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Inflammatory Bowel Disease: Overview. IBD: Overview Prevalence: ~250 cases per 100,000 1 Prevalence: ~250 cases per 100,000 1 –More than 1 million cases.

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Presentation on theme: "Inflammatory Bowel Disease: Overview. IBD: Overview Prevalence: ~250 cases per 100,000 1 Prevalence: ~250 cases per 100,000 1 –More than 1 million cases."— Presentation transcript:

1 Inflammatory Bowel Disease: Overview

2 IBD: Overview Prevalence: ~250 cases per 100,000 1 Prevalence: ~250 cases per 100,000 1 –More than 1 million cases estimated in United States 1 –Ulcerative colitis (UC): 50% 1 –Crohn’s disease (CD): 50% 1 Incidence:  15 cases per 100,000 1 Incidence:  15 cases per 100,000 1 –Onset: 30% between 10 and 19 years of age 2 –Young children: <2% 2 –Peak age of onset: 20s & 30s, again in 60s 3 –Slightly greater risk for women and elderly 4 1 CCFA Library: Basic Facts. Available at: 2 Grand RJ, et al. Clin Invest Med. 1996;19: Hanauer SB. Cecil Textbook of Medicine. 20th ed. Philadelphia, Pa: WB Saunders Co; 1996: Lashner BA. In: Stein SH, Rood RP, eds. Inflammatory Bowel Disease: A Guide for Patients and Their Families. 2nd ed. Philadelphia, Pa: Lippincott-Raven Publishers; 1999:23-29.

3 IBD: Overview (cont’d) Scope of disorder (United States) Scope of disorder (United States) –700,000 physician visits per year –100,000 hospitalizations per year –CD accounts for two thirds Long-term outlook Long-term outlook –Chronic, lifelong disease –Acute flare-ups alternating with remission –Complications and increased mortality –Surgery for 50% to 80% of CD patients Calkins BM. Digestive Diseases in the United States: Epidemiology and Impact. Bethesda, Md: National Institutes of Health; 1994.

4 <4.0 < Risk for Developing CD Empiric Risk for Developing Crohn's Disease (%) Offspr Both Parents MZ Twin Sib Ashk Jew Parent Offspr Ashk Jew DZ Twin Sib Non-Jew Homozygote NOD2 Heterozygote NOD2 General Population

5 Eye inflammation* Liver and bile duct inflammation Skin lesions Arthritis and joint pains Kidney stones Growth failure in children Lower bone density* Subfertility* IBD: Systemic Complications *Higher incidence in women. Gallstones Ovaries Uterus

6 Influence of Gender on Illness-Related Concerns in IBD Study of 343 men and women Study of 343 men and women –Women report higher levels of symptom severity (P=.04) –Higher levels of rating of IBD patient concerns (P<.001) Maunder R, et al. Can J Gastroenterol. 1999;13: Maunder R, et al. Can J Gastroenterol. 1999;13:

7 Patients’ Concerns in IBD Greater in Women Than in Men Greater in Women Than in Men –Feelings about body –Attractiveness –Feeling alone –Having children –Intimacy (CD) –Sexual performance (CD) Independent of Gender Independent of Gender –Energy level –Medication effects –Uncertain nature of IBD –Having surgery –Having ostomy bag –Reaching full potential –Being a burden Maunder R, et al. Can J Gastroenterol. 1999;13: Maunder R, et al. Can J Gastroenterol. 1999;13:

8 Gender-Related Considerations in IBD WomenMen Reproductive issues  fertility after IPAA or proctocolectomy  risk of relapse if disease active at time of conception  fertility with sulfasalazine  Sperm count with methotrexate Disease-related concerns  concern re: body stigma, loss of bowel control — Sexuality  sexual activity because of dyspareunia, abdominal pain, etc  libido and sexual satisfaction after proctocolectomy

9 The Effect of Smoking on Crohn’s Disease in Women There are now two studies that have specifically addressed the gender effect of tobacco There are now two studies that have specifically addressed the gender effect of tobacco Women smokers undergoing surgery are 5 times more likely to have a recurrence than a non-smoker, and recur more quickly 1 Women smokers undergoing surgery are 5 times more likely to have a recurrence than a non-smoker, and recur more quickly 1 Women smokers hastened onset of disease and increased the need for immunomodulators 2 Women smokers hastened onset of disease and increased the need for immunomodulators 2 1 Kane SV, Gastroenterol 2002; 124(5):A Cosnes J Clin Gastro and Hepatol 2004;2:41-48.

10 Special Considerations for Women With IBD

11 Cervical Dysplasia Cervical Dysplasia Menstruation/contraception Menstruation/contraception Body image/sexuality Body image/sexuality Conception/pregnancy/breast-feeding Conception/pregnancy/breast-feeding Menopause/hormone replacement therapy Menopause/hormone replacement therapy Risk of osteoporosis Risk of osteoporosis Adherence Adherence –Physician-patient partnership Overlapping IBS Overlapping IBS

12 Incidence of Abnormal Pap Smears in IBD Abnormal Pap smears associated with both infection and progression to cancer Abnormal Pap smears associated with both infection and progression to cancer Incidence study of women with IBD and a history of abnormal Pap smears Incidence study of women with IBD and a history of abnormal Pap smears Adjusted for smoking, OCP use and parity Adjusted for smoking, OCP use and parity Women with IBD were more likely to have an abnormal Pap Women with IBD were more likely to have an abnormal Pap Use of azathioprine increased risk 3 fold Use of azathioprine increased risk 3 fold Kane SV Am J Gastro 2008;103(3):631-6.

13 IBD: Issues With Menstruation and Contraception

14 Menstrual Cycle and Bowel-Pattern Fluctuations Bowel-pattern fluctuation is common during the menstrual cycle Bowel-pattern fluctuation is common during the menstrual cycle IBD symptoms may increase during the menstrual cycle IBD symptoms may increase during the menstrual cycle Suppression of menses via hormonal contraceptive methods may be considered in presence of debilitating symptoms Suppression of menses via hormonal contraceptive methods may be considered in presence of debilitating symptoms

15 Potential IBD-Related Menstrual Symptoms Most frequently reported symptoms Most frequently reported symptoms –Pelvic pain 52% –Lower back pain 36% –Diarrhea 26% –Irritability 23% –Headache 20% Incidence of any menstrual symptoms significantly higher for IBD patients than for healthy controls (P .01) Incidence of any menstrual symptoms significantly higher for IBD patients than for healthy controls (P .01) Kane SV, et al. Am J Gastroenterol. 1998;93:

16 IBD: Issues With Menstruation There is a trend for patients with CD to be affected by IBD symptoms during menstruation to a greater extent than are patients with UC There is a trend for patients with CD to be affected by IBD symptoms during menstruation to a greater extent than are patients with UC CD patients experienced diarrhea significantly more often than did controls (P=.004) CD patients experienced diarrhea significantly more often than did controls (P=.004) Kane SV, et al. Am J Gastroenterol. 1998;93:

17 OCs and IBD Risk Controversial data Controversial data Increased incidence of CD with use of OCs? Increased incidence of CD with use of OCs? OCs related to flare of CD activity? OCs related to flare of CD activity? Newer OCs with lower estrogen content associated with decreasing incidence of CD in women? Newer OCs with lower estrogen content associated with decreasing incidence of CD in women?

18 CD Flare and OCs Adapted from Cosnes J, et al. Gut. 1999;45: with permission from BMJ Publishing Group. Days After Inclusion Patients With Flare (%) OC use No OC use

19 OCs and IBD Risk Baltimore F:M incidence for year age group Olmstead F:M incidence for year age group US OC use (  5 million) Adapted from Alic M. Gut. 2000;46:140 with permission from BMJ Publishing Group. F:M Incidence Ratio

20 Contraindications for OCs History of thromboembolic disease History of thromboembolic disease Active obstructive liver disease with elevated liver enzymes Active obstructive liver disease with elevated liver enzymes Breast cancer Breast cancer Smokers over the age of 35 Smokers over the age of 35 Pregnancy Pregnancy

21 IBD and Contraception: Conclusions OCs should have lower estrogen content (eg,  35 µg) OCs should have lower estrogen content (eg,  35 µg) Avoid for women with known hypercoagulability Avoid for women with known hypercoagulability Avoid for women with IBD-associated liver disease Avoid for women with IBD-associated liver disease Avoid for women with IBD who smoke Avoid for women with IBD who smoke

22 IBD: Issues With Body Image and Sexuality

23 IBD and Sexuality: Physical Impact Impact of disease Impact of disease –Perianal complications –Draining cutaneous fistulae –Skin lesions –Arthritic deformities –Pain –Fatigue Impact of treatment Impact of treatment –Surgical scars –Stoma –Medication side effects

24 IBD and Sexuality: Psychological Impact Affected aspects Affected aspects –Behavior patterns –Communication –Sexual drive –Sensations connected with sexual activity Negative effects Negative effects –Feeling dirty, unsexy, unattractive –Reduced self-esteem –Loss of former identity –Anxiety over disclosure

25 Sexual Function and IBD No difference in rates of sexual activity No difference in rates of sexual activity Depression a bigger determinant of lower sexual activity Depression a bigger determinant of lower sexual activity Women with IBD more likely to have vaginal dryness, dyspareunia, vaginal infections than healthy controls Women with IBD more likely to have vaginal dryness, dyspareunia, vaginal infections than healthy controls Only 25% of patients wanted to discuss sexuality with their physician Only 25% of patients wanted to discuss sexuality with their physician Timmer A et al. Clin Gastro Hepatol 2007;5:87-94.

26 Maintaining Femininity Following IBD Surgery Body image Body image Sexuality Sexuality Communication Communication Fertility Fertility Pregnancy Pregnancy

27 Sexual Function Following IPAA Usually improved because of improved general well-being Usually improved because of improved general well-being Some problems may continue Some problems may continue –Dyspareunia –Vaginal drying Sexual function improved 16%-25% 1,2 Sexual function improved 16%-25% 1,2 Frequency of intercourse increased 35% 2 Frequency of intercourse increased 35% 2 IPAA = ileal pouch-anal anastomosis. 1 Farouk R, et al. Ann Surg. 2000;231: Damgaard B, et al. Dis Colon Rectum. 1995;38:

28 Women With Restorative Proctocolectomies: Satisfaction With Sexual Relationships 22% improved 22% improved 51% unchanged 51% unchanged 26% less satisfactory 26% less satisfactory Overall 86% moderately to extremely satisfied Overall 86% moderately to extremely satisfied Bambrick M, et al. Dis Colon Rectum. 1996;39:

29 BeforeAfter Dyspareunia * 5%15% Fecal incontinence during intercourse 3%7% Menstrual problems 23%31% Gynecologic Function Before and After IPAA Results of Questionnaire (n=110) 1 *Rates range from 0% to 26% Counihan TC, et al. Dis Colon Rectum. 1994;37: Tiainen J, et al. Scand J Gastroenterol. 1999;34: Sjogren B, Peppen B. Acta Obstet Gynecol Scand. 1995;74: Damgaard B, et al. Dis Colon Rectum. 1995;38: Bambrick M, et al. Dis Colon Rectum. 1996;39:

30 Women With Ileostomies: Sexual Function % Patients No change47% No change47% Adversely affected47% Adversely affected47% –Mild (22%) –Severe (14%) –Moderate (11%) Improved7% Improved7% Awad RW, et al. Br J Surg. 1993;80:

31 Women With Ileostomies: Sexual Concerns Sexual attractiveness decreased 52% Sexual attractiveness decreased 52% –Appliance72% –Stoma16% –Odor4% More women (60%) than men (52%) felt less desirable More women (60%) than men (52%) felt less desirable Sexual intercourse is more difficult Sexual intercourse is more difficult –Psychologically46% –Physically32% Rolstad BS, et al. Dis Colon Rectum. 1983;26: (n=50)

32 Conception and Fertility in Women With IBD

33 Effects of IBD on Fertility Women Women –UC: normal fertility rate overall (92.2%) 1,2 IPAA reduces fertilityIPAA reduces fertility –CD: normal fertility, but pelvic inflammation may block fallopian tubes 3 –Voluntary childlessness higher for IBD patients 4 Men Men –Reversible sperm abnormalities with sulfasalazine 5 –Azathioprine: Semen analysis normal with immunomodulators 6 –Methotrexate caused temporary low sperm count in animals 7 1 Willoughby CP, Truelove SC. Gut. 1980;21: Kane SV. In Kirsner JB, Shorter RG, eds. Inflammatory Bowel Disease. 4th ed Järnerot G. Scand J Gastroenterol. 1982;17: Baird DD, et al. Gastroenterology. 1990;99: Kornbluth A, Sachar DB. Am J Gastroenterol. 1997;92: Rajapakse RO, et al. Am J Gastroenterol. 2000;95: Johnson FE, et al. J Surg Oncol. 1994;55:

34 Effects of CD on Female Fertility: Conflicting Findings In 5 studies, inability of patients to conceive because of CD ranged from 12% to 67% 1-5 In 5 studies, inability of patients to conceive because of CD ranged from 12% to 67% 1-5 Risk of inability to conceive was higher in patients with large-bowel disease than in those with small-bowel disease 1-4 Risk of inability to conceive was higher in patients with large-bowel disease than in those with small-bowel disease 1-4 –Difference sometimes significant 1 –No difference 5 Chances of conceiving increased after surgery for CD 2 Chances of conceiving increased after surgery for CD 2 1 Fielding JF, Cooke WT. Br Med J. 1970;2: De Dombal FT, et al. Br Med J. 1972;3: Homan WP, Thorbjarnarson B. Arch Surg. 1976;111: Khosla R, et al. Gut. 1984;25: Mayberry JF, Weterman IT. Gut. 1986;27:

35 Female Fertility After IPAA Fecundability Ratio Number of Menstrual Periods Observed (time to pregnancy) P Value Reference population 1914— Patients before diagnosis Patients before colectomy Patients after IPAA <.0001 Adapted from Gastroenterology, Vol 122, Olsen KØ, Juul S, Berndtsson I, Öresland T, Laurberg S, Ulcerative Colitis: Female Fecundity Before Diagnosis, During Disease, and After Surgery Compared with a Population Sample, pages 15-19, Copyright 2002 with permission from Elsevier. (n=343)

36 Cumulative Incidence of Pregnancy Within 5 Years Adapted from Gastroenterology, Vol 122, Olsen KØ, Juul S, Berndtsson I, Öresland T, Laurberg S, Ulcerative Colitis: Female Fecundity Before Diagnosis, During Disease, and After Surgery Compared with a Population Sample, pages 15-19, Copyright 2002 with permission from Elsevier. Time to Pregnancy (months) Cumulative Incidence of Pregnancy After surgery Before diagnosis Reference Before surgery

37 Surgical Approaches to Minimize Infertility Possibly delay pelvic surgery Possibly delay pelvic surgery Minimize septic complications Minimize septic complications Decrease adhesion formation Decrease adhesion formation –Ferric hyaluronate adhesion-prevention gel –“Pexing” ovaries Laparoscopic procedures Laparoscopic procedures

38 IBD and Conception: Summary Close to normal fertility with UC, decreased after IPAA Close to normal fertility with UC, decreased after IPAA Conflicting findings regarding influence of CD on ability to conceive Conflicting findings regarding influence of CD on ability to conceive Conflicting findings regarding influence of surgery for CD on ability to conceive Conflicting findings regarding influence of surgery for CD on ability to conceive Some IBD treatments may cause sperm abnormalities in men Some IBD treatments may cause sperm abnormalities in men

39 Pregnancy and Pregnancy Outcomes in Women With IBD

40 Effects of IBD on Pregnancy Outcomes Preterm birth Preterm birth –  risk in both UC and CD 1,2,5 4 of 5 studies: no major impact on risk of congenital abnormalities of 5 studies: no major impact on risk of congenital abnormalities 1-5 Significant  in risk of low birth weight 2-5 Significant  in risk of low birth weight 2-5  risk of maternal/delivery complications 5  risk of maternal/delivery complications 5 1 Baird DD, et al. Gastroenterology. 1990;99: Dominitz JA, et al. Am J Gastroenterol. 2002;97: Porter RJ, Stirrat GM. Br J Obstet Gynaecol. 1986;93: Fonager K, et al. Am J Gastroenterol. 1998;93: Baird DD, et al. Gastroenterology. 1990;99: Dominitz JA, et al. Am J Gastroenterol. 2002;97: Porter RJ, Stirrat GM. Br J Obstet Gynaecol. 1986;93: Fonager K, et al. Am J Gastroenterol. 1998;93: Mahadevan U, et al. Gastroenterol. 2007;133:

41 Meta-analysis 12 studies 12 studies –N= 3907 (CD 1952, UC 1113) vs. 320, 531 Prematurity OR = 1.87 ( ) p<0.001 Prematurity OR = 1.87 ( ) p<0.001 LBW OR = 2.10 ( ), p<0.001 LBW OR = 2.10 ( ), p<0.001 C-section OR = 1.50 ( ) p <0.001 C-section OR = 1.50 ( ) p <0.001 Congen Abnorm. = 2.37 ( ) p <0.001 Congen Abnorm. = 2.37 ( ) p <0.001 –4 studies reported on the incidence IBD vs. controls, no difference –UC vs. controls in two studies (Larzilliere 1998, Dominitz) Cornish Gut 2006;0:1-8.

42 Effect of Pregnancy on UC: Disease Activity at Conception Miller JP. J R Soc Med. 1986;79: Inactive Active No Relapse Relapse Worsened Activity ContinuedActivity Decreased Activity 0 n=528 n= Percent

43 32 Effect of Pregnancy on CD: Disease Activity at Conception Miller JP. J R Soc Med. 1986;79: Inactive Active No Relapse Relapse Worsened Activity ContinuedActivity Decreased Activity 0 n=186 n= Percent

44 Disease activity during pregnancy in women with IBD Majority of patients have inactive to mild disease during pregnancy Majority of patients have inactive to mild disease during pregnancy Mahadevan U, et al. Gastroenterol. 2007;133: Trimester Percentage of patients Disease activity in Crohn’s disease Disease activity in ulcerative colitis

45 Effect of Pregnancy on IBD: Maternal-Fetal HLA Disparity Prepartum disease activity significantly predicts disease activity during pregnancy (P=.008) Prepartum disease activity significantly predicts disease activity during pregnancy (P=.008) In single-locus disparity, no significant difference between DR and DQ prepartum, during trimesters 1-3, or postpartum In single-locus disparity, no significant difference between DR and DQ prepartum, during trimesters 1-3, or postpartum Disparity at both DR and DQ loci significantly predicts disease activity during pregnancy (P=.001) Disparity at both DR and DQ loci significantly predicts disease activity during pregnancy (P=.001) Maternal immune response to paternal HLA antigens may play role in pregnancy-induced remission of IBD Maternal immune response to paternal HLA antigens may play role in pregnancy-induced remission of IBD Kane S, et al. Gastroenterology. 1998;114:A1006. Abstract G4121.

46 Concerns Regarding Pregnancy and Delivery What is the effect of pregnancy on pouch function before and after delivery? What is the effect of pregnancy on pouch function before and after delivery? Should the woman deliver vaginally or have cesarean section? Should the woman deliver vaginally or have cesarean section? Are there unique concerns if cesarean section is performed? Are there unique concerns if cesarean section is performed?

47 Delivery Mode and Perineal Injury Study indicates that more women with IBD have cesarean sections 1 Study indicates that more women with IBD have cesarean sections 1 Vaginal delivery is usually safe for women with inactive perianal symptoms 1 Vaginal delivery is usually safe for women with inactive perianal symptoms 1 1 Ilnyckyji A, et al. Am J Gastroenterol. 1999;94:

48 Pouch Function During and After Pregnancy 10 vaginal deliveries, 6 cesarean sections 10 vaginal deliveries, 6 cesarean sections –No pouch complications 8.1 bowel movements/day during pregnancy vs 6.5/day postpartum 8.1 bowel movements/day during pregnancy vs 6.5/day postpartum 3 women had incontinence during pregnancy, 1 frequent and 2 mild 3 women had incontinence during pregnancy, 1 frequent and 2 mild 1 woman had nighttime incontinence postpartum 1 woman had nighttime incontinence postpartum Scott HJ, et al. Int J Colorectal Dis. 1996;11:84-87.

49 Pregnancy, Delivery, and Pouch Function After IPAA in UC Questionnaires sent to women with IPAA for UC Questionnaires sent to women with IPAA for UC Results Results –49 deliveries for 29 women (25 vaginal, 24 c-sections) –6 pouch-related complications (2 during pregnancy; 4 postpartum) –  stool frequency and incontinence during pregnancy –83% regained prepregnancy function; 17% had some permanent pouch function deterioration not related to delivery method –Delivery method did not affect incontinence, stool frequency Conclusion: Pregnancy is safe for women with IPAA Conclusion: Pregnancy is safe for women with IPAA Ravid A, et al. Dis Colon Rectum. 2002;45:

50 IBD in Pregnancy: Summary Pregnancy outcomes best if patient in remission at time of conception, though even patients in remission can have higher rates of adverse outcomes compared to the general population Pregnancy outcomes best if patient in remission at time of conception, though even patients in remission can have higher rates of adverse outcomes compared to the general population IBD increases the risk of preterm birth and low birth weight and maternal complications IBD increases the risk of preterm birth and low birth weight and maternal complications No significant increase in risk of congenital abnormalities No significant increase in risk of congenital abnormalities Women with IBD have a higher rate of cesarean sections Women with IBD have a higher rate of cesarean sections Pregnancy may not increase the risk of relapse or significantly increase disease activit Pregnancy may not increase the risk of relapse or significantly increase disease activit

51 Management of IBD in Pregnancy

52 Assessment of Disease Activity in Pregnant IBD Patients Laboratory studies (ESR, Hgb, albumin, CRP) Laboratory studies (ESR, Hgb, albumin, CRP) Ultrasound – low risk Ultrasound – low risk Low-dose X-rays pose minimal fetal risk 1 Low-dose X-rays pose minimal fetal risk 1 Endoscopy – low risk if used for appropriate indications 2 Endoscopy – low risk if used for appropriate indications 2 Flexible sigmoidoscopy – low risk 2 Flexible sigmoidoscopy – low risk 2 Colonoscopy – should only be used for life-threatening colonic disease or when only alternative is laparotomy 2 Colonoscopy – should only be used for life-threatening colonic disease or when only alternative is laparotomy 2 ESR = erythrocyte sedimentation rate; Hgb = hemoglobin; CRP = C-reactive protein. 1 Hufton AP. Br J Radiol. 1979;52: Cappell MS, et al. Dig Dis Sci. 1996;41:

53 Drugs in Pregnancy Pharmaceutical companies almost never test products in pregnant women Pharmaceutical companies almost never test products in pregnant women PDR ® disclaimer: use in pregnancy is not recommended unless benefits justify risk to fetus PDR ® disclaimer: use in pregnancy is not recommended unless benefits justify risk to fetus FDA classifications (A, B, C, D, X) FDA classifications (A, B, C, D, X) –Ambiguous –Difficult to interpret and use in counseling PDR ® = Physicians’ Desk Reference ® ; FDA = Food and Drug Administration. Koren G, et al. N Engl J Med. 1998;338:

54 Pregnancy-Risk Categories A:Controlled human studies do not show risk to fetus; chance of risk remote A:Controlled human studies do not show risk to fetus; chance of risk remote B:No evidence of risk to fetus in human studies; chance of risk remote but possible B:No evidence of risk to fetus in human studies; chance of risk remote but possible C:Inadequate studies in humans; risk cannot be ruled out, but benefits may outweigh risks C:Inadequate studies in humans; risk cannot be ruled out, but benefits may outweigh risks D:Positive evidence of fetal risk; benefits might outweigh risks in life-threatening situations when safer drugs are ineffective D:Positive evidence of fetal risk; benefits might outweigh risks in life-threatening situations when safer drugs are ineffective X:Contraindicated in pregnancy X:Contraindicated in pregnancy Briggs GG, et al. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1998.

55 *Safe for use after first trimester. † Increasing use in pregnancy. Briggs GG, et al. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; Physician’s Desk Reference ®. 57th ed. Montvale, NJ: Thompson PDR; Summary: Safety of IBD Medications During Pregnancy Category B Category C Category C Category D Category X LoperamideCiprofloxacin Azathioprine † Methotrexate MesalamineCyclosporine 6-Mercaptopurine † Thalidomide BalsalazideDiphenoxylate CorticosteroidsOlsalazine SulfasalazineTacrolimus Anti-TNF agents Natalizumab Metronidazole*

56 Sulfasalazine in Pregnancy Most side effects linked to sulfapyridine moiety 1 Most side effects linked to sulfapyridine moiety 1 No increase in fetal malformations No increase in fetal malformations Readily crosses placenta, but only minimal amounts in breast milk 2 Readily crosses placenta, but only minimal amounts in breast milk 2 Interferes with folic acid metabolism Interferes with folic acid metabolism –Folate important for neural tube development 3 –Folic acid supplements (1 mg BID) advised prior to conception and throughout pregnancy 1 Stein RB, Hanauer SB. Gastroenterol Clin North Am. 1999;28: Miller JP. J R Soc Med. 1986;79: Czeizel AE, Dudas I. N Engl J Med. 1992;327:

57 Aminosalicylates (B,C) Meta-analysis 7 studies: 642 5ASA, 1158 no med Meta-analysis 7 studies: 642 5ASA, 1158 no med –Congenital anomalies: OR 1.16 (0.76, 1.77) –Stillbirth OR 2.38 (0.65, 8.72) –SAB OR 1.14 (0.65, 2.01) –Preterm delivery 1.35 (0.85, 2.13) –LBW OR 0.93 (0.46, 1.85) Sulfasalazine given w/ folic acid 1 mg BID Sulfasalazine given w/ folic acid 1 mg BID Folic acid: neural tube defects, CV, GU, cleft palateFolic acid: neural tube defects, CV, GU, cleft palate Case reports of congenital malformationCase reports of congenital malformation Placental and Breast Transfer Occurs Placental and Breast Transfer Occurs Potential allergic reaction newborn: watery diarrheaPotential allergic reaction newborn: watery diarrhea SAS not associated with kernicterus or displacement of bilirubin from albuminSAS not associated with kernicterus or displacement of bilirubin from albumin Olsalazine: Pregnancy category C. All others, B Olsalazine: Pregnancy category C. All others, B Rahimi Reprod Toxicol 2008

58 Safety of Mesalamine in Pregnancy *96 taking mesalamine during first trimester. † General population in France. 1 Marteau P, et al. Aliment Pharmacol Ther. 1998;12: Diav-Citrin O, et al. Gastroenterology. 1998;114: Studyn Mean Mesalamine Dosage Incidence of Fetal Malformations (%) PatientsControls Marteau et al 1 123* 2.1 ± 0.8 g/d † Diav-Citrin et al ± 1.6 g/d

59 Topical 5-ASA in Pregnancy Study of 19 pregnancies Study of 19 pregnancies –Maintenance 5-ASA topical therapy at time of conception and throughout pregnancy –Successful full-term pregnancies for all patients, with no fetal abnormalities Minimal excretion of 5-ASA and metabolites in breast milk Minimal excretion of 5-ASA and metabolites in breast milk Many years of safe use Many years of safe use Bell CM, Habal FM. Am J Gastroenterol. 1997;92:

60 Antibiotics Metronidazole (B) /Ciprofloxacin (C) Metronidazole (B) /Ciprofloxacin (C) –Low risk of teratogenicity Metronidazole: prospective controlled study, 2 meta- analysisMetronidazole: prospective controlled study, 2 meta- analysis –However, 2 nd, 3 rd T use, 1 st T cleft lip, palate Ciprofloxacin: prospective controlled study low risk of defectsCiprofloxacin: prospective controlled study low risk of defects –Affinity for bones, arthropathy in children –Breast feeding not advised on MNZL, probably compatible with ciprofloxacin –Minimal benefit in CD and UC with longer use-avoid Rifaximin: Pregnancy C Rifaximin: Pregnancy C –teratogenicity in animal studies –Safety in humans in pregnancy/breastfeeding unknown

61 Corticosteroids in Pregnancy Increased spontaneous abortions, cleft palate, stillbirths in mice; rare teratogenicity in humans (cleft palate) Increased spontaneous abortions, cleft palate, stillbirths in mice; rare teratogenicity in humans (cleft palate) High doses associated with retardation of fetal growth High doses associated with retardation of fetal growth No fetal adrenocortical insufficiency No fetal adrenocortical insufficiency Safety uncertain with long-term use of high doses while breast-feeding Safety uncertain with long-term use of high doses while breast-feeding Active-disease risks greater than drug risks to fetus, so use if needed Active-disease risks greater than drug risks to fetus, so use if needed Briggs GG, et al. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1998.

62 AZA/6-MP in Pregnancy Several studies in transplant recipients have reported safe use during pregnancy 1 Several studies in transplant recipients have reported safe use during pregnancy 1 Study of IBD patients showed no  in prematurity, spontaneous abortion, congenital abnormalities, or childhood neoplasia 2 Study of IBD patients showed no  in prematurity, spontaneous abortion, congenital abnormalities, or childhood neoplasia 2 –Study population included fathers treated with AZA/6-MP In another study, AZA/6-MP did not reduce fertility in men 3 In another study, AZA/6-MP did not reduce fertility in men 3 Risk of birth defects similar to that in general population 4 Risk of birth defects similar to that in general population 4 1 Briggs GG, et al. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; Francella A, et al. Gastroenterology. 2003;124: Dejaco C, et al. Gastroenterology. 2001;121: Library: IBD & Your Family. Available at Accessed March 6, 2003.

63 Azathioprine and Teratogenicity Largest Study to date Largest Study to date 189 pregnant women on AZA who contacted one of seven teratogen information services were compared to a cohort of 230 pregnant women who took non-teratogenic treatments 189 pregnant women on AZA who contacted one of seven teratogen information services were compared to a cohort of 230 pregnant women who took non-teratogenic treatments Rate of major malformations did not differ with six neonates each : Rate of major malformations did not differ with six neonates each : –AZA (3.5%) vs control ( 3.0%) (p =.775; OR 1.17; CI: 0.37, 3.69). Mean birth weight and gestational age were lower in AZA group: Mean birth weight and gestational age were lower in AZA group: –2,995g vs. 3,252g [p =.001] –37.8 weeks vs weeks [p =.001] The AZA group had more prematurity The AZA group had more prematurity –21.4% vs. 5.2% [p <.001] The AZA group had more low birth weight The AZA group had more low birth weight –23% vs. 6.0% [p <.001] Goldstein Birth Defects Res A Clin Mol Teratol Sep 10;79(10):

64 Thiopurines and Nursing 2 infants breast fed with mothers on 6MP 2 infants breast fed with mothers on 6MP –6MP levels by HPLC < 0.09% maternal dose 1 4 mother-infant pairs 3 months post-partum were tested for 6MP metabolites 4 mother-infant pairs 3 months post-partum were tested for 6MP metabolites –All infants were nursing –Maternal levels within therapeutic range –No metabolites found in offspring 2 Moretti M. Ann Pharmacother 2006; Dec (40); Gardiner S. Br J Clin Pharmacol 2006; 62:

65 Cyclosporine in Pregnancy Registry data on transplant recipients 1 Registry data on transplant recipients 1 –No specific congenital abnormalities or birth defects –Prematurity: 56% –Low birth weight: 49.5% Study in 5 women with IBD 2 Study in 5 women with IBD 2 –4 live births, 1 missed abortion –No congenital abnormalities Should be given at experienced IBD centers 3 Should be given at experienced IBD centers 3 1 Armenti VT, et al. Transplantation. 1994;57; Marion JF, et al. Am J Gastroenterol. 1996;91: Kornbluth A, Sachar DB. Am J Gastroenterol. 1997;92:

66 Infliximab (B) Safety Database in Pregnancy: Outcomes of Women Exposed to Infliximab During Pregnancy 0 Proportion of Patients (%) Katz JA, et al. Am J Gastroenterol. 2004;99: Ventura et al. National Center for Health Statistics Vital Health Stat 2000;21:1-59 Hudson et al. Int J Gynaecol Obstet 1997;58: General population Crohn’s disease All infliximab patients (N=96) Infliximab patients with CD (N=82) Live births Therapeutic termination Miscarriages

67 Medications: Biologics Biologics Biologics –Category B: Infliximab, adalimumab, certolizumab –Category C: Natalizumab Infliximab: 102 pregnancies, 54 outcomes 1 Infliximab: 102 pregnancies, 54 outcomes 1 –“Rescue” infliximab successful 2 –Infliximab not detected in breast milk (n=5) –Demonstrated to cross the placenta and detectable in cord blood for up to 6 months from birth 5 Adalimumab: 2 IBD pregnancies in published literature 3,4 Adalimumab: 2 IBD pregnancies in published literature 3,4 –47 reported in OTIS registry Certolizumab: no published data in humans Certolizumab: no published data in humans Natalizumab: IgG4, placental transfer in 1 st trimester Natalizumab: IgG4, placental transfer in 1 st trimester 1 Katz J. Am J Gastroenterol 2004; 99(12): Mahadevan U. APT 2005; 21(6): Vesga L. Gut 2005; 54(6): Mishkin DS. IBD 2006; 12(8): Mahadevan Gastroenterology 2007;132:A-144

68 Methotrexate in Pregnancy Contraindicated during pregnancy Contraindicated during pregnancy –Chromosomal damage, teratogenic –Abortifacient Oligospermia noted during treatment of men Oligospermia noted during treatment of men –Returns to baseline posttreatment –Long-term effects unknown Briggs GG, et al. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1998.

69 Conclusions: IBD Drugs in Pregnancy 5-ASAs and corticosteroids low risk for use during pregnancy and breast-feeding 5-ASAs and corticosteroids low risk for use during pregnancy and breast-feeding Immunosuppressants Immunosuppressants –AZA/6-MP appear low risk during pregnancy –Methotrexate contraindicated Antibiotics Antibiotics –Ampicillin and cephalosporins are low risk –Ciprofloxacin and metronidazole should be avoided for longterm use Biologics: Biologics: –Anti-TNF agents low risk. Infliximab and likely adalimumab cross placenta in third trimester

70 Safety of IBD Medications in Breast-Feeding Low risk to Use When Warranted Limited Data Available Contraindicated Oral mesalamine AzathioprineMethotrexate Topical mesalamine 6-MercaptopurineCyclosporine SulfasalazineInfliximabMetronidazole CorticosteroidsInfliximabAdalimumabCertolizumabTacrolimusNatalizumabCiprofloxacin Physicians’ Desk Reference ®. 57th ed. Montvale, NJ: Thompson PDR; 2003.

71 Management of IBD in Pregnancy: Summary Pregnancy outcomes best if patient in remission at time of conception Pregnancy outcomes best if patient in remission at time of conception Many IBD-specific therapies appear to be low risk in pregnancy Many IBD-specific therapies appear to be low risk in pregnancy Monitoring of fetal growth particularly important Monitoring of fetal growth particularly important May need additional nutritional therapy because of malabsorption May need additional nutritional therapy because of malabsorption

72 Menopause in Women With IBD

73 Menopause Natural menopause results from gradual decline in number of estradiol-producing ovarian follicles Natural menopause results from gradual decline in number of estradiol-producing ovarian follicles Surgical menopause may occur at any age as a result of oophorectomy Surgical menopause may occur at any age as a result of oophorectomy Estradiol decreases; estrone becomes primary circulating hormone Estradiol decreases; estrone becomes primary circulating hormone Testosterone declines at varying rate Testosterone declines at varying rate No data on effect of menopause on IBD No data on effect of menopause on IBD Carr BR, Bradshaw KD. In: Braunwald E, et al, eds. Harrison’s Principles of Internal Medicine. 15th ed. New York, NY: McGraw-Hill; 2002.

74 Menopausal Symptoms Bone loss—may be accelerated in CD and by corticosteroid use Bone loss—may be accelerated in CD and by corticosteroid use Vasomotor symptoms—“hot flashes” (50%–85%) Vasomotor symptoms—“hot flashes” (50%–85%) Increases in total and LDL cholesterol Increases in total and LDL cholesterol Urogenital symptoms (45%) Urogenital symptoms (45%) –Dyspareunia –Dysuria –Incontinence –Urinary tract infections U.S. Preventive Services Task Force. Guide to Clinical Preventive Services, 2nd ed Available at: http/www.ahcpr.gov/clinic/cpsix.htm. Accessed January 28, 2003.

75 Postmenopausal HRT Replaces estrogen in postmenopausal women Replaces estrogen in postmenopausal women Goal: manage symptoms caused by loss of estrogen Goal: manage symptoms caused by loss of estrogen Unopposed estrogen: only for women who have had hysterectomies Unopposed estrogen: only for women who have had hysterectomies Combined estrogen/progestin: recently found to increase risks for breast cancer, heart attacks, stroke Combined estrogen/progestin: recently found to increase risks for breast cancer, heart attacks, stroke

76 HRT Protective Against Disease Activity After Menopause Cohort of post-menopausal women Cohort of post-menopausal women Disease activity pre and post menopause Disease activity pre and post menopause Those taking HRT less likely to have a disease flare in 2 years post menopause Those taking HRT less likely to have a disease flare in 2 years post menopause Dose response for length of use Dose response for length of use Form of menopause did not matter Form of menopause did not matter Kane SV Am J Gastro 2008; 103(5):

77 Potential Benefits vs Risks of HRT Potential Benefits Decrease in vasomotor symptoms Decrease in vasomotor symptoms Slower changes in body morphology Slower changes in body morphology Fewer osteoporotic fractures Fewer osteoporotic fractures Improvement in lipid balance Improvement in lipid balance Reduce IBD flare Reduce IBD flare Potential Risks Increase in invasive breast cancer Increase in invasive breast cancer Side effects: bloating, irritability, weight gain, depression, vaginal bleeding Side effects: bloating, irritability, weight gain, depression, vaginal bleeding Increased risk of thromboembolic events (blood clots, stroke) Increased risk of thromboembolic events (blood clots, stroke) Increase in CVD Increase in CVD Clements D, et al. Gut. 1993;34: Stampfer MJ, et al. N Engl J Med. 1991;325: Women's Health Initiative. JAMA. 2002;288:

78 HRT Guidelines for IBD Patients HRT Guidelines for IBD Patients As with all therapeutic choices, therapy for menopausal symptoms should be individualized As with all therapeutic choices, therapy for menopausal symptoms should be individualized For women with severe osteopenia or osteoporosis, HRT benefits may outweigh risks if alternatives are not feasible For women with severe osteopenia or osteoporosis, HRT benefits may outweigh risks if alternatives are not feasible For women at increased risk for breast cancer, HRT risks may outweigh benefits For women at increased risk for breast cancer, HRT risks may outweigh benefits CVD risk vs benefit is controversial, but risk may outweigh benefit CVD risk vs benefit is controversial, but risk may outweigh benefit

79 Osteoporosis in IBD

80 General Risk Factors for Osteoporosis Advancing age Advancing age Female gender Female gender Family history Family history Alcohol use Alcohol use White/Asian race White/Asian race Smoking Smoking Physical inactivity Physical inactivity Low calcium intake Low calcium intake Small and thin body habitus Small and thin body habitus Valentine JF, Sninsky CA. Am J Gastroenterol. 1999;94: Christchilles EA, et al. Arch Intern Med. 1991;151:

81 Risk of Osteoporosis in IBD Low bone mass in 31% to 59% of IBD patients 1-3 Low bone mass in 31% to 59% of IBD patients 1-3 IBD-related risk factors 4 IBD-related risk factors 4 –Onset of IBD before reaching age of peak bone mass –Inflammatory cytokines –Calcium malabsorption –Vitamin D deficiency (CD patients) –Drugs (corticosteroids, methotrexate, cyclosporine) 1 Compston JE. Aliment Pharmacol Ther. 1995;9: Roux C, et al. Osteoporos Int. 1995;5: Andreassen H, et al. Scand J Gastroenterol. 1997;32: Valentine JF, Sninsky CA. Am J Gastroenterol. 1999;94:

82 Prevention and Treatment of Osteoporosis in IBD Prevention Prevention –Baseline and follow-up measurements of bone density (DEXA) –Lifestyle and nutritional measures (eg, weight-bearing exercise, smoking cessation, calcium supplementation) –Possible HRT for high-risk postmenopausal women Treatment Treatment –Calcitonin– PTH –Bisphosphonates– IV therapies Valentine JF, Sninsky CA. Am J Gastroenterol. 1999;94:

83 Corticosteroid-Induced Bone Loss Bone loss occurs early (weeks to months after initiation of therapy) Bone loss occurs early (weeks to months after initiation of therapy) Cumulative dose, dosage, and duration of corticosteroids may play a role Cumulative dose, dosage, and duration of corticosteroids may play a role Calcium and small doses of vitamin D may confer limited prophylactic benefit Calcium and small doses of vitamin D may confer limited prophylactic benefit Valentine JF, Sninsky CA. Am J Gastroenterol. 1999;94: Van Staa TP, et al. J Bone Mineral Res. 2000;15:

84 Corticosteroid-Induced Loss of Bone Mass Enhanced bone resorption Enhanced bone resorption –Reduced intestinal calcium absorption and calcitonin synthesis –Increased renal calcium excretion, osteoclastic activity, and parathyroid hormone secretion –Enhanced binding of macrophages to bone Reduced bone formation Reduced bone formation –Reduced synthesis of osteoblasts and proliferation of osteoblasts –Impaired gonadal hormone production –Prednisone associated with increased rate of bone loss –Conflicting data regarding budesonide

85 Reducing the Risk of Osteoporosis History and physical lab (25-hydroxy vitamin D, albumin, calcium, PTH) Bone density (DEXA) Minimize corticosteroids Normal T Score Low BMD: T Score <–1 SD Osteoporosis: T Score <–2.5 SD Monitor regularly Hormone (if appropriate) Raloxifene (if appropriate) Calcium Vitamin D General guidelines Repeat DEXA Hormone (if appropriate) Raloxifene (if appropriate) Calcium Vitamin D Bisphosphonates General guidelines Repeat DEXA

86 -4 Months Placebo Ris 5.0 mg *P<.05 vs baseline † P<.05 vs control † P<.05 vs control Prevention Study Treatment Study 12 month diff. = 3.8% 12 month diff. = 2.7% % Change from Baseline Lumbar Spine BMD † * * * † † Bisphosphonates in the Prevention and Treatment of Osteoporosis Cohen S, Levy RM, Keller M, Boling E, et al. Risedronate therapy prevents corticosteroid-induced bone loss: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum. 1999;42: Copyright© American College of Rheumatology. Reproduced with permission of John Wiley & Sons, Inc. Reproduced from J Bone Miner Res. 2000:15; with permission of the American Society for Bone and Mineral Research. 0 Months * † * * † * *

87 Infliximab in Patients With CD and Osteoporosis Prospective, 4-week trial with patients taking corticosteroids Prospective, 4-week trial with patients taking corticosteroids Significant decrease in CDAI with infliximab (P=.0001) Significant decrease in CDAI with infliximab (P=.0001) Increase in surrogate markers for bone turnover Increase in surrogate markers for bone turnover Conclusion: increased bone synthesis with no increase in bone resorption Conclusion: increased bone synthesis with no increase in bone resorption CDAI = Crohn’s disease activity index. Abreu MT, et al. Am J Gastroenterol. 2002;97:S269. Abstract 819.

88 Summary: Osteoporosis and IBD Bone density is unusually low in patients with active IBD who are taking steroids Bone density is unusually low in patients with active IBD who are taking steroids IBD causes other risk factors, eg, poor calcium absorption and disease-related inflammatory processes, that increase risk of bone loss IBD causes other risk factors, eg, poor calcium absorption and disease-related inflammatory processes, that increase risk of bone loss Monitoring BMD is important Monitoring BMD is important Selection of treatment should be considered Selection of treatment should be considered

89 Clinical Management and Adherence Issues in IBD

90 Illness-Related Factors Affecting Adherence in IBD Severity, extent, duration of disease Severity, extent, duration of disease Frequency, duration, intensity of flare-ups Frequency, duration, intensity of flare-ups Type and severity of complications Type and severity of complications Patients with well-controlled disease and few flares are most likely to discontinue maintenance therapy Patients with well-controlled disease and few flares are most likely to discontinue maintenance therapy

91 Treatment-Related Factors Affecting Adherence in IBD Convenience Convenience –Dosage/dosing regimen –Formulation –Method of administration –Pill size Cost/reimbursement Cost/reimbursement Choice of medication Choice of medication –Sulfasalazine, corticosteroids Need to balance efficacy vs safetyNeed to balance efficacy vs safety Start with low doses, titrate slowly upwardStart with low doses, titrate slowly upward –Mesalamine Dose-related efficacy but not toxicityDose-related efficacy but not toxicity Initiate and maintain treatment with high dosesInitiate and maintain treatment with high doses Induction dose = maintenance doseInduction dose = maintenance dose

92 Patient-Related Factors Affecting Adherence Inadequate education 1 ; inadequate skills/knowledge to follow regimen 2 Inadequate education 1 ; inadequate skills/knowledge to follow regimen 2 Patients’ main concerns Patients’ main concerns – Uncertain nature of IBD – Effects of medications 3 Patients’ belief systems (treatment will not help, side effects outweigh benefits) 2 Patients’ belief systems (treatment will not help, side effects outweigh benefits) 2 Psychiatric disorders 4 Psychiatric disorders 4 Male, unmarried, younger age 5,6 Male, unmarried, younger age 5,6 Patterns of nonadherence 7 Patterns of nonadherence 7 1 Martin A, et al. Ital J Gastroenterol. 1992;24: Levy RL, Field AD. Am J Gastroenterol. 1999;94: Drossman DA, et al. Psychosom Med. 1991;53: Nigro G, et al. J Clin Gastroenterol. 2001;32: Kane S. Am J Gastroenterol. 2001;96: Kane S. Am J Gastroenterol. 2001;96(suppl):S Kane S. In: Bayless TM, Hanauer SB, eds. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: BC Decker, 2001:9-11.

93 Prevalence of Nonadherence to IBD Maintenance Therapy Failure to take medication by patients with other illnesses: 25%–50% 1 Failure to take medication by patients with other illnesses: 25%–50% 1 41% of patients on maintenance sulfasalazine do not take prescribed dosages 2 41% of patients on maintenance sulfasalazine do not take prescribed dosages 2 Clinical research protocols overestimate drug adherence Clinical research protocols overestimate drug adherence 1 Blackwell B. Clin Pharmacol Ther. 1972;13: van Hees PAM, van Tongeren JHM. J Clin Gastroenterol. 1982;4:

94 Impact of Nonadherence on Outcomes in IBD *P=.001. Adapted with permission from Am J Med., Vol 114, Kane S, Huo D, Aikens J, Hanauer S. Medication nonadherence and the outcomes of patients with quiescent ulcerative colitis, pages 39-43, Copyright 2003 with permission from Excerpta Medica % of Patients With Quiescent UC Remaining in Remission Time (months) Adherent to 5-ASA therapy (Asacol ® ) Nonadherent to 5-ASA therapy* (Asacol ® )

95 Strategies for Optimizing Patient Adherence IBD is a chronic, lifelong illness IBD is a chronic, lifelong illness Induce then maintain remission Induce then maintain remission Reciprocal patient:clinician relationship Reciprocal patient:clinician relationship Educate patient and family Educate patient and family Individualize therapy/simplify regimen Individualize therapy/simplify regimen Promote emotional/psychological support Promote emotional/psychological support Obtain patient’s commitment to therapeutic objectives Obtain patient’s commitment to therapeutic objectives

96 Guided Self-Management in UC Personalized, guided self-management regimen Personalized, guided self-management regimen Single minute session Single minute session –Relapse recognition –Treatment protocols Patients given written protocols Patients given written protocols Copy to primary MDs Copy to primary MDs Routine treatment and follow-up Routine treatment and follow-up Intervention Group n=101 Control Group n=102 Robinson A, et al. Lancet. 2001;358:

97 Relapses Are Treated Earlier in Self-Managed Patients Reprinted with permission from Elsevier (The Lancet. 2001;358: ). Time (days) Proportion Untreated (%) Intervention group Control group

98 Patient Self-Management Trends in self-management group (vs controls) Trends in self-management group (vs controls) –Fewer relapses (1.53 vs 1.93; P=NS) –Shorter duration of relapse if treated in first 24 h (17.7±17.1 d vs 25.5±37.4 d; P=.16) –82% preferred self-management –95% of controls said they were adopting self-management Robinson A, et al. Lancet. 2001;358:

99 General Conclusions: Special Considerations for Women With IBD Women have more severe symptoms, more disease concerns than men Women have more severe symptoms, more disease concerns than men Menstrual symptoms may be more severe Menstrual symptoms may be more severe OCs may be related to disease-activity flares OCs may be related to disease-activity flares IPAA improvement may be accompanied by feelings of decreased attractiveness IPAA improvement may be accompanied by feelings of decreased attractiveness Most women experience postoperative improvement in sexual activity Most women experience postoperative improvement in sexual activity

100 General Conclusions: Special Considerations for Women With IBD (cont’d) Fertility Fertility –Normal or near normal in UC –May be affected in CD –IPAA reduces fertility –Voluntary childlessness makes data difficult to interpret Pregnancy Pregnancy –IBD has minimal effect on pregnancy outcomes –Conception during remission preferable –Some IBD drugs safe in pregnancy and breast- feeding –Disease activity is greater threat to pregnancy than treatment

101 General Conclusions: Special Considerations for Women With IBD (cont’d) Menopause Menopause –Bone loss, especially in CD, is greatest risk, leads to osteoporosis –Cardiovascular risk increases, equal to risk in men by age 75 –Benefits of HRT are increasingly questioned as risks are observed Osteoporosis Osteoporosis –Common in postmenopausal women, aggravated by CD and steroid therapy –Active plan to prevent bone loss and osteoporosis is vital –Nonsteroidal IBD drugs –Treatment options to preserve bone mass

102 General Conclusions: Special Considerations for Women With IBD (cont’d) Adherence improves outcomes; nonadherence leads to relapse Adherence improves outcomes; nonadherence leads to relapse Patient must understand nature of disease, goals of treatment Patient must understand nature of disease, goals of treatment Treatment plan tailored to patient’s life and needs Treatment plan tailored to patient’s life and needs Adherence improved by good physician-patient communication Adherence improved by good physician-patient communication


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