Estrogen receptor β: the guardian of the endometrium

Abstract

The collective evidence suggests that ERβ has an important role in normal endometrial function and also in most, if not all, benign and malignant endometrial diseases. However, the conduct of studies of endometrial ERβ expression needs to be standardized: agreement is needed regarding the most appropriate control tissue for endometrial cancer studies as well as development of standardized methods for the quantification of ERβ immunohistochemical data, similar to those scoring systems employed for other hormonally regulated tissues such as breast cancer, since these data may have direct clinical implications in guiding therapy.

Pathophysiology of Heavy Menstrual Bleeding

“…After menstrual shedding, the subsequent repair process has been traditionally presumed to be due to the action of estrogen [4][5]14]. However, the very early repair process is not necessarily dependent on estrogen, as the level of estrogen is at a nadir when the re-epithelialization of the endometrial surface occurs; a process that is not impaired in the postmenopausal hypoestrogenic state [5,15].…”

“…The endometrium is under the regulation of ovarian steroid hormones, mainly estrogen and progesterone and their involvement in the monthly endometrial cycle is well established. These ovarian sex steroids exert their effects on the endometrium via the respective steroid hormone receptors [5]. Ovarian androgens and glucocorticoids of adrenal origin may also play a role in this process, although the actions of androgens on the endometrium are yet to be elucidated [4].…”

“…The carcinogenesis process is common in highly regenerative tissues and yet the large number of repetitive regeneration cycles that the endometrium endures does not appear to increase the potential for endometrial carcinogenesis. However, EC is a hormonally driven disease and the continuous, unopposed effect of the mitotic action of estrogen is thought to be the primary oncogenic promoter in at least 80% of endometrial cancers [5]. Therefore, conditions that dysregulate the sequential exposure to pro-future science group Pathophysiology of heavy menstrual bleeding Review gesterone of the estrogen primed endometrium, such as obesity, PCOS, diabetes, estrogen secreting ovarian tumors and tamoxifen use, among others, will increase the risk of EC [69,70].…”

“…The previously proposed theory that re-epithelialization of the luminal epithelial surface is the primary factor in cessation of bleeding [73] is not supported by the histological observations that complete re-epithelialization is frequently seen on days 1 and 2 of the menses, despite continued menstrual bleeding. The stratum basalis of the endometrium maintains tissue integrity during menstrual breakdown of the stratum functionalis [5]. The differences between the cells in the two functionally and possibly phenotypically different layers, are only beginning to be understood [6].…”

“…These contractions may play a role in emptying the uterine cavity of menstrual debris and may also play a haemostatic role by providing a pressure effect on the endometrial vasculature. Although the pivotal role played by myometrial contractility in preventing uterine bleeding following parturition is well established [13], very little is known of the contribution of myometrial contractility in regulation of menstrual bleeding.After menstrual shedding, the subsequent repair process has been traditionally presumed to be due to the action of estrogen [4][5]14]. However, the very early repair process is not necessarily dependent on estrogen, as the level of estrogen is at a nadir when the re-epithelialization of the endometrial surface occurs; a process that is not impaired in the postmenopausal hypoestrogenic state [5,15].…”