Adult Dosing

Moderate to severe menopausal vasomotor symptoms

• Recommended dose range: 1-5 mg IM q3-4 wks

Hypogonadal hypoestrogenism

• 1.5-2 mg IM every month

• In women with an intact uterus, add progestin for at least 10-14 days of a cycle of estrogen administration to reduce the risk of endometrial cancer
• Use the lowest effective dose for the shortest duration
• Reevaluate periodically as clinically appropriate to determine if treatment is still necessary
• Attempts should be made to discontinue or taper medication at 3- to 6-month intervals

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Treatment of moderate to severe vasomotor symptoms associated with the menopause
• Indicated for treatment of hypoestrogenism due to hypogonadism

• Hypersensitivity to any of the ingredients of the product
• Undiagnosed abnormal genital bleeding
• Known, suspected, or history of breast cancer
• Active or history of deep vein thrombosis
• Active or history of pulmonary embolism
• Known or suspected pregnancy
• Known or suspected estrogen-dependent neoplasia
• Active thromboembolism
• Arterial thromboembolic disease within the past 12 months (such as stroke and MI)
• Known liver dysfunction or disease
• Thrombophilic disorder
• Protein C or S deficiency

• Estrogens increase the risk of endometrial cancer. Closely monitor all women taking estrogen therapy; use adequate diagnostic measures such as endometrial sampling to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. Currently there is no evidence that the use of natural estrogens result in a different endometrial risk profile than synthetic estrogens at equivalent estrogen doses
• Do not use estrogens with or without progestins for the prevention of cardiovascular disease. As per the study conducted by the Women’s Health Initiative (WHI), oral conjugated estrogens (CE) 0.625 mg combined with medroxyprogesterone acetate (MPA) 2.5 mg increase the risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli and deep vein thrombosis in postmenopausal women (50-79 years of age) during 5 years of treatment, relative to placebo
• The Women's Health Initiative Memory Study (WHIMS) reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with oral CE plus MPA, relative to placebo. It is not known whether this finding applies to younger postmenopausal women or to women taking estrogen alone therapy
• In the absence of comparable data, these risks should be assumed to be similar for other doses of estrogen/progestin combos and other dosage forms of estrogens and progestins. Use the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman

Renal Dose Adjustment

• Renal impairment: Dose adjustments not defined, caution advised

Hepatic Dose Adjustment

• Hepatic impairment: Contraindicated

• Estrogen-alone and estrogen plus progestin therapy may cause an increased risk of cardiovascular events such as DVT, pulmonary embolism, stroke, and myocardial infarction; discontinue the drug immediately if any of these events occur or be suspected [US Black Box warning]
• Increased risk of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis has been reported in postmenopausal women (50-79 yrs of age) during five years of treatment with oral CE (0.625 mg) combined with MPA (2.5 mg) relative to placebo [US Black Box Warning]
• Risk factors for arterial vascular disease and/or venous thromboembolism should be managed appropriately; discontinue estrogen therapy at least 4-6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization
• Use of unopposed estrogens in a woman with intact uterus may increase the risk of endometrial cancer [US Black Box warning]
• Estrogen plus progestin therapy in postmenopausal women may increase the risk of breast cancer. Perform routine breast examinations; schedule mammograms based on patient age, risk factors, and prior mammogram results
• Estrogen-alone and estrogen plus progestin therapy may increase the risk of dementia in postmenopausal women 65 years of age and older [US Black Box warning]
• A 2- to 4-fold increase in the risk of gallbladder disease requiring surgery has been reported in postmenopausal women receiving estrogen therapy
• Estrogen therapy may cause severe hypercalcemia in women with breast cancer and bone metastases. Discontinue therapy if hypercalcemia occurs and initiate appropriate measures to reduce the serum calcium level
• Retinal vascular thrombosis may occur in women receiving estrogens. Discontinue therapy pending examination if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia or migraine. Permanently discontinue therapy if examination reveals papilledema or retinal vascular lesions
• Use of progestin with estrogen in a continuous regimen has been reported to lower the incidence of endometrial hyperplasia than would be induced by estrogen-alone therapy. However, there is a possible increased risk of breast cancer associated with the use of progestins with estrogens compared to estrogen-alone regimens
• Estrogen use may cause substantial increases in blood pressure; monitor BP at regular intervals during therapy
• Estrogen therapy may be associated with elevations of plasma triglycerides in patients with preexisting hypertriglyceridemia, leading to pancreatitis and other complications
• Estrogens may be poorly metabolized in women with hepatic impairment. Use cautiously in women with a history of cholestatic jaundice associated with past estrogen use or with pregnancy; discontinue the drug in case of recurrence
• Estrogen administration may cause increased thyroid-binding globulin (TBG) levels. Women on thyroid hormone replacement therapy also receiving estrogens may require increased doses of their thyroid replacement therapy. Monitor thyroid function regularly to maintain free thyroid hormone levels in an acceptable range
• Estrogens may cause fluid retention; use cautiously in patients with cardiac or renal dysfunction
• Use cautiously in women with hypoparathyroidism as estrogen-induced hypocalcemia may occur
• Use of estrogen-alone therapy for 10 or more years may increase the risk of ovarian cancer
• Incidences of malignant transformation of residual endometrial implants have been reported in women treated post-hysterectomy with estrogen-alone therapy; consider adding progestins to estrogen therapy in such patients
• Therapy may cause an exacerbation of asthma, diabetes mellitus, migraine, epilepsy, porphyria, hepatic hemangiomas and systemic lupus erythematosus; use with caution in women with these conditions

Cautions: Use cautiously in

• Renal impairment
• Cardiovascular diseases
• Cardiac disease risk
• Hypertension
• Smoking
• Hypothyroidism
• Surgery or prolonged immobilization
• Chorea
• Endometriosis
• Obesity
• Patients >65 yrs
• Tobacco use

Pregnancy Category:X

Breastfeeding: This drug has not been studied during breastfeeding. However, the similar drug, estradiol valerate, has been used to suppress lactation, usually in combination with testosterone. Generally, estradiol cypionate should be avoided in mothers wishing to breastfeed. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 26 Aug 2011). As per manufacturer's data, estrogens decrease the quantity and quality of the milk when administered to nursing mothers. Detectable amounts of estrogens have been found in breast milk; use cautiously in nursing mothers.

• CV: Deep and superficial venous thrombosis; pulmonary embolism, thrombophlebitis, myocardial infarction, stroke, increase in blood pressure, edema, hypertension
• CNS: Headache, migraine, dizziness, chorea exacerbation, irritability, seizure exacerbation, dementia
• PSYCHIATRY: Depression, nervousness, mood disturbances
• GI: Nausea, vomiting, abdominal cramps/bloating, cholestatic jaundice, increased incidence of gallbladder disease, pancreatitis, hepatic hemangioma enlargement, ischemic colitis
• GU: Changes in vaginal bleeding pattern, abnormal withdrawal bleeding/flow, breakthrough bleeding, spotting, dysmenorrhea, vaginitis, vaginal candidiasis, change in amount of cervical secretion, changes in cervical ectropion, ovarian cancer, endometrial hyperplasia, endometrial cancer, breast tenderness/enlargement/pain, nipple discharge, galactorrhea, fibrocystic breast changes, breast cancer, uterine fibroid enlargement
• HEMA: Aggravation of porphyria
• METABOLIC: Weight changes, hypocalcemia, severe hypercalcemia (metastatic breast CA), glucose intolerance
• DERM: Chloasma, melasma, SLE exacerbation, erythema multiforme, erythema nodosum, hemorrhagic eruption, loss of scalp hair, hirsutism, pruritus, rash, urticaria
• EENT: Retinal vascular thrombosis, intolerance to contact lenses, steepening of corneal curvature, vision changes
• RESP: Pulmonary embolism, exacerbation of asthma
• REPRODUCTIVE: Changes in libido
• MUSC: Arthalgia, leg cramps
• HYPERSENSITIVITY: Angioedema, anaphylactoid/anaphylactic reactions
• MISC: Fluid retention

• Estrogen; responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. By a negative feedback mechanism, circulating estrogens regulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH); also, act to reduce the elevated levels of these hormones seen in postmenopausal women
• Single intramuscular injection of estradiol cypionate is absorbed over several weeks
• Metabolized primarily in the liver; CYP450: 3A4 substrate. Also undergoes enterohepatic recirculation. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite
• Renally excreted as conjugates
• Half-life: Unknown

US Trade Name(s)

• Only generic available

US Availability

estradiol cypionate (generic)

• INJ: 5 mg/mL (5 mL vial)

Depo-Estradiol (generic)

• INJ: 5 mg/mL (5 mL vial)

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Endocrine/Metabolic

Sex Hormones

Estrogens

Obstetrics/Gynecology

Sex Hormones

Estrogens