Multiple sclerosis (MS) is an autoimmune disease in which the body’s own immune system attacks the brain and spinal cord (central nervous system, or CNS). According to the National Multiple Sclerosis Society, the latest statistics show that MS is more common in women than men — three times more common, in fact.

Although the cause of MS is unknown, recent studies have shed light on why being female is a risk factor for developing the condition. This connection is likely due to a combination of genetic, sex hormone, and environmental factors.

Genetics and Multiple Sclerosis

One study looked at a specific receptor in both mice and humans called sphingosine-1-phosphate receptor 2 (S1PR2). S1PR2 is particularly plentiful in the CNS. It helps to control the permeability of the blood-brain barrier, or how easy or difficult it is for cells and molecules to pass from the blood to the brain. The blood-brain barrier is controlled by blood vessels around the CNS that keep toxins and diseases from entering the brain. When the blood-brain barrier is permeable — when it allows outside molecules into the CNS — the brain is at risk of damage.

Researchers found that a higher concentration of S1PR2 in the brain leads to a more open brain-blood barrier. They also found higher levels of S1PR2 in both female mice with autoimmune disease and in women with MS. Having more of this receptor may be a key reason why women develop MS more than men.

Another study discussed the role of a separate receptor, peroxisome proliferator-activated receptor (PPAR), in MS. PPAR helps the brain to decrease inflammation, which can calm an overactive immune system.

The study found that key genetic differences in the PPAR genes of men and women may affect the onset of MS. One subtype of PPAR is expressed at higher levels in men, which might allow them to better fight inflammation. Another subtype of PPAR responds strongly to estrogen. Problems with this hormone can create inflammation in women. Both of these PPAR differences may lead to the higher prevalence rates of MS in women.

Sex Hormones and Multiple Sclerosis

Sex hormones can also play a role in developing MS. The adult CNS requires cholesterol. It receives cholesterol from the body and transports it into nerve cells using a molecule called apolipoprotein E (ApoE). From there, the brain can turn cholesterol into the sex hormones that it needs for growth and repair.

Interestingly, studies in mice have found that ApoE deficiency worsens MS in female mice only. This finding suggests that less ApoE can lead to sex hormone disruption in the female brain with MS, as opposed to in the male mice.

Another study found that sex differences in gut bacteria lead to higher testosterone levels in male mice. More testosterone can help protect the male mice from autoimmune disease, but lower testosterone levels in female mice may cause autoimmune disease. The difference in testosterone suggests that sex hormones may contribute to why women develop MS more often.

Environmental Factors and Multiple Sclerosis

The development of MS often involves certain environmental factors. Because women may already have a genetic susceptibility to MS, exposure to these environmental factors may also increase their risk of MS.

Lifestyle risk factors that are associated with MS include:

• Exposure to the Epstein-Barr virus
• Tobacco usage
• High dietary salt intake
• Vitamin D deficiency
• Calcium deficiency
• High saturated fat intake
• Low polyunsaturated fatty acid intake
• Obesity

How Can Women Decrease Their Risk of Developing MS?

Although the genetic risks and environmental factors for MS are complex — and still not completely understood — there are some things that women can do to decrease their risk of developing MS.

Get Enough Vitamin D and Sunlight

Vitamin D is an essential nutrient that the body makes when exposed to direct sunlight. MS risk rises with distance from the equator. In areas farther from the equator, a person may get less sunlight and, therefore, make less vitamin D. Increased vitamin D levels, particularly before age 20, are linked to lower risk of MS later in life.

Quit Smoking

Smoking is a well-documented MS risk factor. It can both increase a person’s MS risk and make their MS symptoms worse.

Eat a Healthy Diet

There is no specific diet linked to an increased risk of MS. However, several dietary factors are related to the immune system and MS. For instance, foods containing vitamins A and D may help regulate the immune system, decreasing MS risk. Higher sodium consumption is linked to worsened MS, and lower intake of polyunsaturated fatty acid is linked with higher MS risk.

Polyphenols are found in plants and can offer protection against many diseases, including diabetes, cardiovascular disease, and cancer. A 2018 survey concluded that a diet high in fruits, vegetables, legumes, and whole grains and low in sugar and red meat was linked with lower prevalence of disability in people with MS.

How Can Women Manage MS Symptoms?

Medications, rehabilitation therapies, or a combination of both can help women with MS manage their symptoms.

Drug Therapies for MS

Medications to help manage MS symptoms, treat relapses, and improve overall quality of life include:

• Injectable medications, such as Avonex (interferon beta 1a), Copaxone (glatiramer acetate), and Rebif (interferon beta 1a)
• Oral medications, such as Aubagio (teriflunomide), Gilenya (fingolimod), and Tecfidera (dimethyl fumarate)
• Infused medications, such as Lemtrada (alemtuzumab), Novantrone (mitoxantrone), and Tysabri (natalizumab)

It is important to note that two medications — Gilenya (fingolimod) and Tysabri (natalizumab) — work either directly or indirectly on S1PR and PPAR receptors, respectively. These drug therapies help to offset genetic sex differences that women with MS may have.

Rehabilitation Therapies for Multiple Sclerosis

Rehabilitation programs can help people with MS preserve or increase their ability to function at home and at work. Therapies recommended for MS include:

• Physical therapy to improve mobility and function
• Occupational therapy to teach techniques and tools to make daily tasks easier
• Vocational rehabilitation to help people stay in their current job or transition to another career
• Speech-language pathology to help people who struggle with speech or swallowing
• Cognitive rehabilitation to help address cognitive difficulties, such as problems with concentration, reasoning, and memory

Talk With Others Who Understand

MyMSTeam is the social network for people with multiple sclerosis and their loved ones. More than 182,000 members come together to ask questions, give advice, and share their stories with others who understand life with multiple sclerosis.

Have something to add to the conversation? Share your thoughts in the comments below, or start a conversation by posting on MyMSTeam.