Jacques Rossouw, M.D.
Women's Health Initiative
National Heart, Lung,
and Blood Institute
July 9, 2002
Press Conference Remarks
Release of the Results of the Estrogen Plus Progestin
Trial of the Women's Health Initiative:
Findings and Implications
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
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
This hormone therapy did not increase the risk of
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
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
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
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
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
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.