The DOI matches its Crossref record; 121 of the 132 references it cites were found in a registry or an index; none of the 73 sources its claims cite is checked for support yet.
Biomarkers in endometriosis: challenges and opportunities
Open accessAbstract
Endometriosis is a debilitating gynecologic disease affecting millions of women across the world, with symptoms including dysmenorrhea, chronic pelvic pain, and infertility. Theorized to stem from the phenomenon of retrograde menstruation, the diagnosis of endometriosis is typically delayed by 8-10 years owing to misinterpretation of symptoms as common menstrual cramps in adolescent girls and young women. With increased incidence of endometriosis in young girls correlated with earlier menarche, the development of diagnostic biomarkers is imperative for diagnosing and treating women afflicted with endometriosis as early as we can. In the past few years, multiple reviews highlighted the list of potential diagnostic candidates in peritoneal fluid, blood, urine, and endometrial biopsies from endometriosis patients in different stages of disease and menstrual cycle. In this review, we explore the opportunities and challenges facing the field of diagnostic biomarkers for endometriosis. We highlight the importance of eutopic endometrium as a source of potential diagnostic biomarkers by looking at the expression levels of noncoding RNA in tissue as well as in blood. Finally, we discuss some of the challenges that hinder our efforts in validating candidate diagnostic biomarkers for endometriosis.
Overview
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Written from the paper’s full text.
TL;DR
This review argues that noninvasive diagnostic biomarkers for endometriosis are urgently needed because diagnosis is typically delayed by 8–10 years, but disease heterogeneity, comorbidities, and nonstandardized sample collection hinder validation. It highlights eutopic endometrium and circulating/tissue noncoding RNAs as promising candidates, while cautioning that inflammatory cytokines and endometrial DNA methylome have not proven sufficiently specific.
Key findings
- Diagnostic delay is substantial: adolescent girls delay seeking medical attention by 4.6 years, and it takes another 4.7 years until diagnosis; overall diagnosis is typically delayed by 8–10 years.
- Endometriosis symptoms are more common than in women without endometriosis: nonmenstrual pelvic pain 38.7% vs. 14.3%, dyspareunia 29.5% vs. 13.4%, and infertility 11.6% vs. 3.4%; economic burden is $1.8 billion in Canada and $18–22 billion in the United States.
- Candidate noncoding RNA biomarkers show diagnostic potential: plasma brain-derived neurotropic factor for stage I–II disease had 91.7% sensitivity and 69.4% specificity; circulating let-7b had 83.3% sensitivity and 100% specificity; miR-17-5p, miR-20a, and miR-22 discriminated severe endometriosis with an AUC of 0.90; a five-lncRNA combination had 89.7% sensitivity and 73.2% specificity.
- Cytokine panels have been tested but are limited: one six-marker panel showed 60%–71% specificity and 87%–92% sensitivity, and a 28-biomarker panel showed 63%–81% specificity and 81%–90% sensitivity, but control selection and nonendometriotic pelvic inflammation can confound results.
Methods
- Design: narrative review of diagnostic biomarkers for endometriosis, focused on opportunities and challenges in validation.
- Data/sample: literature on candidate biomarkers from peritoneal fluid, blood, urine, endometrial biopsies, eutopic endometrium, and epigenetic markers, including miRNA and lncRNA; no primary cohort or new experimental data are reported.
- Main analysis: synthesizes prior reviews, meta-analyses, and selected studies to evaluate biomarker specificity/sensitivity and discuss barriers to clinical validation; evident from the text that this is not a systematic review or meta-analysis.
Limitations
- The paper states that endometriosis is heterogeneous in phenotype and symptoms, with endopelvic and extrapelvic manifestations, and that comorbidities such as autoimmune disorders, migraines, gastrointestinal problems, and adenomyosis can mask or confound biomarker signals.
- The paper states that biomarker studies are limited by unstandardized sample collection, storage, and phenotyping; small sample sizes; lack of representation across all disease stages and menstrual stages; and discrepancies between tissue and blood miRNA expression.
- Evident from the text: as a narrative review, it does not provide a systematic search strategy, quantitative synthesis, or primary validation data, so its conclusions depend on selected published literature.
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Claims the paper makes
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“For decades, both basic and clinical research have been much focused on elucidating the pathogenesis of endometriosis, but they have lumped different phenotypes of the disease, including ovarian, peritoneal, and deep infiltrating endometriosis, as one entity.”
§ Biomarkers in endometriosis: challenges and opportunities > Heterogeneous Nature of Endometriosis and Endometriosis-Associated Symptoms
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In the paper
“which have demonstrated that the endometrium of endometriosis patients displays aberrant molecular expression patterns that give it the ability to implant, invade, and develop into endometriotic foci (27)(28)(29)(30).”
§ Biomarkers in endometriosis: challenges and opportunities > E
What the sources say
- Not checked yetcites [27] Burney, 2007, Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis, Endocrinology source
- Not checked yetcites [28] Bulun, 2006, Progesterone resistance in endometriosis: link to failure to metabolize estradiol, Mol Cell Endocrinol source
- Not checked yetcites [29] Mehasseb, 2011, Estrogen and progesterone receptor isoform distribution through the menstrual cycle in uteri with and without adenomyosis, Fertil Steril source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“For example, Naqvi et al. (26) observed five hypermethylated (MGMT, DUSP22, CDCA2, ID2, and RBBP7) and five hypomethylated (TNFRSF1B, MBPR1B, ZNF681, IGSF21, and TP73) genes in eutopic endometrium of patients compared with endometriosis-free control subjects.”
§ Biomarkers in endometriosis: challenges and opportunities > Assessing the Usefulness of Endometrial Biopsies
What the sources say
- Not checked yetcites [26] Naqvi, 2014, Altered genome-wide methylation in endometriosis, Reprod Sci source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Such heterogeneity of disease phenotype also increases the potential of false-negative laparoscopic surgery in symptomatic women, wherein a ''clean'' pelvic cavity might not necessarily indicate the absence of endometriosis in other areas of the body (Table 1).”
§ Biomarkers in endometriosis: challenges and opportunities > Heterogeneous Nature of Endometriosis and Endometriosis-Associated Symptoms
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Unless accompanied by explorative laparoscopic surgery for complete diagnosis, accurate differential diagnosis in potential endometriosis patients based on symptoms proves to be a difficult challenge.”
§ Biomarkers in endometriosis: challenges and opportunities > Heterogeneous Nature of Endometriosis and Endometriosis-Associated Symptoms
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The concentration of peripheral markers in blood and peritoneal fluid may be diluted with factors that are driving the development of conditions other than endometriosis in patients.”
§ Biomarkers in endometriosis: challenges and opportunities > Comorbidities
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Case studies have shown that symptoms of pelvic pain are not a useful diagnostic parameter to differentiate women with or without endometriosis (54), owing to the similarity of symptoms with other pelvic pain pathologies, such as irritable bowel disease.”
§ Biomarkers in endometriosis: challenges and opportunities > Heterogeneous Nature of Endometriosis and Endometriosis-Associated Symptoms
What the sources say
- Not checked yetcites [54] Ballard, 2010, Can specific pain symptoms help in the diagnosis of endometriosis? A cohort study of women with chronic pelvic pain, Fertil Steril source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“It is highly likely, however, that the altered endometrial response was due to transitory modification in the genome imposed by the external presence of ectopic foci (9).”
§ Biomarkers in endometriosis: challenges and opportunities > In Search of Molecular Patterns Unique to Endometriosis
What the sources say
- Not checked yetcites [9] Guo, 2009, Epigenetics of endometriosis, Mol Hum Reprod source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These conditions may also have underlying immunologic and inflammatory pathologic mechanisms with peripheral increase in cytokines commonly associated with endometriosis, thereby potentially introducing bias in studies using peripheral cytokines as diagnostic indicators of endometriosis.”
§ Biomarkers in endometriosis: challenges and opportunities > Comorbidities
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Owing to ethical constraints, it is unlikely that we will be able to study the early stages of endometriosis development by injecting menstrual fragments into the peritoneal cavity of women.”
§ Biomarkers in endometriosis: challenges and opportunities > In Search of Molecular Patterns Unique to Endometriosis
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 8
- Probably not a substantial claim. 2
In the paper
“Owing to the common misinterpretation of endometriosis-induced pain as menstrualrelated abdominal pain, the diagnosis of endometriosis is typically delayed by 8-10 years: Adolescent girls who suffer from the symptoms of endome-triosis delay seeking medical attention by 4.6 years, and by the time they seek medical attention, it takes another 4.7 years until diagnosis (11).”
§ Biomarkers in endometriosis: challenges and opportunities > E
What the sources say
- Not checked yetcites [11] Greene, 2009, Diagnostic experience among 4,334 women reporting surgically diagnosed endometriosis, Fertil Steril source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Furthermore, As-Sanie et al. demonstrated that increased concentration of glutamine and glutamate within the anterior insula and greater neuronal connectivity from the anterior insula to the medial prefrontal cortex positively correlated with not only pain intensity, but also clinical anxiety and depression in patients (60).”
§ Biomarkers in endometriosis: challenges and opportunities > Heterogeneous Nature of Endometriosis and Endometriosis-Associated Symptoms
What the sources say
- Not checked yetcites [60] As-Sanie, 2016, Functional connectivity is associated with altered brain chemistry in women with endometriosis-associated chronic pelvic pain, J Pain source
Strength:boosted· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Endometriosis is a complex disease with variable phenotypic and symptomatic presentation in women (14,15).”
§ Biomarkers in endometriosis: challenges and opportunities > E
What the sources say
- Not checked yetcites [14] Vercellini, 2007, Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients, Hum Reprod source
- Not checked yetcites [15] Acién, 2013, Endometriosis: a disease that remains enigmatic, Int Sch Res Not Obstet Gynecol
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Furthermore, basic scientific research on the pathogenesis of extrapelvic endometriosis is limited.”
§ Biomarkers in endometriosis: challenges and opportunities > Heterogeneous Nature of Endometriosis and Endometriosis-Associated Symptoms
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The method of obtaining endometrial sample by either pipelle or curette is minimally invasive; however, aside from minimal discomfort for the patient, biopsy can prove to be a useful not only to test endometrial receptivity in infertile women with or without endometriosis (81), but also as a diagnostic tool for endometriosis in an outpatient setting (82).”
§ Biomarkers in endometriosis: challenges and opportunities > Assessing the Usefulness of Endometrial Biopsies
What the sources say
- Not checked yetcites [81] Garcia-Velasco, 2015, Is endometrial receptivity transcriptomics affected in women with endometriosis? A pilot study, Reprod Biomed Online source
- Not checked yetcites [82] Saare, 2016, The influence of menstrual cycle and endometriosis on endometrial methylome, Clin Epigenetics source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Because endometriosis can be found in asymptomatic women, however, the biochemical pathway of nerve stimulation by the release of damage-associated molecular patterns and pathogen-associated molecular patterns by the menstrual debris (58) does not apply to the asymptomatic women, suggesting that the inflammation caused by ''menstruating'' ectopic foci and menstrual debris may not be the sole cause”
§ Biomarkers in endometriosis: challenges and opportunities > Heterogeneous Nature of Endometriosis and Endometriosis-Associated Symptoms
What the sources say
- Not checked yetcites [58] Laux-Biehlmann, 2015, Menstruation pulls the trigger for inflammation and pain in endometriosis, Trends Pharmacol Sci source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Even though GWASs have identified numerous SNPs associated with endometriosis risk across multiple populations, the strengths of the studies are affected by unstandardized methods of biologic sample collection, storage, and phenotyping of samples across studies, which may invariably lead to heterogeneous interpretations and findings (24).”
§ Biomarkers in endometriosis: challenges and opportunities > In Search of Molecular Patterns Unique to Endometriosis
What the sources say
- Not checked yetcites [24] Rahmioglu, 2014, Genetic variants underlying risk of endometriosis: Insights from meta-analysis of eight genome-wide association and replication datasets, Hum Reprod Update source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The studies showed that a panel of cytokines, rather than a single biomarker, improve sensitivity and specificity values, with some panels showing the ability to discriminate between different stages of disease.”
§ Biomarkers in endometriosis: challenges and opportunities > Biomarkers That Were Not So Useful: Inflammatory Cytokines
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The physiologic process of menstruation is an inflammatory event.
None of the sources cited for this claim have been checked yet.
In the paper
“However, one limiting factor hindering the exploration of miRNA as biomarkers in clinical trials is the small sample sizes of patients and lack of representation of all stages of endometriosis, which are also stratified by menstrual stage (85, 109, 110).”
§ Biomarkers in endometriosis: challenges and opportunities > Ahn. Biomarkers in endometriosis. Fertil Steril 2017.
What the sources say
- Not checked yetcites [85] Burney, 2009, MicroRNA expression profiling of eutopic secretory endometrium in women with versus without endometriosis, Mol Hum Reprod source
- Not checked yetcites [109] Cho, 2015, Circulating microRNAs as potential biomarkers for endometriosis, Fertil Steril source
- Not checked yetcites [110] Jia, 2013, Plasma miR-17-5p, miR-20a and miR-22 are down-regulated in women with endometriosis, Hum Reprod source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, miRNA profiling of eutopic endometrium in endometriosis patients would provide pathophysiologic molecular fingerprints that we can use to further understand disease pathogenesis and as potential noninvasive biomarkers for endometriosis.”
§ Biomarkers in endometriosis: challenges and opportunities > MicroRNA and Long Noncoding RNA
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
Laparoscopic surgery remains the current criterion-standard diagnostic tool for endometriosis.
“Laparoscopic surgery remains the current criterion-standard diagnostic tool; however, it is unlikely that women of reproductive age would subject themselves to such an invasive surgery when they can opt to temporarily diminish pain symptoms by means of other therapeutic mechanisms.”
The paper relies on this without support.
Women of reproductive age would be unlikely to subject themselves to laparoscopic surgery when they can opt to temporarily diminish pain symptoms by other therapeutic mechanisms.
“Laparoscopic surgery remains the current criterion-standard diagnostic tool; however, it is unlikely that women of reproductive age would subject themselves to such an invasive surgery when they can opt to temporarily diminish pain symptoms by means of other therapeutic mechanisms.”
The paper relies on this without support.
Only 10% of women develop endometriosis.
“This is critical to elucidate why only 10% of women develop endometriosis although the phenomenon of retrograde menstruation occurs in 76%-90% of reproductive-age women (94)(95)(96).”
The paper relies on this without support.
The physiologic process of menstruation is an inflammatory event.
“The physiologic process of menstruation is an inflammatory event, as is the pathophysiologic process of endometriosis.”
The paper relies on this without support.
There is a need for a diagnostic biomarker for endometriosis.
“Along with the need to better understand the pathophysiology of endometriosis, the need for a diagnostic biomarker for endometriosis has been equally recognized.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The time from the appearance of the first symptoms of the disease to the diagnosis is up to 8 to 10 years [38].”
From Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature) (2021) · cites this paper as [38]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Peritoneal endometriosis classified as both pelvic and extrapelvic
MinorThe paper first places peritoneal implants in the pelvis, then lists typical peritoneal endometriosis among extrapelvic manifestations.
“Endometriosis is often described as occurring in three areas in the pelvis-in the peritoneum, on the ovary, and in the rectovaginal pouch-which are referred to as peritoneal implants, ovarian endometrioma, and deep infiltrating endometriosis, respectively.”
“The extrapelvic manifestations include the typical peritoneal or abdominal wall endometriosis, including endometriosis found on surgical scars on the peritoneum (44,45), the urinary and gastrointestinal tract, the thorax, and the nasal mucosa (42).”
Citations
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11 of the 132 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
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- Nisenblat, 2016, Imaging modalities for the noninvasive diagnosis of endometriosis, Cochrane Database Syst Rev, CD009591
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Cited by
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Exosomal microRNAs and long noncoding RNAs: as novel biomarkers for endometriosis
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“Because early menarche is becoming more common among young girls with endometriosis-related symptoms (Ahn et al. 2017), and knowing that the gold standard for detecting endometriosis is laparoscopic examination, which is an invasive procedure.”
BackgroundNoninvasive evaluation of ovarian endometriosis: a single-center experience
Zhao, K., & Qu, P. (2021) · Annals of Palliative Medicine · doi:10.21037/apm-21-481 · Cited by 10
“It can take 8 to 10 years to receive a diagnosis of endometriosis after symptom onset (5).”
BackgroundAdamyan, L. V., Pivazyan, L. G., Murvatova, K. K., Tarlakyan, V., Zarova, E., Stepanian, A. A., & Mailova, K. S. (2024) · Journal of Endometriosis and Uterine Disorders · doi:10.1016/j.jeud.2024.100100 · Cited by 10
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BackgroundOocyte-Secreted Serum Biomarkers GDF9 and BMP15 in Women with Endometriosis
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“As a sisterhood disease, endometriosis is characterized by the endometrial glands and stroma residing outside of the uterus [68].”
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“There are several lipidomic studies of plasma, [114] serum, [131] follicular fluid [106,132] and endometrium tissues [5,66,118] from patients with endometriosis by chromatography with MS.”
Secretory phase of menstruation and implantation
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“This leads to downstream effects such as phosphorylated STAT3, which in turn helps lead to an estrogen dominant and progesterone resistant state [2,20].”
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“Because the symptoms associated with endometriosis are frequently misattributed to dysmenorrhea, a condition commonly experienced by adolescent girls and young women, significant delays in diagnosis can occur (4).”
Reproductive surgery: decreasing skills and advancing technology—an existential conundrum
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Research Progress of Caspase in Endometriosis
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Antibody Arrays Identified Cycle-Dependent Plasma Biomarker Candidates of Peritoneal Endometriosis
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Computational Models for Diagnosing and Treating Endometriosis
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“Эта гипотеза была сформулирована в недавней обзорной статье канадских авторов [28], которые отметили важность поиска «маркерных» микроРНк в эутопическом эндометрии.”
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Study on diagnostic values and pathological conditions of serum HGF and CA199 in endometriosis.
Xilan, Z., Nie, D., Zhang, L., & Liu, X. (2021) · PubMed Central · Cited by 5
Role of cystatin C levels as an inflammatory marker in predicting endometriosis
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Clues to revising the conventional diagnostic algorithm for endometriosis
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“60 Furthermore, another key issue is the risk of stigma following the failure of empirical medical treatment.”
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“The definitive diagnosis of EMs requires surgical intervention with histological confirmation, as there is no non-invasive diagnostic method available despite ongoing research into various biomarkers in preclinical studies (Ahn et al. 2017; Bjorkman and Taylor 2019; Anastasiu et al.2020).”
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Endometrioma: a new paradigm of diagnostics and therapeutic tactics
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“29,30 Non-invasive diagnostics would also be critical in improving patient access to care, reducing diagnostic delays and addressing the signi fi cant underreporting of these conditions in LMICs.”
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Osteopontin as a marker of endometriosis — the current state of knowledge
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“Currently, the main areas of interest in current research are the search for markers in plasma, urine, uterine fluid or menstrual blood [17].”
Rahmawati, N. Y., Ahsan, F., Santoso, B. I., Mufid, A. F., Sa’adi, A., Dwiningsih, S. R., Tunjungseto, A., & Widyanugraha, M. Y. A. (2024) · Journal of Endometriosis and Pelvic Pain Disorders · doi:10.1177/22840265241231722 · Cited by 3
“26,44,45 A good and reliable bio-marker could be used as an expedient diagnostic tool for endometriosis and the effectiveness of treatment.”
Li, L., Zhang, Y., Zhou, J., Wang, J., & Wang, L. (2024) · Drug Discoveries & Therapeutics · doi:10.5582/ddt.2024.01004 · Cited by 3
“The regulation of miRNAs has been recognized in recent years as a therapeutic strategy in numerous diseases, with several drugs targeting specific miRNAs for therapeutic purposes ( 13,14 ).”
BackgroundShayanfard, A. H., Salehi, Z., Mashayekhi, F., & Zahiri, Z. (2024) · Journal of Human Reproductive Sciences · doi:10.4103/jhrs.jhrs_92_24 · Cited by 3
Sarhangi, N., Mohseni, S., Aminimoghaddam, S., Rashidi, B. H., Haghollahi, F., Qorbani, M., Amoli, M. M., & Shahrabi-Farahani, M. (2019) · PubMed Central · doi:10.22088/ijmcm.bums.8.2.63 · Cited by 3
“com ndometriosis is a debilitating disorder, with a multifactorial pathogenesis, in which the endometrial gland and stroma that normally lines the inside of the uterine cavity, grows outside of the uterus, principally on the pelvic peritoneum, ovaries, and rectovaginal septum (1, 2).”
BackgroundExploring Patient Adherence to Post-Surgical Follow-Up in Pelvic Endometriosis
Szabo, T., Mitranovici, M.-I., Crișan, A., Melinte, I. M., Cotruș, T., Tudorache, V., Moraru, L., Moraru, R., & Micu, R. (2023) · Medicina · doi:10.3390/medicina59071210 · Cited by 2
“Dopaminergic agonists have been shown to reduce angiogenesis by inducing endocytosis of the VEGF receptor 2, while cannabinoids have been found to control pain symptoms [24,28].”
BackgroundHe, Y., Ding, J., Bai, T., Li, Y., Liang, X., Chen, Y., Lin, Y., Cheng, W., & Yu, C. (2024) · Biomolecules and Biomedicine · doi:10.17305/bb.2024.11311 · Cited by 2
“Coupled with the lack of effective non-invasive diagnostic tools, this misinterpretation leads to a delayed diagnosis of EMS—typically by 8–10 years [4].”
Evaluation of Long-COVID Syndrome in a Cohort of Patients with Endometriosis or Adenomyosis
Xholli, A., Perugi, I., Cremonini, F., Londero, A. P., & Cagnacci, A. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14061835 · Cited by 2
“Endometriosis is a chronic gynecological condition of premenopausal women, with about 10% global prevalence and a diagnostic delay ranging from 8 to 10 years [1,2].”
Neykhonji, M., Al-Asady, A. M., Al-Okla, S., Al-Nazwani, N. S., Avan, A., Khazaei, M., & Hassanian, S. M. (2025) · Current Pharmaceutical Design · doi:10.2174/0113816128364775250326161410 · Cited by 2
Mechanisms of KLF10 in Regulating Proliferation of Endometriotic Stromal Cells in Endometriosis
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“LncRNAs are promising therapeutic targets in EM as they are closely associated with gene translation, cargo and expression, in fl ammatory injuries, and drug sensitivity in EM [11].”
Dou, S., Ling, S., Nong, W., Wei, B., Huang, Y., Li, G., Wang, R., & Qin, H. (2025) · Functional & Integrative Genomics · doi:10.1007/s10142-025-01631-z · Cited by 2
“Existing biomarkers have been derived from a variety of sources, including peripheral blood, urine, and endometrial biopsy (Ahn et al. 2017 ; Fassbender and Van-hie 2019; Anastasiu et al. 2020 ; Tian et al. 2020 ).”
Serum miRNA-based diagnostic models for endometriosis: from discovery to validation
Ravaggi, A., Bergamaschi, C., Conforti, J., Ciravolo, G., Zanotti, L., Fabricio, A. S. C., Gion, M., Cappelletto, E., Leon, A. E., Rossetti, D. O., et al. (2025) · Human Reproduction · doi:10.1093/humrep/deaf221 · Cited by 4
Looking at endometriosis–diagnosis and disease mechanisms through a mechanical lens
Thomsen, T., Petite, E., Pierce, C. A., Ellis, T., Acharya, P., & Sohn, L. L. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1716836 · Cited by 2
“Other diagnostic methods include imaging and the utilization of blood-based biomarkers that span several molecular categories [e.g., glycoproteins, cytokines, mRNA, and microRNAs (9–13)].”
Huang, L., Hu, R., Xiong, X., Zhao, C., Xia, L., Ai, X., Yu, M., Wan, Z., Zhao, Y., & Huang, J. (2026) · Journal of Affective Disorders · doi:10.1016/j.jad.2026.121642 · Cited by 2
Examining Diagnostic Options and Classification Systems Available for Endometriosis
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Application of Balneoclimatology and Physiotherapy in Endometriosis
Wójcik, M., Placek, K. M., Drejza, M. A., Goździewicz, T., Pisarska-Krawczyk, M., Luwański, D., Plagens-Rotman, K., Kędzia, W., & Jarząbek‐Bielecka, G. (2023) · Acta Balneologica · doi:10.36740/abal202306112 · Cited by 2
Rahmawati, N. Y., Ahsan, F., Santoso, B. I., Mufid, A. F., Sa’adi, A., Dwiningsih, S. R., Tunjungseto, A., & Widyanugraha, M. Y. A. (2024) · Gynecologic and Obstetric Investigation · doi:10.1159/000538525 · Cited by 2
Sleep disorders and hyperarousal among patients with endometriosis: A case-control survey study
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“Different studies provide evidence of the relationship between the highly inflammatory microenvironment of lesions in endometriosis and pain symptoms [66 – 68].”
Vasodilatation of endometrial microvessels with endometriosis and induction of pain
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Medical Treatment for Endometriosis
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Secretory Phase and Implantation
Marsh, C. A., Schumacher, K., Nothnick, W. B., Taylor, R. N., & Monard, M. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.81304 · Cited by 3
“Local inflammatory factors include endometriosis, adenomyosis, hydrosalpinges, and endometritis [2, 28, 29].”
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Novel Diagnostic Methods for Endometriosis
Tejeswi, A. (2023) · Journal of Student Research · doi:10.47611/jsrhs.v12i4.5766 · Cited by 1
“This further validates the advantageous nature of the emerging lncRNA biomarker (Ahn et al., 2017).”
BackgroundResultInfluentialMenstrual cyclicity: Pathogenicity, predictability, and reproducibility
Ray, A. K., & Roychoudhury, M. (2024) · Journal of Reproductive Healthcare and Medicine · doi:10.25259/jrhm_15_2023 · Cited by 1
Xue, L., Zhang, R., Chen, J., Ge, X.-X., & Chen, J. (2025) · International Journal of Women s Health · doi:10.2147/ijwh.s509603 · Cited by 1
“3,7,8 Elevated expression of UDP-glucose ceramide glucosyltransferase ( UGCG ) has emerged as a promising therapeutic target for EM.”
Lin, M., Seeley, E. H., Ledet, S., Salazar, C., Breen, M., & Eberlin, L. S. (2025) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-025-05930-z · Cited by 1
“Currently, there are no proven pre-operative diagnostic markers of endometriosis [6, 11], and exploratory laparoscopic surgery followed by pathology remains as the main diagnostic and treatment option for patients [12].”
Nitric oxide as a biomarker for patients with endometriosis: a systematic review and meta-analysis
Campara, K., Rodrigues, P., Viero, F. T., da Silva, B., & Trevisan, G. (2025) · Nitric Oxide · doi:10.1016/j.niox.2025.07.002 · Cited by 1
Shaofu Zhuyu Decoction for Treating Endometriosis: A Systematic Review and Meta-Analysis
Kim, S.-B., Yoon, Y.-J., Sung, S.-H., & Park, J.-K. (2025) · Pharmaceuticals · doi:10.3390/ph18091296 · Cited by 2
“Diagnosis typically relies on laparoscopic examination due to the heterogeneous and often nonspecific nature of symptoms, resulting in a prolonged diagnostic delay [5].”
Approaches to the search for immunological markers of endometriosis and the degree of its prevalence
Krechetova, K. L. V., Korotkova, T. D., Inviyaeva, E. V., & Adamyan, L. V. (2025) · Meditsinskiy sovet = Medical Council · doi:10.21518/ms2025-261 · Cited by 1
Extracellular Trap-Related Genes as Potential Diagnostic Biomarkers for Endometriosis
Fang, Y., He, Y.-F., Wang, B.-B., He, J., Yang, D., Chen, G., & Zhou, S. (2025) · International Journal of Women s Health · doi:10.2147/ijwh.s556544 · Cited by 1
Gut microbiota alterations in endometriosis: an observational study in a Spanish female cohort
Martínez‐Lara, A., Sanz, A. D. T., Durán‐González, E., Reyes-Conde, M. L., Díaz-López, C., Pérez-Sánchez, M., Ramírez‐Tejero, J. A., Cotán, D., & Almansa, J. A. H. (2025) · Biology of Reproduction · doi:10.1093/biolre/ioaf272 · Cited by 2
Lisa, Z., Fanta, M., Kokavec, J., & Janoštiak, R. (2026) · Scientific Reports · doi:10.1038/s41598-026-35467-9 · Cited by 2
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“Finding a non-invasive biomarker has been challenging due to disease heterogeneity and comorbidities that can alter its levels [122].”
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“Some studies have shown that inflammation-related cytokines are associated with dysmenorrhea (Ahn et al., 2017; Kiyama, 2020).”
BackgroundApparent lncRNAs involvement in pathogenesis of endometriosis
Kwas, K., Szubert, M., & Wilczyński, J. R. (2024) · Journal of Endometriosis and Pelvic Pain Disorders · doi:10.1177/22840265241298743 · Cited by 1
“12 However, despite the retrograde menstruation theory, it is still not clear why only 10% of women experiencing it develop endometriosis, while this condition affects 90% of all women.”
Ahsan, F., Rahmawati, N. Y., Santoso, B. I., Alditia, F. N., Mufid, A. F., Sa’adi, A., Dwiningsih, S. R., Tunjungseto, A., & Widyanugraha, M. Y. A. (2025) · Laboratory Medicine · doi:10.1093/labmed/lmae107 · Cited by 1
An Overview of Epigenetic Correlates of Human Chronic Pain Conditions
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Endometrial Immune-Inflammatory Gene Signatures in Endometriosis
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Metadata
- Authors
- Ahn, S. H., Singh, V., & Tayade, C.
- Affiliations
- Queen's University (CA)
- Corresponding author
- Tayade, Chandrakant
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 107
- Issue
- 3
- Pages
- 523-532
- ISSN
- 0015-0282 (ISSN-L)
- OpenAlex
- W2586274172
- Cited by
- 242
- References
- 132
- Citations by year
- 2026: 20 · 2025: 32 · 2024: 35 · 2023: 21 · 2022: 18 · 2021: 29 · 2020: 33 · 2019: 27 · 2018: 23 · 2017: 3
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (394924)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Obstetrics and Gynecology › Ectopic Pregnancy Diagnosis and Management
- Health Sciences › Medicine › Obstetrics and Gynecology › Gynecological conditions and treatments
- Keywords
- endometriosis, diagnostic biomarkers, eutopic endometrium, non-coding RNA, peritoneal fluid, blood biomarkers, urinary biomarkers, endometrial biopsy, biomarker validation, delayed diagnosis, retrograde menstruation, infertility, dysmenorrhea, chronic pelvic pain
- MeSH terms
- Biopsy, Endometriosis, Endometrium, Female, Genetic Markers, Humans, Menstrual Cycle, Predictive Value of Tests, Prognosis, Reproducibility of Results, Biomarkers, Comorbidity, Cytokines, Inflammation Mediators, MicroRNAs, RNA, Long Noncoding
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