The week of July eighth saw headlines in all the news media advising women taking Prempro to stop immediately and consult their health care providers because of new evidence that this form of hormone replacement therapy (HRT) causes breast cancer. For the last several years there has been an ongoing debate in the medical literature as to whether HRT, in particular, estrogen therapy, increases a woman’s risk of developing breast cancer and, if so, to what degree. So why did this new evidence make the headlines and what are the researchers really saying?
Members of the research team running a study called the Women’s Health Initiative (WHI) released this information. The study began about five years ago and involves over 16,000 postmenopausal women. This is a randomized placebo-controlled drug study meaning the women were randomly assigned to receive either a form of hormone therapy or a placebo. Hormone therapy consisted of Prempro (an estrogen [Premarin] and a progesterone [Provera]) in women who had not undergone hysterectomy, and Premarin alone in those who had. The main goal of the study was to see if HRT decreased the risk of heart attacks and/or increased the risk of breast cancer. Other outcomes such as the risk of clotting and colon cancer were monitored as well.
Over the course of the study, the researchers periodically reviewed the data. At the beginning of the study they had set what they considered acceptable risk cut-off points for the adverse outcomes, that, if exceeded, would trigger termination of the study. For example, a slight increase in the risk of heart attacks had been noted earlier in the study, but at a level below the predetermined cut-off value, so the study continued. When the researchers looked at the results available as of April 2002, they noted an increase in the number of cases of breast cancer in the group taking Prempro that had not been previously seen. The number of cases in the treated group exceeded the limit so the decision was made to terminate the study. They claimed that the patients receiving the HRT had a 26% increased risk for developing breast cancer. News media reports covering this study included alarming quotes from various physicians such as “…long-term use of this therapy could be harmful…”;”…there is really no safe period…”; and “…this is a dangerous drug….” While the researchers were advising caution and asking women not to get alarmed, coverage of the study certainly had the opposite effect.
While this was clearly a well-designed, valuable study, several points need to be emphasized:
- Other studies have looked at the same question (re: breast cancer risk) and have come to different conclusions. For example, another ongoing randomized study (HERS) that used the same drug could not demonstrate a statistically increased risk of breast cancer in the treated group over almost 7 years of follow up. The most recent update of this study was published in the same medical journal as the WHI study two weeks earlier (JAMA, 3 July 02) and it failed to make headlines.
- The arm of the WHI study that involves 11,000 women taking Premarin alone is continuing, as there has been no increased risk of breast cancer noted in this group.
- While the increased risk was quoted as 26%, this is misleading as this refers to what is called relative risk. The actual increased risk they noted was from 3.0 breast cancers per 1000 women in the placebo group to 3.8 in the Prempro group. According to the researchers, for an individual woman, this translates into an increased risk of approximately one-tenth of 1% per year of treatment.
- There are several other forms of estrogen and progesterone used for HRT. None of these were evaluated in this study and the risk profile for these drugs could be quite different.
- There remain well-established benefits of HRT including decreased risk for osteoporosis and bone fractures, decreased risk of colon cancer, and well-defined cognitive effects including possibly a lower risk of Alzheimer’s Disease. On the other hand, HRT seems less to be the fountain of youth it was once purported to be.
Harbour Women’s Health sponsored educational seminars three and four years ago addressing “Alternatives to Traditional Hormone Therapy.” We have never felt HRT was a cure all, but neither do we feel it has no place in the treatment of menopausal symptoms.
It has always been the policy of Harbour Women’s Health to discuss the use of HRT in the context of risks versus benefits. This is an individual decision that should be made with careful consideration of all the information available at the time. With the publication of the WHI results, this information has changed. However, it is our opinion that the issue remains complex, that the information will continue to evolve as more research is done, and that it is unlikely we have heard the last word on HRT.