Hormone replacement takes more hits. (Flawed Therapy).

Expectations for hormone-replacement therapy for postmenopausal women have turned topsy-turvy in recent years. Initial studies suggesting remarkable benefits from the drugs gave way to reports of little gain. Most recently, the rap sheet on estrogen and progestin includes signs of harm.

The latest bad news for the treatment appears in two articles in the May 28 Journal of the American Medical Association, where scientists report that the hormone combination boosts the risk of dementia and stroke in otherwise healthy women. Another recent report challenges the view that the therapy increases women's feelings of well-being,

The findings all stem from the Women's Health Initiative, a nationwide study that began in the early 1990s and enrolled more than 27,000 women in its hormone-replacement component. In 2002, researchers stopped part of this component, 3 years before its scheduled conclusion, because interim results showed that postmenopausal women taking estrogen-progestin supplements had a greater risk of circulatory disorders, breast cancer, and stroke than women getting inert pills did (SN: 7/27/02, p. 61).

During the study, the scientists had monitored a subgroup of 4,532 healthy women over age 65 for signs of dementia. The researchers had randomly assigned participants to receive hormones or placebos. Over 5 years, 40 women getting hormones were diagnosed with Alzheimer's disease or other dementia, compared with only 21 getting a placebo, coauthor Sally A. Shumaker of Wake Forest University in Winston-Salem, N.C., now reports. That the half receiving hormones actually had greater incidence of dementia came as a surprise because earlier research had suggested the opposite (SN: 2/17/01, p. 110).

"The risk for any individual remains low," says Judith A. Salerno of the National Institute on Aging in Bethesda, Md. However, she says, "we had hoped [hormones] would be a good intervention for the prevention of dementia and other cognitive decline, and this isn't what the study found."

The analysis of stroke included 16,608 postmenopausal women from the nationwide study. Sylvia Wassertheil-Smoller of Albert Einstein College of Medicine in New York and her colleagues report that 1.8 percent of women getting hormones and 1.3 percent of those taking a placebo had had strokes after nearly 6 years in the trial. The findings bolster early results from the study (SN: 7/27/02, p. 61).

Researchers continue to monitor the women taken off the hormones at the study's termination to see whether their risk of dementia, stroke, or other problems diminishes, Shumaker says.

Scientists don't know whether estrogen, progestin, or the combination contributes to the higher risk for these ailments. A separate and continuing portion of the study, involving only women who had a hysterectomy and are receiving just estrogen or a placebo, may shed light on that, says Salerno.

While hormone-replacement therapy was originally prescribed to alleviate menopausal symptoms such as hot flashes, many women reported that the drugs improved their general feeling of well-being. Even that notion took a hit in another study released this month. Jennifer Hays of the Baylor College of Medicine in Houston and her colleagues report in the May 8 New England Journal of Medicine that postmenopausal women on hormones have no better vitality, mental health, or sexual satisfaction than women not taking the drugs do.

Shumaker suggests that many quality-of-life benefits in previous hormone studies may be attributable to a placebo effect. Meanwhile, scientists are continuing to investigate two potential benefits of hormone therapy that still appear to hold--gains in bone density and decreased colorectal cancer risk.