Why Is MS More Common in Women?
According to the National Multiple Sclerosis Society, more than 2.3 million people worldwide are diagnosed with multiple sclerosis (MS)—and about 75% of them identify as female. Recent research also suggests that the number and proportion of women being diagnosed with MS is on the rise.
This type of gender imbalance isn’t entirely unique to multiple sclerosis, either. Many autoimmune diseases are more common in women than in men. While MS isn’t technically an autoimmune disease, it is thought to be immune-mediated. This means that an overactive immune system attacks healthy tissue, though specific antibodies responsible for this attack haven’t been identified.
Not only is MS in women more common, it tends to be diagnosed at earlier ages in women compared to men. And women are more likely to have relapsing-remitting multiple sclerosis (RRMS), the most common type of MS, characterized by periods of worsening disease activity and periods where symptoms are more stable.
Why Are Women More Likely to Develop MS?
It’s nearly impossible to point to one specific factor that contributes to the prevalence of MS in women, experts say. It’s linked to a combination of genetics, environmental factors, the immune-mediated response, hormones, and potentially other factors we don’t fully understand just yet. “It’s kind of that perfect storm within the person,” says Marisa McGinley, D.O., a board-certified neurologist at the Cleveland Clinic’s Mellen Center for Multiple Sclerosis, in Ohio.
Research to help us understand more about why women are more likely to develop MS is ongoing. Here’s what we know so far.
More than 230 genes are thought to be associated with a slightly increased risk of developing multiple sclerosis.
That said, less than 7.3% of the general population is thought to have a genetic risk of developing MS. And while having a family history of MS does slightly increase the risk, many people diagnosed with MS do not have a family history of the condition.
However, these numbers are based on the overall population and aren’t specific to women. “We know that there's something clearly genetically different between men and women, and there's a clear difference in risk between men and women,” says Michael Kornberg, M.D., a board-certified neurologist and assistant professor of neurology at Johns Hopkins Medicine, in Baltimore. “So certainly, genetics is explaining that, but we don't know which genes are driving that in women over men.”
More research is needed to understand the complex relationship between genetics and the prevalence of MS in women.
Researchers have identified a variety of environmental factors that are thought to increase the overall risk of MS, including:
- Geographic location of birth
- Childhood and adolescent obesity
- Previous infection with Epstein-Barr virus (EBV)
- Sunlight exposure/vitamin D deficiency
Many of these are things that we would expect to affect men and women equally, says McGinley.
However, one Danish study published in 2013 suggested a link between childhood obesity and an increased risk of later developing MS. This study suggested that the risk was greater in girls with a high body mass index (BMI) than in boys with a high BMI.
More research is needed to establish the link between other environmental factors and the increased risk of MS in women. “It may certainly be that there is some environmental factor that women are at greater risk for, but again, we just haven't defined exactly what that is,” Kornberg says.
Hormones are also thought to play a role in the sex and gender differences found with MS.
“Before puberty, MS cases are pretty evenly divided between males and females,” Kornberg says. “After puberty, that's when we start to see this clear difference in risk between men and women.” The reason for this is likely related to the hormonal changes that occur during puberty.
“It's certainly suspected that sex hormones, including estrogen, are associated with higher risk of developing MS,” Kornberg says.
While research is limited, one study published in Multiple Sclerosis Journal looked at rates of MS among transgender people. It found that transgender women taking hormone therapy such as estrogens and/or testosterone blockers may be at a notably greater risk of MS, just as cisgender women are. This evidence suggests that higher levels of hormones like estrogen, or lower levels of testosterone, may be risk factors for the development of MS.
Meanwhile, increasing estrogen levels in pregnancy seem to play a protective role in preventing MS relapses, particularly in the second and third trimesters, when estrogen levels peak. Likewise, relapse rates increase significantly in the months after childbirth, when these hormone levels drop.
“This has actually led to some studies looking at a form of estrogen, estriol, in women with MS,” says Patricia K. Coyle, M.D., board-certified neurologist and director of the MS Comprehensive Care Center at Stony Brook Medicine, in New York.
One small 2015 study of women with MS found that oral estriol, when used in combination with a traditional MS therapy, helped reduce rates of MS relapse. But as McGinley says, “None of these [hormonal therapeutic mechanisms] have been taken to large-scale trials yet.”
More research is needed to understand the exact role of certain hormones in the development of MS, and whether options like synthetic estrogen can be safely and successfully used as therapies for people with MS.
Factors Specific to Men
Compared to women, men tend to be diagnosed with MS later in life, often with a less common type known as primary progressive multiple sclerosis (PPMS). PPMS typically has more rapid accumulation of disability and worse outcomes than RRMS.
According to Coyle, the studies on estriol in women “indirectly led to some testosterone studies in men with MS,” which may help shed some light on this difference.
A review published in 2018 notes that reduced testosterone levels are a risk factor for MS among men, suggesting that normal levels of testosterone (generally considered to be 350 to 750 nanograms per deciliter in the blood) may be protective against the development of MS. “But testosterone doesn’t seem to be protective in terms of your progression if you do develop the disease,” Kornberg says.
The role of testosterone is another area that requires further research. A current, ongoing clinical trial is hoping to establish testosterone as a viable therapy for those diagnosed with MS.
Outside of testosterone, factors like delayed health-seeking behaviors often seen among men may also be at play. “It does seem that men may be less likely to seek medical care when they're having symptoms suggestive of MS,” Kornberg says. “At the same time, there's also plenty of research that women are more likely to have their symptoms dismissed by a medical provider early on, and we don't know what the balance is between those two factors.”
MS in Women: What’s on the Horizon?
While there’s still a lot that’s unknown about the higher rates of MS in women compared to men, “this is a very interesting topic that people are focusing on and believe will give us insights into MS,” Coyle says.
The primary goal of understanding sex and gender differences is to help optimize individualized MS care. “This has actually led to how we counsel women and men with MS,” says Coyle, explaining that, as new, relevant insights come along, “we’ll be able to personalize our approach to MS even more so based on sex, gender, and other factors.”
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