The endocrine and paracrine control of menstruation

During the reproductive life, the human endometrium undergoes cycles of substantial remodeling including, at menstruation, a massive but delimited tissue breakdown immediately followed by scarless repair. The present review aims at summarizing the current knowledge on the endocrine and paracrine control of menstruation in the light of recent observations that undermine obsolete dogmas. Menstruation can be globally considered as a response to falling progesterone concentration. However, tissue breakdown is heterogeneous and tightly controlled in space and time by a complex network of regulators and effectors, including cytokines, chemokines, proteases and various components of an inflammatory response. Moreover, menstruation must be regarded as part of a complex and integrated mechanism of tissue remodeling including features that precede and follow tissue lysis, i.e. decidualization and immediate post-menstrual regeneration. The understanding of the regulation of menstruation is of major basic and clinical interest. Indeed, these mechanisms largely overlap with those controlling other histopathological occurrences of tissue remodeling, such as development and cancer, and inappropriate control of menstrual features is a major potential cause of two frequent endometrial pathologies (i.e. abnormal uterine bleeding and endometriosis).

► Menstruation is triggered by a fall in progesterone concentration.
► Various cell types including stromal, epithelial, endothelial and inflammatory cells contribute to menstruation.
► Menstruation is strictly controlled in space and time by factors including prostaglandins, cytokines and chemokines.
► Mechanisms regulating decidualization, menstruation and early post-menstrual repair are integrated.
► Dysregulation of menstruation may lead to endometrial pathologies such as endometriosis or abnormal uterine bleeding.