Uterine bleeding: how understanding endometrial physiology underpins menstrual health

Menstruation is a physiological process that is typically uncomplicated. However, up to one third of women globally will be affected by abnormal uterine bleeding (AUB) at some point in their reproductive years. Menstruation (that is, endometrial shedding) is a fine balance between proliferation, decidualization, inflammation, hypoxia, apoptosis, haemostasis, vasoconstriction and, finally, repair and regeneration. An imbalance in any one of these processes can lead to the abnormal endometrial phenotype of AUB. Poor menstrual health has a negative impact on a person’s physical, mental, social, emotional and financial well-being. On a global scale, iron deficiency and iron deficiency anaemia are closely linked with AUB, and are often under-reported and under-recognized. The International Federation of Gynecology and Obstetrics have produced standardized terminology and a classification system for the causes of AUB. This standardization will facilitate future research endeavours, diagnosis and clinical management. In a field where no new medications have been developed for over 20 years, emerging technologies are paving the way for a deeper understanding of the biology of the endometrium in health and disease, as well as opening up novel diagnostic and management avenues. Abnormal uterine bleeding affects many individuals who menstruate and can have a detrimental impact on physical and mental health. This Review discusses endometrial physiology and the causes underlying abnormal uterine bleeding (including heavy menstrual bleeding). Key points Menstruation is a phenomenon of repeated tissue injury and repair that is a fine balance between proliferation, decidualization, inflammation, hypoxia, apoptosis, haemostasis, vasoconstriction and, finally, repair and regeneration. The endometrium is a dynamic, multicellular tissue highly responsive to sex steroids; subtle variances in the endometrial environment and, therefore, functioning, can lead to abnormal uterine bleeding (AUB). AUB is a debilitating symptom that affects up to one third of reproductive-aged women; comprehensive knowledge of menstrual cycle physiology is crucial for understanding and progressing endometrial physiology research. There is a high prevalence of iron deficiency and iron deficiency anaemia in those with AUB, on a global scale, and this is often under-recognized and under-reported. The terminology and definitions for diagnosing causes of AUB are now standardized in the International Feder