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Cited by 560Endometriosis Research and TreatmentGynecological conditions and treatmentsEctopic Pregnancy Diagnosis and Management

Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature)

Open access
Smolarz, Beata, Szyłło, Krzysztof, Romanowicz, Hanna·2021·International Journal of Molecular Sciences
DOI 10.3390/ijms221910554PMC PMC8508982
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Abstract

Endometriosis is a “mysterious” disease and its exact cause has not yet been established. Among the etiological factors, congenital, environmental, epigenetic, autoimmune and allergic factors are listed. It is believed that the primary mechanism of the formation of endometriosis foci is retrograde menstruation, i.e., the passage of menstrual blood through the fallopian tubes into the peritoneal cavity and implantation of exfoliated endometrial cells. However, since this mechanism is also observed in healthy women, other factors must also be involved in the formation of endometriosis foci. Endometriosis is in many women the cause of infertility, chronic pain and the deterioration of the quality of life. It also represents a significant financial burden on health systems. The article presents a review of the literature on endometriosis—a disease affecting women throughout the world.

AI snapshot

Written from the paper’s full text.

TL;DR

Endometriosis is a chronic, estrogen-dependent gynecological disease whose exact cause remains unexplained, with retrograde menstruation, immune dysfunction, and genetic/epigenetic factors implicated. This narrative review covers its history, epidemiology, classification, pathogenesis, diagnosis, treatment, biomarkers, and genetics, emphasizing the lack of a specific biomarker and fully effective therapy.

Key findings

  • Endometriosis affects 10–15% of women of reproductive age and 35–50% of women with pelvic pain and/or infertility; up to 30–50% of affected women may experience infertility, and annual treatment costs in Europe range from €0.8 billion to €12.5 billion.
  • In a prospective cohort of 81,908 women followed from 1991 to 2013, those eating >2 servings/day of red meat had a 56% higher risk of laparoscopically confirmed endometriosis compared with those eating ≤1 serving/week; no association was found for poultry, fish, shellfish, or eggs.
  • Genetic factors are estimated to account for about 50% of predisposition to endometriosis; monozygotic twin co-occurrence exceeds 80%, and GWAS studies implicate loci/genes including WNT4, CDKN2BAS, GREB1, FN1, and ESR2/CYP19A1.
  • No specific biomarker is validated for diagnosis; IL-6 showed 63% sensitivity and 69% specificity, Ca-125 and Ca-19-9 have partial clinical use, and elagolix (150 mg once daily or 200 mg twice daily) reduced moderate-to-severe endometriosis pain, with the 200 mg dose limited to 6 months because of decreased bone mineral density.

Methods

  • Design: narrative literature review (“Review of Literature”) covering endometriosis epidemiology, classification, pathogenesis, treatment, and genetics.
  • Data/sample: no primary study sample; the paper synthesizes published literature, including cohort studies, GWAS, systematic reviews, and clinical trials.
  • Main analysis: narrative synthesis of cited evidence; no systematic search strategy, inclusion criteria, quality assessment, or meta-analysis of the reviewed literature is described.

Limitations

  • Stated in the paper: no specific endometriosis marker has been identified; treatment remains ineffective; miRNA/lncRNA studies are investigatory and require large, independent, clinically characterized cohorts; and no controlled randomized trials have determined whether exercise benefits women with endometriosis.
  • Evident from the text: as a narrative review, it does not report a reproducible literature search, study selection process, or formal quality appraisal, so conclusions depend on the cited sources and may be subject to selection bias.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/ijms221910554

Cites

202 of 202 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 199 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    A study did not detect differences in perioperative outcomes between robotic surgery and laparoscopy.

    “This study did not detect any differences in perioperative outcomes of surgery between robotic surgery and laparoscopy.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [130] Nezhat, 2015, Robotic-assisted laparoscopy vs conventional laparoscopy for the treatment of advanced stage endometriosis, J. Minim. Invasive Gynecol. source

      Not checked in the free run.

  • Interpretationnone given

    Sampson's theory is still dominant among hypotheses regarding the etiopathogenesis of endometriosis.

    “Despite the passage of such a long period of time and much scientific research, Sampson’s theory is still dominant among other hypotheses regarding the etiopathogenesis of endometriosis.”
    Quote in the paperNot a substantial claim
  • Interpretationreasoning

    Because retrograde menstruation is also observed in healthy women, other factors must also be involved in the formation of endometriosis foci.

    “However, since this mechanism is also observed in healthy women, other factors must also be involved in the formation of endometriosis foci.”
    Quote in the paperSubstantial claim
  • Interpretationcitation

    It has not been possible to fully explain why retrograde transport of menstrual blood, which occurs in nearly 90% of women of childbearing age, only leads to survival of endometrial tissue outside the uterine cavity in a minority of women.

    “It has still not been possible to fully explain why the retrograde transport of menstrual blood, which occurs in nearly 90% of women of childbearing age, only leads to the survival of endometrial tissue outside the uterine cavity in a minority of women [7].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Nap, 2004, Pathogenesis of endometriosis, Best Pract. Res. Clin. Obstet. Gynaecol. source

      Not checked in the free run.

  • Premisecitation

    Retrograde transport of menstrual blood occurs in nearly 90% of women of childbearing age.

    “It has still not been possible to fully explain why the retrograde transport of menstrual blood, which occurs in nearly 90% of women of childbearing age, only leads to the survival of endometrial tissue outside the uterine cavity in a minority of women [7].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Nap, 2004, Pathogenesis of endometriosis, Best Pract. Res. Clin. Obstet. Gynaecol. source

      Not checked in the free run.

  • May combine two claims. 58
  • Classified as probably not a substantial claim. 25
  • The quote only partly states this claim. 2

  • May combine two claims.

    Findingcitation

    There are no controlled and randomized trials determining whether and to what extent exercise can be beneficial for women with endometriosis; researchers have only speculated on this subject.

    “Analysis of the available literature data shows that there are no controlled and randomized trials determining whether and to what extent exercise can be beneficial for women with endometriosis. So far, researchers have only speculated on this subject [140].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [140] Koppan, 2010, Pelvic pain in endometriosis: Painkillers or sport to alleviate symptoms?, Acta Physiol. Hung. source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Complications after DIE surgery include rectal fistula (0.3-2%), intestinal stenosis (2%), and bladder atony (4-6%).

    “Complications after DIE surgery include rectal fistula (0.3–2%), intestinal stenosis (2%), and bladder atony (4–6%) [123,124,125].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [123] Roman, 2013, Postoperative digestive function after radical versus conservative surgical philosophy for deep endometriosis infiltrating the rectum, Fertil. Steril. source

      Not checked in the free run.

    • cites [124] Spagnolo, 2014, Urodynamic Evaluation and Anorectal Manometry Pre- and Post-operative Bowel Shaving Surgical Procedure for Posterior Deep Infiltrating Endometriosis: A Pilot Study, J. Minim. Invasive Gynecol. source

      Not checked in the free run.

    • cites [125] Mabrouk, 2019, Surgical, Clinical, and Functional Outcomes in Patients with Rectosigmoid Endometriosis in the Gray Zone: 13-Year Long-Term Follow-up, J. Minim. Invasive Gynecol. source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In miRNA profiling of eutopic endometrium from women with endometriosis, two miRNAs were elevated and 13 had reduced expression compared to control.

    “A sample of 667 human miRNAs were studied in patients with endometriosis compared to the control group. Two of the study miRNAs were elevated, while 13 miRNAs had reduced levels of expression in eutopic endometrium in endometriosis patients compared to control.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [162] Laudanski, 2015, Profiling of Selected MicroRNAs in Proliferative Eutopic Endometrium of Women with Ovarian Endometriosis, Biomed. Res. Int. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Endometriosis affects 10-15% of women of reproductive age and 35-50% of women with pelvic pain and/or infertility.

    “This disease affects from 10–15% of women of reproductive age and 35–50% of women with pelvic pain and/or infertility.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Lousse, 2008, Potential involvement of iron in the pathogenesis of peritoneal endometriosis, Mol. Hum. Reprod. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Endometriosis also occurs in patients after menopause and in adolescent women.

    “However, it should be noted that there are also cases of patients with endometriosis after menopause, and it also happens in adolescent women [17].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Lousse, 2008, Potential involvement of iron in the pathogenesis of peritoneal endometriosis, Mol. Hum. Reprod. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The vast majority of endometriosis cases occur between menarche and menopause, with the peak between 25 and 45 years of age.

    “The vast majority of cases of endometriosis occur in women between menarche and menopause. The peak of the disease falls in the period between 25 and 45 years of age [18].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] Eskenazi, 1997, Epidemiology of endometriosis, Obstet. Gynecol. Clin. N. Am. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Endometriosis is found in 0.1-53% of women operated on laparoscopically or by laparotomy, of which 12-32% are women after diagnostic laparoscopy due to pelvic pain delays and 10-60% after diagnostic laparoscopy due to disability.

    “Literature data indicate that endometriosis is found in 0.1–53% of women operated on laparoscopically or by laparotomy, of which 12–32% are women after diagnostic laparoscopy due to pelvic pain delays and 10–60% of the patient after diagnostic laparoscopy due to disability [19,20,21].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [19] Lu, 1995, Endometriosis: Current management, Mayo Clin. Proc. source

      Not checked in the free run.

    • cites [20] Dmowski, 1999, Endometriosis at the end of the millenium; the controversy remains, Pol. J. Gyn. Investig.

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    • cites [21] Kao, 2002, Global gene profiling in human endometrium during the window of implantation, Endocrinology source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    Endometriosis is in many women the cause of infertility, chronic pain and deterioration of quality of life.

    “Endometriosis is in many women the cause of infertility, chronic pain and the deterioration of the quality of life.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Endometriosis in 7% of women is associated with genetic predisposition in the family.

    “Endometriosis in 7% of women is associated with their genetic predisposition in the family.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [22] Cramer, 2002, The epidemiology of endometriosis, Ann. N. Y. Acad. Sci. source

      Not checked in the free run.

    • cites [23] Gadomska, 1997, Endometrioza, Medipress Ginekol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Endometriosis represents a significant financial burden on health systems.

    “It also represents a significant financial burden on health systems.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Simoens, 2012, The burden of endometriosis: Costs and quality of life of women with endometriosis and treated in referral centres, Hum. Reprod. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    The exact cause of endometriosis has not yet been established.

    “Endometriosis is a “mysterious” disease and its exact cause has not yet been established.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Despite the frequent occurrence of endometriosis, the mechanism of its formation remains unexplained and a good marker of the disease has not been discovered.

    “Despite such frequent occurrence of this disease, the mechanism of its formation remains unexplained, and a good marker of this disease has still not been discovered [39,40].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [39] Nisenblat, 2016, Blood biomarkers for the non-invasive diagnosis of endometriosis, Cochrane Database Syst. Rev.

      Not checked in the free run.

    • cites [40] Gupta, 2016, Endometrial biomarkers for the non-invasive diagnosis of endometriosis, Cochrane Database Syst. Rev.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In 80% of women with open fallopian tubes there is a retrograde outflow of menstrual blood, while endometriosis occurs only in some.

    “Literature data indicate that in 80% of women with open fallopian tubes there is a retrograde outflow of menstrual blood, while endometriosis occurs only in some.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] Witz, 1997, Semin Reprod Endocrinol, Pathogenesis

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Endometriosis has a significant negative impact on social life, family, and sexual, educational and professional life.

    “Endometriosis has a significant negative impact on aspects of social life, family, and sexual, educational and professional life [27,28,29].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [27] Simoens, 2012, The burden of endometriosis: Costs and quality of life of women with endometriosis and treated in referral centres, Hum. Reprod. source

      Not checked in the free run.

    • cites [28] Nnoaham, 2011, World Endometriosis Research Foundation Global Study of Women’s Health consortium. Impact of endometriosis on quality of life and work productivity: A multi-center study across ten countries, Fertil. Steril. source

      Not checked in the free run.

    • cites [29] Dunselman, 2013, The significant effect of endometriosis on physical, mental and social well-being: Results from an inter-national cross-sectional survey, Hum. Reprod. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Isolated cases of endometriosis have occurred in men treated with hormones for prostate cancer.

    “There have been isolated cases of endometriosis in men around the world who have been treated with hormones for prostate cancer [25].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Martin, 1985, Endometriosis in the male, Am. Surg.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There is generally no association between BMI and the incidence of endometriosis, but there has been a significant increase in the incidence of endometriosis in obese women compared to women with normal body weight.

    “Interestingly, the latest data indicate that there is generally no association between BMI and the incidence of endometriosis, but there has been a significant increase in the incidence of endometriosis in obese women compared to women with normal body weight.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50] Tang, 2020, Is body mass index associated with the incidence of endometriosis and the severity of dysmenorrhoea: A case-control study in China?, BMJ Open source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The presence of lateral parametrial endometriosis can be considered a reflection of more severe disease, ureteral stenosis and dilatation, and voiding dysfunctions, mainly because of involvement of the inferior hypogastric plexus.

    “The presence of lateral parametrial endometriosis (LPE) can be considered a reflection of a more severe disease, ureteral stenosis and dilatation, and voiding dysfunctions, mainly because of the involvement of the inferior hypogastric plexus.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Mabrouk, 2019, Parametrial Endometriosis: The Occult Condition that Makes the Hard Harder, J. Minim. Invasive Gynecol. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Endometriosis foci occur in fetuses.

    “World literature also reports the occurrence of foci of endometriosis in fetuses [24].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Signorile, 2010, New evidence of the presence of endometriosis in the human fetus, Reprod. Biomed. Online source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Endometriosis was found in 2% of women undergoing tubal ligation and 17% of women after surgery to remove the ovaries.

    “This disease was found in 2% of women undergoing tubal ligation and 17% of women after surgery to remove the ovaries [22,23].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [22] Cramer, 2002, The epidemiology of endometriosis, Ann. N. Y. Acad. Sci. source

      Not checked in the free run.

    • cites [23] Gadomska, 1997, Endometrioza, Medipress Ginekol.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Women with deep infiltrating endometriosis may have dysfunctions of the pelvic floor muscles and lower limb muscles, and pain is associated with pelvic floor muscle hypertonia and difficulty in pelvic floor muscle relaxation.

    “Studies indicate that women with DIE may have dysfunctions of the pelvic floor muscles (PFMs) and lower limb muscles (LLMs). Pain was associated with PFM hypertonia and difficulty in PFM relaxation [41].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] Fraga, 2021, Pelvic floor muscle dysfunctions in women with deep infiltrative endometriosis: An underestimated association, Int. J. Clin. Pract. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In 66% of women with endometriosis, the first symptoms appear before the age of 20.

    “In 66% of women with endometriosis, the first symptoms of the disease appear before the age of 20 [32].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Bourdel, 2006, Endometriosis in teenagers, Gynecol. Obstet. Fertil. source

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  • May combine two claims.

    Premisecitation

    The risk of developing endometriosis is lowest in black women, highest in Asian women, and Caucasian women have a higher risk than black women.

    “The risk of developing endometriosis is the lowest in black women, the highest in Asian women. Caucasian women have a higher risk of getting sick than black women [26].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Goldstein, 1980, Laparoscopy on the diagnosis and management of pelvic pain in adolescents, J. Reprod. Med.

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Annual costs of endometriosis treatment in Europe range from €0.8 billion to €12.5 billion depending on the country and are comparable to other chronic diseases such as diabetes.

    “The annual costs of endometriosis treatment in Europe range from €0.8 billion to €12.5 billion depending on the country and are comparable to other chronic diseases such as diabetes [27].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Simoens, 2012, The burden of endometriosis: Costs and quality of life of women with endometriosis and treated in referral centres, Hum. Reprod. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Robotically assisted laparoscopy is associated with longer duration of relief than laparoscopic surgery, but results are controversial.

    “Laparoscopically assisted robotics are associated with longer duration of relief than laparoscopic surgery, but the results are controversial [129,130].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [129] Magrina, 2015, Surgical Excision of Advanced Endometriosis: Perioperative Outcomes and Impacting Factors, J. Minim. Invasive Gynecol. source

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    • cites [130] Nezhat, 2015, Robotic-assisted laparoscopy vs conventional laparoscopy for the treatment of advanced stage endometriosis, J. Minim. Invasive Gynecol. source

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  • May combine two claims.

    Premisecitation

    Gonadoliberin analogues decrease production of real GnRH, resulting in decreased LH and FSH levels and a significant reduction in estrogen levels.

    “Gonadoliberin analogues are substances with a structure similar to GnRH, which “deceive” the hypothalamus, causing a decrease in the production of real GnRH. This results in a decrease in LH and FSH levels and a significant reduction in estrogen levels.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Donnez, J., and Dolmans, M.M. (2021). Endometriosis and Medical Therapy: From Progestogens to Progesterone Resistance to GnRH Antagonists: A Review. J. Clin. Med., 10. source

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  • May combine two claims.

    Premisecitation

    Physical therapy techniques reduce pain and improve quality of life in endometriosis.

    “Physical therapy techniques are known to reduce pain and improve quality of life in endometriosis.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [136] Troyer, 2007, Differential diagnosis of endometriosis in a young adult woman with nonspecific low back pain, Phys. Ther. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Regular exercise is thought to promote reduced menstrual flow, ovarian stimulation, and estrogen effects.

    “Regular exercise is thought to promote reduced menstrual flow, ovarian stimulation, and estrogen effects [139].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [139] Warren, 2001, The effects of intense exercise on the female reproductive system, J. Endocrinol. source

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  • May combine two claims.

    Premisecitation

    Non-steroidal anti-inflammatory drugs inhibit prostaglandin synthesis, reduce the inflammatory process and resolve pain.

    “Non-steroidal anti-inflammatory drugs inhibit the synthesis of prostaglandins, contribute to reducing the inflammatory process and resolve pain [114].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [114] Horne, 2019, Surgical removal of superficial peritoneal endometriosis for managing women with chronic pelvic pain: Time for a rethink?, BJOG source

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    Premisecitation

    Danazol inhibits GnRH secretion, causing decreased LH and FSH secretion by the pituitary gland.

    “Danazol—a derivative of the male sex hormone testosterone. It inhibits the secretion of GnRH, causing a decrease in the secretion of LH and FSH by the pituitary gland.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Donnez, J., and Dolmans, M.M. (2021). Endometriosis and Medical Therapy: From Progestogens to Progesterone Resistance to GnRH Antagonists: A Review. J. Clin. Med., 10. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Although there is a risk of bone loss with elagolix, its effect on long-term risk of fracture is minimal.

    “As evidenced by literature data, although there is a risk of bone loss when elagolix is used, the effect of elagolix on the long-term risk of fracture is minimal [119,120].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [119] Bradley, 2017, Reproductive endocrinology: Elagolix in endometriosis, Nat. Rev. Endocrinol. source

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    • cites [120] Kilpatrick, 2020, Estimating the Effect of Elagolix Treatment for Endometriosis on Postmenopausal Bone Outcomes: A Model Bridging Phase III Trials to an Older Real-World Population, JBMR Plus source

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  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Premisecitation

    A mini-invasive laparoscopic or robot-assisted laparoscopic approach is strongly recommended for endometriosis.

    “In the case of endometriosis, a mini-invasive laparoscopic or laparoscopic approach using a robot is strongly recommended [108].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [108] Youssef, 2015, A new simple technique for 3-dimensional sonographic assessment of the pelvic floor muscles, J. Ultrasound Med. source

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  • May combine two claims.

    Premisecitation

    Physiotherapy in endometriosis focuses on non-invasive conservative treatment of pelvic floor disorders, restores efficiency and function of pelvic tissues and organs, supports surgical treatment, relieves pain, and improves quality of life.

    “Physiotherapy in endometriosis focuses on non-invasive and conservative treatment of pelvic floor disorders in women. It deals with the restoration of the efficiency and function of tissues and organs in the pelvic area, supports the process of surgical treatment, relieves pain, thus improving the quality of life [135].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [135] Vural, 2018, Pelvic pain rehabilitation, Turk. J. Phys. Med. Rehabil. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Laparoscopic rectal nodulectomy with nerve-sparing robots is a feasible and safe treatment for isolated recto-sigmoid DIE.

    “Laparoscopic rectal nodulectomy with nerve-sparing robots has been shown to be a feasible and safe treatment for isolated sting-rectal DIE [133].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [133] Ercoli, 2017, Robotic-assisted conservative excision of retrocervical-rectal deep infiltrating endometriosis: A case series, J. Minim. Invasive Gynecol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Laparoscopy is the recommended surgical technique for treatment of endometriosis regardless of stage.

    “Laparoscopy is the recommended surgical technique for the treatment of endometriosis, regardless of its stage [122].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [122] Schipper, 2012, Video-assisted laparoscopy for the detection and diagnosis of endometriosis: Safety, reliability, and invasiveness, Int. J. Womens Health

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    All recognized methods of pharmacological treatment have similar therapeutic effectiveness but differ in the scope and speed of side effects.

    “All recognized methods of pharmacological treatment have similar therapeutic effectiveness. They differ in the scope and speed of the appearance of side effects.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisereasoning

    A levonorgestrel-releasing intrauterine device has the same effect as progestogen preparations and is recommended especially for women with severe pain.

    “An intrauterine device releasing levonorgestrel is a progesterone derivative. The effect is the same as progestogen preparations. Recommended especially for women with severe pain.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Donnez, J., and Dolmans, M.M. (2021). Endometriosis and Medical Therapy: From Progestogens to Progesterone Resistance to GnRH Antagonists: A Review. J. Clin. Med., 10. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Physical exercise has a beneficial effect on muscle relaxation in patients with endometriosis, helping to break their pain cycle.

    “Physical exercise has been shown to have a beneficial effect on muscle relaxation in patients suffering from endometriosis, which in turn helps to break their pain cycle [141].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [141] Awad, 2017, Efficacy of exercise on pelvic pain and posture associated with endometriosis: Within subject design, J. Phys. Sci.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Cardiovascular activity helps endometriosis patients maintain good energy levels, and exercise can increase serotonin levels.

    “Cardiovascular activity helps endometriosis patients maintain good energy levels. Exercise is one of the most effective strategies for increasing serotonin levels; physical activity and deep breathing exercises can increase the rate of burning serotonin neurons in the brain, which can stimulate the production of mood-enhancing substances.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [143] Carpenter, 1995, The effect of regular exercise on women receiving danazol for treatment of endometriosis, Int. J. Gynaecol. Obstet. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Oral contraceptives lower FSH levels and stabilize the endometrium, leading to a reduction in pain.

    “Oral contraceptives (estrogen-progestogen preparations)—their action consists in lowering the level of FSH and stabilizing the endometrium, which leads to a reduction in pain.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Donnez, J., and Dolmans, M.M. (2021). Endometriosis and Medical Therapy: From Progestogens to Progesterone Resistance to GnRH Antagonists: A Review. J. Clin. Med., 10. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Elagolix is a non-peptide GnRH antagonist that enables dose-dependent reductions in estrogen levels and is effective in relieving moderate to severe endometriosis pain with long-lasting, sustained effects; it may reduce bone mineral density through estrogen reduction.

    “Elagolix is a non-peptide GnRH (gonadotropin-releasing hormone) antagonist. Elagolix enables dose-dependent reductions in estrogen levels and is effective in relieving moderate to severe endometriosis pain with long-lasting, sustained effects. As a GnRH antagonist, elagolix may also reduce bone mineral density through its estrogen reduction mechanism [118].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [118] Shebley, 2020, Clinical Pharmacology of Elagolix: An Oral Gonadotropin-Releasing Hormone Receptor Antagonist for Endometriosis, Clin. Pharm. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Literature data draw attention to the possibility of non-protective effects of exercise in women with endometriosis, which may result from discomfort preventing physical exercise.

    “However, there are literature data that draw attention to the possibility of inferring the non-protective effects of exercise in women with endometriosis, which may result from the discomfort felt that prevents physical exercise [141,144].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [141] Awad, 2017, Efficacy of exercise on pelvic pain and posture associated with endometriosis: Within subject design, J. Phys. Sci.

      Not checked in the free run.

    • cites [144] Lund, 2016, Is acupuncture effective in the treatment of pain in endometriosis?, J. Pain Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    LINC01116 promotes the progression of endometriosis through the miR-9-5p/FOXP1 axis, providing a new therapeutic target for endometriosis patients.

    “A study by the Cui et al. team explains that LINC01116 promotes the progression of endometriosis through the miR-9-5p/FOXP1 axis. This discovery provides a new therapeutic target for endometriosis patients [174].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [174] Cui, 2021, LINC01116 promotes proliferation and migration of endometrial stromal cells by targeting FOXP1 via sponging miR-9-5p in endometriosis, J. Cell Mol. Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The sensitivity of Ca-125 is characteristic of the advanced form of the disease, but its specificity is low because it is often elevated in other gynecological diseases.

    “The sensitivity of Ca-125 is characteristic of the advanced form of the disease, but its specificity is low because it is often elevated in other gynecological diseases [156].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [156] Hirsch, 2016, International Collaboration to Harmonise Outcomes and Measures for Endometriosis. Diagnostic accuracy of cancer antigen 125 for endometriosis: A systematic review and meta-analysis, BJOG source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Oxidative stress intensifies the immune response in places affected by endometriosis, which may exacerbate development of endometriosis.

    “It is known that in places affected by endometriosis, oxidative stress further intensifies the immune response, as a result of which there may be an exacerbation of the development of endometriosis [151,152,153].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [151] Agarwal, 2005, Role of oxidative stress in female reproduction, Reprod. Biol. Endocrinol. source

      Not checked in the free run.

    • cites [152] Christodoulakos, 2007, Pathogenesis of endometriosis: The role of defective ‘immunosurveillance’, Eur. J. Contracept. Reprod. Health Care source

      Not checked in the free run.

    • cites [153] Augoulea, 2009, The role of the oxidative-stress in the endometriosis-relatedinfertility, Gynecol. Endocrinol. source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    Ca-125 and Ca-19-9 concentrations do not give definitive answers in the differential diagnostic and therapeutic process, but they help in decision-making and direction of management and remain a recommended complementary tool.

    “The concentrations of Ca-125 and Ca-19-9 glycoproteins do not give us definitive answers in the differential diagnostic and therapeutic process, but they help in decision-making and direction of management and therefore remain the recommended complementary tool.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    LncRNA H19 may be involved in the pathogenesis of endometriosis, especially in the mechanism of recurrence, and is a novel potential predictor of recurrence; its expression in ectopic and eutopic endometria of endometriosis patients was significantly higher than in normal endometrium.

    “Liu et al. showed that LncRNA H19 may be involved in the pathogenesis of endometriosis especially in the mechanism of recurrence and is a novel potential predictor of the recurrence of endometriosis. In this study LncRNA H19 expression in the ectopic and eutopic endometria of endometriosis patients was significantly higher than that in the normal endometrium [172].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [172] Liu, 2020, LncRNA H19 Overexpression in Endometriosis and its Utility as a Novel Biomarker for Predicting Recurrence, Reprod. Sci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    IL-6 is the most characteristic of endometriosis; its sensitivity is 63% and its specificity is 69%.

    “IL-6 is the most characteristic of endometriosis. Its sensitivity is 63% and its specificity is 69% [149].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [149] Nisenblat, 2016, Combination of the non-invasive tests for the diagnosis of endometriosis, Cochrane Database Syst. Rev.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Altered expression levels of miR-139-5p and miR-375 in ectopic endometrium may regulate HOXA9, HOXA10 and EDN1, which may be related to development of endometriosis.

    “Altered expression levels of miR-139-5p and miR-375 were observed in the tissues of the ectopic endometrium. These microRNAs may regulate the expression of the transcription factors HOXA9 and HOXA10 and the endothelin 1 gene (EDN1) playing a role in vascular homeostasis, which may be related to the development of endometriosis [160].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [160] Liu, 2018, Role of miR-449b-3p in endometriosis via effects on endometrial stromal cell proliferation and angiogenesis, Mol. Med. Rep.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Zhou et al. found that 388 lncRNA transcripts were overexpressed and 188 showed decreased expression in ectopic endometrium compared to eutopic endometrium.

    “Zhou et al. found that 388 transcripts of lncRNA tested showed overexpression and 188 showed decreased expression levels in the ectopic endometrium compared to eutopic endometrium [172].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [172] Liu, 2020, LncRNA H19 Overexpression in Endometriosis and its Utility as a Novel Biomarker for Predicting Recurrence, Reprod. Sci. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Despite ongoing research on biomarkers of endometriosis, there are still no satisfactory results, making it impossible to carry out effective laboratory diagnostics for diagnosis and monitoring of treatment of the disease.

    “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].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [157] May, 2010, Peripheral biomarkers of endometriosis: A systematic review, Hum. Reprod. Update source

      Not checked in the free run.

  • The quote only partly states this claim.

    Interpretationcitation

    No specific miRNA has been validated for diagnostic purposes.

    “To date, no specific miRNA has been validated for diagnostic purposes (systematic review conducted on PubMed®, Latin American and Caribbean Health Sciences Literature (LILACS), MEDLINE® and Web of Science databases using the search terms endometriosis (all fields) AND miRNA (all fields), evaluating all publications up to May 2019) [168].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [168] Monnaka, 2021, Overview of miRNAs for the non-invasive diagnosis of endometriosis: Evidence, challenges and strategies. A systematic review, Einstein source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Altered expression of miR449b3p in endometriosis affects development of the disease.

    “Liu et al. suggested that miR449b3p altered expression in endometriosis affects the development of the disease [159].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [159] Sahin, 2018, microRNA Let-7b: A Novel treatment for endometriosis, J. Cell Mol. Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Monthly bleeding within foci of endometriosis triggers an immune response, causing the foci to increase.

    “There is monthly bleeding within them, which trigger an immune response. This causes the foci of endometriosis to increase [146].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [146] Sourial, 2014, Theories on the pathogenesis of endometriosis, Int. J. Reprod. Med. source

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    Two regions of the genome are associated with an increased risk of endometriosis in European women: one on chromosome 7 and one near the WNT4 gene.

    “The team identified two regions of the genome associated with an increased risk of endometriosis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [183] Nyholt, 2012, Genome-wide association meta-analysis identifies new endometriosis risk loci, Nat. Genet. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The protein encoded by the RHOJ gene is activated by vascular endothelial growth factor and can regulate angiogenesis, adipocyte differentiation, endothelial motility, and cytoskeletal formation.

    “The protein encoded by the RHOJ gene is activated by vascular endothelial growth factor and can regulate angiogenesis and also plays an important role in adipocyte differentiation, endothelial motility, and cytoskeletal formation [190].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [190] Kim, 2014, Vascular RhoJ is an effective and selective target for tumor angiogenesis and vascular disruption, Cancer Cell source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In Japanese population studies, polymorphism rs10965235 in the CDKN2BAS gene at locus 9p21 and rs16826658 in the WNT4 gene area at locus 1p36 are associated with endometriosis.

    “Studies of the Japanese population showed the relationship of polymorphism rs10965235, in the CDKN2BAS gene at locus 9p21 and rs16826658, in the area of the WNT4 gene at locus 1p36 [183].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [183] Nyholt, 2012, Genome-wide association meta-analysis identifies new endometriosis risk loci, Nat. Genet. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SNPs LINC00339-WNT4 at locus 1p36.12 (rs2235529) and RND3-RBM43 at locus 2q23.3 (rs1519761 and rs6757804) are associated with endometriosis.

    “Three of the single nucleotide polymorphisms (SNPs) associated with the disease have been identified: LINC00339-WNT4 at locus 1p36.12 (rs2235529) and RND3-RBM43 at locus 2q23.3 (rs1519761 and rs6757804).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [188] Albertsen, H.M., Chettier, R., Farrington, P., and Ward, K. (2013). Genome-wide association study link novel loci to endometriosis. PLoS ONE, 8. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Polymorphisms rs10928050 of the KAZN gene and rs2427284 of the LAMA5 gene correlate with endometriosis.

    “Christofolini et al. showed a correlation of the polymorphisms rs10928050 of the KAZN gene and the rs2427284 of the LAMA5 gene with endometriosis [194].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [194] Christofolini, 2019, New candidate genes associated to endometriosis, Gynecol. Endocrinol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Genetic and epigenetic conditions are conducive to the development of endometriosis, which is caused by environmental factors, or genetic and epigenetic changes caused by environmental factors are necessary to move from subtle changes to the disease stage.

    “It is believed that genetic and epigenetic conditions are rather conducive to the development of endometriosis, which is caused by environmental factors, or genetic and epigenetic changes caused by environmental factors are necessary to move from subtle changes in endometriosis to the disease stage [179].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [179] Koninckx, 2019, Pathogenesis of endometriosis: The genetic/epigenetic theory, Fertil. Steril. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Rho proteins are involved in cancer transformation and metastasis.

    “Rho are also involved in cancer transformation and metastasis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [190] Kim, 2014, Vascular RhoJ is an effective and selective target for tumor angiogenesis and vascular disruption, Cancer Cell source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Rho proteins regulate the dynamic assembly of cytoskeleton components in several physiological processes, such as cell proliferation and motility.

    “Rho proteins regulate the dynamic assembly of cytoskeleton components in several physiological processes, such as cell proliferation and motility.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [190] Kim, 2014, Vascular RhoJ is an effective and selective target for tumor angiogenesis and vascular disruption, Cancer Cell source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The clinical significance and biological mechanism of lncRNA in the development of endometriosis remain largely unknown.

    “However, the clinical significance and biological mechanism of lncRNA in the development of endometriosis remain largely unknown.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The first GWAS study on endometriosis was published between 2010 and 2011, comprising two papers on the Japanese population and one study of European women.

    “The first GWAS study on endometriosis was published between 2010 and 2011—two papers on the Japanese population and one study of European women [180,181,182].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [180] Uno, 2010, A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese, Nat. Genet. source

      Not checked in the free run.

    • cites [181] Adachi, 2010, Meta-analysis of genome-wide association scans for genetic susceptibility to endometriosis in Japanese population, J. Hum. Genet. source

      Not checked in the free run.

    • cites [182] Painter, 2011, Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis, Nat. Genet. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Since the 1940s, a much higher incidence of endometriosis has been described among women from families in which women suffered from endometriosis, and among siblings, especially monozygotic twins, where co-occurrence exceeds 80%.

    “Since the 1940s, a much higher incidence among women from families in which women suffered from endometriosis has been described, as well as a high incidence among siblings, especially monozygotic twins, where the percentage of co-occurrence exceeds 80% [177].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [177] Hadfield, 1997, Endometriosis in monozygotic twins, Fertil. Steril. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The 7p15.2 locus is among the genes known so far to be responsible for the development of the uterus and placenta.

    “This place is among the genes known so far responsible for the development of the uterus and placenta [182].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [182] Painter, 2011, Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis, Nat. Genet. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The RHOJ gene encodes one of many small proteins of the Rho family that bind GTP.

    “Gen RHOJ encodes one of many small proteins of the Rho family that bind GTP (guanosine-5′-triphosphate), which acts as an energy transporter in the cell.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [190] Kim, 2014, Vascular RhoJ is an effective and selective target for tumor angiogenesis and vascular disruption, Cancer Cell source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Treatment of endometriosis is still ineffective.

    “Unfortunately, the treatment of this disease is still ineffective.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The new mutations can affect both the eutopic endometrium and endometriosis foci, and do not have to occur in the germline cell line.

    “The new mutations can affect both the eutopic endometrium and endometriosis foci, and do not have to occur in the germline cell line.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [203] Zondervan, 2020, Endometriosis, N. Engl. J. Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Estrogen receptors act as transcription factors and play a significant role in endometrial growth and differentiation and in numerous biological functions in eutopic endometrium and endometriosis.

    “Estrogen receptors, acting as transcription factors, play a significant role in endometrial growth and differentiation, as well as in numerous biological functions in eutopic endometrium and endometriosis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [198] Bulun, 2012, Role of estrogen receptor-β in endometriosis, Semin. Reprod. Med. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationnone given

    Recent progress of knowledge, especially at the genetic level, allows the separation of certain molecular shields for new therapeutic methods.

    “However, the progress of knowledge, especially at the genetic level, which has taken place in recent years, allows the separation of certain molecular shields for new therapeutic methods.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The location of the mutation in the genome appears to be specific to the patient and is not repeated in others.

    “The location of the mutation in the genome appears to be specific to the patient and is not repeated in others.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [203] Zondervan, 2020, Endometriosis, N. Engl. J. Med. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

    Interpretationcitation

    The impact of these mutations on the development of endometriosis is complex and requires further evaluation.

    “It is emphasized that the impact of these mutations on the development of the disease is complex and requires further evaluation.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [203] Zondervan, 2020, Endometriosis, N. Engl. J. Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The polymorphisms rs17179740 of the ESR2 gene and rs2899470 of the CYP19A1 gene are associated with the occurrence of endometriosis.

    “Recent studies have shown that the polymorphisms rs17179740 of the ESR2 gene and rs2899470 of the CYP19A1 gene are associated with the occurrence of endometriosis [202].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [202] Smolarz, 2021, Association between single nucleotide polymorphism of the CYP19A1 and ESR2 genes and endometriosis, Arch. Gynecol. Obstet. source

      Not checked in the free run.

73 of 73

  • The paper relies on this without support.

    The ectopic endometrium is functionally similar to the eutopic endometrium.

    “The ectopic endometrium is functionally similar to the eutopic endometrium.”

  • The paper relies on this without support.

    Endometriosis is a benign, estrogen-dependent gynecological disease.

    “Endometriosis is a benign, estrogen-dependent, gynecological disease; however, due to the accompanying ailments and chronic nature, it is a very important medical, social and economic problem.”

  • The paper relies on this without support.

    Endometriosis is chronic and difficult to treat.

    “Treatment of endometriosis is a big medical problem due to the fact that this disease is difficult to treat and is chronic in nature.”

  • The paper relies on this without support.

    Symptoms associated with foci of endometriosis are the main factor determining the need to start treatment.

    “Symptoms associated with the presence of foci of endometriosis are the main factor determining the need to start treatment.”

  • The paper relies on this without support.

    The best therapeutic effects are achieved by combining surgical treatment with pharmacological treatment.

    “The best therapeutic effects are achieved as a result of the combination of surgical treatment with pharmacological treatment.”

  • The paper relies on this without support.

    In women suffering from endometriosis, pelvic floor structures are very often dysfunctional.

    “In women suffering from endometriosis, pelvic floor structures are very often dysfunctional.”

  • The paper relies on this without support.

    Inflammation accompanying recurrent endometriosis can cause tissue damage and formation of adhesions.

    “Inflammation accompanying recurrent endometriosis can cause tissue damage, and thus the formation of scar tissue to heal the affected areas. Unfortunately, a side effect of this process is the formation of adhesions, which, depending on the location, can cause different symptoms.”

  • The paper relies on this without support.

    With peritoneal endometriosis, serum and plasma are not good diagnostic material; attention is paid to the eutopic endometrium.

    “With peritoneal endometriosis, serum and plasma are not good diagnostic material; attention is paid to the eutopic endometrium.”

  • The paper relies on this without support.

    Foci of endometriosis behave in the same way as eutopic endometrium.

    “Foci of endometriosis behave in the same way as eutopic endometrium.”

  • The paper relies on this without support.

    The marker of endometriosis was sought among growth factors and cytokines because the development of ectopic implants is accompanied by invasion, proliferation and angiogenesis.

    “The marker of endometriosis was sought among growth factors and cytokines, because the development of ectopic implants is accompanied by the processes of invasion, proliferation and angiogenesis.”

  • The paper relies on this without support.

    The most promising results for endometriosis markers were obtained for hepatocyte growth factor (HGF), fibroblast growth factor (FGF), epithelial growth factor (EGF), vascular endothelial growth factor (VEGF) and interleukin IL-1, IL-6 and IL-8.

    “The most promising results were obtained for hepatocyte growth factor (HGF), fibroblasts growth factor (FGF), epithelial growth factor (EGF), vascular endothelial growth factor (VEGF) and interleukin IL-1, IL-6 and IL-8.”

  • The paper relies on this without support.

    The most reproducible results for endometriosis markers were obtained for IL-6.

    “The most reproducible results were obtained for IL-6.”

  • The paper relies on this without support.

    YKL-40 is secreted by activated macrophages and neutrophils in various inflamed tissues.

    “YKL-40, a new biomarker of inflammation, is secreted by activated macrophages and neutrophils in various inflamed tissues.”

  • The paper relies on this without support.

    Serum concentrations of YKL-40 are elevated in patients with diseases characterized by inflammation.

    “Serum concentrations of YKL-40 are elevated in patients with diseases characterized by inflammation.”

  • The paper relies on this without support.

    Endometriosis can cause ectopic pregnancy and increases the risk of ectopic pregnancy in women with endometriosis.

    “Endometriosis can be the cause of ectopic pregnancy. The risk of such a pregnancy is therefore increased in women with endometriosis.”

  • The authors state this as an assumption.

    At least some pathogenetic changes in endometriosis arise as somatic mutations absent in the germline and occur during the development of an individual organism.

    “The concept of this research is based on the hypothesis that at least some of the changes arise as a result of somatic mutations absent in the germline and occur during the development of an individual organism.”

  • The paper relies on this without support.

    Endometriosis is associated with cancer as a result of genetic mutations.

    “The association of endometriosis with cancer, which appears as a result of genetic mutations, contributed to the search for pathogenetic mutations occurring in cells during the development of the disease.”

  • The authors state this as an assumption.

    DIE patients with new mutations will be burdened with a higher risk of cancer in the future.

    “However, it can be assumed that these patients will be burdened with a higher risk of cancer in the future [203].”

  • The paper relies on this without support.

    A different expression of aromatase in endometriosis foci compared to eutopic endometrium has been demonstrated.

    “A different expression of aromatase in endometriosis foci has been demonstrated compared to eutopic endometrium.”
19 of 19

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?

  • Certain studies involved oxidative stress with epigenetic alterations in DNA methylation in the pathogenesis of malignant transformation of endometriosis.

    “Even though the pathogenesis of the malignant transformation of endometriosis remains unelucidated, certain studies involved oxidative stress with epigenetic alterations in DNA methylation [1,2,3,4].”

    From Malignancy in Abdominal Wall Endometriosis: Is There a Way to Avoid It? A Systematic Review (2024) · cites this paper as [1]

    Section 10 (Biomarkers; page unavailable) links oxidative stress to the development of endometriosis. Section 11.2 (Somatic Mutations; page unavailable) discusses an association with cancer, but attributes it to genetic mutations. Neither passage links oxidative stress or DNA-methylation changes to malignant transformation. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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.

  • Liu study is cited as Sahin et al.

    Minor

    The text attributes the miR-449b-3p finding to Liu et al. but cites reference 159, which is by Sahin et al. The Liu et al. paper on miR-449b-3p is reference 160.

  • Sahin study is attributed to a different reference

    Minor

    The text attributes the Let-7b findings to Sahin et al. and cites reference 146, but reference 146 is a paper by Sourial et al. The Sahin et al. paper appears as reference 159.

  • Zhou findings are cited to a Liu paper

    Minor

    The text attributes the lncRNA expression counts to Zhou et al. but cites reference 172, which is a Liu et al. paper about H19. The Zhou et al. paper is listed as reference 171.

3 of 3

Cites

Flagged first, then by citations

15 of the 217 references couldn’t be matched to a known paper.

Research works printed but not linked: 7

  1. Rokitansky, 1860, Uber uterusdrusen neubildung, Ztchr Gesselsch Arzte Wein, 16, 577
  2. Kanikowska, 2010, Historia badań nad endometriozą, Polski Przegląd Nauk Zdrowiu, 1, 42
  3. Dmowski, 1999, Endometriosis at the end of the millenium; the controversy remains, Pol. J. Gyn. Investig., 1, 175
  4. Gadomska, 1997, Endometrioza, Medipress Ginekol., 3, 2
  5. Jakiel, 2006, Endometriosis, Przeglad Menopauzalny, 2, 126
  6. Witz, 1997, Semin Reprod Endocrinol, Pathogenesis, 15, 199
  7. Basta, 2012, Stanowisko Zespołu Ekspertów Polskiego Towarzystwa Ginekologicznego dotyczące diagnostyki i metod leczenia endometriozy, Ginekol. Pol., 83, 871

Cited by

Sorted by citations

Related

Authors
Smolarz, B., Szyłło, K., & Romanowicz, H.
Affiliations
Polish Mother’s Memorial Hospital Research Institute (PL)
Corresponding author
Smolarz, Beata
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2021-09-29
Volume
22
Issue
19
Pages
10554
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms221910554
PMC
PMC8508982
OpenAlex
W3202177173
Semantic Scholar
6bb38169b8b9bc128dcf57c83c8755bdfe4c590e
Cited by
560
References
217
Citations by year
2026: 107 · 2025: 144 · 2024: 147 · 2023: 100 · 2022: 60 · 2021: 2
FWCI
12.68
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gynecological conditions and treatments
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
Keywords
endometriosis, epidemiology, classification, pathogenesis, retrograde menstruation, etiological factors, epigenetics, autoimmune factors, infertility, chronic pelvic pain, quality of life, health care costs, genetics
MeSH terms
Adult, Endometriosis, Endometrium, Female, Gene Expression Regulation, Humans, Infertility, Female, Cytokines, Vascular Endothelial Growth Factor A, Cyclooxygenase 2

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

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 ›

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