Release of the Results of the Estrogen Plus Progestin Trial of the Women's Health Initiative: Findings and Implications

Jacques Rossouw, M.D.
Acting Director
Women's Health Initiative
National Heart, Lung, and Blood Institute
July 9, 2002

Press Conference Remarks

Good morning. As Dr. Lenfant said, the results we're presenting today are of tremendous importance to women. Finally, we are filling in details of what has been a fuzzy picture. Choosing whether or not to take postmenopausal hormone therapy is one of the most important health decisions women face. And while much more remains to be learned, today we can finally begin to offer some guidance.
The results are important for various reasons. Millions of American women who have a uterus might consider taking these drugs. As you've heard, about 6 million American women currently use the estrogen plus progestin therapy.
Further, the results have broad applicability. The study found no differences in risk by prior health status, age, or ethnicity.
These results cover a lot of territory--breast cancer, heart attack, stroke, blood clots, fractures, and colorectal cancer--so I can only summarize them here. For more details, please check your press kit for a copy of the JAMA article. Table 2 lists the clinical outcomes. All of the results apply to an average follow-up of 5.2 years.
Let me begin by noting that there was no difference in the number of deaths between the estrogen plus progestin therapy and placebo groups. Also, the percent of women who experienced adverse effects from the estrogen plus progestin therapy was small, and therefore the risk to individual women in the trial was small.
The results show both adverse effects and benefits from the estrogen plus progestin therapy. Crucially, however, the adverse effects outweigh and outnumber the benefits. By outnumber, I mean that more women had adverse effects from the therapy than benefitted from it.
The key adverse effects were more cases of breast cancer and cardiovascular disease, while the main benefits were fewer hip fractures and cases of colorectal cancer.
Women on the estrogen plus progestin therapy had a 26 percent higher incidence of breast cancer than those taking a placebo. The increased risk was not present in the first few years of the study--in fact, it did not appear for 4 years. Women who had used the hormone therapy before entering the study were more likely to develop breast cancer, indicating that the estrogen plus progestin treatment may have a cumulative effect. Otherwise, the increased risk applied to all women, regardless of age, ethnicity, and family history of breast cancer.
These findings are the first confirmation from a rigorous clinical trial that taking estrogen plus progestin increases the risk of breast cancer.
This hormone therapy did not increase the risk of endometrial cancer.
The findings also show a 22 percent increase in total cardiovascular disease, with a 29 percent increase in heart attacks, a 41 percent increase in strokes, and a doubling of the rate of blood clots in the lungs.
For heart attack, the risk began to increase in the first year of estrogen plus progestin use. The increase became more pronounced in the second year, and the difference between the groups persisted throughout the follow-up period.
Thus, as with the HERS trial, WHI found evidence of early cardiovascular harm from the hormone therapy. Unlike HERS, which showed no benefit or harm after 6.8 years of hormone use, WHI found more heart disease in women taking the combined therapy after 5.2 years. This is a key finding because WHI's results apply to healthy women, while HERS involved women with heart disease.
The estrogen plus progestin therapy caused a 41 percent increase in strokes among hormone users, compared with those taking the placebo. This result is substantially higher than the 21 percent increased risk of stroke found in HERS. In WHI, the increase in stroke risk began in the second year of the estrogen plus progestin use and continued throughout the follow-up period. This is the first study to show an increase in strokes for healthy women taking the estrogen plus progestin therapy.
WHI results also show that hormone users had more than double the rate of blood clots in the lungs and double the rate of blood clots in the legs. The increased risk was greatest during the first 2 years of hormone use--fourfold. In subsequent years, the increased risk was twice as great for the estrogen plus progestin users as for those taking the placebo.
HERS and other studies had found similar increases in the risk for blood clots. The increased risk of blood clots in the legs suggests that the process of thrombosis, or clot formation, may play a role in increasing the risk for heart attack and stroke. More research is needed to determine if this is so.
Women also gained some benefits from the estrogen plus progestin therapy. Women taking the therapy had a 34 percent reduction in hip fractures and 24 percent reduction for total fractures. This is the first solid evidence from a clinical study that hormone therapy, in helping to prevent osteoporosis, protects women against fractures.
The estrogen plus progestin therapy also produced a 37 percent reduction in the risk of colorectal cancer. The reduced risk emerged after 3 years of hormone use and became more significant during the remaining follow-up period. However, the number of cases is relatively small and, while some epidemiological studies have also suggested a lower risk, the finding must be confirmed by further clinical studies.
These data are bound to sound frightening to women. So let me be sure you understand their significance. Those data describe the increased risk for an entire population--not the increased risk for an individual woman. The increased risk of breast cancer for each woman in the WHI study who was taking the estrogen plus progestin therapy, for instance, was actually very small. It was less than a tenth of 1 percent per year.
But if you apply that increased risk to an entire population and over several years, the number of women affected increases dramatically and becomes an important public health concern. Considering that millions of American women might consider taking the estrogen plus progestin therapy, that could translate into tens of thousands of cases of breast cancer or cardiovascular disease over several years.
The point is that, while we want to get the word out to women and their doctors that long-term use of this therapy could be harmful, women should not conclude that they will develop breast cancer, or have a heart attack or stroke if they've taken this medication and, even in those who do suffer one of these diseases, the condition may not be due to the therapy.
What then do these findings mean for women who are taking or are considering taking estrogen plus progestin therapy?
First, women should not start or continue to use the therapy to prevent heart disease. The findings show that it doesn't work. In fact, the therapy increases the chance of a heart attack or stroke. Additionally, it increases the risk of breast cancer and blood clots. Women should talk with their doctor about other methods of preventing heart attack and stroke, which have been proven to be effective and safe. These include lifestyle changes and drugs, such as cholesterol-lowering statins and blood pressure medications. Also, as part of a total health program, women should keep up their regular schedule of mammograms and breast self-examinations in order to detect breast cancer early.
Second, women who are taking the therapy to prevent osteoporosis should talk with their doctor and carefully weigh any benefit against their personal risks for cardiovascular disease and breast cancer. Alternate treatments, which are safe and effective, should be considered to prevent osteoporosis and fractures.
Finally, the study did not test the use of estrogen plus progestin for the treatment of menopausal symptoms, although such use has been shown to be effective and we think that the benefits for this may outweigh the risks. We would recommend that women consult their doctor about their individual benefits and risks from such use. If they decide to take the therapy, they should do so for a short period.
As was mentioned, today's findings do not apply to estrogen-only therapy. For those results, we must wait for more findings from the WHI. Those results are expected in about 3 years.
Now, I will hand the proceedings back to Dr. Lenfant and we will welcome your questions. Dr. Lenfant.