Hormone Replacement Therapy Trial Halted Because of Cancer, Cardiac Risk

The use of estrogen and progestin in combination is strongly linked to the risk of breast cancer, heart attack, stroke and blood clots, according to U.S. researchers.

The National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) has halted a major clinical trial of combined estrogen and progestin in healthy menopausal women due to an increased risk of invasive breast cancer. The trial also found increases in coronary heart disease, stroke, and pulmonary embolism in women taking the combination therapy.

Approximately 6 million women in the United States are taking estrogen plus progestin for relief of menopausal symptoms or long-term health reasons.

The trial, a component of the Women's Health Initiative (WHI), included 16,608 women ages 50 to 79 who had not had a hysterectomy. The women were given a combination of estrogen and progestin or a placebo. The trial was slated to run 8.5 years, but was halted after 5.2 years.

Researchers found that the combination therapy reduced the women's risk of developing colon cancer and hip fractures, but the harm was greater than the benefit, concluded the NIH. A report on the study was released by the Journal of the American Medical Association in an expedited article due for publication later this month.

"We have long sought the answer to the question: Does postmenopausal hormone therapy prevent heart disease and, if it does, what are the risks? The bottom-line answer from WHI is that this combined form of hormone therapy is unlikely to benefit the heart. The cardiovascular and cancer risks of estrogen plus progestin outweigh any benefits - and a 26 percent increase in breast cancer risk is too high a price to pay, even if there were a heart benefit. Similarly, the risks outweigh the benefits of fewer hip fractures," said Dr. Claude Lenfant, NHLBI Director.

Specific WHI study findings for the combination hormone therapy group compared to placebo include:

• a 41 percent increase in strokes;
• a 29 percent increase in heart attacks;
• a doubling of rates of blood clots;
• a 22 percent increase in total cardiovascular disease;
• a 26 percent increase in breast cancer;
• a 37 percent reduction in cases of colorectal cancer;
• a one-third reduction in the rates of hip fractures;
• a 24 percent reduction in total fractures; and
• no difference in total mortality (from all causes).

In a second study, published in the journal Cancer Epidemiology, Biomarkers and Prevention, investigators reported on a study that analyzed the type and duration of postmenopausal hormone therapy and the risk of breast cancer.

A total of 5,298 postmenopausal women between the ages of 50 to 79 were included in the study. The women all had a new diagnosis of invasive breast cancer. A control group of 5,571 women was also included in the study.

Participants completed a telephone interview covering hormone use and breast cancer risk factors.

Researchers found that the relative risk for breast cancer increased with longer durations of hormone use. The rate was 2.2 percent per year for estrogen alone and 4 percent per year for estrogen-progestin use. Estrogen-progestin use that was both recent and long-term was more strongly linked with the risk of breast cancer than similar use of estrogen alone.

The use of progestin alone was linked with a doubling of risk for breast cancer. Use of estrogen and progestin appeared to be more strongly linked with risk of breast cancer than estrogen alone, concluded the researchers.

Other sources: JAMA, Cancer Epidemiology, Biomarkers and Prevention