Questions and Answers for Estrogen and Estrogen with
Progestin
Therapies for Postmenopausal Women (Updated)
1. What is FDA announcing today?
The FDA is continuing to encourage all
manufacturers of estrogen and estrogen with progestin drug products
indicated for use by postmenopausal women to update the labeling for
their products. The Women’s Health
Initiative (WHI) trial about estrogens and progestins
continues to have significant public health implications for
postmenopausal women. As new study results from the WHI become
available, FDA is strongly recommending that sponsors update the
labeling for their estrogen- and progestin-containing drug products
to include new information from these studies.
Access to the most current information available is
important to health care providers and
postmenopausal women who are prescribed estrogen- and progestin-containing
drug products. This information will allow individuals to understand the risks of these products and
make appropriate health care decisions.
2. What prompted FDA to request the changes in the
physician prescribing information and patient information leaflet
for all estrogen and estrogen with progestin drug
products?
The Women's Health Initiative (WHI) conducted a
large study sponsored by the National Institutes of Health (NIH) to
determine the effects of estrogen with progestin on the prevention
of heart disease. Results from this study have shown that
postmenopausal women taking estrogen with progestin have an
increased risk of heart attack, stroke, breast cancer, and blood
clots.
An ancillary study of the Women’s Health Initiative
(WHI) called the Women’s Health Initiative Memory Study (WHIMS)
released more results in May 2003. WHIMS results showed that the
combination of estrogen and progestin (Prempro) increased the risk
of dementia in women 65 and older and failed to prevent memory loss.
FDA believes this information should be included in
the physician prescribing information and patient information
leaflet, also referred to as the labeling, for all estrogen and
estrogen with progestin drug products.
3. What are estrogen drug products and what do they treat?
Estrogen is a hormone. It is given either alone to a
woman without a uterus, or is given in combination with progestin to
a woman with a uterus. Estrogen is used to:
- reduce hot flashes in menopause
- treat vaginal dryness, itching, and burning due to menopause
- help reduce chances of getting osteoporosis (thin weak bones)
in menopause
- treat certain conditions in women before menopause if their
ovaries do not make enough estrogen
- ease symptoms of certain cancers that have spread through the
body, in men and women.
4. What are estrogen with progestin drug products?
Estrogen with progestin drug products contain two
kinds of hormones: estrogens and a progestin. Adding progestin
reduces the risk of endometrial cancer in a woman with a uterus.
Estrogen with progestin drug products are given to
postmenopausal women with a uterus to:
- reduce hot flashes
- treat vaginal dryness, itching, and burning
- help reduce chances of getting osteoporosis (thin weak bones)
5. What is menopause?
The ovaries normally stop making estrogens when a
woman is between 45 and 55 years old. This drop in body estrogen
levels causes menopause (the end of monthly menstrual periods) or
the "change of life."
6. What changes do women go through after menopause?
Every woman experiences menopause differently. Some
may not experience any noticeable effects at all. As estrogen levels
begin to drop, women may experience changes such as:
- Hot flashes ("hot flushes") - these symptoms can range from
feelings of warmth in the face, neck, and chest, or sudden strong
feelings of heat and sweating.
- Vaginal changes/vaginal atrophy - the tissues lining the
vagina may become drier, thinner and less elastic.
- Irregular menstruation - the menstrual cycle may become
lighter or heavier and then stop.
- Sleep disturbances or night sweats
- Emotional changes - mood swings, irritability
7. What is the new, important information about all estrogen
and estrogen with progestin drug products?
Estrogen and estrogen with progestin drug products
remain the most effective products available to treat hot flashes
and vaginal symptoms of menopause.
The major points arising from the WHI study and
WHIMS are:
- Postmenopausal women should not take estrogen and progestin to
protect the heart.
- Estrogens and progestins may increase the risk of heart
attack, stroke, blood clots and breast cancer.
- Although other doses of Prempro and other estrogens and
progestins were not studied, it is important to warn postmenopausal women who take
estrogens and progestins about the potential
risks, which must be presumed to be the same.
- When these drugs are being prescribed only to prevent
osteoporosis, health care providers are encouraged to consider other treatments
before
prescribing estrogen or estrogen with progestin.
- Estrogens and estrogen with progestin should be used at the
lowest dose for the shortest duration.
- The estrogen with progestin combination studied in WHIMS does
not prevent dementia or slow progress toward dementia over time.
- Women treated with combination estrogen plus progestin have a
greater risk of developing dementia.
- There is a higher incidence of mammography abnormalities
requiring medical attention.
8. How great are the risks for women taking estrogen with
progestin?
The study results show that of every 10,000 women
per year taking estrogen with progestin, there would be:
- 8 more cases of breast cancer
- 7 more cases of heart attacks
- 8 more cases of stroke
- 18 more cases of blood clots in the lungs and legs
- 23 more cases of dementia in women over 65 years of age
9. Are there any risks that were found to be lowered in women
taking estrogen with progestin?
The WHI study results show that of every 10,000
women per year taking estrogen with progestin drug products, there
would be:
- 6 fewer cases of colon cancer
- 5 fewer cases of hip fracture
10. What are the major changes in the physician prescribing
information and patient information leaflet for estrogens and
estrogen with progestin drug products?
FDA is highlighting the important safety information
from the WHI and the WHIMS study results. The FDA is encouraging all
estrogen and progestin manufacturers to provide similar safety
information for their products. In addition, FDA is asking that
manufacturers of estrogen and progestin products state whether
studies have been conducted to identify the lowest effective dose
for their product.
11. What is FDA's advice to women?
- Estrogens and progestins should not be used to prevent memory
loss, heart disease, heart attacks, or strokes.
- Estrogens provide valuable therapy for many women, but carry
serious risks, and therefore postmenopausal women who use or are
considering using estrogen or estrogen with progestin treatments
should discuss with their physicians whether the benefits outweigh
the risks.
- For hot flashes and significant symptoms of vulvar and vaginal
atrophy, these products are the most effective approved therapies.
These products are also options for women whose significant risk
of osteoporosis outweighs the risks of treatment; other treatments
for prevention of postmenopausal osteoporosis are available.
- Estrogens and progestins should be used at the lowest doses
for the shortest duration to reach treatment goals, although it is
not known at what dose there may be less risk of serious side
effects. Women are encouraged to talk to their health care provider regularly
about whether treatment is still needed.
- There is a higher incidence of abnormal mammograms which
require medical attention.
- Each woman's individual medical situation needs to be
carefully discussed with her health care provider to make the best
decision for her.
12. Is it possible that FDA would think about taking estrogens
and estrogen with progestin drug products off the market?
The FDA is not thinking of taking estrogens or
estrogen with progestin drug products off the market at this time.
The FDA evaluates the ongoing safety and
effectiveness of drugs both before and after their approval. The FDA
monitors the safety of drugs through postmarketing surveillance and
risk assessment programs to identify adverse events that appear
during drug marketing. If changes are warranted, this information is
used to update the physician prescribing information, to develop
educational programs, and, on rare occasions, to reevaluate the
original marketing approval decision.
Currently, the FDA seeks to minimize risks and
maximize benefits of estrogen and estrogen with progestin drug
products by ensuring that women and health care providers fully
understand these risks and benefits.
13. Who should not take estrogens and progestins?
Women should not take estrogens and progestins if
they:
- think they are pregnant
- have unusual vaginal bleeding
- have or had certain cancers
- have had a stroke or heart attack in the past year
- have or have had blood clots
- have liver problems or liver disease
14. Are estrogen and progestin containing drug products safer in
lower doses?
The dose of Prempro used in the WHI study was 0.625
mg, which is the same as 0.625 mg Premarin (conjugated estrogens)
plus 2.5 mg medroxyprogesterone acetate (progestin). It is not known
whether Premarin and Prempro are safer in lower doses. Generally,
medicines should be used at the lowest effective dose. The FDA
approved a lower dose of Prempro in March 2003.
The FDA cannot make further recommendations until
studies are performed using lower doses. That is why the FDA is
asking that manufacturers update their labeling to let doctors
and women know whether studies have been conducted to identify the
lowest effective dose for their product.
15. Are other estrogen and progestin containing drug products
safer than those used in the WHI study?
All estrogen and progestin containing drug products
work in similar ways. Until there are data that show otherwise,
postmenopausal women who take any type of estrogens or progestins
should be similarly warned about risks.
16. How long should women take estrogen or estrogen with
progestin drug products?
FDA recommends that women taking estrogen and estrogen with progestin
drug products discuss regularly with their health care
provider how they are doing with the treatment and if they need to
continue. Estrogens and progestins should be taken for the shortest
duration possible to achieve treatment goals.
17. What are some side effects of estrogens and progestins?
Less common but serious side effects include:
- Breast cancer
- Uterine cancer
- Stroke
- Heart attack
- Blood clots
- Dementia
- Gallbladder disease
- Ovarian cancer
Common side effects include:
- Headache
- Breast pain
- Irregular vaginal bleeding or spotting
- Stomach cramps
- Nausea and vomiting
- Hair loss
These are not all the possible side effects of
estrogen and estrogen with progestin drug products. For more
information, women are encouraged to consult with a health care provider or pharmacist.
18. Should women stop taking estrogens and progestins for
cardiovascular protection?
Estrogens and progestins have never been
FDA-approved for heart attack prevention. The FDA has not allowed
any claims about benefits for prevention of heart disease. Now, the
WHI study findings clearly show an increased risk for heart attack
and stroke in women.
Women should not take estrogens and progestins to
prevent heart attacks or stroke. FDA recommends that women talk to their doctor
about other medications or lifestyle measures (such as smoking
cessation) to reduce the risk of heart attacks.
19. What does this mean for use of estrogen alone?
(4/19/2004)
The estrogen alone substudy of the WHI was stopped by NIH on
March 1, 2004 because estrogen alone does not appear to affect
(either increase or decrease) heart disease in postmenopausal women
without a uterus. At the same time, estrogen alone appears to
increase the risk of stroke, decrease the risk of hip fracture, and
it has not increased the risk of breast cancer after a mean of 6.8
years of follow-up. There are other side effects associated with the
use of estrogen alone that women are encouraged to discuss with
their health care providers.
20. Are there medicines other than estrogen hormones for
prevention of osteoporosis?
Additional drugs that are FDA-approved for the
prevention of postmenopausal osteoporosis include:
- Bisphosphonates - alendronate (Fosamax) and risedronate (Actonel)
- Selective Estrogen Receptor Modulators- raloxifene (Evista)
21. Are the estrogens and progestins in birth control pills (oral
contraceptives) the same as those in the WHI study? Do they have the
same risks?
Oral contraceptives also contain estrogens and
progestins, but different types and doses. All estrogens have
similar side effects. However, the risks of particular side effects
may differ since oral contraceptives are used in younger women with
different health status compared to postmenopausal women.
As with all estrogens, the use of oral
contraceptives is also associated with increased risks of several
serious conditions including heart attack, blood clots, stroke,
liver tumors, and gallbladder disease. These risks are higher in
women with underlying risk factors such as high blood pressure, high
cholesterol, and diabetes, and in those who smoke cigarettes.
22. Will other estrogen and estrogen with progestin drug products
carry the same warnings?
The FDA believes that the new findings regarding
estrogens and progestins are very significant and have a major
public health impact for postmenopausal women. We believe that all
health care providers who prescribe estrogen and progestin drug
products for postmenopausal women, and all postmenopausal women who
use these drugs, need to know about the new risk information. Thus,
the FDA is encouraging all manufacturers who have estrogen and
progestin products approved for treatment of menopausal signs and
symptoms to include the new information for their products. To help
manufacturers include this new risk information, the FDA has
reissued its guidance for labeling these products, including revised
recommendations for patient information.
23. Are estrogens in patches or vaginal creams or vaginal rings
safer than tablet forms?
We do not know if the other forms are safer than the
tablets. Estrogens are available in a variety of forms including
transdermal patches, estrogen gels, and vaginal creams and rings.
Most of the data on the long-term health effects of estrogens come
from studies involving estrogen and progestin oral tablets. Unless
there are data to say otherwise, FDA recommends that postmenopausal women who take
estrogen and progestin in other dosage forms be similarly
warned about risks.
The amount of estrogen that enters the blood stream
from estrogen-containing vaginal creams and rings can vary depending
on the specific product; how it is used, and on factors that vary
from woman to woman. FDA encourages manufacturers to provide drug
blood level information in the physician prescribing information.
However, it is important to realize that little is known about the
relationship between blood levels of estrogens and potential health
risks.
24. If a woman wants to stop taking estrogens, what should she
do?
Women are advised to discuss this issue with their
health care provider before stopping their medication.
25. If estrogens are stopped will that change a woman's sex
drive? In what way?
Estrogen, and estrogen with progestin drug products
have been shown to be effective in treating vaginal dryness,
itching, and burning, which can cause discomfort with intercourse.
By stopping estrogen and progestin, symptoms such as discomfort
during sexual intercourse may return. Women are advised to discuss
their symptoms off estrogens and options with their health care
provider.
25. Will estrogen protect against aging, wrinkles, or other
conditions?
Researchers are investigating the benefits of
estrogen and estrogen with progestin in offering protection from a
number of conditions and diseases such as macular degeneration, a
serious condition that can lead to blindness. At this time there are
no convincing studies to support these claims.
26. What can be done to lower the risks of side effects such as
heart attack, stroke, blood clots or breast cancer while taking
estrogen or estrogen with progestin?
Generally, the safety and effectiveness of medicines
are increased when they are used as directed. Here are some points
for women to consider:
- Talk with a health care provider periodically about whether
estrogens should be continued and how to monitor for side effects.
- If unusual vaginal bleeding develops, see a health care
provider right away.
- Do a self-breast examination regularly and have a breast exam
by a health care provider and mammogram (breast X-ray) regularly.
- High blood pressure, high cholesterol (fat in the blood),
diabetes, tobacco use, and being overweight increase the chances
for getting heart disease. A health care provider can advise on
how to lower the chances for getting heart disease.
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Estrogen and Estrogen with Progestin
Date created: February 10, 2004, Updated: April 19, 2004 |