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Reconsidering
Hormone Replacement Therapy
I have, once
again, become a hormone nibbler. Over the
years, I have written extensively – some might even say ad
nauseam – about the pros and cons of hormone replacement therapy (HRT)
for menopausal women, a subject near and dear to my heart, and to that
of every other woman I know over 50. At first, the
columns were mostly positive, touting the many benefits believed to
inhere in the pills and patches designed to replace the natural estrogen
that women lose at menopause. These
supposed benefits included not just getting rid of the immediate
symptoms of menopause such as hot flashes and vaginal dryness but
prevention of future problems, too. Yeah, I was
troubled by the increased breast cancer risk that comes with longterm
hormone use – who isn’t?. But given my benign family history, I
happily popped my nightly hormone pills, gambling that the overall
benefits were worth it because of the lower risk of osteoporosis and,
especially, heart disease, which kills six times as many women as breast
cancer. Then,
trouble. Several years ago came data from better studies suggesting that
the heart benefits of estrogen replacement were not holding up. I
started biting my hormone pills in half. Until last year, when I had a
bone density scan that seemed to show a small loss of bone over several
years earlier. Back to the
full dose. Now, I’m
nibbling again, possibly on my way toward tapering off for good from my
beloved hormones (I just plain feel good on them). That’s
because of an international position paper being published later this
summer that casts serious doubt on the benefits of hormone therapy. The
paper, called “Women’s Health and Menopause: A Comprehensive
Approach,” is not a new study per se, but pulls together in a coherent
way the research that already exists. Put out by the National Heart,
Lung and Blood Institute, the Office of Research on Women’s Health and
the Giovanni Lorenzini Medical Science Foundation in Milan and Houston,
it essentially makes the case that there are more reasons NOT to take
hormones long term than to take them. In addition,
two new research studies on coronary and non-coronary effects of HRT,
scheduled to come out tomorrow in the Journal of the American
Medical Association, may further weaken the rationale for hormones. The shifting
view of hormone therapy “is one of the most dramatic sea changes that
I have ever seen in clinical medicine,” says Dr. JoAnn Manson, chief
of preventive medicine at Brigham and Women’s Hospital and principal
Boston investigator of the Women’s Health Initiative, a randomized
trial of hormone therapy in 27,000 women. “The field
has been turned upside down in the past four years, since the HERS trial
in 1998,” a randomized study that showed that women who had already
had a heart attack were at increased risk of another in the first year
of hormone therapy, says Manson. “We’re gone from thinking hormone
replacement therapy was a panacea for heart disease prevention to
thinking that it now may even increase the risk.” Dr. Deborah
Grady, director of the University of California, San Francisco/Mt. Zion
Women’s Health Clinical Research Center, agrees: “Until the last few
years,” she says, “we thought it was good for heart disease. Now we
don’t…. If it’s not good for heart disease, it changes the whole
picture.” For the
record, this “new” view of HRT fits with what many lay health
advocates have been saying for years. “We’ve always been skeptical
because the kind of research we wanted had not been done,” says Judy
Norsigian, executive director of the Boston Women’s Health Book
Collective and a co-author of “Our Bodies, Ourselves.” The National
Women’s Health Network in Washington, D.C. puts it even more strongly.
“The widespread popularity of hormone replacement therapy in the
United States is a triumph of marketing over science and advertising
over common sense.” The
international position paper doesn’t go quite that far, but it does
challenge many prevailing views of hormone therapy. One popular
perception, the position paper notes, is that estrogen prevents memory
loss and slows progression of Alzheimer’s disease; the evidence from
clinical trials have not confirmed the Alzheimer’s hypothesis and
trials on normal memory loss are still ongoing. Another is that estrogen improves symptoms of depression. Estrogen does indeed combat the hot flashes and disturbed sleep of menopause that can make women feel lousy. But there’s “no convincing clinical trial data,” the paper says, “that estrogen therapy in postmenopausal women is an effective treatment for major depression.” But the real
nail in the coffin for HRT is its effect on the heart. As the
position paper notes, the 1998 HERS study followed women who had already
had a heart attack for about four years. Unlike
observational studies that simply track women who decide on their own
whether or not to take HRT, this study randomly assigned women to take
HRT or not. (This gets rid of a major source of the potential bias in
observational studies, namely that women who choose HRT are often
healthier, and wealthier, to start with, hence whatever benefits they
experience may be due to other health habits, not hormones per se.) The HERS
study found that in the first year of HRT use, the risk of heart attack
actually increased in women on HRT, though this risk declined somewhat
with longer use. It’s possible that this initial increased risk comes
from blood clots triggered by HRT, notes Dr. Michael F. Holick,,
director of the Bone Healthcare Clinic at Boston Medical Center. Indeed,
the risk of clotting appears to be highest when a woman first starts
using hormones, may then decrease over time back toward baseline. But new data
may make that explanation less likely. Although the initial HERS study
only followed women for about four years, researchers continued to track
thre women for three more years. The results of this longer HERS
follow-up, expected to be published tomorrow in JAMA, are believed to
show that there was no cardiac benefit to HRT. In 1999,
researchers from the Nurses’ Health Study, an ongoing, observational
study looked at a subset of women who already had heart disease. Just as
in the HERS study, the women with pre-existing heart disease showed an
initial increased risk of another heart attack in the first year of
taking HRT, notes Dr. Nananda Col, a menopause specialist at Brigham and
Women’s Hospital. But the
cardiac risks may not even be confined to women who already have heart
disease. Preliminary data from the trial of 27,000 women suggest that
with roughly three years of follow up, HRT slightly increases the risk
of heart disease, stroke, deep vein thrombosis and other
clotting problems even in healthy women, notes Manson of the Brigham. Moreover,
researchers also worry that HRT can raise levels of C-reactive protein,
an inflammatory substance that may contribute to heart attacks. The bottom
line for heart disease, then, is this: HRT does not protect against
heart disease and may even increase risk. So if you’re taking HRT to
improve your cholesterol levels, consider switching to one of the
“statin” drugs that lower cholesterol and the risk of heart attack. And what
about the other reasons women take HRT? Hormones are
still the best thing going for hot flashes – for a few years. there
are other options. Some women eat soy products. Some find that
antidepressants known as SSRIs (selective serotonin reuptake inhibitors)
help control hot flashes. A blood pressure medication called clonidine (Catapres)
may also help; so can vitamin E (400 to 800 International Units a day). As for
osteoporosis prevention, that reason for taking HRT is also weakening,
basically because there other choices. The key. it should go without
saying that, is exercise and diet, just as with heart disease
prevention. So are micronutrients, mainly calcium (1200 milligrams a
day) and vitamin D (600 to 800 International Units). In addition,
bisphosphonate drugs such as Fosamax and Actonel can help restore bone mass and reduce the risk of hip and
other fractures. “Designer”
estrogens such as raloxifene (Evista) can also protect against
osteoporosis, though they have not been shown to reduce hip fracture
risk and can cause hot flashes. On the other hand, raloxifene doesn’t
raise the risk of breast cancer, and may protect against it; moreoever,
a study last year showed it may have cardiovascular benefits among women with a
history of heart disease. Granted,
women “who have used HRT for decades are less likely to get fractures
than those who haven’t,” says Col of Brigham and Women’s Hospital.
But for women who have not taken HRT and who develop osteoporosis in
their 80s, HRT is probably not the best choice anyway: bisphosphonate
drugs are. The list of
drawbacks goes on, seemingly endlessly. HRT seems to increase the risk
of gallbladder disease, often making surgery necessary. And, according
researchers from the Schepens Eye Research Institute in Boston writing
last year in JAMA, it may increase the risk of dry eye syndrome, in
which the eyes become severely dry and irritated. Still, there
may be good news coming. A new drug from Organon, Inc. called tibolone
is drawing rave reviews from scientists for its apparent ability
to provide the good effects of estrogen without the risks.
This synthetic steroid, currently being used in Europe to treat
hot flashes, seems to help protect against osteoporosis and improve sex
drive while not promoting the growth of breast tissue. Dr. Doug
Ross, director for osteoporosis and HRT at Organon, says more studies
are underway, though it will be a few years before the drug is approved,
roughly the time when results from the Women’s Health Initiative will
be reported. Until then?
For me at least, it’s exercise, exercise, exercise. And ever-tinier
nibbles of hormones. Until the next big research paper comes out or I
just plain change my mind again. For more information, you may read: The Truth About Hormone Replacement Therapy, by the National Women’s Health Network (Prima Publishing.)
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