estradiol valerate injection Monarch Pharmaceuticals, Inc.
DELESTROGEN® (estradiol valerate injection,
ESTROGENS HAVE BEEN REPORTED
TO INCREASE THE RISK OF ENDOMETRIAL CARCINOMA IN POSTMENOPAUSAL WOMEN.
Close clinical surveillance of all women
taking estrogens is important. Adequate diagnostic measures, including
endometrial sampling when indicated, should be undertaken to rule
out malignancy in all cases of undiagnosed persistent or recurring
abnormal vaginal bleeding. There is no evidence that “natural”
estrogens are more or less hazardous than “synthetic”
estrogens at equiestrogenic doses.
ESTROGENS SHOULD NOT BE
USED DURING PREGNANCY.
There is no
indication for estrogen therapy during pregnancy or during the immediate
postpartum period. Estrogens are ineffective for the prevention or
treatment of threatened or habitual abortion. Estrogens are not indicated
for the prevention of postpartum breast engorgement.
Estrogen therapy during pregnancy is associated with an increased
risk of congenital defects in the reproductive organs of the fetus,
and possibly other birth defects. Studies of women who received diethylstilbestrol
(DES) during pregnancy have shown that female offspring have an increased
risk of vaginal adenosis, squamous cell dysplasia of the uterine cervix,
and clear cell vaginal cancer later in life; male offspring have an
increased risk of urogenital abnormalities and possibly testicular
cancer later in life. The 1985 DES Task Force concluded that use of
DES during pregnancy is associated with a subsequent increased risk
of breast cancer in the mothers, although a causal relationship remains
unproven and the observed level of excess risk is similar to that
for a number of other breast cancer risk factors.
DELESTROGEN® (estradiol valerate
injection, USP) contains estradiol valerate, a long-acting estrogen
in sterile oil solutions for intramuscular use. These solutions are
clear, colorless to pale yellow. Formulations (per mL): 10 mg estradiol
valerate in a vehicle containing 5 mg chlorobutanol (chloral derivative/preservative)
and sesame oil; 20 mg estradiol valerate in a vehicle containing 224
mg benzyl benzoate, 20 mg benzyl alcohol (preservative), and castor
oil; 40 mg estradiol valerate in a vehicle containing 447 mg benzyl
benzoate, 20 mg benzyl alcohol, and castor oil.
Estradiol valerate is designated chemically as estra-1,3,5(10)-triene-3,
17-diol(17β)-, 17-pentanoate. Graphic formula:
Estrogen drug products act by regulating the transcription
of a limited number of genes. Estrogens diffuse through cell membranes,
distribute themselves throughout the cell, and bind to and activate
the nuclear estrogen receptor, a DNA-binding protein which is found
in estrogen-responsive tissues. The activated estrogen receptor binds
to specific DNA sequences, or hormone-response elements, which enhance
the transcription of adjacent genes and in turn lead to the observed
effects. Estrogen receptors have been identified in tissues of the
reproductive tract, breast, pituitary, hypothalamus, liver, and bone
Estrogens are important in the development
and maintenance of the female reproductive system and secondary sex
characteristics. By a direct action, they cause growth and development
of the uterus, fallopian tubes, and vagina. With other hormones, such
as pituitary hormones and progesterone, they cause enlargement of
the breasts through promotion of ductal growth, stromal development,
and the accretion of fat. Estrogens are intricately involved with
other hormones, especially progesterone, in the processes of the ovulatory
menstrual cycle and pregnancy, and affect the release of pituitary
gonadotropins. They also contribute to the shaping of the skeleton,
maintenance of tone and elasticity of urogenital structures, changes
in the epiphyses of the long bones that allow for the pubertal growth
spurt and its termination, and pigmentation of the nipples and genitals.
Estrogens occur naturally in several forms. The primary
source of estrogen in normally cycling adult women is the ovarian
follicle, which secretes 70 to 500 micrograms of estradiol daily,
depending on the phase of the menstrual cycle. This is converted primarily
to estrone, which circulates in roughly equal proportion to estradiol,
and to small amounts of estriol. After menopause, most endogenous
estrogen is produced by conversion of androstenedione, secreted by
the adrenal cortex, to estrone by peripheral tissues. Thus, estrone—especially
in its sulfate ester form—is the most abundant circulating
estrogen in postmenopausal women. Although circulating estrogens exist
in a dynamic equilibrium of metabolic interconversions, estradiol
is the principal intracellular human estrogen and is substantially
more potent than estrone or estriol at the receptor.
Estrogens used in therapy are well absorbed through the skin, mucous
membranes, and gastrointestinal tract. When applied for a local action,
absorption is usually sufficient to cause systemic effects. When conjugated
with aryl and alkyl groups for parenteral administration, the rate
of absorption of oily preparations is slowed with a prolonged duration
of action, such that a single intramuscular injection of estradiol
valerate or estradiol cypionate is absorbed over several weeks.
Administered estrogens and their esters are handled within
the body essentially the same as the endogenous hormones. Metabolic
conversion of estrogens occurs primarily in the liver (first pass
effect), but also at local target tissue sites. Complex metabolic
processes result in a dynamic equilibrium of circulating conjugated
and unconjugated estrogenic forms which are continually interconverted,
especially between estrone and estradiol and between esterified and
non-esterified forms. Although naturally-occurring estrogens circulate
in the blood largely bound to sex hormone- binding globulin and albumin,
only unbound estrogens enter target tissue cells. A significant proportion
of the circulating estrogen exists as sulfate conjugates, especially
estrone sulfate, which serves as a circulating reservoir for the formation
of more active estrogenic species. A certain proportion of the estrogen
is excreted into the bile and then reabsorbed from the intestine.
During this enterohepatic recirculation, estrogens are desulfated
and resulfated and undergo degradation through conversion to less
active estrogens (estriol and other estrogens), oxidation to nonestrogenic
substances (catecholestrogens, which interact with catecholamine metabolism,
especially in the central nervous system), and conjugation with glucuronic
acids (which are then rapidly excreted in the urine).
When given orally, naturally-occurring estrogens and their esters
are extensively metabolized (first pass effect) and circulate primarily
as estrone sulfate, with smaller amounts of other conjugated and unconjugated
estrogenic species. This results in limited oral potency. By contrast,
synthetic estrogens, such as ethinyl estradiol and the nonsteroidal
estrogens, are degraded very slowly in the liver and other tissues,
which results in their high intrinsic potency. Estrogen drug products
administered by non-oral routes are not subject to first-pass metabolism,
but also undergo significant hepatic uptake, metabolism, and enterohepatic
Indications and Usage
DELESTROGEN (estradiol valerate injection, USP)
is indicated in the:
Treatment of moderate to severe vasomotor symptoms
associated with the menopause. There is no adequate evidence that
estrogens are effective for nervous symptoms or depression which might
occur during menopause and they should not be used to treat these
Treatment of vulval and vaginal atrophy.
Treatment of hypoestrogenism due to hypogonadism,
castration or primary ovarian failure.
Treatment of advanced androgen-dependent carcinoma
of the prostate (for palliation only).
Estrogens should not be used in individuals with
any of the following conditions:
Known or suspected pregnancy (see Boxed WARNINGS). Estrogens may cause fetal harm when administered to a pregnant
Undiagnosed abnormal genital bleeding.
Known or suspected cancer of the breast except in
appropriately selected patients being treated for metastatic disease.
Known or suspected estrogen-dependent neoplasia.
Active thrombophlebitis or thromboembolic disorders.
Induction of malignant
neoplasms.Endometrial cancer. The reported endometrial cancer risk among unopposed estrogen users
is about 2 to 12 fold greater than in nonusers, and appears dependent
on duration of treatment and on estrogen dose. Most studies show no
significant increased risk associated with use of estrogens for less
than one year. The greatest risk appears associated with prolonged
use—with increased risks of 15 to 24-fold for five to ten years
or more. In three studies, persistence of risk was demonstrated for
8 to over 15 years after cessation of estrogen treatment. In one study
a significant decrease in the incidence of endometrial cancer occurred
six months after estrogen withdrawal. Concurrent progestin therapy
may offset this risk but the overall health impact in postmenopausal
women is not known.
Breast Cancer. While
some epidemiologic studies suggest a very modest increase in breast
cancer risk for estrogen alone users versus nonusers, other studies
have not shown any increased risk. The addition of progestin to estrogen
may increase the risk for breast cancer over that noted in non-hormone
users more significantly (by about 24-40%), although this is based
solely on epidemiologic studies, and definitive conclusions await
prospective, controlled clinical trials.
without a uterus who require hormone replacement should receive estrogen-alone
therapy, and should not be exposed unnecessarily to progestins. Women
with a uterus who are candidates for short-term combination estrogen/progestin
therapy (for relief of vasomotor symptoms) are not felt to be at a
substantially increased risk for breast cancer. Women with a uterus
who are candidates for long-term use of estrogen/progestin therapy
should be advised of potential benefits and risks (including the potential
for increased risk of breast cancer). All women should receive yearly
breast exams by a health care provider and perform monthly breast-self
examinations. In addition, mammography examinations should be scheduled
as suggested by providers based on patient age and risk factors.
Congenital lesions with malignant
potential. Estrogen therapy during pregnancy is associated
with an increased risk of fetal congenital reproductive tract disorders,
and possibly other birth defects. Studies of women who received DES
during pregnancy have shown that female offspring have an increased
risk of vaginal adenosis, squamous cell dysplasia of the uterine cervix,
and clear cell vaginal cancer later in life; male offspring have an
increased risk of urogenital abnormalities and possibly testicular
cancer later in life. Although some of these changes are benign, others
are precursors of malignancy.
Gallbladder disease. Two studies have reported a 2- to 4-fold increase in the risk of
gallbladder disease requiring surgery in women receiving postmenopausal
Cardiovascular disease. Large doses of estrogen (5 mg conjugated estrogens per day), comparable
to those used to treat cancer of the prostate and breast, have been
shown in a large prospective clinical trial in men to increase the
risks of nonfatal myocardial infarction, pulmonary embolism, and thrombophlebitis.
These risks cannot necessarily be extrapolated from men to women.
However, to avoid the theoretical cardiovascular risk to women caused
by high estrogen doses, the dose for estrogen replacement therapy
should not exceed the lowest effective dose.
Elevated blood pressure. Occasional blood pressure increases during estrogen replacement
therapy have been attributed to idiosyncratic reactions to estrogens.
More often, blood pressure has remained the same or has dropped. One
study showed that postmenopausal estrogen users have higher blood
pressure than nonusers. Two other studies showed slightly lower blood
pressure among estrogen users compared to nonusers. Postmenopausal
estrogen use does not increase the risk of stroke. Nonetheless, blood
pressure should be monitored at regular intervals with estrogen use.
Hypercalcemia. Administration of estrogens may lead to severe hypercalcemia in
patients with breast cancer and bone metastases. If this occurs, the
drug should be stopped and appropriate measures taken to reduce the
serum calcium level.
Addition of a progestin. Studies of the addition of a progestin for 10 or more days of a
cycle of estrogen administration have reported a lowered incidence
of endometrial hyperplasia than would be induced by estrogen treatment
alone. Morphological and biochemical studies of endometria suggest
that 10 to 14 days of progestin are needed to provide maximal maturation
of the endometrium and to reduce the likelihood of hyperplastic changes.
There are, however, possible risks which may be associated with the
use of progestins in estrogen replacement regimens. These include:
(1) adverse effects on lipoprotein metabolism (lowering HDL and raising
LDL) which could diminish the purported cardioprotective effect of
estrogen therapy (see PRECAUTIONS); (2) impairment
of glucose tolerance; and (3) possible enhancement of mitotic activity
in breast epithelial tissue, although few epidemiological data are
available to address this point (see WARNINGS). The choice of progestin,
its dose, and its regimen may be important in minimizing these adverse
effects, but these issues will require further study before they are
Cardiovascular risk. The effects of estrogen replacement on the risk of cardiovascular
disease have not been adequately studied. However, data from the Heart
and Estrogen/Progestin Replacement Study (HERS), a controlled clinical
trial of secondary prevention of 2,763 post-menopausal women with
documented heart disease, demonstrated no benefit. During an average
follow-up of 4.1 years, treatment with oral conjugated estrogen plus
medroxyprogesterone acetate did not reduce the overall rate of coronary
heart disease (CHD) events in post-menopausal women with established
coronary disease. There were more CHD events in the hormone treated
group than in the placebo group in year 1, but fewer events in years
3 through 5.
Physical examination. A complete medical and family history should be taken prior to the
initiation of any estrogen therapy. The pretreatment and periodic
physical examinations should include special reference to blood pressure,
breasts, abdomen, and pelvic organs, and should include a Papanicolaou
smear. As a general rule, estrogen should not be prescribed for longer
than one year without reexamining the patient.
Hypercoagulability. Some studies have shown that women taking estrogen replacement therapy
have hypercoagulability, primarily related to decreased antithrombin
activity. This effect appears dose- and duration-dependent and is
less pronounced than that associated with oral contraceptive use.
Also, postmenopausal women tend to have increased coagulation parameters
at baseline compared to premenopausal women. There is some suggestion
that low dose postmenopausal mestranol may increase the risk of thromboembolism,
although the majority of studies (of primarily conjugated estrogens
users) report no such increase. There is insufficient information
on hypercoagulability in women who have had previous thromboembolic
Familial hyperlipoproteinemia. Estrogen therapy may be associated with massive elevations of plasma
triglycerides leading to pancreatitis and other complications in patients
with familial defects of lipoprotein metabolism.
Fluid retention. Because estrogens may cause some degree of fluid retention, conditions
which might be exacerbated by this factor, such as asthma, epilepsy,
migraine, and cardiac or renal dysfunction, require careful observation.
Uterine bleeding and mastodynia. Certain patients may develop undesirable manifestations of estrogenic
stimulation, such as abnormal uterine bleeding and mastodynia.
Impaired liver function. Estrogens may be poorly metabolized in patients with impaired liver
function and should be administered with caution.
B. Information for the Patient.
See text of Patient Package Insert.
C. Laboratory Tests.
Estrogen administration should generally be guided
by clinical response at the smallest dose, rather than laboratory
monitoring, for relief of symptoms for those indications in which
symptoms are observable.
D. Drug/Laboratory Test Interactions.
Accelerated prothrombin time, partial thromboplastin
time, and platelet aggregation time; increased platelet count; increased
factors II, VII antigen, VIII antigen, VIII coagulant activity, IX,
X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin;
decreased levels of anti-factor Xa and antithrombin III, decreased
antithrombin III activity; increased levels of fibrinogen and fibrinogen
activity; increased plasminogen antigen and activity.
Increased thyroid-binding globulin (TBG) leading
to increased circulating total thyroid hormone, as measured by protein-bound
iodine (PBI), T4 levels (by column or by radioimmunoassay) or T3 levels
by radioimmunoassay. T3 resin uptake is decreased, reflecting the
elevated TBG. Free T4 and free T3 concentrations are unaltered.
Other binding proteins may be elevated in serum,
i.e., corticosteroid binding globulin (CBG), sex hormone-binding globulin
(SHBG), leading to increased circulating corticosteroids and sex steroids,
respectively. Free or biologically active hormone concentrations are
unchanged. Other plasma proteins may be increased (angiotensinogen/renin
substrate, alpha-1-antitrypsin, ceruloplasmin).
E. Carcinogenesis, Mutagenesis, and Impairment of Fertility.
Long term continuous administration of natural and
synthetic estrogens in certain animal species increases the frequency
of carcinomas of the breast, uterus, cervix, vagina, testis, and liver.
See CONTRAINDICATIONS and WARNINGS.
As a general principle, the administration of any
drug to nursing mothers should be done only when clearly necessary
since many drugs are excreted in human milk. In addition, estrogen
administration to nursing mothers has been shown to decrease the quantity
and quality of the milk.
H. Pediatric Use.
Safety and effectiveness in pediatric patients have
not been established. Large and repeated doses of estrogen over an
extended period of time may accelerate epiphyseal closure. Therefore,
periodic monitoring of bone maturation and effects on epiphyseal centers
is recommended in patients in whom bone growth is not complete.
The following additional adverse reactions have
been reported with estrogen therapy (see WARNINGS regarding induction of neoplasia, adverse effects
on the fetus, increased incidence of gallbladder disease, cardiovascular
disease, elevated blood pressure, and hypercalcemia).
Changes in vaginal bleeding pattern and abnormal
withdrawal bleeding or flow; breakthrough bleeding, spotting.
Increase in size of uterine leiomyomata.
Change in amount of cervical
Abdominal cramps, bloating.
Increased incidence of gallbladder disease.
Chloasma or melasma that may persist when drug is discontinued.
Loss of scalp
Steepening of corneal curvature.
Intolerance to contact lenses.
Central Nervous System.
Headache, migraine, dizziness.
Increase or decrease in weight.
Reduced carbohydrate tolerance.
Aggravation of porphyria.
Changes in libido.
Serious ill effects have not been reported following
acute ingestion of large doses of estrogen-containing oral contraceptives
by young children. Overdosage of estrogen may cause nausea and vomiting,
and withdrawal bleeding may occur in females.
Dosage and Administration
Care should be taken to inject deeply into the upper,
outer quadrant of the gluteal muscle following the usual precautions
for intramuscular administration. By virtue of the low viscosity of
the vehicles, the various preparations of DELESTROGEN (estradiol valerate
injection, USP) may be administered with a small gauge needle. Since
the 40 mg potency provides a high concentration in a small volume,
particular care should be observed to administer the full dose.
DELESTROGEN should be visually inspected for particulate
matter and color prior to administration; the solution is clear, colorless
to pale yellow. Storage at low temperatures may result in the separation
of some crystalline material which redissolves readily on warming.
Note: A dry needle and syringe should be used. Use of
a wet needle or syringe may cause the solution to become cloudy; however,
this does not affect the potency of the material.
For treatment of moderate
to severe vasomotor symptoms, vulval and vaginal atrophy associated
with the menopause, the lowest dose and regimen that will control
symptoms should be chosen and medication should be discontinued as
promptly as possible.
discontinue or taper medication should be made at 3-month to 6-month
The usual dosage is 10 to 20 mg
DELESTROGEN every four weeks.
For treatment of female
hypoestrogenism due to hypogonadism, castration, or primary ovarian
The usual dosage is 10 to
20 mg DELESTROGEN every four weeks.
For treatment of advanced
androgen-dependent carcinoma of the prostate, for palliation only.
The usual dosage is 30 mg or more administered
every one or two weeks.
Treated patients with an intact uterus should be
monitored closely for signs of endometrial cancer, and appropriate
diagnostic measures should be taken to rule out malignancy in the
event of persistent or recurring abnormal vaginal bleeding.
See PRECAUTIONS A.1
concerning addition of a progestin.
DELESTROGEN® (estradiol valerate
Multiple Dose Vials
10 mg/mL (5
mL): NDC 61570-180-01
20 mg/mL (5 mL): NDC
40 mg/mL (5 mL): NDC 61570-182-01
Store at room temperature.
Information for the Patient About
valerate injection, USP)
This leaflet describes when and how to use estrogens,
and the risks and benefits of estrogen treatment.
Estrogens have important benefits but also some risks. You must decide,
with your doctor, whether the risks to you of estrogen use are acceptable
because of their benefits. If you use estrogens, check with your doctor
to be sure you are using the lowest possible dose that works, and
that you don’t use them longer than necessary. How long you
need to use estrogens will depend on the reason for use.
ESTROGENS INCREASE THE
RISK OF CANCER OF THE UTERUS IN WOMEN WHO HAVE HAD THEIR MENOPAUSE
(“CHANGE OF LIFE”).
If you use any estrogen-containing drug, it is important to visit
your doctor regularly and report any unusual vaginal bleeding right
away. Vaginal bleeding after menopause may be a warning sign of uterine
cancer. Your doctor should evaluate any unusual vaginal bleeding to
find out the cause.
ESTROGENS SHOULD NOT BE
USED DURING PREGNANCY.
do not prevent miscarriage (spontaneous abortion) and are not needed
in the days following childbirth. If you take estrogens during pregnancy,
your unborn child has a greater than usual chance of having birth
defects. The risk of developing these defects is small, but clearly
larger than the risk in children whose mothers did not take estrogens
during pregnancy. These birth defects may affect the baby’s
urinary system and sex organs. Daughters born to mothers who took
DES (an estrogen drug) have a higher than usual chance of developing
cancer of the vagina or cervix when they become teenagers or young
adults. Sons may have a higher than usual chance of developing cancer
of the testicles when they become teenagers or young adults.
USES OF ESTROGEN
(Not every estrogen drug
is approved for every use listed in this section. If you
want to know which of these possible uses are approved for the medicine
prescribed for you, ask your doctor or pharmacist to show you the
professional labeling. You can also look up the specific estrogen
product in a book called the “Physicians’ Desk Reference”,
which is available in many book stores and public libraries. Generic
drugs carry virtually the same labeling information as their brand
To reduce moderate or severe
hormones made by the ovaries of normal women. Between ages 45 and
55, the ovaries normally stop making estrogens. This leads to a drop
in body estrogen levels which causes the “change of life’’
or menopause (the end of monthly menstrual periods). If both ovaries
are removed during an operation before natural menopause takes place,
the sudden drop in estrogen levels causes “surgical menopause”.
When the estrogen levels begin dropping, some women develop
very uncomfortable symptoms, such as feelings of warmth in the face,
neck, and chest, or sudden intense episodes of heat and sweating (“hot
flashes” or “hot flushes”). Using estrogen drugs
can help the body adjust to lower estrogen levels and reduce these
symptoms. Most women have only mild menopausal symptoms or none at
all and do not need to use estrogen drugs for these symptoms. Others
may need to take estrogens for a few months while their bodies adjust
to lower estrogen levels. The majority of women do not need estrogen
replacement for longer than six months for these symptoms.
To treat vulval and vaginal
atrophy (itching, burning, dryness in or around the vagina,
difficulty or burning on urination) associated with menopause.
To treat certain conditions
in which a young woman’s ovaries do not produce enough estrogen
To treat certain types
of abnormal vaginal bleeding due to hormonal imbalance when your doctor
has found no serious cause of the bleeding.
To treat certain cancers
in special situations, in men and women.
To prevent thinning of
Osteoporosis is a thinning
of the bones that makes them weaker and allows them to break more
easily. The bones of the spine, wrists and hips break most often in
osteoporosis. Both men and women start to lose bone mass after about
age 40, but women lose bone mass faster after the menopause. Using
estrogens after the menopause slows down bone thinning and may prevent
bones from breaking. Lifelong adequate calcium intake, either in the
diet (such as dairy products) or by calcium supplements (to reach
a total daily intake of 1000 milligrams per day before menopause or
1500 milligrams per day after menopause), may help to prevent osteoporosis.
Regular weight-bearing exercise (like walking and running for an hour,
two or three times a week) may also help to prevent osteoporosis.
Before you change your calcium intake or exercise habits, it is important
to discuss these lifestyle changes with your doctor to find out if
they are safe for you.
Since estrogen use has
some risks, only women who are likely to develop osteoporosis should
use estrogens for prevention. Women who are likely to develop osteoporosis
often have the following characteristics: white or Asian race, slim,
cigarette smokers, and a family history of osteoporosis in a mother,
sister, or aunt. Women who have relatively early menopause, often
because their ovaries were removed during an operation (“surgical
menopause”), are more likely to develop osteoporosis than women
whose menopause happens at the average age.
WHO SHOULD NOT USE ESTROGENS
Estrogens should not be used:
During pregnancy (see Boxed WARNINGS).
If you think you may be pregnant, do not use any form of estrogen-containing
drug. Using estrogens while you are pregnant may cause your unborn
child to have birth defects. Estrogens do not prevent miscarriage.
If you have unusual vaginal
bleeding which has not been evaluated by your doctor (see Boxed WARNINGS).
Unusual vaginal bleeding can be a warning
sign of cancer of the uterus, especially if it happens after menopause.
Your doctor must find out the cause of the bleeding so that he or
she can recommend the proper treatment. Taking estrogens without visiting
your doctor can cause you serious harm if your vaginal bleeding is
caused by cancer of the uterus.
If you have had cancer.
Since estrogens increase the risk of certain
types of cancer, you should not use estrogens if you have ever had
cancer of the breast or uterus, unless your doctor recommends that
the drug may help in the cancer treatment. (For certain patients with
breast or prostate cancer, estrogens may help.)
If you have any circulation
Estrogen drugs should not
be used except in unusually special situations in which your doctor
judges that you need estrogen therapy so much that the risks are acceptable.
Men and women with abnormal blood clotting conditions should avoid
estrogen use (see DANGERS OF ESTROGENS).
When they do not work.
During menopause, some women develop nervous
symptoms or depression. Estrogens do not relieve these symptoms. You
may have heard that taking estrogens for years after menopause will
keep your skin soft and supple and keep you feeling young. There is
no evidence for these claims and such long-term estrogen use may have
After childbirth or when
breastfeeding a baby.
not be used to try to stop the breasts from filling with milk after
a baby is born. Such treatment may increase the risk of developing
blood clots (see DANGERS OF ESTROGENS).
If you are breastfeeding, you should avoid
using any drugs because many drugs pass through to the baby in the
milk. While nursing a baby, you should take drugs only on the advice
of your health care provider.
DANGERS OF ESTROGENS
Cancer of the uterus. Your risk of developing cancer of the uterus gets higher the longer
you use estrogens and the larger doses you use. One study showed that
after women stop taking estrogens, this higher cancer risk quickly
returns to the usual level of risk (as if you had never used estrogen
therapy). Three other studies showed that the cancer risk stayed high
for 8 to more than 15 years after stopping estrogen treatment. Because
of this risk, IT IS IMPORTANT TO TAKE THE
LOWEST DOSE THAT WORKS AND TO TAKE IT ONLY AS LONG AS YOU NEED IT.
Using progestin therapy together with estrogen
therapy may reduce the higher risk of uterine cancer related to estrogen
use (but see OTHER INFORMATION).
If you have had your uterus removed (total
hysterectomy), there is no danger of developing cancer of the uterus.
Cancer of the breast.
Studies examining the risk of breast cancer
among women using estrogen alone and combined estrogen/progestin therapy
have suggested that there may be a mildly increased risk of breast
cancer in women taking the combined therapy.
If you do not have your uterus, there is no need for combined estrogen/progestin
therapy since estrogen alone therapy is sufficient and may pose less
risk for breast cancer.
If you do have your
uterus, you should discuss the benefits and risks of combined estrogen/progestin
therapy with your health care provider. Regular breast exams by a
health professional and monthly self-exams are recommended for all
women. Mammography may also be recommended depending on your age and
Women who use estrogens after menopause are
more likely to develop gallbladder disease needing surgery than women
who do not use estrogens.
Abnormal blood clotting.
Taking estrogens may cause changes in your
blood clotting system. These changes allow the blood to clot more
easily, possibly allowing clots to form in your bloodstream. If blood
clots do form in your bloodstream, they can cut off the blood supply
to vital organs, causing serious problems. These problems may include
a stroke (by cutting off blood to the brain), a heart attack (by cutting
off blood to the heart), a pulmonary embolus (by cutting off blood
to the lungs), or other problems. Any of these conditions may cause
death or serious long term disability. However, most studies of low
dose estrogen usage by women do not show an increased risk of these
In addition to the risks listed above, the following
side effects have been reported with estrogen use.
Nausea and vomiting.
Breast tenderness or
Enlargement of benign tumors (“fibroids”)
of the uterus.
Retention of excess fluid. This
may make some conditions worsen, such as asthma, epilepsy, migraine,
heart disease, or kidney disease.
darkening of the skin, particularly on the face.
REDUCING RISK OF ESTROGEN USE
If you use estrogens, you can reduce your risks by
doing these things:
See your doctor regularly.
While you are using estrogens, it is important
to visit your doctor at least once a year for a check-up. If you develop
vaginal bleeding while taking estrogens, you may need further evaluation.
If members of your family have had breast cancer or if you have ever
had breast lumps or an abnormal mammogram (breast x-ray), you may
need to have more frequent breast examinations.
Reassess your need for
You and your doctor should
reevaluate whether or not you still need estrogens at least every
Be alert for signs of trouble.
If any of these warning signals (or any other
unusual symptoms) happen while you are using estrogens, call your
Abnormal bleeding from
the vagina (possible uterine cancer)
in the calves or chest, sudden shortness of breath, or coughing blood
(possible clot in the legs, heart, or lungs)
Severe headache or vomiting, dizziness, faintness, changes in vision
or speech, weakness or numbness of an arm or leg (possible clot in
the brain or eye)
Breast lumps (possible breast
cancer; ask your doctor or health professional to show you how toexamine your breasts monthly)
the skin or eyes (possible liver problem)
swelling, or tenderness in the abdomen (possible gallbladder problem)
Estrogens increase the risk of developing a condition
(endometrial hyperplasia) that may lead to cancer of the lining of
the uterus. Taking progestins, another hormone drug, with estrogens
lowers the risk of developing this condition. Therefore, if your uterus
has not been removed, your doctor may prescribe a progestin for you
to take together with the estrogen.
know, however, that taking estrogens with progestins may have additional risks. These include: (a) unhealthy
effects on blood fats (especially the lowering of HDL blood cholesterol,
the “good” blood fat which protects against heart disease);
(b) unhealthy effects on blood sugar (which might make a diabetic
condition worse); and (c) a possible further increase in breast cancer
risk which may be associated with long-term estrogen use.
Some research has shown that estrogens taken without progestins may protect women against
developing heart disease. However, this is not certain. The protection
shown may have been caused by the characteristics of the estrogentreated
women, and not by the estrogen treatment itself. In general, treated
women were slimmer, more physically active, and were less likely to
have diabetes than the untreated women. These characteristics are
known to be associated with a reduced risk for heart disease.
You are cautioned to discuss
very carefully with your doctor or health care provider all the possible
risks and benefits of long-term estrogen and progestin treatment as
they affect you personally.
Your doctor has prescribed this drug for you and
you alone. Do not give the drug to anyone else.
If you will be taking calcium supplements as part
of the treatment to help prevent osteoporosis, check with your doctor
about how much to take.
Keep this and all drugs out of the reach of children.
In case of overdose, call your doctor, hospital or poison control
This leaflet provides a summary of the most important
information about estrogens. If you want more information, ask your
doctor or pharmacist to show you the professional labeling. The professional
labeling is also published in a book called the “Physicians’
Desk Reference,” which is available in book stores and public
libraries. Generic drugs carry virtually the same labeling information
as their brand name versions.