Disease Progression Differs More Across MS Type Than Sex of Patients, Study Finds

Marked differences in disease characteristics are observed between male and female patients with multiple sclerosis (MS) but they are more pronounced when comparing patients across clinical subtypes, a new study finds.

The analysis found that although women are more prone to pain, depression, and cognitive impairment in both progressive onset MS and relapsing onset MS, the difference in disease progression was more significant between the two subtypes and should be taken into account for patient treatment.

The study, “Relapsing and progressive MS: the sex-specific perspective,” was published in the journal Therapeutic Advances in Neurological Disorders.

The clinical progression of MS varies from patient to patient and can be broadly classified by its onset. The more common form, accounting for 85% of MS cases, is relapsing onset MS or relapsing-remitting MS (RRMS), which is characterized by acute periods of symptom flare-ups followed by periods of remission. RRMS emerges at around 30 years of age and is 2.7 times more common in women than men.

Accounting for 15% of cases, progressive onset MS is characterized by chronic symptoms that worsen over time. It typically emerges at around 42 years of age, and affects men and women at nearly equal rates.

Researchers sought to analyze variations in disease progression across sexes and MS types by comparing male and female patients among relapsing and progressive onset MS groups.

Patient data were collected from the German MS Society Register. A total of 18,728 patients were included in the study, with 2.6 times as many female patients as male.

Among study participants, the median age at relapsing MS disease onset was 32.1 years for females and 33.2 for males, while progressive MS onset was 43.3 years for females and 42.3 for males. These results indicate, as expected, that disease onset is considerably later in progressive MS.

Interestingly, female patients are only slightly older at the onset of progressive MS and slightly younger at the onset of relapsing MS, compared to males, suggesting that sex alone does not have a significant impact on disease onset. 

Patients, regardless of sex, with progressive MS experienced longer disease duration and higher scores on the expanded disability status scale (EDSS), which quantifies level of disability.

Moreover, progressive MS patients are far more likely to retire early (inability to work due to MS), at rates of 47% for females and 43% for males, compared to relapsing onset MS patients (28% for females and 24% for males). Among patients with relapsing MS, women retire at an earlier age (42.8 vs. 44.2  years old in men) and are more likely to retire early than men.

“Patients with [progressive onset MS] retire at a later age, but after a much shorter period of illness than patients with [relapsing onset MS], and to a greater extent,” the researchers wrote.

The first symptoms experienced vary by disease type and sex of the patient. Although motor impairments are more common in progressive MS, men with relapsing onset MS are more prone to experience motor symptoms first compared to women. In relapsing and progressive MS, women are more likely to experience symptoms in the eyes such as optic nerve inflammation (optic neuritis) and vision loss. 

The difference in initial symptoms is more pronounced across disease types, with women and men with relapsing MS experiencing visual symptoms more than progressive MS patients. Similarly, sensory deficits were more frequent in female patients than males across disease types, but this difference was much less pronounced than between relapsing onset and progressive onset MS.

The team also found that women are more likely to experience fatigue, depression, pain, and cognitive impairment, regardless of disease type, while men experience more sexual dysfunction.

Men with relapsing MS experience spasticity, ataxia, and sexual dysfunction more frequently, while women experience urinary problems. Common MS symptoms such as gait abnormalities, muscle spasms and rigidity, and nerve degeneration as well as less common symptoms, like urination problems, pain, constipation, and speech impairments, were more frequent in patients with progressive onset MS.

Interestingly, disability progression does not vary significantly between men and women within the same MS subtype. By contrast, patients with progressive MS reach a level of disability severe enough to impair daily life at an earlier age than relapsing MS.

“Our analysis shows that the differences in clinical presentation between men and women in MS persist across the different disease courses,” the researchers wrote. “The differences over the course of the disease are greater than the differences within the course of the disease between the sexes.”

According to the team, “physicians should be aware of these differences and take appropriate measures (e.g. optimization of pain therapy, neuropsychological care, measures to promote employment).” 

The researchers noted that their study is limited by the use of non-systematically collected registry data and the variations in methods of diagnosing neuropsychological symptoms.