Review

Digestion 2020;101(suppl 1):98–104 Received: June 28, 2019

Accepted: October 18, 2019
DOI: 10.1159/000504701 Published online: January 29, 2020

Gender Differences in Inflammatory

Bowel Disease
Thomas Greuter a Christine Manser b Valerie Pittet c Stephan R. Vavricka a, d
       

Luc Biedermann a  on behalf of Swiss IBDnet, an official working group of the

 

Swiss Society of Gastroenterology

a Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland; b Department  

of Medicine, Kantonsspital Frauenfeld, Frauenfeld, Switzerland; c Institute of Social and Preventive Medicine,
 

University Hospital Lausanne, CHUV, Lausanne, Switzerland; d Center for Gastroenterology and Hepatology,
 

Zurich, Switzerland

Keywords treatment and adherence to treatment can improve disease

Disease activity · Disease course · Disease phenotype · management and foster a more individualized treatment ap-
Environmental factors · Epidemiology · Extraintestinal proach. In this review, we summarize current knowledge
manifestations · Fatigue · Gender · Genetics · Inflammatory about gender-specific differences in IBD and highlight the
bowel disease · Psychological factors · Sex most clinically relevant aspects. © 2020 S. Karger AG, Basel

Abstract
Immune-mediated diseases typically show a female prepon- Introduction
derance. Looking at all autoimmune diseases combined, 8 of
10 patients are females. Although not as prominent, gender The influence of the menstrual cycle on inflammatory
differences in inflammatory bowel disease (IBD) have been bowel disease (IBD) course has been identified > 2 de-
reported for epidemiology, disease presentation, disease cades ago [1]. So far, most sex-specific IBD studies have
course and complications, medical and surgical therapies, focused on pregnancy and childbirth. However, many
adherence, psychosocial functioning, and psychiatric co-dis- more gender-specific differences (physiological and psy-
orders. While for some factors evidence is rather good, for chological) seem to play an important role in IBD [2].
others data are conflicting. Gastroenterologists dealing with Gender-specific differences in IBD have been reported
IBD patients in daily clinical practice should be aware of gen- for disease presentation, disease course and complica-
der-specific issues for the following reasons: (1) mispercep- tions, medical and surgical therapies, adherence, psycho-
tion of disease presentation potentially delays IBD diagnosis, social functioning, and psychiatric co-disorders. While
which has been shown to have deleterious effects, and (2) for some aspects evidence is rather good, for others data
awareness of gender-specific symptoms and disease sever- are conflicting. In the era of personalized medicine and in
ity allows initiation of early and adequately tailored treat- light of potent biological treatment options, it appears ad-
ment. This might prevent development of complications. equate to treat patients acknowledging their sex. Within
And (3) insights into gender-specific differences in terms of this review, we summarize current knowledge of gender-

[email protected] © 2020 S. Karger AG, Basel Luc Biedermann, MD

www.karger.com/dig Department of Gastroenterology and Hepatology
University Hospital Zurich
Rämistrasse 100, CH–8091 Zurich (Switzerland)
E-Mail luc.biedermann @ usz.ch
specific differences in IBD and IBD management. We female patients [19]. Such a diagnostic delay is a problem
further highlight the most clinically relevant gender-spe- in the female IBD population and has potentially deleteri-
cific aspects. Thereby we provide gastroenterologists with ous consequences. A diagnostic delay has been associated
a roadmap of how to take gender into account when deal- with increased rates of complications in IBD and higher
ing with IBD patients. risk for CD-related intestinal surgery [20].

Epidemiology Environmental Factors

Immune-mediated diseases typically show a female The reasons for the abovementioned gender-specific
preponderance. Looking at all autoimmune diseases differences in IBD epidemiology remain unclear; genet-
combined, 8 of 10 patients are females [3–5]. Such female ic predisposition and different exposition to environ-
predominance is particularly seen for diseases such as mental factors are possible explanations [21]. At least,
Sjogren’s syndrome or systemic lupus erythematosus. In appendectomy and smoking are associated with an in-
gastrointestinal disease, primary biliary cholangitis and creased risk of CD in females [6, 22, 23]. Smoking has
celiac disease are considerably more frequent in women been a well-established and widely accepted risk factor
than men. However, gender-specific differences are much for the development and progression of CD. While tra-
less prominent in other immune-mediated disorders ditionally, smoking was more frequently observed in
such as sarcoidosis, type 1 diabetes, and IBD [5, 6]. Type males across all age groups, this picture has changed
1 diabetes indeed is the only major organ-specific auto- quite dramatically in recent years. Numbers of smoking
immune disorder without a strong female bias; in con- females, particularly those at younger age, have been
trast, a considerable male excess is seen in patients aged steadily increasing. Currently, the highest smoking rates
15–40 years [7]. In IBD, gender-specific differences have among IBD patients have been observed in middle-aged
been reported for Crohn’s disease (CD), but not ulcer- female CD subjects. The reported rate of 51.7% is higher
ative colitis (UC), although data are conflicting and pos- than that seen in male counterparts as well as in the age-
sibly depend on geographic areas. In Europe and the and sex-matched general population (26.6%) [24]. Ac-
United States, CD prevalence appears to be higher in fe- cordingly, a Dutch study revealed that more women
males than in males [8–13], while in Asia the opposite has than men are current smokers in the IBD population
been observed [14–16]. Early-onset CD (<16 years) has [17]. Long time ago, the following dogma was estab-
been reported to be more frequent in males than females lished and has been supported since: smoking is protec-
(20 vs. 12%) [17]. A recent large investigation revealed an tive in UC, while it has deleterious effects in CD patients.
even more complex relation between sex and IBD epide- However, the relation between smoking and IBD may be
miology [18]. Young females at the age of 10–14 years more complex than previously thought. Moreover, it ap-
showed a significantly lower risk for CD compared to pears to be gender-specific. Cosnes et al. [25] identified
men. A reduction in CD incidence of up to 20% has been a protective effect of smoking in terms of UC develop-
reported. In contrast, females with an age of 25–29 years ment and disease course in male patients only. More-
and particularly those older than 35 years are more prone over, a decrease in the need for immunosuppressive
to CD compared to their male counterparts. An increased treatment was seen in smoking male patients, but not
risk of up to 40% has been observed [18]. Older males females [25]. In CD, the deleterious effects of smoking
(>45 years) appear to have a 20% higher incidence rate of
  were seen in females, but not in males [25]. Female IBD
UC compared to women [18]. These results have poten- patients probably have the highest benefit from smoking
tial clinical implications. Since older male patients are cessation and should be encouraged to stop smoking, in
more likely to suffer from the de novo UC, this diagnosis both UC and CD. Given the excess rates of smoking CD
has to be considered particularly in elderly men with a females [24], smoking cessation programs should be tar-
chronic colonic inflammation of unknown etiology. geting those first.
However, data on potentially lower rates of IBD in young A plethora of other gender-specific environmental fac-
females should be interpreted cautiously, and diagnostic tors potentially contribute to the development of IBD and
evaluation should be based on clinical presentation rath- disease complications. There appear to be considerable
er than reported incidence rates. This is particularly true differences in terms of substance exposure between men
in light of the significantly increased diagnostic delay for and women, such as seen for drugs, chemical substances

Gender Differences in IBD Digestion 2020;101(suppl 1):98–104 99

DOI: 10.1159/000504701
related to occupation, sunlight and vitamin D, lifestyle Disease Activity and Phenotype
factors including sleep, and shiftwork. However, the spe-
cific contribution of these factors to IBD has yet to be de- Data regarding the influence of gender on disease activ-
termined in more detail. Of note, hormone exposure dur- ity and disease course are conflicting: in some studies, no
ing childhood, puberty, and menopause/andropause association has been found, while in others male sex has
might play a role in IBD pathogenesis and disease course been identified as an independent prognostic factor for
[6]. A clear gender-specific association with IBD has been severe disease [38, 39]. Some studies – however – reported
established for antibiotics and appendectomy. Antibiotic higher rates of remission in males and increased disease
use is more frequently reported among male patients, and activity in females [40, 41]. Data are more consistent when
boys may develop IBD more often after intake of antibiot- it comes to extraintestinal manifestations (EIM). EIM rep-
ics [26]. Appendectomy has been linked to a higher risk resent 1 important aspect of disease burden and IBD activ-
of CD in female patients [22]. The microbiome has been ity and show a well-established gender-specific distribu-
increasingly recognized as a key player in the pathogen- tion. While peripheral joint affections and skin manifesta-
esis of IBD [27]. Gender-specific differences in the micro- tions such as erythema nodosum, pyoderma gangrenosum,
biota composition have been described [28]. However, and eye disorders are more frequently encountered in fe-
their specific contribution to the development and dis- males, primary sclerosing cholangitis and ankylosing
ease course of IBD remains elusive. spondylitis are more common in males [42]. Overall, EIM
are more common in female IBD patients [17].
IBD phenotype and location also show gender-specif-
Genetics ic differences. Our Swiss group recently described an as-
sociation between sex and upper gastrointestinal tract in-
Female preponderance appears to be higher in familial volvement (L4 according to Montreal classification) [43].
compared to sporadic IBD cases (61 vs. 54%) [29]. More- Male sex and young age were identified as the main risk
over, higher female-to-female transmission rates have factors for the involvement of the upper gastrointestinal
been identified (compared to female-to-male transmis- tract in CD patients [43]. In another study, male sex has
sion) [29]. This so-called female imprinting was specifi- been significantly associated with ileal disease in CD (28
cally seen in CD. These findings shed light on a possible vs. 20% in females) [17]. These findings suggest that IBD
gender-specific genetic predisposition. In addition, sev- presents differently in men and women.
eral known susceptibility gene variants have been linked
to a gender-specific risk increase/decrease for IBD.
Among those are R30Q DLG5 in CD (male-specific risk), Disease Complications
IL-23R variant L310P (protects women, but not men
from developing UC), and a single nucleotide polymor- For some IBD-related complications, a clear associa-
phism in the promoter region of IL-10 (increased risk for tion with male or female sex has been reported. Colon
UC in females) [30–33]. Mechanistic explanations for cancer is more frequent in male IBD patients [44]. In ad-
these differences are however lacking. A further mecha- dition, mortality from colorectal cancer appears to be
nism for gender-specific differences in IBD genetics is re- higher in men than in women [45]. On the other hand,
lated to X-chromosome abnormalities. X-chromosome pulmonary complications show a higher mortality in fe-
abnormalities have been increasingly recognized as a pos- male CD patients [46]. For other complications, gender-
sible contributor to autoimmunity [34, 35]. Loss of the specificity is less clear and data are conflicting. A large
X-chromosome in peripheral T- and B-lymphocytes has prospective study from the Netherlands including 1,106
been associated with various immune-mediated disor- patients with CD and UC and a mean follow-up of 7 years
ders such as primary biliary cholangitis, autoimmune did not identify gender as prognostic factor for the devel-
thyroid disease, Reynolds syndrome, and systemic sclero- opment of IBD complications. These complications in-
sis [34, 36]. Loss of specific X-linked genes might result cluded surgery, cumulative medication use, disease re-
in the formation of autoantibodies [36]. If a similar mech- currence after surgery, and disease severity [38]. In con-
anism is involved in IBD remains unknown. Of note and trast, a smaller study from Israel with 260 CD patients and
in accordance with this hypothesis, Turner syndrome, a a follow-up of 12 years revealed 2 independent prognostic
disease where X-monosomy occurs in every cell, is associ- factors for the development of complications: smoking
ated with an increased rate of IBD [37]. and male sex. The latter showed an OR of 2.6 [39]. In line

100 Digestion 2020;101(suppl 1):98–104 Greuter/Manser/Pittet/Vavricka/

DOI: 10.1159/000504701 Biedermann
 Adherence Initiation of
to treatment biologics

Compliance lower Females less often

in females treated with anti-TNF

Gender-specific treatment Response to

Surgery
considerations treatment

Major abdominal Loss of response

surgery more to ADA in males
frequent in males Drug survival
Inconsistent data lower in females
on ileocecal Side-effects Drug
resection and small of biologics monitoring
bowel resection
Higher rates of More side-effects Different
postoperative in females pharmacokinetics
recurrence in due to gender-specific
Fig. 1. Synopsis of gender-specific treat- females body composition
ment considerations. ADA, adalimumab.

with these findings, a study from Mayo Clinic revealed regardless of intestinal disease activity, a fact that raises
male sex as an independent predictive factor for major concerns about an adequate assessment of patients’ dis-
abdominal surgery including bowel resection and ileoce- ease presentation and progression as well as the physi-
cal resection [47]. The Dutch IBD biobank – however – cian-derived integration of results from diagnostic test-
demonstrated increased rates of small bowel and ileocecal ing. Although data are limited, the following findings
resection in female patients [17]. have been reported. Females are considered to receive no
Osteopenia and osteoporosis represent possible IBD-re- specific IBD treatment in a higher proportion than males
lated complications that are gender-specific. Counterintui- [40]. In addition to medical treatment, major abdominal
tively, osteopenia and osteoporosis were more frequently surgeries appear to be done more often in men than wom-
reported in male (55.9%) than female IBD patients (29.6%) en, although data on intestinal resection and ileocecal re-
in a retrospective single-center study from Germany (with section are conflicting as previously mentioned [17, 47,
dual-energy X-ray absorptiometry scans available for 174 50]. In the Dutch COIN study, there was no large gender-
patients). The gender-specific difference was mainly due to specific difference regarding IBD treatment. Still, male
different rates of osteopenia rather than osteoporosis [48]. CD patients received prednisone more often [17].
Similar findings have been reported in studies from Japan, No clear trend has been identified regarding anti-tu-
the UK, and the Netherlands. Screening for the presence of mor necrosis factor outcome in 2 studies [51, 52]. How-
osteopenia and osteoporosis is important in IBD patients ever, a shorter time until loss of response has been as-
and recommended by current society guidelines. Based on sociated with male sex in patients treated with adalim-
these findings, screening should be particularly promoted umab. In addition, dose intensification was more often
in male patients. However, a recent analysis of the Swiss IBD needed in men than in women [51]. Male gender was
cohort revealed widely differing screening rates with rates identified as an independent predictor of loss of re-
as low as 11% in some centers [49]. sponse and need for dose intensification, together with
known risk factors such as smoking, family history, iso-
lated colonic disease, EIM, and longer disease duration
Treatment and Adherence [51]. In contrast, a more recent investigation with a me-
dian follow-up of 6 years revealed that drug survival was
Gender-specific differences are most impactful when higher in males compared to females (48.1 vs. 30.8%, p =
it comes to IBD management. Indeed, use of and response 0.016). This might be attributed to higher rates of side
to IBD treatment seem to vary between men and women effects to biologics in females than males [53]. Female

Gender Differences in IBD Digestion 2020;101(suppl 1):98–104 101

DOI: 10.1159/000504701
Table 1. Most important aspects that are relevant in daily clinical be quite consistent. The fact that prevalence of depression
practice when dealing with gender-specific issues in IBD is higher in women than in men is not surprising
given comparable results in the general population [55].
Dimension Gender-specific difference
Women tend to use the healthcare system more often and
Epidemiology Higher rates of CD in females in EU and US absence from work seems to be higher [56]. Self-reported
Higher rates of CD in males in Asia quality of life is lower in females than in males [56–58].
Young females with lower risk for CD, older Fatigue represents an important clinical symptom that is
females with higher risk
Older males with higher risk for UC
often underrecognized among physicians involved in
IBD care. Several studies have revealed that fatigue is
Environmental Appendectomy and smoking in females highly frequent in IBD [59–62]. Of note, there is a well-
factors Antibiotic use in males
established gender-specific difference in terms of fatigue:
Genetics Female imprinting in familial IBD female subjects tend to have a higher prevalence of fatigue
Susceptibility gene variants such as IL-23R
variant L310P (protects women but not men
and this finding is reported across all age groups (Swiss
from getting UC) IBD cohort study, unpublished data). These findings are
X-chromosome abnormalities irrespective of the presence or absence of anemia, a typi-
Disease activity EIM more frequent in females cal contributor to the symptoms of fatigue [60]. More-
and phenotype Upper GI involvement in males over, gender-specific difference in the prevalence of fa-
Ileal disease more frequent in males tigue is independent of underlying disease activity [60].
Disease Higher risk and mortality for CRC in males Both frequency and intensity of fatigue are more promi-
complications Higher mortality of pulmonary complications nent in the female population. IBD further has a negative
in females impact on body image, more so in females than in males
Osteopenia more frequent in males [63, 64]. Reduced sexual activity is more frequently re-
Treatment Male gender associated with loss of response ported in female than male IBD patients (66.3 vs. 40.5%,
to anti-TNF p < 0.001) [64]. It is essential that these aspects are not
Drug survival higher in males neglected in daily clinical practice.
More side-effects to anti-TNF in females
Adherence rates lower in females
Psychosocial Depression more frequent in females
factors Self-reported QoL lower in females
Clinical Implications of Gender Differences
Fatigue more frequent in females
The most important aspects that are relevant for gas-
CD, Crohn’s disease; UC, ulcerative colitis; IBD, inflammatory troenterologists, when dealing with gender-specific is-
bowel disease; EIM, extraintestinal manifestations; IL, interleukin; sues in daily practice, are summarized in Table 1. In the
CRC, colorectal cancer; TNF, tumor necrosis factor; QoL, quality
of life. era of personalized medicine and in light of potent bio-
logical treatment options, it may not be adequate any-
more to treat patients without acknowledging their sex.
Tailored treatment strategies for individual patients are
gender (together with smoking) was identified as an in- needed, and for this, sex has to be taken into account as
dependent prognostic factor for nonadherence to bio- an important variable in addition to disease activity, phe-
logical treatment [54]. Neglecting these gender-specific notype, location, behavior, presence of complications,
aspects may potentially result in suboptimal treatment EIM, and so on. While sex as a modulating factor in IBD
of men, women, or both. Figure 1 summarizes factors development and progression has been increasingly rec-
that need to be considered, when it comes to gender- ognized in recent years, data are as of yet conflicting.
specific treatment approaches. Most evident and probably most clinically relevant are
the following aspects: (1) smoking is a problem and risk
factor particularly in females suffering from CD; (2) os-
Psychological Factors teopenia is more frequently observed in men than wom-
en; and (3) side-effects from biologics are higher in fe-
While data regarding epidemiology, disease course, males than males, which is presumably among the major
and treatment can be conflicting, data on psychosocial driving forces for a lower treatment adherence in women.
functioning and psychiatric co-disorders in IBD seem to Based on these findings, clinicians should (1) assess

102 Digestion 2020;101(suppl 1):98–104 Greuter/Manser/Pittet/Vavricka/

DOI: 10.1159/000504701 Biedermann
smoking status in women in particular and encourage Pfizer, Takeda, Tillots, UCB, Vifor and Falk Pharma GmbH. L.B.
smoking cessation in this patient population; (2) screen received consulting fees from Abbvie, MSD, Vifor, Ferring, Pfizer,
Shire, Takeda, UCB, Janssen and travel grants from Abbvie, MSD,
for osteopenia/osteoporosis especially in male IBD pa- Vifor, Pfizer, Takeda. No company representative was involved in
tients; and (3) consider women in particular to be nonad- conception, writing, or financing of this study.
herent to biological treatment. Side-effects should be par-
ticularly inquired. These 3 simple recommendations are
a first step toward a gender-specific IBD management Funding Sources
and will improve patient care.
There is no funding to declare.

Disclosure Statement
Author Contributions
T.G. has a consulting contract with Sanofi-Aventis, received a
travel grant from Falk Pharma GmbH and Vifor, and an unre- T.G. and L.B. drafted and wrote the manuscrcipt and created
stricted research grant from Novartis. S.R.V. received consultant tables and figures. C.M., V.P., and S.R.V. provided critical input at
fees and unrestricted research grants from Abbott, Ferring, MSD, any stage of writing and contributed to the literature research.

References
  1 Kane SV, Sable K, Hanauer SB. The menstru- 12 Whelan G. Epidemiology of inflammatory Cohort Study Group. Diagnostic delay in
al cycle and its effect on inflammatory bowel bowel disease. Med Clin North Am. 1990 Jan; Crohn’s disease is associated with a compli-
disease and irritable bowel syndrome: a prev- 74(1):1–12. cated disease course and increased operation
alence study. Am J Gastroenterol. 1998 Oct; 13 Brahme F, Lindström C, Wenckert A. Crohn’s rate. Am J Gastroenterol. 2013 Nov; 108(11):
93(10):1867–72. disease in a defined population. An epidemio- 1744–53; quiz 1754.
  2 Rosenblatt E, Kane S. Sex-Specific Issues in logical study of incidence, prevalence, mortal- 21 Hausmann J, Blumenstein I. [Gender differ-
Inflammatory Bowel Disease. Gastroenterol ity, and secular trends in the city of Malmö, ences and inflammatory bowel disease]. Z
Hepatol (N Y). 2015 Sep;11(9):592–601. Sweden. Gastroenterology. 1975 Aug; 69(2): Gastroenterol. 2015 Aug;53(8):774–8.
  3 Fish EN. The X-files in immunity: sex-based 342–51. 22 Andersson RE, Olaison G, Tysk C, Ekbom A.
differences predispose immune responses. 14 Prideaux L, Kamm MA, De Cruz PP, Chan Appendectomy is followed by increased risk
Nat Rev Immunol. 2008 Sep;8(9):737–44. FK, Ng SC. Inflammatory bowel disease in of Crohn’s disease. Gastroenterology. 2003
  4 Liang Y, Tsoi LC, Xing X, Beamer MA, Swin- Asia: a systematic review. J Gastroenterol Jan;124(1):40–6.
dell WR, Sarkar MK, et al. A gene network Hepatol. 2012 Aug;27(8):1266–80. 23 Lakatos PL, Vegh Z, Lovasz BD, David G,
regulated by the transcription factor VGLL3 15 Yang SK, Loftus EV Jr, Sandborn WJ. Epidemi- Pandur T, Erdelyi Z, et al. Is current smoking
as a promoter of sex-biased autoimmune dis- ology of inflammatory bowel disease in Asia. still an important environmental factor in in-
eases. Nat Immunol. 2017 Feb;18(2):152–60. Inflamm Bowel Dis. 2001 Aug;7(3):260–70. flammatory bowel diseases? Results from a
  5 Whitacre CC. Sex differences in autoimmune 16 Leong RW, Lau JY, Sung JJ. The epidemiology population-based incident cohort. Inflamm
disease. Nat Immunol. 2001 Sep;2(9):777–80. and phenotype of Crohn’s disease in the Chi- Bowel Dis. 2013 Apr;19(5):1010–7.
  6 Ngo ST, Steyn FJ, McCombe PA. Gender dif- nese population. Inflamm Bowel Dis. 2004 24 Biedermann L, Fournier N, Misselwitz B, Frei
ferences in autoimmune disease. Front Neu- Sep;10(5):646–51. P, Zeitz J, Manser CN, et al.; Swiss Inflamma-
roendocrinol. 2014 Aug;35(3):347–69. 17 Severs M, Spekhorst LM, Mangen MJ, Dijks- tory Bowel Disease Cohort Study Group.
  7 Gale EA, Gillespie KM. Diabetes and gender. tra G, Löwenberg M, Hoentjen F, et al. Sex- High Rates of Smoking Especially in Female
Diabetologia. 2001 Jan;44(1):3–15. Related Differences in Patients With Inflam- Crohn’s Disease Patients and Low Use of
  8 Wagtmans MJ, Verspaget HW, Lamers CB, matory Bowel Disease: Results of 2 Prospec- Supportive Measures to Achieve Smoking
van Hogezand RA. Gender-related differenc- tive Cohort Studies. Inflamm Bowel Dis. 2018 Cessation–Data from the Swiss IBD Cohort
es in the clinical course of Crohn’s disease. May;24(6):1298–306. Study. J Crohn’s Colitis. 2015 Oct;9(10):819–
Am J Gastroenterol. 2001 May;96(5):1541–6. 18 Shah SC, Khalili H, Gower-Rousseau C, Olen 29.
 9 Kyle J. Crohn’s disease in the northeastern O, Benchimol EI, Lynge E, et al. Sex-Based Dif- 25 Cosnes J, Nion-Larmurier I, Afchain P,
and northern Isles of Scotland: an epidemio- ferences in Incidence of Inflammatory Bowel Beaugerie L, Gendre JP. Gender differences in
logical review. Gastroenterology. 1992 Aug; Diseases-Pooled Analysis of Population- the response of colitis to smoking. Clin Gas-
103(2):392–9. Based Studies From Western Countries. Gas- troenterol Hepatol. 2004 Jan;2(1):41–8.
10 Latour P, Louis E, Belaiche J. Incidence of in- troenterology. 2018 Oct; 155(4): 1079–1089. 26 Kronman MP, Zaoutis TE, Haynes K, Feng R,
flammatory bowel disease in the area of Liège: a e3. Coffin SE. Antibiotic exposure and IBD de-
3 years prospective study (1993-1996). Acta 19 Vavricka SR, Spigaglia SM, Rogler G, Pittet V, velopment among children: a population-
Gastroenterol Belg. 1998 Oct-Dec;61(4):410–3. Michetti P, Felley C, et al.; Swiss IBD Cohort based cohort study. Pediatrics. 2012 Oct;
11 Shivananda S, Peña AS, Nap M, Weterman IT, Study Group. Systematic evaluation of risk 130(4):e794–803.
Mayberry JF, Ruitenberg EJ, et al. Epidemiol- factors for diagnostic delay in inflammatory 27 Yilmaz B, Juillerat P, Øyås O, Ramon C, Bravo
ogy of Crohn’s disease in Regio Leiden, The bowel disease. Inflamm Bowel Dis. 2012 Mar; FD, Franc Y, et al.; Swiss IBD Cohort Investi-
Netherlands. A population study from 1979 to 18(3):496–505. gators. Microbial network disturbances in re-
1983. Gastroenterology. 1987 Nov;93(5):966– 20 Schoepfer AM, Dehlavi MA, Fournier N, Saf- lapsing refractory Crohn’s disease. Nat Med.
74. roneeva E, Straumann A, Pittet V, et al.; IBD 2019 Feb;25(2):323–36.

Gender Differences in IBD Digestion 2020;101(suppl 1):98–104 103

DOI: 10.1159/000504701
28 Bolnick DI, Snowberg LK, Hirsch PE, Lauber activity: a subgroup analysis of a large multi- 52 Sprakes MB, Ford AC, Warren L, Greer D,
CL, Org E, Parks B, et al. Individual diet has centre, prospective, internet-based study. J Hamlin J. Efficacy, tolerability, and predictors
sex-dependent effects on vertebrate gut mi- Crohn’s Colitis. 2011 Jun;5(3):203–10. of response to infliximab therapy for Crohn’s
crobiota. Nat Commun. 2014 Jul;5(1):4500. 41 Bokemeyer B, Hardt J, Hüppe D, Prenzler A, disease: a large single centre experience. J
29 Zelinkova Z, Stokkers PC, van der Linde K, Conrad S, Düffelmeyer M, et al. Clinical sta- Crohn’s Colitis. 2012 Mar;6(2):143–53.
Kuipers EJ, Peppelenbosch MP, van der tus, psychosocial impairments, medical treat- 53 Lie MR, Kreijne JE, van der Woude CJ. Sex Is
Woude CP. Maternal imprinting and female ment and health care costs for patients with Associated with Adalimumab Side Effects and
predominance in familial Crohn’s disease. J inflammatory bowel disease (IBD) in Germa- Drug Survival in Patients with Crohn’s Dis-
Crohn’s Colitis. 2012 Aug;6(7):771–6. ny: an online IBD registry. J Crohn’s Colitis. ease. Inflamm Bowel Dis. 2017 Jan;23(1):75–
30 Biank V, Friedrichs F, Babusukumar U, Wang 2013 Jun;7(5):355–68. 81.
T, Stoll M, Broeckel U, et al. DLG5 R30Q vari- 42 Bernstein CN, Blanchard JF, Rawsthorne P, 54 Lopez A, Billioud V, Peyrin-Biroulet C, Pey-
ant is a female-specific protective factor in pe- Yu N. The prevalence of extraintestinal dis- rin-Biroulet L. Adherence to anti-TNF thera-
diatric onset Crohn’s disease. Am J Gastroen- eases in inflammatory bowel disease: a popu- py in inflammatory bowel diseases: a system-
terol. 2007 Feb;102(2):391–8. lation-based study. Am J Gastroenterol. 2001 atic review. Inflamm Bowel Dis. 2013 Jun;
31 Browning BL, Annese V, Barclay ML, Bing- Apr;96(4):1116–22. 19(7):1528–33.
ham SA, Brand S, Büning C, et al. Gender- 43 Greuter T, Piller A, Fournier N, Safroneeva 55 Häuser W, Janke KH, Klump B, Hinz A. Anx-
stratified analysis of DLG5 R30Q in 4707 pa- E, Straumann A, Biedermann L, et al.; Swiss iety and depression in patients with inflam-
tients with Crohn disease and 4973 controls IBD Cohort Study Group. Upper Gastroin- matory bowel disease: comparisons with
from 12 Caucasian cohorts. J Med Genet. testinal Tract Involvement in Crohn’s Dis- chronic liver disease patients and the general
2008 Jan;45(1):36–42. ease: Frequency, Risk Factors, and Disease population. Inflamm Bowel Dis. 2011 Feb;
32 Lin Z, Poritz L, Franke A, Li TY, Ruether A, Course. J Crohn’s Colitis. 2018 Nov; 12(12): 17(2):621–32.
Byrnes KA, et al. Genetic association of non- 1399–409. 56 Nurmi E, Haapamäki J, Paavilainen E, Ran-
synonymous variants of the IL23R with famil- 44 Söderlund S, Brandt L, Lapidus A, Karlén P, tanen A, Hillilä M, Arkkila P. The burden of
ial and sporadic inflammatory bowel disease Broström O, Löfberg R, et al. Decreasing time- inflammatory bowel disease on health care
in women. Dig Dis Sci. 2010 Mar; 55(3): 739– trends of colorectal cancer in a large cohort of utilization and quality of life. Scand J Gastro-
46. patients with inflammatory bowel disease. enterol. 2013 Jan;48(1):51–7.
33 Tedde A, Laura Putignano A, Bagnoli S, Con- Gastroenterology. 2009 May; 136(5): 1561–7; 57 Graff LA, Walker JR, Lix L, Clara I, Raw-
gregati C, Milla M, Sorbi S, et al. Interleu- quiz 1818–9. sthorne P, Rogala L, et al. The relationship of
kin-10 promoter polymorphisms influence 45 Sebastian S, Hernández V, Myrelid P, Kariv R, inflammatory bowel disease type and activity
susceptibility to ulcerative colitis in a gender- Tsianos E, Toruner M, et al. Colorectal cancer to psychological functioning and quality of
specific manner. Scand J Gastroenterol. 2008; in inflammatory bowel disease: results of the life. Clin Gastroenterol Hepatol. 2006 Dec;
43(6):712–8. 3rd ECCO pathogenesis scientific workshop 4(12):1491–501.
34 Svyryd Y, Hernández-Molina G, Vargas F, (I). J Crohn’s Colitis. 2014 Jan;8(1):5–18. 58 Hauser G, Tkalcić M, Stimac D, Milić S, Sincić
Sánchez-Guerrero J, Segovia DA, Mutchinick 46 Jussila A, Virta LJ, Pukkala E, Färkkilä MA. BM. Gender related differences in quality of
OM. X chromosome monosomy in primary Mortality and causes of death in patients with life and affective status in patients with in-
and overlapping autoimmune diseases. Auto- inflammatory bowel disease: a nationwide flammatory bowel disease. Coll Antropol.
immun Rev. 2012 Mar;11(5):301–4. register study in Finland. J Crohn’s Colitis. 2011 Sep;35(Suppl 2):203–7.
35 Libert C, Dejager L, Pinheiro I. The X chro- 2014 Sep;8(9):1088–96. 59 Saraiva S, Cortez-Pinto J, Barosa R, Castela J,
mosome in immune functions: when a chro- 47 Peyrin-Biroulet L, Harmsen WS, Tremaine Moleiro J, Rosa I, et al. Evaluation of fatigue
mosome makes the difference. Nat Rev Im- WJ, Zinsmeister AR, Sandborn WJ, Loftus EV in inflammatory bowel disease - a useful tool
munol. 2010 Aug;10(8):594–604. Jr. Surgery in a population-based cohort of in daily practice. Scand J Gastroenterol. 2019
36 Invernizzi P, Miozzo M, Selmi C, Persani L, Crohn’s disease from Olmsted County, Min- Apr;54(4):465–70.
Battezzati PM, Zuin M, et al. X chromosome nesota (1970–2004). Am J Gastroenterol. 60 Bager P, Befrits R, Wikman O, Lindgren S,
monosomy: a common mechanism for auto- 2012 Nov;107(11):1693–701. Moum B, Hjortswang H, et al. Fatigue in out-
immune diseases. J Immunol. 2005 Jul;175(1): 48 Walldorf J, Krummenerl A, Engler K, Busch patients with inflammatory bowel disease is
575–8. J, Dollinger MM, Seufferlein T, et al. Health common and multifactorial. Aliment Phar-
37 Arulanantham K, Kramer MS, Gryboski JD. care for osteoporosis in inflammatory bowel macol Ther. 2012 Jan;35(1):133–41.
The association of inflammatory bowel dis- disease: unmet needs in care of male patients? 61 Le Berre C, Peyrin-Biroulet L, Buisson A,
ease and X chromosomal abnormality. Pedi- J Crohn’s Colitis. 2013 Dec;7(11):901–7. Olympie A, Ravel MH, Bienenfeld C, et al.
atrics. 1980 Jul;66(1):63–7. 49 Schüle S, Rossel JB, Frey D, Biedermann L, Impact of inflammatory bowel diseases on
38 Romberg-Camps MJ, Dagnelie PC, Kester AD, Scharl M, Zeitz J, et al.; Swiss IBD cohort working life: A French nationwide survey.
Hesselink-van de Kruijs MA, Cilissen M, En- study. Widely differing screening and treat- Dig Liver Dis. 2019 Jul;51(7):961–6.
gels LG, et al. Influence of phenotype at diag- ment practice for osteoporosis in patients 62 Van de Vijver E, Van Gils A, Beckers L, Van
nosis and of other potential prognostic factors with inflammatory bowel diseases in the Swiss Driessche Y, Moes ND, van Rheenen PF. Fa-
on the course of inflammatory bowel disease. IBD cohort study. Medicine (Baltimore). 2017 tigue in children and adolescents with inflam-
Am J Gastroenterol. 2009 Feb;104(2):371–83. Jun;96(22):e6788. matory bowel disease. World J Gastroenterol.
39 Mazor Y, Maza I, Kaufman E, Ben-Horin S, 50 Samuel S, Ingle SB, Dhillon S, Yadav S, Harm- 2019 Feb;25(5):632–43.
Karban A, Chowers Y, et al. Prediction of dis- sen WS, Zinsmeister AR, et al. Cumulative in- 63 Trindade IA, Ferreira C, Pinto-Gouveia J. The
ease complication occurrence in Crohn’s dis- cidence and risk factors for hospitalization effects of body image impairment on the qual-
ease using phenotype and genotype parame- and surgery in a population-based cohort of ity of life of non-operated Portuguese female
ters at diagnosis. J Crohn’s Colitis. 2011 Dec; ulcerative colitis. Inflamm Bowel Dis. 2013 IBD patients. Qual Life Res. 2017 Feb; 26(2):
5(6):592–7. Aug;19(9):1858–66. 429–36.
40 Blumenstein I, Herrmann E, Filmann N, Zo- 51 Billioud V, Sandborn WJ, Peyrin-Biroulet L. 64 Jedel S, Hood MM, Keshavarzian A. Getting
sel C, Tacke W, Bock H, et al. Female patients Loss of response and need for adalimumab personal: a review of sexual functioning, body
suffering from inflammatory bowel diseases dose intensification in Crohn’s disease: a sys- image, and their impact on quality of life in
are treated less frequently with immunosup- tematic review. Am J Gastroenterol. 2011 patients with inflammatory bowel disease. In-
pressive medication and have a higher disease Apr;106(4):674–84. flamm Bowel Dis. 2015 Apr;21(4):923–38.

104 Digestion 2020;101(suppl 1):98–104 Greuter/Manser/Pittet/Vavricka/

DOI: 10.1159/000504701 Biedermann