New wrinkle in hormone debate

For women who have struggled with the symptoms of menopause but are fearful of taking risky hormone pills, there is at last a bit of hope.

Hormone skin patches and gels are far less likely than pills to cause dangerous blood clots, according to a recently published French study.

Patches and gels are already known to be effective for relieving the hot flashes and sleep-interrupting night sweats that plague many menopausal women. No one knows whether they will prove safer than pills in terms of breast cancer, heart attack or stroke risk; a large study currently under way may answer that.

But if they do, it may soften some of the backlash against hormones since a landmark study in 2002 frightened many women away from their use. Critics of that study have long contended that it is the type of estrogen or progestin, the dosage and the method of taking the hormones that may affect the health risks.

The French study, while not the final word, is the strongest evidence yet that this may be true, Dr. JoAnn Manson, chief of preventive medicine at Harvard-affiliated Brigham and Women's Hospital in Boston, wrote in an editorial accompanying the study in the journal Circulation.

Millions of women abandoned hormone pills after the Women's Health Initiative study in 2002 reported higher rates of stroke among those taking estrogen, and of stroke and breast cancer with estrogen-progestin use.

The study tested Wyeth's Prempro and Premarin, which contain synthetic estrogens made from the urine of pregnant horses. Some people believe that estrogens from plant sources are closer to what the human body naturally produces and may be safer. The plant forms are in many competitors' pills and also in patches, creams and gels.

The French researchers compared 271 women ages 45 to 70 who suffered blood clots to 610 similar women without clots. Women taking various hormone pills were more than four times more likely to suffer clots than women not taking hormones or receiving them through patches, gels or creams.

The study was paid for by the French government and partly by hormone drug and patch makers.

Why the difference in risk?

"Part of the reason we think oral estrogens do cause clots is that they pass through the liver and can cause some clotting factors to be produced," said Dr. Karen Bradshaw, director of women's health and an endocrinology specialist at the University of Texas Southwestern Medical Center in Dallas.

Hormones in skin patches are absorbed directly into the bloodstream, and therefore can be given in far lower doses to be effective, she explained.

"This study, like others, may change things" in terms of what hormones women and doctors are willing to use, Bradshaw said. Before the Women's Health Initiative study, Prempro and Premarin accounted for half of the hormones she prescribed. Now they account for about one-fourth, and much of that is the lower dose of Prempro that Wyeth began selling in 2003.

A Wyeth physician, Dr. Eileen Helzner, noted that the French study did not randomly assign some women to get patches and some to get pills — the most rigorous scientific test. At least two previous, smaller studies reached differing conclusions on the clot risk, and more research is needed before definitive conclusions can be made, she said.

She also noted that the federal Food and Drug Administration has not changed its Internet advice that all forms of hormone therapy "have the same risk profile."

Another study under way — the Kronos Early Estrogen Prevention Study, or KEEPS — is directly comparing pills and patches. The University of Washington Medical Center is one of nine centers taking part in the study.