Yes

Estrogen Derivative

Treatment of atrophic vaginitis, atrophic dystrophy of vulva, menopausal symptoms, female hypogonadism, ovariectomy, primary ovarian failure, inoperable breast cancer, inoperable prostatic cancer, mild to severe vasomotor symptoms associated with menopause

X

Hypersensitivity to estradiol or any component; known or suspected pregnancy; porphyria; abnormal genital bleeding of unknown etiology; known or suspected carcinoma of the breast (except in patients treated for metastatic disease); estrogen-dependent tumors; history of thrombophlebitis, thrombosis, or thromboembolic disorders associated with estrogen use

Use with caution in patients with renal or hepatic insufficiency. Estrogens may cause premature closure of epiphyses in young individuals, in patients with a history of thromboembolism, stroke, myocardial infarction (especially >40 years of age who smoke), liver tumor, or hypertension.

Use vaginal tablets with caution in patients with severely atrophic vaginal mucosa or following gynecological surgery due to possible trauma from the applicator.

Estrogens have been reported to increase the risk of endometrial carcinoma; do not use estrogens during pregnancy. Before prescribing estrogen therapy to postmenopausal women, the risks and benefits must be weighed for each patient. Women should be informed of these risks and benefits, as well as possible side effects and the return of menstrual bleeding (when cycled with a progestin), and be involved in the decision to prescribe. Oral therapy may be more convenient for vaginal atrophy and stress incontinence.

>10%:

Cardiovascular: Peripheral edema

Endocrine & metabolic: Enlargement of breasts (female and male), breast tenderness

Gastrointestinal: Nausea, anorexia, bloating

1% to 10%:

Central nervous system: Headache

Endocrine & metabolic: Increased libido (female), decreased libido (male)

Gastrointestinal: Vomiting, diarrhea

<1%: Increase in blood pressure, edema, thromboembolic disorders, myocardial infarction, depression, dizziness, anxiety, stroke, chloasma, melasma, rash, hypercalcemia, folate deficiency, change in menstrual flow, breast tumors, amenorrhea, decreased glucose tolerance, increased triglycerides and LDL, GI distress, cholestatic jaundice, pain at injection site, intolerance to contact lenses, increased susceptibility to Candida infection

Vaginal (Trauma from applicator insertion may occur in women with severely atrophic vaginal mucosa.)

Symptoms of overdose include fluid retention, jaundice, thrombophlebitis, nausea, vomiting

Toxicity is unlikely following single exposures of excessive doses, any treatment following emesis and charcoal administration should be supportive and symptomatic

CYP1A2 and 3A3/4 enzyme substrate

Increased toxicity: Hydrocortisone increases corticosteroid toxic potential; increased potential for thromboembolic events with anticoagulants

Increases the synthesis of DNA, RNA, and various proteins in target tissues; reduces the release of gonadotropin-releasing hormone from the hypothalamus; reduces FSH and LH release from the pituitary

Absorption: Readily absorbed through skin and GI tract; reabsorbed from bile in GI tract and enterohepatically recycled

Distribution: Crosses the placenta; appears in breast milk

Metabolism: Principally degraded in the liver

Protein binding: 80%

Half-life: 50-60 minutes

Elimination: In urine as conjugates; small amounts excreted in feces via bile, reabsorbed from the GI tract and enterohepatically recycled

All dosage needs to be adjusted based upon the patient's response

Prostate cancer: Valerate: I.M.: greater than or equal to 30 mg or more every 1-2 weeks

Prostate cancer (androgen-dependent, inoperable, progressing): Oral: 10 mg 3 times/day for at least 3 months

Female:

Oral:

Breast cancer (inoperable, progressing): 10 mg 3 times/day for at least 3 months

Osteoporosis prevention: 0.5 mg/day in a cyclic regimen (3 weeks on and 1 week off)

Hypogonadism, moderate to severe vasomotor symptoms: 1-2 mg/day in a cyclic regimen for 3 weeks on drug, then 1 week off

Treatment of moderate to severe vasomotor symptoms associated with menopause: 1-2 mg/day, adjusted as necessary to limit symptoms; administration should be cyclic (3 weeks on, 1 week off). Patients should be re-evaluated at 3- to 6-month intervals to determine if treatment is still necessary.

I.M.

Moderate to severe vasomotor symptoms associated with menopause: Cypionate: 1-5 mg every 3-4 weeks; Valerate: 10-20 mg every 4 weeks

Postpartum breast engorgement: Valerate: 10-25 mg at end of first stage of labor

Transdermal twice-weekly patch (Alora™, Esclim®, Estraderm®, Vivelle®):

Moderate to severe vasomotor symptoms associated with menopause, vulvar/vaginal atrophy, hypogonadism: Apply 0.05 mg patch initially (titrate dosage to response) applied twice weekly in a cyclic regimen, for 3 weeks on and 1 week off drug in patients with an intact uterus and continuously in patients without a uterus. Re-evaluate postmenopausal therapy at 3- to 6-month intervals to determine if treatment is still necessary.

Transdermal once-weekly patch (Climara®, Fempatch®):

Moderate to severe vasomotor symptoms associated with menopause: Apply 0.025-0.05 mg/day patch once weekly. Adjust dose as necessary to control symptoms. Patients should be re-evaluated at 3- to 6-month intervals to determine if treatment is still necessary.

Prevention of osteoporosis in postmenopausal women (approved indication for Climara®): Apply patch once weekly; minimum effective dose 0.025 mg/day; adjust response to therapy by biochemical markers and bone mineral density

Vaginal cream:

Atrophic vaginitis, kraurosis vulvae: Vaginal: Insert 2-4 g/day for 2 weeks then gradually reduce to 1/2 the initial dose for 2 weeks followed by a maintenance dose of 1 g 1-3 times/week

Vaginal ring (Estring®):

Postmenopausal vaginal atrophy, urogenital symptoms: Following insertion, Estring® should remain in place for 90 days

Vaginal tablets (Vagifem®):

Atrophic vaginitis: Initial: Insert 1 tablet once daily for 2 weeks; Maintenance: Insert 1 tablet twice weekly; attempts to discontinue or taper medication should be made at 3- to 6-month intervals

Dosing adjustment in hepatic impairment:

Mild to moderate liver impairment: Dosage reduction of estrogens is recommended

Severe liver impairment: Not recommended

Larger doses of vitamin C (eg, 1 g/day in adults) may increase serum concentrations and adverse effects of estradiol. Vitamin C supplements are not recommended, but their effect may be decreased if vitamin C supplement is administered 2-3 hours after estrogen. Dietary intake of folate and pyridoxine may need to be increased.

Children: <10 pg/mL (SI: <37 pmol/L)

Male: 10-50 pg/mL (SI: 37-184 pmol/L)

Female:

Premenopausal: 30-400 pg/mL (SI: 110-1468 pmol/L)

Postmenopausal: 0-30 pg/mL (SI: 0-110 pmol/L)

Decreased antithrombin III

Decreased serum folate concentration

Increased prothrombin and factors VII, VIII, IX, X

Increased platelet aggregability

Increased thyroid binding globulin

Increased total thyroid hormone (T₄)

Increased serum triglycerides/phospholipids

May cause anxiety or depression

None reported

No information available to require special precautions

No effects or complications reported

Use this drug in cycles or term as prescribed. Periodic gynecologic exam and breast exams are important. You may experience nausea or vomiting (small frequent meals may help); dizziness or mental depression (use caution when driving); photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight); rash; loss of scalp hair; enlargement/tenderness of breasts; increased/decreased libido. Report sudden acute pain in legs or calves, chest, or abdomen; shortness of breath; severe headache or vomiting; weakness or numbness of arms or legs; unusual vaginal bleeding; yellowing of skin or eyes; change in color of urine or stool; or easy bruising or bleeding. Pregnancy precautions: Inform prescriber if you are pregnant.

Intravaginal cream: Insert high in vagina. Wash hands and applicator before and after use.

Aerosol topical corticosteroids applied under the patch may reduce allergic reactions; do not apply transdermal system to breasts, but place on trunk of body (preferably abdomen); rotate application sites

Cream, vaginal (Estrace®): 0.1 mg/g (42.5 g)

Injection, as cypionate (depGynogen®, Depo®-Estradiol, Depogen®, Dura-Estrin®, Estra-D®, Estro-Cyp®, Estroject-L.A.®): 5 mg/mL (5 mL, 10 mL)

Injection, as valerate:

Valergen®: 10 mg/mL (5 mL, 10 mL); 20 mg/mL (1 mL, 5 mL, 10 mL); 40 mg/mL (5 mL, 10 mL)

Dioval®, Duragen®, Estra-L®, Gynogen L.A.®: 20 mg/mL (10 mL); 40 mg/mL (10 mL)

Tablet, micronized:

Estrace®: 1 mg, 2 mg

Gynodiol®: 0.5 mg, 1 mg, 1.5 mg, 2 mg

Transdermal system

Alora™:

0.05 mg/24 hours [18 cm²], total estradiol 1.5 mg

0.075 mg/24 hours [27 cm²], total estradiol 2.3 mg

0.1 mg/24 hours [36 cm²], total estradiol 3 mg

Climara®:

0.05 mg/24 hours [12.5 cm²], total estradiol 3.9 mg

0.075 mg/24 hours [18.75 cm²], total estradiol 5.85 mg

0.1 mg/24 hours [25 cm²], total estradiol 7.8 mg

Esclim®:

0.025 mg/day

0.0375 mg/day

0.05 mg/day

0.075 mg/day

0.1 mg/day

Estraderm®:

0.05 mg/24 hours [10 cm²], total estradiol 4 mg

0.1 mg/24 hours [20 cm²], total estradiol 8 mg

Vivelle®:

0.0375 mg/day

0.05 mg/day

0.075 mg/day

0.1 mg/day

Vaginal ring (Estring®): 2 mg gradually released over 90 days

American College of Physicians, "Guidelines for Counseling Postmenopausal Women About Preventive Hormone Therapy," Ann Intern Med, 1992, 117(12):1038-41.

Belchetz PE, "Hormone Treatment for Postmenopausal Women," N Engl J Med, 1994, 330(15):1062-71.

Ettinger B, Friedman GD, Bush T, et al, "Reduced Mortality Associated with Long-Term Postmenopausal Estrogen Therapy," Obstet Gynecol, 1996, 87(1):6-12.