Long-term effects of synthetic progestins cause for concern

Published on March 11, 2008 at 3:26 AM · No Comments

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.

It's also a component in Depo/Provera, an injectible long-lasting contraceptive used by many young women. Millions of women use various hormone therapies with a variety of progestin types for contraception. In the U.S. alone, 80 percent of women have used oral contraceptives.

The UO study, appearing online ahead of regular publication by the journal Heart and Circulatory Physiology, is among the first to focus on the impact of MPA in premenopausal women. Fourteen women, 19-27 years old, took part in the study after passing thorough medical exams to screen out numerous health conditions.

The five-member UO team -- led by Jessica R. Meendering, a former UO doctoral student now a professor of exercise science at the University of Nebraska in Omaha -- studied the effects of the sex hormone estradiol by itself and in combination with MPA on endothelial function of the brachial artery. The health of the endothelium in this artery has been shown to be a telling proxy for the coronary arteries and a good predictor of cardiovascular risk.

When researchers gave an oral version of MPA to determine its impact, they found that it wiped out the positive effects on endothelial function that estradiol had provided. MPA reduced the function by reducing the brachial artery's ability to dilate -- grow bigger in diameter -- in response to the stress of changing blood flow, Kaplan said.

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