The DOI matches its Crossref record; 224 of the 226 references it cites were found in a registry or an index.
Peripheral biomarkers of endometriosis: a systematic review
Open accessAbstract
BACKGROUND: Endometriosis is estimated to affect 1 in 10 women during the reproductive years. There is often delay in making the diagnosis, mainly due to the non-specific nature of the associated symptoms and the need to verify the disease surgically. A biomarker that is simple to measure could help clinicians to diagnose (or at least exclude) endometriosis; it might also allow the effects of treatment to be monitored. If effective, such a marker or panel of markers could prevent unnecessary diagnostic procedures and/or recognize treatment failure at an early stage. METHODS: We used QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria to perform a systematic review of the literature over the last 25 years to assess critically the clinical value of all proposed biomarkers for endometriosis in serum, plasma and urine. RESULTS: We identified over 100 putative biomarkers in publications that met the selection criteria. We were unable to identify a single biomarker or panel of biomarkers that have unequivocally been shown to be clinically useful. CONCLUSIONS: Peripheral biomarkers show promise as diagnostic aids, but further research is necessary before they can be recommended in routine clinical care. Panels of markers may allow increased sensitivity and specificity of any diagnostic test.
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In the citing paper
“Firstly, according to QUADAS (Quality Assessment of Diagnostic Accuracy Studies) guidelines [15,16], samples should be collected at a consistent phase of the cycle and results should be corrected for the cycle phases.”
From A high sensitivity assay is more accurate than a classical assay for the measurement of plasma CRP levels in endometriosis (2011) · cites this paper as [15]
In the citing paper
“Secondly, according to a recently published systematic review, lack of correction for the phase of the menstrual cycle can explain the considerable variability between studies with respect to blood levels of biomarkers in women with endometriosis and controls [15].”
From A high sensitivity assay is more accurate than a classical assay for the measurement of plasma CRP levels in endometriosis (2011) · cites this paper as [15]
In the citing paper
“Studies performed in various compartments in the body as serum, peritoneal, and follicular fluids are not sufficient for precise evaluation [17].”
From Serum levels of androgens and prostate-specific antigen in endometriosis (2014) · cites this paper as [17]
In the citing paper
“In our study, samples were collected at a well defined phase of the cycle and results were corrected for cycle phase, as recommended by the QUADAS (Quality Assessment of Diagnostic Accuracy Studies) guidelines [15,16].”
From A high sensitivity assay is more accurate than a classical assay for the measurement of plasma CRP levels in endometriosis (2011) · cites this paper as [15]
In the citing paper
“Despite the fact that research on biomarkers of endometriosis are still ongoing, there are still no satisfactory results, which makes it impossible to carry out effective laboratory diagnostics used in the diagnosis and monitoring of the treatment of the disease [157].”
From Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature) (2021) · cites this paper as [157]
In the citing 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.”
From Biomarkers in endometriosis: Challenges and opportunities (2017) · cites this paper as [69]
In the citing paper
“Another ovarian tumor marker, CA-19-9, has been shown to be elevated in endometriosis and has a comparable or lower sensitivity than CA-125 for the detection of endometriosis [23].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [23]
In the citing paper
“Despite extensive research, no single biomarker nor a panel of biomarkers in peripheral blood has been validated as a diagnostic test for endometriosis [17, 20].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [20]
In the citing paper
“Overall, most endometriosis biomarker studies have remained at the level of Phase I [23] and only a few have made it to Phase II studies.”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [23]
In the citing paper
“At present, such a test does not exist [17, 20].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [20]
In the citing paper
“Putative endometriosis biomarkers are mostly glycoproteins, growth or adhesion factors, hormones, or proteins related to immunology or angiogenesis [17, 23, 30].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [23]
In the citing paper
“Levels of the sICAM-I have been suggested to rise during early stages of endometriosis (I-II) and decrease at stage III-IV [23].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [23]
In the citing paper
“Its usefulness as biomarker for endometriosis is unclear, as some studies show elevated blood levels in endometriosis patients while other studies do not record a significant difference [23, 67].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [23]
In the citing paper
“Follistatin, an inhibitor of activin, has been shown to be increased in endometriosis patients [23], especially in a subgroup of patients with ovarian endometrioma, and showed good sensitivity and specificity [43].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [23]
In the citing paper
“The inflammatory marker C-reactive protein (CRP) has been shown to be upregulated [23], especially when examined with a high sensitivity assay making it possible to detect subclinical inflammation in women with endometriosis [50].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [23]
In the citing paper
“However, other studies could not find an upregulation [23, 51].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [23]
In the citing paper
“Other growth factors, such as soluble epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) have been investigated, but no difference was found between endometriosis patients and control women [23].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [23]
In the citing paper
“Both total immunoglobulin levels and antiendometrial antibodies have been investigated as potential biomarkers for endometriosis of which the latter showed the most promising results, being more commonly present in endometriosis patients than in controls [23].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [23]
In the citing paper
“Hepatocyte growth factor (HGF) was suggested to be elevated in women with endometriosis [72], although this was not confirmed in an additional study [23, 73].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [23]
In the citing paper
“These studies have shown promising results; however, proteomics technologies are costly and time-consuming [23], and there is a need for better standardization and reproducibility of proteomic technologies before they can be used reliably in clinical research projects [17].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [23]
In the citing paper
“Elevations of fibroblast growth factor-2 (FGF-2), angiogenin, and soluble Flt-I (VEGFR-1) in serum of women with endometriosis have all been recorded [23].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [23]
In the citing paper
“A range of cell populations, including T cells, B cells, natural killer (NK) cells, macrophages/monocytes, and polymorphonuclear neutrophils, has been compared between endometriosis patients and healthy controls [23]. However, for none of these populations the utility as an endometriosis biomarker has been proven [23, 96].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [23]
In the citing paper
“No consensus exists on changes in steroid hormone levels [23].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [23]
In the citing paper
“Contrasting evidence exists on prolactin, leptin, luteinizing hormone (LH), and adiponectin levels in endometriosis patients versus controls, showing either no difference, an increase (prolactin, leptin LH) or a decrease (adiponectin) [23, 75, 76].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [23]
In the citing paper
“Likewise, specific antibodies against carbonic anhydrase, transferrin, α2-HS glycoprotein, lipid peroxide modified rabbit serum albumin, copper oxidized low-density lipoprotein and malondialdehyde-modified low-density lipoprotein, laminin-I, and cardiolipin have shown promise as potential endometriosis biomarkers [23].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [23]
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Dunselman, G. A. J., Vermeulen, N., Becker, C., Calhaz-Jorge, C., D'Hooghe, T., De Bie, B., Heikinheimo, O., Horne, A. W., Kiesel, L., Nap, A., et al. (2014) · Human Reproduction · doi:10.1093/humrep/det457 · Cited by 2,211
Self-citationESHRE guideline: endometriosis
Becker, C. M., Bokor, A., Heikinheimo, O., Horne, A., Jansen, F., Kiesel, L., King, K., Kvaskoff, M., Nap, A., Petersen, K., et al. (2022) · Human Reproduction Open · doi:10.1093/hropen/hoac009 · Cited by 1,712
“…should not use measurement of biomarkers in endometrial tissue, blood, menstrual or uterine fluids to diagnose endometriosis (Mol et al. , 1998; May et al. , 2010; May et al. , 2011; Liu et al. , 2015; Cosar et al. , 2016; Gupta et al. , 2016; Hirsch et al. , 2016; Nisenblat et al. , 2016a;…”
Self-citationEndometriosis is a chronic systemic disease: Clinical challenges and novel innovations
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Zondervan, K. T., Becker, C. M., Koga, K., Missmer, S. A., Taylor, R. N., & Viganò, P. (2018) · Nature Reviews Disease Primers · doi:10.1038/s41572-018-0008-5 · Cited by 1,257
Self-citationSmolarz, B., Szyłło, K., & Romanowicz, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910554 · Cited by 560
Metadata
- Authors
- May, K. E., Conduit-Hulbert, S. A., Villar, J., Kirtley, S., Kennedy, S. H., & Becker, C. M.
- Affiliations
- John Radcliffe Hospital (GB)
- Corresponding author
- Becker, C. M.
- Venue
- Human Reproduction Update
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-05-12
- Volume
- 16
- Issue
- 6
- Pages
- 651-674
- ISSN
- 1355-4786 (ISSN-L)
- 1460-2369
- PMC
- PMC2953938
- OpenAlex
- W2160282642
- Cited by
- 418
- References
- 226
- Citations by year
- 2026: 15 · 2025: 13 · 2024: 13 · 2023: 24 · 2022: 37 · 2021: 29 · 2020: 37 · 2019: 36 · 2018: 27 · 2017: 33 · 2016: 38 · 2015: 32 · 2014: 32 · 2013: 18 · 2012: 23
- FWCI
- 2.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Reproduction Update (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Explore Bristol Research (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- 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, peripheral biomarkers, diagnostic biomarkers, serum biomarkers, plasma biomarkers, urinary biomarkers, biomarker panel, diagnostic accuracy, treatment monitoring, delayed diagnosis
- MeSH terms
- Antibodies, Cell Adhesion, Endometriosis, Female, Glycoproteins, Hormones, Humans, Leukocytes, Biomarkers, Cytokines, Apoptosis, Intercellular Signaling Peptides and Proteins, Proteomics, Vascular Endothelial Growth Factor A
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