esterified estrogens
Estratab, Menest

Available forms
Available by prescription only
Tablets: 0.3 mg, 0.625 mg, 1.25 mg, 2.5 mg

Indications and dosages
 Palliative treatment of advanced inoperable prostatic cancer. Adults: 1.25 to 2.5 mg P.O. daily to t.i.d.
 Breast cancer. Men and postmenopausal women: 10 mg P.O. t.i.d. for 3 or more months.
 Female hypogonadism. Adults: 2.5 mg to 7.5 mg P.O. daily in divided doses in cycles of 20 days on, 10 days off.
 Castration, primary ovarian failure. Adults: 2.5 mg P.O. daily to t.i.d. in cycles of 3 weeks on, 1 week off. Adjust dosage as needed according to severity of symptoms and patient response.
 Vasomotor menopausal symptoms. Adults: 0.3 to 1.25 mg P.O. daily in cycles of 3 weeks on, 1 week off. Dosage may be increased to 2.5 or 3.75 mg P.O. daily, if needed.
 Atrophic vaginitis, atrophic urethritis. Adults: 0.3 to 1.25 mg P.O. daily in cycles of 3 weeks on, 1 week off.
 Osteoporosis prevention. Adults: 0.3 mg P.O. daily; increase to maximum dose of 1.25 mg/day if needed to control concurrent menopausal symptoms.

Pharmacodynamics
Estrogenic action: Esterified estrogen mimics the action of endogenous estrogen in treating female hypogonadism, menopausal symptoms, and atrophic vaginitis. It inhibits growth of hormone-sensitive tissue in advanced, inoperable prostatic cancer and in certain carefully selected cases of breast cancer in men and postmenopausal women.

Pharmacokinetics
Absorption: Well absorbed from the GI tract.
Distribution: About 50% to 80% is bound to plasma protein, particularly the estradiol-binding globulin. Distribution occurs throughout the body with highest levels appearing in fat.
Metabolism: Metabolized primarily in the liver, where estrogens are conjugated with sulfate and glucuronide. Large amounts of free estrogen are distributed into the bile, reabsorbed from the GI tract, and recirculated through the liver.
Excretion: Eliminated through the kidneys in the form of sulfate or glucuronide conjugates.

Contraindications and precautions
Contraindicated in patients with breast cancer (except metastatic disease), estrogen-dependent neoplasia, active thrombophlebitis or thromboembolic disorders, undiagnosed abnormal genital bleeding, hypersensitivity to drug, or history of thromboembolic disease, and in pregnant or breast-feeding women.
 Use cautiously in patients with history of hypertension, mental depression, liver impairment, or cardiac or renal dysfunction and in those with bone diseases, migraine, seizures, or diabetes mellitus.

Interactions
Drug-drug. Anticoagulants: Decreases anticoagulant effects. Monitor patient closely.
Corticosteroids: Enhances corticosteroid effects. Monitor patient’s fluid and electrolyte status and mental status.
Cyclosporine: Increases risk of toxicity. Monitor patient closely.
Dantrolene, other hepatotoxic drugs: Increases risk of hepatotoxicity. Monitor patient carefully.
Drugs that induce hepatic metabolism, such as carbamazepine, barbiturates, phenytoin, primidone, rifampin: Decreases estrogenic effects. Use together cautiously.
Insulin, oral antidiabetics: Increases blood glucose level. Adjust dosage as needed.
Phenytoin: Decreases seizure control. Monitor patient for loss of seizure control.
Tamoxifen: Decreases tamoxifen effectiveness. Monitor patient for drug effects.
Drug-food. Caffeine: Increases serum caffeine levels. Discourage caffeine use.
Drug-lifestyle. Smoking: Increases risk of adverse CV effects. Discourage smoking.

Adverse reactions
CNS: headache, dizziness, chorea, depression, seizures, CVA.
CV: thrombophlebitis; THROMBOEMBOLISM; hypertension; edema; pulmonary embolism, MI.
EENT: worsening of myopia or astigmatism, intolerance of contact lenses.
GI: nausea, vomiting, abdominal cramps, bloating, anorexia, increased appetite, weight changes, pancreatitis, gallbladder disease.
GU: breakthrough bleeding, altered menstrual flow, dysmenorrhea, amenorrhea, endometrial cancer, cervical erosion, altered cervical secretions, enlargement of uterine fibromas, vaginal candidiasis, testicular atrophy and impotence.
Hematologic: increased norepinephrine-induced platelet aggregability.
Hepatic: cholestatic jaundice, hepatic adenoma.
Skin: melasma, rash, hirsutism or hair loss, erythema nodosum, dermatitis.
Other: possible increased risk of breast cancer, breast changes (tenderness, enlargement, secretion), gynecomastia in men.

Effects on lab test results
• May increase levels of triglyceride, glucose, phospholipid, calcium, and clotting factors VII, VIII, IX, and X. May decrease serum folate, pyridoxine, and antithrombin III levels.
• May increase PT, INR, and norepinephrine-induced platelet aggregation.

Overdose and treatment
Serious toxicity after overdose of these drugs hasn’t been reported. Nausea may occur.
 Provide appropriate supportive care.

Special considerations
• Patient should have physical examination before therapy. Patients receiving long-term therapy should be examined yearly.
• Because of risk of thromboembolism, therapy should be discontinued at least 1 month before procedures that cause prolonged immobilization or raise the risk of thromboembolism, such as knee or hip surgery.
• Postmenopausal women who use estrogen replacement for longer than 5 years for menopausal symptoms may be at increased risk for endometrial cancer. This risk is reduced by using cyclic rather than continuous therapy and the lowest possible estrogen dosage. Adding progestins to the regimen decreases risk of endometrial hyperplasia; however, it isn’t known whether progestins affect risk of endometrial cancer.
• No evidence exists that estrogens increase the risk of breast cancer in postmenopausal women, but the relative risk of breast cancer has been shown to increase by 10% in women age 35 and older who are taking estrogen for menopausal symptoms.
• Notify pathologist about estrogen therapy when sending specimens to laboratory for evaluation.
• Monitor serum lipid levels, blood pressure, body weight, and hepatic function regularly.
Pregnant patients
• Drug is contraindicated during pregnancy.
Breast-feeding patients
• Esterified estrogens are contraindicated in breast-feeding women.

Patient education
• Tell patient to read package insert describing estrogen’s adverse effects; also give verbal explanation.
• Emphasize importance of regular physical examinations.
 ALERT Warn patient to immediately report abdominal pain; pain, numbness, or stiffness in legs or buttocks; pressure or pain in chest or shortness of breath; severe headaches; visual disturbances, such as blind spots, flashing lights, or blurriness; vaginal bleeding or discharge; breast lumps; swelling of hands or feet; yellow skin or sclera; dark urine; and light-colored stools.
• Tell diabetic patient to report elevated blood glucose level so that antidiabetic dosage can be adjusted.
• Explain to patient on cyclic therapy for postmenopausal symptoms that, although she may experience withdrawal bleeding during week off drug, fertility isn’t restored.
• Teach woman to perform routine breast self-examination.
• Advise woman of childbearing age to call immediately if she becomes pregnant.
• Teach patient methods to decrease risk of thromboembolism.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use