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Hormone Replacement Therapy
On this page:
Choosing whether or not to use postmenopausal hormone therapy can
be one of the most important health decisions women face as they
age. As with taking any treatment, the decision involves carefully
weighing the risks and benefits involved.
But, until recently, the picture of those risks and benefits has
been unclear. Studies gave conflicting results about the therapy's
effects on breast cancer, heart disease, and other conditions.
Box 1 |
Oral Estrogen and Estrogen/Progestin
Products* |
Estrogen pills: |
Premarin |
conjugated equine estrogens |
Cenestin |
synthetic conjugated estrogens |
Estratab |
esterified estrogens |
Menest |
esterified estrogens |
Ortho-Est |
estropipate (piperazine estrone
sulfate) |
Ogen |
estropipate (piperazine estrone
sulfate) |
Estrace |
micronized 17-beta-estradiol |
Progestin pills: |
Amen |
medroxyprogesterone acetate |
Cycrin |
medroxyprogesterone acetate |
Provera |
medroxyprogesterone acetate |
Micronor |
norethindrone |
Nor-QD |
norethindrone |
Aygestin |
norethindrone acetate |
Ovrette |
norgestrel |
Norplant |
levonorgestrel |
Prometrium |
progesterone USP (in peanut oil) |
Megace |
megestrol acetate (not for uterine
protection) |
Estrogen plus progestin
pills: |
Premphase |
conjugated equine estrogens and
medroxyprogesterone acetate |
Prempro |
conjugated equine estrogens and
medroxyprogesterone acetate |
Femhrt |
ethinylestradiol and norethindrone
acetate |
Activella |
17-beta-estradiol and norethindrone
ecetate |
Ortho-Prefest |
17-beta-estradiol and norgestimate |
* As of Fall
2000
|
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In the summer of 2002, new findings emerged that have finally
begun to fill in some of the picture's details. While much more
remains to be learned, the findings offer women some guidance about
the risks and benefits of using postmenopausal hormone therapy.
This fact sheet discusses those findings and gives you an
overview of such topics as menopause, hormone therapy, and
alternative treatments to the symptoms of menopause and various
health risks that come in its wake. It also provides a list of
sources you can contact for more information.
If you're on hormone therapy–whether short- or long-term
use–you're bound to have a lot of concerns. This fact sheet will
provide some information, but it's important to talk with your
doctor or other health care provider about your health profile.
Being informed is one of the best ways you can protect your
health.
Box 2 |
Gels, Creams, Patches, and Other Hormone
Products* |
Estrogen products: |
Cream |
Estrace |
micronized 17-beta-estradiol |
|
Ortho Dienestrol |
dienestrol |
|
Premarin |
conjugated equine estrogens |
Vaginal Tablet |
Vagifem |
estradiol hemihydrate |
Vaginal Ring |
Estring |
micronized 17-beta-estradiol |
Skin Patch |
Alora |
micronized 17-beta-estradiol |
|
Climara |
micronized 17-beta-estradiol |
|
Esclim |
micronized 17-beta-estradiol |
|
Estraderm |
micronized 17-beta-estradiol |
|
Vivelle |
micronized 17-beta-estradiol |
|
Vivelle-Dot |
micronized 17-beta-estradiol |
Progestin products: |
Vaginal Gel |
Crinone |
progesterone |
Injection |
Depo-Provera |
medroxyprogesterone acetate (not for uterine
protection) |
IUD |
Mirena |
levonorgestrel |
|
Progestasert |
progesterone |
Estrogen plus progestin
products: |
Skin Patch |
Combipatch |
17-beta-estradiol and norethindrone
acetate |
Ortho-Prefest |
17-beta-estradiol and norgestimate |
Injection |
Depo-Testadiol |
testosterone and estradiol
cypionate |
* As of Fall
2000
|
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As you age, significant internal changes take place that affect
your production of the two female hormones, estrogen and
progesterone. The hormones, which are important in regulating the
menstrual cycle and having a successful pregnancy, are produced by
the ovaries, two small, oval-shaped organs.
During the years just before menopause, known as perimenopause,
your ovaries begin to shrink. Levels of estrogen and progesterone
fluctuate as your ovaries try to keep up production of the hormones.
You can have irregular menstrual cycles, along with unpredictable
episodes of heavy bleeding during a period. Perimenopause usually
lasts several years.
Eventually, your periods stop.
Menopause marks the time of your last menstrual period. It is not
considered the last until you have been period-free for 1 year
without being ill, pregnant, breast-feeding, or using certain
medicines, all of which also can cause menstrual cycles to cease.
There should be no bleeding, even spotting, during that year.
Natural menopause usually happens sometime between the ages of 45
and 54.
You also can undergo menopause as the result of surgery. A
surgical procedure, called a hysterectomy, removes the uterus and
sometimes the ovaries and fallopian tubes as well. You go through
menopause if both of your ovaries are removed. Otherwise, the
surgery does not affect menopause, which still occurs naturally.
Whether you go through menopause naturally or surgically,
symptoms can result as your body tries to adjust to the drop in
estrogen levels. These symptoms vary greatly–one woman may breeze
through menopause with few symptoms, while another has difficulty.
Symptoms may last for several months or years, or persist. The most
common symptoms are hot flashes or flushes, sweats, and sleep
disturbances. (A hot flash is a feeling of heat in your face and
upper body, which may cause the skin to appear flushed or red as
blood vessels expand. Hot flashes that occur with severe sweating
during sleep are called night sweats.) But the drop in estrogen also
can contribute to other symptoms, such as changes in the vaginal and
urinary tracts, which can cause painful intercourse, urinary
infections, and the need to urinate more often.
Box 3 |
Hormone Therapy Schedules
- Cyclic or sequential–Estrogen for 25 or 30 days a month,
with progestin added for 10-14 days
- Continuous-combined–Estrogen and progestin daily
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To relieve the symptoms of menopause, doctors may prescribe
postmenopausal hormone therapy. This can involve the use of either
estrogen alone or with another hormone called progesterone, or
progestin in its synthetic form. The two hormones normally help to
regulate a woman's menstrual cycle. Progestin is added to estrogen
to prevent the overgrowth (or hyperplasia) of cells in the lining of
the uterus. This overgrowth can lead to uterine cancer. If you
haven't had a hysterectomy, you'll receive estrogen plus progestin
therapy; if you have had a hysterectomy, you'll receive
estrogen-only therapy. Hormones may be taken daily (continuous use)
or on only certain days of the month (cyclic use).
They also can be taken in several ways, including orally, through
a patch on the skin, as a cream or gel, or with an intrauterine
device (IUD) or vaginal ring. How the therapy is taken can depend on
its purpose. For instance, a vaginal estrogen ring or cream can ease
vaginal dryness, urinary leakage, or vaginal or urinary infections,
but does not relieve hot flashes.
Hormone therapy may cause side effects, such as bleeding,
bloating, breast tenderness or enlargement, headaches, mood changes,
and nausea. Further, side effects vary by how the hormone is taken.
For instance, a patch may cause irritation at the site where it's
applied.
Box
1, Box
2, and Box
3 list products and schedules for various hormone therapies.
There also are nonhormonal approaches to easing the symptoms of
menopause. Box
4 offers a list of some of these alternatives.
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Box 4 |
Alternatives to Hormone Therapy to Help Prevent
Postmenopausal Conditions and Relieve Menopausal
Symptoms
You may want to consider alternatives to
hormone therapy to ease menopausal symptoms. The list below
includes some locally applied hormone products (which may not
carry the same risks as those that deliver medication
throughout the body), dietary supplements, and lifestyle
measures. Talk with your doctor or other health care provider
about the best treatment for you for each symptom.
Be aware that, unlike drugs, the U.S. Food
and Drug Administration (FDA) does not have the authority to
approve dietary supplements before they are sold. The dietary
supplement manufacturer is responsible for insuring that the
product is safe and that any representations or claims made
about it are adequately substantiated and not false or
misleading.
One positive move you can make to feel better
is to adopt a healthy lifestyle–don't smoke, eat a variety of
foods low in saturated fat and cholesterol and moderate in
total fat, maintain a healthy weight, and be physically
active.
For postmenopausal conditions:
Osteoporosis
- See
Box 20 for lifestyle behaviors to protect bone density
- Designer estrogen Raloxifene (Evista), which preserves
bone density
- Bisphosphonates Actonel or Fosamax, which reverse bone
loss and prevent fractures
- Calcitonin (a nasal spray), which may prevent fractures
- Note: Phytoestrogens (see "Hot flashes" below) have not
been shown to reduce fractures
Heart disease
- Lifestyle behaviors, including:
- Following a healthy eating plan
- Limiting consumption of alcoholic beverages
- Not smoking
- Maintaining a healthy weight
- Being physically active
- Preventing and controlling high blood pressure
- Preventing and controlling high blood cholesterol
- Managing diabetes
- Taking prescribed medication to control heart disease
For menopausal symptoms:
Hot flashes
- Lifestyle changes. These include dressing and
eating to avoid being too warm, sleeping in a cool room, and
reducing stress. Avoid spicy foods and caffeine. Try deep
breathing and stress reduction techniques, including
meditation and other relaxation methods.
- Soy. This contains phytoestrogens.
(Phytoestrogens are estrogen-like substances derived from a
plant source.) However, there is no solid evidence that
soy–or other sources of phytoestrogens–really do relieve hot
flashes. Further, the risks of taking soy, especially the
more concentrated forms of soy, such as pills and powders,
are not known. Phytoestrogens from soy can be consumed
through foods or supplements. Soy food products include
tofu, tempeh, soy milk, and soy nuts. These soy products are
more likely to work on mild hot flashes.
- Other sources of phytoestrogens. These include
such herbs as black cohosh, a member of the buttercup
family, wild yam, dong quai, and valerian root.
- Antidepressants, such as Effexor, Paxil, and
Prozac have been proved moderately effective in clinical
trials; however, they have not been approved for this use.
Vaginal dryness
- Vaginal lubricants and moisturizers (available over the
counter).
- Products that release estrogen locally (such as vaginal
creams, a vaginal suppository, called Vagifem, and a plastic
ring, called an Estring)–these are used for more severe
dryness. The ring contains a low dose of estrogen and may
not protect against osteoporosis. It also must be changed
every 3 months.
Mood swings
- Lifestyle behaviors, including getting enough sleep and
being physically active
- Relaxation exercises
- Antidepressant or anti-anxiety drugs
Insomnia
- Over-the-counter sleep aids
- Milk products, such as a glass of milk or cup of
yogurt–choose low- or fat-free varieties
- Do physical activity in the morning or early afternoon–
exercising later in the day may increase wakefulness
- Hot shower or bath immediately before going to bed
Memory problems
- Mental exercises
- Lifestyle behaviors, especially getting enough sleep and
being physically active
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Menopause may cause other changes that produce no symptoms yet
affect your health. For instance, a woman's risk of developing heart
disease begins to rise around menopause. After menopause, women's
rate of bone loss increases. The increased rate can lead to
osteoporosis, which may in turn increase the risk of bone fractures,
usually after age 70.
Through the years, studies were finding evidence that estrogen
might help with some of these postmenopausal health risks–
especially heart disease and osteoporosis. With more than 40 million
American women over age 50, the promise seemed great.
Although erroneously thought of in the past as a "man's disease,"
heart disease is the leading killer of American women. Women
typically develop it about 10 years later than men.
Similarly, menopause is a time of increased bone loss. Bone is
living tissue. Old bone is continuously being broken down and new
bone formed in its place. With menopause, bone loss is greater and,
if not enough new bone is made, the result can be weakened bones and
osteoporosis, which increases the risk of breaks. One of every two
women over age 50 will have an osteoporosis-related fracture during
her life.
Many scientists believed these increased health risks were linked
to the postmenopausal drop in estrogen produced by the ovaries and
that replacing estrogen would help protect against the diseases.
Box 5 |
About Dietary Supplements
If you use dietary supplements
to try to ease hot flashes and other menopausal symptoms, you
should bear these points in mind: The U.S. Food and Drug
Administration (FDA) does not have the authority to approve
dietary supplements before they are marketed, and it's
important to tell your health care provider that you are
taking such remedies.
Dietary supplements are sold over the counter
and may contain phytoestrogens: These are estrogen-like
substances that come from some plants (such as soy) and plant
materials (such as legumes, vegetables, cereals, and some
herbs). For instance, these products may contain black cohosh,
wild yams, dong quai, and valerian root.
Dietary supplement manufacturers are
responsible for making sure that their products are safe. The
FDA must show that a dietary supplement is harmful before it
can limit the product's use or remove it from the market.
Currently, there are no FDA regulations that specifically
establish minimum standards for the manufacture of dietary
supplements in order to insure their identity (tests to insure
that the ingredient is actually what its label claims),
purity, quality, strength, and composition. You may want to
contact a product's manufacturer before buying it.
Furthermore, the possible effects of the
products are not known. Some of the substances they contain
are being studied. For example, soy contains plant estrogens,
which are being studied to see if they have the same risks and
benefits as estrogen.
Some of this research is being supported by
the Office of Dietary Supplements, the National Center for
Complementary and Alternative Medicine, the National Institute
on Aging, and other units of the National Institutes of
Health.
Until more is known about these substances,
you should use them with caution. Also, as noted, tell your
health care provider if you take a dietary supplement or if
you increase your intake of dietary phytoestrogens. There may
be dangerous side effects. An increase in the level of
estrogens in your body could interfere with other prescription
medications you are taking or even cause an
overdose. |
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Early studies seemed to support hormone therapy's ability to
protect women against the diseases that tend to occur after
menopause. For instance, research showed that the treatment does
prevent osteoporosis. However, other findings lacked evidence or
were unclear. No large clinical trials had proved that hormone
therapy prevents heart disease or fractures. Answers also were
needed about other possible effects of long-term use of hormones,
especially on such conditions as breast and colorectal cancers.
Further, prior research on postmenopausal hormone therapy's
effect on heart disease had involved mainly observational studies,
which can indicate possible relationships between behaviors or
treatments and disease, but cannot establish a cause-and-effect tie.
Box 6 |
What We Lean From Different Types of Studies
Medical researchers conduct many types of
studies. The reason is that the studies yield different kinds
of information. Together, the studies help scientists
understand health and disease, and how to educate people so
they can lead healthier lives.
Three main types are: observational studies,
clinical trials, and community prevention studies. Each type
is discussed briefly below:
Observational studies
follow women's medical and lifestyle practices but do not
intervene. Such studies can turn up possible relationships
between various factors and health or illness. Those factors
include population traits, ethnicity, genetic attributes, and
behaviors. For instance, researchers can track women who do
and do not take postmenopausal hormone therapy. The results
may show that the hormone users have fewer heart attacks. But
the results cannot conclude that hormone therapy reduces the
risk of heart disease. Other factors may have played a part.
For instance, compared with women who do not use hormone
therapy, those who do are often healthier, have a higher level
of education and better access to medical care, and are more
willing to follow a prescribed therapy.
Clinical trials control and compare
specific medical interventions, such as the use of
postmenopausal hormone therapy. Women on an intervention are
compared with those who do not receive the treatment.
Researchers try to control all of the experimental conditions
so that any difference between the two groups can be tied to
the intervention.
The most rigorous of these investigations is
the randomized, controlled, double-blinded clinical trial.
Women are randomly assigned to the study groups and, in a drug
trial for instance, neither the women nor the researchers
typically know who is receiving an active drug and who a
placebo. Further, on average women in the two groups will be
similar in age, education, health at the time of entering the
trial, and other factors that may affect the results. These
trials are considered to be the "gold standard" among types of
studies because they yield the most reliable information.
Clinical trials are often done to test whether a possible
relationship uncovered in an observational study is in fact
so. The trials help establish a causal link between a
treatment and a specific medical outcome, such as fewer heart
attacks.
Community prevention studies explore
ways to encourage people to adopt healthier
behaviors. |
There also were some clinical trials, which are considered the
"gold standard" in establishing a cause-and-effect connection
between a behavior or treatment and a disease. The most definitive
clinical trials are those that test the effects of a treatment on
the disease itself. But such clinical trials are time-consuming and
costly. Consequently, early clinical trials of postmenopausal
hormone use tested the therapy's effects on the risk factors or
predictors of various diseases. One of the most important of these
early clinical trials that tested effects on risk factors was the
"Postmenopausal Estrogen/ Progestin Interventions Trial," or PEPI.
Supported by the National Heart, Lung, and Blood Institute (NHLBI)
and other units of the National Institutes of Health (NIH), PEPI
tested the effects of four hormone regimens (one estrogen–only and
three different estrogen plus progestin regimens) on key risk
factors for heart disease and bone mass. Begun in 1987, it followed
875 healthy, postmenopausal women, ages 45-64, for 3 years. About a
third of the women had had a hysterectomy. Participants included
various races but were predominantly white.
Box 7 |
Risk Factors for Uterine Cancer
There are various types of uterine cancer.
The most common is endometrial cancer, which begins in the
lining (endometrium) of the uterus. It is often referred to as
uterine cancer.
Key risk factors for uterine cancer are:
- Age–usually occurs after age 50
- Endometrial hyperplasia–an increase in cells in the
lining of the uterus
- Hormone therapy–using estrogen without progesterone
- Obesity and related conditions
- Tamoxifen–taken to prevent breast cancer
- Race–white women are more likely than African American
women to develop uterine cancer
- Colorectal cancer–those who have an inherited form are
at a higher risk of developing uterine cancer
- Factors that increase exposure to estrogen–not having
children, starting menstruation at an early age, entering
menopause late
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PEPI's results were generally positive:
- Each of the hormone regimens reduced "bad" LDL cholesterol and
raised "good" HDL cholesterol, although estrogen-only raised good
cholesterol the most. (LDL, or low density lipoprotein, carries
cholesterol to tissues, including the arteries, while HDL, or high
density lipoprotein, carries it away, aiding its removal from the
body.)
- All hormone therapies decreased levels of fibrinogen. (High
levels of fibrinogen allow blood clots to form more readily, thus
increasing the risk of heart disease and stroke.)
- On the other hand, a large percentage of those who took
estrogen alone had a high rate of overgrowth of the uterine lining
and other abnormalities. This finding stressed the need for women
with a uterus to use estrogen plus progestin therapy. The added
progestin protects women against uterine cancer.
Box 8 |
Breast Cancer Risk Factors
About 80 percent of breast cancer cases occur
after age 50. One of every eight American women who live to be
85 develops breast cancer. Some factors increase the risk for
breast cancer. However, most women who develop breast cancer
do not have any of the risk factors.
Key factors that increase the risk of
developing breast cancer are:
- Personal history–if you've had it once, you're more
likely to develop it again
- Family history–if your mother, sister, or daughter had
breast cancer, especially at an early age, you're more
likely to develop it
- Other breast changes (not including ordinary
"lumpiness")–such as atypical hyperplasia (an irregular
pattern of cell growth)
- Genetic alterations–changes in certain genes, including
BRCA1 and BRCA2 mutations
Other factors also may increase the risk
of developing breast cancer. These include:
- Race–white women are more likely to develop it than
African American or Asian women
- Estrogen exposure–risk is somewhat increased for those
who began menstruation early (before age 12), had menopause
late (after age 55), never had children, or took hormone
therapy for long periods
- Late childbearing–having a first child after about age
30
- Radiation therapy–if given to the chest more than 10
years ago, especially in women younger than age 30
- Breast density–breasts with a high proportion of lobular
and ductal tissue, which is dense and in which breast
cancers usually appear
- Alcoholic beverage consumption
|
PEPI did not last long enough to tackle some crucial questions
about hormone therapy, such as a possible rise in breast cancer risk.
The first clinical trial to investigate the effects of
postmenopausal hormone therapy directly on diseases was the "Heart
and Estrogen-Progestin Replacement Study," or HERS, which began
enrolling participants in January 1983. HERS tested whether estrogen
plus progestin would prevent a second heart attack or other coronary
event. Altogether, it involved 2,763 postmenopausal women, average
age 67, who already had heart disease. The women received either
estrogen plus progestin or a placebo for about 4 years. (A placebo
is a substance that looks like the real drug but has no biologic
effect.)
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Box 9 |
WHI Findings On Estrogen Plus Progestin
Therapy
Compared with a placebo, after about 5 years
of use, estrogen plus progestin resulted in:
Increased risks
- 26% increase in breast cancer
- 41% increase in strokes
- 29% increase in heart attacks
- Doubled rates of blood clots in legs and lungs
Increased benefits
- 37% less colorectal cancer
- 34% fewer hip fractures
No difference
|
Box 10 |
Estrogen Plus Progestin Pills vs. Placebo
Pills
The rate of the following medical conditions
per 10,000 women per year

|
Box 10 Text Version |
Estrogen Plus Progestin Pills vs. Placebo
Pills
The rate of the following medical conditions
per 10,000 women per year
|
Placebo Pills
|
Estrogen Plus Progestin
Pills |
Breast Cancer |
30 |
38 |
Heart Attack |
30 |
37 |
Stroke |
21 |
29 |
Total Blood Clots |
16 |
34 |
Hip Fracture |
15 |
10 |
Colorectal Cancer |
16 |
10 | |
Findings, released in 1998, showed that those on the hormone
therapy did not have fewer fatal or nonfatal heart attacks. In fact,
the women's risk for a heart attack increased during the first year
of hormone use, declining thereafter. HERS also showed that the
therapy caused an increase in blood clots in the legs and lungs.
More recently, the "HERS Follow-Up Study," which tracked the
women for about 3 more years, found no decrease in heart disease
from use of estrogen plus progestin therapy.
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Box 11 |
What Do the Data Really Mean?
The data sound scary–and confusing. A 41
percent increase in strokes. A 34 percent decline in hip
fractures. Which is more important? The bad news, or the good?
Either way, the percentages
sound big. So it's good to take a moment and check out what
they're really saying.
There are two main ways to express
risk–"relative risk" and "absolute risk." The relative risk
measures and compares the percent change in risk of some
health-related event in a population that has been exposed to
some agent and another that has not. The increase (or
decrease) in absolute risk is an estimate of the number or
proportion of women who will (or will not) develop a disease
when exposed to a particular agent.
Relative risk allows scientists to compare
data. In the WHI study, for example, scientists wanted to find
out the relative risk of breast cancer in women who had and
had not been exposed to the estrogen plus progestin hormone
therapy. After about 5 years, the study had 166 cases of
breast cancer among estrogen plus progestin users, compared
with 124 in the placebo group. However, there were more woman
in the hormone group–8,506, compared with 8,102 in the placebo
group. To be able to compare data from the groups, the cases
were converted into rates per 10,000 women per year. Thus, the
rate of breast cancer in the hormone group was 38 per 10,000
women, compared with 30 per 10,000 women in the placebo group.
This also can be expressed as 38 divided by 30 or 1.26. Since
that is 0.26 greater than an equal risk (or 1.00), the women
on hormone therapy had a 26 percent greater chance of
developing breast cancer than non-users.
What was the increase in absolute risk of
developing breast cancer for women in the WHI study? On
average, in any single year, 0.08 percent more women in the
hormone group developed breast cancer than women in the
placebo group. This means that, if a group of 10,000 women
takes estrogen plus progestin for a year, there will be 8 more
cases of breast cancer among the hormone users than if they
hadn't taken the therapy. Thus, women on the hormone therapy
have only a slightly increased absolute risk of breast cancer
over a year. (See Boxes 9
and 10
for a summary of the relative and absolute risks of breast
cancer and other conditions for women in the estrogen plus
progestin study.)
But, if you count up all the added cases of
breast cancer, heart attacks, strokes, and blood clots in the
lungs and subtract the fewer cases of colorectal cancer and
hip fractures, you'd still get about 100 extra harmful events
among the 10,000 hormone users after 5.2 years–the period the
study ran. Multiply that by 10 years and millions of women and
the number of cases of adverse effects grows.
Remember too that reports of increased risks
do not mean you will develop breast cancer or another
condition if you have been using the hormone therapy. Your
personal and family medical history, along with your lifestyle
and other influences, play a big role in your chance of
developing a disease. |
In 1991, the NHLBI and other units of the NIH launched the
"Women's Health Initiative" (WHI), one of the largest studies of its
kind ever undertaken in the United States. It consists of a set of
clinical trials, an observational study, and a community prevention
study, which altogether involve more than 161,000 healthy,
postmenopausal women.
The observational study is looking for predictors and biological
markers for disease and is being conducted at more than 40 centers
across the United States, while the community prevention study,
which has ended, sought to find ways to get women to adopt healthful
behaviors and was done with the Federal Government's Centers for
Disease Control and Prevention.
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WHI's three clinical trials, conducted at the same U.S. centers,
are designed to test the effects of postmenopausal hormone therapy,
diet modification, and calcium and vitamin D supplements on heart
disease, osteoporotic fractures, and colorectal cancer risk.
Box 12 |
Risk Factors for Stroke
Main risk factors are:
- High blood pressure
- Diabetes
- Cigarette smoking
Other risk factors include:
- Family history–stroke appears to run in some families,
whether due to genetics and/or shared lifestyle
- Heavy consumption of alcoholic beverages
- High blood cholesterol
- Menopause
|
The postmenopausal hormone therapy clinical trial has two parts.
The first involved 16,608 postmenopausal women with a uterus who
took either estrogen plus progestin therapy or a placebo. The second
involves 10,739 women who have had a hysterectomy and are taking
estrogen alone or a placebo.
The estrogen plus progestin trial used 0.625 milligrams of
conjugated equine estrogens taken daily plus 2.5 milligrams of
medroxyprogesterone acetate taken daily (Prempro). Two key reasons
that that combination was chosen are: It is the mostly commonly
prescribed form of the combined hormone therapy in the United
States, and, in several observational studies, it had appeared to
benefit women's health.
The women in the WHI estrogen plus progestin study were aged 50
to 79. They enrolled in the study between 1993 and 1998. Their
health was carefully monitored by an independent panel, called the
Data and Safety Monitoring Board (DSMB).
Box 13 |
Risk Factors for Colorectal Cancer
About 30,000 women a year die of colorectal
cancer–it is the third-leading cause of cancer deaths for
women, after lung and breast cancers.
Factors that increase the
risk of colorectal cancer include:
- Age–risk increases after age 50
- Diet–eating a diet high in fat and calories, and low in
fiber
- Polyps–these are benign growths on the inner wall of the
colon and rectum
- Personal medical history–having had cancer of the ovary,
uterus, or breast; also having had colorectal cancer once
increases the chance of developing it again
- Family medical history–having first-degree relatives
(parents, siblings, or children) with colorectal cancer,
especially at a young age; risk increases even more if many
family members have had colorectal cancer
- Ulcerative colitis–a condition in which the lining of
the colon becomes inflamed
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The study's main goal was to see if the therapy would help
prevent heart disease and hip fractures. Another goal was to see if
those possible benefits were greater than the possible risks from
breast cancer, endometrial (or uterine) cancer, and blood clots.
The study was to have continued until 2005. However, it was
stopped in July 2002 because the DSMB found an increased risk of
breast cancer and that, overall, risks from use of the hormones
outweighed and outnumbered the benefits. "Outnumbered" means that
more women had adverse effects from the therapy than benefitted from
it.
These results show both risks and benefits from use of the
estrogen plus progestin therapy. The key adverse effects were more
cases of breast cancer, heart attacks, strokes, and blood clots. The
main benefits were fewer hip and other fractures and cases of
colorectal cancer.
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Box 14 |
Postmenopausal Hormone Therapy and Ovarian Cancer
Risk
Early studies of postmenopausal hormone
therapy found inconsistent results about its effect on the
risk of ovarian cancer: Some reported increased risk with
estrogen use, while others reported no effect or even a
protective one. Most of those studies were relatively small
and did not take into account the key risk factors for ovarian
cancer .
More recently, two large observational
studies have indicated that long-term estrogen use increases
the risk of ovarian cancer. It's important to keep in mind
that observational studies do not prove that a treatment
causes a disease. The evidence from these studies is cautionary, not
definitive.
Here's more on the studies:
- One study followed 211,581 postmenopausal women from
1982-1996. Of those, 44,260 had used estrogen-only hormone
therapy; the rest did not use hormone therapy. None of the
women had had a hysterectomy, ovarian surgery, or cancer.
Those with 10 or more years of estrogen use had an increased
risk of dying from ovarian cancer–and, while the risk
decreased somewhat long after use was stopped, it was still
higher than that of women who had never used estrogen-only
therapy.
- Another study followed 44,241 women from 1979-1998. It
found that estrogen-only therapy increased the risk of
ovarian cancer. Women who used estrogen alone for 10 or more
years had an 80 percent higher risk of ovarian cancer than
women who had never used the hormone therapy; women who used
estrogen alone for 20 or more years had a 220 percent higher
risk than women who had never used hormone therapy.
The study found no increased risk of ovarian cancer
for users of estrogen plus progestin. However, few women in
the study had used the combination therapy for more than 4
years.
More research is needed to see if estrogen
plus progestin affects ovarian cancer risk–and on other
aspects of postmenopausal hormone use. For instance, another
recent study found that estrogen alone or estrogen plus
progestin used on a sequential basis increased the risk for
ovarian cancer, while estrogen plus progestin used
continuously did not. |
Additionally, there was no increase in deaths from breast cancer
or from other causes. Further, there was no increase in the risk of
endometrial cancer.
Breast cancer. The increased risk of breast cancer
appeared after 4 years of hormone use. After 5.2 years, estrogen
plus progestin resulted in a 26 percent increase in the risk of
breast cancer–or 8 more breast cancers each year for every 10,000
women. Women who had used estrogen plus progestin before entering
the study were more likely to develop breast cancer than others,
indicating that the therapy may have a cumulative effect.
- Heart attack. For heart attack, the risk began to
increase in the first year of estrogen plus progestin use and
became more pronounced in the second year. After 5.2 years, there
were 29 percent more heart attacks in the estrogen plus progestin
group than in the placebo group–or 7 more heart attacks each year
for every 10,000 women. Unlike HERS, which involved women with
heart disease, the increased risk from estrogen plus progestin did
not go back down again.
- Stroke. For the first time, estrogen plus progestin was
shown to cause more strokes in healthy women. By the end of the
study, the estrogen plus progestin group had 41 percent more
strokes than the placebo group–or 8 more strokes each year for
every 10,000 women.
- Blood clots. The risk of total blood clots was greatest
during the first 2 years of hormone use–four times higher than
that of placebo users. By the end of the study, it had decreased
to two times greater–or 18 more women with blood clots each year
for every 10,000 women.
- Fractures. Estrogen plus progestin reduced hip
fractures by 34 percent–or 5 fewer hip fractures for every 10,000
women. This is the first solid evidence from a clinical trial that
hormone therapy, in helping to prevent bone loss and osteoporosis,
protects women against fractures.
- Colorectal cancer. The therapy also lowered the risk of
colorectal cancer by 37 percent–or 6 fewer colorectal cancers each
year for every 10,000 women. This reduction appeared after 3 years
of hormone use and became more significant thereafter. However,
the number of cases of colorectal cancer was relatively small, and
more research is needed to confirm the finding.
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Box 15 |
Risk Factors for Ovarian Cancer
About 1 in 57 American women will develop
ovarian cancer. Most will be over age 50, but younger women
also can develop the disease.
Here are some factors that increase or
decrease the risk of ovarian cancer:
Increases risk
- Age–risk increases as a woman ages
- Family history of ovarian cancer–higher risk if mother
or sister has had ovarian cancer; somewhat higher risk if
other relatives, such as grandmother, aunt, or cousin, have
developed ovarian cancer
- Postmenopausal hormone therapy–may increase risk
- Fertility drugs
- Personal history of breast and/or colon cancer
Decreases risk
- Oral contraceptives–the longer the use, the lower the
risk may be and the decrease may last after use has ended
- Childbearing and breast-feeding
- Tubal ligation (sterilization) or hysterectomy
- Prophylactic (to prevent or protect) oophorectomy
(surgery to remove one or both ovaries)
|
The findings are important for several reasons: As a clinical
trial, they establish a causal link between use of the particular
hormone therapy and its effects on diseases. Further, the findings
finally offer some firm guidance to the millions of American women
who have a uterus and may consider taking the drugs–6 million
already use a form of combination therapy. And, the results apply
broadly–the study found no differences in risk by prior health
status, age, or ethnicity. The findings do not apply to
postmenopausal use of estrogen alone. That arm of the study, which
used 0.625 mg per day of conjugated equine estrogen (Premarin), did
not have the same increased breast cancer risk and continues.
However, an observational study, supported by the NIH's National
Cancer Institute (NCI), recently found that estrogen-only therapy
appeared to increase the risk of ovarian cancer. But other, similar studies have not found such an
increased risk, and the possible relationship between estrogen use
and ovarian cancer remains unclear. WHI participants were informed
of these findings, and the results were reviewed for their
significance to the study's continuation.
Box 16 |
What About Birth Control Pills?
The recent findings about the risks of
long-term postmenopausal hormone therapy do not apply to use
of birth control pills, which have not been found to increase
breast cancer risk.
There had been concern about
the effect of birth control pills on the risk of breast cancer
because, until recently, studies had given conflicting
results. For example, a 1996 analysis of 54 small studies had
found a slight increase among women who were or had recently
used oral contraceptives. But the 54 studies differed in
quality and some included oral contraceptive preparations no
longer in use. Other studies, such as the 1986 "Cancer and
Steroid Hormone" (CASH) study, had found no increased risk.
In June 2002, findings of the "Women's
Contraceptive and Reproductive Experiences Study" (also called
the Women's CARE Study) were released and showed no increased
risk of breast cancer, regardless of length of oral
contraceptive use, timing of use, age at use, or the users'
risk factors for developing breast cancer. The study,
supported by the NIH's National Institute of Child Health and
Human Development, involved more than 9,257 women between the
ages of 35 and 64. The women were interviewed about their
contraceptive use.
Oral contraceptives do pose risks, however:
Combination oral contraceptives increase the risk of blood
clots. Oral contraceptives should not be used if you are at an
elevated risk for blood clots because of diabetes or another
condition, or if you smoke. Taking oral contraceptives and
smoking increases your risk for heart attack and stroke.
Oral contraceptive use has benefits too: It
can reduce the risk of ovarian cancer, endometrial cancer,
colorectal cancer, pelvic inflammatory disease (an infection
that can lead to infertility), and
osteoporosis. |
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How can you sort through the benefits and risks and make a good
decision about whether or not to use postmenopausal hormone therapy?
Here are several points to help you evaluate the findings:
First, it's important to know that, because the study involved
healthy women, only a small number of them had either a negative or
positive effect from estrogen plus progestin therapy.
The percentages describe what would happen to a whole
population–not to an individual woman. For example, the increased
risk of breast cancer for the women in the WHI study who were taking
the estrogen plus progestin therapy was less than a tenth of 1
percent each year.
But if you apply that increased risk to a large group of women
and over several years, then the number of women affected becomes an
important public health concern. As noted, about 6 million American
women take estrogen plus progestin therapy. That would translate
into nearly 6,000 more cases of breast cancer every year– and, if
all of the women took the therapy for 5 years, that might result in
30,000 more cases of breast cancer.
Box 17 |
Talking With Your Doctor
It's important to be involved in your health
care. Ask questions and express your concerns. Here are some
questions that may help you talk with your health care
provider about hormone therapy:
- Why am I taking hormone therapy? Or why should I take
hormone therapy?
- Which hormone therapy am I on?
- What are my risks for heart disease, breast cancer, and
osteoporosis?
- Should I stop taking the hormone therapy?
- What's the best way for me to stop? What side effects
will I have?
- Is there an alternative therapy that I can use
long-term?
- What alternatives can help me prevent heart disease?
- What alternatives can help me prevent osteoporosis?
- What can I do to keep menopausal symptoms from
returning?
Your risk for heart disease, osteoporosis,
and colorectal cancer may change over time. So remember to
regularly review your health status with your doctor or other
health care provider.
It's also important to bear in
mind that your doctor or other health care provider may not be
able to answer all of your questions–many questions about
postmenopausal hormone use remain. For instance, it's not yet
known if increases in disease risk caused by long-term use of
estrogen plus progestin drop after use stops. As with any
treatment, you need to carefully weigh your personal risks
against the possible benefits and make the best choice
possible for your health and lifestyle needs.
Finally, your doctor or other health care
provider can speak with a WHI Principal Investigator about the
study's results. For a list of the Principal Investigators,
check the NHLBI WHI Web site or contact the NHLBI Health
Information Center. |
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Second, bear in mind that percentages aren't fate. Whether
expressing risks or benefits, they do not mean you will develop a
disease. Many factors affect that likelihood, including your
lifestyle and other environmental factors, heredity, and your
personal medical history.
Finally, realize that most treatments carry risks and benefits.
No one can make a treatment choice for you. Talk with your doctor or
other health care provider and decide what's best for your health
and quality of life. Begin by finding out your personal risk profile
for heart disease, stroke, breast cancer, osteoporosis, colorectal
cancer, and other conditions.
Discuss quality of life issues and alternatives to postmenopausal
hormone therapy. Box
17 will help you talk with your health care provider. Then weigh
every factor carefully and choose the best option for your health
and quality of life. And keep the dialogue going–your health status
can change and so can your choice.
Box 18 |
Your Heart Disease Risk Profile
One in three American women dies of heart
disease. Heart disease kills more American women than any
other cause. It also can lead to disability and decrease one's
quality of life. Yet, many women don't take the threat of
heart disease seriously.
But menopause is a time when you
need to get very serious about heart disease because that's
when your risk for it starts to rise. So, it's more important
than ever to talk with your health care provider about how to
lower your risk of heart disease–or, if you already have it,
to keep it under control. Ask about your "heart disease
profile," a check of the heart disease risk factors you
already have or are at an increased risk of developing.
Risk factors are behaviors or conditions that
increase your chance of developing a disease. The more risk
factors you have, the greater your chance of developing the
disease. For heart disease, the risk factors don't just add
their risks–they multiply them. So it's vital to prevent them
or, if you already have any, to keep them under control.
Fortunately, most heart disease risk factors
can be prevented or controlled. Here's a breakdown of both
types:
Risk factors beyond your control
- Being age 55 or older
- Having a family history of early heart disease–this
means having a mother or sister who has been diagnosed with
heart disease before age 65, or a father or brother
diagnosed before age 55
Risk factors you can control
- Cigarette smoking
- High blood cholesterol
- High blood pressure
- Diabetes (high blood sugar)
- Overweight/obesity
- Physical inactivity
|
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While many questions remain, the new WHI findings provide the
basis for some advice about the use of postmenopausal hormone
therapy. Here it is, along with advice for short-term hormone use to
relieve menopausal symptoms:
Short-term estrogen alone or estrogen plus progestin therapy–
- "Short-term" means the shortest time needed to manage
menopausal symptoms. The benefits of such use could outweigh any
risks for you. Most women use the hormone therapy for 2 to 3
years. However, some may require a longer period of treatment.
Talk with your health care provider about your personal risks and
needs.
Long-term estrogen plus progestin therapy–
- Do not use estrogen plus progestin therapy to prevent heart
disease. The new findings show that it doesn't work. In fact, the
therapy increases the chance of a heart attack or stroke. And it
increases the risk of breast cancer and blood clots. What
can you do instead? Talk to your health care provider about other
ways to prevent heart disease and stroke that have been proven to
be safe and effective. These include lifestyle changes and such
drugs as cholesterol-lowering statins and blood pressure
medications. Lifestyle changes include: not smoking, maintaining a
healthy weight, being physically active, and managing diabetes.
Another key part of this is to follow a healthy eating
plan that has a variety of foods and is low in saturated fat and
cholesterol and moderate in total fat. In addition, limiting how
much salt and other forms of sodium you eat will help keep your
blood pressure at a healthy level.
- Do not use long-term postmenopausal hormone therapy if you
already have heart disease. Such use increases the risk of blood
clots. It also increases the risk of heart attack in the first
year of therapy.
- To prevent osteoporosis, talk with your health care provider
about what your personal risks and benefits would be from estrogen
plus progestin therapy. Weigh any benefits against your risk of
heart disease, stroke, and breast cancer. Ask about alternate
approaches that are considered safe and effective in preventing
osteoporosis and fractures. These include oral biphosphonates,
such as alendronate (or Fosamax) and risedronate (or Actonel), and
selective estrogen receptor modulators (SERMs), such as raloxifene
(or Evista). SERMs are also known as designer estrogens. They are
substances that have estrogen-like effects on some tissues and
anti-estrogen effects on others. Other steps to prevent
osteoporosis include consuming enough calcium and vitamin D, being physically active, especially with
weight-bearing exercises (such as walking, jogging, playing
tennis, and dancing), not smoking, and limiting how many alcoholic
beverages you drink. Smoking and drinking alcohol increase your
risk of osteoporosis.
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Box 19 |
Recommended Daily Intakes of Calcium and Vitamin
D |
Age |
Vitamin D |
Calcium |
19-50 |
200 IU* |
1,200 mg** |
51-70 |
400 IU* |
1,200 mg** |
70+ |
600 IU* |
1,200 mg** |
Note: IU=International Units
* not to exceed 2,000 IU ** not to exceed
2,500 mg |
Long-term estrogen-only therapy–
- The WHI has not yet issued findings about the health risks and
benefits of long-term use of estrogen-only therapy. Consult your
health care provider about your personal health profile and needs.
General advice–
- Whether or not you decide to use postmenopausal hormone
therapy, you should keep your regular schedule of mammograms, and
breast and clinical exams.
- In addition to having regular mammograms, you should protect
your health by having certain other tests done too. These include tests for high blood pressure, high
blood cholesterol, high blood glucose (sugar), bone mineral
density, and overweight.
- If you stop taking hormone therapy and your menopausal
symptoms return, consider alternative treatments. Be aware that some of these remedies have not been
proved effective or safe.
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Box 20 |
Boning Up On Osteoporosis
More than 8 million American women have
osteoporosis–and millions more have lost so much bone that
they're likely to develop it.
Osteoporosis can happen at any age but the
risk grows as you get older. The first noticeable sign of
osteoporosis is often losing height or having a bone break
easily. Other signs can be changes in the shape of the spine,
prolonged severe pain in the middle of the back, and tooth
loss.
Risk factors of osteoporosis include:
- Age–risk increases as you grow older
- Being a woman–women have less bone tissue and lose bone
faster than men
- Body size–small, thin-boned women are at greatest risk
- Ethnicity–white and Asian women are at highest risk
- Family history–having parents with a history of
fractures
- Sex hormones–abnormal absence of menstrual periods
(amenorrhea) or menopause
- Anorexia
- Lifetime diet low in calcium and vitamin D
- Certain medications, such as glucocorticoids (prescribed
for various diseases, including arthritis, asthma, and
lupus) or some anticonvulsants
- Physical inactivity or extended bed rest
- Cigarette smoking
- Excessive use of alcoholic beverages
If you think you're at risk for
osteoporosis or if you're menopausal or older, you may want to
ask your doctor or other health care provider about having a
test called a DXA-scan (dual-energy x-ray absorptiometry). It
measures spine, hip, or total body bone mineral density, or
how solid bones are. The results can show the presence and
severity of osteoporosis, or if you're at risk of developing
it or having fractures.
You can prevent osteoporosis. The key steps
are to follow an eating plan that's rich in calcium and
vitamin D and be sure to get regular weight-bearing exercises.
Calcium and vitamin D intake can be taken as supplements but
check with your health care provider first. Too much of either
can cause problems. Recommended daily intakes of calcium and
vitamin D are given in Box
19. Good food sources of calcium include lowfat dairy
foods, canned fish with bones, such as salmon and sardines,
dark-green leafy vegetables, such as broccoli, kale, and
collards, calcium-fortified orange juice, and breads made with
calcium-fortified flour. Vitamin D is made by the body–being
in the sun 20 minutes a day helps most women make enough. But
it's also found in eggs, fatty fish (such as sardines,
mackerel, and salmon), and cereal and milk fortified with
vitamin D. Weight-bearing exercises–done three to four times a
week–that help prevent osteoporosis include walking, jogging,
stairclimbing, weight training, tennis, and dancing.
It's also important not to smoke and to limit
how many alcoholic beverages you drink. Smoking causes the
body to make less estrogen, which protects bones. Too much
alcohol can put you at risk for falling and breaking bones.
Osteoporosis is treated by stopping bone loss
with lifestyle changes and medication. Hormone therapy has
been used to prevent and treat osteoporosis. But other drugs
are available:
- Raloxifene is a SERM. It may cause hot flashes and blood
clots.
- Alendronate (brand name Fosamax) and risedronate (brand
name Actonel) are bisphosphonates, drugs that slow the
breakdown of bone and may increase bone density. Side
effects may include nausea, heartburn, and pain in the
stomach.
- Calcitonin is a naturally occurring non-sex hormone that
increases bone mass in the spine. It is used for women who
are at least 5 years beyond menopause and is taken by
injection or nasal spray. The injection may cause an
allergic reaction and has some unpleasant side effects,
including flushing of the face and hands, urinating often,
nausea, and skin rash. The nasal spray may cause a runny
nose.
|
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You should talk with your health care provider about whether or
not stopping postmenopausal hormone therapy would be good for you.
Also ask about the best way to discontinue the treatment. You can
stop abruptly or by gradually reducing the dose over several months.
However, by abruptly stopping the medication, you may have
menopause-like symptoms. Gradually weaning your body off the
medication can ease this.
Box 21 |
Check It Out
Here's a prescription for
better health:
- Blood pressure–healthy women should have it checked
every 2 years; others may need it checked more often.
- Lipoprotein profile–checks blood levels of LDL, HDL,
total cholesterol, and triglycerides; healthy women should
have it once every 5 years.
- Blood glucose–tests blood levels of glucose (a sugar)
and indicates risk for diabetes; healthy women age 45 and
older should have it, especially if they are overweight; if
it's normal and women are healthy and not overweight, it
should be taken again in 3 years, while others will need it
more often.
- Overweight and obesity check–this is done by calculating
your body mass index (BMI) and measuring your waist
circumference. BMI is a measure of your weight relative to
your height, while waist circumference measures abdominal
fat. Box
22 tells you how to calculate BMI. A BMI of 25 or higher
is overweight or obese. For women, a waist circumference of
more than 35 inches indicates an increased risk for heart
disease and other conditions. Your health care provider also
will check you for other risk factors and conditions
associated with obesity to determine the best treatment.
- Mammogram–a special x ray of the breast; healthy women
age 40 and older should be screened for breast cancer with
mammography once every 1 to 2 years; studies show screening
is especially important for those aged 50-69; women also
should do breast self-exams and have their doctor or health
care provider do a clinical breast exam during routine
physical exams.
- Pap Smear–this test checks a sample of cervical cells
for changes that may lead to cancer; begin by having it as
part of an annual gynecological exam and, if normal 3 years
in a row, talk with your doctor about how often to have it
after that.
- Colonoscopy–examines the inside of the colon and rectum
using a thin, lighted tube called a colonoscope; healthy
women should have it once every 5 years starting at age 50.
- Bone density–this x-ray measures bone thickness and
strength; postmenopausal women with one or more risk factors
for osteoporosis (besides menopause) or who suffer
fractures, and women age 65 and older regardless of added
risk factors should have this test.
- Electrocardiogram (EKG or ECG)–this tests the heart's
electrical activity as it beats; women over age 40 should
have a baseline EKG.
|
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The new findings have provided some details about the dangers and
benefits of postmenopausal hormone therapy, but many questions
remain. The WHI is following women in the estrogen plus progestin
trial to see if and when increased risks and benefits decline after
use of the therapy ends. Also, in 2005, the WHI is expected to
release key information about the effects of postmenopausal
estrogen-only therapy.
Other WHI studies include:
- The observational study is examining other forms of hormone
therapy, including other estrogens, progestins, and SERMs.
- The postmenopausal hormone therapy trial has been
investigating hormones' effects on memory. While the estrogen plus
progestin part of that study ended, the estrogen-only arm
continues.
- A WHI substudy is examining hormones' ability to prevent or
delay Alzheimer's disease and other forms of dementia.
Additionally, scientists funded by the NHLBI, the National Cancer
Institute, the National Institute on Aging, the National Institute
of Arthritis and Musculoskeletal and Skin Diseases, the National
Center for Complementary and Alternative Medicine, the National
Institute of Mental Health, and other units of the NIH are
supporting research on the effects of postmenopausal hormones and
alternative therapies on the symptoms of menopause and conditions
that occur after menopause. The research includes studies of: the
effects of soy phytoestrogens on cardiovascular disease and
osteoporosis, postmenopausal use of phytoestrogens on cardiovascular
risk and health, black cohosh and antidepressants on hot flashes,
botanical dietary supplements on women's health, plant estrogens on
breast cancer, and estrogen on cognition.
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Box 22 |
Check Your BMI
Body mass index–or BMI–relates weight to
height and is used as an indicator of total body fat. It is
used with waist circumference to see if you're overweight or
obese.
Here are three steps to find your BMI:
|
Step 1 |
Multiply your weight* in pounds by
703. |
Step 2 |
Divide the answer by your height in
inches. |
Step 3 |
Divide the answer again by your height in
inches. |
The BMI score means:
|
18.5-24.9 |
Normal |
25.0-29.9 |
Overweight |
30.0 and above |
Obese |
*Weight wearing underwear but no
shoes
|
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The following resources can help you lean more about hormone
therapy-related topics:
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|