Sex-Related Differences in the Phenotype and Course of Inflammatory Bowel Disease: SEXEII Study of ENEIDA

Abstract

Background & Aims: The impact of patient sex on the presentation of inflammatory bowel disease (IBD) has been poorly evaluated. Our aims were to assess potential disparities in IBD phenotype and progression between sexes. Methods: We performed an observational multicenter study that included patients with Crohn's disease (CD) or ulcerative colitis from the Spanish Estudio Nacional en Enfermedad Inflamatoria intestinal sobre Determinantes genéticos y Ambientales registry. Data extraction was conducted in July 2021. Results: A total of 51,595 patients with IBD were included, 52% were males and 25,947 had CD. The median follow-up period after diagnosis was 9 years in males and 10 years in females. In CD, female sex was an independent risk factor for medium disease onset (age, 17–40 y) (relative risk ratio, 1.45; 95% CI, 1.31–1.62), later disease onset (age, >40 y) (relative risk ratio, 1.55; 95% CI, 1.38–1.73), exclusive colonic involvement (odds ratio, 1.24; 95% CI, 1.14–1.34), inflammatory behavior (odds ratio, 1.14; 95% CI, 1.07–1.21), and extraintestinal manifestations (odds ratio, 1.48; 95% CI, 1.38–1.59). However, female sex was a protective factor for upper gastrointestinal involvement (odds ratio, 0.84; 95% CI, 0.79–0.90), penetrating behavior (odds ratio, 0.76; 95% CI, 0.70–0.82), perianal disease (odds ratio, 0.77; 95% CI, 0.71–0.82), and complications (odds ratio, 0.73; 95% CI, 0.66–0.80). In ulcerative colitis, female sex was an independent risk factor for extraintestinal manifestations (odds ratio, 1.48; 95% CI, 1.26–1.61). However, female sex was an independent protective factor for disease onset from age 40 onward (relative risk ratio, 0.76; 95% CI, 0.66–0.87), left-sided colonic involvement (relative risk ratio, 0.72; 95% CI, 0.67–0.78), extensive colonic involvement (relative risk ratio, 0.59; 95% CI, 0.55–0.64), and abdominal surgery (odds ratio, 0.78; 95% CI, 0.69–0.88). Conclusions: There is sexual dimorphism in IBD. The patient's sex should be taken into account in the clinical management of the disease.