ESTRADIOL

(ess-tra-dye'ole)

Alora, Climara, Divigel, Esclim, Estrace, Estraderm, Estrasorb, EstroGel, Evamist, FemPatch, Menorest, Menostar, Vivelle, Vivelle DOT, Estring, Vagifem
ESTRADIOL ACETATE
Femring, Femtrace
ESTRADIOL CYPIONATE
Depo-Estradiol Cypionate, Estro-Cyp
ESTRADIOL VALERATE
Delestrogen, Femogex

Classifications: hormone; estrogen;
Therapeutic: estrogen replacement
Pregnancy Category: X

Availability

Estradiol: 0.025 mg, 0.0375 mg, 0.05 mg, 0.06 mg, 0.075 mg, 0.1 mg patch; 14 mcg/24 h transdermal patch; 0.5 mg, 1 mg, 2 mg tablets; 25 mcg vaginal tablets, 2 mg vaginal ring, 0.1 mg vaginal cream; 2.5 mg/g topical emulsion; 0.06%, 0.1% topical gel; 1.53 mg/actuation transdermal spray;

Cypionate: 5 mg/mL injection;

Valerate: 10 mg/mL, 20 mg/mL, 40 mg/mL injection;

Acetate: 0.45 mg, 0.9 mg, 1.8 mg tablets; 0.05 mg/d, 0.1 mg/d vaginal insert

Action

Natural or synthetic steroid hormone secreted principally by the ovarian follicles, and also by the adrenals, corpus luteum, placenta, and testes. Estrogen binds to a specific intracellular receptor, forming a complex that stimulates synthesis of proteins responsible for estrogenic effects. Promotes endometrial lining development, but long-time use leads to abnormal endometrial hyperplasia, and abnormal bleeding. Conversely, estrogen-stimulated endometrium suddenly deprived of estrogen may bleed within 48–72 h.

Therapeutic Effect

Estradiol (estrogens) effects simulate those produced by the endogenous hormone. May mask onset of climacteric.

Uses

Natural or surgical menopausal symptoms, kraurosis vulvae, atrophic vaginitis, primary ovarian failure, female hypogonadism, castration. Used adjunctively with diet, calcium, and physical therapy to prevent and treat postmenopausal osteoporosis; also for palliation in advanced prostatic carcinoma and inoperable metastatic breast cancer in women at least 5 y after menopause. Combined with progestins in many oral contraceptive formulations.

Contraindications

Known or suspected pregnancy (category X); estrogenic-dependent neoplasms, breast cancer (except in selected patients being treated for metastatic disease). History of thromboembolic disorders; active arterial thrombosis or thrombophlebitis; undiagnosed abnormal genital bleeding; uterine fibroids; endometriosis; history of cholestatic disease; hepatic disease; thyroid dysfunction; blood dyscrasias; hypercalcemia; lupus (SLE).

Cautious Use

Adolescents with incomplete bone growth; endometriosis; hypertension, cardiac insufficiency; diseases of calcium and phosphate metabolism (metabolic bone disease); cerebrovascular disease; mental depression; benign breast disease, family history of breast or genital tract neoplasm; diabetes mellitus; gallbladder disease; preexisting leiomyoma, abnormal mammogram, history of idiopathic jaundice of pregnancy; varicosities; asthma; epilepsy; migraine headaches; liver or kidney dysfunction; jaundice, acute intermittent porphyria, pyridoxine deficiency.

Route & Dosage

Menopause, Atrophic Vaginitis, Kraurosis Vulvae, Female Hypogonadism, Female Castration, Primary Ovarian Failure
Adult: PO 0.45–2 mg/d in a cyclic regimen Topical 2–4 g vaginal cream intravaginally once/d for 1–2 wk, then 1–2 g/d for 1–2 wk, then 1 g 1–3 times/wk; Transdermal patch Estraderm twice weekly; Climara, FemPatch, Menostar qwk in a cyclic regimen; Estrasorb Apply 1 packet to the left thigh and calf and 1 packet to the right thigh and calf once daily in the morning; EstroGel Apply 1.25 g (one-half applicatorful) to one arm every day (usually in the morning). IM Cypionate 1–5 mg once q3–4wk; Valerate 10–25 mg once q4wk; Acetate Insert 1 vaginal ring into the upper third of the vaginal vault. Keep in place continuously for 3 mo, then remove. Divigel Apply one packet to upper thigh daily (alternate legs). Evamist Apply one spray to inner forearm daily, dose may be increased to 2–3 sprays q.d.

Metastatic Breast Cancer
Adult: PO 10 mg t.i.d.

Prostatic Cancer
Adult: PO 1–2 mg t.i.d. IM Valerate 30 mg once q1–2wk

Postpartum Breast Engorgement
Adult: IM Valerate 10–25 mg at end of first stage of labor

Administration

Oral

Give with or immediately after solid food to reduce nausea.
Protect tablets from light and moisture in well-closed container. Protect from freezing, unless otherwise directed by manufacturer.

Intravaginal

Insert calibrated dosage applicator approximately 5 cm (2 in.) into vagina, directing it slightly back toward sacrum. Instill medication by pushing plunger. Patient should remain in recumbent position about 30 min to prevent losing the medication. Observe perineal area before each administration: if mucosa is red, swollen, or excoriated or if there is a change in vaginal discharge, report to physician.

Topical

Cleanse and dry selected skin area. Apply as directed under Route & Dosage.

Transdermal

Cleanse and dry selected skin area on trunk of body, preferably the abdomen. Avoid application to the breasts, to an irritated, abraded, oily area, or to the waistline. If system falls off, it may be reapplied, or if necessary, a new one can be applied. Return to original treatment schedule. Rotate application site with an interval of at least 1 wk between applications to a particular site.

Intramuscular

Give deep into a large muscle.

Store at 15°–30° C (59°–86° F); protect from light and freezing.

Adverse Effects (≥1%)

CNS: Headache, migraine, dizziness, mental depression, chorea, convulsions, increased risk of dementia. CV: Thromboembolic disorders, stroke, CAD, hypertension. Special Senses: Intolerance to contact lenses, worsening of myopia or astigmatism, scotomas. GI: Nausea, vomiting, anorexia, increased appetite, diarrhea, abdominal cramps or pain, constipation, bloating, colitis, acute pancreatitis, cholestatic jaundice, benign hepatoadenoma. Urogenital: Mastodynia, breast secretion, spotting, changes in menstrual flow, dysmenorrhea, amenorrhea, cervical erosion, altered cervical secretions, premenstrual-like syndrome, vaginal candidiasis, endometrial cystic hyperplasia, reactivation of endometriosis, increased size of preexisting fibromyomas, cystitis-like syndrome, hemolytic uremic syndrome, change in libido; in men: gynecomastia, testicular atrophy, feminization, impotence (reversible). Metabolic: Reduced carbohydrate tolerance, hyperglycemia, hypercalcemia, folic acid deficiency, fluid retention. Skin: Dermatitis, pruritus, seborrhea, oily skin, acne; photosensitivity, chloasma, loss of scalp hair, hirsutism. Body as a Whole: Pain and postinjection flare at injection site; sterile abscess; leg cramps, weight changes. Hematologic: Acute intermittent porphyria.

Diagnostic Test Interference

Estradiol reduces response of metyrapone test and excretion of pregnanediol. Increases: BSP retention, norepinephrine-induced platelet aggregability, hydrocortisone, PBI, T₄, sodium, thyroxine-binding globulin (TBG), prothrombin and factors VII, VIII, IX, and X; serum triglyceride, and phospholipid concentrations, renin substrate. Decreases: antithrombin III, pyridoxine and serum folate concentrations, serum cholesterol, values for the T₃ resin uptake test, glucose tolerance. May cause false-positive test for LE cells or antinuclear antibodies (ANA).

Interactions

Drug: barbiturates, phenytoin, rifampin decrease estrogen effect by increasing its metabolism; oral anticoagulants may decrease hypoprothrombinemic effects; interfere with effects of bromocriptine; may increase levels and toxicity of cyclosporine, tricyclic antidepressants, theophylline; decrease effectiveness of clofibrate.

Pharmacokinetics

Absorption: Rapid from GI tract; readily through skin and mucous membranes; slow from IM injections. Distribution: Throughout body tissues, especially in adipose tissue; crosses placenta. Metabolism: Primarily in liver. Elimination: Excreted in urine; excreted in breast milk.

Nursing Implications

Assessment & Drug Effects

Monitor adverse GI effects. Nausea, frequently at breakfast time, usually disappears after 1 or 2 wk of drug use.
Check BP on a regular basis in patients with cardiac or kidney dysfunction or hypertension; monitored carefully.
Note: Severe hypercalcemia (>15 mg/dL) may be caused by estradiol therapy in patients with breast cancer and bone metastasis.
Interrupt estrogen treatment at least 4 wk before surgery associated with a prolonged period of immobilization or vascular complications.

Patient & Family Education

Comply with established dosage schedule. Do not alter unless physician prescribes a change.
Read patient package insert (PPI) carefully.
Notify physician of intermittent breakthrough bleeding, spotting, bleeding, or unexplained and sudden pain.
Determine weight under standard conditions 1 or 2 times/wk; report sudden weight gain or other signs of fluid retention.
Notify physician of positive Homans' sign (calf pain upon flexing foot) and the following symptoms of thromboembolic disorders immediately: Tenderness, swelling, and redness in extremity; sudden, severe headache or chest pain; slurring of speech; change in vision; tenderness, pain, sudden shortness of breath.
Monitor urine or blood glucose & HbA_1C for glycemic control if diabetic.
Decrease caffeine intake, since estrogen depresses caffeine metabolism.
Learn self-examination of breasts and follow a monthly schedule.
Reduce or terminate long-term or high-dosage therapy with estrogens gradually.
Estrogen-induced feminization and impotence in male patients are reversible with termination of therapy.
Estrogen-primed or -stimulated endometrium may bleed 48–72 h after dose is discontinued. In cyclic therapy, estradiol is resumed on schedule before drug-induced vaginal bleeding stops.
Withdrawal bleeding may occur even after oophorectomy and after menopause.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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