Effects of Statins on Endometrium

Principal Investigator: Professor Antoni Duleba, M.D.
Funding for the project: National Institute of Health, U54 with Yale University

Endometriosis is defined as the presence of endometrial stroma-like and endometrial gland-like tissues outside the uterus. It is one of the most common benign gynecologic conditions affecting women of reproductive age and is associated with chronic pelvic pain and infertlility. Formation of endometriotic implants requires ectopic attachment and proliferation of endometrial tissues. Prominent features of endometriosis include inflammatory reaction and increased oxidative stress. Growing evidence indicates that the invasive process of attachment of endometrial tissues may involve matrix metalproteinases (MMPs), especially MMP-3. We have shown that proliferation of endometrial stroma is stimulated by moderate oxidative stress, but inhibited by antioxidants. Statins are inhibitors of 3-hydroxy-3methylglutaryl-coenzyme A (HMG-CoA) with intrinsic antioxidant activity. In our preliminary studies we found that statins inhibit proliferation of endometrial stroma and decrease expression of MMP-3 in a concentration-dependent fashion. Most importantly, we also found that statin induces a dose-dependent inhibition of development of endometriosis in a nude mouse model.

The specific aims of this project are: evaluation of effects of statins on growth and oxidative stress: (i) in endometrial stromal cells and (ii) in endometriotic implants in a nude mouse model. These studies will provide new insight into the mechanisms regulating growth and function of endometrial tissues and development of novel treatments of endometriosis.