BOSTON - For older women, the difficult question of whether to take estrogen for the rest of their lives has grown even more complicated.
On Wednesday, researchers reported new evidence that estrogen supplements after menopause may cut the risk of Alzheimer's disease in half. On Thursday, another study is coming out suggesting that long-term use increases the risk of dying from breast cancer by nearly the same amount.
Women often take estrogen for a couple of years to ease the hot flashes and other symptoms of menopause, and there is little doubt about the safety of this limited use.
More controversial, however, is the idea that women should keep on taking the pills because of estrogen's other well-known benefits: It clearly protects the heart and keeps bones from growing brittle, and might also ward off Alzheimer's.
Estrogen also increases the risk of breast cancer, although by just how much has been unclear. Nevertheless, since heart disease is so much more common than breast cancer in older women, many doctors and their patients assumed that the benefits far outweighed the risks.
The latest study, published in Thursday's issue of the New England Journal of medicine, attempted to see what estrogen supplements do to women's risk of death. It is the first to assess how this risk changes over time.
Like other studies, it found that estrogen dramatically reduces older women's risk of dying from a heart attack. But it found that the risk of breast cancer gradually increases. And after a decade of use, the increasing cancer deaths begin to wipe out the advantages of avoiding heart trouble.
Researchers say these studies emphasize the need for making the decision about long-term estrogen on a person-by-person basis, taking into consideration each woman's risk of heart trouble, breast cancer and other diseases.
Estrogen after menopause "is being increasingly prescribed for long-term use to prevent heart disease and osteoporosis. Based on the uncertainty of the balance of benefits and risks, that should be done only with caution and not routinely," said Dr. JoAnn Manson, one of the researchers at Boston's Brigham and Women's Hospital.
Nearly 9 million American women take Premarin, Wyeth-Ayerst Laboratories' brand of post-menopausal estrogen. It is the nation's most widely prescribed medicine.
The Boston study involves 121,700 women in the Nurses Health Study, including 3,637 who died during 26 years of follow-up.
It found that the risk of dying from any cause was 45 percent lower than expected among nurses who took estrogen supplements for less than five years. Between five and 10 years of use, the risk was 40 percent lower.
However, after more than 10 years on estrogen, the risk of death was just 20 percent lower. This is because these women's risk of dying from breast cancer was 45 percent higher than nonusers'.
The Alzheimer's study, conducted by Dr. Claudia Kawas and others from Johns Hopkins University and published in the June issue of Neurology, found that women who took estrogen had a 54 percent reduction in their risk of the disease.
Dr. Francine Grodstein, who directed the Boston study, noted that only women already at risk for heart disease live significantly longer as a result of the hormone pills. These include women with diabetes, high blood pressure or high cholesterol, or who smoke or have a strong family history of heart problems.
The study suggests that for those with a high risk of heart disease, long-term use of estrogen may be worthwhile. But for women with an elevated risk of breast cancer, the benefits are less clear, especially if they have healthy hearts.
Risks factors for breast cancer include a mother or sister with the disease, having puberty at an early age or having children late in life or not at all.
"It's still a hard decision, but a woman needs to consider her own risk factors," Grodstein said.
Dr. Nananda Col of New England Medical Center in Boston noted that even though the mortality advantage shrank to 20 percent after 10 years of estrogen use, "that really is a huge benefit."
"Does this mean women should stop therapy after 10 years? No," she said.
Certainly, delaying death is not the only reason to take estrogen. Alzheimer's disease and osteoporosis clearly diminish the quality of women's lives, as does treatment for breast cancer or living with heart disease.
Even though the study is probably the most careful look yet at estrogen's risks and benefits, it does not settle the question. Some wonder whether women who choose to take estrogen are already healthier than non-users, and perhaps this explains why they live longer.
One attempt to provide a clearer answer is the Women's Health Initiative, which is randomly assigning 27,500 women to take estrogen alone, estrogen plus progestin, or dummy pills. The results are expected in about eight years.
Breast cancer kills about 43,000 U.S. women a year, compared with 233,000 for heart disease.