INDICATIONS
Estradiol tablets are indicated in the:
1. 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 conditions.
2. Treatment of vulval and vaginal atrophy.
3. Treatment of hypoestrogenism due
to hypogonadism, castration or primary ovarian failure.
4. Treatment of breast cancer (for palliation
only) in appropriately selected women and men with metastatic
disease.
5. Treatment of advanced androgen-dependent
carcinoma of the prostate (for palliation only).
6. Prevention of osteoporosis.
Since estrogen administration is associated with risk,
selection of patients should ideally be based on prospective
identification of risk factors for developing osteoporosis.
Unfortunately, there is no certain way to identify those
women who will develop osteoporotic fractures. Most prospective
studies of efficacy for this indication have been carried
out in white menopausal women, without stratification
by other risk factors, and tend to wshow a universally
salutary effect on bone. Thus, patient selection must
be individualized based on the balance of risks and benefits.
A more favorable risk/benefit ratio exists in a hysterectomized
woman because she has no risk of endometrial cancer (see
BOXED WARNING).
Estrogen replacement therapy reduces bone resorption
and retards or halts postmenopausal bone loss. Case-control
studies have shown an approximately 60 percent reduction
in hip and wrist fractures in women whose estrogen replacement
was begun within a few years of menopause. Studies also
suggest that estrogen reduces the rate of vertebral fractures.
Even when started as late as 6 years after menopause,
estrogen prevents further loss of bone mass for as long
as the treatment is continued. The results of a two-year,
randomized, placebo-controlled, double-blind, dose-ranging
study have shown that treatment with 0.5 mg estradiol
daily for 23 days (of a 28 day cycle) prevents vertebral
bone mass loss in postmenopausal women. When estrogen
therapy is discontinued, bone mass declines at a rate
comparable to the immediate postmenopausal period. There
is no evidence that estrogen replacement therapy restores
bone mass to premenopausal levels.
At skeletal maturity there are sex and race differences
in both the total amount of bone present and its density,
in favor of men and blacks. Thus, women are at higher
risk than men because they start with less bone mass and,
for several years following natural or induced menopause,
the rate of bone mass decline is accelerated. White and
Asian women are at higher risk than black women.
Early menopause is one of the strongest predictors for
the development of osteoporosis. In addition, other factors
affecting the skeleton which are associated with osteoporosis
include genetic factors (small build, family history),
and endocrine factors (nulliparity, thyrotoxicosis, hyperparathyroidism,
Cushing's syndrome, hyperprolactinemia, Type I diabetes),
lifestyle (cigarette smoking, alcohol abuse, sedentary
exercise habits) and nutrition (below average body weight,
dietary calcium intake).
The mainstays of prevention and management of osteoporosis
are estrogen, an adequate lifetime calcium intake, and
exercise. Postmenopausal women absorb dietary calcium
less efficiently than premenopausal women and require
an average of 1500 mg/day of elemental calcium to remain
in neutral calcium balance. By comparison, premenopausal
women require about 1000 mg/day and the average calcium
intake in the USA is 400-600 mg/day. Therefore, when not
contraindicated, calcium supplementation may be helpful.
Weight-bearing exercise and nutrition may be important
adjuncts to the prevention and management of osteoporosis.
Immobilization and prolonged bed rest produce rapid bone
loss, while weight-bearing exercise has been shown both
to reduce bone loss and to increase bone mass. The optimal
type and amount of physical activity that would prevent
osteoporosis have not been established, however in two
studies, an hour of walking and running exercise twice
or three times weekly significantly increased lumbar spine
bone mass.
DOSAGE AND ADMINISTRATION
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: Attempts to discontinue or taper
medication should be made at 3-month to 6-month intervals.
The usual initial dosage range is 1 to 2 mg daily of
estradiol adjusted as necessary to control presenting
symptoms. The minimal effective dose for maintenance therapy
should be determined by titration. Administration should
be cyclic (e.g., 3 weeks on and 1 week off).
For treatment of female hypoestrogenism due to hypogonadism,
castration, or primary ovarian failure: Treatment is usually
initiated with a dose of 1 to 2 mg daily of estradiol,
adjusted as necessary to control presenting symptoms;
the minimal effective dose for maintenance therapy should
be determined by titration.
For treatment of breast cancer, for palliation only,
in appropriately selected women and men with metastatic
disease: Suggested dosage is 10 mg three times daily for
a period of at least three months.
For treatment of advanced androgen-dependent carcinoma
of the prostate, for palliation only: Suggested dosage
is 1 to 2 mg three times daily. The effectiveness of therapy
can be judged by phosphatase determinations as well as
by symptomatic improvement of the patient.
For the prevention of osteoporosis:
Therapy with estradiol tablets to prevent postmenopausal
bone loss should be initiated as soon as possible after
menopause. A daily dosage of 0.5 mg should be administered
cyclically (i.e., 23 days on and 5 days off). The dosage
may be adjusted if necessary to control concurrent menopausal
symptoms. Discontinuation of estrogen replacement therapy
may re-establish the natural rate of bone loss.
HOW SUPPLIED
Estrace 0.5 mg: Round, white scored
tablets imprinted with 021 and MJ on one side.
Estrace 1 mg: Round, lavender scored
tablets imprinted with 755 and MJ on one side.
Estrace 2 mg: Round, turquoise scored
tablets imprinted with 756 and MJ on one side.
Storage: Store at controlled room temperature
15-30°C (59-86°F). Dispense in a tight, light-resistant
container using a child-resistant closure.
REFERENCES
1. Murad, F., Kuret, J. Estrogens and progestins.
In: The Pharmacological basis of Therapeutics.
Goodman L.S., Gilman, A., Rall, T., Nies, A.S. Eds. Pergamon
Press, New York 1990; pg 1384-93.
2. Barnes, R.B., Lobo, R.A. Pharmacology of estrogens.
In: menopause: Physiology and Pharmacology. Mishell,
D.R. Eds. Yearbook Medical Publishers, Inc., Chicago 1987;
pg 301-15.
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