Abstract
Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn’s disease (CD), exhibit clinical heterogeneity, with sex-related differences potentially influencing disease course and prognosis. This study investigates the impact of sex on IBD prognosis in a large cohort. Data were collected from patients diagnosed with IBD at our clinics between July 1993 and April 2025. Demographic, clinical, and treatment variables were analyzed, focusing on sex-based differences in disease onset, disease activity, extraintestinal manifestations (EIMs), treatment escalation, hospitalizations, and surgical interventions. A total of 1774 patients diagnosed with IBD were included in the study. A male predominance (61%) was observed in IBD, with higher male-to-female ratios in both ulcerative colitis (1.6:1) and CD (1.47:1). Female patients presented earlier with IBD (mean age 34.7 vs 37.0 years; P = .001) and had a higher frequency of EIMs, particularly peripheral arthritis and erythema nodosum (P < .001). No significant sex differences were observed in disease severity, hospitalizations, or need for treatment escalation. However, female patients with CD demonstrated higher disease activity at baseline, as measured by the Crohn’s disease activity index. Both sexes exhibited similar rates of biologic therapy use, the number of biologic therapies, hospitalizations, and major surgeries. Despite the male predominance in IBD prevalence, sex-related differences in clinical outcomes were minimal, with both sexes experiencing comparable disease activity, treatment escalation, and need for surgery. However, female patients exhibited a higher frequency of EIMs, highlighting the importance of a sex-based approach in clinical management.
Keywords: Crohn’s disease, inflammatory bowel disease, prognosis, sex, ulcerative colitis
1. Introduction
Inflammatory bowel diseases (IBD), which comprise 2 main subtypes, ulcerative colitis (UC) and Crohn’s disease (CD), are chronic immune-mediated disorders characterized by relapsing-remitting inflammation of the gastrointestinal tract.[1] Cases in which UC and CD cannot be clearly distinguished are referred to as inflammatory bowel disease unclassified (IBDU).[2] Furthermore, clinical outcomes in IBD can be influenced by a range of demographic and social determinants, including sex, age, ethnicity, geography, and socioeconomic status.[3] Previous studies have reported differing results regarding the impact of sex in IBD.
A large-scale prevalence study reported a female predominance in the overall IBD cohort, including both UC and CD subgroups.[4] Epidemiological studies indicate that CD is slightly more prevalent in females than males in Western countries, whereas this pattern is reversed in Asia.[5–7] Conversely, UC shows no consistent sex-based differences in incidence before age 45, but a male predominance has been observed between 15 and 65 years, especially after 45.[7,8] In a meta-analysis evaluating disease localization, males with CD were less likely to have colonic-only involvement but more likely to present with upper gastrointestinal disease and perianal complications. Additionally, males were more likely than females to have extensive UC.[9] Sex-related differences in clinical outcomes have also been reported. Males with IBD may experience worse outcomes, including higher rates of complications such as higher hospital readmission rates,[10] greater need for therapy escalation,[11] and more frequent surgical interventions.[12–15] Conversely, studies suggest that female patients with CD may present more frequent extraintestinal manifestations (EIMs),[16–21] and show greater susceptibility to the harmful effects of smoking in females with IBD.[22] A recently published review of treatment outcomes reported no impact of sex on results.[23] In another study evaluating treatment response to tumor necrosis factor alpha inhibitors, no sex-based differences were observed during maintenance treatment.[24]
The impact of sex-related differences on IBD prognosis remains inadequately understood, despite the increasing body of evidence on this topic. This study aimed to explore the relationship between sex and IBD prognosis using real-world data from a large, well-characterized cohort.
2. Materials and methods
2.1. Participants
Data were collected from consecutive patients diagnosed with IBD at our clinics between July 1993 and April 2025. Patients under 18 years and those with insufficient data were excluded from the study. These patients were diagnosed with comprehensive IBD based on clinical symptoms, laboratory examination, imaging, endoscopy, and pathological findings. Patients who did not meet the diagnostic criteria for either CD or UC were classified as having IBDU. Disease location in patients with CD was classified as ileal (L1), colonic (L2), ileocolonic (L3), and upper gastrointestinal (L4). Disease behavior in CD patients was classified as inflammatory (B1), stricturing (B2), penetrating (B3), and perianal disease (P), according to the Montreal classification system. Disease extension in patients with UC was classified as proctitis (E1), left-sided colitis (E2), and extensive colitis (E3).[25]
2.2. Data collection and baseline characteristics
Data for the study were retrieved from both our hospital’s electronic medical record system and a dedicated online medical database system specifically designed by our team to ensure uninterrupted patient follow-up and documentation. The age at onset of IBD, sex, total disease duration, smoking history, family history of IBD, appendectomy history, and body mass index. EIMs, medical history, steroid dependence history, immunomodulatory resistance, biologic resistance or intolerance, hospitalization due to IBD, and prior abdominal surgery were evaluated. Patients with a history of biologic agent use were categorized into 3 groups based on whether they had used only 1 biologic agent, 2 to 3 agents, or ≥4 biologic agents. In addition, baseline laboratory analysis (C-reactive protein, hemoglobin, and albumin), the Crohn’s disease activity index (CDAI) in CD patients, and total and partial Mayo scores in UC patients were recorded.
2.3. Evaluation of outcomes
Prognosis was evaluated based on 3 key clinical outcomes, which included steroid prescription or flare of disease activity based on a physician’s global assessment, escalation of medical therapy due to disease activity, and hospitalization or major abdominal surgery for CD or total colectomy for UC due to disease activity. Escalation of medical therapy was defined as the requirement for systemic corticosteroids or the initiation, switching, or dose optimization of an immunomodulator, biologic agent, or Janus kinase inhibitor in response to active disease. IBD-related hospitalization was considered any admission primarily due to a disease flare, IBD-related complication, or surgical intervention. Major abdominal surgery was defined as any resectional procedure for CD or total colectomy for UC. These parameters were systematically recorded and compared between sexes to investigate potential sex-related differences in disease prognosis. The results were primarily evaluated based on sex, first in the overall IBD cohort, and then separately in patients with CD and UC.
2.4. Statistical analysis
Statistical analyses were performed using IBM SPSS Statistics version 23.0 (IBM Corp., Armonk). Continuous variables were expressed as mean ± standard deviation (SD) or median with interquartile range. Categorical variables were presented as frequencies (n) and percentages (%). To evaluate sex-based differences in disease prevalence, male-to-female (M/F) ratios were calculated for the overall IBD population and each IBD subtype. The observed ratios were then compared with the expected M/F ratio in the general population, which was determined to be 1.0037 based on national demographic data from 2019 to 2024. Statistical comparisons between the observed and expected M/F ratios were conducted using the Wilson score test. Comparisons of continuous variables between female and male patients were performed using the Mann–Whitney U test. Categorical variables were compared using the Pearson chi-square test or Fisher’s exact test. Subgroup analyses were performed separately for patients with CD and UC to assess sex-based differences within disease types. A P-value <.05 was considered statistically significant.
2.5. Ethical considerations
The study was approved by the ethics committee of the Ankara Bilkent City Hospital (TABED 1-25-1243) on May 7, 2025, and was conducted according to the Declaration of Helsinki.
3. Results
A total of 1937 patients diagnosed with IBD were evaluated for inclusion. Among them, 112 patients diagnosed before the age of 18 and 51 patients with insufficient data were excluded. Ultimately, a total of 1774 patients diagnosed with IBD were included in the study (Fig. 1), comprising 695 females (39.2%) and 1079 males (60.8%). A statistically significant male predominance was observed in the entire cohort and across all IBD subtypes when compared with the expected M/F ratio in the general population (1.0037). Among all IBD patients, the M/F ratio was 1.5525 (1079 males vs 695 females; P < .001). Among patients with CD, the M/F ratio was 1.4667 (506 males vs 345 females; P < .001). Similarly, for UC, the observed M/F ratio was 1.6053 (541 males vs 337 females; P < .001). The highest male predominance was detected in patients with IBDU, where the M/F ratio reached 2.4615 (32 males vs 13 females; P = .005) (data not shown). The mean age at IBD onset was significantly lower in females compared to males (34.7 ± 12.1 vs 37.0 ± 13.1 years, P = .001). However, the total disease duration did not significantly differ between the sexes (122.1 ± 92.5 months in females vs 124.6 ± 96.2 months in males, P = .723). Smoking status differed significantly by sex; a greater proportion of females were nonsmokers (472 females, 67.9% vs 409 males, 37.9%), whereas current smoking was more prevalent among males (124 females, 17.8% vs 276 males, 25.6%) (P < .001). A family history of IBD was reported in 200 patients (11.3% of the total cohort), with no significant sex-based difference (83 females, 11.8% vs 118 males, 10.9%; P = .575). The frequency of prior appendectomy was also similar between sexes (38 females, 5.5% vs 60 males, 5.6%; P = .933) (Table 1).
Figure 1.
Flow diagram of the study. CD = Crohn’s disease, IBDU = inflammatory bowel disease unclassified, UC = ulcerative colitis.
Table 1.
Comparison of demographics and clinical features between female and male patients with IBD.
| Characteristics | Total (n = 1774) | Female (n = 695, 39.2%) | Male (n = 1079, 60.8%) | P-value |
|---|---|---|---|---|
| Age at onset of IBD (years), median (IQR) | 36.1 ± 13.1 | 34.7 ± 12.1 | 37.0 ± 13.1 | 0.001 * |
| Total disease duration (months), median (IQR) | 123.6 ± 94.7 | 122.1 ± 92.5 | 124.6 ± 96.2 | 0.723* |
| Smokers (current/ex/none), n (%) | (400/493/881) | (124/99/472) | (276/394/409) | <0.001 † |
| Family history of IBD, n (%) | 200 (11.3) | 82 (11.8) | 118 (10.9) | 0.575† |
| Appendectomy, n (%) | 98 (5.5) | 38 (5.5) | 60 (5.6) | 0.933† |
| Disease extent in UC, n (%) (n = 878) | ||||
| Proctitis (E1) | 83 (9.5) | 42 (12.5) | 41 (7.6) | 0.047 † |
| Left-sided (E2) | 412 (46.9) | 149 (44.2) | 263 (48.6) | |
| Extensive (E3) | 383 (43.6) | 146 (43.3) | 237 (43.8) | |
| Disease location in CD, n (%) (n = 851) | ||||
| Ileal (L1) | 399 (46.9) | 151 (43.8) | 248 (49.0) | 0.366‡ |
| Colonic (L2) | 96 (11.3) | 44 (12.8) | 52 (10.3) | |
| Ileocolonic (L3) | 352 (41.4) | 149 (43.2) | 203 (40.1) | |
| Upper GI disease (L4) | 4 (0.5) | 1 (0.3) | 3 (0.6) | |
| Disease behavior in CD, n (%) (n = 851) | ||||
| Inflammatory disease (B1) | 615 (72.3) | 260 (75.4) | 355 (70.2) | 0.222† |
| Stenosing (B2) | 105 (12.3) | 36 (10.4) | 69 (13.6) | |
| Penetrating (B3) | 131 (15.4) | 49 (14.2) | 82 (16.2) | |
| Perianal disease in CD, n (%) (n = 851) | 286 (66.4) | 107 (31.0) | 176 (35.4) | 0.186† |
| Unclassified IBD, n (%) | 45 (2.5) | 13 (1.9) | 32 (3.0) | 0.152† |
| Extraintestinal manifestations, n (%) | 848 (47.8) | 388 (55.8) | 460 (42.6) | <0.001 † |
| Peripheral arthralgia | 555 (31.3) | 271 (39.0) | 284 (26.3) | <0.001 † |
| Peripheral arthritis | 159 (9.0) | 90 (12.9) | 69 (6.4) | <0.001 † |
| Ankylosing spondylitis | 99 (5.6) | 33 (4.7) | 66 (6.1) | 0.220† |
| Sacroiliitis | 34 (1.9) | 15 (2.2) | 19 (1.8) | 0.551† |
| Erythema nodosum | 33 (1.9) | 26 (3.7) | 7 (0.6) | <0.001 † |
| Pyoderma gangrenous | 9 (0.5) | 4 (0.6) | 5 (0.5) | 0.746‡ |
| Aphthous ulcer | 270 (15.2) | 130 (18.7) | 140 (13.0) | 0.001 † |
| Uveitis | 27 (1.5) | 13 (1.9) | 14 (1.3) | 0.336† |
| Episcleritis | 6 (0.3) | 3 (0.4) | 3 (0.3) | 0.586‡ |
| Primary sclerosing cholangitis | 27 (1.5) | 11 (1.6) | 16 (1.5) | 0.867† |
| Medical history, n (%) | ||||
| Mesalazine oral | 1376 (77.6) | 541 (77.8) | 835 (77.4) | 0.822† |
| Mesalazine enema | 722 (40.7) | 279 (40.1) | 443 (41.1) | 0.702† |
| Mesalazine suppository | 160 (9.0) | 68 (9.8) | 92 (8.5) | 0.367† |
| Sulfasalazine | 186 (10.5) | 84 (12.1) | 102 (9.5) | 0.077† |
| Budesonide | 263 (14.8) | 104 (15.0) | 159 (14.7) | 0.895† |
| Steroids | 963 (54.3) | 376 (54.1) | 587 (54.4) | 0.901† |
| Thiopurine | 1055 (59.5) | 411 (59.1) | 644 (59.7) | 0.818† |
| Methotrexate | 250 (14.1) | 103 (14.8) | 147 (13.6) | 0.480† |
| Adalimumab | 539 (30.4) | 213 (30.6) | 326 (30.2) | 0.846† |
| Infliximab | 588 (33.1) | 215 (30.9) | 373 (34.6) | 0.112† |
| Vedolizumab | 159 (9.0) | 61 (8.8) | 98 (9.1) | 0.826† |
| Ustekinumab | 173 (9.8) | 73 (10.5) | 100 (9.3) | 0.392† |
| Certolizumab | 35 (2.0) | 17 (2.4) | 18 (1.7) | 0.250† |
| Upadacitinib | 30 (1.7) | 14 (2.0) | 16 (1.5) | 0.397† |
| Tofacitinib | 2 (0.1) | 2 (0.3) | 0 (0.0) | 0.078‡ |
| Steroid dependence, n (%) | 979 (55.2) | 372 (53.5) | 607 (56.3) | 0.259† |
| Immunomodulator resistance, n (%) | 578 (32.6) | 225 (32.4) | 353 (32.7) | 0.881† |
| Thiopurine | 511 (28.8) | 195 (28.1) | 316 (29.3) | 0.577† |
| Methotrexate | 124 (7.0) | 55 (7.9) | 69 (6.4) | 0.221† |
| Biologic resistance/intolerance, n (%) | 451 (25.4) | 173 (24.9) | 278 (25.8) | 0.680† |
| Adalimumab | 293 (16.5) | 115 (16.5) | 178 (16.5) | 0.978† |
| Infliximab | 274 (15.4) | 106 (15.3) | 168 (15.6) | 0.856† |
| Vedolizumab | 90 (5.1) | 42 (6.0) | 48 (4.4) | 0.135† |
| Ustekinumab | 45 (2.5) | 20 (2.9) | 25 (2.3) | 0.463† |
| Certolizumab | 25 (1.4) | 14 (2.0) | 11 (1.0) | 0.083† |
| Biologic agent history, n (%) (n = 887) | ||||
| Only 1 biologic agent | 480 (54.1) | 183 (54.5) | 297 (53.9) | 0.257† |
| 2–3 biologic agents | 350 (39.5) | 126 (37.5) | 224 (40.7) | |
| ≥4 biologic agents | 57 (6.4) | 27 (8.0) | 30 (5.4) | |
| Hospitalization due to IBD, n (%) | 757 (42.7) | 299 (43.0) | 458 (42.4) | 0.811† |
| Prior abdominal surgery, n (%) | 391 (22.0) | 143 (20.6) | 248 (23.0) | 0.232† |
| Major abdominal surgery for CD (n = 851) | 331 (38.9) | 125 (36.2) | 206 (40.7) | 0.188† |
| Total colectomy for UC (n = 878) | 57 (6.5) | 17 (5.0) | 40 (7.4) | 0.169† |
| Baseline CRP (mg/L), median (IQR) | 9.0 (4.7–24.0) | 9.3 (4.5–21.0) | 8.9 (4.8–27.6) | 0.622* |
| Baseline Hb (g/dL), median (IQR) | 12.6 (11.6–13.9) | 12.0 (11.0–13.0) | 13.1 (12.0–14.5) | <0.001 * |
| Baseline albumin (g/dL), median (IQR) | 4.0 (3.9–4.4) | 4.0 (3.9–4.4) | 4.1 (3.9–4.5) | 0.098* |
| Baseline CDAI (CD), mean ± SD (n = 851) | 304.9 ± 114.1 | 316.5 ± 127.5 | 297.0 ± 103.3 | 0.046 * |
| Baseline total Mayo score, mean ± SD (n = 878) | 7.8 ± 2.3 | 7.7 ± 2.4 | 7.8 ± 2.2 | 0.737* |
| Baseline partial Mayo score, mean ± SD (n = 878) | 5.7 ± 2.1 | 5.6 ± 2.2 | 5.7 ± 2.0 | 0.814* |
Bold indicates statistically significant values (P < .05).
B1 = inflammatory behavior, B2 = stricturing behavior, B3 = penetrating behavior, CD = Crohn’s disease, CDAI = Crohn’s disease activity index, E1 = proctitis, E2 = left-sided colitis, E3 = extensive colitis, Hb = hemoglobin, IBD = inflammatory bowel disease, IQR = interquartile range, L1 = ileal, L2 = colonic, L3 = ileocolonic, L4 = upper gastrointestinal, SD = standard deviation, UC = ulcerative colitis.
Mann–Whitney U test was used.
Pearson chi-square test was used.
Fisher’s exact test was used.
In the CD cohort (851), disease location did not significantly differ between females and males (P = .366). Ileal disease (L1) was the most common location in both sexes (151 females, 43.8% vs 248 males, 49.0%), followed by ileocolonic (L3) and colonic disease (L2) (L3: 149 females, 43.2% vs 203 males, 40.1%; L2: 44 females, 12.8% vs 52 males, 10.3%). Disease behavior was also similar between sexes (P = .222), with inflammatory behavior pattern (B1) being the most prevalent (260 females, 75.4% vs 355 males, 70.2%), followed by penetrating (B3) and stenosing (B2) phenotypes (B3: 49 females, 14.2% vs 82 males, 16.2%; B2: 36 females, 10.4% vs 69 males, 13.6%). Perianal disease was slightly more frequent in males (107 females, 31.0% vs 176 males, 35.4%), but the difference was not statistically significant (P = .186) (Table 1).
Among patients with UC (878), disease extension patterns showed a statistically significant sex difference (P = .047). Proctitis (E1) was more commonly reported in females than males (42 females, 12.5% vs 41 males, 7.6%); however, left-sided colitis (E2) and extensive colitis (E3) were comparable between male and female patients (E2: 149 females, 44.2% females vs 263 males, 48.6%; E3: 146 females, 43.3% vs. 237 males, 43.8%) (Table 1).
EIMs were significantly more prevalent in females than in males across the overall cohort (388 females, 55.8% vs 460 males, 42.6%; P < .001). Peripheral arthralgia (271 females, 39.0% vs 284 males, 26.3%; P < .001), peripheral arthritis (90 females, 12.9% vs 69 males, 6.4%; P < .001), and erythema nodosum (26 females, 3.7% vs 7 males, 0.6%; P < .001) were all more common in females. Aphthous ulcers were also significantly more frequent among females (130 females, 18.7% vs 140 males, 13.0%; P = .001). Other EIMs, such as ankylosing spondylitis, sacroiliitis, uveitis, episcleritis, pyoderma gangrenosum, and primary sclerosing cholangitis, did not show statistically significant sex-based differences. In all IBD patients, females presented with lower hemoglobin (12.0 vs 13.1 g/dL, P < .001) while serum C-reactive protein and albumin levels were similar across sexes (Table 1 and Fig. 2).
Figure 2.
Box plots of all inflammatory bowel disease patients’ (A) C-reactive protein (CRP), (B) hemoglobin (Hb), and (C) albumin levels. CRP = C-reactive protein, Hb = hemoglobin.
Use of conventional and advanced therapies was largely comparable between female and male patients. Oral mesalazine was the most commonly used medication (1376 patients, 77.6% in the overall cohort; 541 females, 77.8% vs 835 males, 77.4%; P = .822). Other formulations (enema and suppository), sulfasalazine, budesonide, and systemic steroids showed no significant sex-based differences. Similarly, the use of immunomodulators (thiopurines and methotrexate), biologic agents (adalimumab, infliximab, vedolizumab, ustekinumab, certolizumab, upadacitinib, and tofacitinib), and the number of biologic agents did not differ significantly by sex. Biologic resistance or intolerance rates were nearly identical (173 females, 24.9% vs 278 males, 25.8%; P = .680). Steroid dependence was noted in 979 patients (55.2% of the entire cohort), with no significant sex-based difference (372 females, 53.5% vs 607 males, 56.3%; P = .259) (Table 1).
In the CD subgroup (851), females presented with a higher CDAI score at baseline (316.5 ± 127.5 vs 297.0 ± 103.3, P = .046), and lower hemoglobin (12.0 vs 13.3 g/dL, P < .001), as well as lower serum albumin (4.0 vs 4.1 g/dL, P = .040). EIMs remained significantly more frequent in females (211 females, 61.2% vs 242 males, 47.8%; P < .001), particularly peripheral arthralgia (145 females, 42.0% vs 158 males, 31.2%; P = .001), peripheral arthritis (56 females, 16.2% vs 46 males, 9.1%; P = .002), and erythema nodosum (17 females, 4.9% vs 3 males, 0.6%; P = .009) (Table 2 and Fig. 3).
Table 2.
Subgroup comparison of demographics and clinical features between female and male patients with CD and UC.
| CD (n = 851) | P | UC (n = 878) | P | |||
|---|---|---|---|---|---|---|
| Female (n = 345) | Male (n = 506) | Female (n = 337) | Male (n = 541) | |||
| Age at onset of IBD (years), median (IQR) | 34.9 ± 12.4 | 33.8 ± 12.0 | 0.200* | 34.5 ± 11.9 | 40.2 ± 13.5 | 0.001 * |
| Total disease duration (months), median (IQR) | 115.3 ± 89.1 | 112.8 ± 88.0 | 0.716* | 127.9 ± 94.5 | 135.9 ± 101.8 | 0.343* |
| Smokers (current/ex/none), n (%) | (87/49/209) | (194/153/159) | <0.001 † | (32/49/256) | (76/227/238) | <0.001 † |
| Family history of IBD, n (%) | 34 (9.9) | 51 (10.1) | 0.915† | 41 (12.2) | 65 (12.0) | 0.947† |
| Appendectomy, n (%) | 27 (7.8) | 54 (10.7) | 0.165† | 11 (3.3) | 6 (1.1) | 0.024 † |
| Disease extent in UC, n (%) | ||||||
| Proctitis | 42 (12.5) | 41 (7.6) | 0.047 † | |||
| Left-sided | 149 (44.2) | 263 (48.6) | ||||
| Extensive | 146 (43.3) | 237 (43.8) | ||||
| Disease location in CD, n (%) | ||||||
| Ileal (L1) | 151 (43.8) | 248 (49.0) | 0.366‡ | |||
| Colonic (L2) | 44 (12.8) | 52 (10.3) | ||||
| Ileocolonic (L3) | 149 (43.2) | 203 (40.1) | ||||
| Upper GI disease (L4) | 1 (0.3) | 3 (0.6) | ||||
| Disease behavior in CD, n (%) | ||||||
| Inflammatory disease (B1) | 260 (75.4) | 355 (70.2) | 0.222† | |||
| Stenosing (B2) | 36 (10.4) | 69 (13.6) | ||||
| Penetrating (B3) | 49 (14.2) | 82 (16.2) | ||||
| Perianal disease in CD, n (%) | 107 (31.0) | 176 (35.4) | 0.186† | |||
| Extraintestinal manifestations, n (%) | 211 (61.2) | 242 (47.8) | <0.001 † | 168 (49.9) | 203 (37.5) | <0.001 † |
| Peripheral arthralgia | 145 (42.0) | 158 (31.2) | 0.001 † | 119 (35.3) | 118 (21.8) | <0.001 † |
| Peripheral arthritis | 56 (16.2) | 46 (9.1) | 0.002 † | 31 (9.2) | 23 (4.3) | 0.003 † |
| Ankylosing spondylitis | 20 (5.8) | 43 (8.5) | 0.140† | 13 (3.9) | 22 (4.1) | 0.878† |
| Sacroiliitis | 12 (3.5) | 12 (2.4) | 0.338† | 3 (0.9) | 7 (1.3) | 0.584† |
| Erythema nodosum | 17 (4.9) | 3 (0.6) | 0.009 † | 9 (2.7) | 3 (0.6) | <0.001 † |
| Pyoderma gangrenous | 3 (0.9) | 3 (0.6) | 0.636‡ | 1 (0.3) | 2 (0.4) | 0.857‡ |
| Aphthous ulcer | 67 (19.4) | 60 (11.9) | 0.003 † | 59 (17.5) | 74 (13.7) | 0.124† |
| Uveitis | 9 (2.6) | 8 (1.6) | 0.293† | 4 (1.2) | 6 (1.1) | 0.999C |
| Episcleritis | 2 (0.6) | 1 (0.2) | 0.569‡ | 1 (0.3) | 2 (0.4) | 0.999‡ |
| Primary sclerosing cholangitis | 4 (1.2) | 6 (1.2) | 0.999C | 6 (1.8) | 8 (1.5) | 0.729† |
| Medical history, n (%) | ||||||
| Mesalazine oral | 222 (64.3) | 314 (62.1) | 0.496† | 308 (91.4) | 491 (90.8) | 0.748† |
| Mesalazine enema | 32 (9.3) | 51 (10.1) | 0.698† | 239 (70.9) | 371 (68.6) | 0.463† |
| Mesalazine suppository | 9 (2.6) | 10 (2.0) | 0.540† | 57 (16.9) | 78 (14.4) | 0.319† |
| Sulfasalazine | 49 (14.2) | 51 (10.1) | 0.067† | 31 (9.2) | 46 (8.5) | 0.723† |
| Budesonide | 99 (28.7) | 143 (28.3) | 0.890† | 4 (1.2) | 15 (2.8) | 0.116† |
| Steroids | 182 (52.8) | 277 (54.7) | 0.568† | 188 (55.8) | 298 (55.1) | 0.838† |
| Thiopurine | 260 (75.4) | 379 (74.9) | 0.879† | 148 (43.9) | 252 (46.6) | 0.441† |
| Methotrexate | 93 (27.0) | 131 (25.9) | 0.729† | 8 (2.4) | 15 (2.8) | 0.719† |
| Adalimumab | 154 (44.6) | 236 (46.6) | 0.565† | 59 (17.5) | 87 (16.1) | 0.581† |
| Infliximab | 146 (42.3) | 236 (46.6) | 0.213† | 69 (20.5) | 134 (24.8) | 0.142† |
| Vedolizumab | 38 (11.0) | 51 (10.1) | 0.662† | 23 (6.8) | 47 (8.7) | 0.322† |
| Ustekinumab | 52 (15.1) | 69 (13.6) | 0.556† | 21 (6.2) | 31 (5.7) | 0.760† |
| Certolizumab | 14 (4.1) | 18 (3.6) | 0.717† | 3 (0.9) | 0 (0.0) | 0.056‡ |
| Upadacitinib | 8 (2.3) | 10 (2.0) | 0.733† | 6 (1.8) | 5 (0.9) | 0.351‡ |
| Tofacitinib | 0 (0.0) | 0 (0.0) | n.a. | 2 (0.6) | 0 (0.0) | 0.147‡ |
| Steroid dependence, n (%) | 224 (64.9) | 351 (69.4) | 0.174† | 145 (43.0) | 246 (45.5) | 0.478† |
| Immunomodulatory resistance n (%) | 173 (50.1) | 253 (50.0) | 0.337† | 52 (15.4) | 97 (17.9) | 0.967† |
| Thiopurine | 145 (42.0) | 219 (43.3) | 0.323† | 50 (14.8) | 94 (17.4) | 0.717† |
| Methotrexate | 52 (15.1) | 61 (12.1) | 0.203† | 3 (0.9) | 8 (1.5) | 0.446‡ |
| Biologic resistance/intolerance, n (%) | 123 (35.7) | 185 (36.6) | 0.786† | 50 (14.8) | 93 (17.2) | 0.358† |
| Adalimumab | 83 (24.1) | 130 (25.7) | 0.755† | 32 (9.5) | 48 (8.9) | 0.589† |
| Infliximab | 77 (22.3) | 103 (20.4) | 0.491† | 29 (8.6) | 65 (12.0) | 0.112† |
| Vedolizumab | 27 (7.8) | 28 (5.5) | 0.579† | 15 (4.5) | 20 (3.7) | 0.182† |
| Ustekinumab | 15 (4.3) | 19 (3.8) | 0.665† | 5 (1.5) | 6 (1.1) | 0.627‡ |
| Certolizumab | 11 (3.2) | 11 (2.2) | 0.360† | 3 (0.9) | 0 (0.0) | 0.056‡ |
| Biologic agent history, n (%) (n = 887) | ||||||
| Only 1 biologic agent, n (%) | 124 (53.7) | 193 (53.5) | 0.424† | 59 (56.2) | 99 (53.8) | 0.633† |
| 2–3 biologic agents, n (%) | 86 (37.2) | 145 (40.2) | 40 (38.1) | 78 (42.4) | ||
| ≥4 biologic agents, n (%) | 21 (9.1) | 23 (6.4) | 6 (5.7) | 7 (3.8) | ||
| Hospitalization due to IBD, n (%) | 192 (55.7) | 276 (54.5) | 0.750† | 101 (30.0) | 173 (32.0) | 0.532† |
| Prior abdominal surgery, n (%) | ||||||
| Major abdominal surgery for CD | 125 (36.2) | 206 (40.7) | 0.188† | |||
| Total colectomy for UC | 17 (5.0) | 40 (7.4) | 0.169† | |||
| Baseline CRP (mg/L), median (IQR) | 9.8 (4.0–25.9) | 8.0 (4.4–25.5) | 0.694* | 8.0 (5.0–18.0) | 10.0 (5.0–29.0) | 0.216* |
| Baseline Hb (g/dL), median (IQR) | 12.0 (10.9–13.0) | 13.3 (12.0–14.6) | <0.001 * | 12.0 (11.0–13.0) | 13.0 (11.8–14.3) | <0.001 * |
| Baseline albumin (g/dL), median (IQR) | 4.0 (3.8–4.4) | 4.1 (4.0–4.5) | 0.040 * | 4.0 (3.9–4.4) | 4.0 (3.9–4.5) | 0.840* |
| Baseline CDAI (CD), mean ± SD | 316.5 ± 127.5 | 297.0 ± 103.3 | 0.046 * | |||
| Baseline total Mayo score, mean ± SD | 7.7 ± 2.4 | 7.8 ± 2.2 | 0.737* | |||
| Baseline partial Mayo score, mean ± SD | 5.6 ± 2.2 | 5.7 ± 2.0 | 0.814* | |||
Bold indicates statistically significant values (P < .05).
B1 = inflammatory behavior, B2 = stricturing behavior, B3 = penetrating behavior, CD = Crohn’s disease, CDAI = Crohn’s disease activity index, Hb = hemoglobin, IBD = inflammatory bowel disease, IQR = interquartile range, L1 = ileal, L2 = colonic, L3 = ileocolonic, L4 = upper gastrointestinal, n.a. = not applicable, SD = standard deviation, UC = ulcerative colitis.
Mann–Whitney U test was used.
Pearson chi-square test was used.
Fisher’s exact test was used.
Figure 3.
Box plots of (A) C-reactive protein (CRP), (B) hemoglobin (Hb), and (C) albumin levels in patients with Crohn’s disease (CD); and (D) CRP, (E) Hb, and (F) albumin levels in patients with ulcerative colitis (UC). CRP = C-reactive protein, CD = Crohn’s disease, Hb = hemoglobin, UC = ulcerative colitis.
In the UC subgroup (878), males had a later disease onset (40.2 ± 13.5 vs 34.5 ± 11.9 years, P = .001). Hemoglobin levels were again lower in females (12.0 vs 13.0 g/dL, P < .001), while serum albumin and Mayo scores were similar across sexes. As in the CD group, EIMs were more frequent in females (168 females, 49.9% vs 203 males, 37.5%; P < .001), particularly peripheral arthralgia (119 females, 35.3% vs 118 males, 21.8%; P < .001) and peripheral arthritis (31 females, 9.2% vs 23 males, 4.3%; P = .003) (Table 2 and Fig. 3).
Rates of hospitalization due to IBD were comparable between females and males (299 females, 43.0% vs 458 males, 42.4%; P = .811). Similarly, previous abdominal surgery (143 females, 20.6% vs 248 males, 23.0%; P = .232) and major surgery for CD (125 females, 36.2% vs 206 males, 40.7%; P = .188) did not differ significantly. Total colectomy for UC was slightly more frequent in males (17 females, 5.0% vs 40 males, 7.4%; P = .169), but not statistically significant (Tables 1 and 2).
4. Discussion
Sex-related differences in the epidemiological characteristics and clinical course of IBD have been increasingly recognized in recent years. Recent studies showed that CD is slightly more prevalent in females than in males.[5,7] Sex-related disparities in clinical outcomes have also been reported, suggesting that males with IBD may have worse outcomes, including higher rates of complications such as higher hospital readmission rates,[10] greater need for therapy escalation[11], and more frequent surgical interventions.[12–15] Conversely, studies suggest that female patients with CD may present more frequent EIMs,[16–18] and a greater susceptibility to the harmful effects of smoking.[22] Therefore, this study evaluated the association between sex and IBD outcomes using real-world data from a large IBD cohort.
Our study demonstrated a significant male predominance in IBD diagnoses (1.6:1), despite largely similar disease activity, treatment exposure, and clinical outcomes between the sexes. Consistent with previous epidemiological data from Asia and certain European populations,[5] our cohort revealed a male predominance in IBD, accounting for approximately 61% of all cases. This finding contrasts with multiple population-based cohorts from Western Europe and North America, where sex distribution has been reported as either balanced or with a slight female predominance in CD and equivalent rates in UC until later adulthood.[7] The reasons for these geographic discrepancies remain unclear, but they may relate to genetic, environmental, or sociocultural differences, including smoking prevalence and healthcare access.[3,26] Interestingly, the male predominance observed in our cohort may also be partially influenced by differences in healthcare-seeking behavior or access patterns between sexes, which can vary across regions. In some settings, males may be more likely to receive timely diagnoses due to sociocultural or occupational factors influencing health service utilization. Additionally, the trend toward more balanced sex distribution in Western populations may reflect broader shifts in environmental exposures or public health awareness that affect disease detection. These findings highlight the need for further population-specific research to explore the interaction between biological, behavioral, and systemic factors in shaping IBD epidemiology.
Previous studies have reported worse clinical outcomes in males than in females with IBD. For instance, Mudireddy et al observed higher hospitalization rates among male patients,[10] while Billioud et al reported an increased need for treatment escalation in males receiving adalimumab.[11] Furthermore, several studies have shown that the risk of surgery is also higher in male patients.[12–15] Importantly, in our study, the observed sex disparity in IBD prevalence was not accompanied by a corresponding difference in disease severity or prognosis. Rates of hospitalization, prior abdominal surgery, biologic exposure, number of biologic agents, and steroid dependence were similar between male and female patients. This finding suggests that, although IBD is diagnosed more frequently in males within our cohort, female patients do not exhibit a milder disease course. In exploring potential explanations, a recently published meta-analysis indicated that smoking is associated with increased clinical recurrence, need for surgery, steroid use, and dependence, and consequently a poorer prognosis in patients with CD. However, smoking has not been shown to affect the response to biologic therapy. In contrast to CD, smoking has not been associated with adverse clinical outcomes in UC and may even exert a protective effect.[26] In our cohort, smoking prevalence was significantly higher in males than in females in both disease groups. While this may partly explain the comparable disease course between sexes in UC, it does not account for the similar disease course observed between males and females in the overall IBD cohort or the CD subgroup. Previous studies have shown that female patients with IBD, particularly those with UC, experience significantly longer diagnostic delays compared to males.[27,28] A recent meta-analysis from the Mediterranean region reported a female predominance in UC and a male predominance in CD; however, to the best of our knowledge, data regarding IBD prognosis from our specific region remain limited.[29] We believe these differences may be attributable to genetic predisposition, environmental and nutritional factors, diagnostic delay, and our geographical location in the Mediterranean region.
In our study, one of the most consistent findings was the higher prevalence of EIMs among female patients. Conditions such as peripheral arthralgia, arthritis, erythema nodosum, and aphthous ulcer were significantly more common in female patients with IBD. Among these, aphthous ulcers were substantially more common only in female patients with CD, while no significant difference was found in patients with UC between the sexes. These findings align with prior studies indicating increased susceptibility of females to immune-mediated systemic involvement.[16–18] Multiple mechanisms, including estrogen-mediated immune modulation, genetic predispositions, and behavioral differences such as symptom reporting and healthcare utilization, may explain this pattern. In addition, it is possible that heightened clinical vigilance for EIMs in females, combined with their more frequent reporting of subtle systemic symptoms, may contribute to earlier recognition and documentation of these conditions. Moreover, sex-based differences in inflammatory responses, particularly in mucocutaneous and musculoskeletal systems, may play a role in shaping the phenotypic expression of IBD beyond the gut. These observations underscore the importance of adopting a sex-informed clinical approach in the routine assessment of IBD patients.
In our research, female patients with CD in particular exhibited a greater inflammatory burden as reflected by higher baseline CDAI scores and lower hemoglobin and albumin levels. Nevertheless, treatment escalation patterns did not significantly differ between the sexes. This included comparable hospitalization, surgery due to IBD, the number of biologic agents used, and similar rates of biologic therapy resistance. Immunological factors and lower smoking rates among female patients may attenuate the impact of inflammation on disease progression. Notably, in our cohort, smoking was more prevalent among males than females. Cosnes et al previously reported that smoking is a factor traditionally associated with worse outcomes in CD and protective effects in UC.[22] While this may partially explain the higher frequency of CD in male patients in our cohort, it did not translate into worse outcomes in terms of surgery or hospitalization. Our findings suggest that, although female patients present with higher inflammatory activity and heightened symptom perception, their overall disease trajectory remains similar to that of men. The younger age at diagnosis observed in female patients may reflect earlier immune activation or increased health-seeking behavior, potentially contributing to both higher EIM rates and more marked inflammatory profiles. Taken together, these sex-based differences in clinical presentation and disease phenotype highlight the need for more sex-conscious approaches in both clinical practice and pathophysiological research. Additionally, it is conceivable that subtle sex-based differences in physician decision-making, whether conscious or unconscious, may influence the clinical interpretation of symptoms and thresholds for initiating or escalating therapy. Understanding how provider perceptions and patient-reported experiences intersect across sexes could help ensure more individualized and equitable care.
Our findings should be interpreted in the context of several strengths and limitations. The large sample size and prospectively collected data increase the reliability and generalizability of our findings. However, the retrospective nature of the analysis and lack of longitudinal follow-up regarding treatment response or quality-of-life measures may limit the depth of sex-based outcome interpretation. Moreover, hormonal status, pregnancy, and psychosocial factors, which may influence both disease perception and therapeutic decisions, were not available in our dataset. Additionally, the lack of stratification by menopausal status, contraceptive use, or hormone replacement therapy may have obscured a biologically relevant distinction. Future studies should consider prospective, sex-stratified designs with standardized measurement of hormonal and behavioral factors.
In conclusion, our study highlights a distinct male predominance in IBD diagnoses in a tertiary referral center, without a prognostic advantage. Female patients exhibited a higher burden of systemic inflammation and EIMs, despite similar disease-modifying therapy exposure and clinical outcomes. Further studies are needed to explore the underlying mechanisms driving these differences and to refine therapeutic strategies.
Author contributions
Conceptualization: Ali Atay, Mucahit Ergul, Oguz Ozturk, Kadir Can Acun, Yavuz Cagir, Muhammed Bahaddin Durak, Ilhami Yuksel.
Data curation: Ali Atay, Mucahit Ergul, Oguz Ozturk, Kadir Can Acun, Yavuz Cagir, Muhammed Bahaddin Durak, Ilhami Yuksel.
Formal analysis: Ali Atay, Ilhami Yuksel.
Methodology: Ali Atay, Ilhami Yuksel.
Project administration: Ali Atay, Ilhami Yuksel.
Resources: Ali Atay, Ilhami Yuksel.
Software: Ali Atay, Ilhami Yuksel.
Supervision: Ali Atay, Ilhami Yuksel.
Visualization: Ali Atay, Ilhami Yuksel.
Writing – original draft: Ali Atay, Ilhami Yuksel.
Writing – review & editing: Ali Atay, Mucahit Ergul, Oguz Ozturk, Kadir Can Acun, Yavuz Cagir, Muhammed Bahaddin Durak, Ilhami Yuksel.
Abbreviations
- B1
- inflammatory behavior
- B2
- stricturing behavior
- B3
- penetrating behavior
- CD
- Crohn’s disease
- CDAI
- Crohn’s disease activity index
- E1
- proctitis
- E2
- left-sided colitis
- E3
- extensive colitis
- EIM
- extraintestinal manifestation
- IBD
- inflammatory bowel disease
- IBDU
- inflammatory bowel disease unclassified
- L1
- ileal
- L2
- colonic
- L3
- ileocolonic
- L4
- upper gastrointestinal
- M/F
- male-to-female ratio
- UC
- ulcerative colitis
The authors have no funding and conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
How to cite this article: Atay A, Ergul M, Ozturk O, Acun KC, Cagir Y, Durak MB, Yuksel I. Male predominance in inflammatory bowel disease despite similar disease activity: A large retrospective cohort study. Medicine 2025;XX:XX(e46562).
Contributor Information
Mucahit Ergul, Email: dr.mucahitergul@gmail.com.
Oguz Ozturk, Email: oguzozturk90@gmail.com.
Kadir Can Acun, Email: kacun01@gmail.com.
Yavuz Cagir, Email: yvzcgr@hotmail.com.
Muhammed Bahaddin Durak, Email: doctormbd@gmail.com.
References
- [1].Turner D, Ricciuto A, Lewis A, et al. ; International Organization for the Study of IBD. STRIDE-II: an update on the selecting therapeutic targets in inflammatory bowel disease (STRIDE) initiative of the International Organization for the study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology. 2021;160:1570–83. [DOI] [PubMed] [Google Scholar]
- [2].Prenzel F, Uhlig HH. Frequency of indeterminate colitis in children and adults with IBD – a metaanalysis. J Crohns Colitis. 2009;3:277–81. [DOI] [PubMed] [Google Scholar]
- [3].Andersen V, Pingel J, Søfelt HL, et al. Sex and gender in inflammatory bowel disease outcomes and research. Lancet Gastroenterol Hepatol. 2024;9:1041–51. [DOI] [PubMed] [Google Scholar]
- [4].Lewis JD, Parlett LE, Jonsson Funk ML, et al. Incidence, prevalence, and racial and ethnic distribution of inflammatory bowel disease in the United States. Gastroenterology. 2023;165:1197–205.e2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [5].Prideaux L, Kamm MA, De Cruz PP, Chan FKL, Ng SC. Inflammatory bowel disease in Asia: a systematic review. J Gastroenterol Hepatol. 2012;27:1266–80. [DOI] [PubMed] [Google Scholar]
- [6].Goodman WA, Erkkila IP, Pizarro TT. Sex matters: impact on pathogenesis, presentation and treatment of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2020;17:740–54. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [7].Shah SC, Khalili H, Gower-Rousseau C, et al. Sex-based differences in incidence of inflammatory bowel diseases-pooled analysis of population-based studies from western countries. Gastroenterology. 2018;155:1079–89.e3. [DOI] [PubMed] [Google Scholar]
- [8].Shah SC, Khalili H, Chen C-Y, et al. Sex-based differences in the incidence of inflammatory bowel diseases-pooled analysis of population-based studies from the Asia-Pacific region. Aliment Pharmacol Ther. 2019;49:904–11. [DOI] [PubMed] [Google Scholar]
- [9].Khrom M, Li D, Naito T, et al. ; NIDDK Inflammatory Bowel Disease Genetics Consortium. Sex-dimorphic analyses identify novel and sex-specific genetic associations in inflammatory bowel disease. Inflamm Bowel Dis. 2023;29:1622–32. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [10].Mudireddy P, Scott F, Feathers A, Lichtenstein GR. Inflammatory bowel disease: predictors and causes of early and late hospital readmissions. Inflamm Bowel Dis. 2017;23:1832–9. [DOI] [PubMed] [Google Scholar]
- [11].Billioud V, Sandborn WJ, Peyrin-Biroulet L. Loss of response and need for adalimumab dose intensification in Crohn’s disease: a systematic review. Am J Gastroenterol. 2011;106:674–84. [DOI] [PubMed] [Google Scholar]
- [12].Hofer B, Böttger T, Hernandez-Richter T, Seifert JK, Junginger T. The impact of clinical types of disease manifestation on the risk of early postoperative recurrence in Crohn’s disease. Hepatogastroenterology. 2001;48:152–5. [PubMed] [Google Scholar]
- [13].Peyrin-Biroulet L, Harmsen WS, Tremaine WJ, Zinsmeister AR, Sandborn WJ, Loftus EVJ. Surgery in a population-based cohort of Crohn’s disease from Olmsted County, Minnesota (1970-2004). Am J Gastroenterol. 2012;107:1693–701. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [14].Samuel S, Ingle SB, Dhillon S, et al. Cumulative incidence and risk factors for hospitalization and surgery in a population-based cohort of ulcerative colitis. Inflamm Bowel Dis. 2013;19:1858–66. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [15].Targownik LE, Singh H, Nugent Z, Bernstein CN. The epidemiology of colectomy in ulcerative colitis: results from a population-based cohort. Am J Gastroenterol. 2012;107:1228–35. [DOI] [PubMed] [Google Scholar]
- [16].Bernstein CN, Blanchard JF, Rawsthorne P, Yu N. The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol. 2001;96:1116–22. [DOI] [PubMed] [Google Scholar]
- [17].Wagtmans MJ, Verspaget HW, Lamers CB, van Hogezand RA. Gender-related differences in the clinical course of Crohn’s disease. Am J Gastroenterol. 2001;96:1541–6. [DOI] [PubMed] [Google Scholar]
- [18].Barreiro-de Acosta M, Domínguez-Muñoz JE, Núñez-Pardo de Vera MC, Lozano-León A, Lorenzo A, Peña S. Relationship between clinical features of Crohn’s disease and the risk of developing extraintestinal manifestations. Eur J Gastroenterol Hepatol. 2007;19:73–8. [DOI] [PubMed] [Google Scholar]
- [19].Guillo L, Savoye G, Amiot A, et al. ; EXTRA Study Group. Prevalence of and factors associated with extraintestinal manifestations and their remission in inflammatory bowel disease: the EXTRA-intestinal manifestation prospective study from the groupe d’etude thérapeutique des affections inflammatoires du tube D. Clin Transl Gastroenterol. 2023;14:e00607. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [20].Yüksel I, Ataseven H, Başar O, et al. Peripheral arthritis in the course of inflammatory bowel diseases. Dig Dis Sci. 2011;56:183–7. [DOI] [PubMed] [Google Scholar]
- [21].Yüksel I, Başar O, Ataseven H, et al. Mucocutaneous manifestations in inflammatory bowel disease. Inflamm Bowel Dis. 2009;15:546–50. [DOI] [PubMed] [Google Scholar]
- [22].Cosnes J, Nion-Larmurier I, Afchain P, Beaugerie L, Gendre J-P. Gender differences in the response of colitis to smoking. Clin Gastroenterol Hepatol. 2004;2:41–8. [DOI] [PubMed] [Google Scholar]
- [23].Solitano V, Facciorusso A, Jess T, et al. Comparative risk of serious infections with biologic agents and oral small molecules in inflammatory bowel diseases: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2023;21:907–21.e2. [DOI] [PubMed] [Google Scholar]
- [24].Agrawal M, Petralia F, Tepler A, et al. Gender-based differences in response to tumor necrosis factor inhibitor therapies for ulcerative colitis: individual participant data meta-analyses of clinical trials. Inflamm Bowel Dis. 2023;29:1–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [25].Satsangi J, Silverberg MS, Vermeire S, Colombel J-F. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut. 2006;55:749–53. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [26].Rozich JJ, Holmer A, Singh S. Effect of lifestyle factors on outcomes in patients with inflammatory bowel diseases. Am J Gastroenterol. 2020;115:832–40. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [27].Vavricka SR, Spigaglia SM, Rogler G, et al. ; Swiss IBD Cohort Study Group. Systematic evaluation of risk factors for diagnostic delay in inflammatory bowel disease. Inflamm Bowel Dis. 2012;18:496–505. [DOI] [PubMed] [Google Scholar]
- [28].Sempere L, Bernabeu P, Cameo J, et al. Gender biases and diagnostic delay in inflammatory bowel disease: multicenter observational study. Inflamm Bowel Dis. 2023;29:1886–94. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [29].Sanat ZM, Vahedi H, Malekzadeh R, Fanni Z. Epidemiologic profile of inflammatory bowel disease in Eastern Mediterranean Region (EMRO) countries: a systematic review and meta-analysis. BMC Public Health. 2024;24:1395. [DOI] [PMC free article] [PubMed] [Google Scholar]