estradiol

estradiol

(ess tra dye' ole)

estradiol

Oral:

Estrace, Gynodiol

Transdermal system:

Alora, Climara, Esclim, Estraderm, Menostar, Vivelle, Vivelle Dot

Topical vaginal cream:

Estrace

Vaginal ring:

Estring

Topical emulsion:

Estrasorb

estradiol cypionate

Injection in oil:

Depo-Estradiol

estradiol hemihydrate

Vaginal tablet:

Vagifem

estradiol valerate

Injection in oil:

Delestrogen

Pregnancy Category X

Drug classes

Hormone

Estrogen

Therapeutic actions

Estradiol is the most potent endogenous female sex hormone. Estrogens are important in the development of the female reproductive system and secondary sex characteristics; affect the release of pituitary gonadotropins; cause capillary dilatation, fluid retention, protein anabolism and thin cervical mucus; conserve calcium and phosphorus and encourage bone formation; inhibit ovulation and prevent postpartum breast discomfort. They are responsible for the proliferation of the endometrium; absence or decline of estrogen produces signs and symptoms of menopause on the uterus, vagina, breasts, cervix; relief in androgen-dependent prostatic carcinoma is attributable to competition with androgens for receptor sites, decreasing the influence of androgens.

Indications

·        Topical emulsion, all forms: Palliation of moderate to severe vasomotor symptoms, atrophic vaginitis or kraurosis vulvae associated with menopause

·        Estradiol oral, transdermal, ring, vaginal tablets, estradiol valerate: Prevention of postmenopausal osteoporosis

·        Estradiol oral, transdermal, estradiol cypionate, valerate: Treatment of female hypogonadism, female castration, primary ovarian failure

·        Estradiol oral, estradiol valerate: Palliation of inoperable prostatic cancer

·        Estradiol oral: Palliation of inoperable, progressing breast cancer

·        Prevention of osteoporosis

Contraindications and cautions

·        Contraindicated with allergy to estrogens, allergy to tartrazine (in 2-mg oral tablets), breast cancer (with exceptions), estrogen-dependent neoplasm, undiagnosed abnormal genital bleeding, active or past history of thrombophlebitis or thromboembolic disorders (potential serious fetal defects; women ofchildbearing age should be advised of risks and birth control measures suggested).

·        Use cautiously with metabolic bone disease, renal insufficiency, CHF, lactation.

Available forms

Transdermal—release rates of 0.014, 0.025, 0.0375, 0.05, 0.075, 0.1 mg/24 hr; tablets—0.5, 1, 1.5, 2 mg; injection—5, 10, 20, 40 mg/mL; vaginal cream—0.1 mg/g; vaginal ring—2 mg; vaginal tablet—25 mcg; topical emulsion—0.1 mg

Dosages

ADULTS

·        Moderate to severe vasomotor symptoms, atrophic vaginitis, kraurosis vulvae associated with menopause: 1–2 mg/day PO. Adjust dose to control symptoms. Cyclic therapy (3 wk on/1 wk off) is recommended, especially in women who have not had a hysterectomy. 1–5 mg estradiol cypionate in oil IM every 3–4 wk. 10–20 mg estradiol valerate in oil IM, every 4 wk. The 0.014–0.05-mg system is applied to the skin weekly or twice weekly. If oral estrogens have been used, start transdermal system 1 wk after withdrawal of oral form. Given on a cyclic schedule (3 wk on/1wk off). Attempt to taper or discontinue medication every 3–6 mo.

·        Female hypogonadism, female castration, primary ovarian failure: 1–2 mg/day PO. Adjust dose to control symptoms. Cyclic therapy (3 wk on/1 wk off) is recommended. 1.5–2 mg estradiol cypionate in oil IM at monthly intervals. 10–20 mg estradiol valerate in oil IM every 4 wk. 0.05-mg system applied to skin twice weekly as above.

Vaginal

·        Vaginal cream: 2–4 g intravaginally daily for 1–2 wk, then reduce to one-half dosage for similar period followed by maintenance doses of 1 g one to three times/wk thereafter. Discontinue or taper at 3- to 6-mo intervals.

·        Vaginal ring: Insert one ring high into vagina. Replace every 90 days.

·        Vaginal tablet: 1 tablet inserted vaginally daily for 2 wk; then twice weekly.

Oral

·        Prostatic cancer (inoperable): 1–2 mg PO tid. Administer long-term. 30 mg or more estradiol valerate in oil IM every 1–2 wk.

·        Breast cancer (inoperable, progressing): 10 mg tid PO for at least 3 mo.

·        Prevention of postpartum breast engorgement: 10–25 mg estradiol valerate in oil IM as a single injection at the end of the first stage of labor.

·        Osteoporosis prevention: 0.5 mg/day PO given cyclically—23 days on, 5 days rest—starting as soon after menopause as possible or 0.05 mg/24 hr applied to skin once or twice weekly.

Topical emulsion

·        Apply lotion to legs, thighs, or calves once daily for relief of menopausal symptoms.

PEDIATRIC PATIENTS

Not recommended due to effect on the growth of the long bones.

Pharmacokinetics

Route	Onset	Peak
Oral	Slow	Days

Metabolism: Hepatic; T_1/2: Not known

Distribution: Crosses placenta; enters breast milk

Excretion: Urine

Adverse effects

·        CNS: Steepening of the corneal curvature with a resultant change in visual acuity and intolerance to contact lenses, headache, migraine, dizziness, mental depression, chorea, seizures

·        CV: Increased BP, thromboembolic and thrombotic disease

·        Dermatologic: Photosensitivity, peripheral edema, chloasma, erythema nodosum or multiforme, hemorrhagic eruption, loss of scalp hair, hirsutism,urticaria, dermatitis

·        GI: Gallbladder disease (in postmenopausal women), hepatic adenoma, nausea, vomiting, abdominal cramps, bloating, cholestatic jaundice, colitis, acute pancreatitis

·        GU: Increased risk of postmenopausal endometrial cancer, breakthrough bleeding, change in menstrual flow, dysmenorrhea, premenstrual-like syndrome, amenorrhea, vaginal candidiasis, cystitis-like syndrome, endometrial cystic hyperplasia

·        Hematologic: Hypercalcemia, decreased glucose tolerance

·        Local: Pain at injection site, sterile abscess, postinjection flare

·        Other: Weight changes, reduced carbohydrate tolerance, aggravation of porphyria, edema, changes in libido, breast tenderness

Topical vaginal cream

Systemic absorption may cause uterine bleeding in menopausal women and may cause serious bleeding of remaining endometrial foci in sterilized women with endometriosis.

Interactions

Drug-drug

·        Increased therapeutic and toxic effects of corticosteroids

·        Decreased serum levels of estradiol with drugs that enhance hepatic metabolism of the drug—barbiturates, phenytoin, rifampin, carbamazepine

Drug-lab test

·        Increased prothrombin and factors VII, VIII, IX, and X; thyroid-binding globulin with increased PBI, T₄, increased uptake of free T₃ resin (free T₄ is unaltered), serum triglycerides and phospholipid concentration

·        Decreased antithrombin III, pregnanediol excretion, response to metyrapone test, serum folate concentration

·        Impaired glucose tolerance

Nursing considerations

Assessment

·        History: Allergy to estrogens, tartrazine; breast cancer, estrogen-dependent neoplasm; undiagnosed abnormal genital bleeding; active or previousthrombophlebitis or thromboembolic disorders; pregnancy; lactation; metabolic bone disease; renal insufficiency; CHF

·        Physical: Skin color, lesions, edema; breast examination; injection site; orientation, affect, reflexes; P, auscultation, BP, peripheral perfusion; R, adventitious sounds; bowel sounds, liver evaluation, abdominal examination; pelvic examination; serum calcium, phosphorus; LFTs, renal function tests; Pap smear; glucose tolerance test

Interventions

·        Arrange for pretreatment and periodic (at least annual) history and physical, which should include BP, breasts, abdomen, pelvic organs, and a Pap smear.

·        Do not use to prevent CV events or dementia; may increase risk.

·        Caution patient of the risks of estrogen use, the need to prevent pregnancy during treatment, for frequent medical follow-up, and for periodic rests from drug treatment.

·        Administer cyclically for short-term only when treating postmenopausal conditions because of the risk of endometrial neoplasm; taper to the lowest effective dose, and provide a drug-free week each month.

·        Apply transdermal system to a clean, dry area of skin on the trunk of the body, preferably the abdomen; do not apply to breasts; rotate the site at least 1 wk between applications; avoid the waistline because clothing may rub the system off; apply immediately after opening and compress for about 10 sec to attach.

·        Insert vaginal ring as deeply as possible into upper one-third of vagina. Ring will remain in place for 3 months. Then, remove and evaluate need for continued therapy. If a ring falls out during 3 mo, rinse with warm water and reinsert.

·        WARNING: Arrange for the concomitant use of progestin therapy during long-term estrogen therapy in women with a uterus; this will mimic normal physiologic cycling and allow for a cyclic uterine bleeding that may decrease the risk of endometrial cancer. Women without a uterus do not need progestin.

·        Administer parenteral preparations by deep IM injection only. Monitor injection sites and rotate with each injection to decrease development of abscesses.

Teaching points

·        Use this drug in cycles or short term; prepare a calendar of drug days, rest days, and drug-free periods.

·        Apply transdermal system and vaginal cream properly; insert vaginal tablet as high into the vagina as is comfortable.

·        Insert vaginal ring high in vagina; it should remain in place for 3 months. If it falls out before that time, rinse with warm water and reinsert.

·        Potentially serious side effects include cancers, blood clots, and liver problems; it is very important to have periodic medical examinations throughout therapy.

·        This drug cannot be given to pregnant women because of serious toxic effects to the baby.

·        You may experience these side effects: Nausea, vomiting, bloating; headache, dizziness, mental depression (use caution if driving or performing tasks that require alertness); sensitivity to sunlight (use a sunscreen and wear protective clothing); rash, loss of scalp hair, darkening of the skin on the face; changes in menstrual patterns.

·        Report pain in the groin or calves of the legs, chest pain or sudden shortness of breath, abnormal vaginal bleeding, lumps in the breast, sudden severe headache, dizziness or fainting, changes in vision or speech, weakness or numbness in the arm or leg, severe abdominal pain, yellowing of the skin or eyes, severe mental depression, pain at injection site.

Adverse effects in Italic are most common; those in Bold are life-threatening.