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Endometriosis

Nature Reviews Disease Primers volume 4, Article number: 9 (2018) Cite this article

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Abstract

Endometriosis is a common inflammatory disease characterized by the presence of tissue outside the uterus that resembles endometrium, mainly on pelvic organs and tissues. It affects ~5–10% of women in their reproductive years — translating to 176 million women worldwide — and is associated with pelvic pain and infertility. Diagnosis is reliably established only through surgical visualization with histological verification, although ovarian endometrioma and deep nodular forms of disease can be detected through ultrasonography and MRI. Retrograde menstruation is regarded as an important origin of the endometrial deposits, but other factors are involved, including a favourable endocrine and metabolic environment, epithelial–mesenchymal transition and altered immunity and inflammatory responses in genetically susceptible women. Current treatments are dictated by the primary indication (infertility or pelvic pain) and are limited to surgery and hormonal treatments and analgesics with many adverse effects that rarely provide long-term relief. Endometriosis substantially affects the quality of life of women and their families and imposes costs on society similar to those of other chronic conditions such as type 2 diabetes mellitus, Crohn’s disease and rheumatoid arthritis. Future research must focus on understanding the pathogenesis, identifying disease subtypes, developing non-invasive diagnostic methods and targeting non-hormonal treatments that are acceptable to women who wish to conceive.

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Fig. 1: Staging of endometriosis.
Fig. 2: Hormone signalling in endometriosis.
Fig. 3: Endometriosis models and mediators.
Fig. 4: Pelvic endometriosis.
Fig. 5: Diagnosing endometriosis.
Fig. 6: Simplified algorithm for management of endometriosis-associated infertility.
Fig. 7: Algorithm for management of endometriosis-associated pain.

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Acknowledgements

R.N.T. acknowledges funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development through grants R01-HD33238, U54-HD37321, U54-HD55787, R01-HD55379, U01-HD66439 and R21-HD78818. S.A.M. is also affiliated with the Boston Center for Endometriosis, Boston Children’s Hospital and Brigham and Women’s Hospital and the Division of Adolescent and Young Adult Medicine, Department of Medicine, Boston Children’s Hospital and Harvard Medical School. The authors thank N. Moore (Oxford University Hospitals Foundation Trust, UK) for providing MRI images, D. Barber (Oxford Endometriosis CaRe Centre, UK) for providing ultrasonography pictures and J. Malzahn (Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK) for providing the picture of the histology slide in Fig. 5.

Reviewer information

Nature Reviews Disease Primers thanks I. Brosens, M. J. Canis, S. Ferrero, C. Nezhat, V. Remorgida, M. Simões Abrão and other anonymous referee(s) for the peer review of this work.

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Authors and Affiliations

  1. Oxford Endometriosis CaRe Centre, Nuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, UK

    Krina T. Zondervan & Christian M. Becker

  2. Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK

    Krina T. Zondervan

  3. Department of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan

    Kaori Koga

  4. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Stacey A. Missmer

  5. Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA

    Stacey A. Missmer

  6. Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, UT, USA

    Robert N. Taylor

  7. Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy

    Paola Viganò

Authors
  1. Krina T. Zondervan
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  2. Christian M. Becker
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Contributions

Introduction (K.T.Z.); Epidemiology (S.A.M.); Mechanisms/pathophysiology (R.N.T. and P.V.); Diagnosis, screening and prevention (C.M.B.); Management (K.K.); Quality of life (K.T.Z.); Outlook (K.T.Z.); Overview of the Primer (K.T.Z.).

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Correspondence to Krina T. Zondervan.

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Competing interests

K.T.Z. has received grant funding from the Wellcome Trust, Medical Research Council UK, the US NIH, the European Union and the World Endometriosis Research Foundation (WERF). She also has scientific collaborations with, and has received grant funding from, Bayer AG, MDNA Life Sciences, Roche Diagnostics and Volition Rx and has served as a scientific consultant to AbbVie and Roche Diagnostics. She is Secretary of the World Endometriosis Society (WES), the European Society of Human Reproduction and Embryology (ESHRE) Special Interest Group in Endometriosis and Endometrial Disorders and Wellbeing of Women, and she is Chair of the WES Research Directions Working Group. C.M.B. is a member of the independent data monitoring group for a clinical endometriosis trial by ObsEva. He has received research grants from Bayer AG, MDNA Life Sciences, Volition Rx and Roche Diagnostics as well as from Wellbeing of Women, Medical Research Council UK, the NIH, the UK National Institute for Health Research and the European Union. He is the current Chair of the Endometriosis Guideline Development Group of the ESHRE and was a co-opted member of the Endometriosis Guideline Group by the UK National Institute for Health and Care Excellence (NICE). K.K. has received grant funding from the Ministry of Education, Culture, Sports Science and Technology Japan, the Ministry of Health, Labour and Welfare Japan, Takeda Research Support and MSD. She has also served as a scientific consultant to Bayer AG. She is an ambassador of the WES and a member of the Guideline Development Group of the Japan Society of Obstetrics and Gynecology. S.A.M. has received grant funding from the NIH and the Marriott family foundations and has served as an adviser to and has scientific collaborations with AbbVie, Celmatix and Oratel Diagnostics. She is a treasurer of the WES, Secretary of the WERF, Chair of the American Society of Reproductive Medicine Endometriosis Special Interest Group and a member of the NIH Reproductive Medicine Network Data Safety and Monitoring Board. R.N.T. has received grant funding from Bayer AG, Ferring Research Institute, the NIH and Pfizer and has served as a scientific consultant or adviser to AbbVie, Allergan, the NIH, ObsEva SA and the Population Council. He is the immediate past honorary secretary of the WES. P.V. has received grant funding from Bayer AG and Merck Serono and has served as a scientific consultant to Ferring Pharmaceuticals and Roche Diagnostics. She is a board member of the WES.

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Related links

WERF Endometriosis Phenome and Biobanking Harmonisation Project: https://endometriosisfoundation.org/ephect/

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Zondervan, K.T., Becker, C.M., Koga, K. et al. Endometriosis. Nat Rev Dis Primers 4, 9 (2018). https://doi.org/10.1038/s41572-018-0008-5

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