Relationship between endometriosis and mental health. A systematic review and meta-analysis

Introduction: The chronic gynecological condition endometriosis affects about 10 percent of reproductive aged women and imposes a heavy physical and psychological burden. The impact of pain and infertility is well docu- mented, but the link between endometriosis and mental health (depressive and anxiety), in particular, is not well studied. In this systematic review and meta-analysis, we synthesize evidence on the association between endo- metriosis and mental health outcomes, specifically anxiety and depression.

PubMed, Cochrane Library and Google Scholar were searched comprehensively to identify studies that have reported the association of endometriosis and mental health outcomes. Nine studies were included af- ter applying predefined inclusion and exclusion criteria from 1,632 articles screened. The Newcastle-Ottawa Scale (NOS) was used to assess study qual- ity and random effects meta-analyses were performed using R. Relative risk (RR) values for anxiety and depression among women with endometriosis were pooled as the primary outcomes.

The meta-analysis revealed a significant association between en- dometriosis and anxiety (pooled RR = 2.82; 95% CI: 1.69–4.68, p < 0.001) and depression (pooled RR = 2.93; 95% CI: 1.63–5.25, p < 0.001). Substantial heterogeneity was observed in both analyses (I ² = 100%), reflecting vari- ability in study designs and populations. Funnel plots showed moderate asymmetry, suggesting potential publication bias. Statistical heterogeneity was further quantified with τ ² values of 0.6032 for anxiety and 0.794 for de- pression, indicating considerable between-study variability. These findings underscore the heightened mental health burden in women with endome- triosis.

Endometriosis patients are more likely to develop anxiety and depressive symptoms due to pain and diagnostic evaluation and related psychosocial factors. This study stresses the importance of integrated care, which involves screening and treatment for mental health problems in addi- tion to conventional medical care. Future work should aim to reduce hetero- geneity and examine potential pathways through which these relationships exist in order to develop specific prevention strategies. Key words: endometriosis, anxiety, depression, mental health, systematic review, meta-analysis, Newcastle-Ottawa Scale.

Endometriosis is a chronic gynecological disease, and this disease is defined by the presence of endometrial tissue outside the uterine Obstetrics and Gynecology Systematic review/Meta-analysis Wenwei Li, Huiyan Feng, Qingjian Ye 1986 Arch Med Sci 5, October / 2025 cavity, which can cause inflammation, pain and infertility [1, 2]. The incidence of endometriosis is about 10% of reproductive-aged women world- wide, and it is a  significant source of physical and mental health loss [3]. The condition is often associated with menstrual cramps, pain during intercourse, and chronic pelvic pain that signifi- cantly interferes with daily activities and well-be- ing [4, 5]. Over the past few years, there has been an increased emphasis on the psychologi- cal effects of endometriosis. Research conducted by various authors indicates that this condition elevates the risk of developing depression and anxiety [6, 7]. Endometriosis and mental health relate to different biopsychosocial factors. Pelvic pain caused by endometriosis has a negative impact on both physical well-being and psychological well-being, reducing the ability to cope with stress and increasing feelings of hopelessness [8–10]. Patients with endometriosis are usually diagnosed late, which leads to a longer duration of suffering and frustration [11]. Moreover, due to cultural taboos regarding pain and gynecolog- ical problems, women often lack social support for the psychological ramifications of the disease [12]. These challenges highlight the need to ex- plore the mental health aspects of endometriosis in detail to enhance the understanding of man- agement approaches [13]. Endometriosis and mental health issues are intertwined and cannot be easily separated [14]. The pain is often chronic and thus can cause de- pression and psychological distress; there is often a  delay in receiving a  diagnosis, and menstrual pain is still viewed as normal by society, which makes women feel unheard and unappreciated [15]. Moreover, it has been proposed that there is a bidirectional relationship between endometrio- sis and mental health which may be mediated by such common factors as inflammation, hormon- al imbalance, and neuroendocrine alterations in response to stress [16]. Despite the increasing awareness of such challenges, however, systemat- ic reviews of the literature examining this relation- ship are still scarce [17]. This study reviewed and meta-analyzed the literature on the relationship between endome- triosis and mental health, hoping to identify the risk factors that can predict the mental health of patients with endometriosis and provide certain recommendations for clinical treatment.

The present systematic review and meta-anal- ysis adhered to the guidelines set out by the PRISMA statement. This meta-analysis has been registered in PROSPERO, and the PROSPERO ID of this study is 1067012. The following sections de- scribe the methodological approach used in this research. Search strategy An effective search plan was designed to iden- tify studies that have examined the link between endometriosis and mental health, concentrating on depressive episodes. These databases includ- ed PubMed, Cochrane Library, and Google Schol- ar. Search terms included combinations of the following keywords: “endometriosis”, “mental health”, “depression”, “anxiety”, “psychological distress”, and “quality of life”. The MeSH terms are “endometriosis” and “mental illness”, and the free words are “mental health”, “depres- sion”, “anxiety”, “psychological distress”, and “quality of life”. MeSH terms + free terms were used for searching. The use of Boolean operators such as AND and OR was used to narrow down the search outcomes. The following limitations were applied while searching: Only articles in the English language were considered, and no year

were imposed to ensure comprehen- siveness of coverage. It should be noted that the presented search was updated in [specific month and year]. Inclusion and exclusion criteria Studies were included if they met the following criteria: 1. Participants were women with a confirmed di- agnosis of endometriosis. 2. The study assessed mental health outcomes, specifically depressive events. 3. Original research studies utilizing cross-section- al, cohort, case-control, or population-based designs. 4. Studies reporting quantitative data on depres- sion linked to endometriosis. 5. Articles published in peer-reviewed journals. Exclusion criteria included: 1. Studies with insufficient data on mental health outcomes. 2. Non-original research articles, including reviews, editorials, and case reports. 3. Studies focusing solely on interventions without baseline mental health assessment. 4. Non-English language articles. Study screening Selection of studies for the review was done in three steps. First, titles and abstracts of the articles identified through the database search- es were reviewed for relevance. Second, the titles and abstracts of the searched publications were screened to determine the applicability of the in- Relationship between endometriosis and mental health. A systematic review and meta-analysis Arch Med Sci 5, October / 2025 1987 clusion and exclusion criteria to the full-text ar - ticles. The screening process was conducted in a  blinded manner by two authors, and any dis- agreements were resolved through conferencing or consulting with a third author. Data extraction Data extraction was conducted manually by two authors using a data extraction form. Data elements extracted were the study details such as author, year, country, study type, sample size, and diagnostic criteria used, participant char - acteristics, mental health outcomes such as prevalence of depression, and statistical data such as effect size and confidence intervals. In case of inconsistency in the extracted data, the problem was discussed and resolved among the reviewers. Quality assessment The quality of the included studies was as- sessed based on the Newcastle-Ottawa Scale (NOS) for case-control studies. NOS was used to score all the included literature, and the fol- lowing 8 questions were judged and scored. In addition to the maximum of 2 stars for com- parability, there was a  maximum of 1 star for other items, and the total possible score was 9 stars – the higher the score, the higher the quality of the study [18]. The NOS assesses three domains: inclusion criteria, matching of the groups, and definition of the outcomes. Both authors separately reviewed each study and resolved any difference in opinion to reach a consensus. Table I shows the quality assess- ment of the studies involved in the systematic review and meta-analysis. Table I. Quality assessment of included studies using the Newcastle-Ottawa Scale (NOS) Study authors Selection (max. 4) Comparability (max. 2) Outcome/Exposure (max. 3) Total score (max. 9) Friedl et al., 2015 4 Representativeness of sample, selection of controls, definition of exposure, ascertainment of endometriosis 2 Adjustment for confounders, e.g., age 3 Adequacy of follow- up, blinded outcome assessment, validated measurement tools 9 Škegro et al., 2021 4 Representativeness of sample, consecutive patients, exposure definition, ascertainment of endometriosis 2 Adjustment for pain severity, age 3 Validated tools for mental health, blinded outcome assessment, statistical clarity 9 Gao et al., 2020 4 Population-based registry, validated exposure definition, representativeness, large sample 2 Adjustment for confounders, e.g., age, comorbidities 3 Administrative database, blinded outcome data, validated registry 9 Estes et al., 2021 3 Validated exposure definition, representativeness, incomplete description of controls 2 Adjustment for pain, comorbidities 3 Validated outcome measurement, large cohort, use of health claims 8 Chen et al., 2016 [30] 4 Large sample size, validated exposure, population-based registry, representativeness 2 Adjustment for demographics, comorbidities 3 Adequate follow-up, registry-based outcome assessment, statistical robustness 9 Márki et al., 2017 3 Small sample size but well-defined criteria, validated exposure, limited representativeness 1 Adjustment for demographics only 3 Validated tools for mental health, appropriate follow-up 7 Marschall et al., 2021 3 Small sample size, well- defined criteria, limited representativeness 2 Adjustment for narrative identity, pain 3 Validated mental health tools, robust statistical methods, blinded assessment 8 Wang et al., 2023 4 Population-based registry, large sample, representativeness, validated exposure 2 Adjustment for demographic and clinical factors 3 Validated tools for psychiatric assessment, long follow-up 9 Facchin et al., 2017 3 Limited sample, validated exposure definition, representativeness issues 1 Adjustment for pain only 3 Validated mental health tools, rigorous statistical analyses 7 Wenwei Li, Huiyan Feng, Qingjian Ye 1988 Arch Med Sci 5, October / 2025 Sensitivity/heterogeneity tested by one-by- one elimination method After eliminating each included study in se- quence, a  meta-analysis was re-conducted on the remaining studies to observe the changes in the combined effect size and confidence interval. If significant changes occur after excluding one study, it indicates that the original conclusion may have been overinfluenced by that study, is at risk of bias, or lacks robustness. Heterogeneity of binary categorical variables The L ‘Abbe plot was used for the meta-anal- ysis heterogeneity test of the binary variable data from RCTs. In this study, the presence or absence of depression and anxiety can be de- termined, which was applicable to binary cate- gorical variables. The incidence of events in the treatment group was plotted relative to that in the control group for each study. If the study

were homogeneous, all points would be linearly distributed. Significant deviations from this line indicated heterogeneity in the study results. Meta-regression analysis A regression model to explore the relationship between research characteristics (covariates) and effect size (relative risk – RR) was established, thereby explaining the heterogeneity among dif- ferent studies. This study conducted a  meta-re- gression analysis using a  random effects model. The random effects model assumes that the stud- ies did not have a common effect scale, but rather each had its own effect scale, which was defined as a random variable that follows a normal distri- bution. Data synthesis Meta-analysis was performed using R software, version 4.2.3. Depressive events concerning endo- metriosis were evaluated employing random-ef- fects models as a way of managing heterogeneity of the studies. The main measure of interest was the overall pooled prevalence of depressive symp- toms in women with endometriosis compared to the control group. The heterogeneity was es- timated by the I² statistic. Stata 17 software was used to plot the heterogeneity shown by the elim- ination method and the meta-regression analysis graph.

When the databases were searched exhaus- tively, 1632 articles were found. After excluding the duplicate records and using the inclusion and exclusion criteria, nine articles were included in this systematic review. The PRISMA flow diagram outlining the selection of the included studies is shown in Figure 1. The quality of the included studies was evaluated with the Newcastle-Otta- wa Scale (NOS) for selection, comparability, and outcome/exposure. Table I  presents the quality assessment of the included studies, where all the selected articles have met the methodological standards. NOS scores of all included documents were greater than or equal to 7, and the docu- ments [19–21] were scored with a full score of 9. The overall quality of the included literature was relatively high. Study characteristics The combined studies presented in this review reflect various populations, designs, and geo- graphical areas, providing a  broad perspective Figure 1. PRISMA flow diagram of included studies Records identified from: Databases (n = 1632) Records screened (n = 1053) Reports sought for retrieval (n = 69) Reports assessed for eligibility (n = 48) Studies included in review (n = 9) Records removed before screening: Duplicate records removed (n = 579) Records excluded (n = 984) Reports not retrieved (n = 21) Reports excluded: • Not specifically focusing on effect of endometriosis oh mental health (30) • Unclear results (n = 5) • Lack of analysis of correlation between the variables (4) IdentificationIncluded Screening Relationship between endometriosis and mental health. A systematic review and meta-analysis Arch Med Sci 5, October / 2025 1989Table II. Detailed characteristics of included studies Study authors Year Country Study design Sample size Population Diagnostic

Mental health outcomes Measure- ment tools Key findings Conclusion Friedl et al., 2015 2015 Austria Cross- sectional survey 62 patients, 61 controls Women aged 18–44 with confirmed endometriosis Histological confirmation Anxiety, depression SF-36, HADS-D, EHP-30 Moderate to severe anxiety (29%) and depression (14.5%) in patients. SF-36 showed significant impairments in general health and mental health in patients (p < 0.001). Need for psychosomatic treatment due to elevated mental health burden in patients. Škegro et al., 2021 2021 Croatia Observational cross- sectional 79 women Women with histologically confirmed endometriosis Histological confirmation Depression, anxiety, stress EHP-5, DASS-21, VAS Depression (44.3%), anxiety (25.3%), stress (31.7%). Moderate correlations between EHP-5 and mental health indicators (r > 0.5). Multidisciplinary care required to address mental health and physical symptoms in endometriosis. Gao et al., 2020 2020 Sweden Longitudinal cohort study 854,361 (14,144 patients) Women born 1973–1990, aged 14–43 ICD-9/10 codes in national registry Depression, anxiety, ADHD, alcohol/drug dependence National patient register Women with endometriosis had higher RRs for mental health outcomes: depression (RR = 1.89), anxiety (RR = 1.82), alcohol dependence (RR = 1.93). Bidirectional associations observed between depression/anxiety and endometriosis. Comorbidity with depression/anxiety suggests shared familial liability. Multidisciplinary care recommended. Estes et al., 2021 2021 USA Retrospective cohort study 72,677 patients, 147,251 controls Women aged 18–50 with endometriosis ICD-9/10 codes and laparoscopic confirmation Anxiety, depression, self-directed violence Claims data from health database RRs: Anxiety (1.38), depression (1.48), self-directed violence (2.03). Pain-related comorbidities were significant risk factors. Regular screening and care for mental health outcomes are crucial for women with endometriosis. Chen et al., 2016 [30] 2016 Taiwan Longitudinal cohort study 10,439 patients, 10,439 controls Women aged ≥ 18 with no psychiatric history ICD-9-CM codes, ultra- sonography Major depression, anxiety NHIRD data RRs for depression (1.56), anxiety (1.44). Younger women (< 40 years) at higher risk. Comprehensive care addressing physical and psychological needs is essential. Márki et al., 2017 2017 Hungary Cross- sectional study 193 women Women aged 18–50 years Gynecological evaluation, imaging Anxiety, depression, psychological distress SF-36, HADS, PSS, DERS Anxiety symptoms (54.79%), depressive symptoms (20.32%). Pain and emotion regulation difficulties significantly reduced HRQoL. Pain management and emotional regulation interventions can enhance HRQoL. Wenwei Li, Huiyan Feng, Qingjian Ye 1990 Arch Med Sci 5, October / 2025 on the association between endometriosis and mental health. These studies were conducted in countries such as Austria, Croatia, Sweden, United States, Taiwan, Hungary, Denmark, and Italy and were published between 2015 and 2023. The type of studies used in the review were cross sectional, case control, prospective cohort, and population based. The sample sizes ranged from 62 participants in some research to more than 850,000 women in others. Participants were mainly female endome- triosis patients who were diagnosed using histo- logical confirmation, imaging, or through registry diagnostic codes. Table II displays the study char- acteristics such as diagnostic methods, mental health outcomes, and measurement tools. Mental health outcomes in women with endometriosis Prevalence of depression and anxiety Each of the studies included in the systematic review and meta-analysis found that women di- agnosed with endometriosis had a  significantly higher rate of depression and anxiety, particularly depression and anxiety, compared with the gener- al population. In their study, 27.7% of women with endometriosis had moderate to severe anxiety levels and 14.5% had depressive symptoms [19]. Similarly, high prevalence of depressive symp- toms (44.3%), anxiety (25.3%), and stress (31.7%) among the participants was reported [20]. Specifically, pain severity was found to be a  significant predictor of mental health disorder prevalence. In their cross-sectional study, higher pain severity was positively associated with high- er anxiety and depressive symptoms and lower HRQoL [22]. This was in line with other studies showing that pain has a significant effect on men- tal health status. Factors influencing psychological distress The timing of diagnosis and patient charac- teristics were found to be significant predictors of psychological distress. It was established that shorter time between the diagnosis and the as- sessment was linked to increased anxiety levels [23]. In addition to this, greater self-esteem and self-efficacy were found to be protective factors and women with higher scores on both measures indicated lower levels of depression and anxiety. A  study showed the psychological consequenc- es of the narrative identity of women with en- dometriosis [24]. It was found that women who had a  high level of endogenous factors related to endometriosis had higher levels of depressive symptoms and lower life satisfaction. On the oth- er hand, higher agency and communion themes in Study authors Year Country Study design Sample size Population Diagnostic

Mental health outcomes Measure- ment tools Key findings Conclusion Marschall et al., 2021 2021 Denmark Cross- sectional study 120 women Women aged 18–48 years MRI, ultrasound, surgery Depressive symptoms, life satisfaction, psychological impact BDI-II, SWLS, CES, narrative coding Centrality of endometriosis to identity correlated with depressive symptoms (r = 0.50) and reduced life satisfaction (r = –0.41). Agency themes linked to improved mental health outcomes. Importance of narrative identity in understanding mental health in endometriosis patients. Wang et al., 2023 2023 Taiwan Population- based cohort study 100,770 (20,154 patients) Women aged ≥ 18 ICD-9-CM codes in NHIRD Anxiety, depression, suicide, all-cause mortality NHIRD data RRs: anxiety (2.494), depression (2.773), suicide (1.447), all-cause mortality (2.315). Psychiatric follow-up and multidisciplinary care are vital to improve outcomes. Facchin et al., 2017 2017 Italy Cross- sectional study 210 women Women aged 19–51 years Clinical and/ or surgical diagnosis Depression, anxiety, rumination HADS, RRS, RSES, BES Pelvic pain severity correlated with poorer mental health. High self-esteem and emotional self-efficacy associated with lower depression and anxiety (p < 0.001). Multidisciplinary treatments should address both physical and psychological needs, including self-esteem and emotional regulation. Table II. Cont. Relationship between endometriosis and mental health. A systematic review and meta-analysis Arch Med Sci 5, October / 2025 1991 their stories correlated with better psychological well-being. Association with comorbidities and long- term risks Several authors have described the presence of comorbid depression in patients with endome- triosis. In the study by Gao et al. (2020) [21], the women with endometriosis had 1.89 times higher risk of developing depression and 1.82 times high- er risk of developing anxiety. In a different study, endometriosis was associated with a  more than twofold elevated risk of SV [25]. Furthermore, it was also possible to identify long-term outcomes including suicidality and all- cause mortality. In one study, women with endo- metriosis were at a 44.7% higher risk of suicide and a  231.5% higher risk of all-cause mortality, proving the importance of a holistic approach [26]. Quality of life and mental health In all the studies reviewed, endometriosis was found to be significantly related to decreased HRQoL. There was a  statistically significant de- crease in the general health, vitality, and mental health aspects of the HRQoL scales [19, 22]. These outcomes were mainly associated with psycho- logical distress, pain severity, and the presence of emotional dysregulation. Data synthesis Anxiety outcomes The meta-analysis revealed a  significant associa- tion between endometriosis and anxiety (Figure 2), with a  pooled relative risk (RR) of 2.82 (95%  CI: 1.69–4.68, p < 0.001) under a  random-effects model. This finding indicates that women with en- dometriosis have nearly three times the risk of de- veloping anxiety compared to control groups. The heterogeneity among the studies was substantial, as reflected by an I² value of 100% and τ² = 0.6032 (p < 0.001), suggesting variability in study popula- tions, methodologies, and diagnostic criteria. The precision of the pooled effect was support- ed by the log-transformed RR (logRR = 0.59) and its standard error (SE = 0.12), confirming the ro- bustness of the findings. The 95% confidence in- terval spanned from moderate (RR = 1.69) to high risk (RR = 4.68), further emphasizing the signifi- cant burden of anxiety among women with endo- metriosis. The funnel plot for anxiety outcomes (Figure 3) displayed moderate asymmetry, which may sug- gest the presence of publication bias or small- study effects. This observation was supported by visual inspection and statistical heterogeneity val- ues. The clustering of smaller studies near higher effect sizes, as evident in the plot, highlights the need for sensitivity analyses to ensure the stabili- ty of the pooled estimates. Depression outcomes For depression, the meta-analysis demonstrat- ed a pooled relative risk (RR) of 2.93 (95% CI: 1.63– 5.25, p < 0.001) using a  random-effects model Study logHR SE(logHR) Hazard ratio HR 95% CI Weight Weight (common) (random) Friedl et al., 2015 0.2900 0.0204 1.34 [1.28; 1.39] 19.9% 11.2% Skegro et al., 2021 0.2530 0.0153 1.29 [1.25; 1.32] 35.3% 11.2% Gao et al., 2020 1.8200 0.0485 6.17 [5.64; 6.82] 3.5% 11.1% Estes et al., 2021 1.3800 0.0408 3.97 [3.67; 4.31] 5.0% 11.1% Chen et al., 2016 1.4400 0.1225 4.22 [3.39; 5.47] 0.6% 10.9% Marki et al., 2017 0.5480 0.0357 1.73 [1.62; 1.86] 6.5% 11.2% Marschall et al., 2021 0.5000 0.0255 1.65 [1.57; 1.73] 12.7% 11.2% Wang et al., 2023 2.4940 0.1020 12.11 [9.97; 14.88] 0.8% 11.0% Facchin et al., 2017 0.6260 0.0230 1.87 [1.79; 1.95] 15.7% 11.2% Common effect model 1.66 [1.63; 1.69] 100.0% Random effects model 2.82 [1.69; 4.68] 100.0% Heterogeneity: I2 = 100%, τ2 = 0.6032, p = 0 Figure 2. Forest plot for anxiety outcomes. The pooled relative risk (RR) of 2.82 (95% CI: 1.69–4.68) indicates a sig- nificantly higher risk of anxiety among women with endometriosis 0.1 0.5 1 2 10 Figure 3. Funnel plot for anxiety outcomes. The plot shows slight asymmetry, suggesting potential publication bias 2 5 10 Hazard ratio 0 0.02 0.04 0.06 0.08 0.10 0.12 Standard error Wenwei Li, Huiyan Feng, Qingjian Ye 1992 Arch Med Sci 5, October / 2025 (Figure 4). This result indicates that women with endometriosis have nearly a threefold higher risk of experiencing depressive symptoms or clinical depression compared to controls. The heterogene- ity was pronounced, with I² = 100% and τ² = 0.794 (p < 0.001), reflecting variability across studies in terms of sample sizes, population characteristics, and measurement tools. The log-transformed RR for depression out- comes (logRR = 0.61) and its standard error (SE = 0.15) further validated the precision of the pooled effect. The 95% confidence interval showed a wide range, from moderate risk (RR = 1.63) to substantial risk (RR = 5.25), indicating that the impact of endometriosis on depression may vary based on pain severity, disease stage, and psycho- social factors. The funnel plot for depression outcomes (Fig- ure 5) revealed some asymmetry, which could be attributed to potential publication bias or meth- odological differences across studies. Studies with smaller sample sizes tended to show larger effect sizes, as visualized in the plot. The presence of outliers and clustering in specific regions of the plot suggests that further analyses, such as trim- and-fill methods, may be necessary to address po- tential biases. One-by-one elimination method outcomes The outcomes of this study concerned 9 stud- ies, each study being excluded in turn. The com- bined results of the remaining 8 studies were not Study logHR SE(logHR) Hazard ratio HR 95% CI Weight Weight (common) (random) Friedl et al., 2015 0.1450 0.0128 1.16 [1.13; 1.19] 38.0% 11.2% Skegro et al., 2021 0.4430 0.0204 1.56 [1.49; 1.62] 14.8% 11.2% Gao et al., 2020 1.8900 0.0587 6.62 [5.93; 7.46] 1.8% 11.1% Estes et al., 2021 1.4800 0.0332 4.39 [4.06; 4.62] 5.6% 11.2% Chen et al., 2016 1.5600 0.1862 4.76 [3.46; 7.17] 0.2% 10.7% Marki et al., 2017 0.2030 0.0357 1.23 [1.14; 1.31] 4.8% 11.2% Marschall et al., 2021 0.6070 0.0281 1.83 [1.73; 1.93] 7.8% 11.2% Wang et al., 2023 2.7730 0.1020 16.01 [13.46; 20.09] 0.6% 11.0% Facchin et al., 2017 0.6060 0.0153 1.83 [1.79; 1.90] 26.4% 11.2% Common effect model 1.61 [1.58; 1.63] 100.0% Random effects model 2.93 [1.63; 5.25] 100.0% Heterogeneity: I2 = 100%, τ2 = 0.7940, p = 0 Figure 4. Forest plot for depression outcomes. The pooled relative risk (RR) of 2.93 (95% CI: 1.63–5.25) highlights the elevated risk of depression among women with endometriosis 0.1 0.5 1 2 10 Figure 5. Funnel plot for depression outcomes. Slight asymmetry in the plot suggests potential bias or heterogeneity among the included studies Figure 7. L ‘Abbe plot 1 2 5 10 Hazard ratio 0 0.25 0.50 0.75 1.00 Event rate group 2 0 0.05 0.10 0.15 1.00 0.75 0.50 0.25 0 Standard error Event rate group 1 2.66 2.70 2.90 3.08 3.10 Lower CI limit Estimate Upper CI limit Figure 6. One-by-one elimination method diagram Friedl 2015 Skegro 2021 Gao 2020 Estes 2021 Chen 2016 Marki 2017 Marschall 2021 Wang 2023 Facchin 2017 Meta-analysis estimates, given named study is omitted Relationship between endometriosis and mental health. A systematic review and meta-analysis Arch Med Sci 5, October / 2025 1993 statistically significant (95% CI included 2.82 and 2.93), which was consistent with the original com- bined results (RR = 2.90, 95% CI = 2.70 to 3.08, p < 0.001) (Figure 6), indicating that the results were relatively stable. Heterogeneity of binary categorical variables It can be seen from Figure 7 that some points were far from the reference line, indicating hetero- geneity in the study results. Meta-regression analysis Meta-regression analysis was conducted on 9 included studies. As shown in Table III, I2 = 76.37% (I2 > 50%), indicating that this meta-analysis has certain heterogeneity. However, the p-value > 0.05 suggests that there was no need for subgroup analysis.

This systematic review focuses on understand- ing the association between endometriosis and mental health, providing a  detailed analysis of the interconnection between the two. The results support the hypothesis that women with endo- metriosis have significantly elevated prevalence of depression, anxiety, and psychological distress compared to the general population. This review offers a  more complex view of the contributing factors, which include pain severity, diagnostic latency, and patient-level factors such as self-es- teem and emotional self-efficacy, which supports a biopsychosocial model of treatment. The burden of endometriosis on mental health Endometriosis is defined as a chronic and se- vere disease that has negative impacts on the mental state of women. In line with previous research, the current review shows that women with endometriosis experience high levels of de- pression and anxiety, indicating that the psycho- logical toll of the disease remains high. The high prevalence of these mental health conditions should be attributed to the pain and uncertainty the patients experienced as well as the burden of the disease on their overall functioning. Pain was identified as an important factor that affected mental health. It was confirmed that se- vere pelvic pain, dysmenorrhea, and chronic pain were associated with depressive and anxious symptoms [22]. Chronic pain not only impacts physical performance but also leads to emotion- al fatigue, decreased ability to cope with stress, and increased risk of psychological distress. This finding supports the biopsychosocial model of pain, which holds that pain is not only a  physi- cal phenomenon, but its perception and experi- ence are influenced by biological, psychological, and social factors. An observational case-control study included 344 patients with endometriosis and found that among them, 119 patients had mental disorders and 70 patients had depression. Patients with depression (EM-D) or mental state (EM-P) dyspareunia and dyschezia occurred more frequently. A total of 27,840 women from six Eu- ropean countries were included in the study by Becker et al. (2021) [27]. The most common symp- toms related to endometriosis are dysmenorrhea (61.8%), massive/irregular bleeding (50.8%), and pelvic pain (37.2%). Women reported that en- dometriosis affected their emotions; 55.6% of people felt “frustrated”, depressed or desperate, and 53.2% felt defeated or disappointed with their family/friends [28]. These research results are consistent with the conclusion of this study. Endometriosis can cause both physical pain and mental distress for patients. Medical staff and society should pay attention to the mental condi- tion of patients with endometriosis. From January 2019 to March 2020, 104 women were included in a prospective observational study, and their anx- iety levels decreased after assessment (STAI-Y6 60.0 ±15.0 vs. 40.8 ±14.2). Patients with a high- er baseline anxiety level (test. change –24.3; 95% confidence interval: –29.2 to –19.5) experienced a decrease in anxiety level after the physical ex- amination [29, 30]. Diagnostic delays and psychological implications One of the significant trends identified in the reviewed research is the psychological impact of diagnostic delays. Endometriosis is often diag- nosed only after years of enduring symptoms, during which time women may experience chron- ic pain, mistreatment, and a lack of acknowledg- ment from healthcare providers. This protracted diagnostic journey, characterized by frustration and uncertainty, can exacerbate emotional dis- tress [23]. The fact that a shorter time from the di- Table III. Meta-regression analysis results Variable Coef. Std. err. t P > |t| 95% Conf. Interval Study period –0.0359408 0.0498238 –0.54 0.441 –0.1391346 0.089493 _cons 46.29132 94.07384 0.53 0.413 –179.2943 293.5463 Wenwei Li, Huiyan Feng, Qingjian Ye 1994 Arch Med Sci 5, October / 2025 agnosis is related to increased anxiety also points to the difficulties that women experience in deal- ing with the first stage of accepting an illness that is chronic and cannot be cured. The diagnostic delay carries significant social and cultural implications. The tendency to post- pone or avoid seeking care, coupled with the stigma surrounding menstrual and pelvic pain, contributes to these delays, leaving many wom- en feeling isolated and unheard. Addressing these systemic issues requires enhanced education for both medical professionals and the public, as well as improved diagnostic practices aimed at identi- fying endometriosis more promptly and accurately. Individual characteristics and protective factors In addition to the physical and diagnostic ap- proaches to endometriosis, this article explores the influence of personality traits on mental health. Higher self-esteem, enhanced emotional self-efficacy, and supportive intimate relation- ships are associated with improved psychologi- cal outcomes [23, 24]. These findings have signif- icant implications for endometriosis, indicating that individual resilience and social support can prevent a  significant amount of the mental health burden. Women with higher disease cen- trality are more likely to report depressive symp- toms and lower levels of life satisfaction [24]. On the other hand, the narratives of control are related to improved mental health, implying that the interventions designed to alter the narrative might be beneficial. Psychiatric comorbidities and long-term risks The significant association between endometri- osis and depression found in this review provokes questions regarding the common mechanisms of pathogenesis. Women with endometriosis were at a higher risk of developing depressive and anxiety than those without the disease, and the wom- en who already had depression and anxiety had a  higher likelihood of developing endometriosis [21]. Some of these mechanisms include inflam- mation, hormonal changes, and hypothalamic-pi- tuitary-adrenal axis abnormalities, which need to be explored in future studies. Furthermore, the increased odds of self- harmed/suicide and all-cause mortality supported the potentially lethal consequences of untreated psychological symptoms in women with endome- triosis [25, 26]. These results underscore the need to include mental health assessment and treat- ment as part of standard care for individuals with endometriosis. Implications for clinical practice The outcomes of this review also have import- ant implications for the medical treatment of endometriosis. First, there is a  need for mental health interventions to be incorporated into the treatment of endometriosis. Depression, anxiety, and other psychological symptoms should be screened as part of routine practice, and patients should be guided on where to access psycholog- ical support. Second, the management of pain should be comprehensive, encompassing not only a physical perception of pain, but also psycholog- ical and emotional. Other methods may include cognitive behavioral therapy, mindfulness practic- es, and narrative therapy to support medical and surgical management. Third, this systematic review on the mental health burden of endometriosis has implications for training of healthcare providers. The nature of the disease requires that the providers acknowl- edge the psychosocial aspects of the illness and manage to reassure patients about their feelings. Finally, patient education and involvement should be prioritized. Women should be empowered with resources that will improve their self-esteem, emotional self-efficacy, and coping mechanisms to improve their mental health. Heterogeneity analysis The sample size of the included literature was in line with the efficacy analysis. The results of the one-by-one elimination analysis to test the het- erogeneity of this study showed that after all the included studies were eliminated one by one, the confidence interval and total RR were still within the fluctuation range calculated by the forest plot, indicating that the bias of all the included stud- ies was controllable and stable. The L ‘Abbe plot was used to conduct heterogeneity analysis on binary variables. Basically, all the included studies showed a linear relationship, and the research re- sults were basically homogeneous, which was of certain significance. The results of the meta-re- gression analysis indicated that the included lit- erature could already yield meaningful results and there was no need for subgroup analysis. Hetero- geneity analysis indicates that there was a certain degree of heterogeneity in this study, but the anal- ysis results were still significant. Strengths, limitations, and future directions One of the major strengths of this review is the broad coverage of the studies, originating from various geographic and cultural backgrounds, which increases the external validity of the find- ings. Furthermore, the application of standardized assessment instruments throughout the studies Relationship between endometriosis and mental health. A systematic review and meta-analysis Arch Med Sci 5, October / 2025 1995 enhances the credibility of the documented re- sults. However, there were also some limitations. Many publications were horizontal, which means it was difficult to establish a  causal relationship between endometriosis and mental health. More longitudinal studies are needed to conduct longi- tudinal investigations into this relationship, with a focus on diagnosing the consequences of delays and the outcomes of intervention measures. Fur - thermore, the variability of research types, par - ticipants, and measured mental health impacts complicated the analysis and comparison. Only 9 studies were included in this analysis. The num- ber was too small, which leads to certain het- erogeneity in the meta-analysis, and the results lacked certain persuasiveness. In future research, we will search as many databases as possible and include as many studies as possible in the me- ta-analysis. Additionally, we will extend our search to Embase, Scopus, and gray literature to mini- mize publication bias and improve the complete- ness of evidence. Meanwhile, we will also conduct subgroup analyses on the research design of the included literature, the family economic income of patients with endometriosis, marital status, etc., so that the obtained results are meaningful for the actual treatment. It is also necessary to consider how other aspects such as race, economic status, and cultural customs affect endometriosis and its treatment. Exploring the connection between en- dometriosis and depression/anxiety is helpful for formulating intervention and treatment plans. In conclusion, this systematic review focuses on the high mental health cost that has been re- ported among women with endometriosis, with increased depression, anxiety, and psychological distress recorded. Many factors were found to be associated with these outcomes. They included pain severity, diagnostic delay, and presence of comorbid conditions. In the same vein, self-es- teem, emotional self-efficacy, and social support were revealed as moderators that could buffer the effects of the disease. These conclusions stress the necessity for an interdisciplinary approach to the treatment of endometriosis, in which the evaluation and treat- ment of mental health issues should be included in addition to pain relief and pharmacological treatment. The study highlighted that early diag- nosis and effective care management models for endometriosis are vital to enhance both somatic and psychiatric recovery for affected females. Fu- ture studies should aim to identify the long-term outcomes of these interventions and the under - lying common pathways between endometriosis and depression and anxiety. As highlighted in this review, various interrelated factors need to be ad- dressed with a  view to improving the quality of life of millions of affected women. Funding No external funding. Ethical approval This study was approved by the Institutional Re- view Board of the Third Affiliated Hospital of Sun Yat-sen University (Approval NO: II 2023-292-01). Conflict of interest The authors declare no conflict of interest.

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