Studying Multiple Sclerosis in Males May Help Both Genders
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), 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
- speech difficulties
- difficulty with vision due to inflammation around the optic nerve
- 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
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.
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.
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.
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
Questions & Answers
© 2018 Linda Crampton