Breast cancer risk unaffected: increase in stroke risk halts WHI estrogen-only arm; Data not fully analyzed; experts say no need to change clinical practice yet.

The National Institutes of Health has discontinued the estrogen-only arm of its Women's Health Initiative study 1 year early, citing an increase in the risk of stroke in women taking the study medication.

Although the full results have not yet been released, the NIH said the increase was comparable to the 41% increased relative risk of stroke observed in the WHI combination hormone therapy (HT) arm (29 strokes per year vs. 21 per year for women on placebo). The strokes in the estrogen-only arm occurred over a range of ages--a pattern also seen in the combination HT study, which was also halted early, in 2002.

The use of estrogen only was associated with a decrease in the risk of hip fracture, but that protective effect was not deemed robust enough to balance the increased risk of stroke. Estrogen alone was not associated with an increase in the risk of breast cancer. And similar to the findings of the combination HT arm, the estrogen-only study found no evidence of a protective effect on heart disease.

Given the small size of the increased stroke risk, and the fact that the data have not been fully analyzed, physicians should not make any changes in their clinical practice yet, said Dr. Barbara Alving, director of the WHI.

New practice guidelines may emerge after the results are published; however, estrogen is still the treatment of choice for acute symptoms of menopause, and should be used at the lowest effective dosage for the shortest possible time, as currently recommended by the Food and Drug Administration, she said.

"These data simply tell us that we should not be prescribing estrogen for prevention of long-term chronic disease," Dr. Alving said. "There are other drugs that protect us against heart disease and osteoporosis; if a woman at risk for osteoporosis can't take those other drugs, she can consider estrogen."

The WHI estrogen-alone study included nearly 11,000 women with a prior hysterectomy who were aged 50-79 years at the start of the trial; they were followed for 7 years. It was designed to discover whether estrogen prevents heart disease in healthy older women. Protection against hip fractures was the major secondary outcome, and breast cancer the major possible risk.