Estradiol (Transdermal Patch)
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 BRAND NAMES
 MECHANISM OF ACTION
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. At menopause the ovaries cease to secrete estradiol and most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone by peripheral tissues.
The rapid decline in endogenous estrogen production that occurs during menopause is associated with symptoms such as sweating, hot flushes and sleep disturbance. A couple of years after menopause, increasing numbers of women also report symptoms of urogenital estrogen deficiency such as vaginal dryness, genital pruritus, dyspareunia, dysuria and urinary urgency. Low estrogen levels is associated also with significant bone loss and increased risk for fragility fracture.
The estradiol from the Transdermal Patch replaces the missing or decreasing endogenous estrogen production.
- Treatment of moderate to severe vasomotor symptoms associated with the menopause.
- Treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with the menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.
- Treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure.
- Prevention of postmenopausal osteoporosis. When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and non-estrogen medications should be carefully considered.
The mainstays for decreasing the risk of postmenopausal osteoporosis are weight bearing exercise, adequate calcium and vitamin D intake, and, when indicated, pharmacologic therapy. Postmenopausal women require an average of 1500 mg/day of elemental calcium to remain in neutral calcium balance. Therefore, when not contraindicated, calcium supplementation may be helpful for women with suboptimal dietary intake. Vitamin D supplementation of 400-800 IU/day may also be required to ensure adequate daily intake in postmenopausal women.
Check the patient information leaflet
When estrogen is prescribed for a postmenopausal woman with a uterus, 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 limited to 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.
- Undiagnosed abnormal genital bleeding.
- Known, suspected, or history of cancer of the breast.
- Known or suspected estrogen-dependent neoplasia.
- Active deep vein thrombosis, pulmonary embolism or a history of these conditions.
- Active or recent (e.g., within the past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction).
- Liver dysfunction or disease.
- Known or suspected pregnancy.
 WARNINGS AND PRECAUTIONS
- Cardiovascular Disorders: Estrogen therapies have 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). If a thrombotic event occurs, therapy 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.
- Endometrial cancer: The use of unopposed estrogens (the supplementation of endogenous estrogens without a progestogen) 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.
- Breast cancer: The use of estrogens and progestins by postmenopausal women has been reported to increase the risk of breast cancer
- Gallbladder Disease: A 2 to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported.
- 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 should be taken to reduce the serum calcium level.
- Visual Abnormalities: Retinal vascular thrombosis has been reported in patients receiving estrogens. Discontinue medication pending examination if there is 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 discontinued.
- Hypertriglyceridemia: In patients with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis and other complications.
- 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.
- 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 T4 and T3 serum 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.
- Fluid retention: Estrogens may cause some degree of fluid retention
- Exacerbation of endometriosis: Endometriosis may be exacerbated with administration of estrogens
- Exacerbation of other conditions: Estrogens may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions.
- Inducers of CYP3A4 such as St. John’s Wort preparations (Hypericum perforatum), phenobarbital, phenytoin, carbamazepine, rifampin and dexamethasone 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 cimetidine, erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects.
 PREGNANCY AND LACTATION
 SIDE EFFECTS
Common side effects include:
- Breast pain
- Irregular vaginal bleeding or spotting
- Stomach/abdominal cramps, bloating
- Nausea and vomiting
- Hair loss
Other side effects include:
- High blood pressure
- Liver problems
- High blood sugar
- Fluid retention
- Enlargement of benign tumors of the uterus (“fibroids”)
- Vaginal yeast infection
Less common but serious side effects include:
- Breast cancer
- Cancer of the uterus
- Heart attack
- Blood clots
- Gallbladder disease
- Ovarian cancer