Postmenopausal
Hormone Replacement Therapy -- Is HRT Right For
You?
Adapted by Tracee
Cornforth
- Menopause and Hormone Therapy
- Postmenopausal Use
- Early Findings
- The Women's Health Initiative
- Putting It All Together
- Advice About Postmenopausal Hormone Therapy
- How Do I Stop Postmenopausal Hormone Therapy?
- Questions Remain
- For More Information
Choosing whether or not to use postmenopausal hormone therapy or HRT can be one of the most important health decisions women face as they age. As with taking any treatment, the HRT 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 hormone therapy's effects on breast cancer, heart disease, and other conditions.
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
Oral
Estrogen and Estrogen/Progestin Products*
* As of Fall 2000
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.
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 evonorgestrel 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
Gels,
Creams, Patches, and Other Hormone Products*
* As of Fall 2000
Menopause and Hormone Therapy
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.) 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.
Hormone
Therapy Schedules
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.
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 (see
Box 5). 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 Heart
disease For
menopausal symptoms: Hot
flashes Vaginal
dryness Mood
swings Insomnia Memory
problems
Alternatives
to Hormone Therapy to Help Prevent Postmenopausal Conditions
and Relieve Menopausal Symptoms
Postmenopausal Use
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.
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.
About
Dietary Supplements
Early Findings
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. (See Box 6 for more about 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.
What We
Lean From Different Types of Studies
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.
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:
Risk
Factors for Uterine Cancer
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 (see Box 7).
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: Other
factors also may increase the risk of developing breast
cancer. These include:
Breast
Cancer Risk Factors
PEPI did not last long enough to tackle some crucial questions about hormone therapy, such as a possible rise in breast cancer risk (see Box 8).
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.)
Compared
with a placebo, after about 5 years of use, estrogen plus
progestin resulted in: Increased
risks Increased
benefits No
difference Box
10 [skip
to text version] The
rate of the following medical conditions per 10,000 women
per year
WHI
Findings On Estrogen Plus Progestin Therapy
Estrogen
Plus Progestin Pills vs. Placebo Pills
Box
10 Text Version [skip
to graphical version] The
rate of the following medical conditions per 10,000 women
per year Estrogen
Plus Breast
Cancer 30 38 Heart
Attack 30 37 Stroke 21 29 Total
Blood Clots 16 34 Hip
Fracture 15 10 Colorectal
Cancer 16 10
Estrogen
Plus Progestin Pills vs. Placebo Pills
Placebo Pills
Progestin Pills
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.
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.
What Do
the Data Really Mean?
The Women's Health Initiative
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.
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.
Main
risk factors are: Other
risk factors include:
Risk
Factors for Stroke
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).
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:
Risk
Factors for Colorectal Cancer
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. The key results are shown in Boxes 9 and 10.
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.
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 (see
Box 15). 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
(see
Box 6).
The evidence from these studies is cautionary, not
definitive. Here's
more on the studies: 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.
Postmenopausal
Hormone Therapy and Ovarian Cancer Risk
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.
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. Here's more on the findings--to better understand them, see "Putting It All Together," as well as Box 11:
- 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.
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 Decreases
risk
Risk
Factors for Ovarian Cancer
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 (see Box 14). 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.
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.
What
About Birth Control Pills?
Putting It All Together
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.
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: 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.
Talking
With Your Doctor
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 (see Boxes 7, 8, 12, 13, 15, 18, and 20). 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.
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 Risk
factors you can control For
more on how to start reducing your heart disease risk,
see
the resources list.
Your
Heart Disease Risk Profile
Advice About Postmenopausal Hormone Therapy
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 (see Box 19), 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. For more on osteoporosis, see Box 20.
Age Vitamin
D Calcium 19-50 200
IU* 1,200
mg** 51-70 400
IU* 1,200
mg** 70+ 600
IU* 1,200
mg** *
not to exceed 2,000 IU
Recommended
Daily Intakes of Calcium and Vitamin D
Note: IU=International Units
** 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 (see
Box 21).
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 (see Box 4). Be aware that some of these remedies have not been proved effective or safe.
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: 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:
Boning
Up On Osteoporosis
How Do I Stop Postmenopausal Hormone Therapy?
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.
Here's
a prescription for better health:
Check It
Out
Questions Remain
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.
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. To
find your BMI, use the method below or go to the Aim For A
Healthy Weight Web page at www.nhlbi.nih.gov/health/public/heart/obesity/lose_wt/index.htm,
which offers tables and an automatic calculator. 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. 18.5-24.9 Normal 25.0-29.9 Overweight 30.0
and above Obese
Check
Your BMI
The BMI score means:
*Weight wearing underwear but no shoes
For More Information
The following resources can help you lean more about hormone therapy-related topics:
National
Heart, Lung, and Blood Institute National
Cancer Institute National
Center for Alternative and Complementary Medicine National
Institute on Aging National
Institute of Arthritis and Musculoskeletal and Skin
Diseases NIH
Osteoporosis and Related Bone Diseases~National Resource
Center National
Institute of Child Health and Human Development Food
and Drug Administration Office
on Women's Health National
Women's Health Information Center North
American Menopause Society Alliance
for Aging Research American
Heart Association American
Stroke Association National
Osteoporosis Foundation
National Institutes of Health
NHLBI Health Information Center
P.O. Box 30105
Bethesda, MD 20824-30105
Phone: (301) 592-8573
TTY: (204) 629-3255
Fax: (301) 592-8563
Web site: www.nhlbi.nih.gov
WHI Web site: www.whi.org
National Institutes of Health
Phone: (800) 4-CANCER
(800-422-6237)
Web site: www.nci.nih.gov
National Institutes of Health
NCCAM Clearinghouse
P.O. Box 7923
Gaithersburg, MD 20898-7923
Phone: (888) 644-6226
TTY: (866) 464-3615
International Phone: (301) 519-3153
Fax: (866) 464-3616
Web site: www.nccam.nih.gov
National Institutes of Health
Phone: (800) 222-2225
TTY: (800) 222-4225
Web site: www.nia.nih.gov
National Institutes of Health
NIAMS Information Clearinghouse
1 AMS Circle
Bethesda, MD 20892-3675
Phone: (301) 495-4484 or
(877) 226-4267
TTY: (301) 565-2966
Fax: (301) 718-6366
Web site: www.niams.nih.gov
1232 22nd Street, NW
Washington, DC 20037-1292
Phone: (202) 223-0344 or
(800) 624-BONE
Fax: (202) 293-2356
TTY: (202) 466-4315
Web site: www.osteo.org
National Institutes of Health
NICHD Clearinghouse
P.O. Box 3006
Rockville, MD 20847
Phone: (800) 370-2943
Fax: (301) 984-1473
Email: NICHDClearinghouse@mail.nih.gov
Web site: www.nichd.nih.gov
Department of Health and Human Services
5600 Fishers Lane
Rockville, MD 20857
Phone: (888) INFO-FDA
(888-463-6332)
Web site: www.fda.gov
Department of Health and Human Services
200 Independence Avenue, SW
Room 730B
Washington, DC 20201
Phone: (202) 690-7650
Fax: (202) 205-2631
Web site: www.4women.gov/owh
Department of Health and Human Services
8550 Arlington Boulevard
Suite 300
Fairfax, VA 22031
Phone: (800) 994-WOMAN
(800-994-9662) or
(888) 220-5446
Web site: www.4women.gov
P.O. Box 94527
Cleveland, OH 44101
Phone: (440) 442-7550
Automated Consumer Request Line: (800) 774-5342
Fax: (440) 442-2660
E-Mail: info@menopause.org
Web site: www.menopause.org
2021 K Street, NW
Suite 305
Washington, DC 20006
Phone: (202) 293-2856
Fax: (202) 785-8574
National Center
7272 Greenville Avenue
Dallas, TX 75231
Phone: (800) AHA-USA-1
(800-242-8721)
Web site: www.americanheart.org
National Center
7272 Greenville Avenue
Dallas, TX 75231
Phone: (888) 4-STROKE
(888-478-7653)
Web site: www.strokeassociation.org
1232 22nd Street, NW
Washington, DC 20037-1292
Phone: (202) 223-2226
Web site: www.nof.org
Adapted from NIH
Publication No. 02-5200
October 2002
