Feasibility, acceptability, and exploratory outcomes of a virtual cognitive behavioural therapy-based group intervention for persistent fatigue in endometriosis: The Managing Fatigue in Endometriosis (MEND) programme

Alexandra Spyrelis: Conceptualization; investigation; funding acquisition; writing – original draft; writing – review and editing; formal analysis; project administration; methodology. Maria E. Loades: Conceptualization; writing – original draft; writing – review and editing; supervision; resources. Rizwana Roomaney: Conceptualization; writing – original draft; writing – review and editing; supervision; resources.

Dr Alexandra Spyrelis would like to acknowledge the generous support provided by the National Institute for the Humanities and Social Sciences (NIHSS) to undertake this work. Professor Rizwan Roomaney would like to acknowledge support from the National Research Foundation (NRF) of South Africa in the form of a Thuthuka grant. Dr. Maria Loades (Advanced Fellowship, 302929) is funded by the National Institute for Health Research (NIHR) for this research project. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR, NHS or the UK Department of Health and Social Care.

Enrolled participants ranged in age from 23 to 43 years (mean age = 33.1 years). Most were in a relationship, did not have children, had completed tertiary education, and were employed (Table  1 ). Sociodemographic characteristics of participants. Fifty‐two (52) patients completed the screening survey, of which 43 met the eligibility criteria, resulting in an eligibility rate of 83%. Of the 43 patients invited to provide consent, 21 did so, resulting in an enrolment rate of 49% among eligible candidates. The main reason for non‐consent was due to non‐response to communication about the study, despite the researcher making several attempts at contact (59%). Other reasons included ill health (18%), the provision of incorrect contact information (14%), and the time commitment required (9%). Consenting participants were slightly younger on average (mean age = 32.3 years; SD = 6.10) than eligible participants that did not consent (mean age = 34.2; SD = 6.15) and also had a slightly higher average fatigue score (mean CFQ‐11 score = 24.0) than those that did not consent (mean CFQ‐11 score = 22.36). A study CONSORT flow diagram is provided in Figure  1 , based on the guideline for feasibility and pilot trials (Eldridge, Chan, et al.,  2016 ). Participant flow at each stage of the study. Of 21 enrolled participants, 18 (86%) initiated the programme, having attended at least one session (Table  2 ). Of these 18 participants, 67% ( n  = 12) completed the intervention (attended four or more sessions), resulting in a completion rate of 57% among enrolled participants. Three participants withdrew from the intervention as a result of conflicting work and study commitments, while the remaining 33% ( n  = 6) attended between 1 and 3 sessions. Feasibility outcomes of MEND across the three groups. Session attendance rates ranged from 43% to 76%. The implementation of the programme coincided with the height of intensive nationwide electricity outages (called loadshedding), resulting in many participants not having electricity or internet to attend sessions. Several participants also became ill or had other work or family obligations. The overall drop‐out rate (discontinuing after commencing the intervention) was 28%. A high completion rate for the outcome measures was achieved at baseline (95%), which dropped at post‐treatment (67%) and follow‐up (62%). A review of a sample of session recordings indicated that the RCs delivered the sessions as intended in the manual, which was likely due to the scripted slides that were provided. Several opportunities for future improvement were noted from the recordings, including a need to remove repetitive group discussion questions. The RCs completed all session feedback forms for the three groups ( n  = 18), with ratings regarding the groups' understanding of, participation in, and enjoyment of the activities in each session ranging from 3.67 to 4.75 out of 5, indicating that they were generally well received. The structure and content of the sessions were rated highly, with the exception of a few activities that required additional time to complete. While all study participants were invited to the group interviews, those that dropped out of MEND were non‐responsive to the invitation despite several attempts at contact. A total of eight participants (who had attended at least one session but with varying attendance rates) took part in the group interviews, and six themes were generated during the analysis. Participants enjoyed MEND and felt validated and less isolated from interacting with other patients also struggling with endometriosis and fatigue. I looked forward to it because I felt I was talking to people who really, really understand what I was going through without having to explain a whole lot of things. (Participant 4, 27 years old) I looked forward to it because I felt I was talking to people who really, really understand what I was going through without having to explain a whole lot of things. (Participant 4, 27 years old) Participants found the content helpful in understanding factors affecting their fatigue, particularly sessions focused on sleep, pacing, and unhelpful thought patterns. However, a few participants struggled to fully grasp the concept of CBT. My favourite session was the one where we identified how we fall into those negative patterns and how to get yourself out of that. I suffer from that a lot. Where one thing is bad, everything is bad, and kind of recognizing those steps and stopping myself before I get there has helped a whole lot. (Participant 1, 41 years old) My favourite session was the one where we identified how we fall into those negative patterns and how to get yourself out of that. I suffer from that a lot. Where one thing is bad, everything is bad, and kind of recognizing those steps and stopping myself before I get there has helped a whole lot. (Participant 1, 41 years old) Participants were satisfied with MEND's format, having found the language understandable and the spacing of the sessions ideal, as it allowed them time to implement learnings. Several participants expressed a desire for additional sessions. I just want to say I think it was very, like, well thought out. We could understand, we could talk together about it. (Participant 2, 29 years old) I just want to say I think it was very, like, well thought out. We could understand, we could talk together about it. (Participant 2, 29 years old) Participants found the workbook useful and informative, and referred to it after the sessions or used it to catch up on missed sessions. They also planned to use it to refresh their knowledge in the future. Participants praised the RCs, indicating that they had helped the group to feel comfortable to share their experiences and to understand the content. She is very patient, she went through all of the information in a lot of detail. She gave us ample opportunities to ask questions, to talk. (Participant 5, 33 years old) She is very patient, she went through all of the information in a lot of detail. She gave us ample opportunities to ask questions, to talk. (Participant 5, 33 years old) Some participants felt that the intervention could address endometriosis more broadly, including a focus on pain management, while others felt that this would make it too broad. Participants also suggested adding links to additional resources for information and support for endometriosis. Eight themes were generated from the analysis of data generated from the interviews with both RCs. RCs found the training and training materials sufficiently comprehensive to facilitate MEND. One RC noted that the training could be improved by adding a component on dealing with dominant group members. I think that the training went well and was sufficient in detail. I think your material is very good and put together very well. (RC 1) I think that the training went well and was sufficient in detail. I think your material is very good and put together very well. (RC 1) Both RCs found MEND valuable and enjoyed facilitating the sessions, noting that the participants had benefitted from the supportive structure of the group. They participated, it was really good…And I think it was a safe space for them eventually and we all enjoyed it. (RC 2) They participated, it was really good…And I think it was a safe space for them eventually and we all enjoyed it. (RC 2) Both RCs indicated that participants struggled with unhelpful thoughts, particularly being very self‐critical, and noted that the activities on pacing, relaxation, sleep, and unhelpful thoughts were especially useful. They absolutely loved the mindfulness and the relaxation techniques…the thinking and the fatigue stuff was incredibly helpful for them… I think if anything stuck with them, it is the energy envelope and, and how that works, and to be kind to yourself. (RC 1) They absolutely loved the mindfulness and the relaxation techniques…the thinking and the fatigue stuff was incredibly helpful for them… I think if anything stuck with them, it is the energy envelope and, and how that works, and to be kind to yourself. (RC 1) RCs reported that participant engagement was mixed, with participants sometimes being tired at sessions. They noted that the participants generally became more comfortable over time. Participants' completion of the homework assignments was mixed, with some not completing it due to other responsibilities. By the end, by session five, there were so comfortable they, they joined in their pyjamas (laughs)…this is one space that I do not have to pretend that I am fine or I am looking fine. (RC 2) By the end, by session five, there were so comfortable they, they joined in their pyjamas (laughs)…this is one space that I do not have to pretend that I am fine or I am looking fine. (RC 2) RCs found it challenging to facilitate sessions when participants became emotional, particularly the first session when they shared their disease experiences. One RC struggled to facilitate the session on CBT but was unsure about why this was the case. Some participants were struggling with clinical insomnia, which made it difficult for them to grasp the concept of fatigue. They were very much struggling with real clinical insomnia. And so from that perspective, it was a bit difficult talking to them about fatigue, because the message…was not really being received because they were just like ‘but I just do not sleep and that's why I'm tired’. (RC 1) They were very much struggling with real clinical insomnia. And so from that perspective, it was a bit difficult talking to them about fatigue, because the message…was not really being received because they were just like ‘but I just do not sleep and that's why I'm tired’. (RC 1) RCs were satisfied with the materials and found the session slides, which contained the content and scripts, particularly useful. They felt that the content was sufficiently detailed to provide a thorough understanding of endometriosis. Despite some technical difficulties, such as unstable internet, the RCs noted that the virtual sessions worked well and were convenient and accessible for the participants to attend from home anywhere in the country. However, one RC noted that virtual implementation may impact engagement levels and does not create as much accountability for the homework assignments. Finding a suitable session time for all group members was difficult; participants could not always attend due to other commitments, falling ill or struggling with disease‐related symptoms. Women have families, they have household responsibilities. What are the chances you are going to get them out of the house, and they have got children…to have to leave the house, drive somewhere, show up for an hour and a half, and then still drive back, it is not likely. They are not going take the time for themselves to do that, and it sounds like a lot of effort when you are already fatigued. So, I do think that this made it possible for so many people to attend. (RC 1) Women have families, they have household responsibilities. What are the chances you are going to get them out of the house, and they have got children…to have to leave the house, drive somewhere, show up for an hour and a half, and then still drive back, it is not likely. They are not going take the time for themselves to do that, and it sounds like a lot of effort when you are already fatigued. So, I do think that this made it possible for so many people to attend. (RC 1) One RC suggested that CBT‐related content be included in all sessions to allow more time for participants to grasp the concept. Other suggestions included adding links to mindfulness and relaxation videos on YouTube to the workbook and charging participants for the sessions to ensure their attendance. All the measures showed acceptable reliability for the total sample at baseline, ranging from a = 0.73 to a = 0.93. Table  3 presents the Reliable Change Index (RCI), indicating the number and percentage of participants showing an improvement, no change or deterioration in scores across the seven PROMs between T0 and T1 and T0 and T2, respectively. Counts and percentages of participants demonstrating reliable change by PROM ( N  = 11). Note : Reliable change over time, based on Reliable Change Index, RCI ≥1.96. Measures: BDI‐II, Beck Depression Inventory; CBRQ, Cognitive and Behavioural Responses to Symptoms Questionnaire; CFQ‐11, Chalder Fatigue Questionnaire; EHP‐30, Endometriosis Health Profile; FSS, Fatigue Severity Scale; SEQOL, Stellenbosch Endometriosis Quality of Life; VAS Pain, Visual Analog Scale for Pain. At T1, 55% of participants showed improvement on the CFQ‐11, while 9% worsened. At T2, the proportion of improved participants decreased to 36%, with an increase in worsened scores (18%). More than a third of participants' scores remained unchanged at both timepoints. Improvement on the FSS was limited at T1 (18%), with most participants reporting no change (64%). Notably, improvement rose to 45% at T2, with only 9% of participants showing worsened scores, although 45% demonstrated no change. On the BDI‐II, 36% of participants demonstrated improvements at T1 while 18% worsened and 45% remained unchanged. These figures remained largely stable at T2, with 45% showing improvement, 36% demonstrating no change, and 18% demonstrating worsened scores. Over half of the participants demonstrated improvements (55%) on the SEQOL at TI, with minimal worsening (9%), although 36% remained unchanged. However, at T2, the improvement rate dropped to 36%, with a slight increase in worsened scores (18%) and unchanged scores (45%). Responses on the EHP‐30 were balanced at T1, with 36% demonstrating improvement and 36% worsening, and 26% remaining unchanged. At T2, improvement increased to 45%, although the proportion of unchanged or worsened outcomes remained high (27%). With regard to the CBRQ, T1 results indicate that 55% of participants showed an improvement, although 27% worsened and 18% remained unchanged. At T2, improvement decreased to 36%, with an increase in unchanged scores to 45% and a reduction in worsened scores to 18%. Finally, only 27% of participants demonstrated an improvement in the VAS for Pain scores at T1, and 36% worsened or remained unchanged. At T2, the proportion of participants with improved VAS for Pain scores dropped to 9%, while those reporting no change rose to 64%, and 27% demonstrated worsening. Four themes were generated from the participant group interviews regarding the impact of MEND. Participants reported that they were better able to regulate their activity levels after MEND, being more purposeful about tasks and rest. They also noted being able to identify triggers that worsened their fatigue. While this helped to manage their fatigue, it did not always work to reduce their fatigue levels. Participants also reported making changes to their sleeping habits, which resulted in improved sleep. It made a difference in my life. You get so used to just going, going, going, without stopping or thinking. And this, like, definitely put some hills in the way…And it has been such a game changer for me to just take a step back and think about and just pace myself through a day, through a workout, through work, through a walk, anything. (Participant 3, 37 years old) It made a difference in my life. You get so used to just going, going, going, without stopping or thinking. And this, like, definitely put some hills in the way…And it has been such a game changer for me to just take a step back and think about and just pace myself through a day, through a workout, through work, through a walk, anything. (Participant 3, 37 years old) The greatest effect reported by participants was with regard to their unhelpful cognitions, with many becoming aware of self‐critical thoughts, unrealistic expectations of themselves, and guilt about needing to rest. They applied learnings from MEND to shift these thought patterns and noted an overall improvement in their anxiety levels and broader mental health. I think more than ever my thinking process has changed. I am more aware of my thoughts than previously. I acknowledge also what I feel, which was something I did not do previously. (Participant 8, 25 years old) It has eased my guilt for slowing down when I need to slow down. I am allowing myself to do what I need to do without feeling guilty about it, it has definitely helped me. (Participant 3, 37 years old) I think more than ever my thinking process has changed. I am more aware of my thoughts than previously. I acknowledge also what I feel, which was something I did not do previously. (Participant 8, 25 years old) It has eased my guilt for slowing down when I need to slow down. I am allowing myself to do what I need to do without feeling guilty about it, it has definitely helped me. (Participant 3, 37 years old) Participants reported a sense of control over their disease after MEND and reported a shift from feelings of victimhood to empowerment. Some participants decided to seek professional help to address their physical and mental health challenges as a result of MEND. It gave me some control, you know. Made me start to figure out that I was able to do some things to be in control of my fatigue and of my condition, which I think that a lot of us often feel like we have no control and we are like, we are victims. And that was very empowering. (Participant 1, 41 years old) It gave me some control, you know. Made me start to figure out that I was able to do some things to be in control of my fatigue and of my condition, which I think that a lot of us often feel like we have no control and we are like, we are victims. And that was very empowering. (Participant 1, 41 years old) Participants were grateful for the opportunity to take part and hoped that the study would be useful in creating treatment for fatigue in endometriosis. I just want to say thank you so much. I think it was a once in a lifetime opportunity to be part of something like this so I really appreciate it. (Participant 5, 33 years old) I just want to say thank you so much. I think it was a once in a lifetime opportunity to be part of something like this so I really appreciate it. (Participant 5, 33 years old) While RCs could not physically observe changes among participants in a virtual setting, they reported several improvements for which three themes were generated. RCs reported that participants appeared to apply the pacing principles to actively manage their fatigue and that the programme had helped them to realize the importance of rest and self‐care. However, neither RC commented on whether the participants reported being less fatigued. I think it is the relaxation activities…it is that I am allowed to take care of myself. Like taking care of myself is like an active thing. (RC 1) I think it is the relaxation activities…it is that I am allowed to take care of myself. Like taking care of myself is like an active thing. (RC 1) RCs reported that participants exhibited an improvement in their unhelpful cognitions and were less self‐critical as a result. Several participants had requested additional therapy with the RCs once the study ended. Just that change in thought process and that was what had left its mark. And so, it is easier for them to not become anxious and worked up because they are not guilt‐tripping themselves over what they should be doing. And so, it was making everything in general easier to manage and easier to cope with. (RC 1) …because one of the participants has asked to work with me after the programme is done. They said that they have decided based on being able to observe now how they are operating, how they are functioning, they have decided to seek help from a counsellor or psychologist. (RC 2) Just that change in thought process and that was what had left its mark. And so, it is easier for them to not become anxious and worked up because they are not guilt‐tripping themselves over what they should be doing. And so, it was making everything in general easier to manage and easier to cope with. (RC 1) …because one of the participants has asked to work with me after the programme is done. They said that they have decided based on being able to observe now how they are operating, how they are functioning, they have decided to seek help from a counsellor or psychologist. (RC 2) RCs commented on the utility of the MEND content and had applied some of the concepts in their own therapy work. They felt it could also be useful for other health conditions and expressed gratitude for being included in the study, where they had learnt valuable skills. It has been lovely, even the content that you have had that I have been working with has also left a mark on me… I have learned a lot too. (RC 1) It has been lovely, even the content that you have had that I have been working with has also left a mark on me… I have learned a lot too. (RC 1)

Our study of a novel CBT‐based group intervention delivered virtually by RCs, aimed at reducing fatigue among patients with endometriosis in South Africa, found the intervention to be promising. Appropriate participants were recruited from the target group and the eligibility criteria were feasible (Orsmond & Cohn,  2015 ). The recruitment rate was relatively high, with 83% of interested candidates meeting the eligibility criteria, compared to those reported in the other fatigue studies of between 31% and 89% (Artom et al.,  2018 ; Picariello et al.,  2021 ; van den Akker et al.,  2017 ; van Kessel et al.,  2008 ). This may be because participants self‐selected for MEND, while those in other LTC fatigue studies were targeted at hospitals or outpatient centres where they received treatment (Bøhn et al.,  2024 ; Jim et al.,  2020 ; Menting et al.,  2017 ; Picariello et al.,  2021 ). Only half of eligible participants consented to enrol in MEND (49%), which aligns with enrolment rates in other fatigue studies (Artom et al.,  2018 ; Hewlett, Ambler, et al.,  2011 ). Non‐response to communication was the main reason for this, as well as ill health, inability to commit to the time required or the provision of incorrect contact information. Similar reasons for non‐enrolment were reported in the other fatigue studies, with patients commonly concerned about the time and effort required to participate in interventions (Artom et al.,  2018 ; Menting et al.,  2017 ; Picariello et al.,  2021 ). The MEND communication strategy, which was conducted entirely virtually, may have affected the higher non‐response rate. The findings demonstrate that severely fatigued patients with endometriosis could be recruited and were motivated to participate in MEND. During discussions with eligible candidates about the study, many articulated a need for guidance on how to manage their fatigue. While the MEND intervention initiation rate compares to other fatigue studies (Artom et al.,  2018 ; Gielissen et al.,  2006 ; Menting et al.,  2017 ; Thomas et al.,  2013 ), session attendance rates were lower, varying between 43% and 76% per session (Picariello et al.,  2021 ; Thomas et al.,  2013 ). In total, 57% of enrolled participants completed MEND, while 28% dropped out. Poor attendance mostly stemmed from the crippling nationwide power outages during implementation, which impacted the participants' ability to join the sessions. This suggests that lower retention rates may be driven by external factors rather than the intervention itself. Several participants also became ill, were required to work or had family commitments, which resulted in missed sessions. Ill health and work or family commitments are common barriers to attendance in the other fatigue studies, alongside a lack of interest (Artom et al.,  2018 ; Gielissen et al.,  2006 ; Thomas et al.,  2013 ; van den Akker et al., 2016 ). The MEND completion rate is lower than that seen in the other fatigue studies, which ranged from 64% to 100% (Artom et al.,  2018 ; Bøhn et al.,  2024 ; Jim et al.,  2020 ; Picariello et al.,  2021 ; van den Akker et al., 2016 ; van Kessel et al.,  2008 ). It is possible that fatigue may have influenced participants' decisions to drop out of MEND, given its potential to serve as a barrier to participation (Waite et al.,  2023 ), although this could not be assessed during the current study as these participants did not respond to requests for an interview. The low completion rate, despite self‐selection for the intervention, raises questions about the potential completion rate in a future study. While the data collection procedures were found to be acceptable, completion rates were somewhat low (62% of participants completed all three survey rounds). This aligns with the survey completion rate of 60% reported in Hewlett, Chalder, et al.'s ( 2011 ) RCT among patients with rheumatoid arthritis but is lower than that reported in the studies that aimed to treat fatigue in other LTCs, which ranged from 75% to 100% (Bøhn et al.,  2024 ; Menting et al.,  2017 ; Picariello et al.,  2021 ; Thomas et al.,  2013 ). MEND participants did not consistently complete the home practice assignments, usually due to a lack of available time. A similar finding was noted in Artom et al.'s ( 2018 ) feasibility trial. The survey completion rate could be improved by providing financial incentives in future studies. Further, Artom et al. ( 2018 ) suggest requiring participants to submit photographs of completed homework assignments to ensure accountability. Overall, MEND was well received and found to be acceptable among both participants and RCs. The RCs, who were non‐specialists, reported that the content was well structured and that participants were generally engaged, understood and enjoyed the content and were able to recall key learnings. The participants similarly indicated that they had found MEND to be valuable and enjoyable. They felt supported within the group and appreciated being able to interact with other women struggling with the same challenges. This points to the value of MEND in reducing feelings of isolation, which has been identified as a particular challenge among patients with endometriosis (Culley et al.,  2013 ; Grogan et al.,  2018 ). Despite a small sample size, the Reliable Change Index calculated using the 11 complete cases revealed some promising results. More than half of the participants (55%) demonstrated improvement to the extent of reliable change on the CFQ‐11 from baseline to post‐treatment, which was not entirely sustained at follow‐up (36%). Other fatigue studies have reported similar improvements in fatigue, despite varying intervention models, and have also reported that these effects wore off over time (Bøhn et al.,  2024 ; Kuut et al.,  2023 ; Picariello et al.,  2018 ; van den Akker et al.,  2017 ; van Kessel et al.,  2008 ). Interestingly, only a couple of participants (18%) showed reliable improvement on the FSS at post‐treatment, while almost half (45%) demonstrated an improvement at follow‐up. The mean CFQ‐11 and FSS scores may have deviated from each other over time given the CFQ‐11's focus on physical and mental fatigue versus the FSS' focus on the impact of fatigue on functioning. Interestingly, around half of the participants demonstrated no change on either of the fatigue measures, suggesting that some may have continued to experience persistent fatigue despite the intervention. During the group interviews, participants reported that the intervention had taught them to actively manage their fatigue and to rest regularly, although this did not necessarily reduce their fatigue levels. The findings suggest that MEND may positively affect mental health for some participants, with just more than a third of participants demonstrating reliable improvement in the BDI‐II at post‐treatment (36%) and almost half of participants demonstrating improvement at follow‐up (45%). The high proportion of unchanged scores may reflect a gradual or limited effect of the intervention on depressive symptoms for some participants. Artom et al. ( 2018 ) reported improvements in anxiety and depression using other scales for patients with IBD. Interestingly, van Kessel et al. ( 2008 ) found no significant effect for depression or anxiety in their fatigue intervention trial among patients with MS, while Hewlett, Chalder, et al. ( 2011 ) reported a significant improvement in depression but not anxiety among the control group in their intervention trial among patients with rheumatoid arthritis. Additional studies may be required to determine which components of these interventions are responsible for beneficial outcomes in depression and anxiety. Depression is a common diagnosis among patients with endometriosis and is a common correlate of fatigue, making it difficult to differentiate between the conditions (Billones et al.,  2020 ; Young et al.,  2015 ). The findings also suggest that MEND helped participants to change their cognitive and behavioural responses to their symptoms, in line with the goal of CBT (55% of participants demonstrated a reliable improvement at post‐treatment on the CBRQ, although 37% demonstrated a reliable deterioration). The improvement was not fully sustained at follow‐up, with 36% of participants demonstrating reliable improvement. The only other fatigue intervention study to have used the CBRQ was Picariello et al.'s ( 2021 ) trial, for which the greatest change was seen for fear avoidance. The PROMs for perceived QOL revealed inconsistent patterns, with some participants improving and others worsening at both time points, and many scores remaining unchanged. More than half of the participants (55%) demonstrated reliable improvement on the SEQOL at post‐treatment, which was not entirely sustained at follow‐up (36%). Improvements on the EHP‐30 increased over time from 36% at post‐treatment to 45% at follow‐up. During the group interviews, participants noted that they had gained access to group support and had become less self‐critical as a result of the intervention, which likely had positive results on QOL. However, it is unclear what could have affected worsening QOL as this was not evident in the qualitative data. Other fatigue studies found to improve QOL include those conducted among lymphoma survivors and patients with IBD (Artom et al.,  2018 ; Bøhn et al.,  2024 ). Finally, VAS for Pain scores reflected the least improvement overall. At follow‐up, only 9% of participants showed improvements, while 27% worsened. While MEND did not specifically aim to improve pain levels, pain intensity was measured in the study given its effect on perceptions of fatigue. Improvements in pain have been noted in other studies examining CBT‐based interventions in endometriosis (Donatti et al.,  2022 ). Only one of the other fatigue studies measured the VAS for Pain and found no significant effect (Hewlett, Chalder, et al.,  2011 ). Perceived pain intensity may be more resistant to change or may require different therapeutic strategies. The qualitative feedback from MEND participants indicates that the programme helped to legitimize their experiences of fatigue, thereby reducing their feelings of isolation. Similar findings were reported in a systematic review of fatigue management interventions for patients living with MS (Power et al.,  2021 ). MEND participants also reported having a greater sense of control over their fatigue and broader condition after the intervention, which was also noted among patients with MS (Power et al.,  2021 ). There are several limitations of this study that need to be highlighted. The small sample size and lack of control group limit the ability to draw definitive conclusions about MEND's effectiveness. Since the study was not sufficiently powered to assess efficacy, it was not possible to undertake formal hypothesis testing; the treatment effect estimates are likely to differ from the true effect. The study protocol was not pre‐registered, which raises the risk of selective reporting. The protocol did not formally establish pre‐defined progression criteria. Decisions regarding the feasibility of proceeding to a full RCT were instead informed by a combination of intervention acceptability and preliminary effectiveness trends. Further, given the exploratory nature and limited statistical power of the study, no formal analysis plan was established during the conceptual phase. The study attrition rate was high, and while likely due to external factors, this may indicate challenges in implementing MEND on a large scale. Participants self‐selected into the study and included English‐speaking women that had completed tertiary education and that were employed, which restricts the generalisability of the results to other populations. The study relied on patient self‐reported outcome measures, which can be subject to response bias and social desirability effects. Finally, participants who had dropped out from MEND, and who may have had a different perspective on the intervention, did not respond to requests for an interview; their feedback could therefore not be included.

In conclusion, the study found MEND to be feasible and acceptable among persistently fatigued patients with endometriosis. However, the lower completion rate warrants further investigation to determine the impact of external factors. While patient‐reported outcomes were mixed, the improvements suggest effective targeting of maladaptive responses to illness and that MEND addresses key symptom clusters relevant to complex conditions like endometriosis‐related fatigue. Given these preliminary findings, further research with a larger sample size, a comparison group, a longer follow‐up period and more robust analysis would be valuable to assess the MEND's effectiveness and scalability, to optimize delivery methods and to explore strategies to enhance engagement and completion rates. It would also allow for the identification of moderators and predictors of treatment response, alongside an exploration of ways to sustain the benefits over time, and to assess whether MEND can improve the broader wellbeing of patients with endometriosis beyond fatigue.

Endometriosis, an incurable, complex gynaecological disease, affects between 2% and 10% of reproductive‐aged women worldwide (Zondervan et al.,  2020 ). It is a chronic condition marked by endometrial‐like tissue that grows outside of the uterus, causing lesions, ovarian cysts, and the distortion or fusing of organs (Chiantera et al.,  2017 ; Dunselman et al.,  2014 ). Primary disease symptoms include chronic pelvic pain, heavy menstrual bleeding, and infertility (European Society of Human Reproduction and Embryology (ESHRE),  2022 ). A pervasive disease symptom often overlooked in the literature and clinical practice is persistent fatigue (Taylor,  2019 ). Few large studies have investigated endometriosis‐related fatigue, and its exact prevalence is unknown (Ramin‐Wright et al.,  2018 ). However, it is debilitating for some patients, with studies having found associations with depression, anxiety, poorer quality of life, and lower work productivity and social activity (Álvarez‐Salvago et al.,  2020 ; DiBenedetti et al.,  2020 ; Mundo‐López et al.,  2020 ). Fatigue is complex, subjective, and multi‐faceted. It is characterized by an overwhelming, sustained sense of exhaustion, alongside reduced capacity for mental and physical work, that is not improved with sleep or rest (Ream & Richardson,  1997 ; Shen et al.,  2006 ). The aetiology of endometriosis‐related fatigue is unknown, and interventions aimed at treating it are virtually non‐existent (Roomaney,  2017 ). Persistent fatigue is common in other physical long‐term conditions (LTCs), including multiple sclerosis (MS), inflammatory bowel disease (IBD) and rheumatoid arthritis, and it is common among cancer survivors and patients undergoing haemodialysis (Artom et al.,  2018 ; Jaime‐Lara et al.,  2020 ; Ju et al.,  2019 ; van Kessel et al., 2008 ). There is growing evidence that fatigue in LTCs has complex causal pathways that arise from a combination of both physiological and psychological factors and can therefore be best understood from a biopsychosocial standpoint (Hewlett, Chalder, et al.,  2011 ; van Kessel & Moss‐Morris,  2006 ). While physiological disease processes trigger the onset of fatigue, it is prolonged and worsened by particular cognitive, emotional, and behavioural factors, referred to as perpetuating factors (de Gier et al.,  2023 ). Physiological processes include the physical damage caused by the disease, inflammation, and immune dysfunction (Blanco et al.,  2025 ; Gielissen et al.,  2006 ; Lee & Giuliani,  2019 ). Perpetuating factors include illness beliefs and behaviours, such as irregular activity patterns, disrupted sleep–wake rhythms, catastrophizing, and negative rumination (de Gier et al.,  2023 ; Menting et al.,  2018 ). Cognitive behavioural therapy (CBT) targeting perpetuating factors is effective in reducing fatigue in several LTC patient populations, while also improving their physical and social functioning (Keijmel et al.,  2017 ; Kuut et al.,  2023 ; Thomas et al.,  2013 ; van den Akker et al.,  2017 ). To the authors' knowledge, CBT has not been investigated as a treatment for endometriosis‐related fatigue, prompting the current study. The first study phase aimed to develop a CBT‐based intervention called Managing Fatigue in Endometriosis (MEND), while the second phase aimed to evaluate its feasibility, acceptability, and preliminary indications of effectiveness among a group of fatigued patients with endometriosis in South Africa.

The authors have no relevant financial or non‐financial competing interests to report.

The lead author (AS) co‐designed MEND in collaboration with the co‐authors and expert stakeholders. First, transcripts from 25 interviews with patients with endometriosis‐related fatigue, drawn from a prior study conducted by the research team, were reviewed to understand their experiences (Sibande,  2022 ; Spyrelis et al.,  2024 ). Second, materials from 10 CBT‐based fatigue interventions found to be efficacious in other LTCs were analysed to identify core elements (Gielissen et al.,  2006 ; Hewlett, Ambler, et al.,  2011 ; Keijmel et al.,  2017 ; Kuut et al.,  2023 ; Menting et al.,  2017 ; Poort et al.,  2020 ; Thomas et al.,  2013 ; van den Akker et al.,  2017 ; van Kessel et al.,  2008 ; Voet et al.,  2014 ). Third, publications by well‐known experts in fatigue and CBT were considered (Burgess & Chalder,  2009 ; Moss‐Morris et al.,  2013 ). Based on this review, an intervention theory of change and draft intervention were developed, aligning patient needs with the evidence. The co‐authors, including a specialist in fatigue treatment (ML) and health psychology and endometriosis (RR), critically reviewed the draft material and provided recommendations for refinement. The refined material was shared with expert stakeholders, including a gynaecologist specialized in endometriosis, a psychiatrist specialized in CBT‐focused interventions, a clinical psychologist, a Registered Counsellor, as well as six patients with endometriosis to ensure its accuracy, relevance, and appropriateness. Structured feedback was collected through written responses and individual interviews, informing the final intervention design. MEND targets patients with endometriosis' thoughts, emotions, and behaviours to help them cope with the physical symptom of fatigue by providing psychoeducation about fatigue, addressing disordered sleep patterns, establishing consistent activity patterns, addressing unhelpful thoughts and enhancing skills around coping, accessing social support and relaxation, using Socratic questioning (see File  S1 for session overview and activities). MEND consists of six interactive sessions offered in a group format over 90 minutes each. The group‐based format, limited to a maximum of ten participants, enables discussion and problem solving to build participants' self‐efficacy and to allow them to learn from and support one another. Programme completion was pre‐defined as attendance at a minimum of four of the six sessions. Sessions follow a set structure, each with a recap of the previous session and homework assignment, two to three core activities, and a reflection and discussion of the home practice. MEND includes a scripted intervention manual and session slides, as well as a participant workbook. It was designed to be offered by Registered Counsellors (RCs), which the Health Professions Council of South Africa (HPCSA) defines as the entry‐level category within professional psychology that offers low‐intensity psychological interventions and assessments to individuals and groups (Health Professions Council of South Africa (HPCSA),  2020 ). RCs were required to be experienced in CBT and group therapy and were trained to implement the intervention via a two‐and‐a‐half‐day training session held online by the lead author, who also provided ongoing supervision via regular meetings. Ethical approval for this study was provided by the Health Research Ethics Committee (HREC) at Stellenbosch University. A concurrent triangulation mixed methods study was employed, utilizing an exploratory, single‐arm, within‐subjects repeated measures design among self‐selected participants (Creswell,  2014 ). The primary aim was to assess whether MEND could be conducted successfully and participants' preliminary responses to it, while the secondary aim was to assess early indications of effectiveness. While standard practice requires the pre‐registration of studies to ensure transparency and reproducibility in research (Nosek et al.,  2018 ), this study was not pre‐registered given a lack of awareness regarding the requirements for pre‐registration of feasibility studies during the planning phase. The entire intervention study was conducted online via virtual platforms (Microsoft Teams and Zoom). Participants were recruited online using an advert posted in January and April 2023 to the Facebook pages of local endometriosis support groups. Interested patients were required to complete a screening survey and had to be at least 18 years old, formally diagnosed with endometriosis via surgery or ultrasound, and experiencing clinical levels of fatigue, defined using a cut‐off score of 18 or more on the shortened version of the Chalder Fatigue Questionnaire (CFQ‐11) (Chalder et al.,  1993 ). Patients were excluded if they had any known cognitive impairments or lacked English proficiency. Patients could participate irrespective of disease stage and treatment history but were encouraged not to begin any new treatments for the study's duration. Outcomes were measured at three points in time: at baseline (T0), immediately following the intervention (T1), and at 2‐month follow‐up (T2). Qualitative data were collected from participants and RCs during implementation and at T1. Feasibility was assessed using several indicators: (i) eligibility rate (percentage of screened participants that met the eligibility criteria); (ii) enrolment rate (percentage of eligible participants that provided consent); (iii) retention rate (session attendance rates); (iv) completion rate (percentage of participants who completed four or more sessions); (v) completeness of participant outcome measures; (vi) RC fidelity to the manual (measured using fidelity checklists with session recordings) and (vii) RC feedback on the sessions (collected via session feedback forms regarding participants' understanding of, participation in, and enjoyment of the activities). Acceptability was assessed qualitatively by exploring RC and participant perceptions, experiences of, and satisfaction with the programme, as well as perceived consequences of taking part, via interviews. Semi‐structured interviews were conducted with each RC at T1 to explore their perceptions of the study training, implementation, session content, participant responses to the activities, the MEND manual, as well as suggestions for programme improvement. Group interviews were conducted with participants at T1 to assess their experiences of MEND, the session content and format, the RCs, and suggestions for improvement. Participants completed a sociodemographic questionnaire at T0. MEND's preliminary effectiveness was measured both quantitatively, using patient‐reported outcome measures (PROMs), and qualitatively during the interviews. PROMs included seven well‐validated scales: Fatigue was measured using the CFQ‐11, which assesses the severity of physical and psychological fatigue (sum score: 0–33) (Chalder et al.,  1993 ), and the 9‐item Fatigue Severity Scale (FSS) which assesses the impact of fatigue on functioning (sum score: 9–63) (Krupp et al.,  1989 ). CFQ‐11 scores exceeding 26 indicate severe fatigue (Cella & Chalder,  2010 ; Jackson,  2015 ), while FSS scores above 36 indicate a high level of fatigue (Krupp et al.,  1989 ). Symptoms of depression were measured using the 21‐item Beck Depression Inventory II (BDI‐II) (sum score: 0–63), where scores above 10 indicate mild clinical depression and those above 30 indicate severe depression (Beck et al.,  1988 ). Quality of life (QOL) was measured using two disease‐specific scales, namely, the 35‐item Stellenbosch Endometriosis Quality of Life (SEQOL) scale, which has been validated in South Africa and assesses eight dimensions of wellbeing (sum score: 35–175) (Roomaney & Kagee,  2018 ), and the 30‐item Endometriosis Health Profile (EHP‐30), which is commonly used to assess five dimensions of wellbeing (sum score: 0–120) (Jones et al.,  2001 ). Lower scores indicate better quality of life on both scales. A 29‐item version of the Cognitive and Behavioural Responses to Symptoms Questionnaire (CBRQ) (excluding the embarrassment avoidance cognition scale) was used to measure participants' responses to their symptoms (sum score: 29–145) with lower scores corresponding to a weaker presence of response (de Gier et al.,  2023 ). The single‐item VAS for Pain scale was used to measure pain intensity (ratings: 0–10) with higher ratings indicating greater pain intensity (Hawker et al.,  2011 ). Fatigue was measured using the CFQ‐11, which assesses the severity of physical and psychological fatigue (sum score: 0–33) (Chalder et al.,  1993 ), and the 9‐item Fatigue Severity Scale (FSS) which assesses the impact of fatigue on functioning (sum score: 9–63) (Krupp et al.,  1989 ). CFQ‐11 scores exceeding 26 indicate severe fatigue (Cella & Chalder,  2010 ; Jackson,  2015 ), while FSS scores above 36 indicate a high level of fatigue (Krupp et al.,  1989 ). Symptoms of depression were measured using the 21‐item Beck Depression Inventory II (BDI‐II) (sum score: 0–63), where scores above 10 indicate mild clinical depression and those above 30 indicate severe depression (Beck et al.,  1988 ). Quality of life (QOL) was measured using two disease‐specific scales, namely, the 35‐item Stellenbosch Endometriosis Quality of Life (SEQOL) scale, which has been validated in South Africa and assesses eight dimensions of wellbeing (sum score: 35–175) (Roomaney & Kagee,  2018 ), and the 30‐item Endometriosis Health Profile (EHP‐30), which is commonly used to assess five dimensions of wellbeing (sum score: 0–120) (Jones et al.,  2001 ). Lower scores indicate better quality of life on both scales. A 29‐item version of the Cognitive and Behavioural Responses to Symptoms Questionnaire (CBRQ) (excluding the embarrassment avoidance cognition scale) was used to measure participants' responses to their symptoms (sum score: 29–145) with lower scores corresponding to a weaker presence of response (de Gier et al.,  2023 ). The single‐item VAS for Pain scale was used to measure pain intensity (ratings: 0–10) with higher ratings indicating greater pain intensity (Hawker et al.,  2011 ). During the interviews, participants and RCs were asked about the perceived effect of the intervention, including changes in participant activity levels and mood. MEND was originally intended to be implemented face‐to‐face; however, the lockdowns imposed in response to the COVID‐19 pandemic prevented in‐person group meetings, and the intervention was adapted to be offered entirely online. Two RCs were recruited for the study via a social media advert posted to relevant professional association pages. Eligible participants identified via the screening survey were provided with the study information and required to provide signed consent. At enrolment, participants were invited to complete an online baseline survey containing the sociodemographic questionnaire and the seven PROMs (T0). Participants were assigned to one of three groups. The RCs held an introduction session to troubleshoot any technical issues with their groups and also shared the session meeting links. Sessions were offered weekly, in the evening or on the weekend, and were recorded to assess fidelity. RCs completed a feedback form after each session. After the final session, participants were invited to complete a post‐treatment survey containing the seven PROMs and to participate in a group interview (T1). The RCs were also interviewed at this time point (T1). The participants were invited to complete the follow‐up survey again 2 months after the intervention ended (T2). Sociodemographic and feasibility measures were analysed using frequencies, means, and standard deviations. Total and subscale scores were calculated for each measure in line with published guidelines. A complete case analysis was conducted for the PROMs data, with two incomplete data cases omitted, resulting in a dataset of 11 complete cases across the three survey points. The exploratory study was not sufficiently powered to assess effectiveness using hypothesis testing with p ‐values (Arain et al.,  2010 ; Lee et al.,  2014 ). Therefore, a Reliable Change Index (RCI) was calculated to assess whether changes in the measures were statistically reliable and reflected genuine improvement or deterioration in patients' condition, rather than variations due to measurement error (Jacobson & Truax,  1991 ). For each PROM, a RCI was calculated to assess individual response to treatment from T0 to T1 and T0 to T2, using the Standard Error of Measurement (SEM). Change indices were considered significant if they met or exceeded the ±1.96 statistical threshold (at the 95% confidence level). Interview recordings were transcribed verbatim in English and analysed using ATLAS.ti version 8. The data were read several times for familiarization and coded deductively in line with the predetermined research questions using thematic analysis (Braun & Clarke,  2019 ). Finally, fidelity to the manual was assessed by cross‐checking a random sample of session recordings against a fidelity checklist.

File S1