Multiple Sclerosis: Why Are Women Three Times More Affected? Do Sex Hormones Influence the Progression of Multiple Sclerosis, as Observed in Many Autoimmune Diseases?

 This question is particularly relevant given that multiple sclerosis (MS) affects women more frequently than men, especially those of childbearing age. MS impacts the quality of life for female patients, but thanks to research and advances in imaging, the management of the disease is now less delayed than before.

How Does Multiple Sclerosis Start: What Are the Initial Signs, and How Is the Disease Discovered?

The initial symptoms of multiple sclerosis are highly variable depending on the person, the form, and the stage of the disease. MS can initially present as a sudden flare-up, with the abrupt appearance of one or more neurological symptoms (such as double or reduced vision, muscle weakness, balance disorders, reduced mobility, tingling sensations, urinary problems, etc.). If these symptoms are already present, the flare-up worsens them. Extreme fatigue often accompanies the symptoms of MS. The relapsing-remitting form of MS is the most common, accounting for 85% of cases at the onset of the disease. The diagnosis is made by a doctor who identifies lesions through the symptoms presented by the patient.

MS in Young Women: Why Are They More Frequently Affected, and At What Age?

Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system. It most often affects young adults and is the leading cause of severe non-traumatic disability among people in their thirties. In France, about 110,000 people suffer from multiple sclerosis. The disease is much more common in women, with a ratio of about one man for every three women. However, some forms of MS affect men and women equally.

According to Inserm, symptoms typically appear around the age of 30. Due to its potential progression and the absence of a curative treatment, MS is the leading cause of severe non-traumatic disability in young adults.

Is There a Link Between MS and the Role of Sex Hormones?

There appears to be a relationship between MS and the role of sex hormones. Various studies on estrogen, progesterone, and testosterone have shown that these sex hormones have a crucial neurotrophic and immunomodulatory effect on the central nervous system. The increase in the secretion of these hormones and natural corticosteroids during pregnancy explains the significant reduction in flare-ups for patients in the third trimester of pregnancy. Conversely, the drop in sex hormones after pregnancy explains the recurrence of flare-ups. More recently, scientists have shown that even though male hormones— androgens—are present at very low levels in women, their presence is necessary for the regeneration of the myelin sheath, which is destroyed in multiple sclerosis.

Elisabeth Traiffort, a researcher at Inserm within unit U1195 "Diseases and Hormones of the Nervous System" (Inserm/University of Paris-Saclay), confirms: "Our data suggest the use of appropriate doses of androgens in women with multiple sclerosis and the need to consider the patient's sex in the therapeutic approach to this pathology and possibly other pathologies involving myelin destruction in the central nervous system."

Research on the potential benefits of using sex hormones to prevent flare-ups is ongoing.

Are Multiple Sclerosis and Contraception Compatible?

Contraception is not contraindicated for women with multiple sclerosis. Women of childbearing age who are on long-term treatment for the disease are even required to use effective contraception. This is because taking immunosuppressants and, to a lesser extent, immunomodulators poses risks to embryo and fetal development. Scientific studies also agree that oral contraception does not affect disease progression.

MS and the Desire for Children

Multiple sclerosis does not impact the fertility of affected women and does not pose a risk to pregnancy. However, it is advisable to take certain precautions before conceiving:

• Discussing pregnancy plans with a neurologist allows the pregnancy to be timed during a period when the disease is less active.
• A delay of 3 to 6 months should be observed between the beginning of a pregnancy and the cessation of certain MS treatments.

Symptoms of MS During Pregnancy

From the 1950s, pregnancy and the postpartum period were no longer considered necessarily harmful to the disease. In the early 2000s, European neurologists formed the EDMUS network to conduct the PRIMS study. This study aimed to determine the impact of pregnancy and the postpartum period on disease progression regarding the frequency of flare-ups and disability progression. It included 254 patients for 269 pregnancies, monitored by 128 neurologists in 12 European countries:

• Patients were followed prospectively for up to 24 months after delivery. The included patients were generally 30 years old, had an average of 6 years of relapsing disease, and did not experience significant daily life interference.
• A decreased flare-up score was observed during pregnancy from the first trimester but was particularly dramatic in the third trimester, where flare-up frequency was reduced by 70% compared to the year before pregnancy.
• However, in the first postpartum trimester, flare-up frequency increased by 70% compared to the year before pregnancy. Flare-up scores then returned to normal levels.
• Over the entire pregnancy year (9 months of pregnancy + 3 months postpartum), the same number of flare-ups occurred as in the year before pregnancy. There was only a chronological shift in the onset of flare-ups.
• Disability progression was not impacted by pregnancy. This rate of progression seemed comparable to what is observed in studies on the natural history of the disease. Obstetric outcomes for both mother and child were comparable to those in a healthy female population. Epidural anesthesia and breastfeeding did not appear to adversely affect disease progression. Based on this study, it is possible to affirm that pregnancy and the postpartum period do not worsen MS; they only cause a chronological shift in flare-ups. Recent research suggests that pregnancy might have a long-term protective effect and could prevent or delay the onset of a progressive phase (with worsening symptoms over time) of the disease in affected women.

What Treatment During Pregnancy?

If flare-ups occur during pregnancy, the woman should consult her neurologist, who will assess the need for treatment. The neurologist may prescribe high-dose corticosteroid infusions, which pose little risk to both mother and child.

Multiple Sclerosis at Menopause

At menopause, women no longer produce sex hormones. This phenomenon generally occurs around the age of 52 but can happen earlier, especially due to certain medical treatments, such as immunosuppressants. It is currently difficult to assess the impact of menopause on the frequency of multiple sclerosis flare-ups. However, it is established that hormone replacement therapy (HRT) is not contraindicated. It is even recommended for women with bothersome menopausal symptoms (hot flashes, etc.) when there are no contraindications such as breast cancer or thrombosis risks. HRT can also improve certain sexual problems (vaginal dryness, pain) that are more common in menopausal women with multiple sclerosis.