Endometriosis and ovulatory menstruation: beyond the Sampson principle
Serdar E. Bulun
Serdar E. Bulun
View: Text | PDF
Review

Endometriosis and ovulatory menstruation: beyond the Sampson principle

Abstract

Endometriosis is an estrogen-dependent chronic inflammatory syndrome characterized by viable endometrial tissue outside the uterine cavity and associated with pain and infertility. Endometriosis, as tissue or a pathological process, is dynamic in that its establishment and progression require repeated episodes of retrograde travel of shed endometrial tissue, which implants in the lower abdominal cavity following ovulatory cycles and survives. Estrogen-rich follicular fluid released onto peritoneal surfaces during ovulation may also support endometriotic implants. DNA evidence indicates that endometriosis originates from eutopic endometrial tissue, which may reach the abdominal cavity in a retrograde manner primarily via the uterine tubes. Unlike uterine bleeding associated with non-ovulatory circumstances, retrograde menstruation following an ovulation maximizes shedding of epithelial cells localized to deep invaginations of the basalis portion of the endometrium, which likely carry somatic cancer-driver mutations such as KRAS. The attached endometrial stromal cells are mostly mutation free but display epigenetic defects including overexpression of aromatase and estrogen receptor-β and downregulation of progesterone receptor, causing estrogen excess and progesterone resistance. These tissue clones may form implants in involuting ovarian corpus luteum cysts and peritoneal surfaces and induce tissue remodeling and fibrosis, manifested as deep-infiltrating endometriosis. The first-line treatment for chronic pelvic pain associated with endometriosis is suppression of ovulation, with the goal of relieving pain. Infertility is often managed using in vitro fertilization, which improves the embryo quality and alters endometrial development.

Authors

Serdar E. Bulun

×

Figure 3

Not all forms of uterine bleeding increase the risk of endometriosis.

Options: View larger image (or click on image) Download as PowerPoint
Not all forms of uterine bleeding increase the risk of endometriosis. (A...
(A) Menstrual tissue after a nonpregnant ovulatory cycle. In addition to inducing stromal and epithelial differentiation, progesterone during the secretory phase of the menstrual cycle stimulates the coiling of the spiral arteries (64, 65). When progesterone production is interrupted in a nonpregnant cycle, the spiral arteries of the basalis and functionalis layers go through rapid and intense vasoconstriction and coagulation, leading to the separation of the thick functionalis layer in its entirety. This leads to the presence of large numbers of viable stromal, epithelial, and endothelial cells along with blood in the menstrual tissue. Some of these tissue fragments travel through the tubes into the pelvic cavity. During this process, mutated epithelial cells and epigenetically abnormal populations of stromal cells are deposited on the pelvic peritoneum or the ovaries. (B) Menstrual tissue associated with withdrawal bleeding in a patient on an oral contraceptive (OC). Because the endometrial tissue that is chronically exposed to an estrogen-progestin combination or progestin-only OC does not build a thick functionalis layer, temporary cessation of OC gives rise to menstrual tissue composed primarily of blood and containing very few stromal or epithelial cells (65, 76). This is also the case for the breakthrough bleeding the patient experiences while they are on hormone-containing OC pills used in a continuous manner.