A study of hormone use in nearly 700,000 Danish women over 50 suggests that when it comes to heart attack risk, patches or gels are safer than the combination pills most American women use.

The authors say this is the largest postmenopausal hormones study since the Women's Health Initiative, which randomly assigned 27,000 U.S. women to estrogen or estrogen-plus-progestin pills or to a placebo.

The estrogen-plus-progestin arm found the hormones raised women's heart attack risk, while the estrogen-only found no effect on heart attack risk. Initial findings were reported in 2002 and 2004, respectively.

In the new study, published in the European Heart Journal, researchers used national registries of prescription use and heart attacks to follow all healthy Danish women ages 51-69 from 1995 to 2001.

Overall, they found no effect of hormone use on heart attack risk. But they did find that women who took estrogen-plus-progestin pills had a 35% higher heart attack risk, similar to the Women's Health Initiative finding.

Lead author Ellen Løkkegaard, a gynecologist at Copenhagen's Rigshospitalet, believes her findings about other hormone treatments not covered in the U.S. study are valid.

"The only piece of good news, potentially, is they show a reduced risk in users of non-oral therapies," says the National Heart, Lung, and Blood Institute's Jacques Rossouw, a lead scientist for the Women's Health Initiative.

Patches and gels don't appear to have the same effect on blood-clotting or inflammation as hormone pills, he says.

The new study also suggests that taking estrogen every day but progestin only certain days of the month, which causes monthly vaginal bleeding, is safer on the heart than taking estrogen and progestin every day.

Although Løkkegaard's study overall found no increased heart attack risk in hormone users, it did find that those 51-54 did have a 25% higher risk. The increase might have been because some non-users in that group weren't yet postmenopausal, Løkkegaard says, and naturally have a lower heart disease risk than post-menopausal peers taking hormones.

She says she and her collaborators also have analyzed postmenopausal hormones and breast cancer risk but have not yet reported the findings.