Latest findings by the Women's Health Initiative (WHI)
have confirmed that the health risks of long-term use of combination hormone therapy — wherein both estrogen and progestin are involved — in healthy,
postmenopausal women persist even a few years after stopping the medication,
and clearly outweigh the benefits.
The results of the WHI three-year follow-up study of
the estrogen-plus-progestin clinical trial suggest that three years after the
combination hormone therapy was stopped, many of the health effects of hormones
such as increased risk of heart disease were diminished. However, overall
risks, including the likelihood of stroke, blood clots, and cancer, remained
"The good news is that after women stop taking
combination hormone therapy, their risk of heart disease appears to decrease.
However, these findings also indicate that women who take estrogen plus
progestin continue to be at increased risk of breast cancer, even years after
stopping therapy. Today's report confirms the study's primary conclusion that
combination hormone therapy should not be used to prevent disease in healthy,
postmenopausal women," noted Dr. Elizabeth G. Nabel, Director, the
National Heart, Lung, and Blood Institute (NHLBI).
The follow-up study focussed on 15,730 postmenopausal
women with an intact uterus, aged 50 to 79 years at enrolment, who participated
in the WHI estrogen-plus-progestin clinical trial. Participants were randomly
assigned to receive a combination of estrogen (0.625 milligrams of conjugated
equine estrogens per day) plus progestin (2.5 mg of medroxyprogesterone
acetate) or placebo (inactive pill).
It began in July 2002 after women in the study were
instructed to stop taking combination hormone therapy, and continued through
March 2005, with participants followed for an average of 2.4 years.
The subjects were examined at least once a year, and
received an annual breast examination and mammogram, with biopsies performed as
According to the study report, the numbers of heart
attacks, strokes, and blood clots were not significantly different between the
two groups during the study — overall, 343 cardiovascular events among those
who initially received hormone therapy versus 323 among those who did not.
Besides, the number of deaths was not significantly
different — 233 women in the hormone therapy group died, compared to 196 in the
"After being on combination hormone therapy for
several years, the women's risk of cardiovascular disease was significantly
higher - from a 29 percent increase in heart attacks to a 41 percent increase
in strokes and nearly twice the risk of serious blood clots - compared to the
women who did not take hormones," said Dr. Michael S. Lauer, director of
the NHLBI Division of Prevention and Population Sciences.
"While it is reassuring that heart attack risk
decreased and that the risks for stroke and blood clots did not grow after the
women stopped taking hormones, this study provides further evidence that five
years of combination hormone therapy is harmful. All the accumulated risks do
not simply disappear," he added.
The researchers also report that other effects of
combination hormones, such as decreased risk of colorectal cancer and hip
fractures, also stopped when therapy ended.
"We continue to encourage women to use hormones
only if needed for menopausal symptoms, and for the shortest time possible, and
to adopt and maintain a healthy lifestyle, that is, engage in regular physical
activity, maintain a healthy body weight, consume a diet low in saturated fat,
and to not smoke, to reduce their risks of cardiovascular and other chronic
diseases," said Dr. Marcia Stefanick, professor of medicine at Stanford
University, Stanford, California, and a co-author of the paper, as well as
chair of the WHI Steering Committee.
She feels that women should receive tests for
cholesterol levels, blood pressure and other health risks, and take preventative
measures as needed.
The research team has also reported that the risk of
breast cancer among women continued at a rate similar to that seen during
Participants who had stopped taking estrogen plus
progestin were about 27 percent more likely to develop breast cancer than the
women who didn't take hormones during the study, with 79 women in the
post-treatment group developing breast cancer during the three-year follow-up
study, compared to 60 women in the non-treatment group.
"The hormones' effects on breast cancer appear to
linger. These findings reinforce the importance of women getting regular breast
exams and mammograms, even after they stop hormone therapy," noted Dr.
Leslie Ford, associate director for clinical research in the Division of Cancer
Prevention of the NIH's National Cancer Institute.
The study report, published in the Journal of the
American Medical Association, further reveals a 24 percent increased risk of
developing any form of cancer among women who had been in the treatment group.
A more detailed analysis on the cancer findings is underway.
increased risk of breast cancer clearly plays a role in the increased overall
risk of cancer years after stopping long-term estrogen plus progestin therapy, and
it is important that we continue to follow these women," added Stefanick,
noting that the new results provide further evidence that the health risks of
long-term combination hormone therapy outweigh the benefits.