Sex-Based Differences in Incidence of Inflammatory Bowel Diseases—Pooled Analysis of Population-Based Studies From Western Countries

Shailja C Shah, Hamed Khalili, Corinne Gower-Rousseau, Ola Olen, Eric I Benchimol, Elsebeth Lynge, Kári R Nielsen, Paul Brassard, Maria Vutcovici, Alain Bitton, Charles N Bernstein, Desmond Leddin, Hala Tamim, Tryggvi Stefansson, Edward V Loftus, Bjørn Moum, Whitney Tang, Siew C Ng, Richard Gearry, Brankica Sincic, Sally Bell, Bruce E Sands, Peter L Lakatos, Zsuzsanna Végh, Claudia Ott, Gilaad G Kaplan, Johan Burisch, Jean-Frederic Colombel

Although the incidence of inflammatory bowel diseases (IBD) varies with age, few studies have examined variations between the sexes. We hypothesize that sex hormones are implicated in IBD pathogenesis. We therefore used population data from established cohorts to analyze sex differences in IBD incidence according to age of diagnosis. We identified population-based cohorts of patients with IBD for which incidence and age data were available (17 distinct cohorts from 16 regions of Europe, North America, Australia, and New Zealand). We collected data through December 2016 on 95,605 incident cases of CD (42,831 male and 52,774 female) and 112,004 incident cases of UC (61,672 male and 50,332 female). We pooled incidence rate ratios of Crohn's disease (CD) and ulcerative colitis (UC) for the combined cohort and compared differences according to sex using random-effects meta-analysis. Female patients had a lower risk of CD during childhood, until the age range of 10-14 years (incidence rate ratio, 0.70; 95% CI, 0.53-0.93), but they had a higher risk of CD thereafter, which was statistically significant for the age groups of 25-29 years and older than 35 years. The incidence of UC did not differ significantly for female vs male patients (except for the age group of 5-9 years) until age 45 years; thereafter, men had a significantly higher incidence of UC than women. In a pooled analysis of population-based studies, we found age of IBD onset to vary with sex. Sex hormones might affect pathogenesis of IBD in patients with epigenetic and genetic risk factors. Further studies are needed to investigate mechanisms of sex differences in IBD incidence.