Prevalence and associated factors of clinically significant symptoms of depression and anxiety among women with endometriosis in Iran

This cross-sectional study was conducted between 2023 and 2024 at Shahid Kamali Hospital, a referral center in Karaj, Iran. Findings are specific to Iranian women and may not be generalisable to other populations. The aim was to assess the prevalence of clinically significant symptoms of depression and anxiety among women diagnosed with endometriosis and to identify clinical and demographic factors associated with these outcomes. Women with a confirmed diagnosis of endometriosis by a specialist gynecologist were recruited using a convenience sampling method. Inclusion criteria were: [ 1 ] confirmed diagnosis of endometriosis, and [ 2 ] provision of written informed consent. Exclusion criteria included: [ 1 ] recent bereavement (within the past three months) [ 2 ], presence of chronic medical conditions (e.g., cancer, diabetes, epilepsy, multiple sclerosis), and [ 3 ] infertility. The exclusion of infertile women was intentional to isolate the psychological effects of endometriosis-related pain and disease characteristics from the distinct and substantial psychological burden of infertility itself, which is known to independently influence clinically significant symptoms of depression and anxiety [ 14 ,  15 ]. This rationale has been explicitly discussed in the Discussion and Limitations sections. Between 2023 and 2024, participants were recruited from women attending Shahid Kamali Hospital in Karaj, Iran. Potential participants were identified through the gynecology clinic, where they were being treated for endometriosis. The study was explained to potential participants, and those who met the inclusion criteria were invited to participate. All participants provided written informed consent prior to enrollment in the study. Participants completed a demographic questionnaire and the Hospital Anxiety and Depression Scale (HADS). Clinical data, including disease duration, stage/severity, and pain intensity, were extracted from medical records. Severity was classified using the revised American Society for Reproductive Medicine (rASRM) staging system. Pain intensity was assessed using a standard 10-cm Visual Analog Scale (VAS), ranging from 0 (no pain) to 10 (worst imaginable pain). The VAS is a widely used and validated instrument for the assessment of pain in clinical and epidemiological studies [ 16 ]. The demographic questionnaire gathered information on participants’ age, education level, marital status, employment status, and other relevant demographic characteristics. HADS is a validated and reliable instrument used to assess clinically significant symptoms of anxiety and depression in a general medical setting. It was developed for use in a general medical hospital outpatient clinic. No formal psychiatric diagnostic interview was conducted. Participants completed the HADS questionnaire independently, and a researcher was available only to provide clarification if needed. The tool includes 7 items each for anxiety and depression, scored on a 0–3 scale per item, resulting in possible scores of 0–21 for each subscale. Scores were categorized as: Normal (0–7), Suggestive [ 8 – 10 ], Probable disorder (11 or higher) [ 17 ]. The Persian version of the Hospital Anxiety and Depression Scale (HADS) has been translated and validated in Iranian populations, demonstrating acceptable reliability and validity (Cronbach’s α > 0.78 for both subscales) [ 18 ]. However, it has not been formally validated against a gold standard diagnostic interview in Iran, which should be considered a limitation of this study. Participants were provided with the HADS questionnaire along with clear instructions for completion. The researcher was available to answer any questions. Participants completed the questionnaire independently in a quiet and private setting to ensure confidentiality and reduce potential bias. Clinical data collected from the participants’ medical records included the duration of endometriosis, stage/severity of endometriosis, and pain intensity levels. Severity was classified according to the revised American Society for Reproductive Medicine (rASRM) staging system (minimal, mild, moderate, severe). Pain intensity was measured using the Visual Analog Scale (VAS), ranging from 0 (no pain) to 10 (worst imaginable pain). After completion, the questionnaires were scored according to their respective guidelines (HADS and demographic data). All data from the questionnaires and clinical assessments were entered into SPSS version 22 for statistical analysis. Data accuracy was verified to ensure the integrity of the data. Data was analyzed using SPSS version 22. Descriptive statistics were used to summarize demographic and clinical characteristics. Prevalence rates of clinically significant symptoms of depression and anxiety were calculated with 95% confidence intervals. Univariate logistic regression analyses were performed for all predictors (Supplementary Table 1). Variables with P  < 0.20 were advanced to multivariate models. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were reported. A P-value < 0.05 was considered statistically significant. One-way ANOVA was used to compare mean anxiety and depression scores across severity categories (Table 2 ), after checking assumptions of normality and homogeneity of variance. In the multivariable logistic regression model (Table 3 ), severity was entered as a categorical variable (minimal, mild, moderate, severe) to ensure comparability with Table 2 . Covariates included in the regression models were selected based on prior literature, clinical relevance, and feasibility within the study design. Variables such as age, education level, pain intensity, and disease duration were prioritized due to their established associations with psychological outcomes in endometriosis. Marital status was excluded from the multivariate model but analyzed in univariate regression, and infertility was excluded to isolate the psychological impact of endometriosis-related pain.

A total of 112 women with endometriosis participated in this study. The mean age was 31.6 ± 4.9 years, and the mean BMI was 26.3 ± 3.7 kg/m². Most participants had mild to moderate disease severity, and the average duration of endometriosis was 4.9 ± 4.6 years. The demographic and clinical characteristics of the participants, including disease duration, severity, and pain intensity, are presented in Table 1 . Table 1 Demographic and clinical characteristics of women with endometriosis ( N  = 112) Variable Frequency (Percentage Frequency) Mean ± Standard Deviation Number of Children None 31 (27.7) One 42 (37.5) Two 25 (22.3) Three and More 4 (3.6) Education Illiterate 8 (7.1) Elementary 18 (16.1) Diploma 55 (49.1) Associate’s degree 27 (24.1) Academic 5 (4.5) Nationality Iranian 107 (95.5) Foreign 5 (4.5) Marital Status Single 37 (33.0) Married 75 (67.0) Body Mass Index (kg/m^2) 26.3 ± 3.7 Age (years) 31.6 ± 4.9 Duration of Endometriosis (years) 4.9 ± 4.6 Data are presented as mean ± SD or frequency (%) Demographic and clinical characteristics of women with endometriosis ( N  = 112) Data are presented as mean ± SD or frequency (%) The prevalence of clinically significant symptoms of depression was 59.8% (95% CI: 50.4–68.6), and the prevalence of clinically significant symptoms of anxiety was 54.5% (95% CI: 45.2–63.5). The mean anxiety score was 12.4 ± 5.5, and the mean depression score was 14.3 ± 3.7. No statistically significant association was found between disease severity and either anxiety symptoms ( P  = 0.146) or depressive symptoms ( P  = 0.084). However, univariate logistic regression analyses (Supplementary Table 1) showed that disease duration ( P  = 0.01) and pain intensity ( P  = 0.001) were significantly associated with depressive symptoms, while education level ( P  = 0.001) was significantly associated with anxiety symptoms. Pain intensity (VAS score: 5.2 ± 2.4) was positively correlated with depression symptom severityseverity ( P  = 0.001), but no significant relationship was observed between pain intensity and anxiety symptoms (Table 2 ). Table 2 Mean scores of depression and anxiety according to endometriosis severity Variable Anxiety Score (Mean ± SD) Depression Score (Mean ± SD) Minimal 11.8 ± 4.3 13.9 ± 4.8 Mild 12.6 ± 6.4 13.6 ± 3.0 Moderate 12.4 ± 5.7 14.7 ± 4.3 Severe 12.6 ± 6.03 14.0 ± 4.2 P Value 0.146 0.084 One-way ANOVA was used to compare mean scores across severity categories Mean scores of depression and anxiety according to endometriosis severity One-way ANOVA was used to compare mean scores across severity categories In univariate logistic regression, age, disease duration, and pain intensity were significantly associated with depressive symptoms. These variables were entered into a multivariate logistic regression model, which confirmed their independent associations. Adjusted odds ratios (OR) were as follows: age (OR = 5.443, 95% CI: 3.037–9.756, P  = 0.001), disease duration (OR = 2.915, 95% CI: 1.715–4.955, P  = 0.001), and pain intensity (OR = 3.711, 95% CI: 1.845–4.757, P  = 0.001) (Table 3 ). Table 3 Multivariate logistic regression analysis of factors associated with depression and anxiety depression model Depression Model Variable Adjusted OR Lower 95% CI- Upper 95% CI P -value Number of Children 1.288 0.821–2.019 0.270 Education 1.390 0.844–2.291 0.196 BMI 1.061 0.949–1.190 0.289 Age 5.443 3.037–9.756 0.001 Duration of Endometriosis 2.915 1.715–4.955 0.001 Severity of Endometriosis 0.704 0.277–1.788 0.461 Pain Intensity 3.711 1.845–4.757 0.001 Anxiety Model Variable Adjusted OR 95% CI (Lower–Upper) P-value Education 9.060 4.888-16.894 0.001 Age 1.700 0.588-0.833 0.001 BMI 2.035 0.609-6.799 0.248 Duration of Endometriosis 1.382 0.725-2.635 0.325 Number of Children 1.356 1.564-117.697 0.180 Pain Intensity 1.790 1.697-3.776 0.656 Severity was modeled categorically. Variables with P  < 0.20 in univariate analysis were included in multivariate models Multivariate logistic regression analysis of factors associated with depression and anxiety depression model Severity was modeled categorically. Variables with P  < 0.20 in univariate analysis were included in multivariate models Univariate analysis identified education level as significant, and multivariate analysis confirmed education level (OR = 9.060, 95% CI: 4.888–16.894, P  = 0.001) and age (OR = 1.700, 95% CI: 0.588–0.833, P  = 0.001) as significant correlates. Other variables such as BMI, number of children, and disease severity were not significantly associated with either outcome (Table 3 ). These findings indicate that while disease severity may not directly predict psychological outcomes, longer disease duration and higher levels of pain substantially contribute to clinically significant depressive symptoms, while educational attainment and age influence susceptibility to clinically significant anxiety symptoms.

This study demonstrated a high prevalence of clinically significant depressive and anxiety symptoms among women with endometriosis, with over half of the participants reporting clinically significant symptoms. Longer disease duration and greater pain intensity were significantly associated with depressive symptoms. Univariate analyses revealed that longer disease duration and greater pain intensity were significantly associated with depressive symptoms, while education level was linked to anxiety symptoms. No significant associations were found between disease severity and psychological outcomes, suggesting that subjective experiences of pain and chronicity may play a more critical role than clinical staging. These findings underscore the importance of integrating psychological screening and support into routine endometriosis care, particularly for patients with prolonged disease duration or high pain burden. Addressing mental health in this population requires a multidisciplinary approach that considers both biological and psychosocial dimensions. Future research should explore longitudinal trajectories, include diverse patient subgroups such as those with infertility, and evaluate the effectiveness of targeted interventions aimed at improving psychological well-being and quality of life. This study has several limitations. Its cross-sectional design prevents causal inference between endometriosis and psychological outcomes. The use of convenience sampling from a single referral hospital may limit generalizability. Self-reported measures, while validated, are subject to bias and lack clinical confirmation. Furthermore, the exclusion of women with infertility represents a significant methodological limitation. Infertility is a common comorbidity of endometriosis and is itself a strong risk factor for depression and anxiety. By systematically excluding this subgroup, the representativeness of the sample is reduced, and the applicability of the findings to the broader endometriosis population is restricted. This exclusion may have led to an underestimation of the true psychological burden associated with endometriosis, particularly in women struggling with both pain and reproductive challenges. Additionally, marital status was analyzed in univariate regression but excluded from the final multivariate model. This decision may have limited the ability to fully capture psychosocial influences, as recent evidence highlights the importance of marital status in relation to chronic pelvic pain and psychological distress [ 10 ]. Additionally, variables such as marital status, trauma history, and access to mental health care were not assessed, which may have influenced the findings. Although the Persian version of HADS has been validated in Iran [ 18 ], it has not been formally compared against a gold standard diagnostic interview to establish sensitivity and specificity. This should be considered a limitation of the present study. Future research should adopt longitudinal designs to better understand the temporal and potentially causal relationships between endometriosis and psychological distress. Including diverse subgroups such as women with infertility, varying marital status, and different socioeconomic backgrounds would enhance generalizability and provide a more nuanced understanding of psychosocial burden. Studies incorporating biological markers of inflammation, HPA axis function, and neuroimmune activity could clarify underlying mechanisms linking endometriosis to depressive and anxiety symptoms. Additionally, intervention-based research is needed to evaluate the effectiveness of integrated care models that combine gynecological treatment with psychological support. Exploring culturally tailored approaches may also improve outcomes in underrepresented populations, including those in the Middle East.

This study revealed a high prevalence of clinically significant symptoms of depression (59.8%) and anxiety (54.5%) among women with endometriosis, consistent with prior research indicating elevated psychological distress in this population [ 5 , 6 ]. These rates are notably higher than those reported in the general female population, underscoring the unique vulnerability of women with endometriosis to mental health disorders. Consistent with prior research, our results demonstrated disease duration and pain intensity were the primary factors associated with depressive symptoms, whereas endometriosis severity showed no significant relationship with either depressive or anxiety symptoms [ 6 , 19 ]. This observation supports the growing recognition that subjective pain experience and chronicity are more influential on mental health outcomes than the anatomical stage of disease. Chronic pelvic pain can lead to persistent stress, sleep disruption, and social withdrawal, all of which contribute to mood deterioration [ 3 , 20 ]. Recent studies have elucidated possible biological mechanisms linking endometriosis with depression and anxiety, including systemic inflammation, glial activation, and dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis [ 21 , 22 ]. Chronic inflammation associated with endometriosis increases circulating cytokines such as IL-6, TNF-α, and IL-1β, which can influence neuroplasticity and serotonin metabolism, thereby exacerbating depressive symptoms [ 23 ]. Dysregulation of the HPA axis and altered cortisol secretion patterns may also explain heightened anxiety symptoms and stress sensitivity observed in affected women [ 24 , 25 ]. These biological mechanisms may help explain the associations between longer disease duration, higher pain intensity, and clinically significant depressive symptoms identified in our sample. The psychosocial burden of endometriosis extends beyond pain and inflammation. The chronic and unpredictable nature of symptoms, along with frequent delays in diagnosis, often leads to frustration, helplessness, and diminished self-efficacy, all of which negatively impact quality of life. Dipankar et al. [ 26 ] emphasized that women with endometriosis frequently experience emotional exhaustion, stigma, and invalidation of their symptoms, contributing to heightened psychological distress [ 26 ]. Similarly, Della Corte et al. [ 27 ] highlighted the long-term psychosocial impact of endometriosis across the lifespan, underscoring the need for comprehensive care. These findings support the adoption of a multidimensional model that integrates pain management, psychological support, and social interventions to improve overall well-being [ 27 ]. Importantly, our findings align with evidence from recent large-scale surveys and population-based studies. For example, Cofini et al. [ 10 ], in a national cohort study published in Women’s Health , found that marital status was the only social factor significantly associated with chronic pelvic pain, highlighting the importance of psychosocial determinants [ 10 ]. Similarly, Souza et al. [ 13 ] demonstrated that quality of life impairment due to chronic pelvic pain is independent of endometriosis diagnosis [ 13 ]. Cofini et al. [ 11 ] reported that women’s perceptions of healthcare quality strongly influence psychological outcomes [ 11 ]. Silva et al. [ 12 ] showed that pain and infertility significantly affect quality of life, psychological well-being, and sexual function [ 12 ]. Finally, recent population-based analyses reinforce the need to integrate patient-reported outcomes, symptom severity, and psychosocial factors into clinical care and research frameworks [ 11 – 13 ]. Additionally, qualitative evidence suggests that poor experiences with healthcare providers and limited access to specialized treatment exacerbate psychological distress [ 28 , 29 ]. Our participants, recruited from a tertiary hospital, may represent women with more severe symptoms who actively seek care, potentially explaining the high prevalence of clinically significant depressive and anxiety symptoms in this study. Univariate analyses (Supplementary Table 1) revealed that education level was significantly associated with anxiety symptoms, while marital status showed crude associations but was not significant. Although marital status was excluded from the final multivariate model, recent evidence underscores its relevance, and future studies should incorporate it alongside infertility to better capture psychosocial determinants. Given the close link between pain, chronicity, and mental-health outcomes, clinicians should routinely screen women with endometriosis for clinically significant symptoms of depression and anxiety and refer them for psychological support when appropriate. Emerging integrative approaches such as cognitive-behavioral therapy (CBT), mindfulness-based stress reduction (MBSR), and psychoeducation have shown promise in improving both pain perception and emotional well-being [ 26 ]. Effective multidisciplinary care requires coordination between gynecologists, psychologists, and pain specialists to address both physical and emotional dimensions of the disorder. These findings reflect the unique cultural and healthcare landscape of Iran. Societal stigma and barriers to specialized care likely shape how women experience symptoms and seek help, meaning these results may not represent the experiences of women in other global contexts. Future research should prioritize cross-cultural comparisons to better understand how local environments influence the emotional toll of endometriosis.

Endometriosis is a chronic gynecological condition affecting approximately 10–15% of women of reproductive age worldwide [ 1 , 2 ]. It is characterized by the presence of endometrial-like tissue outside the uterus—most commonly on the ovaries, fallopian tubes, and pelvic peritoneum—which responds to hormonal fluctuations and leads to inflammation, bleeding, and adhesions that cause chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility [ 1 , 3 ]. Beyond its physical manifestations, endometriosis exerts a profound psychosocial and emotional toll. Chaggar et al. [ 4 ] demonstrated that both deep and ovarian endometriosis significantly impair quality of life through the presence of chronic pelvic pain, fatigue, and sexual dysfunction, highlighting how persistent pain adversely influences psychological well-being and daily functioning [ 4 ]. Similarly, Rees et al. [ 5 ] and Van Niekerk et al. [ 6 ] reported elevated levels of anxiety, depression, and social withdrawal among affected women [ 5 , 6 ]. A recent systematic review by Miller et al. [ 7 ] further confirmed that women with endometriosis experience substantially higher rates of depression and anxiety compared with the general population, largely due to the continuous impact of pain on occupational, social, and interpersonal domains [ 7 ]. These findings are consistent with the World Health Organization’s recognition of mental health as an integral component of overall well-being and its emphasis on addressing psychological disorders in chronic medical conditions. In addition, Sepulcri and Amaral [ 8 ] identified pain intensity and disease chronicity as key correlates of anxiety and depression in endometriosis [ 8 ]. A large-scale retrospective study involving 12 million women (2024) corroborated this relationship, underscoring the significant burden of chronic pain and its association with mood disturbances [ 9 ]. Biological mechanisms such as chronic inflammation, glial activation, and hypothalamic–pituitary–adrenal (HPA) axis dysregulation may further exacerbate this link by perpetuating a vicious cycle between physical suffering and emotional distress [ 3 ]. Furthermore, findings from recent large-scale population-based studies strengthen the evidence regarding psychological burden in endometriosis. A major cohort analysis published in Women’s Health demonstrated that social and relational factors including marital status were significantly associated with chronic pelvic pain and psychological outcomes in women with endometriosis [ 10 ]. Additional large observational studies have similarly highlighted the strong association between symptom severity, pain burden, and reduced health-related quality of life in affected women [ 11 – 13 ]. These data collectively underscore the multifactorial determinants of depression and anxiety in this population. Despite growing international evidence, region-specific data remain scarce, particularly from Middle Eastern populations, where cultural norms and healthcare accessibility may influence symptom expression and psychological outcomes. This study aims to examine the prevalence of depression and anxiety among Iranian women with endometriosis and to identify associated clinical and demographic factors. Variables such as age, education level, pain intensity, and disease duration were selected based on prior empirical findings and clinical relevance [ 8 , 9 ]. Although marital status was excluded from the final multivariate model, it was analyzed in univariate regression and is discussed in the Limitations.

Supplementary Material 1. Supplementary Material 1.