Before 2002, physicians commonly prescribed hormone replacement therapy (HRT) to postmenopausal women for a variety of reasons, including relieving menopausal symptoms and decreasing osteoporosis risk. In May 2002, however, the Women’s Health Initiative study of HRT in postmenopausal women (WHI) was stopped early because investigators found that HRT may increase the risk of breast cancer , heart disease , stroke , and blood clots . At the time of the study, more than six million U.S. women were taking HRT.

Now physicians carefully weigh the benefits versus the risks of taking HRT before prescribing it to their patients. Because the WHI indicated that it was mainly long-term (more than five years) HRT use that increased breast cancer risk, some health professionals still prescribe shorter-term HRT to relieve menopausal symptoms.

A study in the June 25, 2003 issue of the Journal of the American Medical Association found that after just one year of HRT, the risk of having an abnormal mammogram significantly increased. Another study in the same issue suggested that taking estrogen replacement therapy alone (ERT, commonly prescribed to women who have had a hysterectomy) did not significantly increase the risk of breast cancer, while taking estrogen plus progestin (combined HRT) increased breast cancer risk, whether the progestin was taken continuously or sequentially.

About the Study

The WHI was designed in 1991 to look at ways to decrease the risk of heart disease, breast and colorectal cancer, and fractures in postmenopausal women. For one part of the study, researchers assigned 16,608 postmenopausal women ages 50(79 to take either combined HRT or a placebo. Women who had undergone a hysterectomy were excluded. During the study, researchers made an alarming discovery. Although the women taking HRT were less likely to develop colorectal cancer or have a hip fracture, they had significantly increased risks of breast cancer, heart disease, stroke, and blood clots. So, after just five years—the study was set to go on for eight—the data safety and monitoring board determined that the risks of taking HRT outweighed the benefits and the study was halted.

For the current study, researchers used the WHI data to look at the effect of combined HRT on breast cancer characteristics and mammography results. All of the women had mammograms and breast examinations before the WHI began and at six-month intervals during the study. The current study compared the size and stage of breast cancer and the number of abnormal mammograms among women taking HRT compared with women taking a placebo.

The second study looked at a group of women ages 65(79. About half of the women (975) had recently been diagnosed with invasive breast cancer and the other half (1,007) had not. The researchers collected detailed histories of all of the women’s past HRT use and divided them into three groups, depending on their HRT regimen:

  • Exclusive ERT users (women who had used ERT, but not combined HRT)
  • Continuous combined HRT users (women who had used progestin 25 days a month or more)
  • Sequential combined HRT users (women who had used progestin fewer than 25 days a month)

The researchers then looked for a connection between the breast cancer cases and use of the different types of HRT.

The Findings

The WHI data showed that invasive breast cancers in women taking HRT were larger and more advanced than those in women taking the placebo. Also, the percentage of women with abnormal mammograms during the first year was significantly higher in the HRT group (9.4%) than in the placebo group (5.4%). During the course of the study, 31.5% of the women in the HRT group had at least one abnormal mammogram, compared with just 22.2% in the placebo group.

The second study found that both continuous and sequential combined HRT similarly increased the risk of developing breast cancer (1.6-fold and 1.8-fold increased risk, respectively).

Interestingly, women who used ERT exclusively—even for 25 years or longer—did not have an increased risk of developing breast cancer.

How Does This Affect You?

The findings of this study add to growing evidence that the risks of taking HRT probably outweigh the benefits. While researchers had assumed that short-term HRT to alleviate menopausal symptoms was safe, this study showed an increase in abnormal mammograms in the first year of HRT. Even if the abnormalities turn out to be harmless (which many of them do), the anxiety and hassle that go along with an abnormal mammogram are no small matter. The researchers calculated that of the three million women still taking HRT, about 120,000 will have abnormal mammograms each year because of it.

There was some question about whether sequential combined HRT posed the same risks as continuous combined HRT. The second study found that both regimens significantly increased breast cancer risk. Also, the study did provide some relief to women taking ERT after a hysterectomy; it showed that taking ERT alone probably does not increase the risk of developing breast cancer. (Women are advised not to take ERT if they still have a uterus since it increases the risk endometrial cancer.)

If you are taking HRT to relieve symptoms of menopause or to decrease your risk of bone fractures, you should schedule a visit with your physician to discuss the risks and benefits of continuing your treatment. There are other options for managing menopausal symptoms and preventing osteoporosis that don’t pose the same risks as HRT.