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http://dx.doi.org/10.5056/jnm18082

Sex-Gender Differences in Irritable Bowel Syndrome  

Kim, Young Sun (Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center)
Kim, Nayoung (Seoul National University Bundang Hospital)
Publication Information
Journal of Neurogastroenterology and Motility / v.24, no.4, 2018 , pp. 544-558 More about this Journal
Abstract
Because of the sex-gender differences that are shown in a diversity of physiological and psychological factors, it can be speculated that the clinical presentation of symptoms as well as treatment strategies in women and men with irritable bowel syndrome (IBS) may differ. Studies have revealed that IBS is more common in women than men. As for the IBS subtype, IBS with constipation is significantly more prevalent among women than men. Sex hormones and gender differences may play important roles in the pathophysiology of IBS. However, its pathophysiologic mechanisms still remain largely unknown, and therapeutic implications are limited. Moreover, women IBS patients have been reported to feel more fatigue, depression, anxiety, and lower quality of life than men IBS patients. Furthermore, there has been evidence of differences in the appropriate treatment efficacy to IBS in men and women, although relatively few men are enrolled in most relevant clinical trials. A more sex-gender-oriented approach in the medical care setting could improve understanding of heterogeneous patients suffering from IBS. An individualized and multicomponent approach including sex and gender issues might help improve the treatment of IBS.
Keywords
Gender; Hormones; Irritable bowel syndrome; Sex;
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1 Kim SY, Choung RS, Lee SK, et al. Self reported sleep impairment in functional dyspepsia and irritable bowel syndrome. J Neurogastroenterol Motil 2018;24:280-288.   DOI
2 Simren M, Abrahamsson H, Svedlund J, Bjornsson ES. Quality of life in patients with irritable bowel syndrome seen in referral centers versus primary care: the impact of gender and predominant bowel pattern. Scand J Gastroenterol 2001;36:545-552.   DOI
3 Choi YJ, Park YS, Kim N, et al. Gender differences in ghrelin, nociception genes, psychological factors and quality of life in functional dyspepsia. World J Gastroenterol 2017;23:8053-8061.   DOI
4 Park JM, Choi MG, Kim YS, et al. Quality of life of patients with irritable bowel syndrome in Korea. Qual Life Res 2009;18:435-446.   DOI
5 Corney RH, Stanton R. Physical symptom severity, psychological and social dysfunction in a series of outpatients with irritable bowel syndrome. J Psychosom Res 1990;34:483-491.   DOI
6 Schumann D, Klose P, Lauche R, Dobos G, Langhorst J, Cramer H. Low fermentable, oligo-, di-, mono-saccharides and polyol diet in the treatment of irritable bowel syndrome: a systematic review and metaanalysis. Nutrition 2018;45:24-31.   DOI
7 Johanson JF, Morton D, Geenen J, Ueno R. Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of lubiprostone, a locally-acting type-2 chloride channel activator, in patients with chronic constipation. Am J Gastroenterol 2008;103:170-177.   DOI
8 Fukudo S, Kinoshita Y, Okumura T, et al. Effect of ramosetron in female patients with irritable bowel syndrome with diarrhea: a phase III longterm study. J Gastroenterol 2016;51:874-882.   DOI
9 Qi Q, Zhang Y, Chen F, Zuo X, Li Y. Ramosetron for the treatment of irritable bowel syndrome with diarrhea: a systematic review and metaanalysis of randomized controlled trials. BMC Gastroenterol 2018;18:5.   DOI
10 Ustun TB. Cross-national epidemiology of depression and gender. J Gend Specif Med 2000;3:54-58.
11 Lee KJ, Kim NY, Kwon JK, et al. Efficacy of ramosetron in the treatment of male patients with irritable bowel syndrome with diarrhea: a multicenter, randomized clinical trial, compared with mebeverine. Neurogastroenterol Motil 2011;23:1098-1104.   DOI
12 Faresjo A, Grodzinsky E, Johansson S, Wallander MA, Timpka T, Akerlind I. A population-based case-control study of work and psychosocial problems in patients with irritable bowel syndrome-women are more seriously affected than men. Am J Gastroenterol 2007;102:371-379.   DOI
13 Halder SL, Locke GR 3rd, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ 3rd. Impact of functional gastrointestinal disorders on healthrelated quality of life: a population-based case-control study. Aliment Pharmacol Ther 2004;19:233-242.   DOI
14 Michalsen VL, Vandvik PO, Farup PG. Predictors of health-related quality of life in patients with irritable bowel syndrome. A cross-sectional study in Norway. Health Qual Life Outcomes 2015;13:113.   DOI
15 Hulme K, Chilcot J, Smith MA. Doctor-patient relationship and quality of life in irritable bowel syndrome: an exploratory study of the potential mediating role of illness perceptions and acceptance. Psychol Health Med 2018;23:674-684.   DOI
16 Frissora CL, Koch KL. The role of gender and biological sex in irritable bowel syndrome. Curr Gastroenterol Rep 2005;7:257-263.   DOI
17 Ouyang A, Wrzos HF. Contribution of gender to pathophysiology and clinical presentation of IBS: should management be different in women? Am J Gastroenterol 2006;101(12 suppl):S602-S609.
18 Ringel Y, Carroll IM. Alterations in the intestinal microbiota and functional bowel symptoms. Gastrointest Endosc Clin N Am 2009;19:141-150, vii.   DOI
19 Camilleri M, Atanasova E, Carlson PJ, et al. Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome. Gastroenterology 2002;123:425-432.   DOI
20 Garsed K, Chernova J, Hastings M, et al. A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea. Gut 2014;63:1617-1625.   DOI
21 Fukudo S, Ida M, Akiho H, Nakashima Y, Matsueda K. Effect of ramosetron on stool consistency in male patients with irritable bowel syndrome with diarrhea. Clin Gastroenterol Hepatol 2014;12:953-959.e4.   DOI
22 Fukudo S, Kinoshita Y, Okumura T, et al. Ramosetron reduces symptoms of irritable bowel syndrome with diarrhea and improves quality of life in women. Gastroenterology 2016;150:358-366.e8.   DOI
23 Lembo A, Pimentel M, Rao SS, et al. Repeat treatment with rifaximin is safe and effective in patients with diarrhea-predominant irritable bowel syndrome. Gastroenterology 2016;151:1113-1121.   DOI
24 Ford AC, Quigley EM, Lacy BE, et al. Effect of antidepressants and psychological therapies, including hypnotherapy, in irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol 2014;109:1350-1365.   DOI
25 Distrutti E, Monaldi L, Ricci P, Fiorucci S. Gut microbiota role in irritable bowel syndrome: new therapeutic strategies. World J Gastroenterol 2016;22:2219-2241.   DOI
26 Kim Y, Kim SH, Whang KY, Kim YJ, Oh S. Inhibition of Escherichia coli O157: H7 attachment by interactions between lactic acid bacteria and intestinal epithelial cells. J Microbiol Biotechnol 2008;18:1278-1285.
27 Da Silva S, Robbe-Masselot C, Ait-Belgnaoui A, et al. Stress disrupts intestinal mucus barrier in rats via mucin O-glycosylation shift: prevention by a probiotic treatment. Am J Physiol Gastrointest Liver Physiol 2014;307:G420-G429.   DOI
28 Shastri P, McCarville J, Kalmokoff M, Brooks SP, Green-Johnson JM. Sex differences in gut fermentation and immune parameters in rats fed an oligofructose-supplemented diet. Biol Sex Differ 2015;6:13.   DOI
29 Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature 2012;489:242-249.   DOI
30 Cheney AM. "Most girls want to be skinny": body (dis)satisfaction among ethnically diverse women. Qual Health Res 2011;21:1347-1359.   DOI
31 Payne S. Sex, gender, and irritable bowel syndrome: making the connections. Gend Med 2004;1:18-28.   DOI
32 Ali A, Toner BB, Stuckless N, et al. Emotional abuse, self-blame and self-silencing in women with irritable bowel syndrome. Psychosom Med 2000;62:76-82.   DOI
33 Bjorkman I, Dellenborg L, Ringstrom G, Simren M, Jakobsson Ung E. The gendered impact of irritable bowel syndrome: a qualitative study of patients' experiences. J Adv Nurs 2014;70:1334-1343.   DOI
34 Pimentel M, Lembo A, Chey WD, et al.. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med 2011;364:22-32.   DOI
35 El-Serag HB. Impact of irritable bowel syndrome: prevalence and effect on health-related quality of life. Rev Gastroenterol Disord 2003;3(suppl 2):S3-S11.
36 Gibson PR,Varney J, Malakar S, Muir JG. Food components and irritable bowel syndrome. Gastroenterology 2015;148:1158-1174, e4.   DOI
37 O'Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology 2005;128:541-551.   DOI
38 Camilleri M, Northcutt AR, Kong S, Dukes GE, McSorley D, Mangel AW. Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial. Lancet 2000;355:1035-1040.   DOI
39 Lunsford TN, Harris LA. Lubiprostone: evaluation of the newest medication for the treatment of adult women with constipation-predominant irritable bowel syndrome. Int J Womens Health 2010;2:361-374.
40 Camilleri M, Mayer EA, Drossman DA, et al. Improvement in pain and bowel function in female irritable bowel patients with alosetron, a 5-HT3 receptor antagonist. Aliment Pharmacol Ther 1999;13:1149-1159.   DOI
41 Katsumata R, Shiotani A, Murao T, et al. Gender differences in serotonin signaling in patients with diarrhea-predominant irritable bowel syndrome. Intern Med 2017;56:993-999.   DOI
42 Scott LJ, Perry CM. Tegaserod. Drugs 1999;58:491-496; discussion 497-498.   DOI
43 Chang L, Ameen VZ, Dukes GE, McSorley DJ, Carter EG, Mayer EA. A dose-ranging, phase II study of the efficacy and safety of alosetron in men with diarrhea-predominant IBS. Am J Gastroenterol 2005;100:115-123.   DOI
44 Ford AC, Brandt LJ, Young C, Chey WD, Foxx-Orenstein AE, Moayyedi P. Efficacy of 5-HT3 antagonists and 5-HT4 agonists in irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol 2009;104:1831-1843.   DOI
45 Zheng Y, Yu T, Tang Y, et al. Efficacy and safety of 5-hydroxytryptamine 3 receptor antagonists in irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. PLoS One 2017;12:e0172846.   DOI
46 Barshop K, Staller K. Eluxadoline in irritable bowel syndrome with diarrhea: rationale, evidence and place in therapy. Ther Adv Chronic Dis 2017;8:153-160.   DOI
47 Lee HH, Choi YY, Choi MG. The Efficacy of hypnotherapy in the treatment of irritable bowel syndrome: a systematic reviewand metaanalysis. J Neurogastroenterol Motil 2014;20:152-162.   DOI
48 Johanson JF, Ueno R. Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety. Aliment Pharmacol Ther 2007;25:1351-1361.   DOI
49 Buscail C, Sabate JM, Bouchoucha M, et al. Association between selfreported vegetarian diet and the irritable bowel syndrome in the French- NutriNet cohort. PLoS One 2017;12:e0183039.   DOI
50 Lembo AJ, Schneier HA, Shiff SJ, et al. Two randomized trials of linaclotide for chronic constipation. N Engl J Med 2011;365:527-536.   DOI
51 Kilminster S, Downes J, Gough B, Murdoch-Eaton D, Roberts T. Women in medicine-is there a problem? A literature review of the changing gender composition, structures and occupational cultures in medicine. Medical Educ 2007;41:39-49.   DOI
52 Heils A, Teufel A, Petri S, et al. Allelic variation of human serotonin transporter gene expression. J Neurochem 1996;66:2621-2624.
53 Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional Bowel Disorders. Gastroenterology 2006;130:1480-1491.   DOI
54 Houghton LA, Heitkemper M, Crowell M, et al. Age, gender and women's health and the patient. Gastroenterology 2016;150:1332-1343, e4.   DOI
55 Wizemann TM, Pardue ML. Exploring the biological contributions to human health: does sex matter? Washington, DC: National Academies Press; 2001.
56 Kim YS, Kim N, Kim GH. Sex and gender differences in gastroesophageal reflux disease. J Neurogastroenterol Motil 2016;22:575-588.   DOI
57 Annandale E, Hammarstrom A. Constructing the 'gender-specific body': a critical discourse analysis of publications in the field of genderspecific medicine. Health 2011;15:571-587.   DOI
58 Ahlawat SK, Cuddihy MT, Locke GR 3rd. Gender-related differences in dyspepsia: a qualitative systematic review. Gender Med 2006;3:31-42.   DOI
59 Flier SN, Rose S. Is functional dyspepsia of particular concern in women? A review of gender differences in epidemiology, pathophysiologic mechanisms, clinical presentation, and management. Am J Gastroenterol 2006;101(12 suppl):S644-S653.
60 Choi YJ, Hwang SW, Kim N, Park JH, Oh JC, Lee DH. Association between SLC6A4 serotonin transporter gene linked polymorphic region and ADRA2A 1291C>G and irritable bowel syndrome in Korea. J Neurogastroenterol Motil 2014;20:388-399.   DOI
61 Chey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol 2012;107:1702-1712.   DOI
62 Lembo AJ, Lacy BE, Zuckerman MJ, et al. Eluxadoline for irritable bowel syndrome with diarrhea. N Engl J Med 2016;374:242-253.   DOI
63 Ford AC, Talley NJ, Spiegel BM, et al. Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. BMJ 2008;337:a2313.   DOI
64 Anderson GD. Sex and racial differences in pharmacological response: where is the evidence? Pharmacogenetics, pharmacokinetics, and pharmacodynamics. J Womens Health (Larchmt) 2005;14:19-29.   DOI
65 Tran C, Knowles SR, Liu BA, Shear NH. Gender differences in adverse drug reactions. J Clin Pharmacol 1998;38:1003-1009.   DOI
66 Kaiser J. Gender in the pharmacy: does it matter? Science 2005;308:1572.   DOI
67 Rademaker M. Do women have more adverse drug reactions? Am J Clin Dermatol 2001;2:349-351.   DOI
68 Meibohm B, Beierle I. Derendorf H. How important are gender differences in pharmacokinetics? Clin Pharmacokinet 2002;41:329-342.   DOI
69 Creed F. The relationship between psychosocial parameters and outcome in irritable bowel syndrome. Am J Med 1999;107(5A):74S-80S.
70 Yamada E, Tsunoda S, Abe T, et al. Factors associated with poor therapeutic response in outpatients with irritable bowel syndrome: a multicenter study in Japan. J Gastroenterol 2017;52:301-307.   DOI
71 Moayyedi P, Ford AC, Talley NJ, et al. The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gut 2010;59:325-332.   DOI
72 Dai C, Zheng CQ, Jiang M, Ma XY, Jiang LJ. Probiotics and irritable bowel syndrome. World J Gastroenterol 2013;19:5973-5980.   DOI
73 Lee BJ, Bak YT. Irritable bowel syndrome, gut microbiota and probiotics. J Neurogastroenterol Motil 2011;17:252-266.   DOI
74 Zahedi MJ, Behrouz V, Azimi M. Low fermentable oligo-di-monosaccharides and polyols diet versus general dietary advice in patients with diarrhea-predominant irritable bowel syndrome: a randomized controlled trial. J Gastroenterol Hepatol 2018;33:1192-1199.   DOI
75 Toner BB, Akman D. Gender role and irritable bowel syndrome: literature review and hypothesis. Am J Gastroenterol 2000;95:11-16.   DOI
76 Bohn L, Storsrud S, Tornblom H, Bengtsson U, Simren M. Selfreported food-related gastrointestinal symptoms in IBS are common and associated with more severe symptoms and reduced quality of life. Am J Gastroenterol 2013;108:634-641.   DOI
77 Varju P, Farkas N, Hegyi P, et al. Low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet improves symptoms in adults suffering from irritable bowel syndrome (IBS) compared to standard IBS diet: a meta-analysis of clinical studies. PLoS One 2017;12:e0182942.   DOI
78 Kim Y, Choi CH. Role of fructose malabsorption in patients with irritable bowel syndrome. J Neurogastroenterol Motil 2018;24:161-163.   DOI
79 Welen K, Faresjo A, Faresjo T. Functional dyspepsia affects women more than men in daily life: a case-control study in primary care. Gender Med 2008;5:62-73.   DOI
80 Lee OY. Asian motility studies in irritable bowel syndrome. J Neurogastroenterol Motil 2010;16:120-130.   DOI
81 Jung HK. Epidemiology of gastroesophageal reflux disease in Asia: a systematic review. J Neurogastroenterol Motil 2011;17:14-27.   DOI
82 Klem F, Wadhwa A, Prokop LJ, et al. Prevalence, risk factors, and outcomes of irritable bowel syndrome after infectious enteritis: a systematic review and meta-analysis. Gastroenterology 2017;152:1042-1054.e1.   DOI
83 Mulak A, Tache Y. Sex difference in irritable bowel syndrome: do gonadal hormones play a role? Gastroenterol Pol 2010;17:89-97.
84 Garcia Rodriguez LA, Ruigomez A, Wallander MA, Johansson S, Olbe L. Defection of colorectal tumor and inflammatory bowel disease during follow-up of patients with initial diagnosis of irritable bowel syndrome. Scand J Gastroenterol 2000;35:306-311.   DOI
85 Heitkemper MM, Chang L. Do fluctuations in ovarian hormones affect gastrointestinal symptoms in women with irritable bowel syndrome? Gend Med 2009;6(suppl 2):152-167.   DOI
86 Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology 2006;130:1480-1491.   DOI
87 Mulak A, Waszczuk E, Paradowski L. Irritable bowel syndrome as an interdisciplinary clinical problem. Adv Clin Exp Med 2008;17:667-675.
88 Lacy BE, Weiser K, Noddin L, et al. Irritable bowel syndrome: patients' attitudes, concerns and level of knowledge. Aliment Pharmacol Ther 2007;25:1329-1341.   DOI
89 Chandar AK. Diagnosis and treatment of irritable bowel syndrome with predominant constipation in the primary-care setting: focus on linaclotide. Int J Gen Med 2017;10:385-393.   DOI
90 Harris LA, Umar SB, Baffy N, Heitkemper MM. Irritable bowel syndrome and female patients. Gastroenterol Clin North Am 2016;45:179-204.   DOI
91 Cuomo R, Andreozzi P, Zito FP, Passananti V, De Carlo G, Sarnelli G. Irritable bowel syndrome and food interaction. World J Gastroenterol 2014;20:8837-8845.
92 Bohn L, Storsrud S, Liljebo T, et al. Diet low in FODMAPs reduces symptoms of irritable bowel syndrome as well as traditional dietary advice: a randomized controlled trial. Gastroenterology 2015;149:1399-1407.e2.   DOI
93 Jung KW, Seo M, Cho YH. et al. Prevalence of fructose malabsorption in patients with irritable syndrome after excluding small intestinal bacterial overgrowth. J Neurogastroenterol Motil 2018;24:307-316.   DOI
94 Lovell RM, Ford AC. Effect of gender on prevalence of irritable bowel syndrome in the community: systematic review and meta-analysis. Am J Gastroenterol 2012;107:991-1000.   DOI
95 Boeckxstaens GE, Drug V, Dumitrascu D, et al. Phenotyping of subjects for large scale studies on patients with IBS. Neurogastroenterol Motil 2016;28:1134-1147.   DOI
96 Talley NJ. Irritable bowel syndrome: definition, diagnosis and epidemiology. Baillieres Best Pract Res Clin Gastroenterol 1999;13:371-384.   DOI
97 Chial HJ, Camilleri M. Gender differences in irritable bowel syndrome. J Gend Specif Med 2002;5:37-45.
98 Song KH, Jung HK, Kim HJ, et al. Clinical practice guidelines for irritable bowel syndrome in Korea, 2017 revised edition. J Neurogastroenterol Motil 2018;24:197-215.   DOI
99 Chang L, Heitkemper MM. Gender differences in irritable bowel syndrome. Gastroenterology 2002;123:1686-1701.   DOI
100 Farhadi A, Banton D, Keefer L. Connecting our gut feeling and how our gut feels: the role of well-being attributes in irritable bowel syndrome. J Neurogastroenterol Motil 2018;24:289-298.   DOI
101 Meerveld BG, Johnson AC. Mechanisms of stress-induced visceral pain. J Neurogastroenterol Motil 2018;24:7-18.   DOI
102 Lee HF, Liu PY, Wang YP, Tsai CF, Chang FY, Lu CL. Sexual abuse is associated withan abnormal psychological profile and sleep difficulty in patients with irritable bowel syndrome in Taiwan. J Neurogastroenterol Motil 2018;24:79-86.   DOI
103 Choi YJ, Kim N, Yoon H, et al. Overlap between irritable bowel syndrome and functional dyspepsia including subtype analyses. J Gastroenterol Hepatol 2017;32:1553-1561.   DOI
104 Lampe JW, Fredstrom SB, Slavin JL, Potter JD. Sex differences in colonic function: a randomised trial. Gut 1993;34:531-536.   DOI
105 Sperber AD, Dumitrascu D, Fukudo S, et al. The global prevalence of IBS in adults remains elusive due to the heterogeneity of studies: a rome foundation working team literature reviw. Gut 2017;66:1075-1085.   DOI
106 Adeyemo MA, Spiegel BM, Chang L. Meta-analysis: do irritable bowel syndrome symtomes vary between men and wome? Aliment Pharmacol Ther 2010;32:738-755.   DOI
107 Drossman DA, Camilleri M, Mayer EA, Whitehead WE. AGA technical review on irritable bowel syndrome. Gastroenterology 2002;123:2108-2131.   DOI
108 Muller-Lissner SA, Bollani S, Brummer RJ, et al. Epidemiological aspects of irritable bowel syndrome in Europe and North America. Digestion 2001;64:200-204.   DOI
109 Warnock JK, Clayton AH. Chronic episodic disorders in women. Psychiatr Clin North Am 2003;26:725-740.   DOI
110 Ghoshal UC, Abraham P, Bhatt C, et al. Epidemiological and clinical profile of irritable bowel syndrome in India: report of the India society of gastroenterology task force. Indian J Gastroenterol 2008;27:22-28.
111 Chang L, Toner BB, Fukudo S, et al. Gender, age, society, culture, and the patient's perspective in the functional gastrointestinal disorders. Gastroenterology 2006;130:1435-1446.   DOI
112 Georgescu D, Reisz D, Gurban CV, et al. Migraine in young females with irritable bowel syndrome: still a challenge. Neuropsychiatr Dis Treat 2017;14:21-28.   DOI
113 Olafsdottir LB, Gudjonsson H, Jonsdottir HH, Bjornsson E, Thjodleifsson B. Natural history of irritable bowel syndrome in women and dysmenorrhea: a 10-year follow-up study. Gastroenterol Res Pract 2012;2012:534204.
114 Choghakhori R, Abbasnezhad A, Amani R, Alipour M. Sex-related differences in clinical symptoms, quality of life, and biochemical factors in irritable bowel syndrome. Dig Dis Sci 2017;62:1550-1560.   DOI
115 Heitkemper MM, Cain KC, Jarrett ME, Burr RL, Hertig V, Bond EF. Symptoms across the menstrual cycle in women with irritable bowel syndrome. Am J Gastroenterol 2003;98:420-430.   DOI
116 Ruigomez A, Garcia Rodriguez LA, Johansson S, Wallander MA. Is hormone replacement therapy associated with an increased risk of irritable bowel syndrome? Maturitas 2003;44:133-140.   DOI
117 Gonenne J, Esfandyari T, Camilleri M, et al. Effect of female sex hormone supplementation and withdrawal on gastrointestinal and colonic transit in postmenopausal women. Neurogastroenterol Motil 2006;18:911-918.   DOI
118 Cairns BE, Gazerani P. Sex-related differences in pain. Maturitas 2009;63:292-296.   DOI
119 Meleine M, Matricon J. Gender-related differences in irritable bowel syndrome: potential mechanisms of sex hormones. World J Gastroenterol 2014;20:6725-6743.   DOI
120 Aloisi AM. Gonadal hormones and sex differences in pain reactivity. Clin J Pain 2003;19:168-174.   DOI
121 Houghton LA, Jackson NA, Whorwell PJ, Morris J. Do male sex hormones protect from irritable bowel syndrome? Am J Gastroenterol 2000;95:2296-2300.   DOI
122 Drossman DA. Functional Gastrointestinal disorder: history, pathophysiology, and Rome IV. Gastroenterology 2016;150:1262-1279.   DOI
123 Kim BJ, Rhee PL, Park JH, et al. Male sex hormones may influence the symptoms of irritable bowel syndrome in young men. Digestion 2008;78:88-92.   DOI
124 Cotter AA, Cashman KD. Effect of 17beta-oestradiol on transepithelial calcium transport in human intestinal-like Caco-2 cells and its interactions with 1,25-dihydroxycholecalciferol and 9-cis retinoic acid. Eur J Nutr 2006;45:234-241.   DOI
125 Miller V, Whitaker K, Morris JA, Whorwell PJ. Gender and irritable bowel syndrome: the male connection. J Clin Gastroenterol 2004;38:558-560.   DOI
126 Lee JY, Kim N, Kim YS, et al. Repeated water avoidance stress alters mucosal mast cell counts, interleukin-$1{\beta}$ levels with sex difference in distal colon of wistar rats. J Neurogastroenterol Motil 2016;22:694-704.   DOI
127 Mulak A, Tache Y, Larauche M. Sex hormones in the modulation of irritable bowel syndrome. World J Gastroenterol 2014;20:2433-2448.   DOI
128 Zheng G, Wu SP, Hu Y, Smith DE, Wiley JW, Hong S. Corticosterone mediates stress-related increased intestinal permeability in a regionspecific manner. Neurogastroenterol Motil 2013;25:e127-e139.   DOI
129 Honda J, Iijima K, Asanuma K, et al. Estrogen enhances esophageal barrier function by potentiating occludin expression. Dig Dis Sci 2016;61:1028-1038.   DOI
130 Braniste V, Leveque M, Buisson-Brenac C, Bueno L, Fioramonti J, Houdeau E. Oestradiol decreases colonic permeability through oestrogen receptor beta-mediated up-regulation of occludin and junctional adhesion molecule-A in epithelial cells. J Physiol 2009;587(Pt 13):3317-3328.   DOI
131 Naliboff BD, Berman S, Chang L, et al. Sex-related differences in IBS patients: central processing of visceral stimuli. Gastroenterology 2003;124:1738-1747.   DOI
132 Aloisi AM, Bachiocco V, Costantino A, et al. Cross-sex hormone administration changes pain in transsexual women and men. Pain 2007;132:S60-S67.   DOI
133 Chang L, Mayer EA, Labus JS, et al. Effect of sex on perception of rectosigmoid stimuli in irritable bowel syndrome. Am J Physiol Regul Integr Comp Physiol 2006;291:R277-R284.   DOI
134 Ragnarsson G, Hallbook O, Bodemar G. Abdominal symptoms are not related to anorectal function in the irritable bowel syndrome. Scand J Gastroenterol 1999;34:250-258.
135 Chang L, Adeyemo M, Karagiannides I, et al. Serum and colonic mucosal immune markers in irritable bowel syndrome. Am J Gastroenterol 2012;107:262-272.   DOI
136 Martin-Vinas JJ, Quigley EM. Immune response in irritable bowel syndrome: a systematic review of systemic and mucosal inflammatory mediators. J Dig Dis 2016;17:572-581.   DOI
137 Cremon C, Gargano L, Morselli-Labate AM, et al. Mucosal immune activation in irritable bowel syndrome: gender-dependence and association with digestive symptoms. Am J Gastroenterol 2009;104:392-400.   DOI
138 Bashashati M, Rezaei N, Shafieyoun A, et al. Cytokine imbalance in irritable bowel syndrome: a systematic review and meta-analysis. Neurogastroenterol Motil 2014;26:1036-1048.   DOI
139 Pigrau M, Rodino-Janeiro BK, Casado-Bedmar M, et al. The joint power of sex and stress to modulate brain-gut microbiota axis and intestinal barrierhomeostasis: implications for irritable bowel syndrome. Neurogastroenterol Motil 2016;28:463-486.   DOI
140 Braniste V, Jouault A, Gaultier E, et al. Impact of oral bisphenol A at reference doses on intestinal barrier function and sex differences after perinatal exposure in rats. Proc Natl Acad Sci USA 2010;107:448-453.   DOI
141 Moussa L, Bezirard V, Salvador-Cartier C, Bacquie V, Houdeau E, Theodorou V. A new soy germ fermented ingredient displays estrogenic and protease inhibitor activities able to prevent irritable bowel syndromelike symptoms in stressed female rats. Clin Nutr 2013;32:51-58.   DOI
142 Mattar AF, Teitelbaum DH, Drongowski RA, Yongyi F, Harmon CM, Coran AG. Probiotics up-regulate MUC-2 mucin gene expression in a Caco-2 cell-culture model. Pediatr Surg Int 2002;18:586-590.   DOI
143 Ait-Belgnaoui A, Payard I, Rolland C, et al. Bifidobacterium longum and Lactobacillus helveticus synergistically suppress stress-related visceral hypersensitivity through hypothalamic-pituitary-adrenal axis modulation. J Neurogastroenterol Motil 2018;24:138-146.   DOI
144 Menon R, Watson SE, Thomas LN, et al. Diet complexity and estrogen receptor $\beta$ status affect the composition of the murine intestinal microbiota. Appl Environ Microbiol 2013;79:5763-5773.   DOI
145 Markle JG, Frank DN, Mortin-Toth S, et al. Sex differences in the gut microbiome drive hormone dependent regulation of autoimmunity. Science 2013;339:1084-1088.   DOI