Sex ratio of multiple sclerosis in Canada: a longitudinal study.
Orton SM., Herrera BM., Yee IM., Valdar W., Ramagopalan SV., Sadovnick AD., Ebers GC., Canadian Collaborative Study Group None.
BACKGROUND: Incidence of multiple sclerosis is thought to be increasing, but this notion has been difficult to substantiate. In a longitudinal population-based dataset of patients with multiple sclerosis obtained over more than three decades, we did not show a difference in time to diagnosis by sex. We reasoned that if a sex-specific change in incidence was occurring, the female to male sex ratio would serve as a surrogate of incidence change. METHODS: Since environmental risk factors seem to act early in life, we calculated sex ratios by birth year in 27 074 Canadian patients with multiple sclerosis identified as part of a longitudinal population-based dataset. FINDINGS: The female to male sex ratio by year of birth has been increasing for at least 50 years and now exceeds 3.2:1 in Canada. Year of birth was a significant predictor for sex ratio (p<0.0001, chi(2)=124.4; rank correlation r=0.84). INTERPRETATION: The substantial increase in the female to male sex ratio in Canada seems to result from a disproportional increase in incidence of multiple sclerosis in women. This rapid change must have environmental origins even if it is associated with a gene-environment interaction, and implies that a large proportion of multiple sclerosis cases may be preventable in situ. Although the reasons why incidence of the disease is increasing are unknown, there are major implications for health-care provision because lifetime costs of multiple sclerosis exceed pound1 million per case in the UK.