Follow-up data from the Women's Health Initiative Trial show that postmenopausal women who stop estrogen/progestin replacement therapy may have an increased risk for cancer for at least several years afterward, according to an article in the March 5 issue of the Journal of the American Medical Association.

The Women's Health Initiative trial of estrogen plus progestin, which included 16,608 postmenopausal women, assessed whether conjugated equine estrogens plus medroxyprogesterone acetate prevents heart disease and hip fractures and increases risk of breast cancer. The trial was stopped in 2002 when data indicated an increased risk of breast cancer and a failure to demonstrate an overall health benefit of the therapy.

Cardiovascular disease and fracture risks were similar between groups, but women who took hormone therapy had an overall higher global risk index reflecting the balance of risks and benefits from a number of endpoints combined, including deaths.

Gerardo Heiss, MD, of the University of North Carolina, Chapel Hill, and colleagues examined the risks and benefits experienced by 15,730 trial participants who had follow-up from July 2002 to March 2005, after they stopped hormone therapy.

The researchers found that the annualized event rates for the outcome "all cancer" was higher during postintervention follow-up for hormone therapy (1.56 percent per year; 281 women) than for placebo (1.26 percent per year; 218 women). This reflected greater risk of invasive breast cancer and other cancers with hormone therapy; rates of colorectal cancer did not differ significantly between groups; rates of endometrial cancer were lower in the hormone therapy group. Although risk of breast cancer remained elevated during follow-up, risk was less than that experienced toward the end of the trial period.

During the postintervention phase, the rate of death from all causes was higher by 15 percent in the group originally assigned to hormone therapy than in those assigned to placebo, but the difference was not statistically significant.

A summary of the risks and benefits, the global index, included outcomes for coronary heart disease, invasive breast cancer, stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture and death due to other causes. The researchers found that this measure was 12 percent higher in women randomly assigned to receive combination hormone therapy compared with placebo and did not materially change after intervention was stopped.