estrogens, esterified

Action

Bind to nuclear receptors in responsive tissues (such as female genital organs, breasts, and pituitary gland), enhancing DNA, RNA, and protein synthesis. In androgen-dependent prostate cancer, compete for androgen receptor sites, inhibiting androgen activity. Also decrease pituitary release of folliclestimulating hormone and luteinizing hormone.

Availability

Tablets: 0.3 mg, 0.625 mg, 1.25 mg, 2.5 mg

Indications and dosages

➣ Moderate to severe vasomotor symptoms or atrophic vaginitis

Adults: 0.3 to 1.25 mg P.O. daily, adjusted to lowest effective dosage; usually given in cycles of 3 weeks on,1 week off

➣ Female hypogonadism

Adults: 2.5 to 7.5 mg P.O. daily in divided doses for 20 days, followed by 10-day rest period. If no bleeding occurs, repeat same dosing schedule. If bleeding occurs before end of rest period, start 20-day estrogen-progestin cycle, with progestin P.O. given during last 5 days of estrogen therapy.

➣ Inoperable prostate cancer

Adults: 1.25 to 2.5 mg P.O. t.i.d.

➣ Selected breast cancers (inoperable, progressing)

Adults: 10 mg P.O. t.i.d. for at least 3 months

➣ Prevention of osteoporosis

Adults: Initially, 0.3 mg P.O. daily, increased as needed to a maximum of 1.25 mg/day

Contraindications

• Hypersensitivity to drug or its components

• Thromboembolic disease (current or previous)

• Undiagnosed vaginal bleeding

• Breast and reproductive cancers (except metastatic disease)

• Estrogen-dependent neoplasms

• Pregnancy

Precautions

Use cautiously in:

• cardiovascular disease, severe hepatic or renal disease, asthma, bone disease, migraines, seizures, breast nodules, fibrocystic breasts

• family history of breast or genital tract cancer

• breastfeeding patients.

Administration

• Administer with food or fluids.

• Give cyclically as prescribed, except when used palliatively for cancer treatment.

Adverse reactions

CNS: headache, dizziness, lethargy, depression, asthenia, paresthesia, syncope, increased risk of cerebrovascular accident (CVA), seizures

CV: hypertension, chest pain, myocardial infarction (MI), thromboembolism

EENT: contact lens intolerance, worsening of myopia or astigmatism, otitis media, sinusitis, rhinitis, pharyngitis

GI: nausea, vomiting, diarrhea, dyspepsia, flatulence, gastritis, gastroenteritis, enlarged abdomen, hemorrhoids, colitis, gallbladder disease, anorexia, pancreatitis

GU: urinary incontinence, dysuria, amenorrhea, dysmenorrhea, endometrial hyperplasia, urinary tract infection, leukorrhea, vaginal discomfort or pain, vaginal hemorrhage, genital eruptions, gynecomastia, breast tenderness, breast enlargement or secretion, reduced libido, erectile dysfunction, testicular atrophy, increased risk of breast cancer, endometrial cancer, hemolytic uremic syndrome

Hepatic: cholestatic jaundice, hepatic adenoma

Metabolic: hyperglycemia, hypercalcemia, sodium and fluid retention, reduced carbohydrate tolerance

Musculoskeletal: leg cramps, back pain, skeletal pain

Respiratory: upper respiratory tract infection, bronchitis, pulmonary embolism

Skin: acne, increased pigmentation, urticaria, pruritus, erythema nodosum, hemorrhagic eruption, alopecia, hirsutism

Other: increased appetite, weight changes, edema, flulike symptoms, hypersensitivity reactions

Interactions

Drug-drug. Corticosteroids: enhanced corticosteroid effects

CYP450 inducers (such as barbiturates, rifampin): decreased estrogen efficacy

Hypoglycemics, warfarin: altered requirement for these drugs

Phenytoin: loss of seizure control

Tamoxifen: interference with tamoxifen efficacy

Tricyclic antidepressants: reduced antidepressant effect

Drug-diagnostic tests. Antithrombin III, folate, low-density lipoproteins, pyridoxine, total cholesterol, urine pregnanediol: decreased values

Cortisol; factors VII, VIII, IX, and X; glucose; high-density lipoproteins; phospholipids; prolactin; prothrombin; sodium; triglycerides: increased values

Metyrapone test: false decrease

Thyroid function tests: false interpretation

Drug-food. Caffeine: increased caffeine blood level

Drug-herbs. Black cohosh: increased risk of adverse reactions

Red clover: interference with estrogen therapy

Saw palmetto: antiestrogenic effects St. John's wort: decreased drug blood level and effects

Drug-behaviors. Smoking: increased risk of adverse cardiovascular reactions

Patient monitoring

• Monitor fluid intake and output, and weigh patient daily.

• Evaluate patient for breast tenderness and swelling. As needed, administer analgesics and apply cool compresses.

See Know that drug increases risk of thromboembolism, CVA, and MI.

• Monitor liver function test results, and assess abdomen for enlarged liver.

• Check serum phosphatase level in patients with prostate cancer, and adjust dosage as appropriate.

• Monitor calcium, glucose, and folic acid levels.

Patient teaching

See Teach patient to recognize and immediately report signs and symptoms of thromboembolism.

See Caution patient not to take drug if she is or plans to become pregnant.

• Teach patient how to perform breast self-examination. Emphasize importance of monthly checks.

• Tell patient to report breakthrough vaginal bleeding.

• Mention that drug may cause contact lens intolerance. Advise patient to report vision changes.

• Inform male patient that drug may cause gynecomastia.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, herbs, and behaviors mentioned above.