Testosterone: Why the Incidence of Multiple Sclerosis is Lower in Men
News Jan 29, 2018 | by Laura Elizabeth Mason, Science Writer, Technology Networks
Researchers have discovered why men are much less likely to develop multiple sclerosis (MS) — high levels of testosterone. Testosterone triggers production of the cytokine IL-33 protecting them from the disease. The team’s findings were published today in the Proceedings of the National Academy of Sciences.1
Senior author, Prof. Melissa Brown, from Northwestern University, commented on the significance of their findings in a recent press release: "Because testosterone levels are seven-to-eight times lower in adult women compared to men, we speculate there are insufficient levels in females to activate this protective pathway …But we showed we can activate the pathway with the guardian molecule, IL-33."
The scientists used a mouse model of MS, experimental autoimmune encephalomyelitis (EAE), to show that when female mice were administered IL-33, their disease symptoms were eliminated.
MS affects >2.3 million individuals worldwide. Most people affected by MS are diagnosed between the ages of 20–50 years.2 MS is a neurological condition that affects the central nervous system. More specifically, it is caused by the individual’s immune system attacking the myelin sheath that surrounds nerve fibers. Damage to this protective sheath results in the interruption of normal signal conduction as nerve axons are no longer adequately insulated. Symptoms can include; vision loss, dizziness, muscle spasms and stiffness, and fatique.3
MS is at least two-to-three times more common in females compared to males.2 Previous research has shown that pregnancy has a temporary beneficial effect on MS activity, indicating that hormones can influence susceptibility of the disease. Limited studies have shown that treating male MS patients with testosterone can improve MS outcomes,4,5 however, short-term testosterone therapy is not a viable treatment for either sex due to associated adverse effects.
"This [research] suggests a mechanism for the reduced incidence of multiple sclerosis and other autoimmune diseases in males compared to females …These findings could lead to an entirely new kind of therapy for MS, which we greatly need." Explained Brown.
The researchers demonstrated that testosterone stimulates mast cells to produce IL-33 and that IL-33 triggers a chemical cascade that prevents the production of Th17 cells in male mice. Th17 cells are directly responsible for nerve demyelination. Lower levels of testosterone in female mice appear to lead to a lack of IL-33. The researchers noted that female mice, produced more Th17 cells than males, leading to a more severe phenotype, however by administering IL-33 they were able to reverse the damaging effects in female mice.
Brown explained that the identification of hormone driven mechanisms, such as the testosterone-driven pathway outlined here, could have important therapeutic implications: "Our findings have identified new and more specific cellular and molecular targets for immune intervention that we hope will lead to better therapies that leave most of the immune system intact," Brown said. "This testosterone-driven protective pathway should also be studied in other female-biased autoimmune diseases."
1. Russi, AE, et al. (2018) Male-specific IL-33 expression regulates sex-dimorphic EAE susceptibility. PNAS. doi: 10.1073/pnas.1710401115
2. National MS Society. (2018) Who Gets MS? Retrieved January 29, 2018, from https://www.nationalmssociety.org/What-is-MS/Who-Gets-MS#section-0
3. Mayo Clinic. (2017, August 04). Multiple sclerosis. Retrieved January 29, 2018, from https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms-causes/syc-20350269
4. Kurth F, et al. (2014) Neuroprotective effects of testosterone treatment in men with multiple sclerosis. Neuroimage Clin. 4:454–460. 19.
5. Sicotte NL, et al. (2007) Testosterone treatment in multiple sclerosis: A pilot study. Arch Neurol. 64:683–688.
New Microscope Captures Detailed 3-D Movies of Cells Deep Within Living SystemsNews
Merging lattice light sheet microscopy with adaptive optics reveals the most detailed picture yet of subcellular dynamics in multicellular organisms.READ MORE
"Genetic Jenga" Helps Understand How Our Genes Control Our CellsNews
To fully understand how our cells work, we can't focus on just one gene, but must instead look at combinations of genes. Researchers have published a study which knocked out multiple genes, like removing bricks from a Jenga tower, to better understand how they work together.READ MORE
How Environmental Pollutants and Genetics Work Together in Rheumatoid ArthritisNews
It is well known that individuals with a particular version of human leukocyte antigen have an increased risk for rheumatoid arthritis, but there has been growing interest in the role of environmental pollutants. In a new mouse study, researchers probed the relationship between the two.READ MORE
Comments | 2 ADD COMMENT
lesley samm | Apr 13, 2018
I started using multiple sclerosis (MS) herbal remedy i purchased from Best Health Herbal Centre January this year. I only used it for a month and two weeks, my condition changed automatically, all my symptoms are gone. Remaining positive have helped me during this treatment. Now am living MS FREE. Hope this will help somebody, remember, do your own research and make your own decisions based on information you have received and digested. Thanks to Best Health Herbal Centre for their amazing work. Forever Grateful!
Johan BOUTELLA | Apr 05, 2018
After my Multiple Sclerosis diagnosis 2 years ago, i stopped all the Multiple sclerosis medicines prescribed due to severe side effects, and decided to go on natural herbal approach. My primary care provider introduced me to Rich Herbs Foundation and i immediately started on their Multiple Sclerosis herbal formula treatment, this herbal treatment has made a tremendous difference for me. My symptoms including shaking, muscle weakness, fatigue, mood swings, numbness, double vision and urinary retention all disappeared after the 4 months treatment! Their website is w w w. richherbsfoundation. c o m. Its just amazing!