Menstrual physiology: implications for endometrial pathology and beyond

Abstract

Background: Each month the endometrium becomes inflamed, and the luminal portion is shed during menstruation. The subsequent repair is remarkable, allowing implantation to occur if fertilization takes place. Aberrations in menstrual physiology can lead to common gynaecological conditions, such as heavy or prolonged bleeding. Increased knowledge of the processes involved in menstrual physiology may also have translational benefits at other tissue sites.

Methods: Pubmed and Cochrane databases were searched for all original and review articles published in English until April 2015. Search terms included 'endometrium', 'menstruation', 'endometrial repair', 'endometrial regeneration' 'angiogenesis', 'inflammation' and 'heavy menstrual bleeding' or 'menorrhagia'.

Results: Menstruation occurs naturally in very few species. Human menstruation is thought to occur as a consequence of preimplantation decidualization, conferring embryo selectivity and the ability to adapt to optimize function. We highlight how current and future study of endometrial inflammation, vascular changes and repair/regeneration will allow us to identify new therapeutic targets for common gynaecological disorders. In addition, we describe how increased knowledge of this endometrial physiology will have many translational applications at other tissue sites. We highlight the clinical applications of what we know, the key questions that remain and the scientific and medical possibilities for the future.

Conclusions: The study of menstruation, in both normal and abnormal scenarios, is essential for the production of novel, acceptable medical treatments for common gynaecological complaints. Furthermore, collaboration and communication with specialists in other fields could significantly advance the therapeutic potential of this dynamic tissue.

Keywords: angiogenesis; endometrium; hypoxia; inflammation; progesterone.

Figure 1

The relevance of menstrual physiology. The perimenstrual endometrium (centre) is exposed to inflammation and hypoxia. Stem cells and EMT are involved at menses to enable scar-free repair (light blue). Aberrations in these processes can lead to gynaecological disorders (mid-blue). Study of endometrial physiology may help delineate the pathogenesis of a number of disorders in other tissue sites (dark blue).

Figure 2

Leukocyte trafficking in the perimenstrual human endometrium (derived from data published and reviews by Bonatz et al., 1992; Salamonsen and Lathbury, 2000; Moffett-King, 2002; Thiruchelvam et al., 2013). Top panel: Sex steroid profiles in the luteo-follicular transition (perimenstrual ‘window’). Bottom panel: Overview of leukocyte traffic in the endometrium with transition from secretory phase through menses/endometrial repair to the proliferative phase of next cycle. Size of cell image reflects abundance.

Figure 3

Endometrial coagulation pathways. Immediate: A platelet plug forms rapidly, relying on interactions with tissue factor, vWF and collagen. Subsequent: intrinsic and/or extrinsic activation of coagulation pathways result in formation of a fibrin clot to ensure haemostasis. Fibrinolysis drives the degradation of the fibrin clot. t-PA and u-PA convert plasminogen to plasmin, which breaks down the fibrin clot. PAI converts plasmin back to plasminogen.