Referee report. For: Holistic approaches to living well with endometriosis [version 2; peer review: 2 approved]

Endometriosis, holistic treatment for endometriosis, complementary treatment for endometriosis, chronic pelvic pain ALL Metrics - Views Downloads How to cite this article Desai J, Strong S and Ball E. Holistic approaches to living well with endometriosis [version 2; peer review: 2 approved]. F1000Research 2024, 13:359 (https://doi.org/10.12688/f1000research.142586.2) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente Select a format first ▬ ✚ Review Revised Holistic approaches to living well with endometriosis [version 2; peer review: 2 approved] * Equal contributors PUBLISHED 08 Nov 2024 Author details Author details 1 Central and North West London NHS Foundation Trust, London, England, UK 2 Department of Obstetrics and Gynaecology, The Royal London Hospital, Barts Health NHS Trust, London, E1 1FR, UK 3 Centre for Maternal & Child Health Research, School of Health Sciences, City University of London, UK 2 Department of Obstetrics and Gynaecology, The Royal London Hospital, Barts Health NHS Trust, London, E1 1FR, UK 3 Centre for Maternal & Child Health Research, School of Health Sciences, City University of London, UK Jessica Desai Roles: Data Curation, Writing – Original Draft Preparation Roles: Data Curation, Writing – Original Draft Preparation Sophie Strong Roles: Conceptualization, Data Curation, Formal Analysis, Supervision, Writing – Original Draft Preparation Roles: Conceptualization, Data Curation, Formal Analysis, Supervision, Writing – Original Draft Preparation Elizabeth Ball Roles: Conceptualization, Methodology, Resources, Supervision, Writing – Review & Editing Roles: Conceptualization, Methodology, Resources, Supervision, Writing – Review & Editing OPEN PEER REVIEW REVIEWER STATUS This article is included in the Endometriosis collection. Endometriosis is a common chronic non curable neuro-inflammatory condition, which can cause endometriosis-related pelvic pain (ERPP). Sufferers may struggle with side effects and/or risks from conventional medical and surgical treatments, or not get pain relief. Increasing numbers of endometriosis patients wish to explore holistic management with fewer side effects, however it is important that medical professionals maintain an evidence-based practice for recommended treatments. We present up-to-date evidence of holistic strategies used for managing ERPP including nutrition, body and mind therapies, acupuncture, traditional Chinese medicine (TCM) and the use of adjunct devices such as phallus length reducers and transcutaneous electrical nerve stimulation (TENS). Nutrition: Gluten-free, low-nickel and high intake of omega-3 polyunsaturated fatty acids diets improve ERPP. Low FODMAP (fermentable oligo-, di-, monosaccharides and polyols), plant-based diet and antioxidant vitamin supplementation is helpful including those with concurrent irritable bowel syndrome. Body and Mind: Cognitive behaviour therapy (CBT) is beneficial in postoperative pain reduction, whilst mindfulness has been shown to reduce pain scores and dyschezia. Progressive muscle relaxation therapy and regular yoga sessions improve ERPP and Quality of life. Acupuncture: Acupuncture and moxibustion show improved pain scores compared to conventional therapies alone. Adjunct devices: TENS improves deep dyspareunia and reduces the number of days pain is experienced. Holistic management strategies for ERPP should be incorporated into routine counselling when discussing conservative, medical and or surgical treatments for endometriosis. The growing evidence presented for the use of holistic management strategies gives hope to those patients who cannot have, or don’t respond to conventional approaches and as an adjunct alongside standard treatments. These findings should be incorporated into the routine counselling when seeing patients in the gynaecology outpatient setting presenting with chronic pelvic pain. Endometriosis, holistic treatment for endometriosis, complementary treatment for endometriosis, chronic pelvic pain Corresponding Author(s) Sophie Strong ([email protected]) Grant information: This study was supported by the Centre for Maternal & Child Health Research, School of Health Sciences, City University of London. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2024 Desai J et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Desai J, Strong S and Ball E. Holistic approaches to living well with endometriosis [version 2; peer review: 2 approved]. F1000Research 2024, 13:359 (https://doi.org/10.12688/f1000research.142586.2) First published: 23 Apr 2024, 13:359 (https://doi.org/10.12688/f1000research.142586.1) Latest published: 08 Nov 2024, 13:359 (https://doi.org/10.12688/f1000research.142586.2) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank the reviewers and have incorporated their suggestions as: We added a concluding sentence to our abstract to highlight the clinical significance of our findings. In the introduction, we have utilised two new references (reference 6 and 7) to discuss the iatrogenic risk of endometriosis surgery. An inclusion and exclusion criteria, search methodology and quality assessment section has been added. We have further discussed the limitations of the papers used in the acupuncture section. We have also included a table, please see Table 1, summarising the significant findings from the body and mind section. Clarification has also been made on whether papers relate to individuals with CPP or those with CPP/endometriosis throughout the text. Espirit2 trial protocol has been referenced, please see reference 5. Section on benefits of botulinum toxin has been added. CBD section has been expanded, please see references 69 and 70. In the nutrition section we have discussed the benefits of specific diets in patients with IBS-like symptoms in association with endometriosis, please refer to reference 23. We have added further information to support reference 75, please refer to reference 76, which provides a more recent update to the research conducted in 1991. We have also amended the conclusion to signify the importance of integrating our findings into clinical practice. We thank the reviewers and have incorporated their suggestions as: We added a concluding sentence to our abstract to highlight the clinical significance of our findings. In the introduction, we have utilised two new references (reference 6 and 7) to discuss the iatrogenic risk of endometriosis surgery. An inclusion and exclusion criteria, search methodology and quality assessment section has been added. We have further discussed the limitations of the papers used in the acupuncture section. We have also included a table, please see Table 1, summarising the significant findings from the body and mind section. Clarification has also been made on whether papers relate to individuals with CPP or those with CPP/endometriosis throughout the text. Espirit2 trial protocol has been referenced, please see reference 5. Section on benefits of botulinum toxin has been added. CBD section has been expanded, please see references 69 and 70. In the nutrition section we have discussed the benefits of specific diets in patients with IBS-like symptoms in association with endometriosis, please refer to reference 23. We have added further information to support reference 75, please refer to reference 76, which provides a more recent update to the research conducted in 1991. We have also amended the conclusion to signify the importance of integrating our findings into clinical practice. We added a concluding sentence to our abstract to highlight the clinical significance of our findings. In the introduction, we have utilised two new references (reference 6 and 7) to discuss the iatrogenic risk of endometriosis surgery. An inclusion and exclusion criteria, search methodology and quality assessment section has been added. We have further discussed the limitations of the papers used in the acupuncture section. We have also included a table, please see Table 1, summarising the significant findings from the body and mind section. Clarification has also been made on whether papers relate to individuals with CPP or those with CPP/endometriosis throughout the text. Espirit2 trial protocol has been referenced, please see reference 5. Section on benefits of botulinum toxin has been added. CBD section has been expanded, please see references 69 and 70. In the nutrition section we have discussed the benefits of specific diets in patients with IBS-like symptoms in association with endometriosis, please refer to reference 23. We have added further information to support reference 75, please refer to reference 76, which provides a more recent update to the research conducted in 1991. We have also amended the conclusion to signify the importance of integrating our findings into clinical practice. See the authors' detailed response to the review by Diego Raimondo See the authors' detailed response to the review by Philippa TK Saunders Endometriosis, an inflammatory women’s disease affecting about 10% of the female population,1 can cause infertility and chronic pelvic pain (CPP) with pain centralisation for many patients.2 The mainstay of treatment has been laparoscopic removal of endometriosis. Hormonal or non-hormonal medication and pain relief can replace or complement this. However, in our tertiary endometriosis centre, many women with ERPP have adopted holistic approaches to manage pain and improve quality of life (QoL). Recent developments call us to reassess and contextualise traditional treatments, and to look for comprehensive approaches, which support patient autonomy and empowerment toward living well with endometriosis. 1. In a systematic review (SR) of surgical outcomes for endometriosis,3 11.8% of patients reported no pain improvement. Women with isolated surface endometriosis in particular may not benefit from surgery,4 which is currently investigated ESPriT2 (NCT04081532).5 2. Postoperative functional impairment after laparoscopy for endometriosis include voiding problems and urinary tract infections.6 Long term functional bowel impairment is associated with colorectal endometriosis surgery.7 3. Since the Covid-19 pandemic ‘Hormone-phobia’ is on the rise on social media platforms, with women sharing negative experiences of hormonal contraceptives, reducing the willingness to try them.8 4. Antidepressants and Gabapentin, previously prescribed as neuromodulators in chronic pain are not as effective as previously thought.9,10 Given the above and understanding that living with chronic conditions can be eased by holistic approaches and self-management,11 we present recent advances. All studies reporting the assessment and outcomes of selected holistic management for pelvic pain were included (randomised and non-randomised controlled trials, cohort studies and case series). We performed a PubMed search with terms to include holistic management strategies for endometriosis, including the search terms applied of: endometriosis with nutrition, diet, cognitive behavioural therapy, mindfulness, yoga, progressive muscle relaxation, physiotherapy, acupuncture, devices, TENS, cannabis, Chinese medicine. We did not perform formal risk of bias assessment, but reported bias risks like high attrition rates for individual studies. The role of nutrition in managing chronic pain conditions is investigated in two SRs.12,13 A high intake of anti-inflammatory nutrients reduces pain severity by modulating inflammation.14 Gut microbiome dysbiosis is hypothesised to cause incorrect immune responses resulting in pain from central sensitisation pathways in inflammatory conditions such as endometriosis. Probiotics and FODMAP diets (omitting fermentable oligo-, di-, monosaccharides and polyols), are beneficial in treating visceral pain.15 More research into diet in endometriosis is recommended,16 given small population sizes with heterogeneity between intervention groups. One SR (one RCT and five observational studies) of low FODMAP, gluten-free and low-nickel diets as well as high intake of omega-3 polyunsaturated fatty acids (average treatment dose palmitoylethanolamide 400 mg & polydatin 40 mg twice daily for 3 months)17–19 reported that all diets, with the exception of low FODMAP reduced pain.20 However, those with endometriosis and irritable bowel syndrome (IBS) may benefit from low-FODMAPs; observational data (n=160) demonstrated symptom improvement compared to patients with IBS alone (72% vs. 40%, respectively, P=0.001).21 Interestingly, women with endometriosis are approximately three times more likely to develop IBS,22 posing diagnostic challenges since symptoms (bloating and diarrhoea) may overlap. Velho et al reviews the benefits of anti-inflammatory (e.g. plant based) diets and antioxidant vitamins supplements including vitamin D.23 Compared to controls, endometriosis patients appear to have more allergic nickel contact mucositis (odds ratio: 2.474; 95% confidence interval: 1.023~5.988; P=0.044),24 causing IBS-like symptoms. Reducing nickel-rich foods e.g. tomatoes, whole wheat, and soy, resulted in improvement of CPP (P<0.05) in a prospective 3-month observational study of 31 endometriosis patients with gastrointestinal symptoms.25 Krabbenborg et al26 observed 157 endometriosis patients asking which of their own dietary modifications had improved their QoL using the EHP-30 score. The commonest diets were the endometriosis diet (omitting foods that appeared to worsen symptoms), gluten free, low-FODMAP, low-lactose and weight loss diets. Although EHP-30 scores did not significantly alter with dietary modification, pain reduction was noted in 71.3% of patients, with gluten-free showing the greatest impact. Dietary modifications have a greater impact with longer adherence. In a placebo-controlled triple-blind RCT (n=120) garlic extract (400 mg daily over 12 weeks) showed a significant reduction in ERPP (P<0.05). Purported mechanisms are reduction in oxidative stresses, prostaglandin production, endometriosis cell proliferation and increased oestrogen elimination.27 Both low and high BMI appear to be associated with endometriosis severity,28 a confounding factor for both endometriosis and obesity being systemic inflammation.29 It is tempting to speculate whether maintaining a normal BMI is beneficial for ERPP, and further studies are needed. Poor mental health may be a result of the impact endometriosis has on physical, sexual, and psychological well-being.30 Strategies such as cognitive behavioural therapy (CBT), yoga and relaxation techniques can be valuable. Increasing evidence suggests psychosocial factors, such as preoperative pain catastrophising independently impact pain experience, severity of symptoms and recurrence of endometriosis.31,32 Patient awareness and self-uptake of psychological approaches for ERPP are increasingly popular, with 93.8% of women sampled in a cross-sectional survey distributed via The Endometriosis Network Canada (n=434) utilising at least one psychological management strategy.33 Please see Table 1 for a summary of the body and mind therapies. CBT CBT is recognised as an effective treatment for chronic pain and associated mental health conditions, including CPP.34 Three recent RCT protocols assessing efficacy of CBT35,36 and yoga with CBT37 on QoL of patients with endometriosis indicate current interest. Boersen’s RCT36 aims to assess CBT in 100 postoperative endometriosis patients. Wu et al38 assessed CBT with usual care compared to usual care alone in post-surgical endometriosis patients in a case-control study (Interventions n=48, Controls n=48), utilising one CBT session before and six sessions post-surgery. During a 6-month follow-up, participants scored on the depression, anxiety, and stress scale (DASS-21). Anxiety scores improved significantly (P=.0091). Authors highlight the important role of patient education in self-management of ERPP following CBT. Mindfulness Mindfulness is a psychological technique that draws on awareness and non-judgemental acceptance of present personal experience. The mindfulness-based stress reduction (MBSR) programme, developed by Kabat-Zinn39 is an adjunct to treatment for chronic pain, through relating physical and psychological conditions. Moreira et al40 assessed the impact of mindfulness on ERPP in an RCT: They adapted the MBSR programme, forming a brief mindfulness-based intervention (bMBI, n=31, usual care controls n=32) with reduced intensity and duration (4-weeks instead of 8-weeks). Formal meditation was practised around the theme of ‘reconceptualising pain.’ The intervention group showed reduction in pain scores, pain unpleasantness and dyschezia. Hansen et al41 found that psychological intervention, improved QoL in a three-armed RCT, without reducing ERPP perception. Endometriosis patients were randomised to three groups: mindfulness and acceptance-based intervention (n=20), non-specific psychological intervention without mindfulness (relaxation and guided physical therapy) (n=19), or waitlist control with usual treatment only (n=19). All participants received usual treatment including analgesia. The ten-week programme (MY-ENDO) combined Kabat-Zinn’s MBSR programme and acceptance and commitment therapy (ACT). There was no significant reduction in ERPP between the MY-ENDO and non-specific psychological intervention (P=0.144, d=0.59). Psychological intervention significantly improved QoL-subscales ‘control and powerlessness’ (P=0.019, d=0.78), ‘emotional well-being’ (P=0.003, d=1.01), and ‘social support’ (P=0.042, d=0.66). QoL was improved through the positive effects on bowel symptoms, specifically diarrhoea (P=0.035, d=0.25), within the two intervention groups, likely due to physical activity undertaken. Further studies are needed to determine whether psychological interventions in general improve QoL or whether it is the mindfulness intervention. Yoga Yoga has a long tradition in managing chronic pain. In an AB-design pilot study (patients served as their own control group) 42 endometriosis patients by Ravins et al,42 participants underwent eight-weeks of conventional therapy followed by eight-weeks of 90-minute endometriosis yoga sessions, bi-weekly. EHP-30 scores and numerical pain rating scale were lower after the yoga sessions (P=0.001). Gonçalves’ RCT,43 randomised 40 women with ERPP to 90-minutes of yoga bi-weekly for 8 weeks (n=28) or no yoga (n=12). Daily pain was significantly lowered by yoga (P=0.0007). EHP-30 domains were assessed at the time of presentation and at 8-weeks; scores for pain (P=0.0046), well-being (P=0.0009), and self-image (P=0.0087) improved significantly over time only in the yoga group. Only 57% of participants in the intervention group completed the yoga programme, highlighting the challenges faced of adhering to regular yoga practice. Saxena et al44 also demonstrated benefits of yoga over conventional care; 30 women with CPP were randomised to yoga therapy and 30 to conventional therapy (non-steroidal anti-inflammatory painkillers (NSAIDs). Pain scores (VAS score) and QoL (World Health Organization WHOQOL-BREF questionnaire) were assessed at baseline and 8-weeks. In contrast to the controls the yoga group showed a significant decrease in pain intensity (P<0.001) and QoL improvement with a significant increase (P<0.001) in physical, psychological, social, and environmental domain scores of WHOQOL-BREF. Enriched environments (more space to move about, increased physical activity and social interactions) suppresses the development of endometriosis in mice by attenuating adrenergic signalling, enhancing autophagy, and reducing leptin levels.45 Extrapolating this to humans, Flores et al46 reported a significant reduction in pelvic pain, perceived stress and improved mood and emotional wellbeing in endometriosis patients who were randomised to outdoor physical activities such group yoga to optimise environmental enrichment as compared to controls. Progressive muscle relaxation (PMR) PMR is an exercise that reduces stress and anxiety through slowly tensing and relaxing muscle groups throughout the body. PMR improved anxiety and depression (P<0.05), and health-related QoL (P<0.05) for patients with endometriosis in an RCT of 100 women receiving Gonadotrophin-releasing hormone (GnRH) agonist treatment, randomly assigned to 12 weeks of PMR training or a control group. 47 Psychological and physical interventions positively impact on QoL in patients with ERPP. However, there remains a lack of high-powered trials in mind and body therapies. Consideration must be taken for the barriers to accessing psychological interventions. Particularly, patients should not feel their pain is less validated if a physiological approach is offered. Nowadays smart-phone applications are often suggested to simplify access to Mindfulness. However, those approaches require co-development with stakeholders to be acceptable and used regularly.48 Pelvic floor muscle physiotherapy Pelvic floor muscle dysfunction (specifically levator ani hypertonia and incomplete relaxation) contributes to ERPP with deep infiltrative endometriosis (DIE).49–51 Pelvic floor physiotherapy (PFP), assessed by 3D/4D trans-perineal ultrasound, increased levator hiatus area (LHA) which in turn improved dyspareunia and pelvic floor muscle relaxation (PFMR) reduced ERPP. Following a successful pilot study,52 Forno et al used trans-perineal ultrasound to assess LHA before and after PFP in an RCT of 34 women with ERPP.53 Participants were assigned to treatment with five PFP sessions (n=17) or no intervention (n=17). Physiotherapy sessions involved the Thiele massage, using digital pressure to elongate and relax muscles, restoring normal tone. PFMR improved on maximum Valsalva manoeuvre in the intervention group compared to the control (20.0 ± 24.8% vs –0.5 ± 3.3%, respectively; P=0.02), and superficial dyspareunia pain scores reduced (P<0.01) Injection of botulinum toxin may have a role in easing CPP, however existing research lacks standardisation of the toxin brand, site of injection, dose and outcome measures.54 A cohort study of 13 women with endometriosis and pelvic floor spasm reported that 4-8 weeks following injection of 100 units of onabotulinumtoxinA into the pelvic floor muscles reduced pain in all women (median VAS=2, range 0–5/10, P<0.0001).55 Previous studies have shown acupuncture to be a suitable tool in reducing ERPP, and is considered a safe therapy with minimal side effects.56,57 Several recent case studies have shown symptomatic improvement with acupuncture.58,59 Yan et al published a protocol for SR and meta-analysis of RCTs on acupuncture benefits for endometriosis symptoms. ESHRE guidelines60 acknowledge that acupuncture may be a beneficial tool, however the studies that were available at that time were limited and not free from bias. Wang et al61 recently published a SR of 15 RCTs (sample sizes between 10 and 54), which assessed the effectiveness of acupuncture and/or moxibustion for the treatment of endometriosis. Compared with sham acupuncture, actual acupuncture was more effective at reducing dysmenorrhea VAS pain score (mean difference [MD] − 2.40, 95% CI [− 2.80, − 2.00]; moderate certainty evidence), pelvic pain VAS score (MD − 2.65, 95% CI [− 3.40, − 1.90]; high certainty evidence) and dyspareunia VAS scores (MD − 2.88, [− 3.83, − 1.93]), lessened the size of ovarian cysts (MD − 3.88, 95% CI [− 7.06, − 0.70]), and improved quality of life. These promising results suggest that acupuncture may be an effective adjunct to treating ERPP. In a multicentre, randomised, single-blind, placebo-controlled trial62 assessing the effects of acupuncture on endometriosis related symptoms (n=106), acupuncture was delivered to the intervention group (n=51) as 30-minute sessions once daily, three times a week, starting one week before expected onset of menstruation, for a total duration of 12-weeks. The control group (n=53) received sham acupuncture. Lower VAS scores were seen in the intervention group at 12 weeks for dysmenorrhoea (-2.82 (-3.47, -2.18) and QoL, (EHP score) -18.88 (-31.88, -5.87)), but not for pelvic pain and dyspareunia. At 24 weeks no statistical benefits were seen, suggesting acupuncture is a suitable immediate therapy for endometriosis related dysmenorrhoea, however the effects of acupuncture may not be sustainable over a long period of time and repeated therapy would be necessary. Notable limitations of this study include the lack of blinding and the inability to assess non-menstrual CPP. Phallus length reducing devices The Ohnut© device is a phallus length reducer worn over the penis or penetrating object with the intention to reduce endometriosis-associated deep dyspareunia, sparing the cervix and retro-cervical area from direct pressure. The effectiveness of this device is currently being assessed in a pilot RCT of 40 participants with ERPP by Zhang63 who will be randomised into an intervention group or a waitlist control group. Transcutaneous electrical nerve stimulation (TENS) A TENS unit passes an electrical current through skin electrodes for targeted pain relief. The spinothalamic nerve tract transmits both pain and touch, but not at the same time (gate control theory).64 Its use has been shown to reduce pain in primary dysmenorrhoea65 and CPP.66,67 Mira et al68 conducted a multicentre RCT of 101 participants with deeply infiltrating endometriosis. The study aimed to identify whether the addition of a TENS unit to hormonal therapy (n=53) would provide a greater therapeutic benefit than hormonal treatment alone (n=48). TENS was used twice a day, 20 minutes per day, for 8 weeks. CPP improved in the intervention group (VAS decreased from 7.11 ± 2.40–4.55 ± 3.08, P<0.001, 36% decrease), but not in controls (VAS from 7.33 ± 2.09–7.06 ± 2.33, P=0.554, 3.68% decrease). A greater improvement in deep dyspareunia was found in the intervention group, 32.67% reduction vs. 13.84% reduction in the controls. There was a decrease in the number of days participants experienced pain from the first week to the eighth week (from 3.27 to 2.22, P=0.028, 32.11% decrease), which was not identified in the control group (from 4.55 to 4.07, P=0.203, 10.54% decrease). This study was conducted over a relatively short time interval, therefore due to the chronic nature of endometriosis, further research is needed to assess whether benefits from TENs units are sustained longer-term. CBD has antioxidant, antifibrotic and anti-inflammatory effects, and has been shown to reduce th diameter, volume and area of endometrioma as well as lesion morphology in endometriosis.69 A SR suggests that CBT use can relieve CPP in up to 95.5% of its users.70 A cross sectional survey71 of 113 women with pelvic, perineal pain, dyspareunia or endometriosis was conducted to gather information regarding patient cannabis use. 26/113 (23%) participants reported cannabis use, of which only 5/26 obtained cannabis through a medical programme, 25 had complete data and were analysed. 15/25 (60%) used a combination of CBD and tetrahydrocannabinol (THC). There was no significant difference between the demographics of cannabis users and nonusers. Overall, 24/25 (96%) of participants reported improvement in symptoms such as pain, depression and sleep disturbance with the use of cannabis. It is important to note that participants from both groups also utilised alternative medications and therapies, and therefore reported symptom improvement cannot be confidently solely attributed to cannabis use. Cannabis use was found to be the most effective form of self-management in an Australian online survey completed by 484 women with endometriosis. Women reported pain relief of 7.6 on a scale of 0-10 with cannabis use (SD 2.0), and 6.3 with hemp oil/CBD oil use (SD 3.0).72 Zhao et al73 performed a non-blinded RCT of 320 patients undergoing endometriosis surgery to investigate the effects of TCM (activating blood circulation and removing blood stasis treatment based on syndrome differentiation; n=131) and Western medicine (GnRH agonist or progesterone’s; n=141) on QOL postoperatively. Pre-treatment WHOQOL-BREF scores, a QOL assessment tool with four domains including physical health, psychological, social relationships and environment, showed no significant difference between the two groups (P>0.05), however post-treatment scores in the TCM group were significantly improved (P<0.05) and the scores of 4 items (mobility, activities of daily living, sexual activity, QOL score) were also statistically significantly better (P<0.05). A Cochrane review by Flower et al74 assessed the effects of Chinese herbal medicine (CHM) for endometriosis. Only two RCTs were included (n=158), neither of which compared CHM with placebo. The first showed no significant difference in ERPP between CHM and gestrinone administration following laparoscopic treatment (95.65% vs. 93.87%; risk ratio (RR) 1.02, 95% confidence interval (CI) 0.93 to 1.12, one RCT). Combined oral CHM and herbal enemas provided better improvement in dysmenorrhoea than with danazol (RR 5.06, 95% CI 1.28 to 20.05; RR 5.63, 95% CI 1.47 to 21.54, respectively). There was no significant difference in lumbosacral pain, rectal discomfort, or vaginal nodule tenderness between CHM and danazol. Flower raises concern about the paucity of robust studies assessing on CHM in endometriosis and that the small size of the current studies. The previous cornerstones of endometriosis care have been shaken. Neuromodulators are less effective than assumed,9 a meaningful proportion do not get pain relief from surgery3 and ⅓ do not respond to progesterone. Complementary, self-management and lifestyle approaches are moving from fringe interest into mainstream endometriosis care. Our review highlights the importance and benefits of integrating these techniques into clinical practice. A historic RCT75 has shown multimodal holistic approaches yield superior outcomes to early laparoscopy in CPP, but authors of recent SR of five studies (n=186 tertiary centre patients) on interprofessional treatment approaches in CPP criticise the paucity of evidence which does not allow for identification of the best interprofessional treatment approach and call for more research.76 Current UK endometriosis centre accreditation weights bowel surgery heavily but patient education and signposting to holistic evidence-based care is left to enthusiastic HCPs, specialist nurses and patient charities, resulting in care inequities. Accreditation hinges on an MDT of surgeons/urologists, but not with pelvic pain physiotherapists, nutritionists and psychologists. Numerous calls for more research into complementary approaches need to be answered by appropriate funding. Within a patient journey, complementary approaches could be used in the following models as a primary approach or in conjunction with routine treatment.4 1. Future women’s health hubs can identify DIE, likely to respond to surgery with specialised scanning (requiring an appropriately trained workforce) even before referral to secondary and tertiary care. Models initiating this is the community would improve patient journeys and shorten the delay in endometriosis patients accessing care. 2. Peri-operatively in the context of pre- and rehabilitation: surgery should no longer be seen in isolation but embedded in education and self-care. It is common knowledge among clinicians that patients recover faster and better from endometriosis surgery if they enter into surgery having practised pre-habilitation. 3. An adjunct to hormonal, surgical and pain-relieving western approaches. 4. 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PubMed Abstract | Publisher Full Text Author details Author details 1 Central and North West London NHS Foundation Trust, London, England, UK 2 Department of Obstetrics and Gynaecology, The Royal London Hospital, Barts Health NHS Trust, London, E1 1FR, UK 3 Centre for Maternal & Child Health Research, School of Health Sciences, City University of London, UK 2 Department of Obstetrics and Gynaecology, The Royal London Hospital, Barts Health NHS Trust, London, E1 1FR, UK 3 Centre for Maternal & Child Health Research, School of Health Sciences, City University of London, UK Jessica Desai Roles: Data Curation, Writing – Original Draft Preparation Roles: Data Curation, Writing – Original Draft Preparation Sophie Strong Roles: Conceptualization, Data Curation, Formal Analysis, Supervision, Writing – Original Draft Preparation Roles: Conceptualization, Data Curation, Formal Analysis, Supervision, Writing – Original Draft Preparation Elizabeth Ball Roles: Conceptualization, Methodology, Resources, Supervision, Writing – Review & Editing Roles: Conceptualization, Methodology, Resources, Supervision, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information This study was supported by the Centre for Maternal & Child Health Research, School of Health Sciences, City University of London. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article Versions (2) Copyright © 2024 Desai J et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. metrics | Views | Downloads | | |---|---|---| | F1000Research | - | - | | PubMed Central Data from PMC are received and updated monthly. | - | - | Citations CITE how to cite this article Desai J, Strong S and Ball E. Holistic approaches to living well with endometriosis [version 2; peer review: 2 approved]. F1000Research 2024, 13:359 (https://doi.org/10.12688/f1000research.142586.2) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. track receive updates on this article Track an article to receive email alerts on any updates to this article. Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions Version 2 VERSION 2 PUBLISHED 08 Nov 2024 Revised Views 0 How to cite this report: Raimondo D. Reviewer Report For: Holistic approaches to living well with endometriosis [version 2; peer review: 2 approved]. F1000Research 2024, 13:359 (https://doi.org/10.5256/f1000research.174168.r338887) The direct URL for this report is: https://f1000research.com/articles/13-359/v2#referee-response-338887 https://f1000research.com/articles/13-359/v2#referee-response-338887 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Reviewer Report 05 Dec 2024 Diego Raimondo, Division of Gynaecology and Human Reproduction Physiopathology, IRCCS AOUBO, Bologna, Italy Approved VIEWS 0 auhtors replied ... Continue reading I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close auhtors replied to all queries Competing Interests: No competing interests were disclosed. Reviewer Expertise: endometriosis CITE HOW TO CITE THIS REPORT Raimondo D. Reviewer Report For: Holistic approaches to living well with endometriosis [version 2; peer review: 2 approved]. F1000Research 2024, 13:359 (https://doi.org/10.5256/f1000research.174168.r338887) The direct URL for this report is: https://f1000research.com/articles/13-359/v2#referee-response-338887 https://f1000research.com/articles/13-359/v2#referee-response-338887 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. Views 0 How to cite this report: Saunders PT. Reviewer Report For: Holistic approaches to living well with endometriosis [version 2; peer review: 2 approved]. F1000Research 2024, 13:359 (https://doi.org/10.5256/f1000research.174168.r338886) The direct URL for this report is: https://f1000research.com/articles/13-359/v2#referee-response-338886 https://f1000research.com/articles/13-359/v2#referee-response-338886 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Reviewer Report 18 Nov 2024 Approved VIEWS 0 The authors have improved the balance so ... Continue reading I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close The authors have improved the balance so it can be moved into the approved category. Competing Interests: No competing interests were disclosed. Reviewer Expertise: Reproductive biologist, specialising in women's health conditions including endometriosis. Translational research focused on improving range of treatments for chronic pelvic pain including self management strategies. CITE HOW TO CITE THIS REPORT Saunders PT. Reviewer Report For: Holistic approaches to living well with endometriosis [version 2; peer review: 2 approved]. F1000Research 2024, 13:359 (https://doi.org/10.5256/f1000research.174168.r338886) The direct URL for this report is: https://f1000research.com/articles/13-359/v2#referee-response-338886 https://f1000research.com/articles/13-359/v2#referee-response-338886 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. Version 1 VERSION 1 PUBLISHED 23 Apr 2024 Views 0 How to cite this report: Saunders PT. Reviewer Report For: Holistic approaches to living well with endometriosis [version 2; peer review: 2 approved]. F1000Research 2024, 13:359 (https://doi.org/10.5256/f1000research.156153.r292395) The direct URL for this report is: https://f1000research.com/articles/13-359/v1#referee-response-292395 https://f1000research.com/articles/13-359/v1#referee-response-292395 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Reviewer Report 22 Jul 2024 Not Approved VIEWS 0 Endometriosis is an incurable disorder and as the authors correctly state patients are often keen to try non-medical approaches to manage symptoms including chronic pain, bloating and fatigue. Some approaches including physiotherapy are often included in multidisciplinary care and information ... Continue reading 2. Horne AW, Vincent K, Hewitt CA, Middleton LJ, et al.: Gabapentin for chronic pelvic pain in women (GaPP2): a multicentre, randomised, double-blind, placebo-controlled trial.Lancet. 2020; 396 (10255): 909-917 PubMed Abstract | Publisher Full Text 3. Velho RV, Werner F, Mechsner S: Endo Belly: What Is It and Why Does It Happen?-A Narrative Review.J Clin Med. 2023; 12 (22). PubMed Abstract | Publisher Full Text 4. Karp BI, Stratton P: Applications of botulinum toxin to the female pelvic floor: Botulinum toxin for genito-pelvic pain penetration disorder and chronic pelvic pain in women.Toxicon. 2023; 230: 107162 PubMed Abstract | Publisher Full Text 5. Genovese T, Cordaro M, Siracusa R, Impellizzeri D, et al.: Molecular and Biochemical Mechanism of Cannabidiol in the Management of the Inflammatory and Oxidative Processes Associated with Endometriosis.Int J Mol Sci. 2022; 23 (10). PubMed Abstract | Publisher Full Text 6. Liang AL, Gingher EL, Coleman JS: Medical Cannabis for Gynecologic Pain Conditions: A Systematic Review.Obstet Gynecol. 2022; 139 (2): 287-296 PubMed Abstract | Publisher Full Text 7. Armour M, Sinclair J, Chalmers KJ, Smith CA: Self-management strategies amongst Australian women with endometriosis: a national online survey.BMC Complement Altern Med. 2019; 19 (1): 17 PubMed Abstract | Publisher Full Text I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close Endometriosis is an incurable disorder and as the authors correctly state patients are often keen to try non-medical approaches to manage symptoms including chronic pain, bloating and fatigue. Some approaches including physiotherapy are often included in multidisciplinary care and information on patient websites includes a wide range of complementary therapies some of which are discussed in this review [https://www.endometriosis-uk.org/]. The authors are to be commended on bringing together information about a very wide range of potential interventions and their assessment that many individuals with symptomatic endometriosis are keen to explore self management and alternative therapies as part of their care plan is something increasingly reported by health care professionals. The section entitled ‘Recent findings’ makes some dogmatic statements and it was not clear they were backed up by the latest data – this was particularly true of nutrition which is a fast moving field. Given the importance of the topic it is of concern that there appears to be an overall lack of ‘balance’ in the paper with a lot of emphasis in the first section placed on a systematic reviews – REFs 1-5, 8,9,12. In some parts of the text it is hard to know if the results discussed relate to individuals with CPP or those with CPP/Endo so careful re-reading and clarification of is advised (examples include yoga, TENS, mindfulness). [table of mind and body therapies?] It is recommended that the authors assemble information from relevant high quality original information from trials in tables – this would be more useful to the reader than simple text. Authors are referred to a number of recent reviews related to the impact of diet, inflammation and the gut brain axis as sources of information. Additional References Esprit2 trial has a published protocol [Ref -1].

6 is to a protocol – the trial has been completed and the correct reference is [Ref -2] In section on nutrition it would be useful to mention GWAS and other data that support patient experience of IBS-like symptoms in association with endometriosis (includes abdominal bloating [Ref-3], diarrhoea etc). Recent paper [Ref-3] No mention of botox for treatment of pelvic floor pain although there are reports it is effective · [Ref -4] The section on cannabinoids is very brief which seems at odds with the widespread use of CBD in management of chronic pain, in some countries they are prescribed and there are several trials for endometriosis CPP underway – add more references. [Ref 5-7] Add more details from Ref 64 – this paper is from 1991 – any follow up papers? The authors are to be commended on bringing together information about a very wide range of potential interventions and their assessment that many individuals with symptomatic endometriosis are keen to explore self management and alternative therapies as part of their care plan is something increasingly reported by health care professionals. The section entitled ‘Recent findings’ makes some dogmatic statements and it was not clear they were backed up by the latest data – this was particularly true of nutrition which is a fast moving field. Given the importance of the topic it is of concern that there appears to be an overall lack of ‘balance’ in the paper with a lot of emphasis in the first section placed on a systematic reviews – REFs 1-5, 8,9,12. In some parts of the text it is hard to know if the results discussed relate to individuals with CPP or those with CPP/Endo so careful re-reading and clarification of is advised (examples include yoga, TENS, mindfulness). [table of mind and body therapies?] It is recommended that the authors assemble information from relevant high quality original information from trials in tables – this would be more useful to the reader than simple text. Authors are referred to a number of recent reviews related to the impact of diet, inflammation and the gut brain axis as sources of information. Additional References Esprit2 trial has a published protocol [Ref -1].

6 is to a protocol – the trial has been completed and the correct reference is [Ref -2] In section on nutrition it would be useful to mention GWAS and other data that support patient experience of IBS-like symptoms in association with endometriosis (includes abdominal bloating [Ref-3], diarrhoea etc). Recent paper [Ref-3] No mention of botox for treatment of pelvic floor pain although there are reports it is effective · [Ref -4] The section on cannabinoids is very brief which seems at odds with the widespread use of CBD in management of chronic pain, in some countries they are prescribed and there are several trials for endometriosis CPP underway – add more references. [Ref 5-7] Add more details from Ref 64 – this paper is from 1991 – any follow up papers? - Is the topic of the review discussed comprehensively in the context of the current literature? No - Are all factual statements correct and adequately supported by citations? No - Is the review written in accessible language? Yes - Are the conclusions drawn appropriate in the context of the current research literature? No

1. Mackenzie SC, Stephen J, Williams L, Daniels J, et al.: Effectiveness of laparoscopic removal of isolated superficial peritoneal endometriosis for the management of chronic pelvic pain in women (ESPriT2): protocol for a multi-centre randomised controlled trial.Trials. 2023; 24 (1): 425 PubMed Abstract | Publisher Full Text2. Horne AW, Vincent K, Hewitt CA, Middleton LJ, et al.: Gabapentin for chronic pelvic pain in women (GaPP2): a multicentre, randomised, double-blind, placebo-controlled trial.Lancet. 2020; 396 (10255): 909-917 PubMed Abstract | Publisher Full Text 3. Velho RV, Werner F, Mechsner S: Endo Belly: What Is It and Why Does It Happen?-A Narrative Review.J Clin Med. 2023; 12 (22). PubMed Abstract | Publisher Full Text 4. Karp BI, Stratton P: Applications of botulinum toxin to the female pelvic floor: Botulinum toxin for genito-pelvic pain penetration disorder and chronic pelvic pain in women.Toxicon. 2023; 230: 107162 PubMed Abstract | Publisher Full Text 5. Genovese T, Cordaro M, Siracusa R, Impellizzeri D, et al.: Molecular and Biochemical Mechanism of Cannabidiol in the Management of the Inflammatory and Oxidative Processes Associated with Endometriosis.Int J Mol Sci. 2022; 23 (10). PubMed Abstract | Publisher Full Text 6. Liang AL, Gingher EL, Coleman JS: Medical Cannabis for Gynecologic Pain Conditions: A Systematic Review.Obstet Gynecol. 2022; 139 (2): 287-296 PubMed Abstract | Publisher Full Text 7. Armour M, Sinclair J, Chalmers KJ, Smith CA: Self-management strategies amongst Australian women with endometriosis: a national online survey.BMC Complement Altern Med. 2019; 19 (1): 17 PubMed Abstract | Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: Reproductive biologist, specialising in women's health conditions including endometriosis. Translational research focused on improving range of treatments for chronic pelvic pain including self management strategies. CITE HOW TO CITE THIS REPORT Saunders PT. Reviewer Report For: Holistic approaches to living well with endometriosis [version 2; peer review: 2 approved]. F1000Research 2024, 13:359 (https://doi.org/10.5256/f1000research.156153.r292395) The direct URL for this report is: https://f1000research.com/articles/13-359/v1#referee-response-292395 https://f1000research.com/articles/13-359/v1#referee-response-292395 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. - Author Response 08 Nov 2024Jessica Desai, Central and North West London NHS Foundation Trust, London, UK08 Nov 2024Author ResponseWe thank you for the suggestions and have made the following adjustments: In some parts of the text it is hard to know if the results discussed relate to ... Continue reading We thank you for the suggestions and have made the following adjustments: In some parts of the text it is hard to know if the results discussed relate to individuals with CPP or those with CPP/Endo so careful re-reading and clarification of is advised (examples include yoga, TENS, mindfulness). [table of mind and body therapies?] - Clarification has been made on relation to CPP/endometriosis throughout the text It is recommended that the authors assemble information from relevant high quality original information from trials in tables – this would be more useful to the reader than simple text. - Please see Table 1 Esprit2 trial has a published protocol [Ref -1]. - Espirit2 trial protocol has now been referenced, please see reference 5

6 is to a protocol – the trial has been completed and the correct reference is [Ref -2] - Reference amended In section on nutrition it would be useful to mention GWAS and other data that support patient experience of IBS-like symptoms in association with endometriosis (includes abdominal bloating [Ref-3], diarrhoea etc). Recent paper [Ref-3] - Please see use of reference 23 in our paper No mention of botox for treatment of pelvic floor pain although there are reports it is effective · [Ref -4] - Section on botulinum toxin added to paper The section on cannabinoids is very brief which seems at odds with the widespread use of CBD in management of chronic pain, in some countries they are prescribed and there are several trials for endometriosis CPP underway – add more references. [Ref 5-7] - CBD section has been expanded, please see references 69, 70 Add more details from Ref 64 – this paper is from 1991 – any follow up papers? - Section expanded, please refer to reference 76We thank you for the suggestions and have made the following adjustments:Competing Interests: No competing interests were disclosed. Close In some parts of the text it is hard to know if the results discussed relate to individuals with CPP or those with CPP/Endo so careful re-reading and clarification of is advised (examples include yoga, TENS, mindfulness). [table of mind and body therapies?] - Clarification has been made on relation to CPP/endometriosis throughout the text It is recommended that the authors assemble information from relevant high quality original information from trials in tables – this would be more useful to the reader than simple text. - Please see Table 1 Esprit2 trial has a published protocol [Ref -1]. - Espirit2 trial protocol has now been referenced, please see reference 5

6 is to a protocol – the trial has been completed and the correct reference is [Ref -2] - Reference amended In section on nutrition it would be useful to mention GWAS and other data that support patient experience of IBS-like symptoms in association with endometriosis (includes abdominal bloating [Ref-3], diarrhoea etc). Recent paper [Ref-3] - Please see use of reference 23 in our paper No mention of botox for treatment of pelvic floor pain although there are reports it is effective · [Ref -4] - Section on botulinum toxin added to paper The section on cannabinoids is very brief which seems at odds with the widespread use of CBD in management of chronic pain, in some countries they are prescribed and there are several trials for endometriosis CPP underway – add more references. [Ref 5-7] - CBD section has been expanded, please see references 69, 70 Add more details from Ref 64 – this paper is from 1991 – any follow up papers? - Section expanded, please refer to reference 76 COMMENTS ON THIS REPORT - Author Response 08 Nov 2024Jessica Desai, Central and North West London NHS Foundation Trust, London, UK08 Nov 2024Author ResponseWe thank you for the suggestions and have made the following adjustments: In some parts of the text it is hard to know if the results discussed relate to ... Continue reading We thank you for the suggestions and have made the following adjustments: In some parts of the text it is hard to know if the results discussed relate to individuals with CPP or those with CPP/Endo so careful re-reading and clarification of is advised (examples include yoga, TENS, mindfulness). [table of mind and body therapies?] - Clarification has been made on relation to CPP/endometriosis throughout the text It is recommended that the authors assemble information from relevant high quality original information from trials in tables – this would be more useful to the reader than simple text. - Please see Table 1 Esprit2 trial has a published protocol [Ref -1]. - Espirit2 trial protocol has now been referenced, please see reference 5

6 is to a protocol – the trial has been completed and the correct reference is [Ref -2] - Reference amended In section on nutrition it would be useful to mention GWAS and other data that support patient experience of IBS-like symptoms in association with endometriosis (includes abdominal bloating [Ref-3], diarrhoea etc). Recent paper [Ref-3] - Please see use of reference 23 in our paper No mention of botox for treatment of pelvic floor pain although there are reports it is effective · [Ref -4] - Section on botulinum toxin added to paper The section on cannabinoids is very brief which seems at odds with the widespread use of CBD in management of chronic pain, in some countries they are prescribed and there are several trials for endometriosis CPP underway – add more references. [Ref 5-7] - CBD section has been expanded, please see references 69, 70 Add more details from Ref 64 – this paper is from 1991 – any follow up papers? - Section expanded, please refer to reference 76We thank you for the suggestions and have made the following adjustments:Competing Interests: No competing interests were disclosed. Close In some parts of the text it is hard to know if the results discussed relate to individuals with CPP or those with CPP/Endo so careful re-reading and clarification of is advised (examples include yoga, TENS, mindfulness). [table of mind and body therapies?] - Clarification has been made on relation to CPP/endometriosis throughout the text It is recommended that the authors assemble information from relevant high quality original information from trials in tables – this would be more useful to the reader than simple text. - Please see Table 1 Esprit2 trial has a published protocol [Ref -1]. - Espirit2 trial protocol has now been referenced, please see reference 5

6 is to a protocol – the trial has been completed and the correct reference is [Ref -2] - Reference amended In section on nutrition it would be useful to mention GWAS and other data that support patient experience of IBS-like symptoms in association with endometriosis (includes abdominal bloating [Ref-3], diarrhoea etc). Recent paper [Ref-3] - Please see use of reference 23 in our paper No mention of botox for treatment of pelvic floor pain although there are reports it is effective · [Ref -4] - Section on botulinum toxin added to paper The section on cannabinoids is very brief which seems at odds with the widespread use of CBD in management of chronic pain, in some countries they are prescribed and there are several trials for endometriosis CPP underway – add more references. [Ref 5-7] - CBD section has been expanded, please see references 69, 70 Add more details from Ref 64 – this paper is from 1991 – any follow up papers? - Section expanded, please refer to reference 76 Views 0 How to cite this report: Raimondo D. Reviewer Report For: Holistic approaches to living well with endometriosis [version 2; peer review: 2 approved]. F1000Research 2024, 13:359 (https://doi.org/10.5256/f1000research.156153.r271069) The direct URL for this report is: https://f1000research.com/articles/13-359/v1#referee-response-271069 https://f1000research.com/articles/13-359/v1#referee-response-271069 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Reviewer Report 02 Jul 2024 Diego Raimondo, Division of Gynaecology and Human Reproduction Physiopathology, IRCCS AOUBO, Bologna, Italy Approved with Reservations VIEWS 0

The abstract is well-structured and provides a clear overview of the topic. However, it could benefit from a concluding sentence that highlights the clinical significance of the findings to enhance reader understanding.

The ... Continue reading 2. Ianieri MM, De Cicco Nardone A, Benvenga G, Greco P, et al.: Vascular- and nerve-sparing bowel resection for deep endometriosis: A retrospective single-center study.Int J Gynaecol Obstet. 2024; 164 (1): 277-285 PubMed Abstract | Publisher Full Text I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close The abstract is well-structured and provides a clear overview of the topic. However, it could benefit from a concluding sentence that highlights the clinical significance of the findings to enhance reader understanding.

The ... Continue reading

The abstract is well-structured and provides a clear overview of the topic. However, it could benefit from a concluding sentence that highlights the clinical significance of the findings to enhance reader understanding.

The introduction is comprehensive and provides adequate context on endometriosis and the challenges associated with its treatment. However, it could benefit from emphasizing more recent research, particularly from the last two to three years. Please discuss on the iatrogenic risk of endometriosis surgery and not only on the risk of recurrence (i.e. Ref [1,2])

The methodology section is detailed and rigorous but could use some clarifications. Inclusion and Exclusion Criteria: Provide more details on the criteria used to include or exclude specific studies. Search Methodology: Describe the databases used and the search terms applied more specifically. Quality Assessment: Describe the metrics or tools used to evaluate the quality of the included studies.

The results are well-presented and supported by a solid evidence base. However, some sections could benefit from more synthesis to improve readability. Nutrition: The information is detailed and pertinent, but a summary table could help visualize the effects of different dietary interventions better. Acupuncture: The acupuncture section is thorough but could benefit from a discussion on the limitations of the cited studies.

The conclusions effectively summarize the key points of the article. However, reinforcing the message on the importance of integrating holistic strategies into clinical practice could enhance the impact. Graphs and Tables: Including more graphs and tables to visualize key data could improve the manuscript's comprehensibility and visual appeal.. The abstract is well-structured and provides a clear overview of the topic. However, it could benefit from a concluding sentence that highlights the clinical significance of the findings to enhance reader understanding.

The introduction is comprehensive and provides adequate context on endometriosis and the challenges associated with its treatment. However, it could benefit from emphasizing more recent research, particularly from the last two to three years. Please discuss on the iatrogenic risk of endometriosis surgery and not only on the risk of recurrence (i.e. Ref [1,2])

The methodology section is detailed and rigorous but could use some clarifications. Inclusion and Exclusion Criteria: Provide more details on the criteria used to include or exclude specific studies. Search Methodology: Describe the databases used and the search terms applied more specifically. Quality Assessment: Describe the metrics or tools used to evaluate the quality of the included studies.

The results are well-presented and supported by a solid evidence base. However, some sections could benefit from more synthesis to improve readability. Nutrition: The information is detailed and pertinent, but a summary table could help visualize the effects of different dietary interventions better. Acupuncture: The acupuncture section is thorough but could benefit from a discussion on the limitations of the cited studies.

The conclusions effectively summarize the key points of the article. However, reinforcing the message on the importance of integrating holistic strategies into clinical practice could enhance the impact. Graphs and Tables: Including more graphs and tables to visualize key data could improve the manuscript's comprehensibility and visual appeal.. - Is the topic of the review discussed comprehensively in the context of the current literature? Yes - Are all factual statements correct and adequately supported by citations? Yes - Is the review written in accessible language? Yes - Are the conclusions drawn appropriate in the context of the current research literature? Yes

1. Seracchioli R, Ferrini G, Montanari G, Raimondo D, et al.: Does laparoscopic shaving for deep infiltrating endometriosis alter intestinal function? A prospective study.Aust N Z J Obstet Gynaecol. 2015; 55 (4): 357-62 PubMed Abstract | Publisher Full Text2. Ianieri MM, De Cicco Nardone A, Benvenga G, Greco P, et al.: Vascular- and nerve-sparing bowel resection for deep endometriosis: A retrospective single-center study.Int J Gynaecol Obstet. 2024; 164 (1): 277-285 PubMed Abstract | Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: endometriosis CITE HOW TO CITE THIS REPORT Raimondo D. Reviewer Report For: Holistic approaches to living well with endometriosis [version 2; peer review: 2 approved]. F1000Research 2024, 13:359 (https://doi.org/10.5256/f1000research.156153.r271069) The direct URL for this report is: https://f1000research.com/articles/13-359/v1#referee-response-271069 https://f1000research.com/articles/13-359/v1#referee-response-271069 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. - Author Response 08 Nov 2024Jessica Desai, Central and North West London NHS Foundation Trust, London, UK08 Nov 2024Author ResponseWe thank you for the suggestions and have made the following adjustments to our paper:

The abstract is well-structured and provides a clear overview of the topic. However, ... Continue reading We thank you for the suggestions and have made the following adjustments to our paper:

The abstract is well-structured and provides a clear overview of the topic. However, it could benefit from a concluding sentence that highlights the clinical significance of the findings to enhance reader understanding. - Abstract concluding sentence adjusted

The introduction is comprehensive and provides adequate context on endometriosis and the challenges associated with its treatment. However, it could benefit from emphasizing more recent research, particularly from the last two to three years. Please discuss on the iatrogenic risk of endometriosis surgery and not only on the risk of recurrence (i.e. Ref [1,2]) - Please refer to reference 6 and 7 cited in the amended submission

The methodology section is detailed and rigorous but could use some clarifications. Inclusion and Exclusion Criteria: Provide more details on the criteria used to include or exclude specific studies. Search Methodology: Describe the databases used and the search terms applied more specifically. Quality Assessment: Describe the metrics or tools used to evaluate the quality of the included studies. - Inclusion and exclusion criteria, search methodology and quality assessment sections added to paper

The results are well-presented and supported by a solid evidence base. However, some sections could benefit from more synthesis to improve readability. Nutrition: The information is detailed and pertinent, but a summary table could help visualize the effects of different dietary interventions better. Acupuncture: The acupuncture section is thorough but could benefit from a discussion on the limitations of the cited studies. - Limitations of paper reference 62 has been added

The conclusions effectively summarize the key points of the article. However, reinforcing the message on the importance of integrating holistic strategies into clinical practice could enhance the impact. - Conclusion has been amended with statement on the importance of integration into clinical practice Graphs and Tables: Including more graphs and tables to visualize key data could improve the manuscript's comprehensibility and visual appeal.. - Please refer to Table 1We thank you for the suggestions and have made the following adjustments to our paper:Competing Interests: No competing interests were disclosed. Close

The abstract is well-structured and provides a clear overview of the topic. However, it could benefit from a concluding sentence that highlights the clinical significance of the findings to enhance reader understanding. - Abstract concluding sentence adjusted

The introduction is comprehensive and provides adequate context on endometriosis and the challenges associated with its treatment. However, it could benefit from emphasizing more recent research, particularly from the last two to three years. Please discuss on the iatrogenic risk of endometriosis surgery and not only on the risk of recurrence (i.e. Ref [1,2]) - Please refer to reference 6 and 7 cited in the amended submission

The methodology section is detailed and rigorous but could use some clarifications. Inclusion and Exclusion Criteria: Provide more details on the criteria used to include or exclude specific studies. Search Methodology: Describe the databases used and the search terms applied more specifically. Quality Assessment: Describe the metrics or tools used to evaluate the quality of the included studies. - Inclusion and exclusion criteria, search methodology and quality assessment sections added to paper

The results are well-presented and supported by a solid evidence base. However, some sections could benefit from more synthesis to improve readability. Nutrition: The information is detailed and pertinent, but a summary table could help visualize the effects of different dietary interventions better. Acupuncture: The acupuncture section is thorough but could benefit from a discussion on the limitations of the cited studies. - Limitations of paper reference 62 has been added

The conclusions effectively summarize the key points of the article. However, reinforcing the message on the importance of integrating holistic strategies into clinical practice could enhance the impact. - Conclusion has been amended with statement on the importance of integration into clinical practice Graphs and Tables: Including more graphs and tables to visualize key data could improve the manuscript's comprehensibility and visual appeal.. - Please refer to Table 1 COMMENTS ON THIS REPORT - Author Response 08 Nov 2024Jessica Desai, Central and North West London NHS Foundation Trust, London, UK08 Nov 2024Author ResponseWe thank you for the suggestions and have made the following adjustments to our paper:

The abstract is well-structured and provides a clear overview of the topic. However, ... Continue reading We thank you for the suggestions and have made the following adjustments to our paper:

The abstract is well-structured and provides a clear overview of the topic. However, it could benefit from a concluding sentence that highlights the clinical significance of the findings to enhance reader understanding. - Abstract concluding sentence adjusted

The introduction is comprehensive and provides adequate context on endometriosis and the challenges associated with its treatment. However, it could benefit from emphasizing more recent research, particularly from the last two to three years. Please discuss on the iatrogenic risk of endometriosis surgery and not only on the risk of recurrence (i.e. Ref [1,2]) - Please refer to reference 6 and 7 cited in the amended submission

The methodology section is detailed and rigorous but could use some clarifications. Inclusion and Exclusion Criteria: Provide more details on the criteria used to include or exclude specific studies. Search Methodology: Describe the databases used and the search terms applied more specifically. Quality Assessment: Describe the metrics or tools used to evaluate the quality of the included studies. - Inclusion and exclusion criteria, search methodology and quality assessment sections added to paper

The results are well-presented and supported by a solid evidence base. However, some sections could benefit from more synthesis to improve readability. Nutrition: The information is detailed and pertinent, but a summary table could help visualize the effects of different dietary interventions better. Acupuncture: The acupuncture section is thorough but could benefit from a discussion on the limitations of the cited studies. - Limitations of paper reference 62 has been added

The conclusions effectively summarize the key points of the article. However, reinforcing the message on the importance of integrating holistic strategies into clinical practice could enhance the impact. - Conclusion has been amended with statement on the importance of integration into clinical practice Graphs and Tables: Including more graphs and tables to visualize key data could improve the manuscript's comprehensibility and visual appeal.. - Please refer to Table 1We thank you for the suggestions and have made the following adjustments to our paper:Competing Interests: No competing interests were disclosed. Close

The abstract is well-structured and provides a clear overview of the topic. However, it could benefit from a concluding sentence that highlights the clinical significance of the findings to enhance reader understanding. - Abstract concluding sentence adjusted

The introduction is comprehensive and provides adequate context on endometriosis and the challenges associated with its treatment. However, it could benefit from emphasizing more recent research, particularly from the last two to three years. Please discuss on the iatrogenic risk of endometriosis surgery and not only on the risk of recurrence (i.e. Ref [1,2]) - Please refer to reference 6 and 7 cited in the amended submission

The methodology section is detailed and rigorous but could use some clarifications. Inclusion and Exclusion Criteria: Provide more details on the criteria used to include or exclude specific studies. Search Methodology: Describe the databases used and the search terms applied more specifically. Quality Assessment: Describe the metrics or tools used to evaluate the quality of the included studies. - Inclusion and exclusion criteria, search methodology and quality assessment sections added to paper

The results are well-presented and supported by a solid evidence base. However, some sections could benefit from more synthesis to improve readability. Nutrition: The information is detailed and pertinent, but a summary table could help visualize the effects of different dietary interventions better. Acupuncture: The acupuncture section is thorough but could benefit from a discussion on the limitations of the cited studies. - Limitations of paper reference 62 has been added

The conclusions effectively summarize the key points of the article. However, reinforcing the message on the importance of integrating holistic strategies into clinical practice could enhance the impact. - Conclusion has been amended with statement on the importance of integration into clinical practice Graphs and Tables: Including more graphs and tables to visualize key data could improve the manuscript's comprehensibility and visual appeal.. - Please refer to Table 1 Alongside their report, reviewers assign a status to the article: - Approved - Approved with reservations - Not approved | Invited Reviewers | || |---|---|---| | 1 | 2 | | | Version 2 (revision) 08 Nov 24 | read | read | | Version 1 23 Apr 24 | read | read | Sign up for content alerts You are now signed up to receive this alert Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' - Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. - You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. - You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). - You work at the same institute as any of the authors. - You hope/expect to benefit (e.g. favour or employment) as a result of your submission. - You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' - You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. - You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. - You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Sign up for content alerts and receive a weekly or monthly email with all newly published articles Already registered? Sign in close Error Sign In If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password. Email us for further assistance. The email address should be the one you originally registered with F1000. Email address not valid, please try again You registered with F1000 via Google, so we cannot reset your password. To sign in, please click here. If you still need help with your Google account password, please click here. You registered with F1000 via Facebook, so we cannot reset your password. To sign in, please click here. If you still need help with your Facebook account password, please click here. Code not correct, please try again Server error, please try again. If your email address is registered with us, we will email you instructions to reset your password. If you think you should have received this email but it has not arrived, please check your spam filters and/or contact for further assistance. Please wait...