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. 2012;7(10):e48078.
doi: 10.1371/journal.pone.0048078. Epub 2012 Oct 25.

Geographical variations in sex ratio trends over time in multiple sclerosis

Maria Trojano  1 , Guglielmo Lucchese, Giusi Graziano, Bruce V Taylor, Steve Simpson Jr, Vito Lepore, Francois Grand'maison, Pierre Duquette, Guillermo Izquierdo, Pierre Grammond, Maria Pia Amato, Roberto Bergamaschi, Giorgio Giuliani, Cavit Boz, Raymond Hupperts, Vincent Van Pesch, Jeannette Lechner-Scott, Edgardo Cristiano, Marcela Fiol, Celia Oreja-Guevara, Maria Laura Saladino, Freek Verheul, Mark Slee, Damiano Paolicelli, Carla Tortorella, Mariangela D'Onghia, Pietro Iaffaldano, Vita Direnzo, Helmut Butzkueven; MSBase Study Group and the New Zealand MS Prevalence Study Group
Collaborators, Affiliations

Geographical variations in sex ratio trends over time in multiple sclerosis

Maria Trojano et al. PLoS One. 2012.

Abstract

Background: A female/male (F/M) ratio increase over time in multiple sclerosis (MS) patients was demonstrated in many countries around the world. So far, a direct comparison of sex ratio time-trends among MS populations from different geographical areas was not carried out.

Objective: In this paper we assessed and compared sex ratio trends, over a 60-year span, in MS populations belonging to different latitudinal areas.

Methods: Data of a cohort of 15,996 (F = 11,290; M = 4,706) definite MS with birth years ranging from 1930 to 1989 were extracted from the international MSBase registry and the New Zealand MS database. Gender ratios were calculated by six decades based on year of birth and were adjusted for the F/M born-alive ratio derived from the respective national registries of births.

Results: Adjusted sex ratios showed a significant increase from the first to the last decade in the whole MS sample (from 2.35 to 2.73; p = 0.03) and in the subgroups belonging to the areas between 83° N and 45° N (from 1.93 to 4.55; p<0.0001) and between 45° N to 35° N (from 1.46 to 2.30; p<0.05) latitude, while a sex ratio stability over time was found in the subgroup from areas between 12° S and 55° S latitude. The sex ratio increase mainly affected relapsing-remitting (RR) MS.

Conclusions: Our results confirm a general sex ratio increase over time in RRMS and also demonstrate a latitudinal gradient of this increase. These findings add useful information for planning case-control studies aimed to explore sex-related factors responsible for MS development.

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Conflict of interest statement

Competing Interests: MT received honoraria for consultancy and/or speaking from Biogen Idec, Sanofi-Aventis, Merck-Serono, Novartis and Bayer-Schering and reseach grants from Merck-Serono, Biogen Idec, Sanofi-Aventis and Novartis. GM is a Novartis Advisory Board member and receives speakers’ bureau from Teva and research grants from Genzyme, Novartis, Biogen Idec, Teva, ONO, UBC and EMD Serono. PD has sat on Advisory Boards for Teva, EMD Serono, Biogen Idec, Novartis and Bayer Schering, he receives research grants from Biogen Idec, CIHR and MS Society of Canada. GI received honoraria for consultation from Biogen Idec, Merck Serono, Teva, Bayer, Novartis and Sanofi Aventis. PG has received research grants from Sanofi Aventis and Biogen Idec, he has also received honoraria for advisory counsels and teaching programs with Novartis Pharma, Teva, EMD Serono, Biogen Idec and Bayer. RB has received research grants from Bayer Schering, Biogen Dompe, Novartis, Sanofi Aventis and Merck Serono; honoraria for speaking from Bayer Scering, Sanofi Aventis and Merck Serono; travel grants from Bayer Schering, Biogen Dompe, Sanofi Aventis, Merck Serono and Novartis. RH has received honoraria as consultant on a Merck Serono advisory board, and as consultant for Biogen Idec. He has received grants from Merck Serono and Biogen Idec. VVP serves on an advisory board for Biogen Idec. He has received travel grants from Biogen Idec, Bayer Schering, Sanofi Aventis, Merck Serono and Novartis Pharma and speaking honoraria from Biogen Idec. JLS’s institution receives non directed funding as well as honoraria for presentations and membership of advisory boards from Sanofi Aventis, Biogen Idec, Bayer Health Care, Merck Serono and Novartis Australia. COG has received honoraria as consultant on scientific advisory boards from Biogen Idec, Bayer Schering, Merck Serono, Teva and Novartis, she has also participated in clinical trials and other research projects promoted by Biogen Idec, GSK, Teva and Novartis. FV serves on advisory Board for Merck Serono. MSlee has participared in advisory boards for Sanofi Aventis, Merck Serono, Biogen Idec, Novartis Pharma and Bayer Schering. HB has served on scientific advisory boards for Biogen Idec, Novartis, and Sanofi Aventis and has received conference travel support from Novartis, Biogen Idec and Sanofi Aventis. He serves on steering committees for trials conducted by Merck Serono, Biogen and Novartis, and he has received research support from Merck Serono, Novartis and Biogen Idec in his capacity as honorary chair of the MSBase Foundation. He is on the editorial board of Multiple Sclerosis International. Co-author Celia Oreja-Guevara is a PLoS ONE Editorial Board member. All other Authors declare that they have nothing to disclose. This does not alter the authors’ adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Plot of gender ratio by six birth decades in MS patients stratified by Latitude.
p-value for trend *0.0425; **<0.0001.
Figure 2
Figure 2. Plot of gender ratio by six birth decades in MS patients from Northern and Southern Europe.
p-value for trend *0.0426; **<0.0004.
Figure 3
Figure 3. Plot of gender ratio by four birth decades in MS patients stratified by Latitude (A) and from Northern and Southern Europe (B).
p-value for trend *<0.001.
Figure 4
Figure 4. Plot of gender ratio by six birth decades in MS patients from Northern Latitude Area (A) and Northern Europe (B) stratified by Relapsing Remitting (RR) and Primary Progressive (PP) disease course.
p-value for trend *<0.001.
See this image and copyright information in PMC

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