Pediatric-onset MS relapse rates rise with start of menstruation
Hormonal changes at puberty may trigger increased disease activity
The rate of relapses in children with pediatric-onset multiple sclerosis (POMS) tends to increase around the time that menstruation begins, a new study reports.
The findings suggest hormonal changes at the onset of puberty may trigger higher disease activity. The use of oral and infusion disease-modifying therapies (DMT) significantly reduced the risk of relapses, however, indicating more aggressive treatment may be warranted for girls with POMS who are beginning to experience puberty, the researchers said.
The study, “Study of the Association Between Menarche and Disease Course in Pediatric Multiple Sclerosis,” was published in Neurology.
POMS is a rare form of multiple sclerosis (MS) that manifests during childhood. In females, it may develop around the time that menstrual periods start, called menarche, when levels of sex-related hormones such as estrogen change dramatically. Studies in adults suggest these hormones may affect MS disease activity, but there hasn’t been much research into how hormonal changes during menarche might affect disease activity in children with POMS.
Here, scientists analyzed more than 700 girls with POMS. Among them, 73 had their first MS symptoms more than a year before menarche (premenarche), 112 had disease onset within a year before or after menarche (known as the perimenarche or near-to-menarche period), and the remaining 551 didn’t develop POMS until years after getting their first period (postmenarche). In most patients, POMS didn’t develop until two or three years after menarche.
“Menarche is an important biological milestone and, in the setting of MS, may be associated with a change in disease course,” the researchers wrote.
Menarche and MS
A form of relapsing MS, POMS is marked by relapses or flares, where symptoms suddenly worsen, separated by remissions, where they ease or go away entirely. The researchers used statistical analyses to compare the rate of relapses before menarche, after menarche, and in the perimenarche period.
Results showed the annual rate of relapses was significantly higher in the perimenarche period (0.65 relapses per year) than in either the pre- or postmenarche periods (0.43 relapses per year in both). The risk of relapse was also 20%-40% higher in the perimenarche period than the other two periods. Collectively, the data are consistent with the idea that hormone changes around the time of menarche may lead to increased MS activity.
“In this large cohort, pediatric MS onset tended to occur in the [two to three] years after menarche, and there were also higher rates of relapses in individuals who were in or had passed through menarche,” the researchers wrote. “This suggests that hormonal changes occurring during menarche that persist through reproductive years may contribute to the higher relapse rate observed at this transition.”
Patients who were taking DMTs, which reduce MS-driving inflammation, were significantly less likely to have flares.
“As expected, DMT also had a strong association with relapse rate, with significant reductions in relapse rates during periods of oral and infusion DMT use,” wrote the researchers, who said the findings have implications for how POMS is treated, especially for children who develop the disease ahead of menarche. It may be worthwhile to use more powerful medicines in girls with POMS who are starting to undergo puberty. “Potential implications of increased disease activity at puberty include consideration of a change in therapeutic approach around this transition if not already on high-efficacy DMT.”
In an editorial published alongside the study, James Nicholas Brenton, MD, a neurologist at the University of Virginia Health System, said the study “provides further evidence to substantiate the influence of biological hormone changes on the timing of MS clinical onset and risk of relapse.”
“Within the clinic, this research supports consideration of a therapeutic change before menarche for those children previously started on low-efficacy DMTs,” Brenton wrote.
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