Inflammatory bowel diseases show a gender bias, as reported for several other immune-mediated diseases. Female-specific differences influence disease presentation and activity, leading to a different progression between males and females. Women show a genetic predisposition to develop inflammatory bowel disease related to the X chromosome. Female hormone fluctuation influences gastrointestinal symptoms, pain perception, and the state of active disease at the time of conception could negatively affect the pregnancy. Women with inflammatory bowel disease report a worse quality of life, higher psychological distress, and reduced sexual activity than male patients.
Study | Study Population | Outcome | |||||||||||||||||||||||
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Wagtmans et al., 2001 [10]. | Wagtmans et al., 2001 [11]. | 541 CD patients (266 males, 275 females). | No difference in mean lag time between onset of symptoms and diagnosis, and no differences in presenting symptoms and initial localization of lesions. Similar percentage of patients who underwent an abdominal operation (81% vs. 77%). No difference in mean lag-time between onset of symptoms and first bowel resection. Lag-time between bowel resection and recurrence of disease shorter in women than in men (4.8 yr vs. 6.5 yr), ileocecal resections more frequent in female than male patients (44% and 32%, respectively). Female patients have significantly more often relatives in the first or second degree affected by CD than male (15% vs. 8.3%). | ||||||||||||||||||||||
Severs et al., 2018 [3]. | Severs et al., 2018 [18]. | Dutch IBD Biobank study: 2118 CD and 1269 UC patients. COIN study: 1139 CD and 1213 UC patients. |
Early onset CD (<16 years) more frequent in males than in females (20% vs. 12%). Male CDs have more often ileal disease (28% vs. 20%) and underwent more often small bowel and ileocecal resection. Male CDs used prednisone more often and suffered more often from osteopenia. IBD-specific healthcare costs did not differ between male and female IBD patients. Extraintestinal manifestations more frequent in female IBD patients than male. | ||||||||||||||||||||||
Mazor et al., 2011 [11]. | Mazor et al., 2011 [33]. | 146 patients with CD (76 females, 70 males) treated during a 10-year period. | The only independent risk factors associated with developing a complication were smoking and male gender. There was no association between developing complications and the presence of selected SNPs ( | p | = 0.07 for tyrosine residue on both alleles in NCF4 SNP rs4821544 and | p | = 0.06 for a guanine residue on both alleles in ATG16L SNP rs2241880). Multivariate analysis using a backwards logistic regression model left only male gender as an independent statistically significant association with complicated disease (OR 2.6017, 95% CI: 1.17 to 5.75). The median time to developing a complication was 4 years, and the most common complication was the need for surgical intervention (54%). | ||||||||||||||||||
Blumenstein et al., 2011 [4]. | Blumenstein et al., 2011 [34]. | 986 patients with IBD (515 CD, 471 UC—537 females, 449 males). | Extended disease duration in women, no significant gender-related differences in demographic and clinical characteristics observed. Men showed a significantly higher remission rate than women ( | p | = 0.025), while women received significantly less immunosuppressive medication compared to men ( | p | = 0.011). Treatment with immunosuppressants was not different in women with child-bearing potential compared to menopausal women. | ||||||||||||||||||
Bokemeyer et al., 2013 [12]. | Bokemeyer et al., 2013 [35]. | 1032 patients with IBD (511 CD, 519 UC, 2 IBD-U). | About one third of the IBD patients were not in clinical remission (CDAI ≥ 150/CAI > 4) (CD: 45%; UC: 27%), although high rates of immunosuppressive drugs (CD: 47%; UC 26%) were administered. This study shows a large burden of active disease associated with an unexpectedly high (co)morbidity and high psychosocial impairments, indicating a reduced health state in IBD patients. | ||||||||||||||||||||||
Greuter et al., 2018 [13]. | Greuter et al., 2018 [36]. | 1638 CD patients (107 presented with upper GI tract involvement at the time of diagnosis, 214 at any time). | In a multivariate logistic regression model, male sex, and diagnosis between 2009 and 2016 (versus before 1995) were independent predictors for presence of upper GI tract involvement at CD diagnosis (odds ratio [OR] 1.600, | p | = 0.021 and OR 2.686, | p | < 0.001, respectively), whereas adult age was a negative predictor (OR 0.388, | p | = 0.001). Patients with upper GI tract involvement showed a disease course similar to control patients (hazard ratio [HR] for any complications 0.887, (95% confidence interval [CI] 0.409–1.920), and a trend towards occurrence of fewer intestinal fistulas (log-rank test | p | = 0.054). | ||||||||||||||
Jussila et al., 2014 [14]. | Jussila et al., 2014 [38]. | 21,964 patients with IBD (5315 CD, 16,649 UC). | Overall mortality was increased among patients with CD (standardized mortality ratio (SMR) 1.33, 95% confidence interval 1.21–1.46) and UC (1.10, 1.05–1.15). SMR was significantly increased for gastrointestinal causes in CD (6.53, 4.91–8.52) and UC (2.81, 2.32–3.34). Patients with UC were found also to have increased SMR from pulmonary (1.24, 1.02–1.46) and cardiovascular disease (1.14, 1.06–1.22) and cancers of the colon (1.90, 1.38–2.55), rectum (1.79, 1.14–2.69) and biliary tract (5.65, 3.54–8.54), whereas SMR from alcohol-related deaths was decreased (0.54, 0.39–0.71). Patients with CD had a significantly increased SMR for pulmonary diseases (2.01, 1.39–2.80), infections (4.27, 2.13–7.63) and cancers of the biliary tract (4.51, 1.23–11.5) and lymphoid and hematopoietic tissue (2.95, 1.85–4.45). | ||||||||||||||||||||||
Peyrin-Biroulet et al., 2013 [5]. | Peyrin-Biroulet et al., 2013 [39]. | 310 patients with CD (154 females, 156 males). | The cumulative probability of major abdominal surgery was 38, 48, and 58% at 5, 10, and 20 years after diagnosis, respectively. Baseline factors significantly associated with time to major abdominal surgery were: ileocolonic (hazards ratios (HRs) 3.3), small bowel (HR, 3.4), and upper gastrointestinal (HR, 4.0) extent, relative to colonic alone; current cigarette smoking (HR, 1.7), male gender (HR, 1.6), penetrating disease behavior (HR, 2.7), and early corticosteroid use (HR = 1.6). Major abdominal surgery rates remained stable, with 5-year cumulative probabilities in 1970–1974 and 2000–2004 of 37.5 and 35.1%, respectively. The cumulative probability of major abdominal surgery in this population-based cohort of Crohn’s disease approached 60% after 20 years of disease, and many patients required second or third surgeries. Non-colonic disease extent, current smoking, male gender, penetrating disease behavior, and early steroid use were significantly associated with major abdominal surgery. | ||||||||||||||||||||||
Walldorf et al., 2013 [15]. | Walldorf et al., 2013 [40]. | 293 patients with IBD (195 CD, 98 UC—110 males, 183 females). | DEXA-scan was performed in 174 patients (59 males, 115 females). Bone mineral density (BMD) was impaired in 38.5% of these patients. Male patients were diagnosed more often with osteopenia or osteoporosis than females (55.9% vs. 29.6%, | p | = 0.03) and had a risk of bone disease comparable to postmenopausal women. Additionally, duration of corticosteroid treatment and IBD were identified as risk factors for osteoporosis. Follow up DEXA-scan demonstrated an overall deterioration of BMD in patients with normal baseline results. | ||||||||||||||||||||
Sigurdsson et al., 2022 [16]. | Sigurdsson et al., 2022 [42]. | 49 young adult male patients with childhood-onset IBD and 245 matched controls. | The group of young adult patients had, in comparison with the controls, significantly smaller median cortical area (126.1 mm | 2 | vs 151.1 mm | 2 | , | p | < 0.001), lower median total vBMD (296.7 mg/cm | 3 | vs. 336.7 mg/cm | 3 | , | p | < 0.001), and lower median cortical vBMD (854.4 mg/cm | 3 | vs. 878.5 mg/cm | 3 | , | p | < 0.001). Furthermore, the patients compared with the controls had lower median trabecular volume fraction (16.8% vs. 18.2%, | p | < 0.001) and thinner median trabeculae (0.084 mm vs. 0.089 mm, | p | < 0.001). The differences between the patients with IBD and controls persisted in multivariable analyses that included adjustments for SMI and physical exercise. |
Heath et al., 2022 [7]. | Heath et al., 2022 [50]. | 1015 patients; 656 CD (59.0% women) and 359 UC (47.9% women). | Women were more likely prescribed budesonide than men (23.6% vs. 13.4%; | p | < 0.0001), more men were exposed to prednisone for IBD management (73.5% vs. 67.4%; | p | = 0.04). Immunomodulator use was higher in men with CD versus women (86.6% vs. 78.3%; | p | = 0.008) and of those exposed, women more commonly experienced ADRs (29.5% vs. 21.2%; | p | = 0.01). Though no sex-related difference was identified, age was a predictor of biologic exposure in women with CD and men with UC, with those > 55 being less likely to receive biologics. |
Study | Study Population | Outcome | |||||||
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Nurmi et al., 2013 [53]. | Nurmi et al., 2013 [97]. | 556 patients with IBD (292 females, 264 males). | Women had seen doctors more often than men ( | p | < 0.001). Women were absent from work more frequently than men ( | p | = 0.01). The amount of physician visits, work absenteeism, and a higher amount of undergone procedures were related to impaired HRQoL ( | p | < 0.001 on all accounts). |
Graff et al., 2006 [54]. | Graff et al., 2006 [98]. | 388 patients with IBD. | Multivariate regression showed that those with active disease had higher levels of distress, health anxiety, and perceived stress, lower social support, well-being and mastery, and poorer disease-specific QOL, relative to those with inactive disease. Participants with either active or inactive disease had suboptimal general QOL. | ||||||
Hauser et al., 2011 [55]. | Hauser et al., 2011 [99]. | 112 IBD patients (51 CD, 61 UC—50 females, 62 males). | Women have expressed significantly lower level of the general HRQoL and more emotional disturbances connected with their disease as well as more frequent bowel symptoms compared with men. | ||||||
Yan et al., 2020 [56]. | Yan et al., 2020 [100]. | 891 IBD patients (522 CD, 363 UC, 6 IBD-U—362 females, 529 males). | Female patients showed a higher tendency to feel that the quality of communication with specialists ( | p | = 0.037) and quality of IBD care ( | p | = 0.019) was less satisfactory than male patients. Female patients with IBD show a larger number of intense concerns, a greater level of psychological disturbance, a higher symptom load, and a poorer QoL than men, resulting in reduced satisfaction ratings. | ||
Pittet et al., 2017 [57]. | Pittet et al., 2017 [101]. | 1102 IBD patients (596 CD, 475 UC, 31 IBD-U—598 females, 504 males). | Women had significantly higher overall levels of concern than did men (sum score: 47.5 vs. 42.8, respectively, | p | < 0.001). Women at home or unemployed had higher concerns about disease-related constraints and uncertainty ( | p | = 0.004). Patients seem to have important gender-specific concerns related to their illness. | ||
Saraiva et al., 2019 [58]. | Saraiva et al., 2019 [102]. | 105 IBD patients (60 CD, 45 UC—60 females, 45 males). | Female gender and active CD were significantly associated with a severe level of fatigue ( | p | = 0.05 and | p | = 0.04). | ||
Bager et al., 2012 [59]. | Bager et al., 2012 [103]. | 425 IBD patients (251 CD, 174 UC). | Female IBD patients tend to experience more fatigue than males. When comparing the IBD patients with disease activity to the IBD patients in remission, all dimensions of fatigue were statistically significant ( | p | <0.05). Fatigue in IBD is common regardless of anaemia or iron deficiency. Fatigue in IBD is most marked for patients <60 years of age. Fatigue is expressed differently between groups. | ||||
Le Berre et al., 2019 [60]. | Le Berre et al., 2019 [104]. | 1410 IBD patients (875 CD, 496 UC, 39 IBD-U). | Among the disabling symptoms at work, fatigue was the most frequent (41%) followed by diarrhea (25%) and fecal incontinence (18%). IBD has a strong negative impact on working life. While work satisfaction remains high, IBD affects career plans. |