Endometriosis is one of the most common chronic diseases in women, with a prevalence of up to 10%. The disease particularly affects women of reproductive age. Endometriosis has a significant impact on the patient's quality of life (QoL). In the current study, we aimed to evaluate the role of early diagnosis of endometriosis on patients' QoL.

In this longitudinal prospective study, 205 women with endometriosis who were referred to the gynecology department of Amir al-Mominin Hospital (Zabol-Iran) in 2021 were evaluated. Patients were divided into two groups based on the time of diagnosis, including early diagnosis and late diagnosis. An Endometriosis Health Profile (EHP) questionnaire was used to collect information about QoL before and 18 months after treatment. Data were analyzed using SPSSv.26 software and significance level was considered less than 0.05.

In both groups with early and late diagnosis, the QoL scores improved without significant difference (p = 0.303). There was a significant difference between lower stages (1 and 2) and higher stages (3 and 4) in terms of treatment effects on patients' QoL, and higher stages of endometriosis affected patients' QoL before and after treatment more than lower stages (P values < 0.05).

Early or late diagnosis of endometriosis doesn't affect patients' QoL and patients benefit from treatment regardless of the time of diagnosis.

Endometriosis has a significant negative impact on women's lives. Unfortunately, current medical treatments often fail to provide adequate pain relief and may cause intolerable side effects. Although many women experiencing primary dysmenorrhoea employ self-management strategies to help alleviate period-related symptoms, there is a paucity of knowledge about how women with endometriosis manage their symptoms through self-management.

A cross-sectional online survey was distributed in Germany, Austria, and Switzerland, between August and December 2022, targeting women aged 18 years or older with a diagnosis of endometriosis. The survey gathered information on (pharmacological and non-pharmacological) self-management strategies employed by the respondents in the previous six months, including their frequency, reasons for non-use, self-rated effectiveness, and impact on reducing endometriosis-related medication. Furthermore, the survey collected data on demographics, medical history, current symptomatology, and medication usage. Descriptive statistical analyses were conducted.

Of the 912 valid responses, 75.4% reported using self-management strategies, with the most prevalent being rest (91.6%), heat (91.1%), and exercise (63.3%). The most highly rated techniques in terms of effectiveness in pain reduction were cannabis, osteopathy, heat, and alcohol, with mean effectiveness ratings of 8.0, 7.3, 7.1, and 6.8, respectively, on the Numerical Rating Scale. Interventions, such as Tai Chi/Qi Gong, yoga/Pilates, herbal medicine, stretching, and meditation/breathing, were rated as being less effective. The lack of information and costs were identified as the primary reasons for not utilising self-management approaches.

The findings of this study may provide evidence for the reimbursement of self-management techniques by health insurance companies for the treatment of endometriosis-associated pain.

Uterine fibroids (UF) are reproductive conditions that occur as tumours in the womb. It is a gynecological outgrowth of diverse sizes often allied with infertility risks that might require surgery to reduce the complication in the worst-case scenario in women. Recent studies have uncovered that estrogen can induce and facilitate other target pathways' action on target cells for UF's pathogenesis, among the targets probed for pharmaceutical intervention. This study screens the interaction effects of 32 phytochemicals from indigenous and adopted potent Chinese plants and herbs; Chamomile, Pomegranate, Red clover, Cinnamomum, and Date palm, against estrogen receptor alpha (ESRα) to serve for anti-UF drug candidates using in silico tools through the molecular mechanisms. The interaction identifies coumestrol as the best-docked candidate (-9.6 kcal/mol) with a correlation to the binding free energy (-30.487 kcal/mol) as compared to the standard drug tamoxifen (-9.3 kcal/mol; -46.928 kcal/mol). The downstream post-docking evaluation reveals coumestrol to have excellent pharmacokinetics, drug-likeness, leadlikeness (no violation), less toxic (LD50; 2991 mg/kg), and highly interactive with ESRα. Coumestrol was top-ranked for ESRα (1QKU) target by PharmMapper among 300 human protein targets, with a z-score of 1.19368. The density functional theory (DFT) and dynamic simulation of 200 ns reveal regions of coumestrol structure and its complex that contribute to the chemical reactivity, stability, flexibility, and compactness of druggability. Ultimately, coumestrol emerged as a potential candidate suitable for anti-UF management, therefore future direction for its application should be on the design and synthesis of new structural derivatives for further in silico, in vitro, and in vivo studies.

MY-ENDO (Mind Your ENDOmetriosis) is a mindfulness- and acceptance-based endometriosis self-management intervention aimed at teaching women with symptomatic endometriosis how to manage and reduce negative physical, psychological, and social consequences of endometriosis. This study aimed at involving women with endometriosis in the co-development process of a digital version of MY-ENDO to investigate their experiences with and attitudes toward the intervention.

The study was designed as a qualitative feasibility study. The empirical material consisted of 35 interviews with seven women who self-reported a diagnosis with endometriosis, based on a semi-structured interview guide. Each participant completed the first four sessions of the intervention and was interviewed before the first and after each of the four sessions (five times in total) during participation. The study was based on a phenomenological approach and the data were analyzed using Braun and Clarke's thematic analysis strategy.

Analysis indicated that the two parts of the program called 'knowledge of the disease' and 'management of the disease' with eight related subthemes were crucial for participants' outcomes. In addition, a generic theme called 'motivation and alliance' was identified.

The digital self-management intervention MY-ENDO was generally experienced and evaluated as positive. It was considered an advantage that the program was specifically tailored to and targeting endometriosis as well as developed in collaboration with patients. Having a contact person was deemed important with regard to maintenance and motivation suggesting potential consequences for the implementation of this digital solution in clinical practice.

Beyond gynecological issues, women with endometriosis have a significant risk of cardiac outcomes. Despite this evidence, the extent and mechanisms of the association remain unclear. The aim of this study was to evaluate the association between endometriosis and the incidence of cerebro-cardiovascular disorders. Using preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines, seven databases were searched as of October 14, 2024, for observational studies assessing the association between endometriosis and cerebro-cardiovascular disorders. The main outcome was major adverse cardiovascular and cerebrovascular event (MACCE) while the secondary outcomes included all-cause mortality, cerebrovascular accident (CVA), ischemic heart disease (IHD), myocardial infarction (MI), arrhythmia, and heart failure (HF). Bias was assessed with the risk of bias in non-randomized studies of exposures (ROBINS-E) tool. Odds ratios with 95% confidence interval (CI) were calculated using random-effects meta- analysis. Evidence certainty was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Robustness was assessed via sensitivity analyses and trial sequential analysis (TSA). Out of 3,141 studies, nine cohort studies encompassing 1,670,589 women (follow-up 7-28 years) were included. Endometriosis was associated with 24% higher odds of MACCE incidence (95%CI: 1.18-1.31, moderate certainty). In addition, having endometriosis increased the odds of CVA by 49% (95%CI: 1.20-1.85, high certainty), IHD by 64% (95%CI: 1.31-2.05, low certainty), MI by 53% (95%CI: 1.18-1.98, high certainty), arrhythmias by 24% (95%CI: 1.12-1.37, high certainty), and HF by 13% (95%CI: 1.03-1.25, high certainty). Endometriosis did not significantly associate with all-cause mortality. Sensitivity analyses and TSA reinforced all of these findings. In conclusion, endometriosis was significantly associated with increased odds of cerebro-cardiovascular disorders. Future research should clarify the underlying mechanisms and develop targeted prevention strategies.

Background: Endometriosis is a chronic, oestrogen-sensitive inflammatory disease, which can have a significant impact on women's wellbeing. Nevertheless, the sleep health of this population has been poorly investigated. This exploratory study aimed at describing sleep health, psychological wellbeing, and prevalence of endometriosis among a sample of female students and at evaluating the impact of endometriosis on sleep health and psychological wellbeing in women suffering from the disease. Methods: Women were recruited with a two-stage procedure in a cross-sectional study using online questionnaires: Insomnia Severity Index, Hospital Anxiety and Depression Scale, and Difficulties in Emotion Regulation Scale-Short form. Furthermore, specific questions were used to measure the five dimensions of sleep health: satisfaction, vigilance, efficiency, duration, and timing. Results: In the first stage of the enrolment procedure, 1068 students (18-45 years old) responded to the questionnaire, and 8.7% reported a physician diagnosis of endometriosis. Additionally, in the second stage of the enrolment procedure, 75 women were recruited through social media and reported a diagnosis of endometriosis. Then, all women with endometriosis (169) were age-matched with 169 women without the disease. Multivariate regression analyses showed a bidirectional association between sleep health and psychological wellbeing in the matched sample. Independent samples t-test showed that women with endometriosis reported more severe insomnia symptoms and lower psychological wellbeing than controls. Statistically significant differences were also found in global sleep health and satisfaction, vigilance, and efficiency. Among women with endometriosis, pain and anxiety symptoms were bidirectionally associated, while sleep health was significantly associated with disease stage and psychological difficulties. Conclusions: Considering and treating sleep difficulties in this population may contribute to an improvement in psychological wellbeing and quality of life.

To assess the prevalence of self-reported symptoms of endometriosis and adenomyosis among university students and identify potential predictors of these diseases among these symptoms.

This cross-sectional study was conducted at a private university in northeastern Brazil. The students were asked to complete an electronic questionnaire using a Google Form link. Participants were asked about general information, the menstrual cycle, and bleeding symptoms. The electronic questionnaire results were compared between two groups: students who self-reported endometriosis/adenomyosis (ENDO/ADENO) and students who self-reported no endometriosis/adenomyosis (NO ENDO/ADENO).

Four (2.9%) students self-reported adenomyosis alone, 26 (18.6%) students self-reported endometriosis alone, and two (1.4%) students self-reported an associated diagnosis of endometriosis and adenomyosis. Participants were divided into two groups: ENDO/ADENO (n=32) and NO ENDO/ADENO (n=108). Participants in the ENDO/ADENO group reported more severe dysmenorrhea, worsening dysmenorrhea in the last 12 months, frequent absence from class, dyspareunia, and dysuria. Worsening dysmenorrhea was a predictor of endometriosis/adenomyosis in university female students (odds ratio = 5.73; 95% confidence interval, 1.91-17.22, p=0.002).

The assessment of menstrual cycle symptoms can be used as a screening tool for patients at risk of endometriosis/adenomyosis. The progressive worsening of dysmenorrhea in the last 12 months was a predictor of endometriosis/adenomyosis diagnosis.

Primary cutaneous endometriosis and inguinal endometriosis (IEM) are rare, representing less than 1% and under 0.6% of extragenital and extrapelvic endometriosis, respectively. Co-occurrence in the same patient is exceedingly rare, with a frequency as low as 5 cases per 100 000. This case presents the first instance of a patient simultaneously afflicted with both types. Endometriosis involves the ectopic presence of endometrial tissue, with primary umbilical endometriosis (PUE) localised in the umbilicus without prior surgery, and IEM affecting the inguinal canal. In a nulliparous woman in her early 30s, lacking surgical history, the diagnosis of PUE, IEM and pelvic endometriosis was made following presentation with chronic pelvic pain and a painful umbilical nodule. This report aims to delineate the presentation, diagnosis and surgical management of patients with umbilical and IEM, shedding light on these rare manifestations.

Endometriosis is a chronic inflammatory estrogen-dependent disease affecting 10% of women worldwide leading to chronic pelvic pain and infertility which may be treated clinically or surgically.

Current literature was reviewed using the keywords 'gonadotropin releasing hormone agonists (GnRHa),' 'endometriosis,' 'infertility' and 'chronic pelvic pain.' Relevant papers prioritizing randomized controlled clinical trials (RCT), systematic reviews, meta-analyses, as well as international guidelines were evaluated.

Available options for relieving endometriosis-associated pain include GnRHa, progestagens, and combined oral contraceptives, all of which block menstruation to control symptoms without curing the disease. GnRHa administration decreases pain and symptom recurrence after surgical treatment, but side effects and costs limit its use. Published studies to test its effectiveness in easing endometriosis-associated pain are heterogeneous, consider different outcomes with no long-term results. Drug choice should be individualized considering the side-effect profile, tolerability, costs, risks, and benefits as one size does not fit all. As we wait for the development of an ideal pharmacological agents, GnRHa with an add-back regimen remains a second-line option to alleviate the painful symptoms in women with endometriosis. Endometriosis management should consider the systemic nature of the disease and the complexity involved in the pathogenesis of symptoms.

Background: Endometriosis is a debilitating and highly stigmatized chronic condition. The relationship between stigma and depressive symptoms among college-attending women with endometriosis symptoms was examined. Method: Data were analyzed from a cross-sectional online survey of undergraduate women (N = 424). Mean anticipated, internalized, and enacted stigma values were calculated. Logistic regression assessed the relationship between stigma score and depressive symptoms. Results: Mean stigma scores were 1.98 (anticipated), 1.46 (internalized), and 1.59 (enacted) on a 5-point scale (1 being the lowest and 5 being the highest); 24.1% reported moderately severe/severe depressive symptoms. In adjusted models, stigma was associated with an increased likelihood of moderately severe/severe depressive symptoms (anticipated (aOR = 1.96, 95% CI:1.49-2.59); internalized (aOR =2.67, 95% CI: 1.88-3.85); enacted (aOR = 1.28, 95% CI: 1.16-1.42)). Conclusion: College attending-women with endometriosis symptoms experience stigma which is significantly associated with depressive symptoms. Stigma reducing interventions are warranted and may have mental health benefits.

Endometriosis, the growth of endometrial-like tissue outside the uterus, causes chronic pain and infertility in 10 % of reproductive-aged women worldwide. Unfortunately, no permanent cure exists, and current medical and surgical treatments offer only temporary relief. Endometriosis is a chronic inflammatory disease characterized by immune system dysfunction. Our previous study showed aberrant activation of signal transducer and activator of transcription 3 (STAT3) in endometriosis. Our transcriptomic analysis of uterine tissue from uterine-specific Stat3 knock-out mice identifies that STAT3 regulates inflammatory and immune-related genes. Here, we evaluate cerium-oxide nanoparticles (nanoceria) as a non-steroidal anti-inflammatory drug for endometriosis theranostics. Our in vitro studies validate the multi-enzymatic properties of nanoceria, enabling the transition of pro-inflammatory macrophages to an anti-inflammatory state in J774 macrophage cells. In vivo, treatment of endometriosis mice with nanoceria reveals its ability to passively accumulate at ectopic lesions. The nanoceria conjugated with indocyanine green are non-invasively trackable to ectopic lesions. Therefore, immune modulation and anti-inflammatory effects of nanoceria significantly reduce development of ectopic lesions while minimizing off-target effects, such as avoiding interference with pregnancy including implantation and decidualization. Our results suggest that aberrant STAT3 activation is a major contributor to endometriosis, and nanoceria offers a novel theranostic approach for endometriosis.

Can a panel of plasma protein biomarkers be identified to accurately and specifically diagnose endometriosis?

A novel panel of 10 plasma protein biomarkers was identified and validated, demonstrating strong predictive accuracy for the diagnosis of endometriosis.

Endometriosis poses intricate medical challenges for affected individuals and their physicians, yet diagnosis currently takes an average of 7 years and normally requires invasive laparoscopy. Consequently, the need for a simple, accurate non-invasive diagnostic tool is paramount.

This study compared 805 participants across two independent clinical populations, with the status of all endometriosis and symptomatic control samples confirmed by laparoscopy. A proteomics workflow was used to identify and validate plasma protein biomarkers for the diagnosis of endometriosis.

A proteomics discovery experiment identified candidate biomarkers before a targeted mass spectrometry assay was developed and used to compare plasma samples from 464 endometriosis cases, 153 general population controls, and 132 symptomatic controls. Three multivariate models were developed: Model 1 (logistic regression) for endometriosis cases versus general population controls, Model 2 (logistic regression) for rASRM stage II to IV (mild to severe) endometriosis cases versus symptomatic controls, and Model 3 (random forest) for stage IV (severe) endometriosis cases versus symptomatic controls.

A panel of 10 protein biomarkers were identified across the three models which added significant value to clinical factors. Model 3 (severe endometriosis vs symptomatic controls) performed the best with an area under the receiver operating characteristic curve (AUC) of 0.997 (95% CI 0.994-1.000). This model could also accurately distinguish symptomatic controls from early-stage endometriosis when applied to the remaining dataset (AUCs ≥0.85 for stage I to III endometriosis). Model 1 also demonstrated strong predictive performance with an AUC of 0.993 (95% CI 0.988-0.998), while Model 2 achieved an AUC of 0.729 (95% CI 0.676-0.783).

The study participants were mostly of European ethnicity and the results may be biased from undiagnosed endometriosis in controls. Further analysis is required to enable the generalizability of the findings to other populations and settings.

In combination, these plasma protein biomarkers and resulting diagnostic models represent a potential new tool for the non-invasive diagnosis of endometriosis.

Subject recruitment at The Royal Women's Hospital, Melbourne, was supported in part by funding from the Australian National Health and Medical Research Council (NHMRC) project grants GNT1105321 and GNT1026033 and Australian Medical Research Future Fund grant no. MRF1199715 (P.A.W.R., S.H.-C., and M.H.). Proteomics International has filed patent WO 2021/184060 A1 that relates to endometriosis biomarkers described in this manuscript; S.B., R.L., and T.C. declare an interest in this patent. J.I., S.B., C.L., D.I., H.L., K.P., M.D., M.M., M.R., P.T., R.L., and T.C. are shareholders in Proteomics International. Otherwise, the authors have no conflicts of interest.

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Endometriosis affects over 190 million women globally, and effective therapies are urgently needed to address the burden of endometriosis on women's health. Using an artificial intelligence (AI)-driven target discovery platform, two unreported therapeutic targets, guanylate-binding protein 2 (GBP2) and hematopoietic cell kinase (HCK) are identified, along with a drug repurposing target, integrin beta 2 (ITGB2) for the treatment of endometriosis. GBP2, HCK, and ITGB2 are upregulated in human endometriotic specimens. siRNA-mediated knockdown of GBP2 and HCK significantly reduced cell viability and proliferation while stimulating apoptosis in endometrial stromal cells. In subcutaneous and intraperitoneal endometriosis mouse models, siRNAs targeting GBP2 and HCK notably reduced lesion volume and weight, with decreased proliferation and increased apoptosis within lesions. Both subcutaneous and intraperitoneal administration of Lifitegrast, an approved ITGB2 antagonist, effectively suppresses lesion growth. Collectively, these data present Lifitegrast as a previously unappreciated intervention for endometriosis treatment and identify GBP2 and HCK as novel druggable targets in endometriosis treatment. This study underscores AI's potential to accelerate the discovery of novel drug targets and facilitate the repurposing of treatment modalities for endometriosis.

Endometriosis is a common gynecological disease that affects approximately 10-15% of reproductive-aged women worldwide. This debilitating disease has a negative impact on the quality of life of those affected. Despite this condition being very common, the pathogenesis is not well understood. Metabolomics is the study of the array of low-weight metabolites in a given sample. This emerging field of omics-based science has proved to be effective at furthering the understanding of endometriosis. In this systematic review, we seek to provide an overview of the application of metabolomics in endometriosis. We highlight the use of metabolomics in locating biomarkers for identification, understanding treatment mechanisms and symptoms, and relating external factors to endometriosis. The literature search took place in the Web of Science, Pubmed, and Google Scholar based on the keywords "metabolomics" AND "endometriosis" or "metabolome" AND "endometriosis". We found 58 articles from 2012 to 2024 that met our search criteria. Significant alterations of lipids, amino acids, as well as other compounds were present in human and animal models. Discrepancies among studies of significantly altered metabolites make it difficult to make general conclusions on the metabolic signature of endometriosis. However, several individual metabolites were elevated in multiple studies of women with endometriosis; these include 3-hydroxybutyrate, lactate, phosphatidic acids, succinate, pyruvate, tetradecenoylcarnitine, hypoxanthine, and xanthine. Accordingly, L-isoleucine and citrate were reduced in multiple studies of women with endometriosis. Including larger cohorts, standardizing testing methods, and studying the individual phenotypes of endometriosis may lead to more separable results.

Endometriosis is a benign, estrogen-dependent, persistent chronic inflammatory heterogeneous condition that features fibrotic adhesions caused by periodic bleeding. The characteristic ectopic lesions are marked by a widely spread dense fibrotic interstitium comprising of fibroblasts, myofibroblasts, collagen fibers, extracellular proteins, inflammatory cells, and active angiogenesis. Fibrosis is now recognized as a critical component of endometriosis because of which current treatments, such as hormonal therapy and surgical excision of lesions are largely ineffective with severe side effects, high recurrence rates, and significant morbidity. The symptoms include dysmenorrhea (cyclic or noncyclic), dyspareunia, abdominal discomfort, and infertility. The significant lack of knowledge regarding the underlying root causes, etiology, and complex pathogenesis of this debilitating condition, hinders early diagnosis and implement effective therapeutic approaches with minimal side effects presenting substantial hurdles in endometriosis management. Emerging research offer a close relationship between endometriosis and fibrosis, which is believed to be tightly linked to pain, a primary contributor to the deterioration of the patient's quality of life. However, the underlying pathophysiological cellular and molecular signaling pathways behind endometriosis-associated fibrosis are poorly addressed. The available experimental disease models have tremendous challenges in reproducing the human characteristics of the disease limiting the treatment effectiveness. Future translational research on the topic has been hindered by the lack of an adequate fibrotic model of endometriosis emphasizing the necessity of etiological exploration. This review article focuses on recent developments in the field and highlight the necessity for novel fibrotic models for early diagnosis, a better understanding the disease's etiology and develop effective anti-fibrotic treatments. By addressing these knowledge gaps, we want to open fresh avenues for a thorough investigation and extended research in the field of endometriosis.

Endometriosis affects 5% to 10% of reproductive age women and may be associated with severely painful and debilitating symptoms as well as infertility. Endometriosis involves hormonal fluctuations, angiogenesis, neurogenesis, vascular changes and neuroinflammatory processes. The neuroinflammatory component of endometriosis makes it a systemic disorder, similar to other chronic epithelial inflammatory conditions.

Inflammatory mediators, mast cells, macrophages, and glial cells play a role in endometriosis which can result in peripheral sensitization and central sensitization. There is overlap between chronic pelvic pain and endometriosis, but the two conditions are distinct. Effective treatment is based on a personalized approach using a variety of pharmacologic and other treatment options.

Hormonal therapies are a first-line approach, but endometriosis is a challenging condition to manage. 'Add-back' hormonal therapy has been effective. Painful symptoms are likely caused by the interplay of multiple factors and there may be a neuropathic component. Analgesics and anticonvulsants may be appropriate. A holistic approach and multimodal treatments are likely to be most effective. In addition to pharmacologic treatment, there are surgical and alternative medicine options. Endometriosis may also have a psychological component.

In New Zealand, an estimated 10% of women and people presumed female at birth have endometriosis, a disease characterised by the presence of tissue similar to the lining of the uterus, outside of the uterus.

The purpose of this study was to characterise the research priorities of New Zealand endometriosis patients and their support networks in alignment with an Australian study. This will allow researchers to be able to ensure their research aligns with closing research gaps prioritised by those who directly experience the impacts of the disease.

There were 1262 responses to an online Qualtrics survey advertised through Endometriosis New Zealand's social media accounts and mailing list to reach endometriosis patients and their support networks.

Overall, the highest research priorities for surgically or radiologically confirmed endometriosis patients, clinically suspected endometriosis patients, chronic pelvic pain patients, and their parents, partners, family members and friends were the management and treatment of endometriosis, followed by understanding endometriosis' cause, and improved capacity to diagnose endometriosis earlier. The key differences between the priorities of symptomatic participants and supporters were that symptomatic participants placed a significantly higher priority on understanding the cause of endometriosis, and supporters placed a significantly higher priority on improving the diagnosis of endometriosis.

There is alignment between the ranking of general research priority areas for endometriosis in Australasia, allowing for clear priorities for future research teams to structure their work around patient-centredness.

Endometriosis is a chronic gynecological disorder characterized by significant chronic pelvic pain (CPP) and infertility, adversely affecting the quality of life for many women worldwide. This review aims to synthesize recent findings on natural bioactive compounds derived from various plant sources that exhibit beneficial effects in the management of endometriosis and related CPP. A thorough search of databases, including PubMed, Scopus, and Google Scholar, was conducted to identify studies evaluating the efficacy of natural compounds on endometriosis and related CPP. In alphabetical order, curcumins, ginsenosides, polyphenols and other secondary metabolites showed promising effects on oxidative stress, inflammation, and pain modulation associated with endometriosis acting on multiple pathways. Most of the selected articles were in vitro and in vivo studies in animal models, with a limited number of clinical trials. The reported natural compounds according to the highlighted multiple bioactivities, might be valuable complementary alternatives as supplements, nutraceuticals, or in advanced personalized nutrition. Further clinical investigations are needed to comprehensively evaluate their therapeutic potential, safety, efficacy and to establish effective treatment protocols.

Endometriosis is a chronic, complex, systemic inflammatory condition that impacts approximately 190 million girls and women worldwide, significantly impacting their quality of life. The effective management of endometriosis requires a multi-disciplinary and holistic approach, one that includes surgical and medical management, such as a laparoscopy and a chronic medical management plan, as well as dietary, nutritional, and lifestyle adjunct interventions, such as pelvic pain physiotherapy and acupuncture. There is growing evidence to support the role of dietary and nutritional interventions in the adjunct management of endometriosis-related pain and gastrointestinal symptoms. However, the implementation of these interventions is often not regulated, as patients with endometriosis often adopt self-management strategies. Diet and nutrition can modulate key players integral to the pathophysiology of endometriosis, such as, but not limited to, inflammation, estrogen, and the microbiome. However, it is unclear as to whether diet plays a role in the prevention or the onset of endometriosis. In this review, we discuss three key players in the pathogenesis of endometriosis-inflammation, estrogen, and the microbiome-and we summarize how diet and nutrition can influence their mechanisms, and consequently, the progression and manifestation of endometriosis. There is a major need for evidence-based, non-invasive adjunct management of this debilitating disease, and diet and nutritional interventions may be suitable.

According to the World Health Organization (WHO), endometriosis affects roughly 10% (190 million) of reproductive-age women and girls in the world (2023). The diagnostic challenge in endometriosis lies in the limited value of clinical tools, making it crucial to address diagnostic complexities in patients with suggestive symptoms and inconclusive clinical or imaging findings. Saliva micro ribonucleic acid (miRNA) signature, nanotechnologies, and artificial intelligence (AI) have opened up new perspectives on endometriosis diagnosis. The aim of this article is to review innovations at the intersection of new technology and AI when diagnosing endometriosis. Aberrant epigenetic regulation, such as DNA methylation in endometriotic cells (ECs), is associated with the pathogenesis and development of endometriosis. By leveraging nano-sized sensors, biomarkers specific to endometriosis can be detected with high sensitivity and specificity. A chemotherapeutic agent with an LDL-like nano-emulsion targets rapidly dividing cells in patients with endometriosis. The developed sensor demonstrated effective carbohydrate antigen 19-9 detection within the normal physiological range. Researchers have developed magnetic iron oxide nanoparticles composed of iron oxide. As novel methods continue to emerge at the forefront of endometriosis diagnostic research, it becomes imperative to explore the impact of nanotechnology and AI on the development of innovative diagnostic solutions.

Endometriosis is an oestrogen-dependent inflammatory disease affecting menstruating women, with varying levels of severity. Oestrogen dysregulation is responsible for chronic inflammation, angiogenesis, endometrial lesion development, progression, and infertility during menarche in afflicted women. The inflammatory mediators associated with this chronic painful disease have been established, with research also indicating the relationship between dysbiosis and disease manifestation. Endometriosis is also present with several painful comorbidities, including endometrial cancer, cardiovascular disease, and autoimmunity. The lack of specific and sensitive non-invasive diagnostic procedures, coupled with poor response to current therapeutic approaches, means that treatment needs remain unmet. Surgical procedures are performed to remove endometriosis ectopic lesions, for which the recurrence rate of disease is up to 50%, with certain patients exhibiting no alleviation of symptoms. This review aims to outline the aetiology of endometriosis, detailing novel diagnostic approaches and potential therapeutic approaches, namely advanced therapeutic medical products (ATMPs), including stem cell therapy and clustered regularly interspaced short palindromic repeats (CRISPR) gene editing. This timely review also provides novel insights into the important recent modalities which may be applied for the diagnosis and therapeutic response of endometriosis, including biomarkers, microfluidic platforms, and organoid systems. Undoubtedly, reliable, reproducible, sensitive, and specific models of endometriosis in humans are urgently needed to investigate and detail the aetiology of this debilitating disease.

Endometriosis is a debilitating and painful gynecological inflammatory disease affecting up to 15% of women and transgender men. Current treatments are ineffective for a substantial proportion of patients, underscoring the need for additional therapies with long-term benefits. Nociceptors release neuropeptides, such as calcitonin gene-related peptide (CGRP), which are known to shape immunity through neuroimmune communication. Given the comorbidity between endometriosis and migraine and the integral role of immune cells and inflammation in endometriosis, we investigated the role of CGRP-mediated neuroimmune communication in endometriosis. Using samples from eight patients with endometriosis and a nonsurgical mouse model of the disease, we found that mouse and human endometriosis lesions contain both CGRP and its coreceptor, receptor activity modifying protein 1 (RAMP1). In mice, nociceptor ablation reduced pain, monocyte recruitment, and lesion size, suggesting that nociceptor activation and neuropeptide release contribute to endometriosis lesion growth and pain. Mechanistically, CGRP changed the phenotype of macrophages to a pro-endometriosis phenotype. CGRP-stimulated macrophages demonstrated impaired efferocytosis and supported increased endometrial cell growth in a RAMP1-dependent manner. Treatment of lesion-bearing mice with US Food and Drug Administration-approved drugs that block CGRP-RAMP1 signaling reduced mechanical hyperalgesia, spontaneous pain, and lesion size. Together, our data demonstrated the effectiveness and underlying cellular mechanisms of nonhormonal and nonopioid CGRP/RAMP1 blockade in a mouse model of endometriosis, suggesting that targeting this axis may lead to clinical benefit for patients with endometriosis.

Inadequate research on female health and performance; the complexity of the research; low menstrual health literacy of athletes, coaches, and support staff; and ethical and cultural sensitivities are all recognized as barriers to effective health monitoring for females in sports. Frameworks have been developed for academics to follow to help improve the quality of female-specific research. However, a similar resource that enables correct terminology, and use of health monitoring techniques has not been provided for sporting organizations, coaches, support staff or athletes. Therefore, this critical commentary presents a new resource, the Menstrual Health Manager. This resource may be used to determine the level of menstrual health monitoring detail that may be used by organisations, coaches or athletes, and specifies what reproductive health details the data will provide. This resource aims to provide organizations and coaches with a means of understanding the data that inform their decisions for female athletes. Utilization of this resource may aid in the consistent use of terminology and methods for female-specific health monitoring in both sports and research.

The study of RAD51 regulators in female reproductive diseases has novel biomarker potential and implications for therapeutic advancement. Regulators of RAD51 play important roles in maintaining genome integrity and variations in these genes have been identified in female reproductive diseases including primary ovarian insufficiency (POI), endometriosis, and polycystic ovary syndrome (PCOS). RAD51 modulators change RAD51 activity in homologous recombination, replication stress, and template switching pathways. However, molecular implications of these proteins in primary ovarian insufficiency, endometriosis, and polycystic ovary syndrome have been understudied. For each reproductive disease, we provide its definition, current diagnostic and therapeutic treatment strategies, and associated genetic variations. Variants were discovered in RAD51, and regulators including DMC1, RAD51B, SWS1, SPIDR, XRCC2 and BRCA2 linked with POI. Endometriosis is associated with variants in XRCC3, BRCA1 and CSB genes. Variants in BRCA1 were associated with PCOS. Our analysis identified novel biomarkers for POI (DMC1 and RAD51B) and PCOS (BRCA1). Further biochemical and cellular analyses of RAD51 regulator functions in reproductive disorders will advance our understanding of the pathogenesis of these diseases.

This study aimed to conduct a bibliometric analysis of research on endometriosis and infertility, focusing on the 100 most-cited (TOP100) articles in the literature.

The design of this study is a bibliometric analysis.

The SCOPUS database was searched using the terms "endometriosis" and "infertility." The productivity and impact of research publications by authors, countries, and journals were assessed using the following indicators: total number of publications, total number of citations (TNC), journal impact factor, and journal citation indicator. The bibliometric analysis was conducted from January 1, 2000, to December 31, 2023, using IBM SPSS™ for Windows and VOSviewer 1.6.20. VOSviewer was used to evaluate the TNC, total number of authors/coauthors, and collaboration network between countries of the TOP100 articles. VOSviewer was also used to create keyword co-occurrence networks.

Of the TOP100 articles, 69 were literature review articles, with a mean of 448.97 ± 513.5 citations (range: 191-2,705). The TOP100 articles were published by 479 authors (mean 5.8 ± 7.3 per study) from 40 countries in 39 high-impact journals. The keyword co-occurrence network revealed a grouping of four clusters, with terms related to pathophysiology, clinical management, assisted reproductive technology, and hormonal treatment of endometriosis.

The main limitation of our study is the use of only one database and TNC as the main bibliometric indicator. Studies need at least 2-3 years after publication to accumulate sufficient citations for bibliometric indicators to be reliable. This means that large number of recent studies were not included in this bibliometric analysis.

This study revealed trends in endometriosis and infertility research, especially in the fields of immunology and genetics. It also highlights the importance of global collaboration to improve diagnostics, treatments, and outcomes.

Menstrual blood, which is often discarded as a waste product, has emerged as a valuable source of health information. The components of menstrual blood, such as endometrial cells, immune cells, proteins, and microbial signatures, provide insights into health. Studies have shown encouraging results for using menstrual blood to diagnose a variety of conditions, including hormonal imbalances, cervical cancer, endometriosis, chlamydia, diabetes, and other endocrine disorders. This review examines the potential of menstrual blood as a non-invasive diagnostic specimen, exploring its composition, promising applications, and recent advances. This review also discusses challenges to utilizing menstrual blood testing, including ethical considerations, the lack of standardized collection protocols, extensive validation studies, and the societal stigma around menstruation. Overcoming these challenges will open new avenues for personalized medicine and revolutionize healthcare for individuals who menstruate.

Endometriosis is a chronic condition that affects millions of women in the United States. Chronic pain can be debilitating and complex to manage. Despite common approaches like hormonal treatments and surgery, many women continue to endure pain. Managing the chronic and multifaceted nature of endometriotic pain necessitates a comprehensive strategy.

This study explores the potential of cannabis in alleviating endometriosis-related pain through an extensive literature search. Cohort studies, case-control studies, cross-sectional surveys, and systematic reviews from January 1996 to August 2022 were eligible for inclusion. Articles were then assessed and included for further analysis if they met the following criteria: (1) Population was women with endometriosis; (2) Discussed the therapeutic use of medical cannabis for endometriosis-related pain.

The literature search revealed 522 articles, with eight articles meeting criteria for analysis: four cross-sectional surveys, two systematic reviews, one retrospective cohort study, and one literature review. Cannabis consumption for symptom relief was common among women with endometriosis, and some even reported that the use of cannabis reduced their use of analgesics.

The use of cannabis for endometriosis-related pain holds significant promise for addressing the often-debilitating comfort experienced by those with this condition. By interacting with the endocannabinoid system, cannabis may provide relief by modulating pain perception, reducing inflammation, relaxing muscles, and alleviating neuropathic discomfort.

Background Endometriosis is a prevalent gynecological disorder characterized by extra-uterine endometrial-like tissue, causing substantial morbidity, including chronic pelvic pain and infertility. Little is known about the correlation between imaging findings and pain severity in endometriosis. Methods We conducted a prospective observational study, enrolling 150 women diagnosed with endometriosis. Clinical, imaging (MRI and transvaginal ultrasound (TVUS)), and histopathological criteria were used for diagnosis. Pain severity was assessed using the Visual Analog Scale (VAS). Statistical analysis included multivariate regression to identify predictors of pain severity. Results Imaging revealed common sites of endometriosis involvement, predominantly ovaries (73.3%) and rectovaginal septum (40%). Deep infiltrating endometriosis (DIE) was present in 30% of patients, predominantly affecting uterosacral ligaments (66.7% of DIE cases). Patients with ovarian endometriomas and DIE exhibited significantly higher VAS scores (7.6 ± 1.5 and 8.0 ± 1.2, respectively) compared to those without (6.5 ± 1.9 and 6.9 ± 1.8, respectively). Surgical intervention led to a significant reduction in VAS scores (from 7.4 ± 1.6 to 3.2 ± 1.7, p < 0.001), correlating with reductions in lesion size and extent observed in follow-up imaging. Conclusion Advanced imaging techniques, particularly MRI and TVUS, play a critical role in assessing pain severity in endometriosis. Ovarian endometriomas and DIE are independent predictors of increased pain severity, guiding personalized treatment strategies. Surgical excision of lesions, particularly in cases of DIE, offers substantial pain relief and improves quality of life, emphasizing the integration of imaging in clinical decision-making for optimal endometriosis management.

Endometriosis, an incurable gynecological disease that causes abnormal growth of uterine-like tissue outside the uterine cavity, leads to pelvic pain and infertility in millions of individuals. Endometriosis can be treated with medicine and surgery, but recurrence and comorbidities impair quality of life. In recent years, nanoparticle (NP)-based therapy has drawn global attention, notably in medicine. Studies have shown that NPs could revolutionize conventional therapeutics and imaging. Researchers aim to enhance the prognosis of endometriosis patients with less invasive and more effective NP-based treatments. This study evaluates this potential paradigm shift in endometriosis management, exploring NP-based systems for improved treatments and diagnostics. Insights into nanotechnology applications, including gene therapy, photothermal therapy, immunotherapy, and magnetic hyperthermia, offering a theoretical reference for the clinical use of nanotechnology in endometriosis treatment, are discussed in this review.

Nanoparticles and nanotechnology may present opportunities to revolutionize the prevention, treatment and diagnosis of a range of reproductive health conditions in women. These technologies are also used to improve outcomes of assisted reproductive technology. We highlight a range of these potential clinical uses of nanoparticles for polycystic ovary syndrome, endometriosis, uterine fibroids and sexually transmitted infections, considering in vitro and in vivo studies along with clinical trials. In addition, we discuss applications of nanoparticles in assisted reproductive technology, including sperm loading, gamete and embryo preservation and preventing preterm birth. Finally, we present some of the concerns associated with the medical use of nanoparticles, identifying routes for further exploration before nanoparticles can be applied to women's reproductive health in the clinic.

Endometriosis (EM) is a gynecological inflammatory disease often accompanied by stress, chronic pelvic pain (CPP), anxiety, and depression, leading to a diminished quality of life. This review aims to discuss the relationship between systemic and local inflammatory responses in the central nervous system (CNS), focusing on glial dysfunctions (astrocytes and microglia) as in critical brain regions involved in emotion, cognition, pain processing, anxiety, and depression. The review presents that EM is connected to increased levels of pro-inflammatory cytokines in the circulation. Additionally, chronic stress and CPP as stressors may contribute to the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, depleting the production of inflammatory mediators in the circulatory system and the brain. The systemic cytokines cause blood-brain barrier (BBB) breakdown, activate microglia in the brain, and lead to neuroinflammation. Furthermore, CPP may induce neuronal morphological alterations in critical regions through central sensitization and the activation of glial cells. The activation of glial cells, particularly the polarization of microglia, leads to the activation of the NLRP3 inflammasome and the overproduction of inflammatory cytokines. These inflammatory cytokines interact with the signaling pathways involved in neural plasticity. Additionally, persistent inflammatory conditions in the brain lead to neuronal death, which is correlated with a reduced volume of key brain regions such as the hippocampus. This review highlights the involvement of glial cells in the pathogenesis of the mental comorbidities of EM (i.e., pain, anxiety, and depression) and to discuss potential therapeutic approaches for targeting the inflammation and activation of microglia in key brain regions.

EPH receptors (EPHs), the largest family of tyrosine kinases, phosphorylate downstream substrates upon binding of ephrin cell surface-associated ligands. In a large cohort of endometriotic lesions from individuals with endometriosis, we found that EPHA2 and EPHA4 expressions are increased in endometriotic lesions relative to normal eutopic endometrium. Because signaling through EPHs is associated with increased cell migration and invasion, we hypothesized that chemical inhibition of EPHA2/4 could have therapeutic value. We screened DNA-encoded chemical libraries (DECL) to rapidly identify EPHA2/4 kinase inhibitors. Hit compound, CDD-2693, exhibited picomolar/nanomolar kinase activity against EPHA2 (Ki: 4.0 nM) and EPHA4 (Ki: 0.81 nM). Kinome profiling revealed that CDD-2693 bound to most EPH family and SRC family kinases. Using NanoBRET target engagement assays, CDD-2693 had nanomolar activity versus EPHA2 (IC50: 461 nM) and EPHA4 (IC50: 40 nM) but was a micromolar inhibitor of SRC, YES, and FGR. Chemical optimization produced CDD-3167, having picomolar biochemical activity toward EPHA2 (Ki: 0.13 nM) and EPHA4 (Ki: 0.38 nM) with excellent cell-based potency EPHA2 (IC50: 8.0 nM) and EPHA4 (IC50: 2.3 nM). Moreover, CDD-3167 maintained superior off-target cellular selectivity. In 12Z endometriotic epithelial cells, CDD-2693 and CDD-3167 significantly decreased EFNA5 (ligand) induced phosphorylation of EPHA2/4, decreased 12Z cell viability, and decreased IL-1β-mediated expression of prostaglandin synthase 2 (PTGS2). CDD-2693 and CDD-3167 decreased expansion of primary endometrial epithelial organoids from patients with endometriosis and decreased Ewing's sarcoma viability. Thus, using DECL, we identified potent pan-EPH inhibitors that show specificity and activity in cellular models of endometriosis and cancer.

Studies have shown that endometriosis significantly has a negative impact on women's mental health and quality of life (QoL), resulting in these participants experiencing a diminished QoL.

This study aimed to evaluate the effect of laparoscopic surgery on the severity of pain and the QoL of women with different types of endometriosis.

In this follow-up study 50 women with endometriosis, who underwent laparoscopic surgery, who met a high visual analog score ( > 6) with impaired QoL, lack of response to analgesics, infertility with pain unresponsive to assisted reproductive therapy, and involvement of other organs such as the bowel or ureter at the Amir Al Momenin hospital, Zabol, Iran, from August 2022 to January 2023 were enrolled. The participants were categorized into 2 groups: those with stage IV endometriosis and those with lower stages (I-III). Groups according to the higher occurrence of grade 4 endometriosis, as 55.1% were affected by it. The pain score was measured using the visual analog score, and the participants' QoL score was measured using the endometriosis health profile questionnaire.

The mean age of participants was 32 yr, with a standard deviation of 8.6 yr. Participants were divided into 2 groups: those with grade 4 endometriosis (55.1%) and those with a grade lower than 4, as classified by the American Society for Reproductive Medicine. Over 12 months, both groups experienced a significant decrease in pain severity and QoL scores (p < 0.0001). However, the changes in pain and QoL scores between the 2 groups were not statistically significant (p = 0.520 and p = 0.984, respectively).

Laparoscopic treatment can reduce pain and QoL scores (increase the QoL indices) in women with endometriosis, regardless of the disease's severity.

Endometriosis affects 10% of reproductive-age women, and yet, it goes undiagnosed for 3.6 years on average after symptoms onset. Despite large GWAS meta-analyses (N > 750,000), only a few dozen causal loci have been identified. We hypothesized that the challenges in identifying causal genes for endometriosis stem from heterogeneity across clinical and biological factors underlying endometriosis diagnosis.

We extracted known endometriosis risk factors, symptoms, and concomitant conditions from the Penn Medicine Biobank (PMBB) and performed unsupervised spectral clustering on 4,078 women with endometriosis. The 5 clusters were characterized by utilizing additional electronic health record (EHR) variables, such as endometriosis-related comorbidities and confirmed surgical phenotypes. From four EHR-linked genetic datasets, PMBB, eMERGE, AOU, and UKBB, we extracted lead variants and tag variants 39 known endometriosis loci for association testing. We meta-analyzed ancestry-stratified case/control tests for each locus and cluster in addition to a positive control (Total N endometriosis cases = 10,108).

We have designated the five subtype clusters as pain comorbidities, uterine disorders, pregnancy complications, cardiometabolic comorbidities, and EHR-asymptomatic based on enriched features from each group. One locus, RNLS , surpassed the genome-wide significant threshold in the positive control. Thirteen more loci reached a Bonferroni threshold of 1.3 x 10 -3 (0.05 / 39) in the positive control. The cluster-stratified tests yielded more significant associations than the positive control for anywhere from 5 to 15 loci depending on the cluster. Bonferroni significant loci were identified for four out of five clusters, including WNT4 and GREB1 for the uterine disorders cluster, RNLS for the cardiometabolic cluster, FSHB for the pregnancy complications cluster, and SYNE1 and CDKN2B-AS1 for the EHR-asymptomatic cluster. This study enhances our understanding of the clinical presentation patterns of endometriosis subtypes, showcasing the innovative approach employed to investigate this complex disease.

Gynecological and obstetric infectious diseases are crucial to women's health. There is growing evidence that links the presence of Fusobacterium nucleatum (F. nucleatum), an anaerobic oral commensal and potential periodontal pathogen, to the development and progression of various human diseases, including cancers. While the role of this opportunistic oral pathogen has been extensively studied in colorectal cancer in recent years, research on its epidemiological evidence and mechanistic link to gynecological diseases (GDs) is still ongoing. Thus, the present review, which is the first of its kind, aims to undertake a comprehensive and critical reappraisal of F. nucleatum, including the genetics and mechanistic role in promoting adverse pregnancy outcomes (APOs) and various GDs, including cancers. Additionally, this review discusses new conceptual advances that link the immunomodulatory role of F. nucleatum to the development and progression of breast, ovarian, endometrial, and cervical carcinomas through the activation of various direct and indirect signaling pathways. However, further studies are needed to explore and elucidate the highly dynamic process of host-F. nucleatum interactions and discover new pathways, which will pave the way for the development of better preventive and therapeutic strategies against this pathobiont.

Currently, the optimal treatment to increase the chance of pregnancy and live birth in patients with colorectal endometriosis and subfertility is unknown. Evidence suggests that that both surgery and in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) are effective in improving live birth rate (LBR) among these women. However, the available evidence is of low quality, reports highly heterogeneous results, lacks direct comparison between both treatment options and does not assess whether a combination strategy results in a higher LBR compared to IVF/ICSI-only treatment. Additionally, the optimal timing of surgery within the treatment trajectory remains unclear. The primary objective of the TOSCA study is to assess the effectiveness of surgical treatment (potentially combined with IVF/ICSI) compared to IVF/ICSI-only treatment to increase the chance of an ongoing pregnancy resulting in a live birth in patients with colorectal endometriosis and subfertility, measured by cumulative LBR. Secondary objectives are to assess and compare quality of life and cost-effectiveness in both groups. Patients will be followed for 40 months after inclusion or until live birth. The TOSCA study is expected to be completed in 6 years.

Endometriosis is linked to increased infertility and pregnancy complications due to defective endometrial decidualization. We hypothesized that identification of altered signaling pathways during decidualization could identify the underlying cause of infertility and pregnancy complications. Our study reveals that transforming growth factor β (TGFβ) pathways are impaired in the endometrium of individuals with endometriosis, leading to defective decidualization. Through detailed transcriptomic analyses, we discovered abnormalities in TGFβ signaling pathways and key regulators, such as SMAD4, in the endometrium of affected individuals. We also observed compromised activity of bone morphogenetic proteins (BMP), a subset of the TGFβ family, that control endometrial receptivity. Using 3-dimensional models of endometrial stromal and epithelial assembloids, we showed that exogenous BMP2 improved decidual marker expression in individuals with endometriosis. Our findings reveal dysfunction of BMP/SMAD signaling in the endometrium of individuals with endometriosis, explaining decidualization defects and subsequent pregnancy complications in these individuals.

Autoimmune diseases are a diverse and complex set of chronic disorders with a substantial impact on patient quality of life and a significant global healthcare burden. Current approaches to autoimmune disease treatment comprise broadly acting immunosuppressive drugs that lack disease specificity, possess limited efficacy, and confer undesirable side effects. Additionally, there are limited treatments available to restore organs and tissues damaged during the course of autoimmune disease progression. Cell therapies are an emergent area of therapeutics with the potential to address both autoimmune disease immune dysfunction as well as autoimmune disease-damaged tissue and organ systems. In this review, we discuss the pathogenesis of common autoimmune disorders and the state-of-the-art in cell therapy approaches to (1) regenerate or replace autoimmune disease-damaged tissue and (2) eliminate pathological immune responses in autoimmunity. Finally, we discuss critical considerations for the translation of cell products to the clinic.

Endometriosis is associated with a range of symptoms that can negatively impact a person's quality of life. While pain and infertility have received at lot of attention, sleep disturbances in individuals with endometriosis has been overlooked in both clinical practice and research. Therefore, the primary aim of this systematic review was to gather evidence from the current literature to illustrate the association between sleep disturbances and endometriosis.

A literature search was conducted using three electronic databases (OVID EMBASE, MEDLINE, and Web of Science). Observational studies, published in English, that involved participants aged 18 years or older that compared sleep outcomes between endometriosis patients and those without a history of endometriosis were included. The quality of each study was assessed using the Joanna Briggs Institute critical appraisal tools.

Nine studies (six case-control and three cross-sectional) were included in this review; 7 with low risk of bias and 2 with moderate risk of bias. The studies demonstrated heterogeneity in the assessment of sleep disturbances. However, 7 studies reported a significant positive association between endometriosis and sleep disturbances. Moreover, this impact on sleep was further complicated by the complex interaction between pain, fatigue and quality of life.

Current studies suggest an association between sleep disturbances and endometriosis, which may provide a blueprint for future clinical recommendations to screen and treat sleep disturbances in individuals with endometriosis to improve their quality of life. Future studies should aim to standardise the methods of assessing sleep disturbances and explore potential contributing factors.

Endometriosis is an inflammatory condition affecting approximately 10% of the female-born population. Despite its prevalence, the lack of noninvasive biomarkers has contributed to an established global diagnostic delay. The intricate pathophysiology of this enigmatic disease may leave signatures in the blood, which, when detected, can be used as noninvasive biomarkers. This review provides an update on how investigators are utilizing the established disease pathways and innovative methodologies, including genome-wide association studies, next-generation sequencing, and machine learning, to unravel the clues left in the blood to develop blood biomarkers. Many blood biomarkers show promise in the discovery phase, but because of a lack of standardized and robust methodologies, they rarely progress to the development stages. However, we are now seeing biomarkers being validated with high diagnostic accuracy and improvements in standardization protocols, providing promise for the future of endometriosis blood biomarkers.