What is the difference between eutopic and ectopic endometrium in patients with adenomyosis?

Eutopic and Ectopic Endometrium in Adenomyosis

In adenomyosis, eutopic endometrium refers to the endometrial tissue located in its normal position lining the uterine cavity, while ectopic endometrium refers to the endometrial-like tissue that has abnormally invaded the myometrium (uterine muscle layer).

Definitions and Characteristics

Eutopic Endometrium in Adenomyosis

• Eutopic endometrium is the normal endometrial tissue that lines the uterine cavity 1
• In adenomyosis patients, the eutopic endometrium shows biological differences compared to that of healthy women without adenomyosis 2
• The eutopic endometrium in adenomyosis exhibits metabolic and molecular abnormalities that affect its normal function 3

Ectopic Endometrium in Adenomyosis

• Ectopic endometrium in adenomyosis refers to endometrial-like tissue that has invaded and is growing within the myometrium (uterine muscle layer) 4
• Adenomyosis is specifically characterized by this ectopic endometrial tissue being present within the myometrium of the uterus 4
• Deep endometriosis (including adenomyosis) is defined as lesions extending deeper than 5 mm under the peritoneal surface or those involving or distorting bowel, bladder, ureter or vagina 1

Biological Differences

Altered Cellular Processes

• Eutopic endometrial stromal cells in adenomyosis show decreased apoptosis (programmed cell death) compared to normal endometrium, making them more resistant to cell death 2
• Endometrial stromal cells from adenomyosis patients demonstrate increased proliferation rates compared to those from women without adenomyosis 2
• The Ki-67 labeling index (a marker of cell proliferation) is significantly higher in adenomyotic endometrial stromal cells (7.7% versus 1.1% in controls) 2

Molecular and Metabolic Abnormalities

• Both eutopic and ectopic endometria in adenomyosis show abnormalities that:
  • Increase angiogenesis (formation of new blood vessels) 3
  • Decrease apoptosis (programmed cell death) 3
  • Allow local production of estrogens 3
  • Create progesterone resistance 3
  • Impair cytokine expression 3

Hormonal Influences

• Adenomyosis is associated with relative 17β-hydroxysteroid dehydrogenase type II deficiency, leading to increased local estrogen production 5
• Progesterone resistance is a key characteristic of both eutopic and ectopic endometrium in adenomyosis 5
• These hormonal alterations help sustain the growth of ectopic endometrial implants 5

Diagnostic Considerations

Imaging Features

• Transvaginal ultrasound (TVUS) is often used to diagnose adenomyosis with a pooled sensitivity and specificity of 82.5% and 84.6%, respectively 1
• Detection of adenomyosis by TVUS may be limited when coexisting with other uterine pathologies like leiomyomas 1
• MRI can display the endometrium even in the setting of adenomyosis, which may obscure the endometrium on ultrasound 1

Cellular Components

• Recent single-cell RNA sequencing studies suggest that epithelial cell clusters may be vital progenitors of both endometriosis and adenomyosis 6
• Specific subclusters of stromal cells, particularly fibroblasts, are involved in the occurrence of adenomyosis 6
• The immune microenvironment appears to be activated in adenomyosis, though this requires further exploration 6

Clinical Implications

Impact on Fertility and Symptoms

• The molecular and cellular changes in both eutopic and ectopic endometrium contribute to symptoms such as dysmenorrhea and abnormal uterine bleeding 3
• Endometriosis and adenomyosis are likely common causes of endometrial receptivity defects affecting fertility 5
• The altered endometrium enhances its ability to infiltrate the junctional zone myometrium and promotes the growth of ectopic tissue 3

Treatment Considerations

• Understanding the differences between eutopic and ectopic endometrium has created new therapeutic options 3
• Treatment approaches may include:
  • Blocking local aromatase production 3
  • Using selective estrogen receptor modulators 3
  • Estrogen-progestin combinations 3
  • Gonadotropin-releasing hormone super agonists 3
• Definitive treatment for symptomatic adenomyosis has traditionally been hysterectomy 4

Research Limitations

• Most studies on adenomyosis have been performed on hysterectomy specimens representing final stages of the disease, limiting our understanding of early disease processes 3
• Further research is needed to better understand the immune characteristics of adenomyosis at the cellular level 6