It is estimated that 20–50% of women between the ages of 45 and 70 in western countries are taking some form of hormone replacement therapy (HRT) . Most of these women are taking HRT to relieve symptoms of menopause or help prevent osteoporosis . However, a number of studies have reported that HRT may increase the risk of breast cancer , heart disease , stroke , and blood clots, and many physicians have stopped prescribing it to their patients.

In June 2003, two large studies reported that HRT increased the risk of having an abnormal mammogram and developing breast cancer. These studies added to the evidence that HRT may put women at risk for breast cancer, but some questions still remained unanswered. Are women on HRT at increased risk of dying from breast cancer? Does estrogen alone—opposed to combination (estrogen plus progestin) HRT—also increase the risk of breast cancer? Are certain HRT regimens less likely to cause breast cancer? And, are former users of HRT still at risk for developing breast cancer?

A study in the August 9, 2003 issue of The Lancet helped answer these questions. Researchers looked at over a million women in the UK and found that current use of HRT—especially combination HRT—was associated with an increased risk of developing and dying from breast cancer. Furthermore, taking alternative regimens of HRT—lower doses or skin patches, for instance—had no significant effect on the risk of developing breast cancer.

About the Study

The women in this study were recruited from the National Health Service Breast Screening Programme (NHSBSP), a program in the UK that invites all women between the ages of 50 and 64 for a breast cancer screening every three years.

A few weeks before their screening, the women completed a mailed questionnaire, which included questions about their HRT use, menopausal status, and other factors that might contribute to breast cancer risk. The women were classified into the following groups:

  • Never users of HRT
  • Past users of HRT
  • Current users of estrogen alone
  • Current users of combination HRT
  • Current users of other or unknown regimens of HRT

The women who had used HRT provided information about their duration of use, estrogen type (equine estrogen or estradiol), progestin type (medroxyprogesterone acetate, norethisterone, or norgesterel/levonorgesterel), progestin use (none, continuous, sequential), dose, and formulation (oral, skin patch, or implanted). The researchers kept track of the women who developed breast cancer for an average of 2.6 years, and the women who died from breast cancer for an average of 4.1 years. Then they calculated the effects of the different types of HRT on the risk of developing and dying from breast cancer.

The Findings

About 70% (1,084,110) of the women who attended the NHSBSP participated in the study, which amounted to 53% of all eligible women in the UK. Over the course of the study, 9,364 women developed breast cancer and 637 died from breast cancer. Half of the women reported having used HRT at some time.

For the main analysis, only the 828,923 women who were confirmed to be postmenopausal were included. Of those women currently using HRT (35%), 91% were using estrogen only or combination HRT. The other 9% were using tibolone (an HRT alternative not available in the United States), other preparations, or did not know what regimen they were using.

The women currently using HRT were significantly more likely to develop breast cancer than the women who had never used HRT. Past users of HRT, however, did not have an increased risk of breast cancer. Compared with never users of HRT, current users had a 22% greater risk of dying from breast cancer, while past users did not have a significantly greater risk.

When comparing current users of HRT, the women using combination HRT had a substantially greater risk of developing breast cancer than the women taking estrogen alone, tibolone, or other preparations. In fact, while all forms of HRT—including estrogen alone—significantly increased the risk of breast cancer, combination HRT caused four times as many extra breast cancers than estrogen alone. Overall, among women currently using HRT, the risk of developing breast cancer increased with increasing duration of use. The estrogen type, progestin type, progestin use, dose, or formulation of HRT did not significantly alter the risk of developing breast cancer.

How Does This Affect You?

This is yet another, sizable study that suggests the risks associated with long-term use of HRT outweigh the benefits. Even though several randomized, placebo-controlled studies have found that HRT increases the risk of breast cancer, researchers still were not sure if alternative HRT regimens also increased this risk. Also, until now, no study had shown whether HRT increased a woman’s chance of dying from breast cancer. The Million Women Study indicated that any type of HRT use increases a woman’s risk of developing breast cancer, and combination HRT probably poses the greatest risk. The good news that came from this study is that women who have used HRT in the past, but have since stopped, do not appear to be at increased risk of developing breast cancer.

Does this study mean that your doctor will take you off of HRT? It depends on your situation. The evidence is certainly mounting that the risks associated with taking HRT are high in the population as a whole. But a fact often ignored in the interpretation of these studies is that the risks posed to individual women are still very small. Your physician may evaluate your individual situation and recommend that you continue to take HRT with close monitoring. There are alternative remedies for relieving the symptoms of menopause and preventing osteoporosis. If you are currently taking HRT and haven’t done so, schedule a visit with your physician to discuss its relative risks and benefits for you.