Popular Long-Acting Contraceptive Linked to Vascular Dysfunction

Long-term use of a contraceptive injected once every three months impairs the arteries' ability to contract and expand, possibly increasing the risk for heart disease, according to research reported in today's rapid access issue of Circulation: Journal of the American Heart Association.

Researchers studied depot medroxyprogesterone acetate (DMPA), commonly known by the brand name Depo-Provera. The drug affects the arteries' ability to "respond to different stimuli and particularly affects the ability of the artery to dilate," says senior author, Dudley J. Pennell, M.D., a professor of cardiology at the Imperial College School of Medicine in London. Problems with arterial response can reduce blood flow, which can damage the heart.

DMPA had been considered a good drug for women who may have some cardiac risk factors such as smoking or high blood pressure or a family history of heart disease, Pennell says. But the new findings suggest that women with cardiovascular disease risk factors "would be wise to review that decision with their physician."

Pennell and colleagues measured vascular function in women who used DMPA for at least a year and compared the results to those of women who didn't use DMPA. They evaluated vascular function by measuring changes in the brachial artery (the artery in the arm where blood pressure is usually measured) using cardiovascular magnetic resonance imaging (CMR).

Twelve women taking DMPA and nine controls completed two brachial artery evaluations by CMR. Researchers evaluated the DMPA group at the end of a three-month DMPA cycle and within 48 hours of a new DMPA injection. They evaluated controls during the first 1-3 days of a menstrual cycle and again when the women were ovulating.

DMPA blocks hormonal signals that activate ovulation, so women using DMPA have very low circulating levels of estradiol, the estrogen produced by ovaries. In the controls, CMR studies were done when circulating levels of estradiol would be lowest (during menstruation) and highest (during ovulation). The DMPA women were evaluated when the estrogen-blocking contraceptive would be at its lowest and highest concentrations in the blood.

Flow-mediated dilatation -- an indicator of endothelial function -- was significantly reduced in the DMPA users: 1.1 percent compared to 8.0 percent in the non users during menstruation.

Estrogen affects the blood vessels' ability to constrict, and this study found that low levels of circulating estradiol correlated with decreased flow-mediated dilatation in both groups of women.

However, DMPA is an effective contraceptive that can be safely used by women who are otherwise healthy and who have no cardiovascular risk factors, Pennell says. DMPA is a very effective birth control method for women who have limited access to health care or for women who have difficulty complying with oral birth control regimens or barrier contraceptives.This research was sponsored by CORDA, The Heart Charity.

Co-authors are Morten B. Sorensen, Ph.D.; Peter Collins, M.D.; Paul J. L. Ong, M.A.; Carolyn M. Webb, Ph.D.; Christopher S. Hayward, M.D.; Elizabeth A. Asbury, M.Sc.; Peter D. Gatehouse, Ph.D.; Andrew G. Elkington, M.B., B.S.; Guang Z. Yang, Ph.D.; and Ali Kubba, M.D., Ch.B.