Age at Menarche and Risk of Multiple Sclerosis: Current Progress From Epidemiological Investigations.

Xia Jiang,Tomas Olsson,Lars Alfredsson

doi:10.3389/fimmu.2018.02600

Xia Jiang, Tomas Olsson + Show 1 more

Open Access

https://doi.org/10.3389/fimmu.2018.02600

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Abstract

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disorder of the brain and spinal cord in which focal lymphocytic infiltration leads to the damage of myelin and axons. As a multi-factorial complex trait, both genetic background and environmental factors are involved in MS etiology. The disease is more prevalent among women, and an overall female-to-male sex ratio of around 3 is usually reported. The fact that the female preponderance is only apparent among patients with disease onset after age 12 points toward a role of puberty in MS. A key marker of female pubertal development is menarche, however, evidence from previous epidemiological investigations has been sparse and conflicting: although some studies have linked earlier age at menarche (AAM) to an increased risk of MS, others have found no association or an inverse association. Understanding the effect of AAM in MS could increase our knowledge to the disease etiology, as well as deliver meaningful implication to patients' care by aiding clinical diagnosis. Therefore, we reviewed all the currently available epidemiological studies conducted for AAM and risk of MS in adult human populations. We found evidence supporting a possible favorable role of late AAM on MS risk, but this should be further confirmed by well-designed large-scale epidemiological studies and meta-analysis. Future work may be focused on Mendelian randomization analysis incorporating genetic markers to provide additional evidence of a putative causal relationship between AAM and MS. More work should be conducted for non-European populations to increase generalizability, and among the males to complementary with results from females. Future work may also be conducted focusing on hormonal reproductive factors other than menarche, and their effects in MS prognosis, severity, and drug response.

Highlights

Multiple sclerosis (MS) is primarily an autoimmune inflammatory disorder of the central nervous system (CNS), characterized by the loss of myelin and damage of axons, leading to a variety of neurological deficits [1]
Puberty Timing and Multiple Sclerosis dominated by widespread microglial activation associated with extensive neurodegeneration and accumulated disability
In a recent study conducted by Bove et al which included the major genetic risk factor of MS (HLA-DRB1∗1501), the risk allele carriers showed an earlier age at onset, and each 1-year later age at menarche was associated with later age at onset after adjusting for multiple potential confounders, consistent with previous findings

Summary

INTRODUCTION

Multiple sclerosis (MS) is primarily an autoimmune inflammatory disorder of the central nervous system (CNS), characterized by the loss of myelin and damage of axons, leading to a variety of neurological deficits [1]. In this subgroup a consistent reduction per 1-year increased AAM regarding MS risk was observed (OR = 0.89, 95%CI = 0.70–1.13), indicating that the potential bias due to using self-reported data was minor [17] These results observed in European populations were further corroborated by two case-control studies conducted in Iran. In a recent study conducted by Bove et al which included the major genetic risk factor of MS (HLA-DRB1∗1501), the risk allele carriers showed an earlier age at onset (as expected), and each 1-year later age at menarche was associated with later age at onset after adjusting for multiple potential confounders (increased by 0.63 years, P=0.033), consistent with previous findings.

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