不规则出血是孕激素避孕药最主要副反应，严重影响该避孕方法的使用率。研究提示孕激素撤退是子宫不规则出血的重要生理基础，也是目前的研究热点。然而对于孕激素撤退的分子机制仍不清楚。前期小鼠孕激素埋植模型研究显示：孕激素维持作用下，小鼠子宫内膜依然崩解，发生出血，并发现NF-κB/TNF-a信号通路激活。推测孕激素维持下可能存在功能性孕酮撤退并激活NF-κB/TNF-a信号通路导致子宫内膜崩解。提示NF-κB/TNF-a信号是连接孕激素与子宫内膜崩解出血的重要纽带，其过程机制仍然不明。本研究以动物模型为基础结合临床材料，从动物、组织、分子水平明晰功能性孕酮撤退的特有机制和NF-κB/TNF-a信号在内膜崩解过程中，发生出血的作用机制。利用动物模型的优势，通过宫腔和阴道局部给药探讨孕激素维持状态下内膜崩解的炎症机制和和微环境干预新模式的效果。为改善孕激素避孕药所致不规则出血提供重要理论。

Irregular uterine bleeding, a major side effect of long-acting progestogen(p)-only contraceptives in women, is the main reason for discontinuation of their use. To understand the mechanisms of irregular bleeding, a mouse model of endometrial breakdown was adapted to test the response of endometrium to progestogens. Progestogen is responsibility for maintaining decidualization. However, in our previous study suggested that the decidual endometrium breakdown as well as NF-κB/TNF-a signal activated when progestogens maintaining in mouse model and cell model. We hypothesized that functional progesterone withdrawal(F-PW) occurs progesterone maintaining. However the mechanisms of endometrial tissue breakdown by implantable progesterone in NF-κB/TNF-a signal pathway is not clear. We will study the expression of progesterone receptor (PR) isoforms and factors interacting with PR in the model to clear the mechanisms of F-PW. The mouse model offer several advantages for studying the inflammatory mechanisms of endometrial tissue breakdown and intervention pattern of microenvironment intervening by vagina and uterine local delivery of inhibitors of cascade signaling factors interacting with progesterone receptor in maintaining progesterone .In addition, administration with RNAi or inhibitor in cell culture will provide a model to study the relations among cell apoptosis, progesterone maintaining and NF-κB/TNF-a signal pathway. The combined results from the model and clinical research will provide the basic data/information which may help devise strategies for treating irregular bleeding associated with P-only contraceptives in women.