The Menstrual Endometrium: From Physiology to Future Treatments

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.