Public release date: 9-Mar-2008

The widely used synthetic progestin medroxyprogesterone acetate (MPA) decreased endothelial function in premenopausal women in a study done at the University of Oregon. The finding, researchers said, raises concerns about long-term effects of MPA and possibly other synthetic hormones on vascular health in young women.

The vascular endothelium lines the inside of blood vessels. In recent years, it has been found to be a dynamic organ that serves an important role in the prevention of atherosclerosis.

“The logical conclusion of this study is that over a long period of time it would not be good to have exposure to an agent that is reducing blood vessel flexibility, because it could be associated with the development of heart disease or related problems,” said co-author Dr. Paul F. Kaplan, a long-time Eugene gynecologist and senior researcher in the UO’s human physiology department. He stressed, however, that a longer, larger study is needed.

MPA is the progestin that was used in the Women’s Health Initiative (WHI), including a clinical study on hormone-replacement therapy halted because of health concerns in postmenopausal women. MPA is the active ingredient of Provera, which is used to treat abnormal uterine bleeding, induce menstrual cycles and relieve symptoms of the menopause.

UO researchers also found that MPA had an effect on concentrations of endothelin-1, a peptide that promotes cell division and serves as a mediator of inflammation. It also acts as a constricting factor for blood vessels. When peptide levels rise, endothelin-1 is suspected to play a key role in many diseases of the airways, pulmonary circulation, inflammatory lung diseases and vasoconstriction of blood vessels. UO researchers saw levels decline with estradiol alone, but increase substantially with the addition of MPA, negating the benefits of the estrogen.

Kaplan stressed that this project was a starting point of “major basic science research, so this study does not say women should change what they are doing.”

“We can say that we saw vascular changes in the arteries of the arm that have been shown in previous studies involving coronary arteries,” he added. “This study does let us say that whatever changes we are seeing are important not just for the arm but probably for most of the major arteries in the body, and this is important for cardiac disease.”