Endometriosis as female reproductive system disorder: mechanisms, diagnosis and clinical management

Document Type : Review Paper


1 Member of Research Committee, Medical School, Hamedan University of Medical Sciences, Hamedan, Iran

2 Department of Anatomical Sciences, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran


Endometriosis is a gynecological, chronic, and inflammatory disease affecting one in ten women globally. It occurs when tissues similar to the endometrial layer of the uterus grow outside the uterine body leading to inflammation, pain, and infertility. The most common site of endometriotic lesions is the pelvic cavity, especially the ovaries. Thus, at the same time as menstruation, these points initiate bleeding, which results in many difficulties. So far, several mechanisms of endometriosis have been suggested, such as retrograde menstruation, the influence of environmental and genetic factors, and hormonal causes. In some cases, this pathologic condition occurs following pregnancy or pelvic surgery. Disease management also involves the use of painkillers and contraceptive hormones for a relatively long time or even the use of laparoscopy to remove the pathologic lesions. In this review, the mechanisms of endometriosis were discussed, as well as various aspects of the disease in the field of diagnosis and treatment were assessed.

Graphical Abstract

Endometriosis as female reproductive system disorder: mechanisms, diagnosis and clinical management


  • Endometriosis is a chronic and inflammatory gynecological disease that affects 10% of women.
  • Various factors such as environmental and genetic factors and hormonal factors can change the endometriosis risk.
  • Painkillers and contraceptive hormones can be good ways to treat the endometriosis.


Main Subjects

1. Matalliotakis M, Zervou MI, Matalliotaki C, Rahmioglu N, Koumantakis G, Kalogiannidis I, Prapas I, Zondervan K, Spandidos DA, Matalliotakis I, Goulielmos GN. The role of gene polymorphisms in endometriosis. Mol Med Rep 2017; 16(5): 5881-5886.
2. Menni K, Facchetti L, Cabassa P. Extragenital endometriosis: assessment with MR imaging. A pictorial review. Br J Radiol 2016; 89(1060): 20150672.
3. Sapkota Y, Steinthorsdottir V, Morris AP, Fassbender A, Rahmioglu N, De Vivo I, Buring JE, Zhang F, Edwards TL, Jones S, Dorien O. Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism. Nat Commun 2017; 8(1): 1-2.
4. Koninckx PR, Ussia A, Adamyan L, Wattiez A, Gomel V, Martin DC. Pathogenesis of endometriosis: the genetic/epigenetic theory. Fertil Steril 2019; 111(2): 327-340.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
5. Parasar P, Ozcan P, Terry KL. Endometriosis: epidemiology, diagnosis and clinical management. Curr Obstet Gynecol Rep 2017; 6(1): 34-41.
6. Chapron C, Marcellin L, Borghese B, Santulli P. Rethinking mechanisms, diagnosis and management of endometriosis. Nat Rev Endocrinol 2019; 15(11): 666-682.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
7. Nnoaham KE, Hummelshoj L, Webster P, d'Hooghe T, de Cicco Nardone F, de Cicco Nardone C, Jenkinson C, Kennedy SH, Zondervan KT. Reprint of: Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril 2019; 112(4S1).
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
8. Bricou A, Batt RE, Chapron C. Peritoneal fluid flow influences anatomical distribution of endometriotic lesions: why Sampson seems to be right. Eur J Obstet Gynecol Reprod Biol 2008; 138(2): 127-134.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
9. Vercellini P, Viganò P, Somigliana E, Fedele L. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol 2014; 10(5): 261.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
10. Falconer H, D’Hooghe T, Fried G. Endometriosis and genetic polymorphisms. Obstet Gynecol Surv 2007; 62(9): 616-628.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
11. Lowe WL, Reddy TE. Genomic approaches for understanding the genetics of complex disease. Genome Res 2015; 25(10): 1432-1441.
12. Treloar SA, Wicks J, Nyholt DR, Montgomery GW, Bahlo M, Smith V, Dawson G, Mackay IJ, Weeks DE, Bennett ST, Carey A. Genomewide linkage study in 1,176 affected sister pair families identifies a significant susceptibility locus for endometriosis on chromosome 10q26. Am J Hum Genet 2005; 77(3): 365-376.
13. Smarr MM, Kannan K, Louis GM. Endocrine disrupting chemicals and endometriosis. Fertil Steril 2016; 106(4): 959-966.
14. Yang M, Mercy AO, Efehi N, Venera M, Liu X, Ebadi AG, Toughani M. Evaluation of Physicochemical and DPPH· Cleaning Activity of Ultrasonic Assisted Extraction of Polysaccharide from Leonurus japonicas. Rev Chim 2020; 71(4): 601-614.
15. Galvankar M, Singh N, Modi D. Estrogen is essential but not sufficient to induce endometriosis. J Biosci 2017; 42(2): 251-263.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
16. Streuli I, Gaitzsch H, Wenger JM, Petignat P. Endometriosis after menopause: physiopathology and management of an uncommon condition. Climacteric 2017; 20(2): 138-143.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
17. Tomassetti C, D'Hooghe T. Endometriosis and infertility: Insights into the causal link and management strategies. Best Pract Res Clin Obstet Gynaecol 2018; 51: 25-33.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
18. Liang H, Khan ZI, Ahmad K, Nisar A, Mahmood Q, Ebadi AG, Toughani M. Assessment of Zinc and Nickel Profile of Vegetables Grown in Soil Irrigated with Sewage Water. Rev Chim 2020; 71(4): 500-511.
19. Jerman LF, Hey-Cunningham AJ. The role of the lymphatic system in endometriosis: a comprehensive review of the literature. Biol Reprod 2015; 92(3): 64-61.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
20. Vercellini P, Consonni D, Dridi D, Bracco B, Frattaruolo MP, Somigliana E. Uterine adenomyosis and in vitro fertilization outcome: a systematic review and meta-analysis. Hum Reprod 2014b; 29(5): 964-977.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
21. Okada H, Tsuzuki T, Murata H. Decidualization of the human endometrium. Reprod Med Biol 2018; 17(3): 220-227.
22. Yang M, Efehi N, Jin Y, Zhang Q, Ebadi AG, Toughani M. Hot Water Extraction of Crude Polysaccharide from Codonopsis pilosula and Determination of the Rheological Properties. Rev Chim 2020; 71(5): 441-449.
23. Lebovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril. 2001; 75: 1-0.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
24. Howard FM. Endometriosis and mechanisms of pelvic pain. J Minim Invasive Gynecol 2009; 16(5): 540-550.
25. Sinaii N, Plumb K, Cotton L, Lambert A, Kennedy S, Zondervan K, Stratton P. Differences in characteristics among 1,000 women with endometriosis based on extent of disease. Fertil Steril 2008; 89(3): 538-545.
26. Wang Y, Dou S, Zhang Q, Ebadi AG, Chen J, Toughani M. Bacterial Separation and Community Diversity Analysis of Petroleum Contaminated Soil in Yumen Oilfield. Rev Chim 2020; 71(3): 595-607.
27. Chapron C, Lang JH, Leng JH, Zhou Y, Zhang X, Xue M, Popov A, Romanov V, Maisonobe P, Cabri P. Factors and Regional Differences Associated with Endometriosis: A Multi-Country, Case–Control Study. Adv Ther. 2016;33(8):1385-407.
28. Kennedy S, Bergqvist A, Chapron C, D’Hooghe T, Dunselman G, Greb R, Hummelshoj L, Prentice A, Saridogan E. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod 2005; 20(10): 2698-2704.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
29. Bao S, Ebadi A, Toughani M, Dalle J, Maseleno A, Yıldızbası A. A new method for optimal parameters identification of a PEMFC using an improved version of Monarch Butterfly Optimization Algorithm. Int J Hydrogen Energy 2020; 45(35): 17882-17892.
30. Nisenblat V, Bossuyt PM, Shaikh R, Farquhar C, Jordan V, Scheffers CS, Mol BW, Johnson N, Hull ML. Blood biomarkers for the non‐invasive diagnosis of endometriosis. Cochrane Database Syst Rev. 2016(5).
31. Fassbender A, Vodolazkaia A, Saunders P, Lebovic D, Waelkens E, De Moor B, D'Hooghe T. Biomarkers of endometriosis. Fertil Steril 2013; 99(4): 1135-1145.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
32. Petraglia F, Hornung D, Seitz C, Faustmann T, Gerlinger C, Luisi S, Lazzeri L, Strowitzki T. Reduced pelvic pain in women with endometriosis: efficacy of long-term dienogest treatment. Archives Gynecol Obstet 2012; 285(1): 167-173.
33. Yang M, Abdalrahman H, Sonia U, Mohammed A, Vestine U, Wang M, Ebadi AG, Toughani M. The application of DNA molecular markers in the study of Codonopsis species genetic variation, a review. Cell Mol Biol 2020; 2: 23-30.
34. Santulli P, Marcellin L, Tosti C, Chouzenoux S, Cerles O, Borghese B, Batteux F, Chapron C. MAP kinases and the inflammatory signaling cascade as targets for the treatment of endometriosis? Expert Opin Ther Targets 2015; 19(11): 1465-1483.
35. Ferrero S, Alessandri F, Racca A, Maggiore UL. Treatment of pain associated with deep endometriosis: alternatives and evidence. Fertil Steril 2015; 104(4): 771-792.
36. Jacobson TZ, Duffy JM, Barlow DH, Farquhar C, Koninckx PR, Olive D. Laparoscopic surgery for subfertility associated with endometriosis. Cochrane Database Syst Rev 2002; (4): CD001398.
37. De Ziegler D, Borghese B, Chapron C. Endometriosis and infertility: pathophysiology and management. Lancet 2010; 376(9742): 730-738.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
38. Vercellini P, Somigliana E, Vigano P, Abbiati A, Barbara G, Crosignani PG. Surgery for endometriosis-associated infertility: a pragmatic approach. Hum Reprod 2009; 24(2): 254-269.
39. Wen L, Zhang Y, Yang B, Han F, Ebadi AG, Toughani M. Knockdown of Angiopoietin-like protein 4 suppresses the development of colorectal cancer. Cell Mol Biol 2020; 66(5): 117-124.
40. Lazzeri L, Di Giovanni A, Exacoustos C, Tosti C, Pinzauti S, Malzoni M, Petraglia F, Zupi E. Preoperative and postoperative clinical and transvaginal ultrasound findings of adenomyosis in patients with deep infiltrating endometriosis. Reprod Sci 2014; 21(8):1027-1033.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
41. Sallam HN, Garcia‐Velasco JA, Dias S, Arici A, Abou‐Setta AM. Long‐term pituitary down‐regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004635.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed