Women who once used hormone replacement therapy may still have an increased risk of cancer years after they stop taking the drugs, finds a new study.

But the good news is that the risks of heart disease, stroke and blood clots in those women fall after the drugs are stopped.

The findings come from a follow-up look at the women who participated in the Women's Health Initiative. The WHI is an ongoing, 15-year project involving over 161,000 postmenopausal women, and is considered one of the most far-reaching studies on women's health ever undertaken in the U.S.

The HRT wing of the study involved 16,608 healthy postmenopausal women who took a combination of estrogen plus progestin. The study was originally designed to look at what effect HRT would have on the women's risks for cardiovascular disease, cancer and fractures.

Women in the study were randomly assigned to receive a combination of estrogen (0.625 milligrams of conjugated equine estrogens per day) plus progestin (2.5 mg of medroxyprogesterone acetate), or placebo.

The trial was abruptly stopped in July 2002, after researchers discovered a disturbing increase in the risk of breast cancer and cardiovascular disease in those women taking hormone therapy compared with those who received a placebo.

Researchers, led by Dr. Gerardo Heiss, a professor of epidemiology in the University of North Carolina School of Public Health, have been continuing to monitor the health of those women ever since.

This latest report, published in the Journal of the American Medical Association, looked at how the women fared during the first three years after the study was stopped.

They found that the yearly rates for all cancers were still higher among the women who had been on HRT compared to the placebo group -- (281 diagnoses compared to 218).

Women who had stopped HRT were about 27 per cent more likely to develop breast cancer than the women who didn't take hormones during the study, with 79 women in the HRT group developing breast cancer during the three-year follow-up, compared to 60 women in the placebo group.

The finding suggests that the hormones' effects on breast cancer appear to linger. But although the risk of breast cancer remained higher in those three years, the risk was at least lower than the cancer rates the researchers noted towards the end of the WHI study.

Still, the results were surprising to Heiss, who expected cancer rates among the women to drop off shortly after hormone therapy was stopped.

"The WHI investigators did not expect to find an increased overall risk of cancer after stopping the estrogen plus progestin," Heiss said.

"The increased risk is small, but the follow-up did indicate there are higher levels of breast cancer, lung cancer, stroke and death among those who had taken this therapy."

Heiss says his findings suggest that women who once took estrogen-progestin HRT should work to control their other risk factors for cancer, such as obesity, smoking and alcohol intake. As well, they should be closely screened for cancer as recommended by health care practitioners.

"This is good advice for everyone though, whether they have taken estrogen plus progestin for 3.5 to 8.5 years -- as in this study -- or not," Heiss notes.

The researchers also found that the risk of heart attacks and stroke events was comparable between the two groups during the three years after the women stopped taking the drugs, suggesting that the increased cardiovascular risks seen during the trial period weakened after the trial was stopped.

As well, the researchers found:

  • The rates of colorectal cancer did not differ significantly between the two groups, suggesting that the decreased risk of colorectal cancer seen during the study faded when therapy ended
  • The rates of endometrial cancer were lower in the estrogen plus progestin group
  • The risk of osteoporosis-related fractures was similar among women in both groups
  • The number of deaths was not significantly different (233 women who had been in the HRT group died, versus 196 women in the placebo group)

Dr. Elizabeth G. Nabel, director of the National Heart, Lung, and Blood Institute, which sponsored the WHI study, says this study is further proof that the risks of combination HRT outweigh the benefits.

"Today's report confirms the study's primary conclusion that combination hormone therapy should not be used to prevent disease in healthy, postmenopausal women," she says. 

The current recommendations on HRT state that it should be used for menopausal symptoms, not to prevent heart disease, and should only be taken at the smallest dose and for the shortest time possible.