US estrogen plus progestin HRT trial stopped due to increased risk of breast cancer, stroke and heart attack

A major trial of the risks and benefits of combined estrogen and progestin in healthy menopausal women has been stopped because long-term use increases the risk of breast cancer by 26%, stroke by 41% and heart attacks by 29%.

The multicentre, Women's Health Initiative (WHI) trial was stopped July 9 by the National Heart, Lung, and Blood Institute (NHLBI) and the National Institutes of Health. An estimated 6 million postmenopausal American women take estrogen plus progestin hormone replacement therapy.

“The details of these results are of tremendous importance and will certainly influence medical practice for years to come,” Dr. Claude Lenfant, director of the NHLBI, said at a July 9 news conference.

Study participants also had a statistically significant increase in coronary heart disease, stroke and pulmonary embolism. There were benefits to the combined hormone therapy, including fewer cases of hip fractures and colon cancer, but on balance the harms were greater.

The report from the WHI investigators appeared in the July 17 issue of the Journal of the American Medical Association (JAMA). The 8-year study was scheduled to run until 2005 but ended after an average follow-up of 5.2 years. The trial, involving 16 608 women age 50 to 79, was designed to examine the effect of estrogen plus progestin on the prevention of heart disease and hip fractures, and any associated change in risk for breast and colon cancer. Study participants were randomly assigned a daily dose of estrogen plus progestin, or placebo.

In 2000 and again in 2001, WHI investigators, in compliance with a recommendation from the study's Data and Safety Monitoring Board, informed participants of a small increase in heart attacks, strokes and blood clots among women taking the hormones. The board recommended stopping the trial on May 31.

Study findings for the estrogen plus progestin group compared to placebo include:

· 41% increase in strokes

· 29% increase in heart attacks

· doubling of rates of venous thromboembolism

· 22% increase in total cardiovascular disease

· 26% increase in breast cancer

· 37% reduction in cases of colorectal cancer

· 33% reduction in hip fractures

· 24% reduction in total fractures

· no difference in total mortality (all causes).

— Barbara Sibbald, CMAJ