Studying Multiple Sclerosis in Males May Help Both Genders

Updated on February 2, 2018
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Linda Crampton is a teacher with a first class honors degree in biology. She writes about human biology and the scientific basis of disease.

Some effects of multiple sclerosis
Some effects of multiple sclerosis | Source

A Frustrating Disease

Multiple sclerosis is a condition in which myelin—the fatty insulation around nerve cells—is damaged due to inflammation. Myelin plays a major role in the conduction of nerve impulses. Serious problems may develop if the substance is injured. At the moment, multiple sclerosis (MS) can't be cured, but it can be helped. New research suggests that understanding a process that occurs in males with MS may lead to a better treatment for both genders.

For a long time, researchers have known that younger women are three or even four times more likely to get MS than younger men. Scientists at the Northwestern Feinberg School of Medicine have discovered how gender and testosterone lower the risk of the disease, at least in mice. If the system works in humans as well, scientists may be able to create a new and perhaps more effective way of treating the illness.

A nerve cell or neuron
A nerve cell or neuron | Source

In the peripheral nervous system, Schwann cells spiral around the axon of the neuron. The layers of their fatty membrane form the myelin sheath. In the central nervous system (brain and spinal cord), oligodendrocytes make the myelin sheath instead of Schwann cells.

Multiple Sclerosis or MS

MS is an autoimmune condition in which a person’s immune system attacks myelin in the central nervous system. The symptoms of MS depend on the location and extent of the damage. The patient develops demyelination areas in the brain, which are known as lesions or plaques.

The patient may experience problems such as:

  • difficulty in movement
  • coordination problems
  • balance problems
  • tingling
  • numbness
  • speech difficulties
  • difficulty with vision due to inflammation around the optic nerve
  • fatigue
  • dizziness
  • cognitive problems
  • bladder and/or bowel problems

The symptoms may not be continuous. The most common form of the disorder is known as relapsing-remitting multiple sclerosis. In this condition, the patient experiences flare-ups in which inflammation and symptoms are worse alternating with periods when symptoms are weaker. Some people do experience symptoms continually, however. The disease may be progressive or may become so at some point.

Not all of the symptoms listed above may be present in someone with MS and ones not listed may appear. A doctor must be consulted to diagnose the cause of the symptoms and to provide treatment. The information in this article is intended for general interest only.

Information About MS From the Khan Academy

T Cells

The discovery about MS in mice is related to the action of T cells, or T lymphocytes. Lymphocytes are a type of white blood cell. White blood cells work to protect us from disease.

There are two major types of lymphocytes: B and T. Like other types of blood cells, they are made in the red bone marrow. B cells mature in the bone marrow. T cells are sent to the thymus gland to mature, which explains their "T" designation.

There are several types of T cells. The ones involved in multiple sclerosis are a type of helper T cell. Helper T cells are also known as CD4+ cells because they have a glycoprotein called CD4 on their membrane. The different kinds of helper T cells are identified as Th followed by a number. Th17 is an important helper T cell with respect to multiple sclerosis development.

A human lymphocyte; B and T lymphocytes are difficult to distinguish visually
A human lymphocyte; B and T lymphocytes are difficult to distinguish visually | Source

An Interesting Study in Mice

Researchers have suspected for some time that the presence of testosterone is at least part of the reason for the lower incidence of MS in men. Testosterone is a hormone that helps sperm to develop and gives men their distinctive male characteristics. Women may be surprised to learn that their ovaries make testosterone as well as the female hormone estrogen. The testosterone level is far lower in females than males, however.

The scientists at Northwestern University investigated a "mouse model" of multiple sclerosis. Model organisms are often specially treated so that they have symptoms and internal processes resembling those of a human disease. The researchers' discovery involved the action of mast cells, which are part of the immune system. The discovery also involved the activity of IL-33 (or interleukin 33), which is a type of cytokine released by mast cells. Cytokines are cell signaling molecules.

The researchers discovered that testosterone caused mast cells to release IL-33 in male mice. The IL-33 then stimulated a chain of events that prevented the development of Th17 cells. Th17 cells can attack myelin in mice (and perhaps in humans as well), so preventing their development was beneficial for the animals.

The female mice in the Northwestern University experiment exhibited a higher level of myelin attack by Th17 than the males. Perhaps very significantly, when females were given IL-33, the attack on their myelin stopped. This suggests that the chemical could be used as a medicine, at least in a mouse model of MS.

Research in lab mice may apply to humans, but this isn't always the case.
Research in lab mice may apply to humans, but this isn't always the case. | Source

Th17 in Other Autoimmune Diseases

Th17 cells are thought to play a role in other autoimmune diseases besides MS, including rheumatoid arthritis and psoriasis. Like other helper T-cells, Th17 cells help to fight pathogens (microbes that attack disease). Studying the factors that transform Th17 from a destroyer of microbes to an attacker of human tissue in an autoimmune condition is an important area of research.

Th17 cells appear to be pro-inflammatory. The inflammatory response is often helpful. It brings extra blood and agents from the immune system to an injured or infected area. This helps to repair damage and destroy pathogens. Excessive or prolonged inflammation may be harmful and may damage healthy tissue, however. In autoimmunity, Th17 cells appear to trigger inappropriate inflammation. The cells make a cytokine called IL-17, which is also being studied for its role in inflammation and autoimmunity.

Types of Multiple Sclerosis

A Possible Link Between Testosterone Level and MS in Men

The results from Northwestern University sound impressive, but they were discovered in mice, not humans. Clinical trials are needed in order to discover whether the treatment has benefits for humans.

The studies may not be quite as straightforward as they seem. While males do have a much lower incidence of MS than females, they also have a greater tendency to develop a progressive form of the disease as well as a greater tendency to develop brain atrophy and cognitive problems.

A few trials involving men with multiple sclerosis have been performed and have shown that administering testosterone can be helpful. There are problems with some of the trials, however, such as a small sample size or the way in which the experiment was run.

The following studies related to testosterone and multiple sclerosis in men are widely quoted.

  • Researchers at the University of California studied ten men with MS who were not receiving disease-modifying treatment. They found that treatment with a testosterone gel decreased the percentage of CD4+ cells in the men, among other changes. They also found that brain atrophy slowed and cognitive function increased.
  • The Swedish Medical Center reports that in a study of 96 men with MS, those with a lower level of testosterone had worse symptoms. As the center says, however, this is an association rather than proof that low testosterone is responsible for the more severe symptoms.

According to the Harvard Medical School researcher in the video below, evidence suggests that testosterone is both anti-inflammatory and neuroprotective. As she says, though, clinical trials are needed to prove this.

Testosterone and MS Information From a Harvard Researcher

Medical Researchers Discuss Hormones and MS

The doctor and medical researcher in the video above says that data supports the possible association between testosterone level and MS in males. It's important that people with multiple sclerosis don't take supplemental testosterone without a doctor's advice and without being monitored, however. The researcher recommends that a man doesn't take a supplement unless he has another problem known to be caused by low testosterone. Testosterone administration can cause side effects, including cardiovascular problems. It’s not a suitable treatment for MS in females or for males with a normal testosterone level. IL-33 or another substance in the pathway that inhibits Th17 cell development may be, however.

In the video below, a doctor from the University of Pennsylvania also discusses the link between hormones and multiple sclerosis. Like the researcher in the first video, he says that a higher level of testosterone appears to be protective and that estrogen may be pro-inflammatory. He points out that although the ratio of women to men with MS is around 3:1 in younger people who get the disease, in people who are older at disease onset the ratio is not as extreme. This may be partly because the testosterone level sometimes decreases in a man as he ages, decreasing his protection. The fact that the estrogen level decreases in a female after menopause may also play a role.

A Doctor Discusses Testosterone and MS

As the doctor in the above video says, although the possible associations between hormones and multiple sclerosis are fascinating and might lead to better treatments, the details of the associations need to be elucidated.

Hope for the Future

There is no cure for multiple sclerosis yet. Drugs that help to relieve symptoms and modify the course of the disease exist, however. The discovery of better treatments would be wonderful, especially if they prevent progression of the disease as well as ease current symptoms.

Testosterone levels in the body of males with MS and the stimulation of pathways to myelin destruction need to be clarified. The results of this research might be very helpful for both men and women with multiple sclerosis, however.

References

Information about multiple sclerosis from the Mayo Clinic

Males with MS may hold a key for treating the disease from Northwestern University

Th17 cells in inflammation and autoimmunity (abstract) from the National Institutes of Health

Immune modulation in male multiple sclerosis patients treated with testosterone from Medscape

Testosterone level is associated with worse disease severity in men from the Swedish Medical Center

Hormones and MS information from the Multiple Sclerosis Trust

© 2018 Linda Crampton

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    • AliciaC profile image
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      Linda Crampton 2 weeks ago from British Columbia, Canada

      I agree, Larry. I wish better treatments were available for all of them, including one that affected my family.

    • Larry Rankin profile image

      Larry Rankin 2 weeks ago from Oklahoma

      All the wasting diseases are just the sadest.

      Great read.

    • AliciaC profile image
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      Linda Crampton 2 weeks ago from British Columbia, Canada

      I agree, Dora. It's sad that there isn't a cure at the moment. I hope the situation doesn't stay this way for long.

    • MsDora profile image

      Dora Weithers 2 weeks ago from The Caribbean

      I have met a few victims of this disease; it is depressing to know that there isn't a cure. Thanks for the information and explanations and the hope of better treatments.

    • AliciaC profile image
      Author

      Linda Crampton 2 weeks ago from British Columbia, Canada

      Hi, Bede. Yes, those would definitely be side effects of testosterone treatment to be avoided! I hope researchers find a substance involved in testosterone's action that can be used as a medicine without producing the side effects. Thank you very much for commenting.

    • AliciaC profile image
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      Linda Crampton 2 weeks ago from British Columbia, Canada

      Hi, Heidi. Yes, inappropriate inflammation appears to be a major factor in a range of health problems. Understanding more about it could be very helpful for scientists looking for new ways to deal with diseases. As always, thanks for the visit.

    • AliciaC profile image
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      Linda Crampton 2 weeks ago from British Columbia, Canada

      Hi, Mary. I don't personally know anyone with MS, but my sister does. The disease has certainly affected her friend's life. I hope the research into the cause of the disease not only continues but also intensifies. Thank you for the comment.

    • Bede le Venerable profile image

      Bede 2 weeks ago from Minnesota

      Thank you for the informative article, Linda. The treatments on mice give hope for those who suffer from this disease. I wonder if injecting more testosterone into women with MS might have adverse effects, such as more masculine characteristics? Apparently, women body builders who have taken steroids have developed male features: deeper voice, facial hair and the like.

    • heidithorne profile image

      Heidi Thorne 2 weeks ago from Chicago Area

      I do hope they find a cure one day! It seems that so much of our health revolves around inflammation. Once science has realized that, it seems we're making some progress with these life-limiting conditions. Thanks for sharing your insight and helpful information, as always!

    • Blond Logic profile image

      Mary Wickison 2 weeks ago from Brazil

      I've known a couple people with MS but never knew much about it. It is encouraging to know that the research being carried out is returning positive outcomes.

      Thank you for researching it and explaining it to those of us with a non-medical background.

    • AliciaC profile image
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      Linda Crampton 2 weeks ago from British Columbia, Canada

      Hi, Peg. Thanks for the visit. I appreciate your comment.

    • PegCole17 profile image

      Peg Cole 2 weeks ago from Dallas, Texas

      You've really put a lot of research into this study. I admire your ability to understand all of this technical information well enough to write about it.

    • AliciaC profile image
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      Linda Crampton 2 weeks ago from British Columbia, Canada

      Thank you very much, Kari. I hope the new discoveries are useful for people with MS. It would be great if they helped people with a different autoimmune disease, too.

    • k@ri profile image

      Kari Poulsen 2 weeks ago from Ohio

      I love the fact that you keep up on the latest medical news and then write it for us. The IL-33 sounds hopeful. It would be wonderful to discover a way to prevent and/or lessen the symptoms of MS.

    • AliciaC profile image
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      Linda Crampton 2 weeks ago from British Columbia, Canada

      Thanks, Bill. I'm hoping for a better future for people with MS.

    • AliciaC profile image
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      Linda Crampton 2 weeks ago from British Columbia, Canada

      Thank you very much, Devika.

    • AliciaC profile image
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      Linda Crampton 2 weeks ago from British Columbia, Canada

      I agree, Mary. People may have MS for a large portion of their lives. I wish more could be done to help them.

    • billybuc profile image

      Bill Holland 2 weeks ago from Olympia, WA

      I go on MS Walks for donations. It's a frustrating disease which affects the entire family. Well done here, Linda. Awareness needs to be raised and raised some more about this disease.

    • DDE profile image

      Devika Primić 2 weeks ago from Dubrovnik, Croatia

      MS testing allows more hope for those affected. A useful and well-researched hub.

    • aesta1 profile image

      Mary Norton 2 weeks ago from Ontario, Canada

      I really hope they discover the treatment soon especially because its onset is quite early in women.

    • AliciaC profile image
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      Linda Crampton 2 weeks ago from British Columbia, Canada

      Hi, Flourish. Every time I write about multiple sclerosis, I think of you. I'm so sorry that you have to deal with it in your life. I hope for your sake and for everyone else with the disease that better treatments are discovered very soon. Exploring the biology of the condition is interesting, but it's important that the scientific discoveries lead to the creation of effective medications as soon as possible.

    • FlourishAnyway profile image

      FlourishAnyway 2 weeks ago from USA

      As someone who has lived with MS for more than 15 years, I can attest that it’s a life altering disease. I truly hope progress comes. There has to be some hormonal link, as many pregnant women who already know they have MS see complete alleviation of symptoms during pregnancy then relapse after giving birth. MS is a lonely disease and men are outnumbered by women, making it particularly isolating for them. I really feel badly for the kids who are diagnosed with it. With girls developing earlier and earlier, that’s additional anecdotal evidence of a potential hormonal connection. With all the emphasis on big data, I just don’t understand why there aren’t faster advances. Your article was very well written and I particularly appreciated how you broke down a very complex disease complex.

    • AliciaC profile image
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      Linda Crampton 2 weeks ago from British Columbia, Canada

      Thank you very much, Hari. I appreciate your visit and comment.

    • shprd74 profile image

      Hari Prasad S 2 weeks ago from Bangalore

      Very comprehensive and useful hub. Bookmarking this hub linda.

      - hari

    • AliciaC profile image
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      Linda Crampton 2 weeks ago from British Columbia, Canada

      Thanks for sharing your experience, Jackie. There is so much that we don't know about diseases and the body. I think it's important to investigate all the possibilities. I'm sorry about the loss of your friend.

    • Jackie Lynnley profile image

      Jackie Lynnley 2 weeks ago from The Beautiful South

      I have seen MS in my family and lost my very best friend to it. I do hope something is soon done.

      I read many testimonies that bee therapy has helped and even cured people of this disease, whether it is true or not.

      I probably would not even have paid attention to this but having been stung a number of times by accident in my woods and never having pain in my ankles again that had been plaguing me just made me sure there is something to this and I do wish the MS Society would take it more seriously. If I had known my friend was suffering before her death with MS I would have tried my best to get her to give it a try.

      I do not mean to take away from your article, which is always so well done but this is just my personal experience.

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