Epidemiological study and clinical consequences of endometriosis and PCOS co-occurrence in a clinical population of women: a cross-sectional study

This study included 380 women diagnosed with endometriosis. The majority of participants (51.1%) were between 20 and 30 years of age, while the smallest group (7.9%) were over 50 years. Among these patients, 93 (24.5%) were diagnosed with PCOS according to Rotterdam criteria. The demographic and clinical characteristics of the study population are presented in Table  1 . Table 1 Demographic and clinical characteristics of the study population Variables Frequency (%) PCOS Yes 93 (24.5%) No 287 (75.5%) Marital status Single 75 (19.7%) Married 222 (58.4%) widow 32 (8.4%) divorced 51 (13.4%) Underlying diseases None 185 (48.7%) Diabetes 55 (14.5%) Blood hypertension 49 (12.9%) Infertility Yes 58 (15.3%) No 322 (84.7%) Demographic and clinical characteristics of the study population Patients with both endometriosis and PCOS showed significantly worse clinical outcomes compared to those with endometriosis alone (Table  2 ). The most substantial differences were observed in quality of life (91.4% vs. 10.5%, p  < 0.001), symptom severity (84.9% vs. 12.2%, p  < 0.001), and pain intensity (76.3% vs. 16.7%, p  < 0.001). Significant differences were also found in dyspareunia (60.2% vs. 44.6%, p  = 0.009) and infertility (25.6% vs. 15.4%, p  = 0.043). In contrast, the rate of miscarriage did not differ significantly between the groups (41.0% vs. 47.1%, p  = 0.350). Table 2 Comparison of clinical outcomes between endometriosis patients with and without PCOS Variable PCOS P value Yes (%) No (%) 0.043 Infertility 25.6 15.4 symptom severity (severe) 84.9 12.2 < 0.001 pain intensity (severe) 76.3 16.7 < 0.001 dyspareunia 60.2 44.6 0.009 miscarriage 41.0 47.1 0.350 quality of life (poor) 91.4 10.5 < 0.001 Based on Chi-square test Comparison of clinical outcomes between endometriosis patients with and without PCOS Based on Chi-square test The age-adjusted logistic regression analysis demonstrated that PCOS comorbidity was associated with significantly increased odds of infertility (OR = 1.88, 95% CI: 1.01–3.50, p  = 0.048) and poor quality of life (OR = 91.0, 95% CI: 40.0-206.0, p  < 0.001). No significant association was found between PCOS comorbidity and miscarriage (OR = 0.78, 95% CI: 0.46–1.31, p  = 0.341). These results are summarized in Table  3 . The exceptionally high odds ratio for poor quality of life reflects a very strong association, likely influenced by the stark contrast in outcome distribution between the groups, where poor quality of life was nearly universal in the comorbid group but uncommon in the endometriosis-only group. Table 3 Age-Adjusted logistic regression analysis of PCOS comorbidity association with clinical outcomes Outcome Adjusted OR* 95% CI p -value Infertility 1.88 1.01–3.50 0.048 Poor Quality of Life 91.0 40.0-206.0 < 0.001 Miscarriage 0.78 0.46–1.31 0.341 *Adjusted for age Age-Adjusted logistic regression analysis of PCOS comorbidity association with clinical outcomes *Adjusted for age

This study indicates that women with both endometriosis and PCOS exhibit a more severe clinical profile compared to those with endometriosis alone. Specifically, comorbidity was associated with higher rates of infertility, greater symptom severity, increased pain intensity, more frequent dyspareunia, and reduced quality of life, as observed in our data. These findings suggest that the co-occurrence of PCOS and endometriosis may be linked to overlapping endocrine, inflammatory, and metabolic mechanisms. Recognizing this comorbidity has practical clinical implications, highlighting the need for individualized diagnostic and management strategies. Further research with larger sample sizes and standardized assessment tools is warranted to clarify the underlying biological pathways and to optimize care for this patient population.

The findings of this study highlight that the coexistence of endometriosis and PCOS has notable clinical relevance among women in Zabol. We observed a 24.5% prevalence of PCOS among patients with endometriosis, which is higher than previously reported rates, such as 16.5% reported by Kristin et al. [ 14 ]. This difference may reflect variations in study population characteristics, diagnostic criteria, or regional genetic and environmental factors. Consistent with the literature, which demonstrates that the co-occurrence of these two disorders significantly increases the risk of adverse reproductive outcomes [ 13 ], our results demonstrated that PCOS comorbidity nearly doubled the odds of infertility (OR = 1.88, 95\% CI: 1.01–3.50). This heightened risk suggests that the shared and distinct pathological mechanisms synergistically impair fertility. However, the exact endometrial factors contributing to this combined subfertility remain complex and need further elucidation. For instance, while PCOS is associated with endometrial dysfunction, recent evidence from propensity score matched studies suggests that the incidence of chronic endometritis (CE), a localized inflammatory condition, is not significantly increased in infertile women with PCOS compared to non-PCOS controls [ 26 ]. This finding may guide future research to focus on other shared mechanisms beyond localized inflammation of the endometrium, such as metabolic and hormonal dysregulation, as drivers of the combined effect on infertility. The potential mechanisms underlying the concurrent impact of these two disorders on infertility may include hormonal imbalance in PCOS leading to ovulatory dysfunction and impaired oocyte quality in endometriosis. Chronic pelvic inflammation, oxidative stress, and immune dysregulation are additional contributing factors that may jointly impair fertility outcomes. Previous studies have similarly highlighted that inflammatory and hormonal interactions can compromise endometrial receptivity and implantation rates in affected women (Dinsdale et al., 2020; Palomba et al., 2021) [ 12 , 27 ]. These mechanisms collectively provide a plausible explanation for the higher infertility rates observed in women with both conditions in our study. The co-occurrence of endometriosis and PCOS observed in this study may indicate potential shared biological mechanisms. Although these conditions are often viewed as distinct entities, emerging molecular and genetic data suggest that certain immunologic and inflammatory pathways could contribute to both. Recent genomic studies, such as those by Shigesi et al. (2020) [ 28 ] has demonstrated significant genetic overlap between endometriosis and other immune-related disorders, implying that immune dysregulation may be a unifying mechanism. Given that both endometriosis and PCOS are characterized by chronic low-grade inflammation, it is plausible that shared genetic variants affecting cytokine regulation (e.g., TNF-α, IL-6) and immune response might predispose women to both diseases. These findings, together with our clinical data, support the hypothesis that immune and inflammatory imbalance plays a pivotal role in the coexistence of these conditions. We hypothesize that the previously established immune–genetic interplay in endometriosis may also underlie its coexistence with PCOS, as both disorders share chronic low-grade inflammation as a central pathophysiological feature. Endometriotic lesions secrete inflammatory mediators such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), while PCOS is similarly associated with a persistent inflammatory state that promotes insulin resistance and metabolic dysfunction. This pro-inflammatory microenvironment—potentially driven by common immune-related genetic variants as reported by Shigesi et al.—might therefore facilitate the initiation and mutual exacerbation of both conditions [ 28 – 31 ]. Hormonal dysregulation further contributes to the interplay between endometriosis and PCOS. Insulin resistance, a central feature of PCOS, may exacerbate endometriotic lesion development by enhancing local aromatase activity and increasing estrogen production, thereby promoting lesion growth [ 31 , 32 ]. This complex bidirectional interaction indicates that the coexistence of these disorders is unlikely to be coincidental, instead reflecting a multifactorial mechanism involving shared genetic predisposition, immune dysregulation, systemic inflammation, and reciprocal hormonal influences. Regarding symptom severity, our findings demonstrated that women with concurrent endometriosis and PCOS exhibited a higher prevalence of severe clinical manifestations compared to those with endometriosis alone. This observation aligns with previous reports by Harris et al. (2016) and Barry et al. [ 32 , 33 ]. The increased severity of symptoms may result from multiple factors, including excessive endometrial proliferation in PCOS, ectopic endometrial tissue growth in endometriosis, chronic pelvic inflammation, and potential irritation of pelvic nerves. A notable finding of this study was the significant association between the co-occurrence of endometriosis and PCOS and reduced quality of life (OR = 91). The unusually high odds ratio likely reflects the limited number of participants with favorable quality of life and the imbalanced distribution of the data. Therefore, this result should be interpreted with caution, and future studies with larger sample sizes and standardized assessment tools are warranted to validate this relationship. These findings are in line with previous reports by Parker et al. (2014) and Simoens et al. (2012) [ 16 , 34 ]. The observed reduction in quality of life may be attributed to a combination of physical and psychological factors, including menstrual irregularities, chronic pain, depression, and anxiety. Conversely, our results did not demonstrate a statistically significant association between the co-occurrence of these conditions and increased rates of miscarriage, abnormal bleeding, or urinary symptoms, consistent with the findings of Matorras et al. [ 35 ]. This study has several limitations that should be considered when interpreting the results. The most significant limitation is the lack of surgical confirmation for endometriosis diagnoses. As laparoscopy remains the gold standard, reliance on clinical and ultrasonographic criteria may have introduced misclassification bias, potentially affecting the accuracy of the reported prevalence rates. Secondly, the single-center design, recruiting from a tertiary hospital in Zabol, may limit the generalizability of our findings. The patient population at a referral center likely represents a subgroup with more severe symptoms, which may not be representative of the broader community and could lead to an overestimation of the observed associations. Finally, the absence of a control group of women without endometriosis or PCOS restricts our ability to make robust comparisons with a healthy baseline population and to fully isolate the specific effects of the comorbidity.

Endometriosis and polycystic ovary syndrome (PCOS) are among the most prevalent endocrine and gynecological disorders affecting women of reproductive age globally [ 1 ]. Endometriosis, defined by the presence of endometrial-like tissue outside the uterus, is a major cause of chronic pelvic pain and infertility [ 2 ]. In contrast, PCOS is a heterogeneous endocrine disorder characterized by ovulatory dysfunction, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology [ 3 ], with a reported global prevalence ranging from 5% to 20% [ 4 ]. These two disorders not only impose a substantial clinical and socioeconomic burden but also represent major challenges in reproductive medicine due to their complex etiology and chronic course. Although these two disorders present distinct clinical features, increasing evidence suggests that they may share overlapping pathophysiological mechanisms. The pathogenesis of endometriosis is intricate and not yet fully elucidated [ 5 – 7 ]. The disease has been linked to the presence of ectopic endometriotic lesions, which have been shown to trigger a chronic inflammatory response [ 8 , 9 ]. Similarly, PCOS is associated with hormonal imbalance, chronic inflammation, and metabolic disturbances. Both disorders may result from abnormal prenatal hormonal programming and dysregulation of the hypothalamic–pituitary–ovarian (HPO) axis. Estrogen dysregulation is a central feature, with systemic hyperestrogenemia—particularly estrone excess—in PCOS, and local estrogen overproduction within endometriotic lesions. Moreover, immune dysfunction, genetic susceptibility, and insulin resistance have been proposed as shared biological mechanisms that further support their potential intersection [ 10 , 11 ]. Biological support for this overlap is further strengthened by the novel ‘diametric disorder’ hypothesis, which suggests that endometriosis and PCOS represent opposite extremes of hypothalamic-pituitary-gonadal axis development, mediated by low and high prenatal testosterone exposure, respectively [ 12 ]. This model provides a unifying framework that helps explain their apparent contrast yet possible coexistence. clinically, the coexistence of endometriosis and PCOS has important implications. Each disorder independently contributes to infertility and reduced quality of life, but their co-occurrence may exacerbate symptom severity and complicate diagnosis and management [ 13 ]. However, despite the potential clinical significance, this overlapping phenotype has been insufficiently investigated, particularly in specific populations where environmental, lifestyle, or genetic factors may influence disease expression. Understanding this intersection is crucial for improving diagnostic accuracy and patient outcomes. The co-occurrence of PCOS and endometriosis is a clinically significant finding, with prevalence varying across different study populations. Among women undergoing gynecologic surgery for related issues, the overlap can be substantial, with one study reporting that nearly 5% of women had both conditions in an operative cohort [ 13 ]. Even more strikingly, among women with infertility and/or pelvic pain, the incidence of suspected endometriosis in those diagnosed with PCOS can be as high as 74\%, demonstrating a strong association between the two disorders [ 14 ]. While the prevalence of PCOS alone is high among infertile women in certain regions of Iran, emphasizing the regional burden of this condition [ 15 ], data on the combined prevalence of both disorders in specific Iranian clinical settings remain scarce.The convergence of epidemiological evidence and a plausible pathophysiological model underscores that the co-occurrence of endometriosis and PCOS is not merely coincidental but a clinically significant comorbidity that warrants focused investigation, particularly regarding its impact on clinical outcomes such as infertility and quality of life. The convergence of epidemiological evidence and a plausible pathophysiological model underscores that the co-occurrence of endometriosis and PCOS is not merely coincidental but a clinically significant comorbidity that warrants focused investigation, particularly regarding its impact on clinical outcomes such as infertility and quality of life. The diagnosis of endometriosis is typically delayed by an average of 6.7 year, largely attributable to the necessity of invasive procedures, such as laparoscopy [ 16 ]. Conversely, the diagnosis of PCOS is made using clinical criteria, including hyperandrogenism, ovulatory disorders, and sonographic findings [ 17 ]. These diagnostic differences highlight the clinical challenges in identifying and managing patients when both disorders coexist, as overlapping symptoms may obscure accurate recognition of each condition. Despite the existence of fundamental clinical and pathophysiological differences between these two diseases, as well as the conventional practice of studying them separately, emerging evidence suggests a possible overlap between them [ 18 – 20 ]. Recent studies have indicated a correlation between prenatal androgen levels and the development of both conditions [ 12 , 13 , 21 ] “This overlap has important implications for clinical diagnosis and management. Infertility is a prevalent complication associated with both diseases, affecting up to 15% of couples [ 22 ]. However, data on the coexistence of endometriosis and PCOS, particularly in specific populations such as women in Zabol, Iran, remain scarce. Investigating this relationship in such a regional context is important, as environmental and genetic factors may influence disease expression and clinical outcomes. Therefore, the present cross-sectional study aimed to determine the prevalence of PCOS co-occurrence in a clinical population of women with endometriosis in Zabol and to evaluate its impact on key outcomes, including infertility rates, symptom severity, and health-related quality of life. This was an analytical retrospective cross-sectional study that analyzed data from 380 women diagnosed with endometriosis who were referred to the gynecology department of Amir al-Momenin Hospital in Zabol between 2018 and 2023. The study protocol was approved by the Ethics Committee of Zabol University of Medical Sciences (Approval Code: IR.ZBMU.REC.1402.136). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Participants were selected using a convenience sampling method. The sampling frame included all eligible women presenting to the center during the study period who met the inclusion criteria. We acknowledge that convenience sampling may limit the generalizability of our findings; however, it was deemed the most feasible approach for this clinical setting, and all consecutive eligible cases were invited to participate to minimize selection bias. The inclusion criteria were as follows: Diagnosis of endometriosis based on clinical evaluation and imaging findings (transvaginal ultrasound or MRI), as laparoscopic confirmation was not available for this cohort. Diagnosis of PCOS according to the Rotterdam criteria (2003) [ 23 ]. Diagnosis of endometriosis based on clinical evaluation and imaging findings (transvaginal ultrasound or MRI), as laparoscopic confirmation was not available for this cohort. Diagnosis of PCOS according to the Rotterdam criteria (2003) [ 23 ]. Patients were excluded if they had a surgical history that could interfere with disease diagnosis or staging, Systemic diseases of a severe nature (such as uncontrolled diabetes mellitus, chronic hypertension, thyroid disorders, autoimmune diseases including lupus or rheumatoid arthritis, and severe hepatic or renal disease) have the capacity to impact the quality of life of the patient, as well as their fertility, incomplete medical records, or if they declined to participate. Data were collected using a researcher-designed checklist that included: age, body mass index (BMI), marital status, and education level. history of infertility, symptom severity, pelvic pain intensity, dyspareunia, and quality of life. In this study, female infertility was defined as the failure to achieve a clinical pregnancy after 12 months of regular, unprotected sexual intercourse in women under 35 years of age, or after 6 months in women aged 35 and above, based on medical records and clinical evaluation. Cases with known male factor infertility were excluded from this definition. Pain and dyspareunia were assessed using a 10-cm Visual Analog Scale (VAS), scored from 0 (no pain) to 10 (worst imaginable pain) [ 24 ]. Quality of life was evaluated using the validated Persian version of the Endometriosis Health Profile-30 (EHP-30) questionnaire. Each of the 30 items was rated on a 5-point Likert scale (0 = never to 4 = always), and domain scores were transformed to a standardized 0–100 scale, where higher values indicate poorer quality of life. For categorical analysis, participants were divided into two groups according to the median total EHP-30 score: those with scores above the median were classified as having weak (poor) quality of life, and those at or below the median were considered to have good quality of life [ 25 ]. Data analysis was performed using Stata version 17 software. Descriptive statistics were used to summarize the demographic and clinical characteristics of the study population. Categorical variables were presented as frequency and percentage (n, %), and continuous variables were presented as mean ± standard deviation. For comparing qualitative (categorical) variables between the two groups, the Chi-square test was used. An independent samples t-test was employed to compare quantitative variables between the endometriosis-only group and the endometriosis with PCOS group. To further investigate the association between PCOS comorbidity and key clinical outcomes while controlling for potential confounders, binary logistic regression analysis was performed. The model was adjusted for age, and the results were expressed as adjusted odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) and p -values. A p -value of less than 0.05 was considered statistically significant for all tests.