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Studying Multiple Sclerosis in Males May Help Both Genders

Linda Crampton is a writer and teacher with a first-class honors degree in biology. She often writes about the scientific basis of disease.

Damage to myelin in multiple sclerosis

Damage to myelin in multiple sclerosis

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.

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), cells known as oligodendrocytes make the myelin sheath.

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.

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 appears to be an important helper T cell with respect to multiple sclerosis development.

Scientists know that Th17 cells promote inflammation and that this is their normal function. It might sound strange that the body has developed a pro-inflammatory cell type. Inflammation is a vital and often useful process, however. It involves increased blood flow to an area. The blood carries cells and substances that can destroy pathogens and remove damaged cells. Inflammation that continues for too long or is excessive and out of control can be harmful to tissues, however.

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

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

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 the following sequence of events in male mice.

  • Testosterone caused mast cells in the mice to release IL-33.
  • The IL-33 then stimulated a chain of events that prevented the development of Th17 cells.
  • Th17 cells can and sometimes do attack myelin in mice (and perhaps in humans as well). The reduction in their Th17 concentration was beneficial for the mice with respect to the state of their myelin.

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.

Th17 in Other Autoimmune Diseases

Th17 cells are thought to play a role in other autoimmune diseases besides MS, including rheumatoid arthritis and psoriasis. Studying the factors that transform Th17 from a helpful cell to an attacker of human tissue in an autoimmune condition is an important area of research. In autoimmunity, Th17 cells appear to trigger inappropriate inflammation. We need to know why this occurs. The cells make a cytokine called IL-17, which is also being studied for its role in inflammation and autoimmunity.

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.

Medical Researchers Discuss Hormones and MS

The 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.

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.

References

This content is accurate and true to the best of the author’s knowledge and does not substitute for diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed health professional. Drugs, supplements, and natural remedies may have dangerous side effects. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.

© 2018 Linda Crampton

Comments

Linda Crampton (author) from British Columbia, Canada on April 27, 2018:

I hope so, too, Peggy. MS is a horrible condition, as you say. It would certainly be wonderful to find a cure for the disease.

Peggy Woods from Houston, Texas on April 27, 2018:

Hopefully they will continue to do research and ultimately find a cure. That would be wonderful. Multiple Sclerosis is a horrible disease.

Linda Crampton (author) from British Columbia, Canada on March 21, 2018:

I hope you stay in remission and that no further problems develop, Larry. The information about trigeminal neuralgia sometimes leading to multiple sclerosis is new for me. I hope it never applies to you.

Larry W Fish from Raleigh on March 21, 2018:

A very interesting article for me, Linda. As you know I have Trigeminal Neuralgia, a condition that causes severe facial pain. Luckily I have been in remission for 10 weeks now. I know that in some cases although it is a small percentage a person with Trigeminal Neuralgia can develop Multiple Sclerosis. I have been told not to worry, but i still have that feeling in the back of my mind.

Linda Crampton (author) from British Columbia, Canada on February 07, 2018:

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

Larry Rankin from Oklahoma on February 07, 2018:

All the wasting diseases are just the sadest.

Great read.

Linda Crampton (author) from British Columbia, Canada on February 04, 2018:

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.

Dora Weithers from The Caribbean on February 04, 2018:

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.

Linda Crampton (author) from British Columbia, Canada on February 04, 2018:

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.

Linda Crampton (author) from British Columbia, Canada on February 04, 2018:

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.

Linda Crampton (author) from British Columbia, Canada on February 04, 2018:

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 from Minnesota on February 04, 2018:

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.

Heidi Thorne from Chicago Area on February 04, 2018:

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!

Mary Wickison from Brazil on February 04, 2018:

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.

Linda Crampton (author) from British Columbia, Canada on February 03, 2018:

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

Peg Cole from Northeast of Dallas, Texas on February 03, 2018:

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.

Linda Crampton (author) from British Columbia, Canada on February 03, 2018:

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.

Kari Poulsen from Ohio on February 03, 2018:

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.

Linda Crampton (author) from British Columbia, Canada on February 03, 2018:

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

Linda Crampton (author) from British Columbia, Canada on February 03, 2018:

Thank you very much, Devika.

Linda Crampton (author) from British Columbia, Canada on February 03, 2018:

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

Bill Holland from Olympia, WA on February 03, 2018:

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.

Devika Primić from Dubrovnik, Croatia on February 03, 2018:

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

Mary Norton from Ontario, Canada on February 03, 2018:

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

Linda Crampton (author) from British Columbia, Canada on February 02, 2018:

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 from USA on February 02, 2018:

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.

Linda Crampton (author) from British Columbia, Canada on February 02, 2018:

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

Hari Prasad S from Bangalore on February 02, 2018:

Very comprehensive and useful hub. Bookmarking this hub linda.

- hari

Linda Crampton (author) from British Columbia, Canada on February 02, 2018:

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 from the beautiful south on February 02, 2018:

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.