Endometriosis and adenomyosis: shared pathophysiology

Fertil Steril. 2023 May;119(5):746-750. doi: 10.1016/j.fertnstert.2023.03.006. Epub 2023 Mar 15.


Endometriosis and adenomyosis are closely related disorders. Their pathophysiologies are extremely similar. Both tissues originate from the eutopically located intracavitary endometrium. Oligoclones of endometrial glandular epithelial cells with somatic mutations and attached stromal cells may give rise to endometriosis if they travel to peritoneal surfaces or the ovary via retrograde menstruation and/or may be entrapped in the myometrium to give rise to adenomyosis. In both instances, the endometrial cell populations possess survival and growth capabilities conferred by somatic epithelial mutations and epigenetic abnormalities in stromal cells. Activating mutations of KRAS are the most commonly found genetic variant in endometriotic epithelial cells, whereas the adenomyotic epithelial cells almost exclusively bear KRAS mutations. Epigenetic abnormalities in the stromal cells of endometriosis and adenomyosis are very similar and involve an abnormal expression pattern of nuclear receptors, including the steroid receptors. These epigenetic defects give rise to excessive local estrogen biosynthesis by aromatase and abnormal estrogen action via estrogen receptor-β. Deficient progesterone receptor expression results in progesterone resistance in both endometriosis and adenomyosis.

Keywords: Adenomyosis; KRAS; aromatase; endometriosis; progesterone resistance.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomyosis* / genetics
  • Adenomyosis* / metabolism
  • Endometriosis* / metabolism
  • Endometrium / metabolism
  • Estrogens
  • Female
  • Humans
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Uterine Diseases* / metabolism


  • Proto-Oncogene Proteins p21(ras)
  • Estrogens