INFLAMMATORY BOWEL DISEASE - PART 9 pdf

294 Bauer and Lashner Chapter 15 / Gender-Specific Issues in IBD 295 295 From: Clinical Gastroenterology: Inflammatory Bowel Disease: Diagnosis and Therapeutics Edited by: R. D. Cohen © Humana Press Inc., Totowa, NJ 15 Gender-Specific Issues in Inflammatory Bowel Disease Sunanda V. Kane, MD CONTENTS INTRODUCTION SELF-IMAGE ISSUES THE MENSTRUAL CYCLE FERTILITY CONTRACEPTION EFFECT OF IBD ON PREGNANCY EFFECT OF PREGNANCY ON IBD T REATMENT OF IBD DURING PREGNANCY SURGERY AND PREGNANCY SURGICAL OUTCOMES MENOPAUSE SUMMARY REFERENCES INTRODUCTION The incidence of Crohn’s disease (CD) in women has been increasing over the past few decades. It is not clear whether this is a result of improved diagnostic techniques, an increase in smoking habits by young women (patients with CD tend to be smokers compared to people with- out CD), or other factors not yet identified. However, the consequence of this trend is a growing population of patients with gender-specific needs and concerns related to their medical care. Every component of the reproductive cycle can potentially effect disease course or symp- tomatology. Because the diagnosis of CD or ulcerative colitis (UC) is 296 Kane often made in the childbearing years, fertility and pregnancy are important issues that previously have been handled exclusively by gynecologists. Gastroenterologists caring for women with inflammatory bowel disease (IBD) should be aware of these issues and their appropriate management. SELF-IMAGE ISSUES Maunder et al. reported consistently higher levels of symptom sever- ity and rating of IBD patient concerns in women than men (1). Patient concerns that differed by gender included attractiveness, intimacy, and sexual performance. Women also had stronger concerns about self- image, feeling alone, and fearful of having children. Active disease can lead to fatigue and loss of libido, in addition to the embarrassment of fecal incontinence. Corticosteroids to treat active disease leads to Cushingoid features along with weight gain and mood swings. Perineal involvement in CD can be physically deforming, as well as resulting in dyspareunia and self-consciousness. The presence of an ostomy or other surgical scars can also lead to a lower self-esteem (2). THE MENSTRUAL CYCLE For girls diagnosed with IBD before or during puberty, the onset of menses (menarche) can be delayed. This can be secondary to chronic inflammation or a poor nutritional status that directly affects steroid hormone production. Menarche usually occurs once active disease is treated appropriately. Disease activity can also affect the menstrual cycle after the onset of menarche. This can be manifested by irregular or skipped periods, or an increase in disease symptoms during the premenstrual or menstrual phase. A recent study corroborates this phenomenon (3). The premen- strual syndrome (PMS) includes gastrointestinal symptoms, but women with IBD complain of these symptoms above and beyond that found in the normal population. Some women consider these “mini- flares”. In reality, this is a cyclic, predictable phenomenon, which is neither random or “all in the head”. Rather than treating these symptoms as active IBD, conservative treatment to alleviate symptoms is more appropriate, as symptoms will tend to resolve in a few days’ time. Table 1 lists those preparations that can be used as alternatives to standard medications to provide relief from menstrual-related symptoms. Some women have such debilitating symptoms that the elimination of menses is the only way to provide relief. This can be achieved with the short-term injectable contraceptives (Depo-Provera ® ) or hormones Chapter 15 / Gender-Specific Issues in IBD 297 (Lupron ® ). At this time, a hysterectomy is not recommended for this indication, but those women who undergo this procedure for other gynecologic reasons find their IBD symptoms improve. FERTILITY Overall, the fertility rates for women with IBD are essentially the same as those of the normal population. Early studies showing lower fertility rates had not taken into account an increased voluntary child- lessness rate in women with IBD. Active CD, however, can reduce fertility in several ways, depending upon the location of inflammation. Active inflammation in the colon has been shown to decrease fertility, as well as any inflammation or scarring directly involving the fallopian tubes or ovaries. Women who have had any surgical resection are at risk for adhesions, which can also impair tubal function. Ileo-anal anastomosis has also been linked to decreased fertility in women. None of the medications used to treat IBD has an effect on female fertility, but it is important to remember that sulfasalazine therapy reduces sperm motility and count in males. Although there is no mini- mum required time period with quiescent disease prior to a planned conception, the longer the better. Open discussions between patient and physician are the best way to ensure the best outcome of a pregnancy. If a woman is doing well and in remission, there is every reason to expect the pregnancy to proceed smoothly. If active disease is present, it is likely to continue through pregnancy and will place the pregnancy at greater risk for a complication (4). This risk appears to be higher in CD Table 1 Oral Preparations to Alleviate Menstrual Symptoms Commercial Preparations Supplements, Vitamins, and Herbs Pamprin ® Calcium (1500 mg/d) Doan’s Pills ® Magnesium (up to 400 mg/d) Pre-lief ® Vitamin E (400 mg/d) Midol ® * Vitamin C (1000 mg/d) Vitamin B6 (100 mcg/d) Chamomile tea Black cohosh Evening primrose oil (1500 mcg/d) Dong quai Yam extract (480 mcg/d) *Should be used with caution as this contains ibuprofen. 298 Kane than in UC. The main priority is to establish and maintain remission before the patient conceives. One of the problems in CD is the accurate definition of remission. In CD, a patient may feel fine even though she has an elevated C-reactive protein (CRP), an abnormal colonoscopy, and/or X-ray. Some women remain childless for fear of disease transmission to their offspring. Current data suggests that this risk is low; 7% if one parent has CD and less if one parent has UC. However, the risk of IBD increases as high as 37% if both parents have the disease. The risk of inheriting IBD is higher in Jewish (7.8%) than in non-Jewish (5.8%) families. It is important to remember that IBD is not a genetic disorder in a true Mendelian fashion. Even with genetic predisposition, other factors are necessary to produce expression of either disease. CONTRACEPTION The management of contraception in those women with IBD who do not wish to become pregnant differs from that for normal women. The most important goal still remains the selection of the most reliable method of birth control. Barrier methods of contraception are accept- able but are not as effective as alternatives. The use of intrauterine devices is not usually recommended, as any complaint of abdominal pain could potentially delay the correct diagnosis of active IBD vs pel- vic inflammatory disease. The data regarding the safety of oral contraceptives (OC) in IBD is conflicting. Early studies suggested an increased risk for the develop- ment of CD and UC, but did not account for tobacco use (5–8). Reports from Europe, where contraceptives contain a higher estrogen content, continue to show modest increases in risk for the development of CD after adjusting for cigarette use (odds ratios 1.2–2.0) (9). Other data suggest that oral contraceptive use may exacerbate disease activity (10,11). Two small prospective studies have found an increased risk of disease recurrence after induction of remission in CD with OC use. No information is available for a possible similar risk in UC. On the other hand, some physicians successfully use oral contracep- tives to treat cyclic symptoms that appear to be related to the menstrual cycle, to tamper the effect of fluctuating hormone levels. At this time, no standard guidelines exist for oral contraception use, as there are many preparations available. The variable amounts of progesterone and estro- gen are the factors that determine the side-effect profile. The choice of which oral contraceptive preparation to use has to be individualized, taking into consideration other factors including patient history, parity, Chapter 15 / Gender-Specific Issues in IBD 299 and personal preferences. It does appear prudent to try to prescribe a formulation that contains the lowest amount of estrogen possible. EFFECT OF IBD ON PREGNANCY Women with IBD in remission are no more likely to experience spon- taneous abortion, stillbirth, or children born with a congenital abnor- mality (12). Figure 1 summarizes results of 24 published reports comparing outcomes in women with IBD vs the normal population. Some work has suggested that babies born to women with IBD are of smaller birth weight (13). When a woman has active disease, premature birth is a greater concern. The presence of IBD does not appear to have an impact on mater- nal complications related to pregnancy, including hypertension or pro- teinuria (14). However, active perianal disease may worsen after a vaginal delivery. One retrospective of a study of women with CD found that 18% of those without previous perianal disease developed such disease after delivery, usually involving an extensive episiotomy (15). Otherwise, the presence of IBD does not have a significant impact on the method of delivery, nor is it an indication for Cesarean section. EFFECT OF PREGNANCY ON IBD For women with quiescent UC, the rate of relapse is approx the same in pregnant vs nonpregnant patients. This is in contrast to the presence of active disease at the time of conception, which is associated with continued or worsening disease activity in approx 70% of women (12). Comparable observations are seen in Crohn’s disease. Figures 2 and 3 illustrate pregnancy-related disease activity as reported by Miller et al. (4)). The older literature suggested a trend for disease to flare in the first trimester, but this was documented prior to the accepted practice of maintenance therapy, continued even during pregnancy. It is important to remember that hemoglobin and albumin levels decrease and ESR increase during pregnancy. Because of these normal physiologic changes, disease assessment during pregnancy should rely more on clinical symptoms than laboratory parameters. Ultrasound exams are clearly safe, and there is no evidence that if indicated, a sigmoidoscopy will induce premature labor (16). Colonoscopy should only be performed when extent and severity of disease specifically need to be ascertained. There is data that has suggested that a history of child bearing changes the natural history of CD (17). Women who were pregnant had fewer resections or longer intervals between resections as compared to women 300 Kane who had not had children but otherwise similar disease. One possible explanation is the inhibition of macrophage function by relaxin. Relaxin is a hormone produced exclusively during pregnancy, which may result in less fibrosis and stricture formation by this inhibition of macrophages. Fig. 1. Adverse outcomes in pregnancy in IBD vs normals. Fig. 2. Natural history of disease during pregnancy: UC. Fig. 3. Natural history of disease during pregnancy: CD. Chapter 15 / Gender-Specific Issues in IBD 301 TREATMENT OF IBD DURING PREGNANCY The key principle to management is to remember that the greatest risk to pregnancy is active disease, not active therapy. Because there are limited definitive data available on the safety of IBD medications in pregnancy, the focus, therefore, should be on establishing remission before conception and maintaining remission during pregnancy. Sulfasalazine readily crosses the placenta, but has not been associated with any fetal abnormalities. However, patients taking sulfasalazine should also be supplemented with folic acid before conceiving to decrease the risk of neural tube defects. A dose of 1 mg bid would be appropriate. The safety of mesalamine during pregnancy has been demonstrated in a number of trials (18,19). In two separate studies, women taking 2–3 g/d had no increased incidence of fetal abnormalities than that in normal healthy women. Topical 5-ASA agents are likewise safe during pregnancy. The data regarding immunomodulator therapy (azathioprine, 6-MP) is more conflicting. There are no large studies on the use of these medi- cations during pregnancy in women with IBD. To date, our information comes from the transplantation literature and from small retrospective series in IBD. It is generally believed by the most experienced IBD clinicians that immunosuppressives such as 6-MP, azathioprine, and cyclosporine can be used safely during pregnancy if the mother’s health mandates therapy. Methotrexate, another immunomodulatory medica- tion, is contraindicated in pregnancy. Infliximab was recently reclassi- fied as a “Category B” drug in pregnancy, and open-label experience thus far has suggested that it may be safe to use. Corticosteroids have not been associated with teratogenicity in humans and can be used as required to control disease activity. Pred- nisone crosses the placenta less efficiently than other steroid formula- tions such as betamethasone or dexamethasone. Only limited data is available regarding the safety of antibiotics as treatment for CD. Cur- rently, ampicillin, cephalosporins, and erythromycin are believed safe, as well as ciprofloxacin. Metronidazole has been used to treat vaginitis in women during the first trimester of pregnancy but no controlled trials have definitively shown its safety. Table 2 details the safety of those medications used in IBD. The medications known to be safe for breastfeeding include sulfasalazine, the mesalamine preparations (Asacol ® , Pentasa ® , Rowasa ® , Colazal™, Canasa™) and corticosteroids. Negligible levels of infliximab (Remicade ® ) have been detected in breast milk. Mothers planning on nursing should discontinue the use of cyclosporine, met- 302 Kane ronidazole, ciprofloxacin, and methotrexate. No data is available regarding the thiopurines and should be discussed on a case-by-case basis. Table 3 summarizes the safety data regarding medications and their use during breastfeeding. Current studies are underway studying medication levels in breast milk, to assess for any increased risk of immunosuppression of the infant. SURGERY AND PREGNANCY The indications for surgery during pregnancy are identical to that of nonpregnant patients. These include obstruction, perforation, abscess, and hemorrhage. Pregnancy has not been shown to complicate stoma function. Women may experience some prolapse as a result of abdomi- nal pressure, but no increased risk to the pregnancy is encountered. For those women who have had ileoanal pull through procedures, an increase in the number of bowel movements during pregnancy has been reported, but no increased risk for pouchitis or delivery complications has been reported (20). SURGICAL OUTCOMES There has been a varying incidence of dyspareunia following pelvic surgery, ranging from 0 to 26%. This variation may be due to the het- erogeneous nature of surgeries or underreporting of symptoms to physicians (21–23). After ileo-anal anastomosis, one report found 15% incidence of dyspareunia, and an increase in menstrual problems (2). Fertility may also be decreased following such surgery. MENOPAUSE Menopause, whether natural or surgical, leads to many physiologic changes in a woman’s body. Just as oral contraceptives can help with controlling symptoms, there is data to suggest that some of the gas- trointestinal symptoms associated with IBD have decreased in women who have achieved menopause. Women with UC are at no greater risk for an early menopause than women without IBD. There is some data that suggest that women with CD may enter menopause earlier than normal women, but a mechanism has yet to be established (7). What is certain however, is that the risk for osteoporosis is substan- tially higher because of steroid exposure, decreased dairy product con- sumption secondary to lactose intolerance, and malabsorption related to inflamed gastrointestinal mucosa. It is recommended, therefore, that Chapter 15 / Gender-Specific Issues in IBD 303 Table 2 Safety of IBD Medication During Pregnancy Safe to Use When Indicated Limited Data Contraindicated Oral Mesalamine Olsalazine Methotrexate Topical Mesalamine Azathioprine Thalidomide Sulfasalazine 6-mercaptopurine Ciprofloxacin* Cyclosporine Infliximab Corticosteroids Metronidazole * Ciprofloxacin’s use should be delayed until after the first trimester, if possible. Table 3 Safety of IBD Medications During Breastfeeding Safe to Use When Indicated No Data Contraindicated Oral Mesalamine Olsalazine Methotrexate Topical Mesalamine Azathioprine Thalidomide Sulfasalazine 6-mercaptopurine Cyclosporine Corticosteroids Ciprofloxacin Infliximab Metronidazole every woman with IBD undergo a bone density scan to assess for bone loss. If present, then replacement calcium and vitamin D are essential, with the addition of bisphosphonates as indicated. The issues regarding hormone replacement therapy (HRT) are iden- tical to those in normal women for bone loss and cardioprotection. Family history for any breast or uterine cancer, or a personal history of either these or thromboembolic events need to be taken into consider- ation when deciding on HRT. SUMMARY • The menstrual cycle can affect IBD symptoms. • Fertility is not affected in UC, but can be in active CD. • There is no increase in bad outcome with quiescent IBD. •Active disease at conception increases the risk for adverse outcomes. • The majority of medications for IBD are safe in pregnancy and breastfeeding. •Active disease is more deleterious than active therapy. [...]... epidural anesthesia warranted? 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