Pronunciation:

(ES troe pih pate)

U.S. Brand Names:

Synonyms:

Generic Available:

Canadian Brand Names:

Use:

Pregnancy Risk Factor:

Pregnancy Implications:

Lactation:

Contraindications:

Warnings/Precautions:

Cardiovascular-related considerations: Estrogens with or without progestin should not be used to prevent coronary heart disease. Use caution with cardiovascular disease or dysfunction. May increase the risks of hypertension, myocardial infarction (MI), stroke, pulmonary emboli (PE), and deep vein thrombosis; incidence of these effects was shown to be significantly increased in postmenopausal women using conjugated equine estrogens (CEE) in combination with medroxyprogesterone acetate (MPA). Nonfatal MI, PE, and thrombophlebitis have also been reported in males taking high doses of CEE (eg, for prostate cancer). Estrogen compounds are generally associated with lipid effects such as increased HDL-cholesterol and decreased LDL-cholesterol. Triglycerides may also be increased; use with caution in patients with familial defects of lipoprotein metabolism. Whenever possible, estrogens should be discontinued at least 4-6 weeks prior to surgeries associated with an increased risk of thromboembolism or during periods of prolonged immobilization.

Neurological considerations: The risk of dementia may be increased in postmenopausal women; increased incidence was observed in women 65 years of age taking CEE in combination with MPA.

Cancer-related considerations: Unopposed estrogens may increase the risk of endometrial carcinoma in postmenopausal women. Estrogens may increase the risk of breast cancer. An increased risk of invasive breast cancer was observed in postmenopausal women using CEE in combination with MPA; a smaller increase in risk was seen with estrogen therapy alone in observational studies. An increase in abnormal mammograms has also been reported with estrogen and progestin therapy. Estrogen use may lead to severe hypercalcemia in patients with breast cancer and bone metastases; discontinue estrogen if hypercalcemia occurs.

Estrogens may cause retinal vascular thrombosis; discontinue permanently if papilledema or retinal vascular lesions are observed on examination. Use with caution in patients with diseases which may be exacerbated by fluid retention, including asthma, epilepsy, migraine, diabetes or renal dysfunction. Use with caution in patients with a history of severe hypocalcemia, SLE, hepatic hemangiomas, porphyria, endometriosis, and gallbladder disease. Use caution with history of cholestatic jaundice associated with past estrogen use or pregnancy. Safety and efficacy in pediatric patients have not been established. Prior to puberty, estrogens may cause premature closure of the epiphyses, premature breast development in girls or gynecomastia in boys. Vaginal bleeding and vaginal cornification may also be induced in girls.

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 effects of progestin when added to estrogen therapy. Estrogens with or without progestin should be used for shortest duration possible consistent with treatment goals. Conduct periodic risk:benefit assessments.

When used solely for prevention of osteoporosis in women at significant risk, nonestrogen treatment options should be considered. When used solely for the treatment of vulvar and vaginal atrophy, topical vaginal products should be considered.

Adverse Reactions:

Cardiovascular: Edema, hypertension, venous thromboembolism

Central nervous system: Dizziness, headache, mental depression, migraine

Dermatologic: Chloasma, erythema multiforme, erythema nodosum, hemorrhagic eruption, hirsutism, loss of scalp hair, melasma

Endocrine & metabolic: Breast enlargement, breast tenderness, libido (changes in), increased thyroid-binding globulin, increased total thyroid hormone (T4), increased serum triglycerides/phospholipids, increased HDL-cholesterol, decreased LDL-cholesterol, impaired glucose tolerance, hypercalcemia

Gastrointestinal: Abdominal cramps, bloating, cholecystitis, cholelithiasis, gallbladder disease, nausea, pancreatitis, vomiting, weight gain/loss

Genitourinary: Alterations in frequency and flow of menses, changes in cervical secretions, endometrial cancer, increased size of uterine leiomyomata, vaginal candidiasis

Hematologic: Aggravation of porphyria, decreased antithrombin III and antifactor Xa, increased levels of fibrinogen, increased platelet aggregability and platelet count; increased prothrombin and factors VII, VIII, IX, X

Hepatic: Cholestatic jaundice

Neuromuscular & skeletal: Chorea

Ocular: Intolerance to contact lenses, steeping of corneal curvature

Respiratory: Pulmonary thromboembolism

Miscellaneous: Carbohydrate intolerance

Overdosage/Toxicology:

Drug Interactions:

Anticoagulants: Increase potential for thromboembolic events

Corticosteroids: Estrogens may enhance the effects of hydrocortisone and prednisone.

CYP1A2 inducers: May decrease the levels/effects of estrogens. Example inducers include aminoglutethimide, carbamazepine, phenobarbital, and rifampin.

CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of estrogens. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.

Ethanol/Nutrition/Herb Interactions:

Ethanol: Routine use increases estrogen level and risk of breast cancer; avoid ethanol. Ethanol may also increase the risk of osteoporosis.

Food: Folic acid absorption may be decreased.

Herb/Nutraceutical: St John's wort may decrease levels. Avoid black cohosh, dong quai (has estrogenic activity). Avoid red clover, saw palmetto, ginseng (due to potential hormonal effects).

Stability:

Mechanism of Action:

Pharmacodynamics/Kinetics:

Absorption: Well absorbed

Metabolism: Hepatic and in target tissues; first-pass effect

Dosage:

Oral:

Moderate to severe vasomotor symptoms associated with menopause: Usual dosage range: 0.75-6 mg estropipate daily; use the lowest dose and regimen that will control symptoms, and discontinue as soon as possible. Attempt to discontinue or taper medication at 3- to 6-month intervals. If a patient with vasomotor symptoms has not menstruated within the last 2 months, start the cyclic administration arbitrarily. If the patient has menstruated, start cyclic administration on day 5 of bleeding.

Female hypogonadism: 1.5-9 mg estropipate daily for the first 3 weeks, followed by a rest period of 8-10 days; use the lowest dose and regimen that will control symptoms. Repeat if bleeding does not occur by the end of the rest period. The duration of therapy necessary to product the withdrawal bleeding will vary according to the responsiveness of the endometrium. If satisfactory withdrawal bleeding does not occur, give an oral progestin in addition to estrogen during the third week of the cycle.

Female castration or primary ovarian failure: 1.5-9 mg estropipate daily for the first 3 weeks of a theoretical cycle, followed by a rest period of 8-10 days; use the lowest dose and regimen that will control symptoms

Osteoporosis prophylaxis: 0.75 mg estropipate daily for 25 days of a 31-day cycle

Atrophic vaginitis or kraurosis vulvae: 0.75-6 mg estropipate daily; administer cyclically. Use the lowest dose and regimen that will control symptoms; discontinue as soon as possible.

Elderly: Refer to Adults dosing. A higher incidence of stroke and invasive breast cancer were observed in women >75 years in a WHI substudy using conjugated equine estrogen.

Dosing adjustment in hepatic impairment:

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

Severe liver impairment: Not recommended

Monitoring Parameters:

Menopausal symptoms: Assess need for therapy at 3- to 6-month intervals

Prevention of osteoporosis: Bone density measurement

Test Interactions:

Dietary Considerations:

Patient Education:

Additional Information:

Based on preliminary findings, the FDA has requested labeling changes be made to estrogen products used in postmenopausal women. The updates include information from the Women's Health Initiative Memory Study (WHIMS) as well as information collected from the completed CEE/MPA arm of the WHI study. Complete analysis of the WHI data is forthcoming, and will include all information collected through February, 2004.

Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Mental Health: Effects on Mental Status:

Mental Health: Effects on Psychiatric Treatment:

Dosage Forms:

Tablet: 0.625 mg [estropipate 0.75 mg]; 1.25 mg [estropipate 1.5 mg]; 2.5 mg [estropipate 3 mg]

Ogen®: 0.625 mg [estropipate 0.75 mg]; 1.25 mg [estropipate 1.5 mg]; 2.5 mg [estropipate 3 mg]

Ortho-Est®: 0.625 mg [estropipate 0.75 mg]; 1.25 mg [estropipate 1.5 mg]

International Brand Names: