The role of tissue factor in regulating endometrial haemostasis: implications for progestin-only contraception

Abnormal uterine bleeding accounts for the unacceptably high discontinuatio n rate of progestin-only contraceptives. Previously, we found that in-vivo and in-vitro decidualization of human endometrial stromal cells was associa ted with elevated concentrations of tissue factor (TF), the primary initiat or of haemostasis, Moreover, enhanced TF expression required progesterone r eceptor (PR) and epidermal growth factor receptor (EGFR) mediation. In the current study, endometrial biopsies were sampled from bleeding (BL) and non -bleeding (NBL) sites under camera-directed hysteroscopic guidance after De po-provera injections. When compared with control biopsies, immunohistochem ical examination revealed that 3 months of Depo-provera contraception reduc ed TF concentrations at the BL sites. However, there were ample EGFR and PR concentrations at BL and NBL sites. Moreover, there was a trend towards th e appearance of pathologically enlarged blood vessels at the BL sites, The use of Western blotting revealed that after 3 months of Depo-provera, conce ntrations of both PRE and PRA isoforms were lower at BL versus NBL sites wi th decreased PRA concentrations attaining statistical significance. Separat e sampling of endometrial BL and NBL sites as shown here for Depo-provera c ontraception could prove particularly useful in identifying local factors t hat determine the onset of bleeding during the more protracted time-course of Norplant(R) contraception.