Diagnostic delays in endometriosis contribute to underdiagnosis and undertreatment. The objective of this review was to evaluate existing and emerging nonsurgical diagnostic tools that, after validation, may reduce diagnostic delays. Studies were selected from a comprehensive PubMed literature search using the keywords: endometriosis, diagnosis, biomarker, imaging, and statistics. English-language studies reporting potential diagnostic performance with an area under the curve (AUC) ⩾ 0.8 and/or sensitivity and specificity ⩾ 80% were included. Of 309 studies, 91 studies investigating 81 unique diagnostic modalities met eligibility criteria. Sixty studies evaluated biomarkers in blood/serum, three in urine, three in saliva, three in leukorrhea, ten in peritoneal fluid, eleven evaluated endometrial biopsy-related markers, and twelve assessed imaging modalities. Biomarkers with the highest reported AUC included CK-19 and TNF-α in blood, urinary proteomic markers (five peptides m/z = 1433.9, 1599.4, 2085.6, 6798.0, and 3217.2 Da), salivary miRNAs (hsa-miR-135a), tRNA-Leu-AAG-01 in leukorrhea, vasoactive intestinal peptide (VIP) in endometrial nerve fibers, caldesmon levels in endometrial biopsies, and MRI-based imaging techniques. Across modalities, findings were largely derived from single-center studies with heterogeneous populations, underscoring the need for large, multicenter prospective validation studies to establish reproducibility and clinical utility.
Chronic endometritis (CE) is an inflammatory disorder of the endometrium, whose pathogenesis has not been fully elucidated. Although CE may be asymptomatic or it may present with subtle symptoms, it may cause significant adverse outcomes on human reproduction including an increased risk of recurrent miscarriages (RM) and recurrent implantation failure (RIF). The diagnostic procedure includes hysteroscopy with a targeted biopsy from areas suspected of having abnormalities. Histopathological assessment involves the identification of immunohistochemical markers for plasma cells, such as CD138 and MUM-1. The treatment of CE in women with a history of RIF may increase clinical pregnancy rates, implantation rates and ongoing pregnancy rates/live birth rates. It mainly concerns antibiotic therapy, with doxycycline as the first-line treatment. Surgical removal is necessary in cases of lesions such as fibroids, polyps or severe intrauterine adhesions. We aimed to summarize current knowledge in the field of the effective diagnosis and treatment of CE.
Endometriosis (END) is a gynecological disease marked by the presence of endometrial-like tissue outside the uterus, inducing estrogen-driven inflammation that manifests through chronic pelvic pain, dysmenorrhea, and infertility, which impacts life quality. The pathophysiology of END involves genetic factors, hormonal imbalances, and immune disorders, generating pro-angiogenic and inflammatory environment. Resveratrol (RES), a naturally occurring polyphenol, recently became known as a potential therapeutic product owing to its diverse biological functions. This review examines the pathophysiological origins of END and clarifies the processes by which RES has therapeutic benefits. Resveratrol offers a novel, non-hormonal treatment strategy for endometriosis management by exhibiting anti-proliferative, anti-invasive, anti-adhesive, pro-apoptotic, antioxidant, anti-inflammatory, anti-angiogenesis, and hormone-modulating properties.
Introduction: Evidence for the role of extracellular vesicles (EVs) in endometriosis pathophysiology suggests EVs may be a novel avenue for biomarker exploration. This study employed small particle flow cytometry to investigate plasma EVs with endometrial stromal cell markers and cervicovaginal fluid EVs with immunological receptors as diagnostic biomarkers of endometriosis.Methods: Blood and cervicovaginal fluid were collected from consenting patients undergoing surgery for suspected endometriosis. EVs were isolated from plasma (n = 15 per group) and cervicovaginal fluid (n = 20 per group), stained overnight with antibody probes, labelled with Aco-430 membrane stain then analysed by flow cytometry (Cytek Aurora). The proportions and antigen density of positive EVs were compared between people with endometriosis and symptomatic controls.Results: Measuring triple-positive EVs was deemed unsuitable given the variability in staining when multiplexing antibodies. Small proportions of antigen positive EVs were detected for all proteins investigated, however, no differences were observed for CD10+, CD90+, CD10+CD90+ and CD140b+ plasma EVs, or CCR2+, CD55+, CD59+ and CD82+ cervicovaginal fluid EVs.Conclusions: Although the EV populations did not distinguish endometriosis from symptomatic controls, this study provides valuable methodological insights into EV phenotyping to support future biomarker research and advance understanding of EV-mediated mechanisms in endometriosis.
Introduction: Pelvic floor disorders are common and debilitating conditions affecting women. This study aims to determine the prevalence of pelvic floor disorders among Ethiopian women and to identify associated risk factors. Method: This systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. Primary studies were identified through electronic searches of Google Scholar, HINARI, MEDLINE, and PubMed. Result: A total of 23 papers meeting the inclusion criteria were included in this systematic review and meta-analysis of pelvic floor disorders. Sixteen studies were used for the pooled prevalence analysis. In Ethiopia, the pooled prevalence of pelvic floor disorders was 22% (95% confidence interval (CI) = 16, 28). The following factors were found to be associated with pelvic floor disorders: age at first delivery under 20 years (pooled odds ratio (POR) = 5.08, 95% CI = 3.1, 8.33), multiparity (POR = 4.23, 95% CI = 2.9, 6.16), age 40 years or older (POR = 3.67, 95% CI = 2.21, 6.11), carrying heavy objects (POR = 3.73, 95% CI = 2.98, 4.68), chronic cough (POR = 4.68, 95% CI = 2.21, 9.94), instrumental-assisted vaginal delivery (POR = 3.7, 95% CI = 2.45, 5.57), menopause (POR = 3.62, 95% CI = 2.53, 5.18), history of chronic constipation (POR = 3.37, 95% CI = 2.25, 5.02), prolonged labor (POR = 4.63, 95% CI = 2.56, 8.38), and sphincter damage (POR = 3.93, 95% CI = 1.85, 8.32). Conclusion: Pelvic floor disorders represent a major but often overlooked health issue for Ethiopian women, with substantial implications for their well-being. Addressing these disorders requires coordinated efforts in prevention, early diagnosis, and management, as well as broader social and health system changes to reduce stigma and improve access to care.
Introduction: Irritable Bowel Syndrome (IBS) is a prevalent digestive disorder characterized by abdominal pain and changes in bowel movements without any structural disorders. The present study aims to explore the impact of group Cognitive Behavioral Therapy (CBT) on resilience, functional anxiety, and the severity of IBS symptoms in patients from Hamadan, Iran. Methods: This study employed a semi-experimental, pre-test-post-test design with a control group. The participants were patients diagnosed with IBS referred to the gastroenterology clinic at Ibn Sina Hospital in Hamedan, Iran. A total of 40 patients were selected through simple random sampling and divided into experimental and control groups. The intervention consisted of CBT, based on the framework by Leahy et al. To measure the outcomes, this study used the Connor-Davidson Resilience Scale (CD-RISC) (2003), the Zung Self-Rating Anxiety Scale (SAS) (1970), and the Irritable Bowel Syndrome Severity Score (IBSSS). After completing the intervention, this research administered a post-test to both groups using the same questionnaires. Results: The study utilized multivariate and univariate covariance analyses to examine the data and test the research hypotheses. The results revealed that group CBT sessions led to notable differences between the experimental and control groups. Specifically, the subjects in the experimental group showed a significant reduction in functional anxiety, a decrease in the severity of IBS, and an increase in resilience compared to the control group. Conclusion: The results indicate that group CBT significantly reduces functional anxiety and the severity of IBS symptoms while boosting resilience.
Endometriosis is clinically associated with chronic inflammatory process, pain, and poor quality of life. Exercise has a broad spectrum of action in the prevention and therapeutic of a wide range of diseases. The present study has the proposal to investigate whether exercise interventions possess beneficial impact on pain outcome on endometriosis. A comprehensive systematic literature search of Pubmed/MEDLINE, Cochrane, Embase, and Web of Science databases was conducted (from May 2024 to April 2025), for randomized, controlled (control non-exercised groups), exercise trials involving individuals with endometriosis diagnosis. The risk of bias was assessed by Rob 2 tool, the quality and reporting of exercise interventions by TESTEX scale, and the certainty of evidence by GRADE system. Four studies were included in the analysis. Despite presenting a high risk of bias, an overall positive effect of physical exercise interventions relative to the non-exercised controls was observed (SMD 95% = −1.017 (−1.355 to −0.679); p < 0.001) regarding general pain (primary outcome) related to endometriosis. With respect to specific pain types related to endometriosis symptomatology (secondary outcome), physical exercise interventions were able to significantly reduce catastrophizing pain and pelvic pain, but not dyschezia, dysmenorrhea, dyspareunia, or dysuria. These results could be important for the clinical care of women with endometriosis-related chronic pain. However, given the heterogeneity, high risk of bias, and low quality of the included studies it can be challenging to draw reliable conclusions. This data unveils the promising potential applicability of exercise for health promotion in patients with pain resulting from endometriosis.
Objective: To systematically evaluate the epidemiology, diagnostic modalities, and treatment strategies for urinary tract endometriosis (UE), with the goal of informing evidence-based clinical practice. Materials and methods: A comprehensive search of PubMed, Ovid, Embase, MEDLINE, and the Cochrane Library was conducted from January 1976 to March 2023. The protocol was registered with INPLASY (INPLASY202420054). Original studies reporting clinical, diagnostic, or therapeutic aspects of urinary tract endometriosis (UE) involving the bladder, ureter, kidney, or urethra were included, while reviews, editorials, and duplicate publications were excluded. Three reviewers independently screened articles, extracted relevant data, and categorized findings by site of involvement and diagnostic or treatment modality. A narrative synthesis of the results was performed. Results: A total of 137 studies were included. Bladder endometriosis was the most common subtype (80%–85%), followed by ureteral involvement (9%–23%). MRI and transvaginal ultrasound showed the highest sensitivity and specificity for diagnosis. Minimally invasive surgery, particularly robotic-assisted laparoscopy, was associated with favorable outcomes and lower recurrence rates. Conclusion: UE is a rare and underdiagnosed manifestation of deep infiltrating endometriosis. Early recognition with appropriate imaging and multidisciplinary surgical planning improves outcomes. Larger prospective studies are needed to inform standard guidelines.
Endometriosis is a chronic gynecological condition with profound consequences. Despite increasing research, studies on health-related quality of life (HRQoL) in endometriosis remain fragmented, often neglecting the interplay between medical and psychosocial aspects. This narrative review aims to provide an integrated perspective on the medical and psychosocial factors influencing HRQoL in individuals with endometriosis. A comprehensive literature search identified peer-reviewed studies examining both qualitative and quantitative research. Medical aspects such as chronic pain, dysmenorrhea, infertility, dyspareunia, fatigue, and treatment side effects were strongly associated with reduced HRQoL. Psychosocial aspects included depression, anxiety, self-esteem, body-image, coping strategies, illness perceptions, and social and work-related challenges. Treatment-related aspects, including diagnostic delay and patient-centered care, emerged as important factors associated with HRQoL. The findings highlight the necessity of a holistic approach to improve patients’ HRQoL. However, research on the implementation and effectiveness of such approaches remains scarce. Future research should prioritize adolescents, longitudinal designs, and integrative analytic frameworks to better capture both short and long-term effects of the complex interactions between medical and psychosocial factors relevant to HRQoL in those affected.
The development of novel therapies for endometriosis is a rapidly evolving field, encompassing diverse approaches to address this complex and chronic condition. Current treatment modalities, predominantly hormonal therapies and surgical interventions, fall short of providing optimal outcomes, necessitating a quest for more effective and targeted solutions. Endometriosis is a multifaceted disorder with intricate connections to various factors, including the immune system, genetics, menstrual patterns, and cellular metaplasia. Immunotherapy emerges as a promising avenue, recognizing the pivotal role of the immune system in the disease’s development and progression. Studies reveal immune system imbalances in women with endometriosis, including altered cytokine production and compromised immune cell function. Potential immune therapy targets encompass G-CSF treatment, hypoxia alleviation, TNF antagonists, and vaccinations. Intriguingly, intra-uterine ethiodized oil administration demonstrates a positive impact on fertility, influencing immune cells and enhancing endometrial receptiveness. Notably, immune checkpoint inhibitors, such as the PD-1/PD-L1 pathway, are being explored for endometriosis treatment. Endometrial stem cells and epigenetic alterations contribute to the pathogenesis of endometriosis, presenting potential targets for intervention. Understanding the microbiome’s influence on endometriosis is also emerging. Investigating microbiome-based biomarkers and personalized treatment strategies adds another layer to the evolving landscape of endometriosis management. In conclusion, the pursuit of novel endometriosis treatments is rapidly advancing, with immunotherapy, stem cell therapy, epigenetic targeting, and microbiome research opening new possibilities. Integrating these approaches while prioritizing patient safety and individualized care holds promise for improved management of this challenging condition.
Purpose: This study aimed to investigate the reciprocal relationship between endometriosis-related pain and the consumption of cannabinoids and opioids. Additionally, this study explores whether pain-related anxiety acts as a mediator in this relationship by adopting a transactional model of adaptation to endometriosis.Methods: This cross-sectional study included 334 adult women diagnosed with endometriosis. An online questionnaire, distributed through social networks and patient associations, gathered data on pain intensity, substance use (cannabis, CBD, and opioids), pain-related anxiety, distress tolerance, and anxiety sensitivity.Results: Descriptive statistics revealed that 74.25% of participants reported using at least one substance. Pain was positively correlated with the severity level of CBD, opioid use, and pain-related anxiety. The severity level of cannabis uses negatively correlated with distress tolerance. Path modeling demonstrated that substance use predicted pain intensity, and that pain intensity is associated with pain-related anxiety, subsequently influencing substance use. The model suggests a transactional relationship between pain, pain-related anxiety, and substance use.Conclusions: These findings underscore the need for tailored therapeutic approaches for women with endometriosis. Substance use is associated with increased pain intensity, indicating a complex interplay. This study highlights the importance of considering psychosocial factors such as pain-related anxiety in understanding the relationship between substance use and pain in endometriosis. A comprehensive approach to care involving both medical and psychological perspectives is essential. Further studies are also required.
Introduction: Endometriosis is a condition of chronic inflammation. Data imply an association with severe autoimmune spectrum. This paper analyses the relationship between autoimmune co-morbidities and phenotypes such as the more severe forms of disease, and assesses how well immunological markers may predict advanced disease. Methods: This case-control study included 100 women of reproductive age who had endometriosis verified by laparoscopy. Based on the presence of autoimmune diseases, such as antiphospholipid syndrome (APS), rheumatoid arthritis (RA), autoimmune thyroid disorders (ATD), systemic lupus erythematosus (SLE), and type 1 diabetes mellitus (T1D), participants were divided into the study group (n = 40) and the control group (n = 60). Results: Patients with autoimmune comorbidities had a higher proportion of advanced-stage disease (stage IV; 70.0% and 5.0%; p < 0.01), especially those with antiphospholipid syndrome (APS) and type-1 diabetes mellitus. The prevalence of deep infiltrating endometriosis was also higher in the autoimmune group (p = 0.03). Autoimmunity was an independent predictor of stage IV endometriosis (AUC = 0.832). For APS, the association was very strong (OR: 48.9; p < 0.001), and similarly for T1DM (OR: 57.0; p = 0.002). Correlation analysis further showed that advanced disease is positively and significantly correlated with APS, RA, and ATD (all p < 0.001). Conclusion: The current study has emphasized that a pronounced relation exists between endometriosis and autoimmune disorders. Utilization of autoimmune screening tests can contribute to a better diagnosis and personalized treatment of endometriosis.
The rising incidence of Postural Orthostatic Tachycardia Syndrome (POTS) has presented a clinical challenge, as these patients can be refractory to traditional interventions. The aim of this study was to characterize clinical and demographic factors of endometriosis patients who were referred for the tilt table test. 297 endometriosis patients confirmed by laparoscopic biopsy and who completed a tilt table were identified via the electronic medical record (EMR). Descriptive statistics were performed and t-test comparisons represented between group differences. 26.2% of patients had a positive tilt table for POTS. Those with POTS were more likely to be younger (p < 0.001), non-Hispanic (p = 0.003), and be diagnosed with EDS (p = 0.02). They were more likely to be prescribed cardiovascular agents and have an intrauterine device (IUD). There were no differences between groups for prevalence or severity of gastroparesis, depression, anxiety, or self-reported symptoms of autonomic dysfunction. Future study is warranted to determine the clinical significance of POTS in women with endometriosis.
Background: Adenomyosis is a common benign uterine condition typically associated with pelvic pain, heavy menstrual bleeding, and dysmenorrhea. While its histopathological features are well established, there are no well-documented English literature reports specifically characterizing multinucleated giant cell reaction (GCR) inside adenomyosis.Case presentation: A 43-year-old woman, gravida 1 para 1, presented with a 10-year history of progressively worsening pelvic pain that markedly impaired her quality of life. She was a known adenomyosis patient based on serial ultrasonographic examinations. She was treated with several medical therapies, including different progestogens (including dienogest for 9 months), repeated GnRH-analog injections, and escalating analgesics up to tramadol hydrochloride, without symptom relief. Her pain continued to worsen and eventually became unmanageable. After receiving Institutional Review Board (IRB) and insurance approvals, anesthesia clearances, and informed consent; she underwent a total abdominal hysterectomy with bilateral opportunistic salpingectomy. On gross examination, the uterus showed diffuse adenomyosis with areas of dark discoloration. Microscopic analysis confirmed adenomyosis with a striking GCR with haphazardly arranged nuclei surrounding brownish pigment deposits between smooth muscle fibers. No evidence of granulomatous disease was found. Remarkably, her pain disappeared completely after surgery, and she experienced a dramatic improvement in quality of life.Conclusion: This case appears to be the first to describe a multinucleated giant cell reaction (GCR) within adenomyosis. It broadens the known histopathologic features of adenomyosis and suggests that a chronic inflammatory response to repeated intramyometrial bleeding may play a role in severe, treatment-resistant symptoms. Recognizing this finding can help avoid diagnostic confusion and may encourage further research into inflammatory pathways involved in refractory adenomyosis.
Accessory cavitated uterine malformation (ACUM) is a possible cause of disabling dysmenorrhea. We present a case that is clinically atypical due to the late onset of symptoms (in the fourth decade of life, after pregnancy and cessation of suppressive hormone therapy), but at the same time, sonographically, fully corresponds to a typical ACUM, being one of the largest ever documented. Gynecologists and pelvic imagers should be familiar with the diagnostic criteria and consider ACUM as one of the differential diagnoses in women with pelvic pain and cystic myometrial lesion, especially when it is solitary.
Background: Dienogest (DNG) is a fourth-generation progestin used frequently for medical treatment of endometriosis. dienogest has been known as an effective treatment in alleviating pain, preventing recurrence, and enhancing the quality of life in patients. Considering the contradictory results regarding the side effects of DNG, such as the risk of decreasing bone mineral density, physiologic disorder, menometroraghy, and its effects in the treatment of endometriosis, this study was conducted to assess the efficacy and side effects of DNG 2 mg daily for 24 weeks in Iranian women with endometriosis. Methods: Before and 24 weeks after starting treatment with DNG, lumbar and pelvic bone mineral density (BMD) was measured. Changes in the severity of dysmenorrhea and dyspareunia and side effects were recorded using a visual analog scale. Results: The change in the investigated variables before and after the intervention was compared using chi-square and paired t-test. The mean age of the patients was 35.42 +/- 4.76 years. Following the intervention, Dysmenorrhea and dyspareunia were significantly decreased (p < 0.001). Total pelvic and vertebra BMD did not change substantially after the intervention, except for L1, which was significantly reduced after treatment (0.37 +/- 0.96-0.22 +/- 0.89; p = 0.01). Conclusion: The results of this study suggested that 24 weeks of treatment with DNG had no significant adverse effect on BMD. On the other hand, the use of DNG in endometriosis patients was associated with improvement in dysmenorrhea and dyspareunia scale.
Background: Endometriosis is a common gynecological condition that in sporadic cases can mimic an ovarian malignancy. We report a unique case of endometriosis characterized by massive hemorrhagic ascites and a mass-like plaque on the uterine surface. Atypical endometriosis is recognized as a potential precursor to ovarian malignancies.Case presentation: A 51-year-old woman with no significant medical history presented with abdominal pain, massive ascites and abnormal findings on ultrasound and CT. This, together with an elevated CA-125 level pre-operatively raised suspicion for ovarian malignancy. Diagnostic laparoscopy with frozen section biopsy was executed and the uterus and adnexa were removed. The final diagnosis however revealed an atypical presentation of endometriosis.Conclusion: This case highlights a rare manifestation of endometriosis that closely mimics ovarian malignancy. Clinicians should consider this differential diagnosis when encountering similar presentations.
Introduction: Endometriosis, a chronic inflammatory disease often beginning in adolescence, significantly impacts quality of life. Delayed diagnosis contributes to prolonged suffering, educational disruption, and high healthcare costs. Promoting menstrual health education in schools may aid early recognition and intervention. This study aimed to implement and evaluate Endo-Teach, a menstrual health and endometriosis education program for seventh and eighth grade students, assessing its effectiveness in improving their understanding of endometriosis.Methods: The implementation of the teaching package Endo-Teach, developed by a group of specialists at the certified endometriosis center of the Bern University Hospital, Switzerland, was evaluated using a voluntary questionnaire distributed before and after the class.Results: Within a total collective of 177 students, the mean age was 14.37 years. Awareness of endometriosis among adolescents was initially low (30.4%). Just over half (50.6%) of female adolescents reported having very painful menstruation; 54.5% of the adolescents reporting very painful period or insecurity about it needed to take pain medication, and 23.6% missed school regularly due to menstrual pain. The teaching package was evaluated as clear (96.5%) and educative (97.7%).Conclusion: The teaching package Endo-Teach in its actual form is a valid option to promote awareness of menstrual health and endometriosis in secondary schools. In Switzerland, the prevalence of severe menstrual pain in secondary-school students, including the use of pain medication and school absenteeism, is high, whereas awareness of endometriosis is low. This shows that offering age-appropriate educational measures in a broader context is important to reduce the burden of the disease.
