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 conditions.
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 woman.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.
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.Women 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 estrogens.
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.