{'fraction_non_alphanumeric': 0.045704478276070305, 'fraction_numerical': 0.025935225502971743, 'mean_word_length': 5.134529147982063, 'pattern_counts': {'":': 0, '<': 18, '<?xml version=': 0, '>': 6, 'https://': 1, 'lorem ipsum': 0, 'www.': 1, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Psychosocial factors associated with pain and health‐related quality of life in Endometriosis: A systematic review

Abstract Background and Objective Endometriosis is associated with pain and impaired health‐related quality of life (HRQoL). Psychosocial factors have been associated with pain and HRQoL in other conditions, suggesting their potential relevance in Endometriosis. However, the role of psychosocial factors in this population has not been systematically explored yet. This systematic review aims to explore the association of psychosocial factors with pain intensity/severity and HRQoL in women with Endometriosis. Databases and Data Treatment Observational and experimental studies that explored the association of psychosocial factors with pain and HRQoL in women with Endometriosis were eligible. The following databases were searched: Medline, Embase, Cochrane library, Web of Science, PsychInfo and Cumulative index of nursing and allied health literature. The methodological quality was assessed, and findings were synthesized using narrative synthesis. Results Twenty‐seven studies were eligible for inclusion, which included 5419 women with Endometriosis. Catastrophising and anxiety were the factors most consistently associated with greater pain, whilst depression, anxiety and stress were related to worse HRQoL. Findings regarding depression and pain were mixed, and research on social factors was limited. Conclusions This systematic review highlights the role of psychosocial factors in Endometriosis. Anxiety, depression and catastrophising are suggested as potential treatment targets. The review also indicates the lack of research on other potentially important psychosocial factors, such as avoidance, perceived injustice and social support. Significance This systematic review explored the role of psychosocial factors in Endometriosis, suggesting that these are associated with pain and health‐related quality of life (HRQoL). Among the psychosocial factors included, anxiety, depression and catastrophising were the factors most often associated with pain and HRQoL in Endometriosis. These findings highlight the need to target psychological factors in the treatment of women with Endometriosis.


| INTRODUCTION
Endometriosis is a gynaecological condition in which endometrial cells grow in the surrounding areas outside the uterus, such as the ovaries and fallopian tubes (Farquhar, 2007). The prevalence of Endometriosis is around 10% in reproductive-age women (Rogers et al., 2009); however, the prevalence in infertile women can reach 40% (Meuleman et al., 2009). The primary symptoms of Endometriosis include chronic pelvic pain, dysmenorrhea (menstrual pain), dyspareunia (pain during sexual intercourse), dysuria and dyschezia (painful urination and defecation) and infertility (Ballard et al., 2008;Farquhar, 2007).
Recent meta-analyses have demonstrated that Endometriosis has a negative impact on mental health and quality of life, similar to that of chronic pain (Van Barneveld et al., 2022;Wang et al., 2021). Pain in Endometriosis is associated with greater depression and anxiety (Gambadauro et al., 2019;Pope et al., 2015), as well as poorer health-related quality of life (HRQoL) (Jia et al., 2012). Pain is a central symptom in Endometriosis as 64.2% of women with this condition report pelvic pain or dysmenorrhea (Ballard et al., 2008). Surgical removal of scar tissue has been used as a treatment option in Endometriosis; however, 20% of women with Endometriosis do not report pain improvement, and for some, the pain temporarily decreases but eventually returns (Abbott et al., 2004). Research in persistent pain demonstrates the influential and interactive role of psychosocial factors on pain, indicating that pain is better understood as a biopsychosocial experience (Gatchel et al., 2007). Systematic reviews in persistent pelvic pain and Vulvodynia have shown that psychosocial factors are associated with greater pain and worse quality of life (Chisari, Monajemi, et al., 2021;Riegel et al., 2014,), and they have also suggested that different psychosocial factors may be operating across different conditions. In Endometriosis, depression (Facchin et al., 2016), anxiety (Facchin et al., 2017;Lagana et al., 2017) and catastrophising (Martin et al., 2011) have been associated with greater pain.
Women with Endometriosis often experience stigma, invalidation and dismissal from health professionals (Cox et al., 2003;Lamvu et al., 2020;Sims et al., 2021). These experiences not only have an impact on the diagnosis of this condition, which takes 8-9 years on average (Ghai et al., 2020;Tewhaiti-Smith et al., 2022) but also increase psychological distress. For instance, feelings of pain invalidation by medical professionals have been shown to increase shame and depressive symptoms (Boring et al., 2021). Understanding the role of psychosocial factors in relation to outcomes in Endometriosis could raise awareness among healthcare professionals about their importance in the conceptualisation and management of this condition; this, in turn, can contribute to a shift from a biomedical view of the condition to a broader conceptualization that is more comprehensive. To support this, previous research testing psychological interventions in Endometriosis has shown significant improvements in participants' quality of life (Kold et al., 2012;Van Niekerk et al., 2019). To date, no systematic reviews have been conducted to examine the association between psychosocial factors, pain and HRQoL in Endometriosis. A systematic review investigating psychosocial factors could provide greater insight into the role of these variables in the context of Endometriosis, thus furthering biopsychosocially informed research and healthcare.
This systematic review aims to explore the association of psychosocial factors with (1) pain intensity and severity and (2) HRQoL in women with Endometriosis.

| Protocol
This systematic review was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Page et al., 2021a(Page et al., , 2021b. The systematic review protocol is available at: https://www.crd.york.ac.uk/prosp ero/displ ay_record. php?Recor dID=238130

| Eligibility criteria
Eligible studies had a quantitative observational or experimental design and explored the association, through correlation or regression analyses, of psychosocial factors with pain intensity and severity, and HRQoL in women with Endometriosis. Only studies published in English with full-text available were included, and no publication date restrictions were applied. Women aged 16 years or older who had a confirmed diagnosis of endometriosis were included. This age limit was applied because all the female puberty milestones are reached by the age of 16 (Brix et al., 2019) and Endometriosis is most commonly diagnosed in women of reproductive age (i.e., 15-49) (Haas et al., 2012). Psychosocial factors refer to any cognitive (e.g., catastrophising), emotional (e.g., anxiety), behavioural (e.g., coping) and social factors (e.g., relationship status), as well as personality traits (e.g., neuroticism).

| Search strategy and selection
A systematic search was conducted on Medline, Embase, Psychinfo, Cumulative index to nursing and allied health literature (CINAHL), Cochrane library and Web of Science in April 2021. The database search was performed using key terms for pain, HRQoL and psychosocial factors combined with the operators "OR" and "AND". Various keywords were used to describe psychological (e.g., catastrophising) and social factors (e.g., social support), which were combined using the operator "OR". Exploded terms and Medical Subjects Headings (MeSH) were used to maximize results. Publication date restrictions were not applied. The full search terms are presented in Table S1. Identified studies from the database search were assessed in three stages using the PRISMA 2020 flowchart for systematic reviews (Page et al., 2021a(Page et al., , 2021b. Articles were saved on EndNote X9 reference manager (Clarivate, 2013). These were then sorted alphabetically, and duplicates were removed. Titles, abstracts and full texts were screened initially by the first author (MK) using predefined eligibility criteria, and ineligible studies were excluded for reasons. Double screening was conducted by the other two coauthors (SW and CC). The screening procedure is presented in the PRISMA 2020 flowchart (Figure 1) (Page et al., 2021b).

| Data extraction and synthesis
Data from the included studies were extracted by MK. Extracted information included: study details (reference, country); study design; sample size; sociodemographic characteristics (age); outcome variable(s); outcome measure(s) (i.e., pain and HRQoL); psychosocial factor(s); psychological measure(s); statistical analysis; key findings. Findings of the systematic review were presented using narrative synthesis, according to the synthesis without meta-analysis (SWiM) in systematic reviews (Campbell et al., 2020). Due to the heterogeneity of the psychosocial factors included and the fact that many studies did not report the effect sizes, a metaanalysis was not performed.

| Risk of bias assessment
The methodological quality and risk of bias of eligible full-text articles were assessed using an adapted Critical Appraisal Skills Programme [CASP] checklist (CASP, 2019). Tailoring the quality assessment tool is recommended in the Cochrane Handbook (Higgins et al., 2011). The adapted checklist was developed by the authors and was based on the case-control and cohortstudy CASP checklists. It included eight questions with a three-point response scale (i.e., "yes", "no" and "cannot tell"). To assess the quality of studies, the "yes" answers (i.e., yes = 1) were added up. Scores from 0 to 2 were classified as low quality, scores from 3 to 5 as medium quality and scores from 6 to 8 as high quality. As this was an adapted scale, this tool did not undergo its own validation. The CASP checklist that was used is presented in Table S2.

| Effect measures
The primary outcomes were pain intensity/severity, and HRQoL in Endometriosis. These were explored using associations (i.e., bivariate correlations and regression coefficients) between psychosocial factors and the outcome measures. Correlation coefficients were interpreted as small (r = 0.10), medium (r = 0.30) and large (r = 0.50). Similarly, the effect sizes of regression coefficients were classified as small (f 2 = 0.02), medium (f 2 = 0.15) and large (f 2 = 0.35). This classification was informed by Cohen's effect size guide (1992). The effect sizes for the regression were calculated using the r 2 coefficient, when available (Table 1).

| RESULTS
The database search resulted in 5286 records. Following the removal of duplicates and the screening of title and abstract, 211 full-text articles were assessed for inclusion. 27 studies were included in this systematic review. The number of studies included at each stage is presented in the PRISMA flowchart ( Figure 1).

| Overview of studies
All included studies were observational, and 26 of them were cross-sectional. One study (Martin et al., 2011) was prospective and had a 12-month follow-up. A mixedmethod study was included (Zarbo et al., 2019), but only the quantitative data were extracted. The 27 included studies composed of 5419 participants in total. Two studies included the same sample (Melis et al., 2014(Melis et al., , 2015. Overall, the age of participants ranged between 17 and 71 years old, and the mean age ranged between 30.5 and 36.7 years old. Nine studies took place in Italy, three in Brazil, two in the United States and two in Poland whilst the remaining 11 studies took place in various countries. One study (De Graaff et al., 2013) was multicentre and participants were F I G U R E 1 Study flow diagram according to PRISMA 2020 (Page et al., 2021a(Page et al., , 2021b Table 2. Psychological factors were grouped as general distress (anxiety, depression, stress, generalized worry and somatisation), cognitive factors (catastrophising, beliefs, self-efficacy, rumination, self-esteem, illness acceptance), behavioural factors (self-care activities), emotion regulation factors (emotion regulation and alexithymia), social factors (relationship status, presence of partner and marital satisfaction) and personality traits (character/temperament traits).
The included studies assessed pain and HRQoL. Pain was assessed using numerical rating, visual analogue scales or the short-form McGill pain questionnaire (SF-MPQ) (Melzack, 1975). Given that studies used different terms to quantify pain (i.e., pain intensity or severity), albeit they used the SF-MPQ (Carey et al., 2014;Martin et al., 2011;Zarbo et al., 2019), the terms pain intensity and pain severity were considered synonymous in this review. HRQoL was measured using the Endometriosis health profile-30 (EHP-30) (Jones et al., 2001) or the short-form health survey (SF-36) (Ware Jr & Sherbourne, 1992). To explore these outcomes in relation to psychosocial factors, 14 studies used bivariate correlations (Pearson's r and Spearman rho), ten studies used simple or multiple linear regression, whilst three studies used both Pearson's r correlation and multiple linear regression.

| Risk of bias
Twenty-two studies were rated as medium methodological quality, and five studies as high quality (Andysz & Merecz-Kot, 2021;De Graaff et al., 2013;Martin et al., 2011;Martins et al., 2021;O'Hara et al., 2021). The risk of bias assessment for each study is presented in Table S3.

| MAIN RESULTS
The findings of included studies for pain and HRQoL are presented below and are also shown in Tables 3 and 4. Eight studies did not report the r 2 coefficient of the regressions, and thus, it was not possible to calculate the effect size. In two studies, the standardized regression coefficient β was not given, and therefore only the unstandardised B regression coefficients are presented in the results.

| Generalized worry
One study explored the association between pain and generalized worry, in which a positive correlation was found (r = 0.32, p < 0.001) (Zarbo et al., 2019).

| Catastrophising
Three studies explored the association between pain and catastrophising in Endometriosis. Zarbo et al. (2019) found that catastrophising was linked with greater pain at baseline (r = 0.268, p < 0.001), whilst Martin et al. (2011) reported that baseline catastrophising predicted pain severity at 12 months (β = 0.18, p < 0.05, r 2 = 0.03). In both studies, the effect size of the association was small. In another study (Carey et al., 2014), catastrophising was not associated with the total pain score (p = 0.055) but with the affective pain score (β = 0.66, p < 0.01).

| Self-efficacy
One study found that self-efficacy, defined as "someone's belief that they are able to carry out a behaviour" (Bandura, 1977), was associated with improved physical (B = 1.30, p < 0.001) and mental HRQoL (B = 1.55, p < 0.001), after controlling for demographic characteristics and pain (O'Hara et al., 2021).

| Beliefs about pain control
One study (Bylinka & Oniszczenko, 2016) found that beliefs about internal control of pain (i.e., the individual's belief that they can control pain) were linked with greater pain intensity (r = −0.31, β = −0.24, p < 0.01). Doctor control beliefs (i.e., beliefs that doctors can control pain) were correlated with more pain (r = 0.33, p < 0.01), however, the regression analysis was not significant (p > 0.05).
Beliefs that pain is controlled by chance events (e.g., belief that being in pain depends on luck) were not associated with pain (p > 0.05).
van Aken et al. (2017) found that pain cognition was associated with impaired HRQoL, measured by the EHP-30 (r = 0.58, β = 0.42, p < 0.001) and SF-36 (r = 0.58, β = 0.42, p < 0.001). van Aken et al. (2017) defined pain cognition as "the psychological aspects of pain catastrophising, pain anxiety and pain vigilance." This was measured using the average z scores of these three questionnaires. Andysz and Merecz-Kot (2021) explored illness acceptance in relation to HRQoL and found that after controlling for baseline variables (e.g., infertility, pain catastrophising), acceptance was linked with better pain-related HRQoL (β = −0.27, p < 0.001). More specifically they used the pain subscale of EHP-30, which assesses the effect of pain on the patient's life.

| Behavioural factors
Interestingly, a greater number of self-care activities was associated with worse physical HRQoL (B = -0.41, p < 0.05) but not with mental HRQoL (p > 0.05) (O'Hara et al., 2021). The authors assessed activities that people used to manage symptoms of Endometriosis, such as changing diet, exercising or taking supplements.

| Temperament and character traits
Two studies tested the association between temperament/personality traits and pain intensity/severity in Endometriosis. Facchin et al. (2016) found that harm avoidance, defined as "the tendency to be fearful, worried and sensitive to criticism" (Naylor et al., 2017), was linked with greater pelvic pain (B = 0.08; p < 0.01). Conversely, self-directedness, defined as "someone's belief that they can control their life and solve their problems" (Farmer & Goldberg, 2008), was associated with less pain (B = -0.05; p < 0.05). Bylinka and Oniszczenko (2016) reported that endurance, which refers to "the ability to go through challenging or demanding situations" (Strelau & Zawadzki, 1993) was associated with greater pain intensity (r = −0.51; β = 0.56, p < 0.001).

| Social factors
None of the included studies assessed social factors in relation to pain in Endometriosis.
Three studies explored the association between social/dyadic factors and HRQoL. O'Hara et al. (2021) found that being in a stable relationship was associated with improved mental HRQoL (B = 3.51, p < 0.001) but not with physical HRQoL (p > 0.05). Similarly, De Graaff et al. (2013) reported that after controlling for pain and number of comorbidities, having a partner present was linked with better mental (β = 0.14; p < 0.001), but not physical (p > 0.05) HRQoL. Martins et al. (2021) found that greater marital satisfaction was correlated with improved HRQoL (r = 0.193; p < 0.05), however this association was not significant after controlling for covariates (e.g., psychological comorbidity) in regression (β = −0.003, p > 0.05).

| DISCUSSION
This is the first systematic review, to our knowledge, to explore the association between psychosocial factors with pain and HRQoL in Endometriosis. Pain and HRQoL were the two outcomes studied. The psychosocial factors most frequently explored were depression, anxiety and catastrophising. Many psychosocial factors were only researched once, and there was scarce research into social factors.

| Psychological factors associated with pain
The positive association between anxiety and pain found in this review is consistent with systematic reviews in general pelvic pain (Lagana et al., 2017;Riegel et al., 2014;Vitale et al., 2020). However, the included studies that examined anxiety and pain were cross-sectional, so the direction of association is unclear. Conversely, the associations between depression and pain were mixed, since three studies reported significant positive associations, and three studies did not. Similar to anxiety, all these studies were cross-sectional. These findings are surprising since previous systematic reviews have shown significant associations between depression and pelvic pain in Endometriosis and Vulvodynia (Chisari, Monajemi, et al., 2021;Gambadauro et al., 2019;Pope et al., 2015).
A possible explanation for these mixed results is that a confounder, such as cognitive appraisal or coping behaviours, could disrupt the association between affective outcomes and pain in Endometriosis, and none of these studies controlled for confounders. Research in persistent pain indicates that patients' appraisal of the impact and controllability of pain mediates the association between depression and pain (Gatchel et al., 2007;Turk et al., 1995). Furthermore, other unmeasured psychosocial variables may mask the association between depression and pain. Eriksen et al. (2008) reported that emotion suppression, which is prevalent in Endometriosis (Zarbo et al., 2018), could result in the underreporting of depressive symptoms and mask the association between depression and pain. Stigma is another factor that could mediate the association between pain invalidation and depression (Boring et al., 2021). Further research, which controls for confounders and has longitudinal designs, is needed to elucidate the relationship between depression and pain in this population.
In addition to anxiety and depression, catastrophising was linked with greater pain in three studies, one of which was longitudinal (Martin et al., 2011). The positive association between catastrophising and pelvic pain is consistent with previous systematic reviews (Chisari, Monajemi, et al., 2021;Huang et al., 2020). The role of catastrophising in persistent pain has been highlighted in the fear-avoidance model (Vlaeven et al., 2016). According to this, catastrophic interpretations of pain symptoms could increase physiological arousal, avoidance behaviour and fear, which could, in turn, increase pain and disability (Gatchel et al., 2007;Vlaeven et al., 2016). Fear-avoidance has been associated with pain in women with chronic pelvic pain and sexual pain (Gatchel et al., 2007;Thomtén et al., 2014). Previous studies have also found that catastrophising mediates the association between depression and pain (Kim et al., 2021;Wood et al., 2013). The mediating role of catastrophising may further explain the mixed findings earlier discussed regarding the association between depression and pain in Endometriosis.
The review also found that other psychological factors were associated with pain; however, these were explored only once and therefore, their implications may be limited. For instance, rumination, alexithymia and beliefs about internal control of pain were all associated with greater pain in Endometriosis. Previous research on the role of perceived pain control (Gatchel et al., 2007) and alexithymia (Di Tella & Castelli, 2016) in persistent pain showed mixed results. As for rumination, previous research has found a positive correlation between rumination and pain severity, although this was not significant in regression analysis (Craner et al., 2016). Lastly, endurance and selfdirectedness were associated with decreased pain, whereas harm avoidance was linked with greater pain. A critical review suggests that people living with persistent pain present higher harm avoidance and lower self-directedness compared to controls (Naylor et al., 2017), and these coping strategies may in turn increase or decrease pain levels.

| Psychological factors and healthrelated quality of life
Overall, the studies of the review found that depression and anxiety were associated with worse HRQoL. These findings are in line with previous systematic reviews, according to which, depression and anxiety negatively impact HRQoL in other long-term health conditions (Ali et al., 2010;Blakemore et al., 2014). Catastrophising was also linked with worse HRQoL in this review; this was found to partially mediate the association between pelvic pain and HRQoL in Endometriosis (Mundo-López et al., 2020). The mediating effect of catastrophising on the association between pain and HRQoL has also been found in Fibromyalgia (Galvez-Sánchez et al., 2020).
A range of psychological factors in relation to HRQoL was only explored once in Endometriosis. These include negative body attitude, alexithymia and difficulties in emotion regulation, which were associated with impaired HRQoL. Previous research in persistent pain indicates that alexithymia is associated with reduced functioning (Di Tella & Castelli, 2016), and emotion regulation with impaired quality of life (Agar-Wilson & Jackson, 2012). Similarly, body image has been linked with worse quality of life in Fibromyalgia (Akkaya et al., 2012). One study found that illness acceptance was associated with improved HRQoL, even after controlling for covariates. Acceptance of pain has also been linked with greater quality of life in people with chronic back pain (Mason et al., 2008). Lastly, this review found that self-efficacy was linked with improved HRQoL, which is confirmed by previous research in persistent pain (Gatchel et al., 2007).

| Social factors associated with pain and health-related quality of life
Overall, social factors were narrowly researched. None of the included studies assessed social factors in relation to pain, whilst only three studies assessed the association between social/dyadic factors and HRQoL. More specifically, the presence of a partner was associated with better mental, but not physical HRQoL (De Graaff et al., 2013;O'Hara et al., 2021), whilst marital satisfaction was not significantly associated with HRQoL after controlling for covariates (Martins et al., 2021). Findings indicate that relationship status and satisfaction may influence only the mental component of HRQoL. Another included study found that being in a stable relationship was associated with reduced rumination in Endometriosis, whilst rumination was linked with greater pain (Facchin et al., 2017). The lack of existing research on the association of social factors with pain and HRQoL was surprising, considering the clear interpersonal and social impact of genitopelvic pain (Rosen & Bergeron, 2019). Indeed, social and interpersonal factors influence a range of physiological and psychological outcomes in persistent pain (Gatchel et al., 2007) and Vulvodynia (Bergeron & Rosen, 2020). The significant psychosocial impact of Endometriosis has also been highlighted in qualitative research, which showed that Endometriosis disrupts the personal identity of women (Cole et al., 2021). Furthermore, a significant social context for women with endometriosis is the experience within the healthcare system. This affects the psychological experience of women, who may feel disbelieved, uncertain and unsafe with no guarantee of support for debilitating symptoms (Sims et al., 2021;Tewhaiti-Smith et al., 2022). It also can directly affect physiological outcomes due to factors like delay in diagnosis and lack of access to treatment (Tewhaiti-Smith et al., 2022). Thus, further research is needed to investigate the association between social factors and pain and interference in this population.

CLINICAL PRACTICE AND FUTURE RESEARCH
To better represent the findings of this review and orient future research, a summary figure is provided (Figure 2). This highlights the role of depression, anxiety and catastrophising in pain and HRQoL. Given the relevance of these factors, efforts to improve emotional functioning may lead to improvements in pain and quality of life in this population. Future research and clinicians could explore psychosocial approaches that may improve emotional functioning, reduce pain impact, and enhance women's quality of life, such as Cognitive Behavioural Therapy and Acceptance and Commitment Therapy. These have been successfully applied to persistent pain (Trindade et al., 2021;Williams et al., 2020), suggesting their potential in Endometriosis.
This review also highlights the lack of existing research into social factors. The lack of social factors calls for more research in the field. Previous research has indicated that experiences of dismissal have been reported by women with Endometriosis (Cox et al., 2003). Similarly, women with Endometriosis report that clinicians are not willing to understand their individual needs (Lamvu et al., 2020). This is consistent with past research that also highlights that pain symptoms expressed by women are more often underestimated (Samulowitz et al., 2018;Zhang et al., 2021). This suggests social and systemic factors need further exploration and consideration, as potentially relevant constructs such as perceived injustice (Sullivan et al., 2008) have yet to be applied to Endometriosis.
Lastly, research on protective factors for pain and HRQOL (e.g., cognitive flexibility, acceptance) needs further research. This would also help clinicians focus on what is important for women with Endometriosis, potentially reducing distress and impact.

| LIMITATIONS
This systematic review presents limitations. Firstly, all studies except one were cross-sectional, which means that causal relationships cannot be inferred. Research on social and dyadic factors, especially in relation to pain in Endometriosis was very limited. Given that most studies did not include confounders in the regression analysis, F I G U R E 2 Summary figure of psychosocial factors in relation to pain and HRQoL in endometriosis. Green arrows represent positive associations; red arrows negative associations; double arrows bidirectional associations; solid arrows associations found in women with endometriosis; dotted arrows associations are hypothetical associations. Depression is associated with greater pain and worse HRQoL, whilst pain also impairs HRQoL. There is a bidirectional association between pain and depression, and pain and catastrophising. Note 1: HRQoL: Health-related quality of life Note 2. Green arrows represent positive associations; red arrows represent negative associations; double arrows represent bidirectional associations; solid arrows reflect associations found in the included studies of women with Endometriosis; dotted arrows display hypothetical associations. Note 3: Depression is associated with greater pain and worse HRQoL, whilst pain also impairs HRQoL. There is a bidirectional association between pain and depression, and pain and catastrophising. any associations found could be partially or completed attributed to other variables. Studies did not include women under the age of 17 and most of them were conducted in developed Western countries. The authors were unable to access unpublished studies or translate non-English papers, which may have led to increased publication bias.

| CONCLUSIONS
The systematic review explored psychosocial factors in relation to pain and HRQoL in Endometriosis. The review indicates that catastrophising and anxiety are associated with greater pain, whereas anxiety and depression are related to worse HRQoL. Research on other psychosocial factors, particularly social variables needs further exploration. Nevertheless, the review findings indicate that a psychosocial conceptualisation of Endometriosis is supported. Targeting depression, anxiety, and catastrophising in future treatments of women with Endometriosis may lead to improved outcomes and is therefore warranted.

AUTHOR CONTRIBUTIONS
Michail Kalfas: draft protocol, develop and perform search strategy, obtain full-text reports, carry out study screening, interpret findings and draft final review. Claudia Chisari: draft protocol, develop search strategy, carry out study screening, interpret findings and draft final review. Sula Windgassen: draft protocol, develop search strategy, carry out study screening, interpret findings and draft final review. All authors discussed the results and commented on the manuscript.