Progesterone Resistance and Endometrial Disease

Serdar E. Bulun, M.D.

Progesterone action in uterine tissue is essential for implantation of an embryo and maintenance of pregnancy. Several articles in this issue cover cellular and molecular aspects of progesterone action in endometrium.

Progesterone resistance is an evolving concept. The ultimate proof for progesterone resistance would be the demonstration of a disrupting mutation of the progesterone receptor in a woman. Based on progesterone receptor knockout studies in female mice, the expected human phenotype would involve pathologies related to uterine and breast tissue. Such a case has not been described to date. Many investigators in endometrial research, however, observed various molecular and possibly clinical manifestations of defective progesterone action in endometrial or endometriotic tissue in many women with endometriosis. This led to the concept of “functional progesterone resistance” in eutopic and ectopic endometrial tissues of these women. We made an attempt to include most if not all of these investigators to contribute to this issue as authors.

It is also plausible to hypothesize that defective progesterone action might be associated with an increased risk of developing endometrial malignancy. After all, progesterone action is inevitable to prevent the development of estrogen-dependent endometrial cancer. Thus we included an article that discusses the possible roles of deficient progesterone action in endometrial malignancy. We hope this issue will serve as an up-to-date document that reflects the progress made in the field of progesterone action and resistance during the past 5 to 10 years.