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Endometriosis is estimated to affect up to 15% of women of reproductive age1-3
Endometriosis is defined as the presence of endometrial-like tissue outside the uterus, which may cause symptoms of debilitating pain and/or infertility.3-5
The pathogenesis of endometriosis involves a complex and multifaceted network of factors. Retrograde menstruation is considered the most widely accepted contributing mechanism, although other theories have been and continue to be postulated.6-8
A higher risk of developing endometriosis has also been associated with age, height, reproductive-related factors and genetics.1,9-14
The clinical symptoms of endometriosis can negatively impact women’s overall quality of life and relationships15,16
The most common symptoms include:2,3,7
- Dysmenorrhea
- Non-cyclic pelvic pain
- Dyspareunia
- Dysuria
- Dyschezia
- Fatigue
- Subfertility or infertility
Endometriosis is also associated with a significant socio-economic impact, interfering with women’s academic performance and work productivity.16,18,19
The exact prevalence of endometriosis remains unknown
Estimates range from 10–15% of women of reproductive age,1-3 to 20–50% of infertile women and up to 70% of women with symptoms of chronic pelvic pain.1,3,20
- Parasar P, Ozcan P, Terry KL et al. Curr Obstet Gynecol Rep 2017;6:34–41. Return to content
- Eisenberg VH, Weil C, Chodick G et al. BJOG 2018;125:55–62. Return to content
- Dunselman GA, Vermeulen N, Becker C et al. Hum Reprod 2014;29:400–412. Return to content
- Johnson NP and Hummelshoj L, for the World Endometriosis Society Montpellier Consortium. Hum Reprod 2013;28:1552–1568. Return to content
- Klemmt PAB and Starzinski-Powitz A. Curr Womens Health Rev 2018;14:106–116. Return to content
- Aznaurova YB, Zhumataev MB, Roberts TK et al. Reprod Biol Endocrinol 2014;12:50. Return to content
- Agarwal N and Subramanian A. J Lab Physicians 2010;2:1–9. Return to content
- Zondervan KT, Becker CM, Koga K et al. Nat Rev Dis Primers 2018;4:9. Return to content
- Burney RO, Hamilton AE, Aghajanova L et al. Mol Hum Reprod 2009;15:625–631. Return to content
- Matalliotakis IM, Cakmak H, Fragouli YG et al. Arch Gynecol Obstet 2008;277:389–393. Return to content
- Missmer SA, Hankinson SE, Spiegelman D et al. Obstet Gynecol 2004;104:965–974. Return to content
- Ohlsson Teague EM, van der Hoek KH, van der Hoek MB et al. Mol Endocrinol 2009;23:265–275. Return to content
- Signorello LB, Harlow BL, Cramer DW et al. Ann Epidemiol 1997;7:267–741. Return to content
- Tan A, Luo R, Liang H et al. Mol Med Rep 2018;18:2841–2849 Return to content
- Gao X, Yeh YC, Outley J et al. Curr Med Res Opin 2006;22:1787–1797. Return to content
- Culley L, Law C, Hudson N et al. Hum Reprod Update 2013;19:625–639 Return to content
- Ballard KD, Seaman HE, de Vries CS et al. BJOG 2008;115:1382–1391. Return to content
- de Graaff AA, D’Hooghe TM, Dunselman GA et al. Hum Reprod 2013;28:2677–2685. Return to content
- Nnoaham KE, Hummelshoj L, Webster P et al. Fertil Steril 2011;96:366–373. Return to content
- Meuleman C, Vandenabeele B, Fieuws S et al. Fertil Steril 2009;92:68–74. Return to content
The natural course of endometriosis is variable, but, in most women, is characterized by a worsening of symptoms without effective treatment1-3
Finding the right treatment for each individual patient will depend on factors such as age, symptoms, desire for pregnancy, feelings toward surgery and treatment history, and may include:1,3-6
Analgesics
Combined oral contraceptive pill
Progestogens
GnRH agonists
Surgery (for women in whom medical treatment has failed)
Treatment should be personalized to individual patient needs, with medical treatment as the first-line therapeutic option 1,3-5
Endometriosis is a chronic condition that requires lifelong management. While surgical options have traditionally been the mainstay of treatment, recommendations, guidelines and general consensus are increasingly moving towards non-invasive and empirical treatments, and avoidance of repeated surgical procedures.1,3-5,7
A paradigm shift in the treatment landscape
Limitations of some existent medical treatments include non-suitability for long-term treatment, side effects, insufficient efficacy and impact on fertility.1,3,5,6,8, In addition, COCs have been used off-label for the management of endometriosis-related pain, with limited published trials and low-quality evidence supporting their effectiveness in menstrual and pelvic pain associated with endometriosis. 9-13
COC – combined oral contraceptive; GnRH – gonadotropin-releasing hormone
- Dunselman GA, Vermeulen N, Becker C et al. Hum Reprod 2014;29:400–412. Return to content
- D'Hooghe TM and Debrock S. Hum Reprod Update 2002;8:84–88. Return to content
- Johnson NP and Hummelshoj L, for the World Endometriosis Society Montpellier Consortium. Hum Reprod 2013;28:1552–1568. Return to content
- NICE 2017. Endometriosis: diagnosis and management. Available at: www.nice.org.uk/guidance/ng73 [Accessed February 2021]. Return to content
- Leyland N, Casper R, Laberge P et al. J Obstet Gynaecol Can 2010;32:S1–32. Return to content
- ACOG. Obstet Gynecol 2010;116:223–236. Return to content
- ASRM. Fertil Steril 2014;101:927–935. Return to content
- Ferrero S, Evangelisti G and Barra F. Expert Opin Pharmacother 2018;19:1109–1125. Return to content
- Casper RF. Fertil Steril 2017;107:533–536. Return to content
- Harada T, Momoeda M, Taketani Y et al. Fertil Steril 2008;90:1583–1588. Return to content
- Muzii L, de Tucci C, Achilli C et al. Am J Obstet Gynecol 2016;214:203–211. Return to content
- Jensen JT, Schlaff W and Gordon K. Fertil Steril 2018;110:137–152. Return to content
- Swailum MB, Wahba KA, Labib KM et al. Austin J Obstet Gynecol 2017;4:1082. Return to content
Endometriosis is estimated to affect 10% of women in the reproductive age group (usually 15–49 years old).1 The average age at diagnosis is around 30 years.2,3
- Kuznetsov L, Dworzynski K, Davies M et al. BMJ (Clinical research ed) 2017;358:j3935. Return to content
- Sinaii N et al. Fertil Steril 2008;89:538–545. Return to content
- Bernuit D, Ebert A, Halis G et al. J Endometriosis 2011;3:73–85. Return to content
Estrogen may promote the implantation of endometrial tissue in the peritoneum, has proliferative and antiapoptotic effects on endometrial cells and may stimulate inflammation.1-2
- Bulun SE, Gurates B, Fang Z et al. J Reprod Immunol 2002;55(1-2):21–33. Return to content
- Brosens I, Brosens JJ and Benagiano G. Reprod Biomed Online 2012;24(5):496–502. Return to content
The precise relationship between the severity of symptoms and the extent of endometriosis disease according to staging criteria is not clear.1,2
- Sinaii N, Plumb K, Cotton L et al. Fertil Steril 2008;89:538–545. Return to content
- Johnson NP, Hummelshoj L, Adamson GD et al. Hum Reprod 2017;32:315–324. Return to content
The limited effectiveness associated with COC use in endometriosis may be due to the fact that:
- Only limited published trials and low-quality evidence on the effectiveness of COCs for pelvic pain and dysmenorrhea in endometriosis are available1-5
- Preparations containing a high dose of estrogen and progesterone can result in estrogen dominance and progesterone resistance, leading to the progression of endometriosis1,6
- Studies have shown a potential increase in the risk of endometriosis development following COC cessation7,8
- An international study showed that ~70% of women had used multiple different COCs for the treatment of endometriosis-related pain, suggesting recurrent pain and the need for switching contraceptives1
COC – combined oral contraceptive
- Casper RF. Fertil Steril 2017;107:533–536. Return to content
- Harada T, Momoeda M, Taketani Y et al. Fertil Steril 2008;90:1583–1588. Return to content
- Muzii L, de Tucci C, Achilli C et al. Am J Obstet Gynecol 2016;214:203–211. Return to content
- Jensen JT, Schlaff W and Gordon K. Fertil Steril 2018;110:137–152. Return to content
- Swailum MB, Wahba KA, Labib KM et al. Austin J Obstet Gynecol 2017;4:1082. Return to content
- Ferrero S, Evangelisti G and Barra F. Expert Opin Pharmacother 2018;19:1109–1125. Return to content
- Chapron C, Souza C, Borghese B et al. Hum Reprod 2011;26:2028–2035. Return to content
- Vercellini P, Eskenazi B, Consonni D et al. Hum Reprod Update 2011;17:159–170. Return to content
Until recently, a combination of laparoscopy and biopsy for histological confirmation of endometriotic lesions was the gold standard for the diagnosis of endometriosis.1 However, advances in recent years have moved society guidelines and the consensus in the field towards non-invasive methods based on clinical/physical examination, symptoms, patient history, and diagnostic imaging.2-4
Despite these advances, many women still have to face a diagnostic delay of 6-10 years, mainly due to delayed referral by primary care physicians, which may be caused by confounding symptoms, misdiagnosis, trivialization of women’s experiences and normalization of symptoms. 5-8 The successful identification of diagnostic parameters in endometriosis would facilitate efficient, non-invasive, and accurate diagnosis, thereby reducing the burden of the disease and related morbidity. 9
Endometriosis requires lifelong management and, while surgical options have traditionally been the preferred approach, disease recurrence and complications associated with this treatment option have highlighted the usefulness of non-invasive and empirical treatments and the need to avoid repeated surgical procedures.2,4,10-12
Current first- and second-line medical treatments available for endometriosis-related pain include NSAIDs, hormonal therapies and GnRH analogues, but these are still associated with limitations and unmet needs that need to be addressed (including adverse events and reduced efficacy).2,4,10,13,14
GnRH – gonadotropin-releasing hormone; NSAID – nonsteroidal anti-inflammatory drug
- Hirsch M, Begum MR, Paniz E et al. BJOG 2018;125:556–564. Return to content
- Dunselman GA, Vermeulen N, Becker C et al. Hum Reprod 2014;29:400–412 Return to content
- Ulrich U, Buchweitz O, Greb R et al. Geburtshilfe Frauenheilkd 2014;74:1104–1118. Return to content
- Leyland N, Casper R, Laberge P et al. J Obstet Gynaecol Can 2010;32:S1–32. Return to content
- Bernuit D, Ebert A, Halis G et al. J Endometriosis 2011;3:73–85. Return to content
- Nnoaham KE, Hummelshoj L, Webster P et al. Fertil Steril 2011;96:366–373. Return to content
- Hudelist G, Fritzer N, Thomas A et al. Hum Reprod 2012;27:3412–3416. Return to content
- All-Party Parliamentary Group on Women’s Health. Available at: http://www.appgwomenshealth.org/news/2017/3/27/the-all-party-parliamentary-group-on-womens-health- report-launched [Accessed February 2021]. Return to content
- Agrawal S, Tapmeier T, Rahmioglu N et al. Int J Mol Sci 2018;19:599. Return to content
- Johnson NP and Hummelshoj L, for the World Endometriosis Society Montpellier Consortium. Hum Reprod 2013;28:1552–1568. Return to content
- NICE 2017. Endometriosis: diagnosis and management. Available at: www.nice.org.uk/guidance/ng73 [Accessed February 2021]. Return to content
- ASRM. Fertil Steril 2014;101:927–935. Return to content
- ACOG. Obstet Gynecol 2010;116:223–236. Return to content
- Ferrero S, Evangelisti G and Barra F. Expert Opin Pharmacother 2018;19:1109–1125. Return to content
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