Understanding Potential Factors Contributing to Sex-Based Disparities in Multiple Sclerosis

In the research paper titled “Insights into the mechanism of oligodendrocyte protection and remyelination enhancement by the integrated stress response,” Dr. Chen and her colleagues investigated whether the collective use of both Sephin1 and BZA can be better equipped to repair myelin during inflammation. Dr. Chen explained how Multiple Sclerosis (MS) is a chronic immune-mediated CNS demyelinating disease affecting 2.5 million people. The onset of MS is between the ages of 20-40 years, with females being at a higher risk than males. The statistics show the sex ratio between females and males is 3:1. In the article titled “Why Multiple Sclerosis Affects More Women than Men,” posted on WebMD, discusses the widening gender gap for MS in the last 50 years. According to the article, there is no clear-cut explanation for the cause of MS, however, there are some theories that could potentially explain the sex differences. 

One potential factor contributing to the higher risk of MS in women compared to men is immune system differences. According to the article, women are more susceptible to developing autoimmune diseases. An immune system protein called interleukin-33 (IL-33) plays a role in promoting immune system communication. Studies have shown men to produce more IL-33 than women during infections, explaining why women are more prone to having an autoimmune response. Nervous system differences may also play a role. Men are more likely to experience nerve damage with MS than women, which could be due to women’s bodies producing higher levels of estrogen than men. Hormonal changes are another important consideration. Researchers have found that before puberty, boys and girls develop MS at similar rates, however, as they enter adolescence and adulthood, their bodies begin producing different hormones. Further research is still needed on the potential connection between sex hormones and MS. Genetic mutations, particularly in genes such as major histocompatibility complex (MHC), have also been associated with increased MS risk. Research suggests that women with MS often show changes in these genes, and daughters are more likely than sons to inherit them. However, researchers note that one gene alone is unlikely to cause MS. Lifestyle factors such as diet, smoking, stress, etc., can influence the expression of MS-related genes.

Another article titled “Multiple Sclerosis: Why Are Women More at Risk?” published on John Hopkins Medicine, additionally discusses the role of vitamin D deficiency and body fat from obesity as potential factors for a higher risk of MS in women. Dr. Calabresi, the director of the John Hopkins Multiple Sclerosis Center, and his team including Dr. Mowry have found that those with lower vitamin D levels are at a higher risk of MS, and more frequent relapses. Dr. Mowry’s studies are investigating whether vitamin D supplements could help reduce MS relapse. Dr. Mowry also explains that weight can influence the likelihood of developing MS due to its connection to inflammation. Women are more likely to be obese than men, and belly fat specifically is associated with increased inflammation.

While much research is still needed to understand why females are at a higher risk for multiple sclerosis than males, significant strides have been made in understanding this gender disparity. These articles provide valuable insight into the complex interactions between genetic, hormonal, and environmental factors, as well as body system differences that contribute to the increased prevalence of MS in females.

References: 

Chen, Y., Quan, S., Patil, V., Kunjamma, R. B., Tokars, H. M., Leisten, E. D., Chan, J., Wong, Y., & Popko, B. (2023). Insights into the mechanism of oligodendrocyte protection and remyelination enhancement by the integrated stress response. bioRxiv : the preprint server for biology, 2023.01.23.525156. https://doi.org/10.1101/2023.01.23.525156

Ellis, R. R. R. (n.d.). Why Multiple Sclerosis Affects More Women Than Men. WebMD. https://www.webmd.com/multiple-sclerosis/ms-affects-women-more-than-men 

Multiple Sclerosis: Why Are Women More at Risk?. Johns Hopkins Medicine. (2023, February 9). https://www.hopkinsmedicine.org/health/conditions-and-diseases/multiple-sclerosis-ms/multiple-sclerosis-why-are-women-more-at-risk