If you are currently trying to make the decision between
synthetic HRT and natural hormone replacement, the following
results of ongoing WHI (Women's Health Initiative) studies
may help you reach an informed decision.
Following are portions of two press releases from the
National Institutes of Health, a division of the U.S.
Department of Health and Human Services, along with links to
the full text.
"NIH Asks Participants in Women's Health Initiative
Estrogen-Alone Study to Stop Study Pills, Begin Follow-up
Phase.
Statement from Barbara Alving, M.D., Director of the
Women's Health Initiative and Acting Director of the
National Heart, Lung, and Blood Institute.
The National Institutes of Health (NIH) has instructed
participants in the estrogen-alone study of the Women's
Health Initiative (WHI), a large multi-center trial, to
stop taking their study pills and to begin the follow-up
phase of the study.
Letters have been sent to all participants in the
estrogen-alone study, 11,000 healthy postmenopausal women
who have had a hysterectomy, informing them of a recent NIH
review of the study data. After careful consideration of
the data, NIH has concluded that with an average of nearly
7 years of follow-up completed, estrogen alone does not
appear to affect (either increase or decrease) heart
disease, a key question of the study. At the same time,
estrogen alone appears to increase the risk of stroke and
decrease the risk of hip fracture. It has not increased the
risk of breast cancer during the time period of the
study.
The increased risk of stroke in the estrogen-alone study
is similar to what was found in the WHI study of estrogen
plus progestin when that trial was stopped in July 2002. In
that study, women taking estrogen plus progestin had 8 more
strokes per year for every 10,000 women than those taking
the placebo. The NIH believes that an increased risk of
stroke is not acceptable in healthy women in a research
study. This is especially true if estrogen alone does not
affect (either increase or decrease) heart disease, as
appears to be the case in the current study...
The WHI estrogen study was designed to assess the effect
of long-term use of hormone therapy in healthy
postmenopausal women on the prevention of heart disease and
hip fractures, and any associated change in risk for breast
cancer. It was not designed to evaluate the short-term
risks and benefits of hormones for the treatment of
moderate to severe menopausal symptoms... The
estrogen-alone study involved women ages 50 to 79 years.
Study participants were randomly assigned to a daily dose
of estrogen-- 0.625 mg/day of conjugated equine estrogen
(Premarin(tm))--or a placebo.
The NIH decision to stop the estrogen-alone trial was
made on February 2, 2004. In November and December 2003,
the WHI Data and Safety Monitoring Board (DSMB), an
independent advisory committee which regularly reviews
study data and oversees the safety of study participants,
reviewed the latest data from the estrogen-alone study. The
DSMB was split as to whether the study pills should be
stopped or whether the pills should be continued, provided
that a letter would be sent to the participants clearly
informing them of the stroke risks and other findings.
After careful review, the NIH decided that women in the
estrogen-alone study should stop taking their study
pills..."
"NHLBI Stops Trial of Estrogen Plus Progestin Due
to Increased Breast Cancer Risk, Lack of Overall
Benefit
The National Heart, Lung, and Blood Institute (NHLBI) of
the National Institutes of Health (NIH) has stopped early a
major clinical trial of the risks and benefits of combined
estrogen and progestin in healthy menopausal women due to
an increased risk of invasive breast cancer. The large
multi-center trial, a component of the Women's Health
Initiative (WHI), also found increases in coronary heart
disease, stroke, and pulmonary embolism in study
participants on estrogen plus progestin compared to women
taking placebo pills. There were noteworthy benefits of
estrogen plus progestin, including fewer cases of hip
fractures and colon cancer, but on balance the harm was
greater than the benefit. The study, which was scheduled to
run until 2005, was stopped after an average follow-up of
5.2 years.
Participants in this component of WHI, like most women
with a uterus who take hormone therapy, were given
progestin in combination with estrogen. This practice is
known to prevent endometrial cancer. A separate WHI study
of estrogen alone in women who had a hysterectomy before
joining the WHI hormone program continues unchanged
because, at this point, the balance of risks and benefits
of estrogen alone is still uncertain.
The report from the WHI investigators on the estrogen
plus progestin study findings will be published in the July
17 issue of The Journal of the American Medical Association
(JAMA); because of the importance of the information, the
study is being released early on Tuesday, July 9, as an
expedited article on the JAMA Web site. (Full text version
available to all at jama.com.)
"We have long sought the answer to the question: Does
postmenopausal hormone therapy prevent heart disease and,
if it does, what are the risks? The bottom-line answer from
WHI is that this combined form of hormone therapy is
unlikely to benefit the heart. The cardiovascular and
cancer risks of estrogen plus progestin outweigh any
benefits--and a 26 percent increase in breast cancer risk
is too high a price to pay, even if there were a heart
benefit. Similarly, the risks outweigh the benefits of
fewer hip fractures," said NHLBI Director Claude Lenfant,
M.D.
"Menopausal women who might have been candidates for
estrogen plus progestin should now focus on well-proven
treatments to reduce the risk of cardiovascular disease,
including measures to prevent and control high blood
pressure, high blood cholesterol, and obesity. This effort
could not be more important: heart disease remains the
number one killer of American women," added Lenfant.
The estrogen plus progestin trial of the WHI involved
16,608 women ages 50 to 79 years with an intact uterus. An
important objective of the trial was to examine the effect
of estrogen plus progestin on the prevention of heart
disease and hip fractures, and any associated change in
risk for breast and colon cancer. The study did not address
the short-term risks and benefits of hormones for the
treatment of menopausal symptoms.
About 6 million women in the U.S. are taking estrogen
plus progestin for a variety of reasons, including symptom
relief, because their doctors advised it, or for long-term
health.
"Women with a uterus who are currently taking estrogen
plus progestin should have a serious talk with their doctor
to see if they should continue it. If they are taking this
hormone combination for short-term relief of symptoms, it
may be reasonable to continue since the benefits are likely
to outweigh the risks. Longer term use or use for disease
prevention must be re-evaluated given the multiple adverse
effects noted in WHI," said Jacques Rossouw, M.D., acting
director of the WHI.
According to Rossouw, the adverse effects of estrogen
plus progestin applied to all women, irrespective of age,
ethnicity, or prior disease status.
"When the estrogen-only trial is completed, a comparison
of the results of these two trials may provide a better
idea of the roles of estrogen, compared to estrogen plus
progestin, in health and disease," said Marcia Stefanick,
Ph.D., chair of the WHI Steering Committee and Associate
Professor of Medicine, Stanford University, Palo Alto,
California.
Women enrolled in the estrogen plus progestin study were
randomly assigned to a daily dose of estrogen plus
progestin (0.625 mg of conjugated equine estrogens plus 2.5
mg of medroxyprogesterone acetate) or to a placebo.
Participants were enrolled in the study between 1993 and
1998 at over 40 clinical sites across the country.
In 2000 and again in 2001, WHI investigators complied
with a recommendation from the study's Data and Safety
Monitoring Board (DSMB) to inform participants of a small
increase in heart attacks, strokes, and blood clots in
women taking hormones. The DSMB, an independent advisory
committee charged with reviewing results and ensuring
participant safety, found that the actual number of women
having any one of these events was small and it did not
cross the statistical boundary established to ensure
participant safety. Therefore, the group recommended
continuing the trial due to the still uncertain balance of
risks and benefits.
Then, at the DSMB's regularly scheduled meeting on May
31, 2002, the data review revealed for the first time that
the number of cases of invasive breast cancer in the
estrogen plus progestin group had crossed the boundary
established as a signal of increased risk.
"In designing the trial and following the results, the
safety of the patients was of the utmost importance," said
Garnet Anderson, Ph.D., a biostatistician who led the
analysis at the Fred Hutchinson Cancer Research Center,
Seattle, Washington. "Because breast cancer is so serious
an event, we set the bar lower to monitor for it. We
pre-specified that the change in cancer rates did not have
to be that large to warrant stopping the trial. And the
trial was stopped at the first clear indication of
increased risk," she added. She also noted that, at that
point, there was no indication of increased risk for breast
cancer in the estrogen-only group.
The DSMB's May 31 recommendation to stop the trial was
based on the finding of increased breast cancer risk,
supported by the evidence of overall health risks exceeding
any benefits. Following the NHLBI's decision to stop the
study, the Institute and the investigators have worked
intensively to develop information materials for
participants. On July 8, participants started receiving
letters informing them about the results and telling them
that they should stop study medications. Participants will
be contacted by their clinical centers for further
counseling and will continue to have clinic visits so that
their health outcomes can be followed...
Specific study findings for the estrogen plus progestin
group compared to placebo include:
* A 41 percent increase in strokes
* A 29 percent increase in heart attacks
* A doubling of rates of venous thromboembolism (blood
clots)
* A 22 percent increase in total cardiovascular
disease
* A 26 percent increase in breast cancer
* A 37 percent reduction in cases of colorectal
cancer
* A one-third reduction in hip fracture rates
* A 24 percent reduction in total fractures
* No difference in total mortality (of all
causes)"...
Visit the National Institutes of Health site for more
information about WHI studies
