Puberty Onset and Pediatric Multiple Sclerosis Activity in Boys

Background: While sex steroid hormones have been shown to have immune effects, it is not know if age or puberty affects disease course in boys with MS. We have previously shown an association in girls with menarche and risk of relapse.

Objectives: To determine the association of age of onset and puberty with relapse rate in boys with pediatric multiple sclerosis (MS).

Methods: Patients from the UCSF Regional Pediatric MS Center were included in this retrospective study. We used the age of disease onset to stratify patients into three groups approximating pubertal stage: age less than 11 years, between 11-14 years, and greater than 14 years, which correspond to pre-, peri-, and post-puberty, respectively. Negative binomial regression was used to determine the association between pubertal status at disease onset with relapse rate.

Results: 58 male pediatric patients with onset of relapsing-remitting MS before 18 years of age participated to the analyses (<11 onset, n=21; 11-14 onset, n=21; >14 onset, n=16). Median follow-up was 3.17 years (IQR 1.42-5.35). 60% of patients identified as White, and 43% as Hispanic. Univariate negative binomial regression models demonstrated 2.4 fold increased relapse rate for boys with disease onset in the peri-puberty age group compared to the post-puberty age group (IRR = 2.43, 95% CI 1.33-4.47, p=0.004). Adjustments for race, ethnicity, and use of disease-modifying therapy did not significantly change these results (IRR = 2.39, 95% CI 1.20-4.79, p = 0.014). There were no difference in relapse rate between the pre-pubertal onset group and post-pubertal onset group.

Conclusions: Pubertal onset of MS may be associated with increased relapses in boys. Further investigation may contribute to a better understanding of the role of pubertal biological effects and MS activity and pathophysiology.