Chicago (7/17/02)- Once considered a boon to women during and after
menopause, the risks of hormone supplementation now appear to outweigh the
putative benefits, at least in some patients, according to the results of
a huge clinical trial.
Federal health authorities stopped the trial, part of the Women's Health
Initiative (WHI), when it became clear that post-menopausal women who were
taking a common combination of estrogen and progestin had an increased risk
for developing breast cancer and cardiovascular disease. The study involved
16,608 women across the United States. It is the first randomized trial to
study the effects of long-term treatment with the hormone combination on these
"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
In brief, the study revealed that when compared with placebo, women taking
the hormone combination had:
The study also showed some apparent benefits associated with hormone use.
- A 37 % reduction in cases of colorectal cancer
- A one-third reduction in hip fracture rates
- A 24 % reduction in total fractures
In editorial accompanying the publication in JAMA, Suzanne W. Fletcher, MD,
M. Sc., and Graham A. Colditz, MD Dr.P.H., of the Harvard Medical School,
suggest that the time may have come to stop prescribing estrogen/progestin
for preventive purposes.
"The whole purpose of healthy women taking long-term estrogen/progestin therapy
is to preserve health and prevent disease. The results of this study provide
strong evidence that the opposite is happening for important aspects of women's
health, even if the absolute risk is low. Given these results, we recommend
that clinicians stop prescribing this combination for long-term use."
Ovarian Cancer Risk
In a related report in the same issue of the journal JAMA that announced
the results, researchers from the National Cancer Institute reported an increased
risk of ovarian cancer among women receiving estrogen replacement therapy.
In a study that tracked the health of 44,241 women for approximately 20 years,
the researchers found women taking estrogen had a 60% increased risk of ovarian
cancer compared to those who were not. The risk increased with length of estrogen
"The main finding of our study was that postmenopausal women who used estrogen
replacement therapy for 10 or more years were at significantly higher risk
of developing ovarian cancer than women who never used hormone replacement
therapy," said James V. Lacey, Jr., Ph.D., lead author of the study from National
Cancer Institute's Division of Cancer Epidemiology and Genetics.
The NCI study primarily looked at the long-term effects of estrogen use alone.
The study did not report an increased risk for ovarian cancer among women
who used combination hormone replacement therapy. However, Dr. Lacey cautioned
that the study had not followed enough women for a long enough period to say
whether taking the combined therapy has any effect on ovarian cancer.
Caveats and Limitations
It is important to keep the WHI study in perspective. The study looked at
the effect of one combination of hormones taking for a long period of time.
The findings may not apply to women who take hormone replacement therapy for
only a short-period to ease the symptoms of the menopausal transition. The
WHI investigators stress that the current results do not necessarily apply
to lower dosages of these drugs, to other formulations of oral estrogens and
progestins, or to estrogens and progestins administered through the transdermal
route. Indeed, they say it is still possible that transdermal estradiol with
progesterone, may provide a different risk-benefit profile.
A parallel WHI trial of estrogen only in women who have had a hysterectomy
will continue. The trial is scheduled to end in March 2005, by which time
the average follow-up with be about 8.5 years.
During the time in which the WHI trial has been conducted, many new treatments
have been found that offer an alternative to hormone replacement for reducing
fracture risk associated with osteoporosis. In addition, there has been a
growing awareness of the need to inform women of strategies to reduce the
risk for cardiovascular disease.
"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," stressed Dr. Lenfant.
The research appears in the July 17, 2002 issue of JAMA.