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  • Review Article
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Endometriosis: pathogenesis and treatment

Nature Reviews Endocrinology volume 10, pages 261–275 (2014)Cite this article

Subjects

Key Points

  • Endometriosis is characterized by the presence of ectopic endometrium causing pain, infertility or lesion progression; it affects ∼5% of women of reproductive age, with a prevalence peak between 25 years and 35 years of age

  • Interaction of the number and amount of menstrual flows with genetic and environmental factors seems to determine the likelihood of development as well as the phenotypic manifestation of the disease

  • Although pain can be managed via pharmacological inhibition of ovulation and menstruation, lesions are not eradicated; surgery is generally associated with pain relief, but its benefit is often temporary

  • Medical therapy for infertility is inefficacious, whereas laparoscopic elimination of endometriotic lesions and adnexal adhesions increases the chances of conception moderately; in vitro fertilization is a valid alternative to surgery

  • Endometriosis is associated with a 50% increase in the risk of ovarian cancer; preventive interventions are possible, but screening of patients with endometriosis for ovarian cancer is presently not justified

  • Primary prevention of endometriosis is not currently feasible; treatment should be tailored to fit individual needs, and a shared decision-making approach between patient and clinician is encouraged

Abstract

Endometriosis is defined as the presence of endometrial-type mucosa outside the uterine cavity. Of the proposed pathogenic theories (retrograde menstruation, coelomic metaplasia and Müllerian remnants), none explain all the different types of endometriosis. According to the most convincing model, the retrograde menstruation hypothesis, endometrial fragments reaching the pelvis via transtubal retrograde flow, implant onto the peritoneum and abdominal organs, proliferate and cause chronic inflammation with formation of adhesions. The number and amount of menstrual flows together with genetic and environmental factors determines the degree of phenotypic expression of the disease. Endometriosis is estrogen-dependent, manifests during reproductive years and is associated with pain and infertility. Dysmenorrhoea, deep dyspareunia, dyschezia and dysuria are the most frequently reported symptoms. Standard diagnosis is carried out by direct visualization and histologic examination of lesions. Pain can be treated by excising peritoneal implants, deep nodules and ovarian cysts, or inducing lesion suppression by abolishing ovulation and menstruation through hormonal manipulation with progestins, oral contraceptives and gonadotropin-releasing hormone agonists. Medical therapy is symptomatic, not cytoreductive; surgery is associated with high recurrence rates. Although lesion eradication is considered a fertility-enhancing procedure, the benefit on reproductive performance is moderate. Assisted reproductive technologies constitute a valid alternative. Endometriosis is associated with a 50% increase in the risk of epithelial ovarian cancer, but preventive interventions are feasible.

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Figure 1: Epidemiological factors and molecular mechanisms involved in endometriosis development.
Figure 2: Visual examples of the most frequent forms of endometriosis.
Figure 3: Flow-chart of infertility treatment from an endometriosis-centred perspective.
Figure 4: An ovarian endometriotic cyst with a papillary clear cell carcinoma.

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Acknowledgements

D. Alberico, D. Dridi, A. M. Sanchez and C. Vercellini are greatly acknowledged for their support.

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  1. Department of Obstetrics and Gynecology, Fondazione Cà Granda, Ospedale Maggiore Policlinico, Via Commenda 12, 20122, Milan, Italy

    Paolo Vercellini, Edgardo Somigliana & Luigi Fedele

  2. Division of Genetics and Cell Biology, Reproductive Sciences Laboratory, San Raffaele Scientific Institute, Via Olgettina 60, 20136, Milan, Italy

    Paola Viganò

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  1. Paolo Vercellini
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P. Vercellini, P. Viganò and E. Somigliana researched data for the article, provided a substantial contribution to discussion of the content, wrote the article and reviewed/edited the manuscript before submission. L. Fedele provided a substantial contribution to discussion of the content and reviewed/edited the manuscript before submission.

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Vercellini, P., Viganò, P., Somigliana, E. et al. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol 10, 261–275 (2014). https://doi.org/10.1038/nrendo.2013.255

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