Endometriosis and adenomyosis: shared pathophysiology

Endometriosis and adenomyosis are sister entities with similar molecular mechanisms. Repetitious episodes of ovulation and menstruation are indispensable for both conditions. Clinically, the history of an event that disrupts the endomyometrial junction such as pregnancy, increases the risk of adenomyosis. Abnormal endometrial cells either get entrapped in the myometrium and survive and thrive in this ectopic location or implant, survive, and invade peritoneal surfaces or an involuting corpus luteum cyst (endometrioma) via retrograde menstruation. Activating somatic mutations in KRAS are encountered as the key events in both endometriosis and adenomyosis. In endometriotic epithelial cells, several other genes are also affected by mutations. In adenomyosis, however, epithelial KRAS mutations are almost exclusively found in the great majority of the lesions. The stromal cells of both tissues exhibit widespread epigenetic defects that lead to excessive estrogen formation, abnormal estrogen action via ESR2, and progesterone resistance.