Journal of Women's Health Care
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Psychosomatic Interactions in Irritable Bowel Syndrome, Endometriosis, and Healthy Subjects: An Experience Sampling Method Study

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Introduction

Irritable bowel syndrome (IBS) and endometriosis are two common diseases characterized by recurrent abdominal pain with often severe consequences for quality of life [1]. The etiologies of the diseases are uncertain, but a multifactorial pathophysiology has been proposed for each of them. Validated tests based on biological markers for diagnosis are not available for either disease, and diagnosis often relies on descriptive symptom-based diagnostic criteria. Likewise, disease-severity is mainly defined by patientreported symptom experience.

Many studies have examined the two conditions separately, but the literature on the associations and overlap between endometriosis and IBS is sparse, although it is increasing. It is well-known that patients with endometriosis frequently have gastrointestinal (GI) symptoms [2]. For example, in a cross-sectional study up to 69% of endometriosis patients experienced nausea accompanying pain, and 50% reported relief of their pelvic pain after a bowel movement. Several other studies reported that women with endometriosis have a twofold risk to also fulfill the diagnostic criteria for IBS, while in women initially diagnosed with IBS, some studies reported a threefold risk of having an endometriosis diagnosis [3]. Whether this overlap should be regarded as two separate disorders occurring concomitantly in the same individual, or as uncertainty about the true diagnosis due to unknown underlying pathologies, is not yet clear.

A common feature in both IBS and endometriosis is central sensitization in which contributing factors such as psychological stressors are present. Hence, psychological diseases like depression and anxiety disorders occur more frequently in these conditions [4]. As in functional somatic syndromes in general, an integrated multidisciplinary approach is suggested in patients’ management to achieve an adequate diagnostic workup and a personalized therapy, in order to target symptom severity, complexity and treatment resistance due to fragmented trajectories [5]. For this purpose, we previously developed an electronic smartphone-based patient-reported outcome measure specifically for the use of the Experience Sampling Methodology (ESM) in both populations with endometriosis and IBS (MADE ANONYMOUS). ESM is a momentary assessment method collecting repeated measurements randomly during the day, concerning the current symptom state in the natural environment of the subjects. These repeated in-the-moment assessments result in an individual pattern of symptoms and provide insight into the complex interplay between longitudinal symptom formations and possibly associated daily life factors like psychological stressors.

This study aimed to compare the association between psychological factors and abdominal symptoms, and their interaction with limitations in daily activities, in patients with endometriosis, patients with IBS and healthy controls (HC) by using the ESM.

Methods

This study uses data from two separate observational studies that were executed as part of validation projects of the ESM tool. Both studies were approved by the medical ethics committee and were executed according to the tenets of the revised Declaration of Helsinki (64th World Medical Association General Assembly, Fortaleza, Brazil; October 2013).

Study participants

Both patients with endometriosis and IBS were recruited at the outpatient clinics, a secondary/tertiary referral centre. Furthermore, endometriosis patients were recruited by the Dutch Endometriosis Foundation (Endometriose Stichting). The diagnosis of endometriosis was established by physical examination, imaging techniques, or laparoscopy. Patients reported endometriosisrelated complaints (Dysmenorrhoea, Pelvic pain, or Dyspareunia) on average at least one day per week in the last 3 months. Patients were excluded in case of any other organic explanation for chronic pelvic pain besides endometriosis. IBS patients were diagnosed according to the Rome IV criteria [6]. Reason for exclusion in IBS was abdominal surgery in the past (except for uncomplicated appendectomy, cholecystectomy, and/or hysterectomy). HC were recruited through advertisements by social media. Controls were eligible when not reporting any (present or past disorder associated with) chronic pelvic pain. Both patient groups and HC consisted of non-pregnant women, aged 18 years or older, who understood the Dutch language and were able to utilize the ESM application. All subjects gave written informed consent prior to participation.

Data collection

At baseline, patients were asked to fill in an electronic clinical case report form (eCRF) concerning demographic information and medical history in Castor electronic data capture [7]. During the 7-day study period, subjects completed repeated real-time questionnaires using the ESM tool.

ESM tool

All participants downloaded the smartphone application “MEASuRE” (Maastricht Electronic Abdominal Symptom REcording) on their smartphone, which contained either an endometriosis- or IBS-specific ESM questionnaire that was previously developed (MADE ANONYMOUS). Subjects were instructed to carry their smartphone with them during the study week and to complete the real-time questionnaires as often as possible. The MEASuRE application was set to send out an auditory and text signal 10 times a day at random moments between 07:30 AM and 10:30 PM, with intervals of at least 15 minutes and a maximum of 3 hours. These real-time assessments contained questions about somatic symptoms, psychological symptoms, contextual or social information, and the use of food and medication.

For this study, only overlapping data in both questionnaires regarding abdominal pain and psychological factors were analyzed. The questions were identical between the different moments during the day and are scored on an 11-point Numeric Rating Scale (0= not at all to 10= very severely). Without any response within 10 minutes after a notification, a questionnaire became unavailable and considered as missing data afterwards.

Statistical analysis

All analyses were performed in IBM SPSS Statistics 25. Continuous outcomes were tested for normality using the Shapiro-Wilk test. In the case of normal distribution, the mean and standard deviation (SD) are presented. In case of non-normal distribution, the median and interquartile range (IQR) are presented. Data were analyzed using the Kruskal–Wallis one-way ANOVA in the case of ordinal data and the chi-square test for categorical and dichotomous data. Turkey’s HSD post-hoc tests were performed in case of a significant difference for means or medians between the groups. To exclude the effect of differences in compliance between subjects, mean scores per participant were calculated before analyzing an average group score. A p-value of < 0.05 was considered statistically significant.

Associations between somatic and psychological symptoms were analyzed by using linear mixed models as ESM data are based on a hierarchical, multi-level structure with repeated measurements (level 1) nested within days (level 2) and within-subjects (level 3). All models are based on random intercept and an autoregressive (AR(1)) covariate structure for repeated measures.

Results

Patient characteristics

Table 1 shows the patient characteristics of 55 healthy controls (HC), 26 IBS patients, and 34 endometriosis patients. HC were significantly younger and had a lower BMI compared to IBS and endometriosis patients. More endometriosis patients reported a history of uncomplicated abdominal surgery (68%) compared to IBS patients (15%) and HC (16%). The use of (contraceptive) hormones was not significantly different between the three groups. On average, 65% of endometriosis patients reported the use of pain medication during the study, compared to 19% of IBS patients and 11% of HC (p<.001). The use of caffeine, nicotine, alcohol or other addictive substances was not significantly different between groups.

Table 1. Patient characteristics.

For abdominal pain, momentary assessments contained a question regarding nine abdominal locations, in which the selection of more locations was possible. Figure 1 shows significant differences in the frequency of reported locations of abdominal pain for IBS compared to endometriosis patients. This figure shows that IBS patients (green) were more likely to experience pain in the umbilical region (region 5) and on the left abdominal side (region 6) compared to endometriosis patients (orange). Endometriosis patients were more likely to experience pain in the lower abdomen/pelvic area (region 8) and on the lower right side of the abdomen (region 7) compared to IBS patients. Pain in regions 1-4 and 9 were not experienced differently between IBS and endometriosis patients.

Figure 1:Reported location of abdominal pain in patients with IBS and endometriosis.

Associations between “limitations in functioning” and somatic symptoms

During momentary assessments, patients were asked to complete the question of whether they feel limited in their daily activities because of their complaints. Mean (SD) scores for feeling limited (on a scale from 0-10) were 2.51 (2.89) for endometriosis, 1.34 (2.12) for IBS and 0.23 (0.95) for HC. Table 2 shows the association between somatic symptoms and the experience of feeling limited because of complaints in that very moment. In this table estimates show a Beta-coefficient which represents the direction (positive or negative) of the association. Abdominal somatic symptoms were associated with the feeling of being limited in all groups, except for experiencing abdominal distension in the healthy control group. Although differences in associations between groups were not tested, associations of feeling limited because of gastro-intestinal symptoms seemed less strong for healthy controls.

Associations between “functional limitations” and affect

Table 3 shows the association between affective symptoms and the experience of feeling limited in daily activities because of complaints. In endometriosis and IBS patients, both positive and negative affective symptoms were significantly associated with the experience of feeling limited. For HC, these associations seemed less strong or not significant.

Table 3. Average psychological symptom scores for IBS vs endometriosis patients vs HC, measured in real-time, several times a day. At first average scores per participant were calculated to exclude the effect of compliance.

Associations between abdominal pain and affect

Table 4 shows the association between abdominal pain and affective symptoms. In IBS and endometriosis patients, both positive and negative affective symptoms were significantly associated with abdominal pain, with the exception of feeling cheerful in IBS patients. In HC, “feeling dispirited” and “feeling cheerful” were also associated with abdominal pain but this association seemed less strong. For example, in IBS and endometriosis patients a one point increase in feeling dispirited was on average associated with a significant increase of 0.15 points in abdominal pain. For HC this increase in abdominal pain was only 0.05 points. However, differences in associations between groups were not statistically tested (Table 5 and 6).

Table 4. Associations between “limitations in functioning because of complaints” and somatic symptoms.