Reproduction Abstracts

Endometrial function is orchestrated by endogenous ovarian steroid hormones, oestradiol (E) and progesterone (P). P plays a crucial role in the functional modification of the endometrium in preparation for pregnancy (differentiation of stromal fibroblasts, maturation of spiral arterioles and influx of immune cells). In the peri-menstrual phase cyclical tissue ‘injury and repair’ in the local endometrial environment is a consequence of P-withdrawal which initiates a cascade of changes including focal hypoxia, vessel breakdown and tissue shedding (menstruation). Initiation of menses may be reversed with P add-back up to 36 h following its withdrawal but beyond 36 h menstruation is inevitable. A spectrum of synthetic therapeutics exist that are capable of activating (agonists), or blocking (antagonists) the action of P. Persistent exogenous local delivery of progestogen (agonist) to the endometrial cavity (levonorgestrel-releasing intrauterine system; LNG-IUS) has dramatic impacts on endometrial function and menstrual bleeding. Selective progesterone receptor modulators (SPRMs) for example, Asoprisnil and Ulipristal acetate (UPA) are compounds with mixed agonist/antagonist properties. Administration of ligands (LNG; Asoprisnil; UPA) for the progesterone receptor (PR) also has a dramatic impact on the function and architecture of the endometrium (a complex multicellular tissue). The SPRMs induce unique PRM-associated endometrial changes (PAEC), the full significance of which is yet to be determined. Each of these PR ligands results in a profound suppression of uterine bleeding. The mechanisms that underpin these impressive clinical impacts remain a crucially important area for research especially if such compounds are to achieve their full clinical utility.