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New results from the Women's Health Initiative document that several of the health risks and benefits of combined menopausal hormone therapy go away within three years. However, some health risks of long-term estrogen plus progestin use persist, even a few years after stopping the drugs, and clearly outweigh the benefits.
Results of the WHI three-year follow-up study of the estrogen-plus progestin clinical trial appear in the March 5 issue of the Journal of the American Medical Association.
The WHI trial of estrogen plus progestin assessed whether conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) prevents heart disease and hip fractures and increases the 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. The trial showed that women in the CEE plus MPA group had higher risks of coronary heart disease, stroke and venous thromboembolism and lower risks of fracture and colorectal cancer.
Dr. Gerado Heiss, of the University of North Carolina, Chapel Hill, N.C., and colleagues, including the Public Health Sciences Division’s Dr. Garnet Anderson examined the risks and benefits experienced by 15,730 trial participants after they stopped hormone therapy.
“At this point, it appears that both the adverse effects on cardiovascular diseases and the benefits for fractures and colorectal cancer have dissipated," Anderson said. "Breast cancer and total cancer rates are still somewhat elevated and for the first time we are seeing some suggestion that mortality rates may be slightly increased. Cancer deaths seem to account for most of this difference. While these data do not change the overall guidelines for use of these medicines, they do reinforce the importance of continued vigilance in breast screening for women who have used them in the recent past.”
The follow-up study began in July 2002 and continued through March 2005, with participants followed for an average of 2.4 years. All study participants had an annual WHI clinic visit and received an annual breast examination and mammogram.
In contrast to the other effects, the risk of breast cancer continued at a rate similar to that seen during treatment. Women who had been randomized to the estrogen-plus progestin group were about 27 percent more likely to develop breast cancer than the women who had been randomized to placebo, with 79 women in the post-treatment group developing breast cancer during the three-year follow-up study, compared to 60 women in the non-treatment group.
Researchers also report a 24 percent increased risk of developing any form of cancer among women who had been in the treatment group. Overall, there were 63 more diagnoses of cancer during the follow-up study, or three per 1,000 participants per year, among women who had taken combination hormone therapy compared to women who did not take hormones during the study (281 diagnoses compared to 218). A more detailed analysis of the cancer findings is under way.
The study also found that other effects of combination hormones, such as decreased risk of colorectal cancer and hip fractures, stopped when therapy ended.
The Food and Drug Administration recommends that hormone therapy never be used to prevent heart disease, and, when hormone therapy is used for menopausal symptoms, it should only be taken at the smallest dose and for the shortest time possible.
The National Heart, Lung and Blood Institute of the National Institutes of Health funded the study, which involved researchers from dozens of institutions nationwide. In addition to Anderson, co-authors from the Hutchinson Center were Drs. Andrea LaCroix, Ross Prentice, Shirley Beresford, and WHI statistician Aaron Aragaki.
[Article adapted from news releases from the National Institutes of Health and JAMA.]