The Truth About Hormone Replacement Therapy

By the National Women’s Health Network

From their beginnings, estrogen replacement therapy (ERT, the use of estrogen alone) and hormone replacement therapy (HRT, the use of estrogen together with progestogen) have been controversial.  A major part of the problem is the lack of solid information women have to make wise choices.  Most of what we know about ERT and HRT comes from women who chose to use the drugs and who agreed to participate in observational studies.  These are not controlled studies in which one group is randomly assigned to take a drug and another not to take the drug or to take a different drug.  Although controlled studies are the gold standard of modern medicine, there are few on hormone therapy.  And most controlled trials are too short to give much useful information about harmful outcomes.  The health problems that appeared in the observational studies have not been proven conclusively to be caused by hormones.  

Breast Cancer Risk

Many factors in women’s reproductive lives, such as their age when their periods started and when they reached menopause, influence their likelihood of developing breast cancer1 .  Similarly, it seems that taking estrogen also influences the risk of breast cancer(1).  A few years ago, a welcome summary of nearly every study of estrogen replacement therapy and breast cancer was published.  Looking at the experience of more than 52,000 women in 21 countries, the researchers found that women who used ERT for five or more years increased their risk of breast cancer by about 35 percent(2).  The risk lasts as long as a woman takes hormones but disappears within five years after she stops hormone use.  What would happen to younger women if they didn’t take hormones and just continued to menstruate?  Because the researches had access to so much data, they were able to compare risks.  They found that each additional year of menstruation increased the risk by 2.3 percent.  Not much difference, is there?  The similar level of risks adds strength to the conclusion that ERT may in some way promote breast cancer.  Unfortunately, it’s unusual for women to hear such a clear and definitive description of the relationship between ERT and breast cancer.  Instead, we often hear messages from our clinicians that imply there are only a few studies that have found any risk of breast cancer and dozens that have found no increased risk at all(3). These messages are misleading.  They ignore the crucially important issue of how long a woman has taken hormones.  Although many studies have found no increased risk of breast cancer in women who have “ever” used ERT, the problem with these studies is that women who have “ever” used ERT are likely to have used it for a relatively short period of time.  Using ERT for three to five years or less doesn’t appear to increase the risk of breast cancer, but using it for five years or longer clearly does.  Unfortunately, the risk of death from breast cancer associated with hormone therapy is less clear, because studies that look at this issue present conflicting results.  The Nurses Health Study’s most recent follow-up found a 43 percent increased risk of death due to breast cancer after ten years of hormone use(4), and a smaller study by researcher Bruce Ettinger and others in California found an increased risk of 89 percent after an average of 18 years’ use(5).  On the other hand, a very large study conducted by the American Cancer Society found that women who reported “ever” using estrogen when they were interviewed in 1982 were 16 percent less likely to die of breast cancer during the next ten years than were women who hadn’t used ERT/HRT(6).  Not until 2000 had we had much data on the effect of progestins added to ERT on breast cancer risk.  In the past, physicians hope that progestins would have the same beneficial effect on the breast as they have on the uterine lining and lower any increased cancer risk caused by estrogens alone.  This argument never made biological sense, because progestins and progesterone slow cell division in the uterus, while in the breast they increase it.  Early studies looking at HRT users seemed to show progestins didn’t lower risk of breast cancer(7,8,9).  These studies weren’t taken very seriously by the average clinician, in part because they involved only small numbers of women.  Then, in the year 2000, two large studies confirmed the earlier reports and demonstrated that progestins seem to increase breast cancer risk beyond that of ERT taken alone(10,11). As in women who used ERT alone, it seems to take five years before risk increases.  After that, the risk increases slightly with each additional year on HRT.  Some women want to know whether the risks of HRT are greater for women who have an inherited risk of breast cancer.  Despite this widespread concern, there is only one study specific to this topic.  Conducted in Iowa and published in 1997, it is an observational study with inherent weaknesses, but it did follow a large group of women.  It found that women with a family history of breast cancer who took HRT were no more likely to get breast cancer than women with a family history who did not take HRT.  While one observational study is not definitive, we believe women with a family history of breast cancer probably don’t need to worry about the breast cancer risk of HRT any more than women in general.

Adapted from The Truth About Hormone Replacement Therapy, by the National Women’s Health Network (NWHN), the permission from Prima Publishing, a division of Random House.  Copyright 2002.  To buy the book, contact the publisher at 800-733-3000 or the NWHN at 202347-1140 or womenshealthnetwork.org

References

1.Colditz, G. A., “The relationship between estrogen levels, use of hormone replacement therapy, and breast cancer,” Journal of the National Cancer Institute, vol 90, no. 11, 1998, pp.814-23

2.Collaborative Group on Hormonal Factors in  Breast Cancer, “Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer,” Lancer, vol 350 1997, pp. 1047-59.

3.Gambrell, R.D. “Hormone replacement therapy and breast cancer risk,” Archives of Family Medicine, vol. 5, no. 6, 1996, pp. 341-48

4.Grodstein F, et al., “Postmenopausal hormone therapy and morality,” New England Journal of Medicine, vol. 336, 1997, pp. 1769-75

5.Ettinger, B., et al. “Reduced mortality associated with long-term postmenopausal estrogen therapy,” Obstetrics & Gynecology, vol. 87 no. 1, 1996, pp 6-12.

6.Willis, D.B., et al., “Estrogen replacement therapy and risk of fatal breast cancer in a prospective cohort of postmenopausal women in the United States,” Cancer Causes Control, vol. 7, 1996, pp. 449-57.

7.Colditz, G.A., et al. “The use of estrogens and progestins and the risk of breast cancer in postmenopausal women,” New England Journal of Medicine, vol. 332, 1995, pp. 1589-93.

8.Begkvist, L., et al.  “The risk of breast cancer after estrogen and estrogen-progestin replacement,” New England Journal of Medicine, vol 321, no. 5,1989, pp 293-297.

9.Ewertz, M., et al. “Influence of non-contraceptive exogenous and endogenous sex hormones on breast cancer risk in Denmark,” International Journal on Cancer, vol. 42, 1988, pp. 832-38

10.Ross, R.K., et al. “Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin, “Journal of the National Cancer Institute, vol 92, no. 4, pp. 328-32.

11.Schairer, C., et al. “Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk,” Journal of the American Medical Association, vol. 283, no. 440, 2000, pp. 485-91.