Long-term insights: Seven years of conservative management for deep endometriosis in the bowel

GBS participated in the study design and execution and was the primary author responsible for writing and preparation of the manuscript. USK contributed to the statistical analysis and the writing. MSH participated in the study design and writing of the paper. AGE participated in the study design and execution, conducted statistical analysis, contributed to the writing, and served as the supervisor of the paper. All authors reviewed and approved the final version of the manuscript.

All participants completed and signed an informed consent form prior to participation. The study was approved by the Central Denmark Region Committees on Health Research Ethics (no. 1‐10‐72‐1‐19) the August 26, 2019, and the Danish Data Protection Agency (no. 1‐16‐02‐657‐15) the March 1, 2020.

Of the 80 patients invited to participate, three were lost to follow‐up and four did not complete the informed consent form or Questionnaire 3, leaving data from 73 (91%) patients for analysis (Figure  2 ). During the follow‐up period, 11 patients (15%) had bowel surgery, three underwent total oophorectomy (4%), six (8%) entered natural menopause, and one was pregnant (1%) at the time of follow‐up. Flowchart. Fifty‐two fertile patients with bowel DE undergoing conservative management of the disease were eligible for analysis, and mean follow‐up was 6.9 years (0.4). Table  1 displays data from Questionnaire 1 at baseline and Questionnaire 3 at follow‐up. Seven patients gave birth during the follow‐up period (four patients had one child, three patients had two children). Nine patients underwent endometriosis surgery without bowel resection or oophorectomy; thus, they were not excluded from the study (six for endometriomas, one for retrocervical DE, and two had simple laparoscopies). Thirteen percent of the patients were without medical treatment at follow‐up, and a few patients were treated with combined oral contraceptives (COCs). Baseline demographic data of patients with conservatively managed deep endometriosis in the bowel in the 7‐year follow‐up study. Clinical examination. One missing since the posterior vaginal fornix could not be examined. Evaluated by TVUS. Evaluated by MRI. Forty patients had an MRI available for analysis. In Table  2 , data from SF‐36, EHP‐30, and clinical symptoms from baseline to follow‐up are shown. SF‐36, EHP‐30 Quality of life (QoL), and clinical symptoms of patients with conservatively managed bowel deep endometriosis in the 7‐year follow‐up study. Note : SF‐36: Score from 0 to 100: Higher scores reflect better perceived health and well‐being. EHP‐30: Score from 0 to 100: Lower score reflects lower impact on quality of life. Danish women age 35–44 years. No differences between baseline and follow‐up were observed in the SF‐36 or EHP‐30 questionnaires. A statistically significant reduction was observed in the levels of dysmenorrhea. Sixty‐one percent had no menstrual bleeding at follow‐up owing to medical treatment. Comparable levels of intermenstrual pain and dyschezia were observed, and there was a general tendency towards lower intake of painkillers at follow‐up. Table  3 and Table  S1 provide a detailed overview of bowel and urinary symptoms evaluated by LARS and ICIQ‐FLUTS at baseline and follow‐up. No changes were seen in the ~7‐year period. Fifteen percent of patients reported major LARS at follow‐up. In ICIQ‐FLUTS (analysis made between reports at 1 year and follow‐up), urgency and stress incontinence were the most prominent symptoms described at both timepoints. Urgency incontinence had a score of 1 (0–3) and stress incontinence a score of 1 (0–4), but no statistically significant change was seen during follow‐up. Bowel symptoms and Low Anterior Resection Score (LARS) in patients conservatively managed for deep endometriosis in the bowel in the 7‐year follow‐up study. Note : No LARS (0–20 points): No or mild functional issues after surgery. Minor LARS (21–29 points): Moderate functional problems affecting QoL. Major LARS (30–42 points): Severe functional issues, significantly impacting daily life. Test of differences between baseline and follow‐up, Wilcoxon signed rank. Among the 73 patients who provided informed consent and were eligible for analysis, initial comparisons were made between those who proceeded to surgery and those who continued conservative management. Analysis was made from Questionnaire 2. Eleven patients went through bowel resection, and three had total oophorectomy and went into SUR+ group ( n  = 14), leaving 59 patients for the SUR− group, where none were in a state of menopause or pregnant at timepoint for analysis (Figure  2 ). Median time to surgery was 2.3 (IQR: 1.1–4.6) years from timepoint for analysis, and seven patients (50%) went through surgery within the first 2 years of follow‐up. In total, 19% needed surgical treatment throughout the time period of 6.9 years. Demographic data are shown in Table  4 with no differences between the groups. Demographic data from Questionnaire 2 (1 year) of patients with bowel endometriosis conservatively managed (SUR−) compared with patients undergoing surgery (SUR+). Comparison of previous surgery versus no surgery. Comparison of hormonal treatment versus no treatment. Clinical examination (1 missing). TVUL. MRI: 56 patients had MRI available for analysis. N  = 45 in SUR− and n  = 11 in SUR+. 20 missings. Comparison of deep endometriosis in sacrouterine ligaments vs. absence of sacrouterine ligament endometriosis. 17 missings. As seen in Table  5 , the SUR+ group scored significantly lower (mean 63.9 (22.8)) than the SUR− group (mean 78.6 (19.4)) in the domain “Bodily pain” in SF‐36. This corresponded to results of EHP‐30 where the SUR+ group showed higher scores in “Pain,” “Control and powerlessness” and “Self‐image.” These differences did not persist when analysis was repeated at 7 years of follow‐up from Questionnaire 3 (data not shown). Quality of life (QoL) and clinical symptoms from Questionnaire 2 (1 year) in patients conservatively managed (SUR−) compared with patients undergoing surgery (SUR+). 1.1 (0.4–2.9) b Danish woman age 35–44 years. Comparison of painkiller use vs. no painkiller use. Larger bowel lesions (infiltration length and depth) were observed in the SUR+ group, and levels of dyschezia “Average” and “Worst pain” were higher when compared to the SUR− group. Moreover, there was a tendency towards a higher score of “Worst” intermenstrual pain in SUR+, although not significant. No differences was observed in the LARS and ICIQ scores (Tables  S2 and S3 ).

This 7‐year follow‐up study on 52 patients diagnosed with bowel DE undergoing conservative management reveals sustained levels in terms of EHP‐30, SF‐36 QoL, LARS score, and ICIQ‐FLUTS. Significant improvement in dysmenorrhea was seen. This could be biased from a change made regarding questions on dysmenorrhea, which automatically led to a score of zero if the individual had amenorrhea. Scores for dyschezia, intermenstrual pain, and use of pain‐relieving medication remained at the same levels throughout the follow‐up period. It is plausible that patients with rectosigmoid endometriosis have altered bowel function compared with normally functioning individuals. Walter et al. 16 studied normal bowel habits in the Swedish population. The eligible population was screened with colonoscopy for other gastrointestinal pathology, and patients with IBS and/or an intake of medications with gastrointestinal side effects were excluded, leaving 124 normal subjects for analysis (including 76 patients). They found the mean frequency of stools per week among the healthy patients was 9.2. In this study, we find almost all (96%) of patients having less than three stools per day, corresponding to less than 21 stools pr. week. In the study from Walter et al., 18% reported experiencing urgency and 24% had a feeling of incomplete evacuation. Relative to this, the present study found 33% ( n  = 17) with a strong urge to rush to the toilet at least once per week and 27% ( n  = 14) had to open their bowel again within 1 h of the last bowel opening. The above observations indicate that patients with bowel endometriosis experience similar frequencies and perceptions of incomplete evacuation as healthy controls; however, an increased urgency to defecate is found. Despite having severe DE, patients in the present study exhibited relatively high SF‐36 scores across all domains. Compared with age‐matched Danish normative data, modest reductions were observed in the domains of “General health”, “Vitality”, “Social functioning”, “Role emotional”, and “Mental health”, with “Vitality” being the most affected at follow‐up. In a review by Sima et al., 12 patients with all types of endometriosis were found to have lower SF‐36 scores across the domains, with the greatest reduction observed in “Physical functioning” (values as low as 78.9), compared with those in the present study. Collectively, these findings indicate that, in this cohort, women may experience selective reductions in certain aspects of health‐related quality of life compared with the general population, while overall functioning remains comparatively preserved relative to broader endometriosis populations. Endometriosis Health Profile scores were found to be low reflecting best health status. This was comparable to the findings from Ceccaroni et al. 9 where patients conservatively managed with bowel endometriosis had marginally higher scores except for the “Pain” item with the caveat that the authors used EHP‐5 instead of EHP‐30. Also, comparable levels of the EHP‐30 items were found by Hudelist et al. 17 and Dobo et al., 18 who followed up 3.4 years and 1 year after surgery, respectively. This suggests that selected patients managed conservatively may have a quality of life comparable to that of patients who have undergone surgery. The distribution of LARS scores at 7‐year follow‐up, 59% with no LARS, 25% with minor LARS, and 15.4% with major LARS, is consistent with the findings of Reh et al., 18 who reported a comparable distribution in 109 premenopausal patients with bowel endometriosis: 54% had no LARS, 28% had minor LARS, and 17% had major LARS. The authors also demonstrated that even in a healthy population without endometriosis, LARS‐like symptoms were present. This supports the need for evaluating patients with bowel endometriosis in both pre‐ and post‐surgical settings, as relying solely on postoperative assessments can be misleading, potentially overstating the negative impact of colorectal surgery. A study of 580 patients by Ceccaroni et al. 9 showed that fertile patients with bowel DE who received hormonal treatment had better scores for psychological well‐being, pain levels, and bowel function compared to patients who did not receive treatment. 9 Moreover, the authors found markedly better outcomes among patients after menopause when compared to patients of fertile age. The mean age of the patients managed conservatively was 40.6 years. In our series, mean age was 37.7 years at baseline, and results may reflect that disease is more manageable conservatively during late fertile years. Patients over 40 years of age and up until menopause may respond more favorably to treatment, and the disease may be less aggressive during late fertile years. In a previous study, we found patients having bowel surgery performed to be younger than patients who were managed conservatively, underscoring the above‐mentioned possible relation. 7 At the point of analysis, the SUR+ group had lower QoL in the SF‐36 with regards to “Bodily Pain”, while in EHP‐30, the items of “Pain”, “Control, and Powerlessness” and “Self‐image” were seen with higher scores also reflecting worse QoL when compared to the SUR− group. The scores align with observations from other studies prior to surgery. 17 , 18 What is particularly interesting in the present study is that similar results can be seen well in advance of surgery, not just immediately before the procedure. Moreover, we found a larger mean length and depth of the nodules on the rectum among those having surgery and larger scores of average and worst dyschezia, which could reflect the fact that patients with larger nodules have more profound symptoms, although we did not find this in a previous study. 6 The diminished quality of life, as assessed by the questionnaires, may reflect a need for surgery and could potentially be used as a preliminary screening measure. The primary strengths of this study are the prospective, extended follow‐up period, and the high response rate to the questionnaires. These factors enhance the robustness of the findings, offering a more thorough and reliable assessment of long‐term outcomes. The lack of a control group is a limitation of this study. Including one would have allowed for a clearer distinction between the consequences of severe DE and the natural presence of symptoms in healthy individuals, thereby strengthening the validity and interpretability of the findings. The team at Aarhus University Hospital prioritizes a conservative approach if possible as the first‐line therapeutic treatment in the clinical management of DE. Hence, there was a high feasibility of including these patients and extensive experience treating patients with bowel DE, not undergoing surgery for the disease. Information on dyspareunia and dysuria was not incorporated into the questionnaires at baseline or follow‐up, which could have provided valuable insights. No data were collected during the first year of follow‐up for patients who underwent surgery in that same year, which might have provided valuable insights and enabled analysis at baseline rather than at the timepoint 1 year in the SUR+ vs. SUR− analysis. When a diagnosis of bowel endometriosis has been made and in cases where there is no absolute indication for surgery such as occlusive symptoms, ureteral obstruction, large adnexal masses, it is important to evaluate whether the patients can be managed conservatively. It may be necessary to wait for the effects of hormonal treatment, for example, 3 months, before making the decision for surgery; an approach that needs patients' counseling and shared decision‐making. Furthermore, it is preferable that centers managing endometriosis achieve an optimal balance between medical and surgical therapies. A lesion‐focused surgical approach has proven effective in various cases and should be considered for patients experiencing severe symptoms and reduced quality of life, particularly when medical therapy is ineffective or poses significant side effects. From our perspective, the preferred approach to bowel DE involves initial conservative medical therapy, supplemented by surgical intervention when necessary, and followed by ongoing medical management. 19 Thus, early diagnosis, ideally accompanied by timely and appropriate treatment, may help reduce the risk of chronic pelvic pain and infertility while also offering patients a clear understanding of their symptoms.

This long‐term follow‐up study, of patients with bowel DE managed conservatively, demonstrates that a substantial proportion of patients maintain stable quality of life and symptom burden over a nearly 7‐year period. Patients who later required surgery had higher pain levels, worse quality of life scores, and larger lesion dimensions years before intervention. Ultimately, timely diagnosis and individualized, symptom‐oriented management, balancing medical and surgical strategies, may be the way forward in improving outcomes for patients with bowel DE.

The prevalence of endometriosis is estimated to be up to 10%, and therefore, millions of patients are affected by the disease. 1 It is a chronic and frequently painful gynecological condition characterized by the presence of endometrial like tissue outside the uterus and is stimulated by estrogen. 2 In the abdominal cavity, endometriosis is commonly divided into three subtypes: peritoneal endometriosis, ovarian endometriosis, and deep endometriosis (DE). 3 DE represents the most severe manifestation of the disease, where infiltration below the peritoneum and into structures such as the bladder, pelvic ligaments, uterus, vaginal fornices, and bowel is seen. 4 Affected individuals commonly endure a spectrum of disabling symptoms, notably pelvic pain, gastrointestinal and urinary dysfunction, infertility, and significant emotional and social impacts. 1 Even so, DE often goes undiagnosed or mismanaged, leading to years of suffering and a reduced quality of life. 5 Hormones, such as oral contraceptives, oral gestagens, and the hormonal intrauterine device, are well‐established treatment options for endometriosis, providing considerable ease from symptoms and allowing affected patients to avoid major surgery along with its associated risks. 6 , 7 , 8 , 9 , 10 , 11 Most of the literature emphasizes the surgical treatment of DE, and few studies cover the long‐term effects of conservative management (non‐surgical treatment). The primary aim of this follow‐up study was to investigate quality of life and clinical symptoms in a cohort of patients with bowel DE undergoing conservative management of the disease. The secondary aim was to evaluate potential initial differences in quality of life (QoL) or clinical parameters between individuals who underwent surgery and those managed conservatively during the follow‐up period.

The authors have stated explicitly that there are no conflicts of interest in connection with this article.

This cohort is derived from a previous study, at the Department of Obstetrics and Gynecology, Aarhus University Hospital, which included participants who were conservatively managed for bowel DE approximately 7 years ago. 6 Of 98 eligible patients, 80 completed the study, which included questionnaires (Questionnaire 1 and 2), clinical examination, and transvaginal ultrasonography at baseline and at 1‐year follow‐up (Figure  1A ). (A) Timeline for follow‐up of conservative management in women with bowel deep endometriosis (DE). (B) Timeline for analysis of groups “Surgery (SUR+) vs. no surgery (SUR−)” in women with bowel deep endometriosis (DE). *Demographic and clinical data, Short Form36, Endometriosis Health Profile 30 and LowAnterior Resection Score. **Demographic and clinical data, Short Form36, Endometriosis Health Profile 30, LowAnterior Resection Score and International Consultation on Incontinence Questionnaire ‐ Female Lower Urinary Tract Symptoms. Between December 2021 and January 2022, these patients were contacted and invited to complete a ~7‐year follow‐up questionnaire (Questionnaire 3). A decision was made not to invite the participants for a new clinical examination and transvaginal sonography, since an earlier study has shown significant intra‐ and interobserver variation in measuring rectosigmoid lesions with no correlation with clinical symptoms and QoL during the first year of follow‐up. 6 Patients who entered menopause during the 7‐year period, were pregnant at follow‐up, underwent bowel surgery or bilateral oophorectomy were excluded from the analysis assessing conservative management of bowel DE. Conservative management was defined as not requiring oophorectomy or bowel surgery. Questionnaire 3 was administered online through REDCap®. The online 7‐year follow‐up questionnaire (Questionnaire 3) was nearly identical to Questionnaire 1 and 2 administered at baseline and 1 year, respectively. It consisted of the 36‐Item Short Form Survey (SF‐36), Endometriosis Health Profile 30 (EHP‐30), Low Anterior Resection Score (LARS), and the International Consultation on Incontinence Questionnaire–Female Lower Urinary Tract Symptoms (ICIQ‐FLUTS) together with registration of demographic data, surgeries, parity, clinical symptoms, hormonal treatment, and use of painkillers (Figure  1A ). A 0–10 numerical rating scale (NRS) was used to assess the intensity of pain, both on average and when most severe. The ICIQ‐FLUTS was not included in Questionnaire 1 but was incorporated into Questionnaire 2. Furthermore, Questionnaire 3 included an additional question about the presence of menstrual bleeding, with participants reporting amenorrhea subsequently exempted from questions on dysmenorrhea. SF‐36 is a questionnaire used to measure health‐related quality of life. It consists of 36 questions covering various aspects of both physical and mental health and is divided into the following eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health Perceptions, Vitality, Social Functioning, Role Emotional, and Mental Health. Each domain is scored independently on a scale from zero to 100, where zero indicates the poorest possible health status and 100 indicates the best. Hence, higher scores reflect better perceived health and well‐being. 12 The EHP‐30 questionnaire is specifically designed to assess the quality of life in patients with endometriosis. It consists of 30 questions focusing on the physical, emotional, and social consequences of the disease. EHP‐30 evaluates factors such as pain, fatigue, fertility, mental health, and the impact the disease has on daily life. 13 Responses to each item in the EHP‐30 are converted into scores on a scale from zero to 100, where a score of zero indicates no impact on quality of life, and a score of 100 reflects the maximum negative impact. The LARS questionnaire was originally designed to evaluate bowel function in patients with rectal cancer following low anterior resection; however, it has also been utilized to assess bowel function after radical resection of bowel endometriosis. 14 , 15 It measures symptoms such as fecal incontinence, frequent bowel movements, abdominal pain, and the sensation of incomplete bowel emptying. The scale allows for evaluation of the effects of surgery on bowel function and the patient's daily life. The LARS score is divided into three categories based on the total points. No LARS (0–20 points) reflects no or mild functional issues after surgery, Minor LARS (21–29 points) reflects moderate functional problems affecting quality of life, and Major LARS (30–42 points) reflects severe functional issues, significantly impacting daily life. 14 ICIQ‐FLUTS is a validated questionnaire used to assess symptoms related to urinary tract disorders in patients, particularly symptoms of lower urinary tract function. The questionnaire consists of 12 items assessing lower urinary tract symptoms divided into three categories: filling symptoms (nocturia, urgency, bladder pain, and daytime frequency), voiding symptoms (hesitancy, straining, and intermittency), and incontinence symptoms (urge‐related incontinence, frequency of incontinence, stress‐related incontinence, passive incontinence, and nocturnal enuresis). Each item is rated on a five‐point numerical scale to evaluate the presence and severity of the symptom, followed by a ten‐point visual analogue scale to measure the level of associated bother or disturbance. Scores are calculated for each category: the Filling score (F‐score) ranges from zero to 16, the Voiding score (V‐score) from zero to 12, and the Incontinence score (I‐score) from 0 to 20. Higher scores indicate more severe symptoms. The secondary aim of this study was to assess differences between patients with rectosigmoid endometriosis having bowel surgery or bilateral oophorectomy (SUR+) and patients continuing conservative management (SUR−). For this analysis, Questionnaire 2 was used (Figure  1B ) to evaluate whether the SUR− and SUR+ groups already differed several years before the surgery was performed. This timepoint was selected for comparison because no data from Questionnaire 1 were available for patients who underwent surgery ( n  = 7) during the first year (baseline to 1 year), as these patients had been excluded according to the previous study protocol. 6 To evaluate changes in EHP‐30, SF‐36, and numerical rating scale scores throughout the follow‐up period, values at baseline were compared with values at follow‐up using a paired t ‐test for continuous data if data were normally distributed; otherwise, the non‐parametric Wilcoxon signed‐rank test was applied. Normally distributed data are presented as means with standard deviation (SD), non‐normally distributed data as median with range. The chi‐squared test was used for categorical data. Comparing categorical characteristics of those in the surgery versus the non‐surgery group, we calculated risk ratios (RR) with 95% confidence intervals (95% CI). Statistical significance was defined as p  < 0.05. All analyses were performed using Stata®.

Table S1. Table S2. Table S3.