Institute of Clinical Medicine, University of Oslo, Campus Ahus, Oslo, Norway.
Department of Neurology, Akershus University Hospital, Lørenskog, Norway.
J Neurol. 2018 Jun;265(6):1295-1302. doi: 10.1007/s00415-018-8832-9. Epub 2018 Mar 21.
Increasing female: male ratio in multiple sclerosis (MS) has been assigned to cohort effects, with females in more recent birth cohorts possibly being more exposed or vulnerable to environmental risk factors than males. We collected MS mortality data in Norway from 1951 to 2015 from The Norwegian Cause of Death registry. Age-Period-Cohort analysis was conducted using log-linear Poisson models, including sex interaction terms. MS was registered as the underlying, contributing or direct cause in 6060 deaths. MS associated mortality remained stable with a slight preponderance among males until after 1980, and have since increased preferentially among females. Throughout the study period the mean annual increase was 1.25% for females and 0.3% for males (p < 0.0001). Age-period-cohort analysis revealed limited evidence of cohort effects for the gender differences; the best fitting model only included gender-age and gender-period interaction terms. The period effect evened out for males in the last three decades but increased for females, especially among the oldest age-groups. In conclusion, the increased female: male mortality ratio in MS associated mortality is driven mainly by increased mortality among females in the three last decades, particularly in the older age groups. It is best explained by disproportional period effects, providing evidence of time-varying external factors including improved access to diagnosis among females.
多发性硬化症（MS）中女性与男性比例的增加归因于队列效应，与男性相比，最近出生队列中的女性可能更容易受到环境风险因素的影响或更易受其影响。我们从挪威死因登记处收集了 1951 年至 2015 年的挪威多发性硬化症死亡率数据。采用对数线性泊松模型进行年龄-时期-队列分析，包括性别交互项。MS 被登记为根本、促成或直接死因的有 6060 例死亡。MS 相关死亡率在 1980 年之前一直保持稳定，男性略占优势，此后女性中发病率逐渐增加。在整个研究期间，女性的平均年增长率为 1.25%，男性为 0.3%（p<0.0001）。年龄-时期-队列分析显示，性别差异的队列效应证据有限；最佳拟合模型仅包括性别-年龄和性别-时期交互项。在过去的三十年中，男性的时期效应趋于平稳，但女性的时期效应增加，尤其是在年龄最大的年龄组中。总之，MS 相关死亡率中女性与男性死亡率比值的增加主要是由于最近三十年来女性死亡率的增加，尤其是在年龄较大的年龄组中。这主要是由不断变化的外部因素（包括女性获得诊断的机会增加）的时期效应引起的，这为时间变化的外部因素提供了证据。
