Estradiol patch equivalent

Use continuous oestrogen and cyclic progestogen combinations at peri-menopause or if less than 12 months amenorrhoea. Only use these if patient has had a hysterectomy or in combination with a progestogen or Mirena if intact uterus. Suggested alternative doses for use with the oestrogen preparations above where fixed dose therapy is not suitable. Low dose progestogen-only contraceptive pills Microlut 30mcg levonorgestrel , and Noriday mcg norethisterone are used by some clinicians in various doses but there is limited data for dosages of these pills required for endometrial protection.

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In the same substudy, invasive breast cancers were larger, were more likely to be node positive, and were diagnosed at a more advanced stage in the CE 0. 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 6 [see Clinical Studies Consistent with the WHI clinical trial, observational studies have also reported an increased risk of breast cancer with estrogen plus progestin therapy, and a smaller increase in the risk for breast cancer with estrogen-alone therapy, after several years of use.

The risk increased with duration of use and appeared to return to baseline over about 5 years after stopping treatment only the observational studies have substantial data on risk after stopping. Observational studies also suggest that the risk of breast cancer was greater, and became apparent earlier, with estrogen plus progestin therapy as compared to estrogen-alone therapy.

These studies have not generally found significant variation in the risk of breast cancer among different estrogen plus progestin combinations, doses, or routes of administration.

The use of estrogen-alone and 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.

After an average follow-up of 5. A meta-analysis of 17 prospective and 35 retrospective epidemiology studies found that women who used hormonal therapy for menopausal symptoms had an increased risk for ovarian cancer. The primary analysis, using case-control comparisons, included 12, cancer cases from the 17 prospective studies. The relative risks associated with current use of hormonal therapy was 1. The relative risk associated with combined current and recent use discontinued use within 5 years before cancer diagnosis was 1.

The exact duration of hormone therapy use associated with an increased risk of ovarian cancer, however, is unknown.

The relative risk of probable dementia for CE-alone versus placebo was 1. The absolute risk of probable dementia for CE-alone versus placebo was 37 versus 25 cases per 10, women-years 8 [see Use in Specific Populations 8. After an average follow-up of 4 years, 40 women in the CE plus MPA group and 21 women in the placebo group were diagnosed with probable dementia.

The absolute risk of probable dementia for CE plus MPA versus placebo was 45 versus 22 cases per 10, women-years 8 [see Use in Specific Populations 8. When data from the two populations in the WHIMS estrogen-alone and estrogen plus progestin ancillary studies were pooled as planned in the WHIMS protocol, the reported overall relative risk for probable dementia was 1.

Since both ancillary studies were conducted in women aged 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women 8 [see Use in Specific Populations 8. A 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported.

Estrogen administration may lead to severe hypercalcemia in women with breast cancer and bone metastases. Discontinue estrogens, including estradiol transdermal system twice-weekly , if hypercalcemia occurs, and take appropriate measures to reduce the serum calcium level. Retinal vascular thrombosis has been reported in women receiving estrogens.

Discontinue estradiol transdermal twice-weekly pending examination if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine. Permanently discontinue estrogens, including estradiol transdermal system twice-weekly , if examination reveals papilledema or retinal vascular lesions.

Studies of the addition of a progestogen 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 progestogens with estrogens compared to estrogen-alone regimens.

These include an increased risk of breast cancer. 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. In women with preexisting hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis.

Discontinue estradiol transdermal twice-weekly if pancreatitis occurs. Estrogens may be poorly metabolized in women with hepatic impairment. Exercise caution in any woman with a history of cholestatic jaundice associated with past estrogen use or with pregnancy.

In the case of recurrence of cholestatic jaundice, discontinue estradiol transdermal system twice-weekly. Estrogen administration leads to increased thyroid-binding globulin TBG levels. Women with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T 4 and T 3 serum concentrations in the normal range.

Women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy. Monitor thyroid function in these women during treatment with estradiol transdermal system twice-weekly to maintain their free thyroid hormone levels in an acceptable range.

Estrogens may cause some degree of fluid retention. Monitor any woman with a condition s that might predispose her to fluid retention, such as cardiac or renal impairment. Discontinue estrogen-alone therapy, including estradiol transdermal system twice-weekly , with evidence of medically concerning fluid retention. Estrogen-induced hypocalcemia may occur in women with hypoparathyroidism.

Consider whether the benefits of estrogen therapy, including estradiol transdermal system twice-weekly , outweigh the risks in such women. A few cases of malignant transformation of residual endometrial implants have been reported in women treated post-hysterectomy with estrogen-alone therapy. Consider the addition of progestogen therapy for women known to have residual endometriosis post-hysterectomy.

Involvement of skin hives, pruritus, swollen lips-tongue-face and either respiratory tract respiratory compromise or gastrointestinal tract abdominal pain, vomiting are noted.

Angioedema involving the tongue, glottis, or larynx, may result in airway obstruction. Do not give estradiol transdermal system twice-weekly to any woman who develops angioedema during treatment with estradiol transdermal system twice-weekly. Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema.

Consider whether the benefits of estrogen therapy outweigh the risks in such women. Estrogen therapy, including estradiol transdermal system twice-weekly , may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraines, porphyria, systemic lupus erythematosus, and hepatic hemangiomas. Serum follicle-stimulating hormone FSH and estradiol levels have not been shown to be useful in the management of moderate to severe vasomotor symptoms and moderate to severe symptoms of vulvar and vaginal atrophy.

Laboratory parameters may be useful in guiding dosage for the treatment of hypoestrogenism due to hypogonadism, castration and primary ovarian failure. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

There were no clinical trials conducted with the revised formulation of estradiol transdermal system twice-weekly. The revised formulation of estradiol transdermal system twice-weekly is bioequivalent to the original formulation of estradiol transdermal system twice-weekly. The following adverse reactions have been reported with the original formulation of estradiol transdermal system twice-weekly therapy:.

The following additional adverse reactions have been identified during post-approval use of estradiol transdermal system twice-weekly. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Genitourinary System: Vaginal hemorrhage and abnormal withdrawal bleeding or flow, breakthrough bleeding, spotting, uterine leiomyomata, vaginitis, vaginal discharge, ovarian cancer, endometrial hyperplasia, dysmenorrhea. Breast: Enlargement, pain, nipple discharge, fibrocystic breast changes, breast cancer.

Cardiovascular: Deep venous thrombosis, pulmonary embolism, thrombophlebitis. Gastrointestinal: Nausea, vomiting, abdominal cramps, bloating, cholelithiasis, liver function tests abnormal, diarrhea. Skin: Application site reactions include localized bleeding, bruising, burning, discomfort, dryness, eczema, edema, erythema, erythema multiforme, erythema nodosum, inflammation, irritation, pain, papules and vesicles.

Other skin reactions include paresthesia, skin discoloration, skin pigmentation, urticaria, swelling, loss of scalp hair, hirsutism, pruritus, and rash. Central Nervous System: Migraine, dizziness, chorea, nervousness, affect liability, irritability. Miscellaneous: Decrease in weight, reduced carbohydrate tolerance, edema, arthralgias, leg cramps, changes in libido, purpura, hypersensitivity, anaphylactic reaction, anaphylactoid reaction, angioedema.

Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and grapefruit juice may increase plasma concentrations of estrogens and may result in adverse reactions. Estradiol transdermal system twice-weekly is not indicated for use in pregnancy.

There are no data with the use of estradiol transdermal system twice-weekly in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects including cardiac anomalies and limb-reduction defects following exposure to combined hormonal contraceptives estrogen and progestins before conception or during early pregnancy.

In the U. Estrogens are present in human milk and can reduce milk production in breast-feeding women. This reduction can occur at any time but is less likely to occur once breast-feeding is well-established. Estradiol transdermal system twice-weekly is not indicated for use in pediatric patients. Clinical studies have not been conducted in the pediatric population. If estrogen is administered to patients whose bone growth is not complete, periodic monitoring of bone maturation and effects on epiphyseal centers is recommended during estrogen administration.

There have not been sufficient numbers of geriatric women involved in clinical studies utilizing estradiol transdermal system twice-weekly to determine whether those over 65 years of age differ from younger subjects in their response to estradiol transdermal system twice-weekly. In the WHIMS ancillary studies of postmenopausal women 65 to 79 years of age, there was an increased risk of developing probable dementia in women receiving estrogen-alone or estrogen plus progestin when compared to placebo [see Warnings and Precautions 5.

Since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women 8 [see Warnings and Precautions 5.

Overdosage of estrogen may cause nausea, vomiting, breast tenderness, abdominal pain, drowsiness and fatigue, and withdrawal bleeding may occur in women. Treatment of overdose consists of discontinuation of estradiol transdermal system twice-weekly therapy with institution of appropriate symptomatic care. Estradiol Transdermal System, USP twice-weekly contains estradiol hemihydrate in a multipolymeric adhesive. The system is designed to release estradiol continuously upon application to intact skin.

Five dosage strengths of estradiol transdermal system twice-weekly are available to provide nominal in vivo delivery rates of 0.

Each corresponding system has an active surface area of 2. The composition of the systems per unit area is identical. The molecular weight is Estradiol transdermal system twice-weekly is comprised of 3 layers. Proceeding from the visible surface toward the surface attached to the skin, these layers are 1 a translucent polyolefin film printed with brown ink, 2 an adhesive formulation containing estradiol, silicone adhesive, acrylic adhesive, dipropylene glycol, povidone and oleyl alcohol, and 3 an oversized slit polyester release liner which is attached to the adhesive surface and must be removed before the system can be used.

The active component of the system is estradiol. The remaining components of the system are pharmacologically inactive. 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 secretes 70 to mcg 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 in 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. Note that there is high interindividual variability i. As an example, some people may get relatively low estradiol levels with the oral route and others may get relatively low levels with the transdermal route. Conversely, some people may get relatively high levels with the transdermal route or with injections.

For data showing the substantial variability even with injections, see Aly W. Due to the variability in estradiol levels between individuals, the appropriate doses will often not be the same for different people. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA.

The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. These medications are called selective estrogen receptor modulators, or SERMs. Do not use estradiol without first talking to your doctor if you have a circulation, bleeding, or blood-clotting disorder; undiagnosed, abnormal vaginal bleeding; or any type of breast, uterine, or hormone-dependent cancer.

Using estradiol may be dangerous in some cases if you have any of the conditions listed above. You may not be able to use estradiol, or you may require a dosage adjustment or special monitoring during treatment, if you have any of the conditions listed above. Long-term treatment with estradiol may increase the risk of a stroke.