that pregnancy can influence MS disease activity. Relapse rates typically decrease during pregnancy, particularly in the later stages, although they may temporarily increase in the months after birth as hormone levels return to pre-pregnancy levels. Importantly, pregnancy does not appear to worsen long-term MS outcomes.
More recently, studies have also explored whether pregnancy may influence the likelihood of developing MS. Some studies suggest that women who have experienced pregnancy may develop the first signs of MS later than women who have never been pregnant, although researchers are still investigating this relationship.
While these findings do not mean pregnancy prevents MS, they suggest that reproductive and hormonal factors may play a role in shaping MS risk and the timing of disease onset. Researchers continue to investigate the biological mechanisms underlying these observations.
How menopause may affect MS
Another important life stage being explored by researchers is menopause. Studies examining the relationship between menopause and MS have reported mixed findings, with some suggesting increased disability or symptom burden with menopause, and others finding little effect of menopause once age and disease duration are taken into account. Researchers continue to investigate how hormonal changes during menopause may influence MS symptoms and progression.
Symptoms such as fatigue, sleep disturbances and heat sensitivity may become more prominent during menopause and can overlap with MS symptoms. This highlights the importance of discussing symptom changes with healthcare professionals and ensuring care is tailored to an individual’s stage of life.
Looking ahead
Researchers are gaining an increasingly detailed understanding of why women are more likely than men to develop MS. The discovery of EBV as a major driver of MS, together with growing insights into the role of hormones, immune function and genetics, has transformed our understanding of the disease in recent years.
While there is still no single explanation for the higher risk of MS in women, researchers are beginning to uncover how biological sex may interact with environmental and lifestyle factors to influence susceptibility. Understanding these interactions could help identify new opportunities for prevention, earlier diagnosis and more personalised approaches to treatment.
Although many questions remain unanswered, each new discovery brings us closer to understanding why women are disproportionately affected by MS and how this knowledge may ultimately improve outcomes for everyone living with the disease.
