Effect of puberty on multiple sclerosis risk and course

Waubant, Emmanuelle

doi:10.1177/1352458517737393

Cited by 11 publications

(9 citation statements)

References 14 publications

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“…In paediatric MS, the prepubertal onset is extremely rare with a sex ratio of 1:1 6. However, after puberty, the incidence rises dramatically with a female preponderance, suggesting that key immune changes occur during or after puberty under the influence of sex hormones 5…”

Section: Discussionmentioning

confidence: 99%

“…Epidemiological studies have shown that, after puberty, the incidence and prevalence of MS are significantly higher in women compared with men 5. In addition, female patients also experience a more active disease (higher relapse rate and higher number of active lesions at MRI), suggesting that sex-specific differences in the immune-pathophysiology of the disease may contribute to a more prominent inflammatory disease in female patients with MS already from adolescence 5–9…”

Section: Introductionmentioning

confidence: 99%

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Choroid plexus enlargement in paediatric multiple sclerosis: clinical relevance and effect of sex

Margoni

Gueye

Meani

et al. 2022

J Neurol Neurosurg Psychiatry

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BackgroundChoroid plexus (CP) enlargement has been suggested as a reliable marker of neuroinflammation in adult multiple sclerosis (MS). We investigated CP volume in patients with paediatric MS compared with matched healthy controls (HC), possible sex-related effect, and the associations with clinical and structural MRI variables.MethodsBrain 3.0 T dual-echo and three-dimensional (3D) T1-weighted sequences were selected retrospectively from 69 patients with paediatric MS and 23 age-matched and sex-matched HC. CP volume was manually obtained from 3D T1-weighted scans by two expert raters.ResultsCP segmentation was highly reproducible (intraobserver agreement: rater I=0.963, rater II=0.958; interobserver agreement=0.968). Compared with HC, patients with paediatric MS showed higher normalised CP volume (p<0.001). Both female and male patients with paediatric MS showed higher normalised CP volume compared with sex-matched HC (women: p<0.001 and men: p=0.021), with a significant disease×sex interaction (p=0.040). In patients with MS, a higher normalised CP volume was significantly associated with higher brain lesional volume (β=0.252, p=0.017), larger lateral ventricle volume (β=0.470, false discovery rate (FDR)-p<0.001), lower normalised brain volume (β=−0.413, FDR-p=0.002) and lower normalised thalamic volume (β=0.291, FDR-p=0.046). No associations with disease duration, Expanded Disability Status Scale score, normalised cortical and white matter volumes were found (FDR-p≥0.172). A significant effect of the disease in the negative association between normalised volumes of CP and thalami was observed (FDR-p=0.046).ConclusionsCP enlargement occurs in paediatric MS, suggesting its early involvement in the pathophysiology of the disease. The higher CP volume, which is found especially in female patients, supports the hypothesis of sex-related differences occurring already in paediatric MS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Choroid plexus enlargement in paediatric multiple sclerosis: clinical relevance and effect of sex

Margoni

Gueye

Meani

et al. 2022

J Neurol Neurosurg Psychiatry

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“…Menarche represents the end of puberty and is regulated by genetic and several environmental factors (BMI, diet, and exercise). 15,16 It has been hypothesized that early menarche or earlier sexual maturation will involve more prolonged exposure to sexual hormones, which might be related to an increased risk of MS. A Canadian study reported an increased risk of MS in women with a younger age at menarche—menarche in controls occurred at 12.6 years compared to 12.4 years in patients with MS ( p = 0.00017)—but did not find any association between age at menarche and age at MS onset. 9 Our study did not include controls and cannot address this specific question; however, we did not find a relationship between age at puberty and age at MS onset or long-term clinical course of the disease (risk of second attack, McDonald MS, risk of disability) even after controlling for age at CIS, topography, OB, MRI, treatment, and body size self-perception at menarche.…”

Section: Discussionmentioning

confidence: 99%

Menarche, pregnancies, and breastfeeding do not modify long-term prognosis in multiple sclerosis

et al. 2019

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ObjectiveTo investigate the effect of menarche, pregnancies, and breastfeeding on the risk of developing multiple sclerosis (MS) and disability accrual using a multivariate approach based on a large prospective cohort of patients with clinically isolated syndrome (CIS).MethodsA cross-sectional survey of the reproductive information of female participants in a CIS cohort was performed. We examined the relationship of age at menarche with the risk of clinically definite MS (CDMS), McDonald 2010 MS, and Expanded Disability Status Scale (EDSS) 3.0 and 6.0. The effect of pregnancy (before and after CIS) and breastfeeding in the risk of CDMS, McDonald 2010 MS, and EDSS 3.0 was also examined. Univariate and multivariate analyses were performed and findings were confirmed using sensitivity analyses and a propensity score model.ResultsThe data of 501 female participants were collected. Age at menarche did not correlate with age at CIS and was not associated with the risk of CDMS or EDSS 3.0 or 6.0. Pregnancy before CIS was protective for CDMS in the univariate analysis, but the effect was lost in the multivariate model and did not modify the risk of EDSS 3.0. Pregnancy after CIS was protective for both outcomes in univariate and multivariate analyses when pregnancy was considered a baseline variable, but the protective effect disappeared when analyzed as a time-dependent event. Breastfeeding did not modify the risk for the 3 outcomes.ConclusionsThese results demonstrate that menarche, pregnancies, and breastfeeding did not substantially modify the risk of CDMS or disability accrual using a multivariable and time-dependent approach.

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“…For each variant, effect estimates on both childhood and adult obesity measures are included in a weighted multivariable regression model. 16 In addition, given the proposed role for pubertal timing in MS and its correlation with body weight status, 34,35 we repeated the analysis with age at puberty as a third exposure (along with childhood and adult obesity measures) using genetic determinants of age at menarche as previously reported (n=329,245). 35,36 The genetic architecture of pubertal timing across both sexes is highly correlated (rg=0.75; p=1.2x10 -79 ), allowing these variants to provide insight into pubertal timing in males as well.…”

Section: Multivariable Mendelian Randomizationmentioning

confidence: 99%

Childhood obesity and multiple sclerosis: A Mendelian randomization study

et al. 2021

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Background: Higher childhood body mass index (BMI) has been associated with an increased risk of multiple sclerosis (MS). Objective: To evaluate whether childhood BMI has a causal influence on MS, and whether this putative effect is independent from early adult obesity and pubertal timing. Methods: We performed Mendelian randomization (MR) using summary genetic data on 14,802 MS cases and 26,703 controls. Large-scale genome-wide association studies provided estimates for BMI in childhood ( n = 47,541) and adulthood ( n = 322,154). In multivariable MR, we examined the direct effects of each timepoint and further adjusted for age at puberty. Findings were replicated using the UK Biobank ( n = 453,169). Results: Higher genetically predicted childhood BMI was associated with increased odds of MS (odds ratio (OR) = 1.26/SD BMI increase, 95% confidence interval (CI): 1.07–1.50). However, there was little evidence of a direct effect after adjusting for adult BMI (OR = 1.03, 95% CI: 0.70–1.53). Conversely, the effect of adult BMI persisted independent of childhood BMI (OR = 1.43; 95% CI: 1.01–2.03). The addition of age at puberty did not alter the findings. UK Biobank analyses showed consistent results. Sensitivity analyses provided no evidence of pleiotropy. Conclusion: Genetic evidence supports an association between childhood obesity and MS susceptibility, mediated by persistence of obesity into early adulthood but independent of pubertal timing.

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Effect of puberty on multiple sclerosis risk and course

Cited by 11 publications

References 14 publications

Choroid plexus enlargement in paediatric multiple sclerosis: clinical relevance and effect of sex

Choroid plexus enlargement in paediatric multiple sclerosis: clinical relevance and effect of sex

Menarche, pregnancies, and breastfeeding do not modify long-term prognosis in multiple sclerosis

Childhood obesity and multiple sclerosis: A Mendelian randomization study

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