Diagnosis Of Endometriosis Research Articles

Endometriosis of the appendix mimicking appendicitis: Histomorphology and case report

Introduction: Even though endometriosis is relatively common among women of reproductive age, endometriosis of the appendix is rare. It has various clinical presentations and sometimes mimics appendicitis. Diagnosis is made from microscopic examination. Case Description: Here, we report a case of a 42-year-old woman with severe right lower abdominal pain. An appendectomy was performed, and the tissue specimen was analyzed. Endometrial glands and stroma were found in the muscularis propria and serosa. The diagnosis of appendiceal endometriosis was established histologically. Conclusion: Endometriosis of the appendix is a rare case. It can mimic appendicitis and is hard to detect preoperatively. A histopathology examination was recommended to confirm the diagnosis.

Intra- and interobserver reproducibility of transvaginal ultrasound for the detection and measurement of endometriotic lesions of the bowel.

The number and invasion depth of endometriotic bowel lesions, total length of bowel affected by endometriosis, lesion-to-anal verge distance, and extent of pouch of Douglas obliteration are important factors in preoperatively determining risk and complexity of endometriosis surgery. The intra- and interobserver reproducibility of transvaginal ultrasound in the evaluation of many of these parameters has not yet been investigated. Our study aimed to assess the intra- and interobserver reproducibility of transvaginal ultrasound between an experienced and less experienced examiner for all of these parameters. This prospective observational cross-sectional study was conducted between July 2019 and November 2020. Fifty consecutive premenopausal women who underwent transvaginal ultrasound examination in our clinic for the first time, were examined by the same two operators during the same attendance. Outcomes of interest were the inter-rater reproducibility of transvaginal ultrasound for detecting the presence, number, depth and size of bowel endometriotic nodules, lesion-to-anal-verge distance, total length of bowel affected, and pouch of Douglas obliteration. The intraobserver reproducibility was assessed for the continuous parameters. Cohen's kappa (κ) statistic, Cohen's weighted kappa (κ), proportions of agreement, intraclass correlation coefficient (ICC) and Bland-Altman limits of agreement were used to assess the reproducibility of the parameters. The inter-rater agreement and reliability were very good for identifying bowel endometriosis, the number and invasion depth of bowel nodules, determining whether the maximum nodule length was <3 cm, and lesion-to-anal-verge distance <8 cm (proportion of agreement 0.92, 0.94, 0.97, 0.94, 0.96; κ 0.92, 0.91, 0.92, 0.82, 0.89). The inter-rater agreement and reliability were good for assessing pouch of Douglas obliteration (proportion of agreement 0.86, κ 0.80). The intra-rater reliability for the mean nodule diameter (ICC 0.93 and 0.97) and total length of bowel affected (ICC 0.94 and 0.91) were excellent for operators A and B, respectively. The inter-rater reliability for the mean nodule diameter was good (ICC 0.80), and moderate for the total length of bowel affected (ICC 0.70). The Bland-Altman limits of agreement demonstrated clinically acceptable ranges for these two parameters. This study demonstrated a high intra- and inter-rater reproducibility of transvaginal ultrasound in the diagnosis of bowel endometriosis and measurement of its various components.

Thoracic Endometriosis Syndrome (TES) in Martinique, a French West Indies Island.

Endometriosis is a female disease that affects 5-10% of women of childbearing age, with predominantly pelvic manifestations. It is currently declared as a public health priority in France. Thoracic endometriosis syndrome (TES) is the most common extra-pelvic manifestation. The objective of this study was to describe the epidemiological and clinical characteristics, and outcomes of patients with TES in Martinique. We performed a descriptive, retrospective study including all patients managed at the University Hospital of Martinique for TES between 1 January 2004 and 31 December 2020. During the study period, we identified 479 cases of pneumothorax, of which 212 were women (44%). Sixty-three patients (30% of all female pneumothorax) were catamenial pneumothorax (CP) including 49 pneumothoraxes alone (78% of catamenial pneumothorax) and 14 hemopneumothorax (22% of catamenial pneumothorax). There were 71 cases of TES, including 49 pneumothoraxes (69%), 14 hemopneumothoraxes (20%) and 8 hemothorax (11%). The annual incidence of TES was 1.1 cases/100,000 inhabitants. The prevalence of TES was 1.2/1000 women aged from 15 to 45 years and the annual incidence of TES for this group was 6.9/100,000. The annual incidence of CP was 1 case/100,000 inhabitants. The average age at diagnosis was 36 ± 6 years. Eight patients (11%) had no prior diagnosis of pelvic endometriosis (PE). The mean age at pelvic endometriosis diagnosis was 29 ± 6 years. The mean time from symptom onset to diagnosis was 24 ± 50 weeks, and 53 ± 123 days from diagnosis to surgery. Thirty-two patients (47%) had prior abdominopelvic surgery. Seventeen patients (24%) presented other extra-pelvic localizations. When it came to management, 69/71 patients (97%) underwent surgery. Diaphragmatic nodules or perforations were found in 68/69 patients (98.5%). Histological confirmation was obtained in 55/65 patients who underwent resection (84.6%). Forty-four patients (62%) experienced recurrence. The mean time from the initial treatment to recurrence was 20 ± 33 months. The recurrence rate was 16/19 (84.2%) in patients who received medical therapy only, 11/17 (64.7%) in patients treated by surgery alone, and 17/31 (51.8%) in patients treated with surgery and medical therapy (p = 0.03). We observed a very high incidence of TES in Martinique. The factors associated with this high incidence in this specific geographical area remain to be elucidated. The frequency of recurrence was lower in patients who received both hormone therapy and surgery.

Dysmenorrhea in adolescents requires careful investigation of endometriosis-an analysis of early menstrual experiences in a large case-control study.

Recent evidence shows that endometriosis, a significant cause of infertility, may already present in adolescents. Dysmenorrhea, often leading to school absences, is a key symptom of the maturing menstrual cycle but also of endometriosis. However, it is often perceived as "normal" and left untreated. In adolescents, laparoscopy, the standard procedure to diagnose endometriosis, is performed particularly cautiously. To improve reproductive health in adolescents, we evaluate associations between early menstrual experiences and endometriosis. Retrospective data on early menstrual experiences from 563 women with surgically/histologically verified endometriosis and from 563 age-matched controls were compared. Study participants were recruited in Switzerland, Germany, and Austria. Information on menstrual experiences was collected via a structured questionnaire. The bivariate analysis showed that early menarche (p = 0.004), dysmenorrhea and negative memories of menarche (p < 0.001) were significantly associated with a diagnosis of endometriosis. After controlling for confounders in bivariate regression analysis occurrence of dysmenorrhea (p = <0.001, OR 5,74, 95% CI 3.82-7.22) especially with onset >3 years after menarche ((p = <0.001, OR 3.42, 95% CI 2.09-5.64) remained statistically significant predictors for diagnosis of endometriosis. Dysmenorrhea in mothers and mothers' perceived attitude towards menstruation were not associated with the occurrence of Endometriosis. Dysmenorrhea and onset of dysmenorrhea at menarche or several years after it are strongly associated with the development of endometriosis. As mothers perceived attitudes towards menstruation show no significant association with their daughters' experiences, physical symptoms accompanying menarche and menstrual period pain in adolescents seem to be very reliable predictors in diagnosis of endometriosis. Therefore, dysmenorrhea in adolescents requires careful investigation of possible endometriosis, especially if it does not respond to medical management. The study was registered on ClinicalTrials.gov, identifier (NCT02511626).

Diagnostic and therapeutic approaches for endometriosis: a patent landscape.

The aim of this review is to analyze the patent filings and to systematize the main technological trends in patent protection for the diagnosis and therapeutics for endometriosis. Patent literature has also been explored to identify active inventors and applicants in this field. Patent search was carried out in the freely accessible patent search databases namely, patentscope using various combinations of the keywords "Endometriosis OR Adenomyosis" AND "Diagnostic OR Therapeutics" were used along with wildcard search queries in the "Title", "Abstract" and "Descriptions" fields. A patent search revealed 144 patents describing inventions for diagnostic and therapeutic purposes of endometriosis. These patents include 26 patent applications in the diagnostic utility and 116 patent applications under the therapeutic approaches. Out of these 116 patent applications, 43 describe traditional medicines for endometriosis. Two patent applications describe inventions that can fall into both categories. Efforts are being made to improve current diagnostic instruments.Hormonal alteration methods is the most common field of invention, followed by surgical interventions for therapeutics. A general trend of increase in patent application filings has been observed with a slight decrease in recent years.

Users' Concerns About Endometriosis on Social Media: Sentiment Analysis and Topic Modeling Study.

Endometriosis is a debilitating and difficult-to-diagnose gynecological disease. Owing to limited information and awareness, women often rely on social media platforms as a support system to engage in discussions regarding their disease-related concerns. This study aimed to apply computational techniques to social media posts to identify discussion topics about endometriosis and to identify themes that require more attention from health care professionals and researchers. We also aimed to explore whether, amid the challenging nature of the disease, there are themes within the endometriosis community that gather posts with positive sentiments. We retrospectively extracted posts from the subreddits r/Endo and r/endometriosis from January 2011 to April 2022. We analyzed 45,693 Reddit posts using sentiment analysis and topic modeling-based methods in machine learning. Since 2011, the number of posts and comments has increased steadily. The posts were categorized into 11 categories, and the highest number of posts were related to either asking for information (Question); sharing the experiences (Rant/Vent); or diagnosing and treating endometriosis, especially surgery (Surgery related). Sentiment analysis revealed that 92.09% (42,077/45,693) of posts were associated with negative sentiments, only 2.3% (1053/45,693) expressed positive feelings, and there were no categories with more positive than negative posts. Topic modeling revealed 27 major topics, and the most popular topics were Surgery, Questions/Advice, Diagnosis, and Pain. The Survey/Research topic, which brought together most research-related posts, was the last in terms of posts. Our study shows that posts on social media platforms can provide insights into the concerns of women with endometriosis symptoms. The analysis of the posts confirmed that women with endometriosis have to face negative emotions and pain daily. The large number of posts related to asking questions shows that women do not receive sufficient information from physicians and need community support to cope with the disease. Health care professionals should pay more attention to the symptoms and diagnosis of endometriosis, discuss these topics with patients to reduce their dissatisfaction with doctors, and contribute more to the overall well-being of women with endometriosis. Researchers should also become more involved in social media and share new science-based knowledge regarding endometriosis.

Utilization of healthcare prior to endometriosis diagnosis: a Danish case-control study.

Do women with endometriosis have higher utilization of primary and secondary healthcare prior to diagnosis compared to women without endometriosis? Women with a hospital-based diagnosis of endometriosis had an overall higher utilization of both primary and secondary healthcare in all 10 years prior to diagnosis. Endometriosis is associated with a diagnostic delay, but only a few studies have investigated the potential consequences of this delay with regard to the utilization of healthcare. To the best of our knowledge, no study has investigated it in a period corresponding to the estimated diagnostic delay. This national Danish registry-based case-control study included 129 696 women. Cases were women with a first-time hospital-based diagnosis of endometriosis between 1 January 2000 and 31 December 2017. We identified 21 616 cases using density sampling. Each case was matched on age at the date of diagnosis (index date) to five women without diagnosed endometriosis (n = 108 080). The utilization of healthcare was assessed for the 10 years before the index. Cases had significantly higher use of healthcare in all 10 years preceding the index. The mean number of yearly contacts with the GP was 9.99 for cases and 7.85 for controls, with an adjusted incidence rate ratio of 1.28 (1.27; 1.29). For hospital contacts, the association increased slightly in the first 9 years and was most profound in the last year preceding index when the adjusted incidence rate ratio was 2.26 (95% CI 2.28; 2.31). We were not able to include women with an endometriosis diagnosis from the general practitioner or private gynaecologist. Therefore, our results are only applicable to hospital-based diagnoses of endometriosis. We do not have information on the specific reasons for contacting the healthcare providers and we can therefore only speculate that the higher utilization of healthcare among cases was related to endometriosis. This study is in agreement with the other known studies on the subject. Future studies should include specific reasons for contacting the healthcare system and thereby identify any specific contact patterns for women with endometriosis. With this knowledge, healthcare professionals could be better at relating certain healthcare seeking behaviour to endometriosis earlier and thereby reduce the time from onset of symptoms to diagnosis. This study is supported by grants from the project 'Finding Endometriosis using Machine Learning' (FEMaLe/101017562), which has received funding from The European Union's Horizon 2020 research and innovation program and Helsefonden (21-B-0141). K.Z. report grants from Bayer AG, Roche Inc. and Volition, royalties from Oxford-Bayer scientific collaboration in gynaecological therapies, non-financial collaboration with the World Endometriosis Society and World Endometriosis Research Foundation and is a Wellbeing of Women research advisory committee member. All this is outside the submitted work. The other authors have no conflict of interest to declare. N/A.

Modern non-invasive diagnosis of endometriosis

Introduction. Endometriosis is a disease characterized by an overgrowth of morphologically and functionally endometrium-like tissue outside the uterine cavity. Early diagnosis of endometriosis is very difficult. The gold standard for diagnosis is the surgical method − laparoscopy, performed for infertility, pelvic pain or the presence of pelvic masses. However, this approach is currently being reconsidered, and the search for endometriosis markers for earlier diagnosis of this disease is relevant.The purpose of the literature review was to summarize the current data on promising noninvasive markers of endometriosis determined in various biological media.Materials and methods. Scientific literature was searched in PubMed, ResearchGate, and Elibrary databases for 2017−2022 using a combination of Russian and English keywords: endometriosis, endometrioma, endometriosis pathogenesis, peritoneal fluid, biomarkers, serum markers.Results. We evaluated more than 30 putative biomarkers in peritoneal fluid, serum, urine, and saliva, as well as their combinations in publications that met the selection criteria. Studies have evaluated the diagnostic value and efficacy of endometriosis biomarkers, but the results of these studies have sometimes been inconsistent. We were unable to identify a single biomarker or combination of biomarkers that was unequivocally clinically useful. The most significant changes in biochemical composition were observed in peritoneal fluid, but it requires invasive intervention to obtain it.Discussion. Saliva and urine studies have shown promising results in terms of diagnostic accuracy, but the evidence was of low quality for introduction into clinical guidelines. A number of serum biomarkers may be useful either for detecting endometriosis at early stages or for differentiating ovarian endometrioma from other benign ovarian masses, but the evidence for meaningful conclusions is insufficient. Conclusion None of the biomarkers have shown sufficient accuracy for clinical use outside of the research environment, yet research in this area remains promising.

Use of the Free Endometriosis Risk Advisor App as a Non-Invasive Screening Test for Endometriosis in Patients with Chronic Pelvic Pain and/or Unexplained Infertility.

Endometriosis is a prevalent condition that affects millions of individuals globally, leading to various symptoms and significant disruptions to their quality of life. However, the diagnosis of endometriosis often encounters delays, emphasizing the pressing need for non-invasive screening. This retrospective cross-sectional study aimed to evaluate the utility of the Endometriosis Risk Advisor (EndoRA) mobile application in screening for endometriosis in patients with chronic pelvic pain and/or unexplained infertility. The study consisted of 293 patients who met specific criteria: they were English-speaking individuals with chronic pelvic pain and/or unexplained infertility, owned smartphones, and had no prior diagnosis of endometriosis. The results demonstrated that the EndoRA score exhibited a high sensitivity of 93.1% but a low specificity of 5.9% in detecting endometriosis. The positive predictive value was 94.1%, while the negative predictive value was 5.0%. Although the study had limitations and potential selection bias, its findings suggest that EndoRA can serve as a valuable screening tool for high-risk individuals, enabling them to identify themselves as being at an increased risk for endometriosis. EndoRA's non-invasive nature, free access, and easy accessibility have the potential to streamline evaluation and treatment processes, thereby empowering individuals to seek timely care and ultimately improving patient outcomes and overall well-being.

Current Diagnostic Possibilities for the Initial Forms of External Endometriosis

Background. Routine use of ultrasound methods does not always allow detecting endometriosis in the early stages. It is necessary to develop more accurate criteria for the diagnosis of endometriosis in its initial stages of development. Objective: to assess ultrasound and biological markers of endometriosis “small” forms of different localization in infertile women.Material and methods. Ultrasound examination of 208 infertile patients with initial stages of external endometriosis (1–15 points by revised American Fertility Society (rAFS) classificatoon) was performed (main group). The control group consisted of 195 healthy women of childbearing age. To verify the diagnosis, it is suggested to use a panel of biomarkers, including interleukins (IL) 1β and 6, CA125, HE4 as well as the ROMA (Risk of Ovarian Malignancy Algorithm) index in the dynamics of the menstrual cycle.Results. On ultrasound scans, 56 (94.9%) patients had small one- and two-sided ovarian cysts corresponding to endometriosis stage 1–2 (rAFS), and in 3 (5.4%) of them, the ultrasound result was questionable. Detectability during the initial ultrasound examination in the Douglas space was 76.9%, in the rest of cases the ultrasound picture was doubtful. Peritoneal endometriosis was detected only in 5 patients. In the remaining cases (88.9%), additional studies were necessary, including surgical (laparoscopy). The average content of CA125 in the main group on days 3–5 of the menstrual cycle was 42.6 (2.1) U/ml, on days 21–23 – 39.6(2.2) U/ml (p=0.32); in the control group, 5.1 (0.4) and 4.8 (0.7) U/ml, respectively (p = 0.71). The increase in CA125 in the main group was almost 8 times higher than in the control group, however, according to the indicators of HE4 and the ROMA index, statistically significant differences in the groups were not obtained. In the dynamics of the menstrual cycle, the content of ILs in the main group significantly decreased by days 21–23 of the cycle, while the content of CA125 and HE4 remained practically unchanged. Such sharp fluctuations of the considered biomarkers were not detected in the control group. However, even on days 21–23 of the cycle, the average content of ILs and CA125 in women of the main group remained statistically significantly higher than in the control group.Conclusion. In infertile women with dubious ultrasound criteria of external endometriosis, the use of IL1β and IL-6, which stimulate the immune inflammatory response, as well as tumor markers CA125, HE4 and ROMA index allows to differentiate the disease in the initial stages.

Challenges in diagnosing and managing endometriosis in general practice: A Western Australian qualitative study.

To reduce diagnostic delay for women with endometriosis-related symptoms, we need to understand general practitioners' (GPs) perspectives on the challenges they face in diagnosing and managing endometriosis. Qualitative interviews were conducted with nine Western Australian GPs to explore their knowledge, experiences andchallenges with the diagnosis and management of endometriosis. Three themes were identified as challenges: eliciting symptoms, with subthemes of multiple and complex symptoms, clinician experience and awareness, time constraints and screening opportunities; delivering patient-centred care, with subthemes of cultural factors and health literary, perceived gender biases and women's choices and priorities; and system and service, which included learning on the job, clearer diagnostic pathways, access to services and collaborative care models. GPs can be better supported in dealing with endometriosis through raising awareness and education; recognition ofendometriosis as a complex chronic condition; and the development of pragmatic guidelines, with increased access to local centres for excellent andcollaborative care.

Examining the co-occurrence of endometriosis and polycystic ovarian syndrome

Polycystic ovarian syndrome and endometriosis are 2 of the most common reproductive disorders among women but are thought to be unrelated. This study aimed to examine the overlap and common symptoms of polycystic ovarian syndrome and endometriosis. The study population included the Endometriosis, Natural History, Diagnosis, and Outcomes Study (2007-2009) operative cohort: 473 women, aged 18 to 44 years, who underwent a diagnostic and/or therapeutic laparoscopy or laparotomy at 1 of 14 surgical centers located in Salt Lake City, Utah, or San Francisco, California, in addition to a population cohort composed of 127 women from the surgical centers' catchment areas. Age and site-adjusted multinomial regression models were used to estimate adjusted prevalence ratios and 95% confidence intervals of reproductive history characteristics among women with endometriosis only, women with polycystic ovarian syndrome only, and women with both endometriosis and polycystic ovarian syndrome. Among the operative cohort, 35% had endometriosis only, 9% had polycystic ovarian syndrome only, and 5% had endometriosis and polycystic ovarian syndrome. Among the population cohort, 10% had endometriosis only, 8% had polycystic ovarian syndrome only, and 2% had endometriosis and polycystic ovarian syndrome. In the operative cohort, a history of subfertility was associated with a higher adjusted probability of having both conditions (adjusted prevalence ratio, 10.33; 95% confidence interval, 3.94-27.08), followed by having endometriosis only (adjusted prevalence ratio, 2.45; 95% confidence interval, 1.56-3.84) or polycystic ovarian syndrome only (adjusted prevalence ratio, 1.15; 95% confidence interval, 0.51-2.61), than having neither condition. In addition, experiencing chronic pelvic pain within the past 12 months was associated with a higher probability of having both conditions (adjusted prevalence ratio, 2.53; 95% confidence interval, 1.07-6.00) than having neither condition. Among a cohort of women undergoing gynecologic laparoscopy or laparotomy, our study found that nearly 1 in 20 women had both an incident endometriosis diagnosis and symptoms consistent with polycystic ovarian syndrome. Among a population cohort of women not seeking gynecologic care, polycystic ovarian syndrome and endometriosis overlap prevalence was approximately 1 in 50 women.

The added value of CA125, HE4, and CA72-4 as markers for ovarian endometriosis diagnosis.

This study aimed to evaluate the prognostic value as diagnosis makers of cancer antigen (CA)125, human epididymis 4 (HE4), and CA72-4 serum levels in ovarian endometriosis (OvEndo). The serum levels of CA125, HE4, and CA72-4 were measured using enzyme-linked immunosorbent assay (ELISA) technique for a group of 29 cases of OvEndo and a control (CTR) group of 26 cases. Results were compared between groups and statistical correlation was analyzed between the three biomarkers. (i) For CA125, we found a statistically significant difference in-between the mean serum levels of the two groups: 9.02 U∕mL in the OvEndo group versus 7.1 U∕mL in the CTR group (p=0.0158). (ii) A similar situation was found for CA72-4 levels in OvEndo group, where the mean serum level was 6.1 U∕mL compared to 3.5 U∕mL in the CTR group, showing a significant difference (p=0.0185). (iii) The mean serum level of HE4 in the OvEndo group was 7.6 ng∕mL versus 7.8 ng∕mL in the CTR group, and we found it highly significant (p=0.0001). HE4 levels were highly correlated with CA72-4 levels (p<0.0001), while CA125 levels were not correlated with HE4 and CA72-4. Measurements of CA125 can be used in the diagnosis of OvEndo mainly in association with HE4 serum levels, which are lower in endometriosis patients. CA72-4 levels are highly correlated with HE4 levels in patients with OvEndo, while no correlation with the other two markers was found. This correlation needs further investigation to establish if it may be used as a possible diagnostic tool in clinical practice.

Bowel wall thickness measured by MRI is useful for early diagnosis of bowel endometriosis

ObjectiveTo evaluate MRI features of bowel endometriosis (BE) and verify its clinical significance compared with pathological diagnosis.Materials and methodsSince 2018, patients clinically diagnosed with deep endometriosis (DE) and planned to undergo surgery were enrolled prospectively. MRI parameters including traction, thickening sign of the rectum, obliteration of the Douglas Pouch, sign of adenomyosis, and pelvic adhesion were extracted. Uni- and multi-variate analyses were performed to explore their association with pathological diagnosis of BE. ROC curve was utilized to ascertain the appropriate cutoff value for predicting the presence and assessing the severity of BE.ResultsA total of 226 patients with DE were recruited, and 154 BE cases were pathologically confirmed. Logistic regression analysis revealed that thickness of the rectal wall, traction sign of the rectum, and obliteration of the Douglas Pouch were independent factors to predict the presence of BE with the OR 1.59 (95% CI: 1.29–1.96), 0.24 (95% CI: 0.09–0.67), and 0.17 (95% CI: 0.07–0.40), respectively (p all < 0.01). A cutoff value of 6.0 mm for the thickness of rectal wall resulted in the highest predictive value of BE (specificity: 90.3%; sensitivity: 78.6%). For patients with measured thickness of the rectal wall over 6.0 mm, 72.1% (93/129) was confirmed BE with lesions infiltrated more than muscular layer.ConclusionThis prospective study indicates that based on precise definition of visualized features on MRI images, BE could be recognized pre-operatively. DE patients with thickness of rectal wall exceeding 6.0 mm have a greater probability of BE.Clinical relevance statementBased on precise definition of visualized features and accurate measurement on MRI images, bowel infiltrating among deep endometriosis patients could be recognized pre-operatively.Key Points• Precise definition of measurable MRI parameters made it possible for early detection of bowel endometriosis.• Thickening sign, traction sign of the rectum, and obliteration of the Douglas Pouch were typical radiological indicators for bowel endometriosis.• Bowel involvement is more sensitive to be detected among pelvic deep endometriosis patients with the thickness of the rectal wall over 6.0 mm.

Phthalate exposure and risk of ovarian dysfunction in endometriosis: human and animal data.

Objective: We aimed to explore the correlations between and possible mechanisms of common environmental endocrine disruptors, phthalates, and ovarian dysfunction in endometriosis. Methods: Subjects were included in the case group (n = 107) who were diagnosed with endometriosis by postoperative pathology in Fujian Maternal and Child Hospital from February 2018 to February 2021, and the women who were excluded from endometriosis by surgery were as the control group (n = 70). The demographic information of the subjects were evaluated by questionnaire, and the clinical characteristics were evaluated by medical records and 3-year follow-up results. Gas chromatography‒mass spectrometry was used to quantify 10 metabolites of phthalates, including dimethyl ortho-phthalate (DMP), mono-n-methyl phthalate (MMP), dioctyl ortho-phthalate (DEP), mono-ethyl phthalate (MEP), di-n-butyl ortho-phthalate (DBP), mono-butyl phthalate (MBP), benzylbutyl phthalate (BBzP), mono-benzyl; phthalate (MBzP), diethylhexyl phthalate (DEHP) and mono-ethylhexyl phthalate (MEHP), in the urine samples of the subjects. Furthermore, a total of 54 SD rats were exposed to DEHP 0, 5, 50, 100, 250, 500, 1,000, 2000, and 3,000mg/kg/day for 2weeks. The SD rats' body weight, oestrus cycle changes, and serum anti-mullerian hormone (AMH) levels were evaluated. After sacrifice, the mass index of the rat uterus and bilateral ovaries were calculated. Finally, bioinformatics analysis of rat ovarian tissues was performed to explore the possible mechanism. SPSS 24.0 (IBM, United States) was used for data analysis. p-value <0.05 was considered statistically significant. Results: The human urinary levels of DMP (p < 0.001), MMP (p = 0.001), DEP (p = 0.003), MEP (p = 0.002), DBP (p = 0.041), MBP (p < 0.001), BBzP (p = 0.009), DEHP (p < 0.001), and MEHP (p < 0.001) were significantly higher in women with endometriosis than in controls. Notably, DEHP was a significant risk factor for endometriosis (OR: 11.0, 95% CI: 5.4-22.6). The area under the ROC curve increased when multiple phthalates were diagnosed jointly, reaching 0.974 as the highest value, which was helpful for the diagnosis of endometriosis. In vivo experiments showed that after DEHP exposure in rats, the mass index of the ovary and uterus decreased in a dose-dependent manner; the oestrus cycle of SD rats was irregularly prolonged and disordered; and the serum AMH level was negatively correlated with the DEHP exposure dose (Rho = -0.8, p < 0.001). Bioinformatics analysis of rat ovarian tissues showed that seven genes involved in the steroid biosynthesis pathway were upregulated and may play a negative role in ovarian function. Conclusion: Exposure to phthalates, especially DEHP, is associated with the occurrence of endometriosis and affects women's reproductive prognosis and ovarian function. The steroid biosynthesis pathway may be related to ovarian dysfunction. The detection of phthalate in urine may become a new biological target for the diagnosis of endometriosis.

Urinary cadmium and endometriosis prevalence in a US nationally representative sample: results from NHANES 1999-2006.

Is exposure to toxic metal cadmium associated with increased endometriosis prevalence among a nationally representative sample of the US population? Concentrations of urinary cadmium, a long-term biomarker (10-30 years) of cadmium exposure, were associated with an increased prevalence of endometriosis. Cadmium exhibits estrogenic properties and may increase the risk of endometriosis, a gynecologic condition associated with substantial morbidity, for which estrogen has a central pathogenic role. Previous epidemiological studies of cadmium and endometriosis have yielded mixed results, with null, positive, and inverse associations being reported. We conducted a cross-sectional study using data from four cycles of the National Health and Nutrition Examination Survey (NHANES) 1999-2006. The study population comprised participants aged 20-54 years who had an endometriosis diagnosis, available data on urinary cadmium, and a glomerular filtration rate ≥60 ml/min/1.73 m2 (unweighted n = 1647). Urinary cadmium was measured by inductively coupled plasma-mass spectrometry, and we used urinary creatinine concentrations and covariate-adjusted standardization to account for urinary dilution. Self-reported diagnosis of endometriosis was ascertained by interview. We examined the association between quartiles of urinary cadmium and endometriosis using log-binomial regression to estimate adjusted prevalence ratios (aPRs) and 95% CIs. We observed twice the prevalence of endometriosis for participants with cadmium concentrations in the second quartile (versus the first quartile) (aPR 2.0, 95% CI: 1.1, 3.9) and the third quartile (versus the first quartile) (aPR 2.0, 95% CI: 1.1, 3.7). Our data also suggested a 60% increased prevalence of endometriosis with urinary cadmium concentrations in the fourth quartile (versus the first quartile) (aPR 1.6, 95% CI: 0.8, 3.2). In a sensitivity analysis, restricting the study population to premenopausal participants with an intact uterus and at least one ovary (unweighted n = 1298), stronger associations accompanied by wider CIs were observed. We were limited by the ascertainment of urinary cadmium and endometriosis diagnosis at a single time point, given the cross-sectional study design, and we relied on self-report of endometriosis diagnosis. However, urinary cadmium characterizes long-term exposure and findings from validation studies suggest that misclassification of self-reported endometriosis diagnosis may be minimal. This study suggests that cadmium is associated with an increased endometriosis prevalence. Given the substantial morbidity conferred by endometriosis and that the general population is ubiquitously exposed to cadmium, further research is warranted to confirm our findings. This work was supported by the National Institute of Nursing Research (grant R00NR017191 to K.U.) of the National Institutes of Health. The authors report no conflict of interest. N/A.

Exosomal microRNAs and long noncoding RNAs: as novel biomarkers for endometriosis.

Endometriosis is a gynecological inflammatory disorder characterized by the development of endometrial-like cells outside the uterine cavity. This disease is associated with a wide range of clinical presentations, such as debilitating pelvic pain and infertility issues. Endometriosis diagnosis is not easily discovered by ultrasound or clinical examination. Indeed, difficulties in noninvasive endometriosis diagnosis delay the confirmation and management of the disorder, increase symptoms, and place a significant medical and financial burden on patients. So, identifying specific and sensitive biomarkers for this disease should therefore be a top goal. Exosomes are extracellular vesicles secreted by most cell types. They transport between cells' bioactive molecules such as noncoding RNAs and proteins. MicroRNAs and long noncoding RNAs which are key molecules transferred by exosomes have recently been identified to have a significant role in endometriosis by modulating different proteins and their related genes. As a result, the current review focuses on exosomal micro-and-long noncoding RNAs that are involved in endometriosis disease. Furthermore, major molecular mechanisms linking corresponding RNA molecules to endometriosis development will be briefly discussed to better clarify the potential functions of exosomal noncoding RNAs in the therapy and diagnosis of endometriosis.

Correlations between endometriosis, lipid profile, and estrogen levels.

To explore the association between serum lipids and the occurrence and development of endometriosis using a retrospective review of clinical data. A total of 177 patients who underwent laparoscopic or open surgery due to benign ovarian masses, 117 patients with endometriosis (53 stage III and 64 stage IV), and 60 patients with benign ovarian masses without endometriosis were selected from the gynecology department of Maternal and Child Health Hospital of Hubei Province, between January 1, 2020, and October 30, 2022, to search for endometriosis occurrence by retrospectively analyzed the patients clinical data Risk factors for development and to explore the relationship between blood lipids and endometriosis. The scores of estradiol (E2), carbohydrate antigen 125 (CA125), and pain in the endo - and non-endometriosis groups were significantly different (P < .05), but there was no significant correlation between these 3. There were significant differences (P < .05) in E2, triglyceride (TG), CA125, and the size of the masses between patients with stage III and IV endometriosis. TG, E2, and CA125 were found to be valuable as separate indicators for the prediction of endometriosis, and the 3 indicators could improve the accuracy of the diagnosis of endometriosis when combined. Triglycerides may be positively correlated with the severity of endometriosis. The combination of TG, E2 and CA125 can improve the accuracy of the diagnosis of endometriosis staging.

PET/CT imaging in invasive endometriosis: a way to minimize missed diagnosis and reduce invasive interventions.

Heterogeneous and nonspecific symptoms make invasive endometriosis a difficult entity to diagnose. Small lesions with absent associated changes can be easily missed in cross-sectional imaging. Even when the lesions satisfy the thresholds for various investigations, their appearance changes with cyclical fluctuations in the hormonal levels. Therefore, newer approaches are needed to achieve correct diagnosis. Six females in reproductive age group (mean age = 32.5 ± 4.3 years) were retrospectively selected, wherein the diagnosis of invasive endometriosis was confirmed after 18F-FDG-PET/CT. Indications for PET/CT were staging in 4 patients, suspected progression in 1 and suspected inflammatory bowel disease in one patient. The study was repeated in proliferative phase in two patients and in the menstrual phase in another patient. FNAC was available in two patients and a drop in CA125 was documented in the last patient. In five patients metabolically active lesions were seen in PET/CT and in the last, activity was absent despite symptoms. Repeat menstrual phase imaging in the last patient confirmed the diagnosis. In two patients with metabolically active lesions at baseline, resolution was seen in proliferative phase PET/CT. In the other two patients, repeat study was not indicated as FNAC revealed normal endometrial tissue and in the last patient, significant drop in CA125 was documented after just 2 weeks. In all of these patients, the final diagnosis was of invasive endometriosis. In reproductive-age women, PET/CT acquisition should be optimized in the context of menstrual cycle. This approach can be used to non-invasively rule in/rule out endometriosis, especially with repeat imaging in proper menstrual phase.

Influence of interleukin-8 polymorphism on endometriosis-related pelvic pain

Endometriosis presents a pro-inflammatory microenvironment influenced by cytokines, such as interleukin (IL)-8, which expression may be influenced by genetic polymorphisms. Therefore, we aimed to investigate the role of interleukin (IL)-8 rs4073 polymorphism in endometriosis’ development and its related symptoms. A case-control study was conducted with 207 women with endometriosis and 193 healthy controls. Polymorphism was genotyped using a TaqMan validated assay. Associations were evaluated by binary logistic regression, using odds ratios (OR) and 95 % confidence intervals (CI), and P ≤ 0.05 was considered significant. Cases were younger (36 ± 6.8 versus 39 ± 8.4) and had lower body mass index (26.5 ± 5.3 versus 35.7 ± 6.3 Kg/m2) than controls (P < 0.001). Higher prevalence of symptoms and infertility was observed in cases, compared to controls (P < 0.001). Minor allele frequencies of IL-8 rs4073 (T) were 42.3 % and 39.9 % for cases and controls, respectively, and no associations were found between IL and 8 rs4073 polymorphism and endometriosis’ prevalence or staging. However, the polymorphism was associated with chronic pelvic pain among cases (OR = 0.54; 95 %CI = 0.29–0.98). The IL-8 rs4073A > T polymorphism may contribute to lower IL-8 expression and, consequently, decrease endometriosis-related pelvic pain. These findings can support the early diagnosis of endometriosis’ painful symptoms, preventing its complications, and allowing an individualized treatment.