Womans
Health News
Bad
News About Hormone Replacement Therapy
Many of us have been jaded by the constant onslaught of “the
latest” medical news, much of which seems to contradict
what we just heard or read about the week before.
But
on July 9, millions of us – patients and health care providers
alike – paid rapt attention when the federal government’s
National Institutes of Health released findings from a major
clinical trial, warning of the risks associated with a widely
used type of hormone replacement therapy (HRT) that combines
two female hormones, estrogen and progestin.
It’s
estimated that 6 million postmenopausal American women currently
take Prempro or similar combined estrogen-progestin drugs to
ease menopause symptoms and to improve their health and well-being.
Risks Outweigh Benefit, Study Found
The
study, called the Women’s Health Initiative (WHI), found
that the combined drugs caused increases in breast cancer, heart
attacks, strokes and blood clots. Although the risk to an individual
woman may be small, the number of cases occurring in the population
at large can be great, researchers said. And those risks outweigh
the drugs' actual benefits – a small decrease in hip fractures
and a decrease in cases of colorectal cancer. The study was
released four years earlier than expected because of researchers’
concerns.
The
WHI study is the first-ever long-term randomized controlled
clinical trial – considered the gold standard by medical
researchers – of hormone replacement therapy. The WHI
was established in 1991 by the government to address the most
common causes of death, disability and impaired quality of life
in postmenopausal women. The Medical College of Wisconsin is
one of 40 WHI clinical sites nationwide where study participants
are seen and monitored.
The
Women’s Health Initiative is a 15-year multimillion-dollar
endeavor, and one of the largest US prevention studies of its
kind. The study was designed to look at the effects not only
of HRT, but also diet modification and vitamin and mineral supplements.
Some 67,000 women from across the country, ranging in age from
50 to 79, are participating in the WHI clinical trials. In addition
to those women, the study is also following the medical history
and health habits of an additional 100,000 women to examine
the relationship between lifestyle, health and risk factors
with specific disease outcomes. Final results are due out in
2006.
More
than 16,600 U.S. women are participating in the combined estrogen-progestin
portion of the trial, among them 438 women who are in the Medical
College of Wisconsin group. They were sent letters telling them
to discontinue taking those drugs. The WHI is continuing to
study the effects of ERT, or estrogen-alone drugs, used by women
who have had a hysterectomy. WHI has not stopped that portion
of the study.
Jane
Morley Kotchen, MD, Professor and Director of Epidemiology at
MCW, is the principal investigator for MCW’s portion of
the study. She admits she was caught by surprise by the early
release.
“The
breast cancer risks for women on the combined estrogen-progestin
therapy are similar to risks that have been found in other studies,”
she notes, although she says the cardiovascular findings were
not anticipated. “A decreased risk of coronary heart disease
had been hypothesized for women on active hormone therapy, so
the finding of slightly greater risks for women on the active
hormone therapy was unexpected. Overall, the health risks for
women taking combined estrogen plus progestin therapy were found
to outweigh the benefits. The trial was stopped because the
risk-benefit balance, as indicated by a global indicator of
overall risk, was unfavorable and the breast cancer risks crossed
the predetermined safety boundaries.”
The
WHI’s Data and Safety Monitoring Board – an independent
advisory committee charged with reviewing results and ensuring
participant safety – set the limits of acceptable risk
for breast cancer at an unusually low level of cases per thousand.
When that level was reached, the trial was stopped and results
were released early.
Another
Medical College faculty member who served as a WHI investigator
agreed that the early release of the findings was surprising.
For Vanessa Barnabei, MD, PhD, the medical risks and benefits
that caused such a national media furor when the WHI released
its combined estrogen-progestin study results had been indicated
by earlier patient studies, although earlier studies were regarded
as “observational,” and had not met the strict standards
of the WHI. Dr. Barnabei is an Associate Professor of Obstetrics
and Gynecology at MCW and Director of MCW Physicians’
Division of General Obstetrics and Gynecology.
“Early
harm from heart disease and stroke were suggested several years
ago, and women in the study were informed about it at that time,”
Dr. Barnabei says. “And the breast cancer risks have been
suspected. The numbers and magnitude of risk are no different
today than they were then.”
Risk
‘Relatively Small’ for Individual Women
In a news release from the NIH on July 9, Jacques Rossouw, MD,
acting director of the WHI, summarized the risk findings:
"The WHI results tell us that during one year, among 10,000
postmenopausal women with a uterus [as opposed to those who
have had their uterus removed] who are taking estrogen plus
progestin, eight more will have invasive breast cancer, seven
more will have a heart attack, eight more will have a stroke,
and 18 more will have blood clots, including eight with blood
clots in the lungs, than will a similar group of 10,000 women
not taking these hormones. This is a relatively small annual
increase in risk for an individual woman,” he said.
Dr.
Barnabei said that she found it interesting that the WHI has
continued with the estrogen-only portion of the study. She says
scientists have known that progestin can act to influence breast
growth and development while reducing the risk of uterine cancer.
And an article in the January 26, 2000, Journal of the American
Medical Association reported that researchers at the National
Cancer Institute had found that women who are current or recent
users of combined estrogen and progestin had a higher relative
risk of breast cancer than women who only take estrogen.
What
Patients Should Know
Dr. Rossouw, the acting WHI director, offered this advice: “Women
with a uterus who are currently taking estrogen plus progestin
should have a serious talk with their doctors 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.”
Dr.
Barnabei says she always cautions patients about the potential
for increased breast cancer risks. First, she rules out women
who are not candidates for HRT– those with vaginal bleeding
of an unknown cause, suspected breast cancer or history of breast
cancer, history of endometrial cancer or certain cancers of
the uterus, chronic liver disease such as cirrhosis or a history
of blood clots.
For women who are eligible for HRT, the primary reason for HRT
is symptom relief, she says, with less emphasis on using hormone
therapy for disease prevention: “I explain the known risks
and benefits. And I do remind them that the risk for breast
cancer does increase naturally for all women as they age, along
with heart disease and osteoporosis.”
Dr.
Barnabei tells her patients who want to stop HRT that they can
certainly quit anytime. “First of all, with menopause,
we’re not treating a disease,” she says. “Stopping
HRT has no major consequences except perhaps a return of menopausal
symptoms.”
Non-HRT
Options Effective for Some
For both women who want to stop taking HRT and for women who
choose not to start HRT, Dr. Barnabei discusses alternative
therapies. “For almost everyone, there are other treatment
options. I take them through all the major organ systems in
the body that undergo change with menopause. I assess their
personal risks and discuss options.”
For
instance, she tells women they can reduce their risk of heart
disease by stopping smoking and by keeping their weight, cholesterol
levels and blood pressure under control. Prozac and some other
antidepressants can relieve hot flashes. Biphosphonate drugs
such as Fosamax help protect against osteoporosis. So can another
prescription drug, Evista (raloxiphene HCl), which also claims
to lower total cholesterol and prevent breast cancer. However,
Dr. Barnabei says that because women on Evista experience more
hot flashes, it raises questions about how that might affect
the brain. Some researchers have suspected a link between hot
flashes and Alzheimer’s. “We don’t have long-term
data, so we don’t know.” And Evista has been found
to exaggerate vaginal dryness, she says. Evista belongs to a
class of drugs called SERMs, or Selective Estrogen Receptor
Modulators. A SERM being used in Europe, tibolone, may be more
effective without the side effects found in Evista.
Herbal Remedies: Effectiveness and Safety at Issue
As women have become more doubtful about HRT, many have grown
interested in using herbal remedies instead. Dr. Barnabei urges
women to be cautious: “Just because something is derived
from a plant does not necessarily mean it’s safe. Some
herbal remedies work a bit, but some don’t work at all.
And many have potentially dangerous health risks. We have even
less data on herbal remedies (which are not regulated by the
government) than we do on HRT.”
A popular herbal remedy is black cohosh, which “seems
safe for most women. But I have serious reservations about soy,”
Dr. Barnabei says. “It’s not the panacea women would
like to think it is. To get any relief from hot flashes, you’d
have to consume a high quantity, about 40 grams per day or more,
and that raises calorie intake issues.” Soy has gained
popularity in the United States because it’s such a staple
in the Japanese diet, where women generally have lower rates
of breast cancer and menopausal symptoms. “However,”
she notes, “Asian women do seem to be at higher risk for
osteoporosis.”
Other
widely used remedies for relief of menopausal symptoms are St.
John’s Wort and wild yam. With St. John’s Wort,
women typically take three tablets a day for two to three months
before finding relief. Yams contain a protein or protein-like
substance that is similar to the progesterone hormone. But,
Dr. Barnabei says, “By itself it can’t have a hormone-like
effect because our bodies lack an enzyme needed to convert it.”
Besides
Drs. Kotchen and Barnabei, three other Medical College of Wisconsin
faculty members are investigators of the WHI study: Joan M.
Neuner, MD, MPH, Assistant Professor of Medicine; Mary Ann C.
Gilligan, MD, MPH, Assistant Professor of Medicine; and Theodore
A. Kotchen, MD, Professor of Medicine. Dr. Neuner’s focus
is metabolism and nutrition; Dr. Gilligan’s area of interest
is cancer prevention and genetic screening for cancer; Dr. Theodore
Kotchen is an endocrinologist.
Although
these early findings from the WHI raise some cautions and pose
some questions, Dr. Kotchen says, “The most important
thing about what we know is that women need to understand the
risks and benefits so they can make informed choices.”
This
article includes information from:
Froedtert & Medical College Obstetrics and Gynecology Clinic
Source
Article Created: 2002-06-27
Article Updated: 2002-07-12
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