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Rethinking mechanisms, diagnosis and management of endometriosis

Abstract

Endometriosis is a chronic inflammatory disease defined as the presence of endometrial tissue outside the uterus, which causes pelvic pain and infertility. This disease should be viewed as a public health problem with a major effect on the quality of life of women as well as being a substantial economic burden. In light of the considerable progress with diagnostic imaging (for example, transvaginal ultrasound and MRI), exploratory laparoscopy should no longer be used to diagnose endometriotic lesions. Instead, diagnosis of endometriosis should be based on a structured process involving the combination of patient interviews, clinical examination and imaging. Notably, a diagnosis of endometriosis often leads to immediate surgery. Therefore, rethinking the diagnosis and management of endometriosis is warranted. Instead of assessing endometriosis on the day of the diagnosis, gynaecologists should consider the patient’s ‘endometriosis life’. Medical treatment is the first-line therapeutic option for patients with pelvic pain and no desire for immediate pregnancy. In women with infertility, careful consideration should be made regarding whether to provide assisted reproductive technologies prior to performing endometriosis surgery. Modern endometriosis management should be individualized with a patient-centred, multi-modal and interdisciplinary integrated approach.

Key points

  • Endometriosis is a chronic, inflammatory, hormonal, immune, systemic and heterogeneous disease with three different phenotypes (superficial, ovarian endometrioma and deep infiltrating endometriosis), which is associated with adenomyosis in 30% of patients.

  • Diagnosis of endometriosis (and adenomyosis) should be based on patient interviews, examination and imaging; endometriosis diagnosis should no longer be considered synonymous with immediate surgery.

  • Modern management of endometriosis should be patient focused rather than focused on the endometriotic lesions; medical treatment can be administered without histological confirmation.

  • Pain symptoms should be treated without delay to avoid central sensitization, as this can become autonomous, occurring independently of the peripheral stimulus, and can explain coexisting chronic pain syndromes.

  • Medical treatment should be the first therapeutic option for patients with pelvic pain who have no immediate desire for pregnancy; assisted reproductive technologies can be performed without previous surgery for selected patients with infertility.

  • Endometriosis management should be individualized according to the patient’s intentions and priorities; management strategies can vary from country to country as pain perception and health-care systems differ around the world.

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Fig. 1: The heterogeneous characteristics of endometriosis and adenomyosis.
Fig. 2: The concept of ‘endometriosis life’.
Fig. 3: Imaging of endometriosis and adenomyosis by TVUS.
Fig. 4: Imaging of endometriosis and adenomyosis by MRI.
Fig. 5: Endometriosis management algorithm for patients without an immediate desire for pregnancy.
Fig. 6: Approaches for management of endometriosis.

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Acknowledgements

The authors thank staff members for their contribution to the multidisciplinary management and clinical research of endometriotic patients: (i) Gynecological Surgery: H. Foulot, A. Bourret, P. Marzouk, G. Pierre, M. C. Lafay-Pillet, F. Decuypere, L. Campin and M. C. Lamau; (ii) Gynecological Endocrinology: G. Plu-Bureau, L. Maitrot-Mantelet and J. Hugon-Rodin; (iii) Assisted Reproductive Technology: M. Bourdon, C. Maignien, S. Eskenazi and F. Kefelian; (iv) Reproductive Biology: J. P. Wolf, C. Patrat, K. Pocate-Cheriet and C. Chalas; (v) Obstetrics: F. Goffinet; (vi) Intestinal Surgery: B. Dousset, S. Gaujoux, and M. Leconte; (vii) Urological Surgery: M. Peyromaure and N. Barry Delongchamps; (viii) Thoracic Surgery: M. Alifano; (ix) Radiology: A. E. Millischer, C. Bordonne and F. Bourret-Cassaigne; (x) Pathology: B. Terris, M. C. Vacher-Lavenu and P. A. Just; (xi) Pelvic Pain Center : S. Perrot; (xii) Psychologist: V. Antoine; (xiii) Epidemiology: P. Y. Ancel; (xiv) Biochemistry: D. Borderie and (xv) Paramedical Staff : K. Hillion, M. Meno, S. Odic and V. Blanchet. The authors also wish to thank F. Batteux, S. Chouzenoux and their team and D. Vaiman and his team (Development, Reproduction and Cancer, Institut Cochin, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité, Paris, France) for their collaboration in the scientific research.

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C.C. supervised the project. All of the authors researched data for the article, substantially contributed to discussions of the content and wrote the article. C.C. and P.S. carried out the review and editing of the mauscript.

Corresponding author

Correspondence to Charles Chapron.

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Competing interests

Until recently, C.C was the president of the Society of Endometriosis Disorders (SEUD) and of the Society of Gynecological and Pelvic Surgery (SCGP). Over the past 3 years, C.C. has been a consultant for AbbVie, Bayer, Gedeon Richter and Ipsen. P.S. has been a consultant for Gedeon Richter and Ipsen. L.M. has been a consultant for Ipsen. B.B. has no potential conflicts of interest to disclose.

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Nature Reviews Endocrinology thanks S. Ferrero, K. Koga and P. Rogers for their contribution to the peer review of this work.

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Glossary

Ureterohydronephrosis

The dilatation of the renal pelvis and/or calyces and ureter as a result of obstruction.

Adhesions

Fibrous bands of scar-like tissue that form between tissues and organs, connecting structures that are not normally connected.

Menorrhagia

Menstrual periods with abnormally heavy or prolonged bleeding.

Metrorrhagia

Uterine bleeding at irregular intervals, particularly between the expected menstrual periods.

Müllerian metaplasia

Tissues derived from the celomic epithelium, such as the peritoneum, have the potential to differentiate into epithelium and stroma.

Central sensitization

The amplification of pain by the central nervous system.

Myofascial pain

Pain that originates from myofascial trigger points in skeletal muscle, sometimes in seemingly unrelated parts of the body.

Vulvodynia

Chronic pain that affects the vulvar area and sometimes has no identifiable cause.

Dysmenorrhea

Pain during menstruation.

Myometrial hypertonia

Intense and persistent uterine myometrial contraction.

Adnexal masses

Lumps in tissues of the adnexa of the uterus (such as the ovaries and fallopian tubes).

Retroverted uterus

The position of the uterus, tipped backwards so that its fundus is aimed towards the rectum.

Operative laparoscopy

Minimally invasive surgery for therapeutic interventions with a few small cuts in the abdomen.

Fertility preservation

The procedure used to help retain the ability to procreate, including gamete and/or gonad cryopreservation.

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Chapron, C., Marcellin, L., Borghese, B. et al. Rethinking mechanisms, diagnosis and management of endometriosis. Nat Rev Endocrinol 15, 666–682 (2019). https://doi.org/10.1038/s41574-019-0245-z

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