conjugated estrogens (Rx)

>10%

Abdominal pain (15-17%)

Back pain (13-14%)

Breast enlargement

Breast tenderness (7-12%)

Headache (26-32%)

Arthralgia (7-14%)

Pharyngitis (10-12%)

Sinusitis (6-11%)

Diarrhea (6-7%)

1-10%

Depression (5-8%)

Dizziness (4-6%)

Nervousness (2-5%)

Flatulence (6-7%)

Vaginitis (5-7%)

Leukorrhea (4-7%)

Leg cramps (3-7%)

Increased cough (4-7%)

Pruritus (4-5%)

Frequency Not Defined

Amenorrhea

Breakthrough bleeding

Corneal curvation change

Melasma

Spotting

Vaginal moniliasis

Weight changes

Contraindications

Known anaphylactic reaction or angioedema

Known protein C, protein S, or antithrombin deficiency; other known thrombophilic disorders

Active or history of breast cancer

Arterial thromboembolic disease (stroke, MI), thrombophlebitis, DVT/PE, thrombogenic valvular disease

Liver disease, liver tumors

Uncontrolled hypertension, diabetes mellitus with vascular involvement, jaundice with previous oral contraceptive use

Estrogen-dependent neoplasia

Undiagnosed abnormal vaginal bleeding

Cautions

Use caution in diabetes mellitus, hyperlipidemias, hypertension, hypothyroidism, advanced age, hepatic or renal impairment, uterine leiomyomata, porphyria, patients with defects of lipoprotein metabolism, hypertriglyceridemia, ovarian cancer, systemic lupus erhythematosus, exacerbation of endometriosis or other conditions, smoking, diseases exacerbated by fluid retention

Manage appropriately 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)

In patients with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis and other complications

Estrogens may be poorly metabolized in patients with impaired liver function; exercise caution in patients with a history of cholestatic jaundice associated with past estrogen use or with pregnancy; in the case of recurrence, discontinue medication

Patients dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of thyroid replacement therapy; these patients should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range

A 2 to 4-fold increase in risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens reported

Retinal vascular thrombosis 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

There are, possible risks that may be associated with use of progestins with estrogens compared to estrogen-alone regimens, including a possible increased risk of breast cancer, adverse effects on lipoprotein metabolism (e.g., lowering HDL, raising LDL), and impairment of glucose tolerance

Discontinue if any of the following develop: Jaundice, signs of venous thromboembolism, visual problems (may cause contact lens intolerance), massive blood pressure increase, major surgery or prolonged immobilization occurring in 4 weeks, new migraine, depression

Women with protein C or S deficiency (inherited thrombophilia), may have increased risk of venous thromboembolism

Do not use with conditions that predispose to hyperkalemia

Conditions exacerbated by fluid retention (asthma, epilepsy, migraines, cardiac or renal dysfunction)

Risk of hypercalcemia in patients with breast cancer and bone metastases

Increased risk of ovarian and endometrial cancer reported in women who used hormonal therapy for menopausal symptoms

Long-term postmenopausal estrogen treatment has been associated with increased risk of breast cancer, MI, stroke, DVT/PE, and dementia

Patients on warfarin or other oral anticoagulants: Estrogens increase thromboembolic risk; increase in anticoagulant dosage may be warranted

Discontinue therapy if pancreatitis occurs; estrogen compounds generally associated with increased triglyceride levels

Cases of anaphylaxis and angioedema have been reported; exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema

Use caution in individuals with severe hypocalcemia

Pregnancy category: X

Lactation: Use controversial; estrogens are excreted into breast milk in small quantities; use with caution

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Replaces endogenous estrogen; important for development and maintenance of female reproductive system and secondary sexual characteristics

Antiandrogenic effect provides benefit in prostate cancer

Absorption

Bioavailability: Readily absorbed from gastrointestinal (GI) tract

Onset: 2-4 weeks (PO-menopause)

Peak plasma time: 7 hr (PO)

Distribution

Protein bound: 80%

Metabolism

Metabolized in liver to inactive sulfates and glucuronides

Metabolites: Estradiol, estrone, estriol

Elimination

Excretion: Mainly in urine as conjugates with small amount of unchanged drug; most estrogens are also excreted in bile and undergo enterohepatic recycling

IV Incompatibilities

Additive, syringe, Y-site: Ascorbic acid, acidic solutions, protein hydrolysate

IV Compatibilities

Solution: D5W, NS, invert sugar solutions

Y-site: Heparin/hydrocortisone, potassium chloride, vitamins B and C

IV Preparation

Reconstitute with 5 mL of diluent provided

First withdraw air from vial, then add diluent slowly and aseptically with gentle agitation

Stable at 2-8°C for 60 days

Do not use if agent darkens or precipitates

IV/IM Administration

IM: Acceptable

IV: Administer slowly to avoid flushing reaction

Infusion not recommended; injection into running infusion can be performed

Storage

Refrigerate reconstituted injection

Intact vials are stable for 24 months at room temperature