The Menstrual Endometrium: From Physiology to Future Treatments

Abstract

Abnormal uterine bleeding (AUB) is experienced by up to a third of women of reproductive age. It can cause anaemia and often results in decreased quality of life. A range of medical and surgical treatments are available but are associated with side effects and variable effectiveness. To improve the lives of those suffering from menstrual disorders, delineation of endometrial physiology is required. This allows an increased understanding of how this physiology may be disturbed, leading to uterine pathologies. In this way, more specific preventative and therapeutic strategies may be developed to personalise management of this common symptom. In this review, the impact of AUB globally is outlined, alongside the urgent clinical need for improved medical treatments. Current knowledge of endometrial physiology at menstruation is discussed, focusing on endocrine regulation of menstruation and local endometrial inflammation, tissue breakdown, hypoxia and endometrial repair. The contribution of the specialised endometrial vasculature and coagulation system during menstruation is highlighted. What is known regarding aberrations in endometrial physiology that result in AUB is discussed, with a focus on endometrial disorders (AUB-E) and adenomyosis (AUB-A). Gaps in existing knowledge and areas for future research are signposted throughout, with a focus on potential translational benefits for those experiencing abnormal uterine bleeding. Personalisation of treatment strategies for menstrual disorders is then examined, considering genetic, environmental and demographic characteristics of individuals to optimise their clinical management. Finally, an ideal model of future management of AUB is proposed. This would involve targeted diagnosis of specific endometrial aberrations in individuals, in the context of holistic medicine and with due consideration of personal circumstances and preferences.

Modulatory Activity of Aju Mbaise Polyherbal Formulation on Serum Proinflammatory Cytokines and Prostaglandin Levels in Nulliparous and Parturient Female Albino Rats

“…Dysmenorrhea and menorrhagia, which exaggerate tissue destruction in normal menstruation, are pathologies of menstruation which present with cramps and abnormal uterine bleeding (AUB). Current treatment strategies adopt the use of non-steroidal anti-inflammatory drugs which target the inhibition of cyclooxygenase enzymes [16] via a reduction in body levels of pro-inflammatory cytokines [17]. In this study, the extract may have achieved this effect of pro-inflammatory cytokine lowering via the same pathway, which may be the reason for its acclaimed analgesic property and a promising agent for the management of postpartum and menstruation-associated pains [5] to serve as an alternative to other agents which are in current for such health issues [18][19][20].…”

Association of heavy menstrual bleeding with cardiovascular diseases in US female hospitalizations

“…33 In addition, reduced expression of HOXA10 and 11 genes, altered function of estrogen receptor β and progesterone receptor, and increased matrix metalloproteinases and nuclear factor kappa B activities have been reported to influence inflammation. 34, 35 In HMB patients, increased levels of tissue plasminogen activator affecting hemostasis, fibrin, and D-dimers have also been reported. 10, 36 The related treatments such as hormonal-based treatments including combined oral contraceptives or progestin-only contraceptives, and hemostatic therapy affecting these pathways have been developed for HMB.…”

Gene expression associated with vaginal bleeding in women using the 52‐mg levonorgestrel hormonal intrauterine device: A prospective study

“…Its purpose is to regulate uterine bleeding and facilitate optimal endometrial repair. 25 Dysregulation of biochemical pathways can lead to pathologic responses, including AUB. There is a hypothesis that AUB of endometrial origin 15 may result from excessive inflammatory processes, which are characterized by elevated levels of tumor necrosis factor and cyclooxygenase (COX) present in the endometrium of women with AUB.…”