A new British study sounds an alarm for some women who use the injectable contraceptive Depo-Provera.
The alert applies only to women at increased risk of cardiovascular disease because of a risk factor such as diabetes, high cholesterol or a family history of heart disease, says Dr. Dudley J. Pennell, leader of the study. Even those women could still go on using the contraceptive, with some adjustments, he says.
However, a warning is needed because the study shows that Depo-Provera can reduce the ability of arteries to widen, so that they might not respond to a need for increased blood flow, says Pennell, a professor of cardiology at the Imperial College School of Medicine in London. That failure could result in a blockage that would cause a heart attack, he adds.
His study contradicts the conventional wisdom that Depo-Provera is safer than other contraceptives for women at increased risk of heart disease.
Pharmacia, the company that markets Depo-Provera, says the study does not contradict existing evidence that the drug is safe.
It has “a well-proven safety profile,” says Dr. Joel Krasnow, medical director of the Pharmacia Women’s Healthcare division. In both a World Health Organization ( news – web sites) study of 15,000 users and a U.S. trial including 775 users, “no cases of thrombolytic disease, heart attack, or stroke were reported,” Krasnow says.
Pennell says he investigated the effect of Depo-Provera on the arteries because it acts by blocking the hormonal signals that cause ovulation, which means that it lowers blood levels of the estrogen hormone estriadol. That hormone acts on the endothelium, the sensitive layer of cells that line the inner artery walls.
“Endothelial cells operate to make arteries bigger and smaller, particularly to make them get bigger, or dilate,” Pennell says. “When arteries can dilate, they are healthy. When they cannot dilate, they are not.”
Pennell’s study, reported in today’s issue of Circulation, included a small group of women — 12 who were taking Depo-Provera and nine who were not. He used a technique called magnetic resonance imaging (MRI) to measure the flexibility of the brachial artery, the artery in the arm where blood pressure usually is measured.
The nine non-users were tested during menstruation, when circulating levels of estriadol are low, and during ovulation, when levels are high. The 12 users were measured 48 hours after they had an injection of Depo-Provera, which is done every three months for contraception, and three months after their last injection.
Tests showed the ability of the arteries to dilate was reduced substantially in the Depo-Provera users. Their arteries dilated an average of 1.1 percent after a temporary blockage with a blood pressure cuff, compared to 8 percent dilation in the non-users.
“Two recent studies suggest that persons with reduced endothelial function are at greater risk of cardiovascular disease,” Pennell says. “At this stage of our understanding, it is a very reasonable conclusion that if you have a drug that causes endothelial dysfunction, it doesn’t make sense to give it to women with risk factors for cardiovascular disease.”
That conclusion applies only to women with known risk factors, Pennell emphasizes. “If you are a young person taking Depo-Provera and have no risk factors, there is no reason to worry,” he says. “Continue as you are. But if you are on it because your doctor feels it is safer for you because you have cardiovascular risk factors, it might not be good for you.”
He suggests that “if you are a long-term user of this drug — the women in our study averaged four years of use — and you have risk factors for heart disease, it is sensible to discuss your options with your physician.”
One option is to switch temporarily to a barrier contraceptive device, such as an IUD, Pennell says. “Or you could use a barrier method completely,” he says. “Or you could from time to time switch from Depo-Provera to a combined pill. It has estrogen that will help return the endothelium to normal function.”
He has one final word: “There is absolutely no reason to panic. But a woman who is a long-term user of Depo-Provera and has cardiovascular risk factors should make an appointment to see her physician, with no rush, to discuss her options.”
Pharmacia’s Krasnow notes that Pennell and his colleagues “studied a small, non-randomized sample of users” and that “the authors clearly state that they cannot determine the clinical impact on cardiovascular events from this study.” He adds that “health-care providers must carefully consider any medication, including Depo-Provera, before prescribing, particularly for women with pre-existing cardiac risk factors.”