On the sex ratio of multiple sclerosis.

An interesting feature that multiple sclerosis (MS) shares with many other immune-mediated diseases is that susceptibility is higher in females than males. 1,2 However, the female-to-male ratio (sex ratio) of MS appears to vary significantly in time and space. A recent meta-analysis of epidemiological studies has shown that the worldwide sex ratio of MS has been substantially increasing over the last century. 3 This increase is particularly clear in large population-based studies from Denmark and Canada. 3,4 In the latter, the sex ratio of MS patients born in the 1930s was lower than 2 and then increased to more than 3 females for each male patient in the latest birth cohort analysed (1976–1980). 4 This intriguing epidemiological phenomenon warrants particular attention since the sex ratio of MS parallels MS incidence and the increasing frequency of MS among females is a key driver for the worldwide increasing prevalence of this devastating disorder. 3 A change occurring within a century is too short a time for a genetic cause, suggesting that environmental factor/s are at work in a sex-specific manner. In this issue of the Multiple Sclerosis Journal, Boström and colleagues investigate sex ratio trends of MS in Sweden using data from several thousand MS patients identified through the National Swedish MS register. Mean sex ratios were 2.62 in the analysis by year of birth (performed between 1931 and 1985) and 2.57 in the analysis by year of onset (performed between 1946 and 2005). In both cases sex ratio figures appeared stable and no increase with time was observed. While these findings appear to be in conflict with those reported by the studies mentioned above, several considerations are warranted. First, comparing results obtained from different countries is not always straightforward and when assessing temporal trends the baseline characteristics need to be taken into account. Boström and colleagues report sex ratios which are consistently above 2 while in both the Canadian and Danish data baseline sex ratios were considerably lower. Perhaps the environmental factor driving the increasing sex ratio of MS in Canada and Denmark was already present at baseline in Sweden. Alternatively this putative agent may be less able to increase female incidence in a population in which the latter is already relatively high. Second, even when baseline levels are similar, inter-country differences should not be too surprising since environmental factors can vary substantially between regions and their effect is likely modified …