Gender Differences in MG Onset Shift After Age 40, Study Reports

Myasthenia gravis (MG) onset is more common in men ages 40-70 than in women in the same age range. There are also gender differences in the incidence of MG-related manifestations and comorbid autoimmune diseases, according to a new study.

This finding is in contrast to the higher prevalence of early-onset MG in women.

The study, “A tri-modal distribution of age-of-onset in female patients with myasthenia gravis is associated with the gender-related clinical differences,” appeared in the International Journal of Neuroscience.

Age of MG onset is known to vary between genders. While early-onset MG (EOMG) is more prevalent in women, late-onset MG (LOMG) is more common in men.

Besides a higher prevalence among women, EOMG has also been associated with higher rates of hyperplasia (enlargement) but lower rates of tumor (thymoma) in the thymus, and higher levels of auto-antibodies against the acetylcholine receptor (anti-AChR) than LOMG. Also, women with EOMG have shown high incidence of comorbidity with other autoimmune diseases.

The researchers, from Israel, had previously divided women with MG into three groups according to age of onset — up to age 40 (EOMG), ages 40-70 (intermediate-onset, IOMG) and older than 70 (LOMG).

Aiming to explore whether the different groups of women with MG presented clinical differences, the investigators compared their clinical, laboratory, and thymus pathology data as well as in relation to male patients. The files from 127 patients — 62 women and 65 men — were retrospectively analyzed. The researchers included only patients who had a minimum two years of disease duration to avoid misclassification between generalized and ocular MG.

The results showed that the average age of MG onset differed significantly between women and men — 51.9 years in women and 61.3 in men. As previously shown, women could be separated into three groups, while men showed an increasing prevalence until age 75, a finding that could be related to a decline in testosterone levels, according to the authors. The youngest age of onset was 15 years.

EOMG was more common among women (23 patients, 37.1%) compared to men (nine patients, 13.9%). Conversely, IOMG was more frequent in men (34, 52.3%) than in women (20, 32.3%). The prevalence of LOMG was similar in men (22, 33.8%) and women (19, 30.6%). Men ages 46-55 had higher MG incidence than women.

Ocular MG was observed in five EOMS patients (15.6%), 18 with IOMG (33.3%), and nine with LOMG (21.6%). The higher incidence in IOMG was mostly driven by 13 men (38.2%).

A total of 100 patients (78.7%) had anti-AChR antibodies — 21 with EOMG (65.6%), 42 with IOMG (77.8%), and 37 with LOMG (90.2%). Patients with LOMG and men had higher rates of anti-AChR antibodies compared to those with EOMG and to women, respectively. Also, significantly more men with IOMG had anti-AChR antibodies than women in this subgroup (88.2% vs.60%).

Anti-muscle-specific kinase antibodies were detected in only three women (4.8%) — two with EOMG and one with LOMG.

The data further showed that 21 patients (16.5%) had hyperplasia of the thymus — 11 with EOMG (34.4%), seven with IOMG (13%), and three with LOMG (7.3%). The incidence of thymic hyperplasia was significantly higher in EOMG than in IOMG and LOMG.

Women had higher rates than men (27.4% vs. 6.2%), a difference driven by the IOMG subgroup, as it included six women (30.0%) but only one man (2.9%). Women with LOMG had the highest rate of hyperplasia of the thymus (43.5%). Also, women with EOMG or IOMG had higher incidence of this manifestation than those with LOMG.

Eight patients had thymoma (6.3%) — six with EOMG (18.7%) and two with IOMG (3.7%). Men with EOMG showed higher incidence of thymoma (three patients, 33.3%) than those with IOMG (one, 2.9%) or LOMG (0%).

Fifteen patients (12 women) also had other autoimmune disease, including seven with Hashimoto’s thyroiditis, three with Graves’ disease, two with systemic lupus erythematosus, two with polymyositis, and one with rheumatoid arthritis.

A comorbid autoimmune disease was found in two women with EOMG (8.7%), five women (25.0%) and one man (2.9%) with IOMG, and five women (26.3%) and two men (9.1%) with LOMG.

Overall, “[women] with IOMG were responsible for the gender-related differences in several major clinical features of MG,” the scientists wrote. “Our current study results demonstrated that significantly more males with IOMG were positive to anti-AChR than females with IOMG, and that these increased rates among males with IOMG [were] not related to thymic pathologies.”

The team also noted that the “opposite trend of MG incidence in ages between 40-70 years is unique to MG,” and warrants further study.