Even short-term combined hormone therapy use presents risks

Combined hormone therapy appears to increase the risk that women will have abnormal mammograms and breast biopsies and may decrease the effectiveness of both methods for detecting breast cancer, according to a report in the Feb. 25 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

“This study provides additional information for women on the health effects of combined hormone therapy. The increased risk of abnormal mammograms and breast biopsies can affect women economically and emotionally,” said co-author Dr. Anne McTiernan.

Dr. Rowan Chlebowski, of the Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center, and colleagues, including McTiernan and co-authors Drs. Garnet Anderson, Chu Chen, all of the Public Health Sciences Division, studied 16,608 post-menopausal women who participated in the Women’s Health Initiative clinical trial, beginning in 1993 through 1998.

The researchers randomly assigned 8,506 women to receive a combination of estrogen (0.625 milligrams of conjugated equine estrogens per day) plus progesterone (2.5 milligrams of medroxyprogesterone acetate per day), while 8,102 took a placebo. Each woman received a mammogram and breast examination yearly, with biopsies performed based on physicians’ clinical judgment.

During the 5.6 years of the study, 199 women in the combined hormone group and 150 women in the placebo group developed breast cancer. Mammograms with abnormal results were more common among women taking hormones than among women taking placebo (35 percent vs. 23 percent); women taking hormones had a 4 percent greater risk of having a mammogram with abnormalities after one year and an 11 percent greater risk after five years.

Breast biopsies also were more common among women taking hormones than among those assigned to placebo (10 percent vs. 6.1 percent). “Although breast cancers were significantly increased and were diagnosed at higher stages in the combined hormone group, biopsies in that group less frequently diagnosed cancer (14.8 percent vs. 19.6 percent),” the authors said.

“The effects of combined hormone therapy on abnormal mammograms and breast biopsies were reduced somewhat after stopping hormone therapy, but continued for at least 12 months after stopping therapy,” McTiernan said.

Use of combined hormones increases breast density, which increases the risk of breast cancer and may delay diagnosis, the authors note. However, researchers did not measure breast density in the current study.

“Use of conjugated equine estrogens plus medroxyprogesterone acetate for approximately five years resulted in more than one in 10 and one in 25 women having otherwise avoidable mammogram abnormalities and breast biopsies, respectively, and compromised the diagnostic performance of both,” the authors conclude. They suggest that doctors incorporate information about this adverse effect on breast-cancer detection into risk-benefit discussions with women considering even short-term combined hormone therapy.

[This article was adapted from a news release from JAMA, The Journal of the American Medical Association.]