Endometriosis Clinical Update
Ongoing updates of key clinical trial advances and new study data for common conditions.

By Lisa Kuhns, PhD

Published May 25, 2022.


Endometriosis is a gynecological condition affecting 2% to 10% of women of reproductive age.1,2 It is characterized by the abnormal growth of endometrium-like tissue outside of the uterus.2 During a typical menstrual cycle, endometrial tissue builds up and is shed if a woman does not become pregnant. The misplaced endometrial tissue in women with endometriosis, however, responds to the hormonal changes of the menstrual cycle by building up and breaking down, causing small bleeding inside the pelvis.1

Endometriosis accounts for 35% to 50% of women presenting with infertility and pain management. Endometriosis often goes undiagnosed because it does not show specific symptoms or remains asymptomatic for a long period. It causes symptoms such as pain, dysmenorrhea, dyspareunia, lower abdominal and/or back pain, and infertility at a later stage when metastasis and growth outside the uterus starts. The types of endometriosis are distinguished based on their location and include superficial peritoneal endometriosis, ovarian endometriomas, and deep endometriotic nodules.2


The specific cause of endometriosis is unknown. Epigenetic mutations, external and internal influences, and chronic conditions impact the development, however. Theories as to the cause of endometriosis include retrograde menstruation, immunologic dysfunction, metaplasia, remnant Mullerian cells, genetics, and anatomic spread. The Sampson model proposes that endometriosis occurs because of retrograde menstruation with endometrioid tissue implantation and growth outside of the uterus. It has expanded to include molecular characteristics like epigenetic defects.3

The immune system, or immunologic dysfunction, is also involved in endometriosis development. Patients with endometriosis have elevated levels of immunocompetent cells. An altered immune response to the displaced endometrial tissue involves the activation of macrophages. Macrophages respond to endometriosis as a wound and activate mechanisms that lead to ectopic cell survival and tissue vascularization, which supports the growth and development of endometrial-like tissue.3

The metaplastic theory suggests that endometriotic lesions change from one normal type of tissue to another normal type of tissue.4 This theory is based on peritoneal and endometrial cells coming from the common embryologic predecessor, the coelomic epithelium. Evidence suggests that endometriotic foci may be found in both the respiratory and urinary tract epithelium, not only the mesothelial pleura.3

Screening and Diagnosis

The European Society of Human Reproduction and Embryology Guideline Development Group recommends clinicians consider an endometriosis diagnosis if patients present with cyclical and noncyclical signs and symptoms of dysmenorrhea, deep dyspareunia, dysuria, dyschezia, painful rectal bleeding or hematuria, shoulder tip pain, catamenial pneumothorax, cyclical cough/hemoptysis/chest pain, cyclical scar swelling and pain, fatigue, and infertility.5

Initial diagnoses of endometriosis include collecting the patient’s medical history, gynecologic examination with specula, and two-handed examination.1 Additional examinations used during a diagnosis include laparoscopy, biopsies, ultrasound, computed tomography (CT) scan, and magnetic resonance imaging (MRI) scan.

Ultrasounds are the basic tool used during diagnosis, and examinations are helpful to visualize the flow of menstrual blood to the peritoneal cavity. The gold standard in endometriosis diagnoses was laparoscopic surgery with confirmation in histopathological examination in the past, but the 2022 revision of endometriosis guidelines published by The European Society of Human Reproduction and Embryology only recommends laparoscopy for patients with negative imaging results or when empiric treatment is unsuccessful or inappropriate.5,6 Endometriosis is classified in different stages: stage 1, minimal; stage 2, mild;  stage 3, moderate; and stage 4, severe. The stages are based on the location, amount, depth and size of the endometrial tissue; the extent of the tissue spread; pelvic structure involvement; pelvic adhesion extent; and fallopian tube blockage.1

Treatment and Management

Treatment approaches should take into consideration the personal circumstances of each patient, such as overall health and medical history, current symptoms, extent of the disease, patient tolerance of medicine and procedures, expectations for the disease course, and the desire for pregnancy. General treatment options may include watching the disease, pain management, hormone therapy, and surgical techniques.1

Pharmacological treatment is used for pain management and inhibiting the development and regression of endometrial foci. It can also restore fertility. Groups of medicines used in endometriosis treatment include nonsteroidal anti-inflammatory drugs, hormonal drugs, hormonal contraceptives, selective progesterone receptor modulators, and aromatase inhibitors.6 The 2022 guideline recommends using gonadotropin-releasing hormone (GnRH) antagonists as a second-line treatment option.5

The European Society of Human Reproduction and Embryology Guideline Development Group recommends that clinicians offer hormone treatments that include combined hormonal contraceptives, progestogens, GnRH agonists or GnRH antagonists as an option to reduce pain in women with endometriosis. Combined hormonal contraceptives are recommended to reduce endometriosis-associated dyspareunia, dysmenorrhea, and nonmenstrual pain. Women can also be offered a combined hormonal contraceptive pill. Progestogens can reduce endometriosis-associated pain, but clinicians should analyze the side effects when prescribing them. If hormonal contraceptives or progestogens are ineffective, GnRH agonists are prescribed as second line. Aromatase inhibitors can be used in combination with oral contraceptives, progestogens, GnRH agonists, or GnRH antagonists.5

Surgical treatment is used for the symptoms of pelvic pain, infertility in endometriosis, and endometrial ovarian cysts. Surgical treatment can be sparing or radical. Sparing treatment is used in women who are adolescents or of childbearing age planning to become pregnant. Radical treatment is used in patients who do not intend to become pregnant or continue to have pain despite pharmacological treatment.6

To determine the best treatment step for endometriosis-related infertility, the Endometriosis Fertility Index is used to support decision-making. Updated guidelines recommend that women who wish to become pregnant should not receive postoperative hormone suppression, and the extended administration of GnRH is not recommended before assisted reproductive technology treatment.5


Endometriosis is a leading cause of pain and infertility in women of childbearing age and adolescents. It requires long-term treatment and monitoring in most cases, but with a proper diagnosis, can be treated in a manner suitable for the patient. There remains a clinical unmet need for improving diagnosis and treatment of endometriosis, but new evidence-based guidelines can help clinicians in diagnosis and in finding suitable treatments for their patients.


1.         Johns Hopkins Medicine. Endometriosis. Accessed May 11, 2022.

2.         Kapoor R, Stratopoulou CA, Dolmans MM. Pathogenesis of endometriosis: new insights into prospective therapies. Int J Mol Sci. 2021;22(21):11700. doi:10.3390/ijms222111700

3.         Mikhaleva LM, Radzinsky VE, Orazov MR, et al. Current knowledge on endometriosis etiology: a systematic review of literature. Int J Womens Health. 2021;13:525-537. doi:10.2147/IJWH.S306135

4.         Medscape. Endometriosis: Practice Essentials, Background, Pathophysiology. Published online January 25, 2022. Accessed May 11, 2022.

5.         European Society of Human Reproduction and Embryology. Endometriosis Guideline of the European Society of Human Reproduction and Embryology. 2022. Accessed May 16, 2022.

6.         Smolarz B, Szyłło K, Romanowicz H. Endometriosis: epidemiology, classification, pathogenesis, treatment and genetics (Review of Literature). Int J Mol Sci. 2021;22(19):10554. Doi:10.3390/ijms221910554