Figure 6.

Potential mechanisms of “primary” and “secondary” endometrial AUB

As the corpus luteum regresses in the absence of pregnancy, progesterone levels fall. This occurs irregularly in those with ovulatory or iatrogenic AUB. Progesterone withdrawal causes a local inflammatory response in the endometrium and may be increased in those with primary endometrial AUB. An increase in vasoactive factors results in intense vasoconstriction of spiral arterioles to limit blood loss; this may be decreased in primary endometrial AUB. Vasoconstriction may induce transient tissue hypoxia and stabilization of HIF-1, the master regulator of the cellular response to hypoxia, to coordinate endometrial repair. There is evidence that this is less intense in those with endometrial AUB. Efficient hemostasis limits menstrual blood loss at menstruation and this is defective in women with coagulopathy AUB. Structural and nonstructural pathologies have the potential to disrupt endometrial physiology at menstruation, leading to abnormal uterine bleeding; these mechanisms remain undefined.

AUB, abnormal uterine bleeding; HIF-1, hypoxia-inducible factor 1.

Critchley. Menstruation: science and society. Am J Obstet Gynecol 2020.