Seven hormonal biomarkers for diagnosing endometriosis: Meta-analysis and adjusted indirect comparison of diagnostic test accuracy
Abstract
Objective To compare the diagnostic accuracy of different hormonal biomarkers and to find the most effective hormonal biomarker for the diagnosis of endometriosis.Data sources We conducted a systematic search using PubMed, EMBASE, Cochrane Library, and China Biomedical Literature to identify relevant studies from the first day of databases to August 2018.Methods of study selection Two independent reviewers screened for study eligibility and extracted data. Random controlled trials, cross-sectional studies, case-control studies, and cohort studies evaluating the diagnostic accuracy of hormonal markers for endometriosis were included.Tabulation, integration, and results We included 17 studies that involved 1279 participants and evaluated 7 hormonal biomarkers. The pooled sensitivity and specificity in endometriosis were .79 (.71, .86) and .89 (.82, .94) for aromatase, .30 (.18, .46) and .80 (.65, .90) for human chorionic gonadotropin/luteinizing hormone receptor, .75 (.66, .83) and .47 (.34, .60) for estrogen receptor (ER)-α, .65 (.56, .74) and .68 (.55, .80) for ER-β, .45 (.38-.52) and .92 (.85-.97) for serum prolactin, .69 (.51, .83) and .30 (.16, .49) for estrogen sulfotransferase, and .73 (.60-.84) and .48 (.33-.63) for 17β-hydroxysteroid dehydrogenase type 2 (17βHSD2). Compared with human chorionic gonadotropin/luteinizing hormone receptor, ER-α, ER-β, estrogen sulfotransferase, and 17βHSD2, aromatase had a higher sensitivity, specificity, positive likelihood ratio, and diagnostic odds ratio. The specificities of aromatase and serum prolactin were comparable, but the sensitivity, positive likelihood ratio, and positive likelihood ratio of serum prolactin were much lower than that of aromatase.Conclusion Aromatase may be an excellent diagnostic test for endometriosis. However, because of the moderate quality of the included studies and the limited sample size, this result requires more research to validate. (PROSPERO registration number: PROSPERO 2018 CRD42018105126.).
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Serum prolactin levels are significantly elevated in women with endometriosis, but prior examinations mainly focused on patients with endometriosis and accompanying infertility.
“It has also been documented that serum prolactin levels are significantly elevated in women with endometriosis, however, the examinations were mainly focused on patients with endometriosis and accompanying infertility [23,24,25].”
From Diagnostic Significance of Selected Serum Inflammatory Markers in Women with Advanced Endometriosis (2021) · cites this paper as [23]
Cites
QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies
Whiting, P. F., Rutjes, A. W. S., Westwood, M. E., Mallett, S., Deeks, J. J., Reitsma, J. B., Leeflang, M. M. G., Sterne, J. A. C., Bossuyt, P. M. M., & the QUADAS-2 Group* (2011) · Annals of Internal Medicine · doi:10.7326/0003-4819-155-8-201110180-00009 · Cited by 14,199 · see citing works
Giudice, L. C., & Kao, L. C. (2004) · The Lancet · doi:10.1016/s0140-6736(04)17403-5 · Cited by 3,166 · see citing works
Deeks, J. J., Macaskill, P., & Irwig, L. (2005) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2005.01.016 · Cited by 2,910 · see citing works
Giudice, L. C. (2010) · New England Journal of Medicine · doi:10.1056/nejmcp1000274 · Cited by 1,924 · see citing works
Hall, J. M., & McDonnell, D. P. (1999) · Endocrinology · doi:10.1210/endo.140.12.7179 · Cited by 1,078 · see citing works
Immunobiology of endometriosis
Lebovic, D. I., Mueller, M. D., & Taylor, R. N. (2001) · Fertility and Sterility · doi:10.1016/s0015-0282(00)01630-7 · Cited by 857 · see citing works
Simpson, E. R., Clyne, C., Rubin, G., Boon, W. C., Robertson, K., Britt, K., Speed, C., & Jones, M. (2002) · Annual Review of Physiology · doi:10.1146/annurev.physiol.64.081601.142703 · Cited by 773 · see citing works
Cancer-associated mutations in endometriosis without cancer
Anglesio, M. S., Papadopoulos, N., Ayhan, A., Nazeran, T. M., Noë, M., Horlings, H. M., Lum, A., Jones, S., Senz, J., Seckin, T., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1614814 · Cited by 628 · see citing works
Al‐Sukhni, E., Milot, L. M., Fruitman, M., Beyene, J., Victor, J. C., Schmocker, S., Brown, G. M., McLeod, R. S., & Kennedy, E. D. (2012) · Annals of Surgical Oncology · doi:10.1245/s10434-011-2210-5 · Cited by 576 · see citing works
Consensus on current management of endometriosis
Johnson, N. P., Hummelshoj, L., for the World Endometriosis Society Montpellier Consortium, Abrao, M. S., Adamson, G. D., Allaire, C., Amelung, V., Andersson, E., Becker, C., Birna Árdal, K. B., et al. (2013) · Human Reproduction · doi:10.1093/humrep/det050 · Cited by 558 · see citing works
Estrogen receptor alpha and beta in health and disease
Jia, M., Dahlman‐Wright, K., & Gustafsson, J.-Α. (2015) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2015.04.008 · Cited by 543 · see citing works
Endometriosis: a high-risk population for major chronic diseases?
Kvaskoff, M., Mu, F., Terry, K. L., Harris, H. R., Poole, E. M., Farland, L., & Missmer, S. A. (2015) · Human Reproduction Update · doi:10.1093/humupd/dmv013 · Cited by 439 · see citing works
Blood biomarkers for the non-invasive diagnosis of endometriosis
Nisenblat, V., Bossuyt, P. M., Shaikh, R., Farquhar, C. M., Jordan, V., Scheffers, C. S., Mol, B. W., JOHNSON, N. P., & Hull, M. L. (2016) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012179 · Cited by 388 · see citing works
Endometriosis: The pathophysiology as an estrogen-dependent disease
Kitawaki, J., Kado, N., Ishihara, H., Koshiba, H., Kitaoka, Y., & Honjo, H. (2002) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(02)00260-1 · Cited by 370 · see citing works
No role for quality scores in systematic reviews of diagnostic accuracy studies
Whiting, P. F., Harbord, R. M., & Kleijnen, J. (2005) · BMC Medical Research Methodology · doi:10.1186/1471-2288-5-19 · Cited by 333 · see citing works
Zeitoun, K., Takayama, K., Sasano, H., Suzuki, T., Moghrabi, N., Andersson, S., Johns, A., Meng, L., Putman, M., Carr, B., et al. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.12.5301 · Cited by 308 · see citing works
Kitawaki, J., Noguchi, T., Amatsu, T., Maeda, K., Tsukamoto, K., Yamamoto, T., Fushiki, S., Osawa, Y., & Honjo, H. (1997) · Biology of Reproduction · doi:10.1095/biolreprod57.3.514 · Cited by 305 · see citing works
Combination of the non-invasive tests for the diagnosis of endometriosis
Nisenblat, V., Prentice, L., Bossuyt, P. M., Farquhar, C. M., Hull, M. L., & JOHNSON, N. P. (2016) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012281 · Cited by 227 · see citing works
Aromatase: biologic relevance of tissue-specific expression
(2004) · Seminars in Reproductive Medicine · doi:10.1055/s-2004-823023 · Cited by 190 · see citing works
Endometrial biomarkers for the non-invasive diagnosis of endometriosis
Gupta, D., Hull, M. L., Fraser, I. S., Miller, L., Bossuyt, P. M., JOHNSON, N. P., & Nisenblat, V. (2016) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012165 · Cited by 174 · see citing works
Estrogen metabolizing enzymes in endometrium and endometriosis
Dassen, H., Punyadeera, C., Kamps, R., Delvoux, B., Van Langendonckt, A., Donnez, J., Husen, B., Thole, H., Dunselman, G., & Groothuis, P. (2007) · Human Reproduction · doi:10.1093/humrep/dem310 · Cited by 141 · see citing works
Kitawaki, J., Kusuki, I., Koshiba, H., Tsukamoto, K., Fushiki, S., & Honjo, H. (1999) · Fertility and Sterility · doi:10.1016/s0015-0282(99)00424-0 · Cited by 133 · see citing works
Expression of estrogen receptor alpha and beta in peritoneal and ovarian endometriosis
Matsuzaki, S., Murakami, T., Uehara, S., Canis, M., Sasano, H., & Okamura, K. (2001) · Fertility and Sterility · doi:10.1016/s0015-0282(01)01783-6 · Cited by 133 · cited 1× · see citing works
“Previous studies suggested that the predominant expression of ER-a in both glandular epithelial and stromal cells may be essential for the development and growth of peritoneal and ovarian endometriosis [54].”
BackgroundTop ten endometriosis research priorities in the UK and Ireland
Horne, A. W., Saunders, P. T. K., Abokhrais, I. M., & Hogg, L. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31344-2 · Cited by 131 · see citing works
Lei, Z. M., Reshef, E., & Rao, V. B. (1992) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.75.2.1379262 · Cited by 123 · see citing works
Li, H., Yao, L., Jin, P., et al. (2018) · The Breast · doi:10.1016/j.breast.2018.04.018 · Cited by 117 · see citing works
Minegishi, T. (1997) · Molecular Human Reproduction · doi:10.1093/molehr/3.2.101 · Cited by 87 · see citing works
Licht, P., Russu, V., Lehmeyer, S., & Wildt, L. (2001) · PubMed · Cited by 81 · see citing works
Informing women with endometriosis about ovarian cancer risk
Kvaskoff, M., Horne, A. W., & Missmer, S. A. (2017) · The Lancet · doi:10.1016/s0140-6736(17)33049-0 · Cited by 80 · see citing works
Andoh, K., Kubota, T., Takada, M., Tanaka, H., Kobavashi, N., & Maekawa, T. (1987) · Cancer · doi:10.1002/1097-0142(19870215)59:4 · Cited by 75 · see citing works
Prolactin and cortisol levels in women with endometriosis
Lima, A. P., Moura, M. D., & Rosa e Silva, A. A. M. (2006) · Brazilian Journal of Medical and Biological Research · doi:10.1590/s0100-879x2006000800015 · Cited by 70 · see citing works
Hudelist, G., Czerwenka, K., Keckstein, J., Haas, C., Fink-Retter, A., Gschwantler-Kaulich, D., Kubista, E., & Singer, C. F. (2007) · Reproductive Sciences · doi:10.1177/1933719107309120 · Cited by 70 · see citing works
Kitawaki, J., Koshiba, H., Ishihara, H., Kusuki, I., Tsukamoto, K., & Honjo, H. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.9.6829 · Cited by 69 · see citing works
Bouchoucha, N., Samara‐Boustani, D., Pandey, A. V., Bony-Trifunovic, H., Hofer, G., Aigrain, Y. Y., Polak, M., & Flück, C. E. (2014) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2014.03.008 · Cited by 65 · see citing works
Matsuzaki, S., Canis, M. J., Pouly, J. L., Déchelotte, P. J., & Mage, G. (2006) · Fertility and Sterility · doi:10.1016/j.fertnstert.2005.08.017 · Cited by 61 · see citing works
Dheenadayalu, K., Mak, I., Gordts, S., Campo, R., HIGHAM, J. M., Puttemans, P., WHITE, J. O., Christian, M., Fusi, L., & Brosens, J. J. (2002) · Fertility and Sterility · doi:10.1016/s0015-0282(02)03324-1 · Cited by 49 · see citing works
Evaluation of Serum ProlactinLevels in Patients with Endometriosisand Infertility
Gregoriou, G., Bakas, P., Vitoratos, N., et al. (1999) · Gynecologic and Obstetric Investigation · doi:10.1159/000010133 · Cited by 41 · see citing works
Are we employing the most effective CA 125 and CA 19-9 cut-off values to detect endometriosis?
Xavier, P. A. F., Beires, J., Belo, L., Rebelo, I., Martinez‐de‐Oliveira, J., Lunet, N., & Barros, H. (2005) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2005.04.003 · Cited by 38 · see citing works
Lei, Z. M., Rao, C. V., Lincoln, S. R., et al. (1993) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.76.3.7680356 · Cited by 37 · see citing works
A predictive model for endometriosis
Wölfler, M. M., Nagele, F., Kolbus, A., Seidl, S., Schneider, B., Huber, J. C., & Tschugguel, W. (2005) · Human Reproduction · doi:10.1093/humrep/deh796 · Cited by 33 · see citing works
New paradigms in the diagnosis and management of endometriosis
Kavoussi, S. K., Lim, C. S., Skinner, B. D., Lebovic, D. I., & As‐Sanie, S. (2016) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/gco.0000000000000288 · Cited by 33 · see citing works
Conservative surgical management of endometriosis in women with pelvic pain
Frishman, G. N., & Salak, J. R. (2006) · Journal of Minimally Invasive Gynecology · doi:10.1016/j.jmig.2006.06.023 · Cited by 28 · see citing works
Serum Prolactin and CA-125 Levels as Biomarkers of Peritoneal Endometriosis
Bilibio, J. P., de Souza, C. A. B., Rodini, G. P., Andreoli, C., Genro, V. K., Conto, E. D., & Cunha‐Filho, J. S. (2014) · Gynecologic and Obstetric Investigation · doi:10.1159/000362272 · Cited by 28 · see citing works
Endometrial aromatase mRNA as a possible screening tool for advanced endometriosis and adenomyosis
Hatok, J., Žúbor, P., Galo, S., Kirschnerova, R., Dobrota, D., Danko, J., & Račay, P. (2010) · Gynecological Endocrinology · doi:10.3109/09513590.2010.491925 · Cited by 27 · see citing works
Cyp19a1(Aromatase) Expression in the X enopusBrain at Different Developmental Stages
Coumailleau, P., & Kah, O. (2014) · Journal of Neuroendocrinology · doi:10.1111/jne.12142 · Cited by 22 · see citing works
Serum Prolactin and CA-125 Levels as Biomarkers of Peritoneal Endometriosis
Bilibio, J. P., & Cunha‐Filho, J. S. (2015) · Gynecologic and Obstetric Investigation · doi:10.1159/000441790 · Cited by 19 · see citing works
Ji, Q., Chen, P., Aoyoma, C., et al. (2002) · Molecular and Cellular Probes · doi:10.1006/mcpr.2002.0421 · Cited by 18 · see citing works
Hudelist, G., Huber, A., Knöefler, M., Haider, S., Kolbus, A., Czerwenka, K. F., Helmy, S., Kubista, E., & Singer, C. F. (2008) · Reproductive Sciences · doi:10.1177/1933719108316907 · Cited by 13 · see citing works
P450 arom y microambiente estrogénico en endometrios eutópicos de mujeres con endometriosis
P, M. C. J., Claudio Pinto, O., Alessandra Alves, L., Alberto Palomino, A., Ariel Fuentes, G., Boric, M. A., & Margarita Vega, B. (2004) · Revista médica de Chile · doi:10.4067/s0034-98872004001200004 · Cited by 10 · see citing works
Liu, A., Guan, Z., Zhang, Z.-M., Wei, L., & Li, Y. (2008) · PubMed · Cited by 9 · see citing works
Ishii, R., Saito, T., Shao, L., et al. (2013) · Journal of Medical Virology · doi:10.1002/jmv.23599 · Cited by 9 · see citing works
[Diagnostic value of the detection of aromatase cytochrome P450 and CA125 for endometriosis].
Zeng, F., & Xue, M. (2005) · PubMed · Cited by 4 · see citing works
The Expression of Aromatase Cytochrome P450 in Eutopic Endometrium and its Clinical Significance
Wang, H. (2003) · Journal of Practical Obstetrics and Gynecology · Cited by 1 · see citing works
Jian-tin, M. (2012) · Chinese Journal of Laboratory Diagnosis · Cited by 1 · see citing works
Diagnostic value of serum CA125 level and endometrial aromatase detection to endometriosis
Xia-li, X. (2011) · Journal of Chinese Practical Diagnosis and Therapy · Cited by 1 · see citing works
Preliminary research of the detection of aromatase cytochrome P450 for endometriosis in infertility
Yu, H. (2008) · Clinical Medicine · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Diagnostic Significance of Selected Serum Inflammatory Markers in Women with Advanced Endometriosis
Kokot, I., Piwowar, A., Jędryka, M., Sołkiewicz, K., & Kratz, E. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052295 · Cited by 76 · see citing works
“It was highlighted that despite the high specificity, the sensitivity of serum prolactin for the diagnosis of endometriosis remained unacceptably low [23].”
Background
- Authors
- Gao, Y., Shen, M., Ma, X., Li, J., Wang, B., Wang, J., & Tian, J.
- Affiliations
- Lanzhou University (CN)
- Lanzhou University Second Hospital (CN)
- Gansu Provincial Hospital (CN)
- Corresponding author
- Tian, Jinhui
- Venue
- Journal of Minimally Invasive Gynecology
- Publisher
- Elsevier BV
- Published
- 2019-09
- Volume
- 26
- Issue
- 6
- Pages
- 1026-1035.e4
- ISSN
- 1553-4650 (ISSN-L)
- OpenAlex
- W2935373464
- Cited by
- 18
- References
- 56
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 4
- FWCI
- 0.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Minimally Invasive Gynecology (publishedVersion)
- PubMed (publishedVersion)
- Lanzhou University Institutional Repository (submittedVersion)
- Funders
- Science and Technology Plan Project of Gansu Province (17JR5RA236)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
- Health Sciences › Medicine › Obstetrics and Gynecology › Gynecological conditions and treatments
- Keywords
- endometriosis, hormonal biomarkers, diagnostic accuracy, aromatase, estrogen receptor alpha, estrogen receptor beta, serum prolactin, estrogen sulfotransferase, 17β-hydroxysteroid dehydrogenase type 2, indirect comparison, sensitivity and specificity, biomarker selection
- MeSH terms
- Cross-Sectional Studies, Diagnostic Techniques, Endocrine, Diagnostic Techniques, Obstetrical and Gynecological, Diagnostic Tests, Routine, Endometriosis, Female, Hormones, Humans, Predictive Value of Tests, Sensitivity and Specificity, Reproducibility of Results, Biomarkers, Case-Control Studies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
