No

Estrogen Derivative

Atrophic vaginitis; hypogonadism; primary ovarian failure; vasomotor symptoms of menopause; prostatic carcinoma; osteoporosis prophylactic

X

Undiagnosed vaginal bleeding; hypersensitivity to estrogens or any component; thrombophlebitis, liver disease, known or suspected pregnancy, carcinoma of the breast, estrogen dependent tumor

Use with caution in patients with asthma, epilepsy, migraine, diabetes, cardiac or renal dysfunction; estrogens may cause premature closure of the epiphyses in young individuals; safety and efficacy in children have not been established; estrogens have been reported to increase the risk of endometrial carcinoma; do not use estrogens during pregnancy

>10%:

Cardiovascular: Peripheral edema

Endocrine & metabolic: Breast tenderness, hypercalcemia, enlargement of breasts

Gastrointestinal: Nausea, anorexia, bloating

1% to 10%:

Central nervous system: Headache

Endocrine & metabolic: Increased libido

Gastrointestinal: Vomiting, diarrhea

Local: Pain at injection site

<1%: Increase in blood pressure, edema, thromboembolic disorder, myocardial infarction, hypertension, depression, dizziness, anxiety, stroke, chloasma, melasma, rash, breast tumors, amenorrhea, alterations in frequency and flow of menses, decreased glucose tolerance, increased triglycerides and LDL, GI distress, cholestatic jaundice, intolerance to contact lenses, increased susceptibility to Candida infection

Symptoms of overdose include fluid retention, jaundice, thrombophlebitis

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

CYP1A2 enzyme inducer

Increased toxicity:

Hydrocortisone increases corticosteroid toxic potential

Increased potential for thromboembolic events with anticoagulants

Refrigerate injection; at room temperature, the injection is stable for 24 months

Reconstituted solution is stable for 60 days at refrigeration

Compatible with normal saline, dextrose, and inert sugar solution

Incompatible with proteins, ascorbic acid, or solutions with acidic pH

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 from GI tract

Metabolism: To inactive compounds in the liver

Elimination: In bile and urine

Adolescents and Adults:

Female:

Osteoporosis in postmenopausal women: Oral: 0.625 mg/day, cyclically (3 weeks on, 1 week off)

Dysfunctional uterine bleeding:

Stable hematocrit: Oral: 1.25 mg twice daily for 21 days; if bleeding persists after 48 hours, increase to 2.5 mg twice daily; if bleeding persists after 48 more hours, increase to 2.5 mg 4 times/day; some recommend starting at 2.5 mg 4 times/day. ( Note: Medroxyprogesterone acetate 10 mg/day is also given on days 17-21.)

Unstable hematocrit: Oral: I.V.: 5 mg 2-4 times/day; if bleeding is profuse, 20-40 mg every 4 hours up to 24 hours may be used. Note: A progestational-weighted contraception pill should also be given (eg, Ovral® 2 tablets stat and 1 tablet 4 times/day or medroxyprogesterone acetate 5-10 mg 4 times/day)

Alternatively: I.V.: 25 mg every 6-12 hours until bleeding stops

Hypogonadism: Oral: 2.5-7.5 mg/day for 20 days, off 10 days and repeat until menses occur. If bleeding does not occur by the end of this period, repeat dosage schedule. If bleeding occurs before the end of the 10-day period, begin a 20-day estrogen-progestin cyclic regimen with 2.5-7.5 mg estrogen daily in divided doses for 1-20 days. During the last 5 days of estrogen therapy, give an oral progestin. If bleeding occurs before this regimen is concluded, discontinue therapy and resume on day 5 of bleeding.

Moderate to severe vasomotor symptoms: Oral: 0.625 mg/day either cyclically or daily; alternatively, may give 1.25 mg/day cyclically

Postpartum breast engorgement: Oral: 3.75 mg every 4 hours for 5 doses, then 1.25 mg every 4 hours for 5 days

Atrophic vaginitis, kraurosis vulvae:

Oral: 0.3-1.25 mg or more daily depending on tissue response of the patient; administer cyclically (3 weeks of daily estrogen and 1 week off)

Vaginal: 2-4 g instilled/day 3 weeks on and 1 week off

Female castration and primary ovarian failure: Oral: 1.25 mg/day cyclically (3 weeks on, 1 week off). Adjust according to severity of symptoms and patient response. For maintenance, adjust to the lowest effective dose.

Male/Female: Uremic bleeding: I.V.: 0.6 mg/kg/dose daily for 5 days

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 estrogens. Vitamin C supplements are not recommended, but their effect/interaction 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 mg/24 hours (SI: <35 mmol/day) (values at Mayo Medical Laboratories)

Adults:

Male: 15-40 mg/24 hours (SI: 52-139 mmol/day)

Female:

Menstruating: 15-80 mg/24 hours (SI: 52-277 mmol/day)

Postmenopausal: <20 mg/24 hours (SI: <69 mmol/day)

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 rarely cause anxiety or depression

None reported

No information available to require special precautions

No effects or complications reported

Follow prescribed schedule and dose. Periodic gynecologic exam and breast exams are important with long-term use. Consult prescriber for specific dietary recommendations. 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 (reversible); enlargement/tenderness of breasts (both male and female); increased (female)/decreased (male) libido; or headache (use of mild analgesic may help). Report swelling of extremities or unusual weight gain; chest pain or palpitations; sudden acute pain, warmth, or weakness in legs or calves; shortness of breath; severe headache or vomiting; or unusual vaginal bleeding, amenorrhea, or alterations in frequency and flow of menses.

Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not get pregnant during or for 1 month following therapy. Consult prescriber for instruction on appropriate barrier contraceptive measures. This drug may cause severe fetal defects. Consult prescriber if breast-feeding.

May also be administered intramuscularly; administer at bedtime to minimize occurrence of adverse effects; when administered I.V., drug should be administered slowly to avoid the occurrence of a flushing reaction

Cream, vaginal: 0.625 mg/g (42.5 g)

Injection: 25 mg (5 mL)

Tablet: 0.3 mg, 0.625 mg, 0.9 mg, 1.25 mg, 2.5 mg

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

Barrett-Connor E, Brown WV, Turner J, et al, "Heart Disease Risk Factors and Hormone Use in Postmenopausal Women," JAMA, 1979, 241:2167-9.

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

Christopherson WM, "Liver Tumours and the Pill," Br Med J, 1975, 4:756.

Cust MP, Ganagar KF, Hillard TC, et al, "A Risk-Benefit Assessment of Estrogen Therapy in Postmenopausal Women," Drug Saf, 1990, 5(5):345-58.

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

Neistein LS, Adolescent Health Care - A Practical Guide, 2nd ed, Baltimore: Urban & Schwarzenberg, 1991, 661-6.

Neistein LS, Adolescent Health Care - A Practical Guide, 3rd ed, Baltimore: Urban & Schwarzenberg, 1996.

The Writing Group for the PEPI Trial, "Effects of Estrogen or Estrogen/Progestin Regimens on Heart Disease Risk Factors in Postmenopausal Women," JAMA, 1995, 273(3):199-208.