Smoking and Increased Risk of Multiple Sclerosis: Parallel Trends in the Sex Ratio Reinforce the Evidence

Natalia Palacios, Alvaro Alonso, Henrik BrØnnum-Hansen, Alberto Ascherio

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Purpose: Smoking behavior in industrialized nations has changed markedly over the second half of the 20th century, with diverging patterns in male and female smoking rates. We examined whether the female/male incidence of multiple sclerosis (MS) changed concomitantly with smoking, as would be expected if smoking truly increased MS risk. Methods: We identified relevant studies reporting male and female age-specific incidence of MS throughout the world using within-country birth cohorts as units of observation. We then correlated the male/female ratio of MS incidence in each birth cohort with the corresponding male/female ratios in smoking behavior obtained from national statistics. We also examined in depth the within-country trends of smoking and MS in Canada and Denmark, two populations in which statistics on MS are readily available. Results: We show that, on the natural log scale, the gender ratio of MS is correlated with the gender ratio of smoking (r = 0.16; 95% confidence interval [CI]: 0.06, 0.26; p = 0.002). Additionally, we estimated an overall incidence rate ratio of 1.50 (95% CI: 1.17, 2.01) of MS for ever-smokers as compared with never-smokers. The trend in the gender ratio of smoking, however, is driven by a decline in smoking among men, rather than by an increase in women as observed for MS incidence. Conclusions: Our results are consistent with the hypothesis that smoking increases the risk of MS and explains in part the divergence in MS incidence rates in men and women. Some other factor, however, must account for the increasing MS incidence among women.

Original languageEnglish (US)
Pages (from-to)536-542
Number of pages7
JournalAnnals of epidemiology
Issue number7
StatePublished - Jul 2011

Bibliographical note

Funding Information:
The authors would like to thank Leslie Unger for administrative support and Eilis O’Reilly for statistical support. We would also like to thank the anonymous reviewers of this manuscript for their insightful comments. Dr. Ascherio is the recipient of grants from the U.S. National Institutes of Health/National Institute of Neurological Diseases and Stroke for the investigation of Multiple Sclerosis. Natalia Palacios, at the inception of this project was supported by the Training Program in Environmental Epidemiology funded under grant T32 ES07069 and is currently supported under NIH Career Development K01 Award 1K01ES019183-01 . The Danish Multiple Sclerosis Society finances the Danish Multiple Sclerosis Registry. No human subjects were involved in this research.


  • Epidemiology
  • Multiple Sclerosis
  • Sex Ratio
  • Smoking


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