Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/3818
Predicate | Object |
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rdfs:label |
Menest (Tablet)
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dailymed-instance:dosage |
When estrogen is prescribed for a postmenopausal
woman with a uterus, a progestin should also be initiated to reduce
the risk of endometrial cancer. A woman without a uterus does not
need progestin. Use of estrogen, alone or in combination with a progestin,
should be with the lowest effective dose and for the shortest duration
consistent with treatment goals and risks for the individual woman.
Patients should be reevaluated periodically as clinically appropriate
(e.g., 3-month to 6-month intervals) to determine if treatment is
still necessary For women who have a uterus, adequate diagnostic measures, such
as endometrial sampling, when indicated, should be undertaken to rule
out malignancy in cases of undiagnosed persistent or recurring abnormal
vaginal bleeding. Patients should be started
at the lowest dose. 1. Given cyclically for
short term use only: For treatment of moderate
to severe vasomotor symptoms, or moderate to severe symptoms of vulvar
and vaginal atrophy associated with the menopause. Administration should be cyclic (e.g., 3 weeks on and 1 week off). USUAL DOSAGE RANGES: Vasomotor symptoms���1.25 mg daily.
If the patient has not menstruated within the last 2 months or more,
cyclic administration is started arbitrarily. If the patient is menstruating,
cyclic administration is started on day 5 of bleeding. Moderate to severe symptoms
of vulvar and vaginal atrophy���0.3 mg to 1.25 mg
or more daily, depending upon the tissue response of the individual
patient. Administer cyclically. 2. Given cyclically:
Female hypogonadism; female castration; primary ovarian failure.<br/>USUAL DOSAGE RANGES:: Female hypogonadism���2.5 to 7.5 mg daily, in divided doses for 20 days, followed
by a rest period of 10 days' duration. If bleeding does not
occur by the end of this period, the same dosage schedule is repeated.
The number of courses of estrogen therapy necessary to produce bleeding
may vary depending on responsiveness of the endometrium. If bleeding occurs before the end of the 10 day period,
begin a 20 day estrogen-progestin cyclic regimen with Menest (esterified
estrogens tablets), 2.5 to 7.5 mg daily in divided doses, for 20 days.
During the last 5 days of estrogen therapy, give an oral progestin.
If bleeding occurs before this regimen is concluded, therapy is discontinued
and may be resumed on the fifth day of bleeding. Female castration and primary ovarian failure���1.25 mg daily, cyclically. Adjust dosage upward or downward
according to severity of symptoms and response of the patient. For
maintenance, adjust dosage to lowest level that will provide effective
control. 3. Given chronically: Inoperable progressing
prostatic cancer���1.25 to 2.5 mg three times daily. The effectiveness
of therapy can be judged by phosphatase determinations as well as
by symptomatic improvement of the patient. Inoperable
progressing breast cancer in appropriately selected men and postmenopausal
women.���Suggested dosage is 10 mg three times daily for a period
of at least 3 months. 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. The lowest effective dose of Menest
has not been determined.
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dailymed-instance:descripti... |
Esterified estrogens is a mixture of the sodium
salts of the sulfate esters of the estrogenic substances, principally
estrone, that are of the type excreted by pregnant mares. The content
of total esterified estrogens is not less than 90 percent and not
more than 110 percent of the labeled amount. Esterified estrogens
contain not less than 75 percent and not more than 85 percent of sodium
estrone sulfate, and not less than 6 percent and not more than 15
percent of sodium equilin sulfate, in such proportion that the total
of these two components is not less than 90 percent, all percentages
being calculated on the basis of the total esterified estrogens content.<br/>Inactive Ingredients:: Ethyl cellulose, fragrances, hydroxypropyl cellulose,
hypromellose 2910, lactose, magnesium stearate, methylcellulose, polyethylene
glycol, sodium bicarbonate, shellac, starch, stearic acid, titanium
dioxide, and vanillin. Dyes in the form of aluminum lakes are contained
in each tablet strength as follows: 0.3 mg Tablet: FD&C
Yellow No. 6, D&C Yellow No. 10. 0.625 mg Tablet: FD&C
Yellow No. 6, D&C Yellow No. 10. 1.25 mg Tablet: FD&C Yellow No. 6, D&C Yellow No.
10, FD&C Blue No. 1. 2.5 mg
Tablet: D&C Red No. 30.
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dailymed-instance:clinicalP... |
Endogenous estrogens are largely responsible for
the development and maintenance of the female reproductive system
and secondary sexual characteristics. Although circulating estrogens
exist in a dynamic equilibrium of metabolic interconversions, estradiol
is the principal intracellular human estrogen and is substantially
more potent than its metabolites, estrone and estriol, at the receptor
level. The primary source of estrogen in normally
cycling adult women is the ovarian follicle, which secrets 70 to 500mcg of estradiol daily, depending on the phase of the menstrual cycle.
After menopause, most endogenous estrogen is produced by conversion
of androstenedione, secreted by the adrenal cortex, to estrone by
the peripheral tissues. Thus,estrone and the sulfate conjugated form,
estrone sulfate, are the most abundant circulating estrogens in postmenopausal
women. Estrogens act through binding to nuclear
receptors in estrogen-responsive tissues. To date, two estrogen receptors
have been identified. These vary in proportion from tissue to tissue. Circulating estrogens modulate the pituitary secretion
of the gonadotropins, luteinizing hormone (LH) and follicle stimulating
hormone (FSH), through a negative feedback mechanism. Estrogens act
to reduce the elevated levels of these hormones seen in postmenopausal
women.<br/>Distribution: The distribution of exogenous estrogens is similar
to that of endogenous estrogens. Estrogens are widely distributed
in the body and are generally found in higher concentrations in the
sex hormone target organs. Estrogens circulate in the blood largely
bound to sex hormone binding globulin (SHBG) and albumin.<br/>Metabolism: Exogenous estrogens are metabolized in the same manner
as endogenous estrogens. Circulating estrogens exist in a dynamic
equilibrium of metabolic interconversions. These transformations take
place mainly in the liver. Estradiol is converted reversibly to estrone,
and both can be converted to estriol, which is the major urinary metabolite.
Estrogens also undergo enterohepatic recirculation via sulfate and
glucuronide conjugation in the liver, biliary secretion of conjugates
into the intestine, and hydrolysis in the gut followed by reabsorption.
In postmenopausal women, a significant proportion of the circulating
estrogens exist as sulfate conjugates, especially estronesulfate,
which serves as a circulating reservoir for the formulation of more
active estrogens.<br/>Excretion: Estradiol, estrone, and estriol are excreted in the
urine along with glucuronide and sulfate conjugates.<br/>Drug Interactions: In vitro and in vivo studies have shown that estrogens
are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore,
inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism.
Inducers of CYP3A4 such as St. John's Wort preparations (Hypericum
perforatum), phenobarbital, carbamazepine, and rifampin may reduce
plasma concentrations of estrogens, possibly resulting in a decrease
in therapeutic effects and/or changes in the uterine bleeding profile.
Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole,
itraconazole, ritonavir and grapefruit juice may increase plasma concentrations
of estrogens and may result in side effects.<br/>Clinical Studies:<br/>Women's Health Initiative Studies.: The Women's Health Initiative (WHI) enrolled
a total of 27,000 predominantly healthy postmenopausal women to assess
the risks and benefits of either the use of oral 0.625 mg conjugated
estrogens (CE) per day alone or the use of oral 0.625 mg conjugated
estrogens plus 2.5 mg medroxyprogesterone acetate (MPA) per day compared
to placebo in the prevention of certain chronic diseases. The primary
endpoint was the incidence of coronary heart disease (CHD) (nonfatal
myocardial infarction and CHD death), with invasive breast cancer
as the primary adverse outcome studies. A���global index���included the earliest occurrence of CHD, invasive breast cancer, stroke,
pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip
fracture, or death due to other cause. The study did not evaluate
the effects of CE or CE/MPA on menopausal symptoms. The CE/MPA substudy was stopped early because, according to the predefined
stopping rule, the increased risk of breast cancer and cardiovascular
events exceeded the specified benefits included in the���global
index.���Results of the CE/MPA substudy, which included 16,608
women (average age of 63 years, range 50 to 79; 83.9% White, 6.5%
Black, 5.5% Hispanic), after an average follow-up of 5.2 years are
presented in Table 1 below: adapted from JAMA, 2002; 288:321-333 includes metastatic and non-metastatic breast
cancer with the exception of in situ breast cancer a subset of the events was combined in a���global
index���, defined as the earliest occurrence of CHD events, invasive
breast cancer, stroke, pulmonary embolism, endometrial cancer, colorectal
cancer, hip fracture, or death due to other causes not included in Global Index nominal confidence intervals unadjusted for multiple looks
and multiple comparisons For those outcomes
included in the���global index,���absolute excess risks
per 10,000 women-years in the group treated with CE/MPA were 7 more
CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast
cancers, while absolute risk reductions per 10,000 women-years were
6 fewer colorectal cancers and 5 fewer hip fractures. The absolute
excess risk of events included in the���global index���was 19 per 10,000 women-years. There was no difference between the
groups in terms of all-cause mortality.<br/>Women's Health Initiative Memory Study: The Women's Health Initiative Memory Study
(WHIMS), a substudy of WHI, enrolled 4,532 predominantly healthy postmenopausal
women 65 years of age and older (47% were age 65 to 69 years, 35%
were 70 to 74 years, and 18% were 75 years of age and older) to evaluate
the effects of CE/MPA (0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone
acetate) on the incidence of probable dementia (primary outcome) compared
with placebo. After an average follow-up of
4 years, 40 women in the estrogen/ progestin group (45 per 10,000
women-years) and 21 in the placebo group (22 per 10,000 women-years)
were diagnosed with probable dementia. The relative risk of probable
dementia in the hormone therapy group was 2.05 (95% CI, 1.21 to 3.48)
compared to placebo. Differences between groups became apparent in
the first year of treatment. It is unknown whether these findings
apply to younger postmenopausal women.
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dailymed-instance:activeIng... | |
dailymed-instance:contraind... |
Menest should not be used in women with any of the
following conditions:
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dailymed-instance:supply |
Tablets: 0.3 mg yellow, film-coated
oblong tablet imprinted with M72 100's: NDC 61570-072-01 0.625 mg orange, film-coated oblong tablet imprinted with
M73 100's: NDC 61570-073-01 1.25 mg
green, film-coated oblong tablet imprinted with M74 100's:
NDC 61570-074-01 2.5 mg pink, film-coated oblong
tablet imprinted with M75 50's: NDC 61570-075-50
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dailymed-instance:boxedWarn... |
ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER 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 the use of���natural���estrogens results in a different endometrial risk profile than synthetic
estrogens at equivalent estrogen doses. (See WARNINGS, Malignant neoplasms, Endometrial cancer.) CARDIOVASCULAR AND OTHER RISKS Estrogens with and without progestins should
not be used for the prevention of cardiovascular disease. The Women's Health Initiative (WHI) study reported increased
risks of myocardial infarction, stroke, invasive breast cancer, pulmonary
emboli, and deep vein thrombosis in postmenopausal women (50 to 79
years of age) during 5 years of treatment with oral conjugated estrogens
(CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg)
relative to placebo
The Women's Health Initiative Memory Study (WHIMS), a substudy
of WHI, reported increased risk of developing probable dementia in
postmenopausal women 65 years of age or older during 4 years of treatment
with oral conjugated estrogensplus medroxyprogesterone acetate relative
to placebo. It is unknown whether this finding applies to younger
postmenopausal women or to women taking estrogen alone therapy. Other doses of conjugated estrogens with medroxyprogesterone acetate,
and other combinations and dosage forms of estrogens and progestins
were not studied in the WHI clinical trials and, in the absence of
comparable data, these risks should be assumed to be similar. Because
of these risks, estrogens with or without progestins should be prescribed
at the lowest effective doses and for the shortest duration consistent
with treatment goals and risks for the individual woman.
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dailymed-instance:activeMoi... | |
dailymed-instance:inactiveI... |
dailymed-ingredient:D&C_yellow_No._10,
dailymed-ingredient:FD&C_yellow_No._6,
dailymed-ingredient:ethyl_cellulose,
dailymed-ingredient:fragrances,
dailymed-ingredient:hydroxypropyl_cellulose,
dailymed-ingredient:hypromellose_2910,
dailymed-ingredient:lactose,
dailymed-ingredient:magnesium_stearate,
dailymed-ingredient:methylcellulose,
dailymed-ingredient:polyethylene_glycol,
dailymed-ingredient:shellac,
dailymed-ingredient:sodium_bicarbonate,
dailymed-ingredient:starch,
dailymed-ingredient:stearic_acid,
dailymed-ingredient:titanium_dioxide,
dailymed-ingredient:vanillin
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dailymed-instance:precautio... |
A. GENERAL:<br/>1. Addition of a progestin when a woman has not had a hysterectomy: Studies of the addition of progestin for 10 or more
days of a cycle of estrogen administration, or daily with estrogen
in a continuous regimen, have reported a lowered incidence of endometrial
hyperplasia than would be induced by estrogen treatment alone. Endometrial
hyperplasia may be a precursor to endometrial cancer. There are, however, possible risks that may be associated with the
use of progestins with estrogens compared to estrogen- alone regimens.
These include a possible increased risk of breast cancer.<br/>2. Elevated blood pressure: In a small number of case reports, substantial increases
in blood pressure have been attributed to idiosyncratic reactions
to estrogens. In a large, randomized, placebo-controlled clinical
trial, a generalized effect of estrogens on blood pressure was not
seen. Blood pressure should be monitored at regular intervals with
estrogen use.<br/>3. Hypertriglyceridemia: In patients with pre-existing hypertriglyceridemia,
estrogen therapy may be associated with elevations of plasma triglycerides
leading to pancreatitis and other complications.<br/>4. Impaired liver function and past history of cholestatic
jaundice: Estrogens may be poorly metabolized in patients with
impaired liver function. For patients with a history of cholestatic
jaundice associated with past estrogen use or with pregnancy, caution
should be exercised and in the case of recurrence, medication should
be discontinued.<br/>5. Hypothyroidism: Estrogen administration leads to increased thyroid-binding
globulin (TBG) levels. Patients with normal thyroid function can compensate
for the increased TBG by making more thyroid hormone, thus maintaining
free Tand Tserum concentrations in the normal
range. Patients dependent on thyroid hormone replacement therapy who
are also receiving estrogens may require increased doses of their
thyroid replacement therapy. These patients should have their thyroid
function monitored in order to maintain their free thyroid hormone
levels in an acceptable range.<br/>6. Fluid retention: Because estrogens may cause some degree of fluid
retention, patients with conditions that might be influenced by this
factor, such as a cardiac or renal dysfunction, warrant careful observation
when estrogens are prescribed.<br/>7. Hypocalcemia: Estrogens should be used with caution in individuals
with severe hypocalcemia.<br/>8. Ovarian cancer: The CE/MPA substudy of WHI reported that estrogen
plus progestin increased the risk of ovarian cancer. After an average
follow-up of 5.6 years, the relative risk for ovarian cancer for CE/MPA
versus placebo was 1.58 (95% confidence interval 0.77���3.24)
but was not statistically significant. The absolute risk for CE/MPA
versus placebo was 4.2 versus 2.7 cases per 10,000 women-years. In
some epidemiologic studies, the use of estrogen alone, in particular
for ten or more years, has been associated with an increased risk
of ovarian cancer. Other epidemiologic studies have not found these
associations.<br/>9. Exacerbation of endometriosis: Endometriosis may be exacerbated with administration
of estrogens. A few cases of malignant transformation of residual
endometrial implants have been reported in women treated post-hysterectomy
with estrogen alone therapy. For patients known to have residual endometriosis
post-hysterectomy, the addition of progestin should be considered.<br/>10. Exacerbation of other conditions: Estrogens may cause an exacerbation of asthma, diabetes
mellitus, epilepsy, migraine or porphyria, systemic lupus erythematosus,
and hepatic hemangiomas and should be used with caution in women with
these conditions.<br/>B. PATIENT INFORMATION: Physicians are advised to discuss the PATIENT INFORMATION
leaflet with patients for whom they prescribe Menest.<br/>C. LABORATORY TESTS: Estrogen administration should be initiated at the
lowest dose approved for the indication and then guided by clinical
response, rather than by serum hormone levels (e.g., estradiol, FSH).<br/>D. DRUG/LABORATORY TEST INTERACTIONS:<br/>E. CARCINOGENESIS, MUTAGENESIS, AND IMPAIRMENT OF FERTILITY: Long-term continuous administration of estrogen,
with and without progestin, in women with and without a uterus, has
shown an increased risk of endometrial cancer, breast cancer, and
ovarian cancer. 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.<br/>F. PREGNANCY: Menest should not be used during pregnancy.<br/>G. NURSING MOTHERS: Estrogen administration to nursing mothers has been
shown to decrease the quantity and quality of the milk. Detectable
amounts of estrogens have been identified in the milk of mothers receiving
this drug. Caution should be exercised when Menest is administered
to a nursing mother.<br/>H. PEDIATRIC USE: Safety and effectiveness in pediatric patients have
not been established.<br/>I. GERIATRIC USE: In the Women's Health Initiative Memory Study,
including 4,532 women 65 years of age and older, followed for an average
of 4 years, 82% (n = 3,729) were 65 to 74 while 18% (n = 803) were
75 and over. Most women (80%) had no prior hormone therapy use. Women
treated with conjugated estrogens plus medroxyprogesterone acetate
were reported to have a two-fold increasein the risk of developing
probable dementia. Alzheimer's disease was the most common
classification of probable dementia in both the conjugated estrogens
plus medroxyprogesterone acetate group and the placebo group. Ninety
percent of the cases of probable dementia occurred in the 54% of women
that were older than 70. It is
unknown whether these findings apply to estrogen alone therapy.
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dailymed-instance:overdosag... |
Serious ill effects have not been reported following
acute ingestion of large doses of estrogen-containing drug products
by young children. Overdosage of estrogen may cause nausea and vomiting,
and withdrawal bleeding may occur in females.
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dailymed-instance:genericMe... |
Estrogens, esterified
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dailymed-instance:fullName |
Menest (Tablet)
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dailymed-instance:adverseRe... |
See BOXED WARNINGS, WARNINGS and PRECAUTIONS. The following additional adverse
reactions have been reported with estrogens and/or progestin therapy.<br/>1. Genitourinary system: Changes in vaginal bleeding pattern and abnormal
withdrawal bleeding or flow; breakthrough bleeding; spotting; dysmenorrhea,
increase in size of uterine leiomyomata; vaginitis, including vaginal
candidiasis; change in amount of cervical secretion; changes in cervical
ectropion; ovarian cancer; endometrial hyperplasia; endometrial cancer;
premenstrual like syndrome, amenorrhea during and after treatment;
cystitis like syndrome.<br/>2. Breasts: Tenderness, enlargement, pain, nipple discharge,
galactorrhea; fibrocystic breast changes; breast cancer.<br/>3. Cardiovascular: Deep and superficial venous thrombosis; pulmonary
embolism; thrombophlebitis; myocardial infarction; stroke; increase
in blood pressure.<br/>4. Gastrointestinal: Nausea, vomiting; abdominal cramps, bloating; cholestatic
jaundice; increased incidence of gall bladder disease; pancreatitis,
enlargement of hepatic hemangiomas.<br/>5. Skin: Chloasma or melasma, that may persist when drug is
discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption;
loss of scalp hair; hirsutism; pruritus, rash.<br/>6. Eyes: Retinal vascular thrombosis; steepening of corneal
curvature; intolerance to contact lenses.<br/>7. Central nervous system: Headache; migraine; dizziness; mental depression;
chorea; nervousness; mood disturbances; irritability; exacerbation
of epilepsy, dementia.<br/>8. Miscellaneous: Increase or decrease in weight; reduced carbohydrate
tolerance; aggravation of porphyria; edema; arthalgias; leg cramps;
changes in libido; urticaria, angioedema, anaphylactoid/anaphylactic
reactions; hypocalcemia; exacerbation of asthma; increased triglycerides.
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dailymed-instance:warning |
See BOXED WARNINGS. The use of unopposed estrogens in women who have a uterus
is associated with an increased risk of endometrial cancer.<br/>1. Cardiovascular disorders: Estrogen and estrogen/progestin therapy has been
associated with an increased risk of cardiovascular events such as
myocardial infarction and stroke, as well as venous thrombosis and
pulmonary embolism (venous thromboembolism or VTE). Should any of
these occur or be suspected, estrogens should be discontinued immediately. Risk factors for arterial vascular disease (e.g., hypertension,
diabetes mellitus, tobacco use, hypercholesterolemia, and obesity)
and/or venous thromboembolism (e.g., personal history or family history
of VTE, obesity, and systemic lupus erythematosus) should be managed
appropriately.<br/>a. Coronary heart disease and stroke: In the Women's Health Initiative study (WHI),
an increase in the number of myocardial infarctions and strokes has
been observed in women receiving CE compared to placebo. These observations
are preliminary. In the CE/MPA substudy of WHI, an increased risk of coronary
heart disease (CHD) events (defined as nonfatal myocardial infarction
and CHD death) was observed in women receiving CE/MPA compared to
women receiving placebo (37 vs 30 per 10,000 women-years). The increase
in risk was observed in year one and persisted. In the same substudy of WHI, an increased risk of stroke was observed
in women receiving CE/MPA compared to women receiving placebo (29
vs 21 per 10,000 women-years). The increase in risk was observed after
the first year and persisted. In postmenopausal
women with documented heart disease (n = 2,763, average age 66.7 years)
a controlled clinical trial of secondary prevention of cardiovascular
disease (Heart and Estrogen/Progestin Replacement study; HERS) treatment
with CE/MPA (0.625mg/2.5mg per day) demonstrated no cardiovascular
benefit. During an average follow-up of 4.1 years, treatment with
CE/MPA did not reduce the overall rate of CHD events in postmenopausal
women with established coronary heart disease. There were more CHD
events in the CE/MPAtreated group than in the placebo group in year
1, but not during the subsequent years. Two thousand three hundred
and twenty-one women from the original HERS trial agreed to participate
in an open label extension of HERS, HERS II. Average follow-up in
HERS II was an additional 2.7 years, for a total of 6.8 years overall.
Rates of CHD events were comparable among women in the CE/MPA group
and the placebo group in HERS, HERS II and overall. 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.<br/>b. Venous thromboembolism (VTE): In the Women's Health Initiative study (WHI),
an increase in VTE has been observed in women receiving CE compared
to placebo. These observations are preliminary. In the CE/MPA substudy of WHI, a 2-fold
greater rate of VTE, including deep venous thrombosis and pulmonary
embolism, was observed in women receiving CE/MPA compared to women
receiving placebo. The rate of VTE was 34 per 10,000 women-years in
the CE/MPA group compared to 16 per 10,000 women-years in the placebo
group. The increase in VTE risk was observed during the first year
and persisted. If feasible, estrogens should
be discontinued at least 4 to 6 weeks before surgery of the type associated
with an increased risk of thromboembolism, or during periods of prolonged
immobilization.<br/>2. Malignant neoplasms:<br/>a. Endometrial cancer: The use of unopposed estrogens in women with intact
uteri has been associated with an increased risk of endometrial cancer.
The reported endometrial cancer risk among unopposed estrogen users
is about 2- to 12-fold greater than in non-users, 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-foldfor five to ten years
or more and this risk has been shown to persist for at least 8 to
15 years after estrogen therapy is discontinued. Clinical surveillance of all women taking estrogen/progestin combinations
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 the use of natural estrogens results
in a different endometrial risk profile than synthetic estrogens,
of equivalent estrogen dose. Adding a progestin to estrogen therapy
has been shown to reduce the risk of endometrial hyperplasia, which
may be a precursor to endometrial cancer.<br/>b. Breast cancer: The use of estrogens and progestins by postmenopausal
women has been reported to increase the risk of breast cancer. The
most important randomized clinical trial providing information about
this issue is the Women's Health Initiative (WHI) substudy
of CE/MPA .
The results from observational studies are generally consistent with
those of the WHI clinical trial and report no significant variation
in the risk of breast cancer among different estrogens or progestins,
doses, or routes of administration. The CE/MPA
substudy of WHI reported an increased risk of breast cancer in women
who took CE/MPA for a mean follow- up of 5.6 years. Observational
studies have also reported an increased risk for estrogen/progestin
combination therapy, and a smaller increased risk for estrogen alone
therapy, after several years of use. In the WHI trial and from observational
studies, the excess risk increased with duration of use. From observational
studies, the risk appeared to return to baseline in about five years
after stopping treatment. Inaddition, observational studies suggest
that the risk of breast cancer was greater, and became apparent earlier,
with estrogen/progestin combination therapy as compared to estrogen
alone therapy. In the CE/MPA substudy, 26% of
the women reported prior use of estrogen alone and/or estrogen/progestin
combination hormone therapy. After a mean follow-up of 5.6 years during
the clinical trial, the overall relative risk of invasive breast cancer
was 1.24 (95% confidence interval 1.01���1.54), and the overall
absolute risk was 41 vs 33 cases per 10,000 women-years, for CE/MPA
compared with placebo. Among women who reported prior use of hormone
therapy, the relative risk of invasive breast cancer was 1.86, and
the absolute risk was 46 vs 25 cases per 10,000 women-years, for CE/MPA
compared with placebo. Among women who reported no prior use of hormone
therapy, the relative risk of invasive breast cancer was 1.09, and
the absolute risk was 40 vs 36 cases per 10,000 women-years for CE/MPA
compared with placebo. In the same substudy, invasive breast cancers
were larger and diagnosed at a more advanced stage in the CE/MPA group
compared with the placebo group. Metastatic disease was rare with
no apparent difference between the two groups. Other prognostic factors
such as histologic subtype, grade and hormone receptor status did
not differ between the groups. The use of estrogen
plus progestin has been reported to result in an increase in abnormal
mammograms requiring further evaluation. All women should receive
yearly breast examinations by a healthcare provider and perform monthly
breast self-examinations. In addition, mammography examinations should
be scheduled based on patient age, risk factors, and prior mammogram
results.<br/>3. Dementia: In the Women's Health Initiative Memory Study
(WHIMS), 4,532 generally healthy postmenopausal women 65 years of
age and older were studied, of whom 35% were 70 to 74 years of age
and 18% were 75 or older. After an average follow-up of 4 years, 40
women being treated with CE/MPA (1.8%, n = 2,229) and 21 women in
the placebo group (0.9%, n = 2,303) received diagnoses of probable
dementia. The relative risk for CE/MPA versus placebo was 2.05 (95%
confidence interval 1.21���3.48), and was similar for women
with and without histories of menopausal hormone use before WHIMS.
The absolute risk of probable dementia for CE/MPA versus placebo was
45 versus 22 cases per 10,000 women-years, and the absolute excess
risk for CE/MPA was 23 cases per 10,000 women-years. It is unknown
whether these findings apply to younger postmenopausal women. It is unknown whether these findings apply
to estrogen alone therapy.<br/>4. Gallbladder disease: A 2- to 4-fold increase in the risk of gallbladder
disease requiring surgery in postmenopausal women receiving estrogens
has been reported.<br/>5. Hypercalcemia: Estrogen administration may lead to severe hypercalcemia
in patients with breast cancer and bone metastases. If hypercalcemia
occurs, use of the drug should be stopped and appropriate measures
taken to reduce the serum calcium level.<br/>6. Visual abnormalities: Retinal vascular thrombosis has been reported in
patients receiving estrogens. Discontinue medication pending examination
if there is a sudden partial or complete loss of vision, or a sudden
onset of proptosis, diplopia, or migraine. If examination reveals
papilledema or retinal vascular lesions, estrogens should be permanently
discontinued.<br/>7. Hepatic adenoma: Benign hepatic adenomas appear to be associated with
the use of oral contraceptives. Although benign, and rare, these may
rupture and may cause death through intra-abdominal hemorrhage. Such
lesions have not yet been reported in association with other estrogen
or progestagen preparations but should be considered in estrogen users
having abdominal pain and tenderness, abdominal mass, or hypovolemic
shock. Hepatocellular carcinoma has also been reported in women taking
estrogen-containing oral contraceptives. The relationship of this
malignancy to these drugs is not known at this time.
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Menest is indicated in the:
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Menest
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