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| Drug Name: | Estradiol |
| Manufacturer: | Mylan Pharmaceuticals Inc. |
| Other Info: | Mylan Pharmaceuticals Inc.Morgantown, WV 26505REV FEBRUARY 1999PL:ESTRT:R1 |
| Clinical Trials: | |
Estradiol Tablets, USP 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 show 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 WARNINGS).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 to 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.Estrogens should not be used in individuals with any of the following conditions:1.Known or suspected pregnancy (see BOXED WARNINGS).
Estrogens may cause fetal harm when administered to a pregnant woman.2.Undiagnosed abnormal genital bleeding.3.Known or suspected cancer of the breast except in appropriately selected patients being treated for metastatic disease.4.Known or suspected estrogen-dependent neoplasia.5.Active thrombophlebitis or thromboembolic disorders.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 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 (see PRECAUTIONS).
NIH - Clinical Trials