Patches and gels are already known to be effective for relieving the hot flashes and sleep-interrupting night sweats that plague many 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 proof yet that this may be true, said Dr. JoAnn Manson, chief of preventive medicine at Harvard-affiliated Brigham and Women's Hospital in Boston. She has no financial ties to hormone drugmakers and just published a book giving women advice on hormone use.
Evidence is mounting that the method of taking a drug and possibly the dose are important factors, she wrote in an editorial accompanying the study in the journal Circulation.
Millions of women abandoned hormone pills after the Women's Health Initiative study reported in 2002 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 UT Southwestern Medical Center.
Hormones through skin patches are directly absorbed 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 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 year after the Women's Health study.
Premarin and Prempro remain top sellers in the United States, according to IMS Health, a drug marketing information firm.
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."
However, some women already have moved to patches.
Barbara Isaac, a research nurse and women's health study coordinator at Albert Einstein College of Medicine, switched to Vivelle, sold by Novogyne Pharmaceuticals, after years of taking Prempro and Premarin.
"It's a tiny little patch. It's the size of a small postage stamp. You put it on your belly and change it twice a week," she said.
Although she is 63 and has used hormones for more than a decade, she is not willing to quit.
"I have a very busy life. My sleep is important to me," she said. Before starting on hormones she had "drenching, drenching sweats — you could just wring me out," she said.
"My doctor who prescribed this for me is 70 or 71 and she still uses it," she added.
Isaac and Manson are helping conduct the Kronos Early Estrogen Prevention Study, or KEEPS, which is directly comparing pills and patches.
Ironically, some hormone patches seem to carry greater risks of blood clots than pills when used for birth control. The FDA recently required new warnings on one such contraceptive patch — Ortho-McNeil Pharmaceutical's Ortho Evra.
Also, women should tell their doctors about any other drugs, vitamins or supplements they are taking. The herbal supplement St. John's wort can decrease blood-estrogen levels, undermining the relief any hormone treatment can give. So can certain antibiotics and other drugs.