Inflammatory bowel diseases (IBD), namely Crohn disease (CD) and ulcerative colitis (UC), are common in Western society. Because at least half of the patients suffering from these diseases are women, it is important that physicians are aware of their gender-specific needs. There are multiple important concerns for women with UC and CD including issues of body image and sexuality, menstruation, contraception, screening for cervical cancer, matters related to menopause and hormone replacement therapy, osteoporosis, and the overlap seen between IBS and IBD. In this article, we have addressed these important, non–pregnancy-related issues faced by women with IBD.
Inflammatory bowel diseases (IBD), namely Crohn disease (CD) and ulcerative colitis (UC), are common in Western society, with as many as 1.4 million people in the United States and 2.2 million persons in Europe carrying these diagnoses. Although there are no significant gender differences reported among patients with UC, CD does have a slight female predominance, with a male-to-female ratio of 1.0:1.8. Because at least half of the patients suffering from these diseases are women, it is important that physicians are aware of their gender-specific needs. When considering matters specific to women with IBD, most discussions and articles revolve around pregnancy and IBD. There are, however, multiple other important concerns for women with UC and CD, including issues of body image and sexuality, menstruation, contraception, screening for cervical cancer, matters related to menopause and hormone replacement therapy, osteoporosis, and the overlap seen between irritable bowel syndrome (IBS) and IBD. In this article, we have addressed these important, non–pregnancy-related issues faced by women with IBD. Fertility, pregnancy, and IBD are discussed in a separate article by Dr Sunanda Kane, elsewhere in this issue.
Body image/sexuality
Many of the symptoms, morbidities, and quality-of-life issues in patients with IBD affect women’s body image and sexuality. Sexual dysfunction in this population was first highlighted by Moody and colleagues in 1992, when they described decreased sexual activity in women with CD. They interviewed 50 women with IBD and age-matched controls. Twenty-four percent of the women with CD versus 4% of controls reported abstinence from sexual activity. The most common reason for decreased frequency of sexual activity was dyspareunia, which was reported by as many as 60% of patients with CD. Abdominal pain, diarrhea, and fear of fecal incontinence were other reasons for decreased frequency of sexual intercourse in this group of patients.
A year later, Moody and Mayberry looked at the perceived sexual dysfunction among patients with IBD. Although differences in the frequency of sexual intercourse between the patients with IBD and controls did not reach statistical significance, patients with IBD cited numerous reasons why they limited their sexual activity, including fear of fecal incontinence, fatigue, abdominal pain, and urgency.
More recent studies have shown that women with IBD indicate that sexual function is significantly affected by their disease. In a survey of 336 women with IBD ages 18 to 65, 63% reported low sexual activity. In this study, there was no specific feature of IBD that explained the high prevalence of sexual dysfunction. Psychosocial factors did, however, play a large role. The greatest risk factor was depressed mood, which affected all aspects of sexuality.
Discussion of sexual health in the context of disease activity is essential to facilitate psychosocial adjustment to living with IBD. Unfortunately, physicians do not adequately address sexuality in women with these diseases. Borum and colleagues surveyed women with IBD addressing the frequency at which physicians (gastroenterologists, primary care physicians, and obstetricians/gynecologists) discuss issues related to IBD, sexuality, and sexual function. Of the 64 women surveyed, 12 (18.8%) reported that their gastroenterologist more frequently addressed issues of sexuality than their primary care physician (0%) or obstetrician/gynecologist (0%). The discussion of sexuality was reportedly initiated in all cases by the patient rather than the gastroenterologist.
It is important that physicians are aware of the impact IBD can have on women’s body image and sexuality. Physicians need to do a better job at addressing issues of self-image and sexuality with their patients with IBD and provide support and disease-specific information to help with these issues. Although as gastroenterologists most of us remain focused on management of IBD disease activity, it is important to remember that issues of body image and sexuality are equally important to patients and it is our duty as physicians to make every attempt to initiate and discuss these issues with them.
Menstruation
The premenstrual syndrome in women has been well described, dating back to 1973 when Timonen and Procope first reported the symptoms of premenstrual irritability, depression, diarrhea, and constipation in healthy women. Fluctuations of hormonal levels during the menstrual cycle appear to influence gastrointestinal (GI) symptoms, resulting in nausea, constipation, and diarrhea. Although there are a few studies looking at the effects of the menstrual cycle on GI symptoms of patients with bowel disorders, less is available specifically with regard to IBD. One of the best studies reported in the literature to date was by Kane and colleagues, in which they studied bowel symptoms and patterns in patients with IBD and IBS. In this study, patients with UC, CD, and IBS as well as healthy controls were interviewed. Reports of changes in patients’ bowel habits and other symptoms during the premenstrual and menstrual phases of the cycle were compared with those of healthy women. Ninety-three percent of all patient participants reported experiencing premenstrual symptoms, the most common being emotional irritability followed by depression and weight gain. Patients with CD had more symptoms in general than controls. Premenstrual diarrhea was more common in patients with IBS and IBD than in controls, as was nausea for patients with CD or IBS versus controls. Patients with IBD and IBS were more likely to have a cyclical pattern to bowel habits, with diarrhea being the most common symptom.
Parlak and colleagues, in their prospective study, investigated the difference between healthy women and those with IBD regarding GI and non-GI symptoms during the menstrual cycle. They found that GI symptoms and frequency of defecation were higher in patients with UC and CD than in controls. Patients with CD had more GI symptoms in all 3 phases of the menstrual cycle, whereas controls and patients with UC had fewer symptoms in the postmenstrual phase. The cyclic pattern present in healthy women persisted in patients with UC and CD.
These studies make it clear that the variation in GI symptoms during the menstrual cycle is prevalent. Sometimes patients with IBD may interpret the variation in bowel patterns occurring with the menstrual cycle as disease flare. Therefore, the menstrual cycle and its effect on bowel patterns should be taken into consideration when evaluating patients for disease activity.
Menstruation
The premenstrual syndrome in women has been well described, dating back to 1973 when Timonen and Procope first reported the symptoms of premenstrual irritability, depression, diarrhea, and constipation in healthy women. Fluctuations of hormonal levels during the menstrual cycle appear to influence gastrointestinal (GI) symptoms, resulting in nausea, constipation, and diarrhea. Although there are a few studies looking at the effects of the menstrual cycle on GI symptoms of patients with bowel disorders, less is available specifically with regard to IBD. One of the best studies reported in the literature to date was by Kane and colleagues, in which they studied bowel symptoms and patterns in patients with IBD and IBS. In this study, patients with UC, CD, and IBS as well as healthy controls were interviewed. Reports of changes in patients’ bowel habits and other symptoms during the premenstrual and menstrual phases of the cycle were compared with those of healthy women. Ninety-three percent of all patient participants reported experiencing premenstrual symptoms, the most common being emotional irritability followed by depression and weight gain. Patients with CD had more symptoms in general than controls. Premenstrual diarrhea was more common in patients with IBS and IBD than in controls, as was nausea for patients with CD or IBS versus controls. Patients with IBD and IBS were more likely to have a cyclical pattern to bowel habits, with diarrhea being the most common symptom.
Parlak and colleagues, in their prospective study, investigated the difference between healthy women and those with IBD regarding GI and non-GI symptoms during the menstrual cycle. They found that GI symptoms and frequency of defecation were higher in patients with UC and CD than in controls. Patients with CD had more GI symptoms in all 3 phases of the menstrual cycle, whereas controls and patients with UC had fewer symptoms in the postmenstrual phase. The cyclic pattern present in healthy women persisted in patients with UC and CD.
These studies make it clear that the variation in GI symptoms during the menstrual cycle is prevalent. Sometimes patients with IBD may interpret the variation in bowel patterns occurring with the menstrual cycle as disease flare. Therefore, the menstrual cycle and its effect on bowel patterns should be taken into consideration when evaluating patients for disease activity.
Contraception
Because IBD often affects women during their childbearing years, women with IBD need effective contraceptive options to avoid unintended pregnancies. Smaller family sizes and voluntary childlessness is seen more frequently in women with IBD. Marri and colleagues examined the considerations about pregnancy in patients with IBD. Their survey found that 18.0% of patients with CD and 14.0% with UC had a higher rate of voluntary childlessness compared with 6.2% in the general population. In addition, contraception use in the IBD population was lower than in the general population. Of all patients with IBD in this survey, 76% used contraception before the diagnosis of IBD and 82% after its diagnosis. Contraceptive options were similar to the general population with the most common choices being oral contraception (OC), barrier methods, and abstinence.
When women with IBD decide to proceed with pregnancy, it should be a planned event when the disease is well controlled. For this reason, the choice of contraception in patients with IBD is a very important issue. Ideally, it should have a very low to no failure rate and should have minimal to no effect on IBD disease activity. Although women with IBD have the same contraceptive choices as women without IBD, certain contraceptive methods may have specific cautions for patients with IBD. Barrier methods have typical user failure rates, which may make these methods inappropriate for use by women who are using teratogenic drugs. The use of intrauterine devices (IUDs) remains controversial in patients who are immunosuppressed. A literature review of immunosuppressed patients with primarily HIV or systemic lupus erythematosus found no increased risk of pelvic infection with the use of IUDs. There are, however, limited case reports of patients with IBD who have exacerbation of IBD symptoms after insertion of IUDs. Furthermore, Okoro and Kane point out that any complication with an IUD could be misinterpreted by both the patient and the treating physician as an IBD flare up instead of possible pelvic inflammatory disease.
There are many issues specific to patients with IBD that must be considered regarding the use of OCs. Most of the absorption of OCs occurs in the small bowel. Patients with CD with inflammation or ulceration of the small bowel or those with increased transit as a result of surgery may have reduced efficacy of OCs. For patients with UC, pharmacokinetic studies have suggested that their plasma concentrations of steroid hormones are similar to that of healthy volunteers.
There have been concerns regarding flare up of disease activity in patients with IBD who are taking OCs. Zapata and colleagues, in their meta-analysis of contraceptive use among women with IBD, looked at 5 studies on this topic. None of the identified studies demonstrated a significant increased risk of disease relapse in patients with IBD who were taking OCs.
Another concern related to the use of OCs in the IBD population is that of thrombosis. There is evidence to suggest an increased risk of thrombosis in patients with IBD, particularly in those with active or more extensive disease. There are, however, no prospective studies looking at increased risk of thrombosis in patients with IBD who are taking OCs.
The risk with the use of OCs in the pathogenesis of IBD was reviewed by Cornish and colleagues. Their meta-analysis found that women exposed to OCs had a pooled relative risk (RR) of 1.51 and 1.46 when adjusted for smoking and an increased RR with the length of exposure. The RR for women with UC taking OCs was 1.53 and 1.28 when adjusted for smoking. The risk for patients who stopped using OCs reverted to that of the nonexposed. The reduction in estrogen and progesterone content in OCs in the past 2 decades did not appear to reduce the RR of IBD. However, doses were not recorded in many of the studies. The investigators did not recommend that female patients stop OCs but rather that clinicians discuss possible risks with patients and consider alternative forms in patients with a strong family history of IBD.
Cervical screening
In patients with IBD, data regarding the risk of cervical abnormality and cervical cancer has thus far been limited and inconsistent. In a recent population-based, nested, case-control study, Huftless and colleagues evaluated the risk of cervical cancer among women with IBD from 1996 to 2006. In this retrospective study, 1244 patients with IBD between the ages 15 and 68 from the Kaiser system in Northern California were assessed for a history of aminosalicylate and immunosuppressant use and the diagnosis of cervical cancer. After adjusting for age, ethnicity, and smoking history, Huftless and colleagues found that women with IBD had a nonsignificant, 45% increased risk of cervical cancer over women with no IBD. They also noted a 4% increase in the number of Pap smears received by women with IBD compared with women with no IBD. Patients exposed to aminosalicylates and immune modulators and corticosteroids were found to have elevated risks of cancer but none of the associations were statistically significant. None of the patients with cervical cancer had an exposure to infliximab.
Another study looking at the positive association of cervical abnormalities and IBD is that done by Bhatia and colleagues in 2006. This study demonstrated that a diagnosis of IBD in women correlates with an increased risk of abnormal Pap smear. Eighteen percent of patients with IBD had an abnormal Pap smear compared with 5% of controls. The type of IBD and exposure to immunosuppressive medications were not associated with increased risk of abnormal Pap smear. In 2008, Kane and colleagues also found a significantly higher incidence of abnormal Pap smears in patients with IBD (42.5%) compared with controls (7%).
Other studies have not supported the relationship between IBD and cervical abnormalities. Lees and colleagues recently published data that found no difference in rates of abnormal Pap smears between patients with IBD and controls. However, there were significantly more abnormal Pap smears in patients with IBD who were current smokers compared with ex-smokers and those who had never smoked. Similarly, Singh and colleagues found no association between cervical abnormalities and UC. The increase in risk in women with CD was limited to those exposed to 10 or more prescriptions of OCs. Only the combined exposure to corticosteroids and immunosuppressants was associated with increased risk of cervical abnormalities.
Further studies are needed to assess if, in fact, women with IBD indeed have a higher incidence of cervical abnormality, and if they do, what is the underlying etiology? If women with IBD are found to have an increased incidence of cervical abnormality, there needs to be a system to ensure adequate cervical cancer screening to prevent unnecessary morbidity and mortality. Cervical testing protocols before and during immunosuppressant therapy may also be warranted.
Menopause/hormone replacement therapy
Although IBD most commonly affects women in their reproductive years, we know that there is a bimodal peak of onset of both UC and CD and women may develop IBD for the first time after menopause. Furthermore, women whose disease onset occurred during their reproductive years will eventually go through menopause either naturally or surgically. It is important to understand the effects of IBD on menopause and vice versa. There are, however, very few data regarding menopause in patients with IBD. In 1989, Lichtarowicz and colleagues surveyed women with CD regarding details of their menstrual cycles, age of menopause, history of surgery, smoking habits, and use of OCs. Of the 146 patients with CD who responded, 48 (34%) had undergone physiologic menopause at a mean age of 47.6 years compared with 49.6 years for the control group. The investigators concluded that CD was associated with premature menopause.
Conversely, Kane and colleagues, in their retrospective review, sought to characterize the effects of menopause on IBD activity and identify possible modifiers of disease activity. They found a median age of menopause to be 48.2 years, similar to historical controls. In their study of 65 women, 20 with UC and 45 with CD, there was no apparent correlation between having a flare in the premenopausal state and postmenopausal state. However, when looking at hormone use, there appeared to be a protective effect in the use of hormone replacement therapy (HRT) on disease activity. Women with IBD using HRT compared with those not using HRT were 82% less likely to have a flare in the first 2 years of menopause. Those on HRT who did have a flare appeared to have less severe flares, as they did not require escalation of therapy to immunomodulator but rather required only an increased dose of mesalamine.
The use of HRT in women has recently become controversial since the Women’s Health Initiative was published, showing no cardiovascular benefit with unopposed estrogen and a small increase in risk of breast cancer, coronary heart disease, stroke, and venous thromboembolism with combined therapy. Until more research is available on the relationship between HRT and IBD, each individual patient’s personal and family history should be considered before deciding on the use of hormones in the postmenopausal state.
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