estropipate
Ogen, Ortho-Est

Available forms
Estropipate is available as estrone sodium sulfate. Available by prescription only.
Tablets: 0.625 mg, 1.25 mg, 2.5 mg, 5 mg

Indications and dosages
 Atrophic vaginitis, kraurosis vulvae, vasomotor menopausal symptoms. Adults: 0.625 to 5 mg P.O. daily for 21 days, followed by 7 days off therapy.
 Female hypogonadism, primary ovarian failure, or after castration. Adults: 1.25 to 7.5 mg P.O. daily for 3 weeks, followed by 8 to 10 days off therapy. Cycle may be repeated if no withdrawal bleeding occurs within 10 days of discontinuing therapy.
 Prevention of osteoporosis. Adults: 0.625 mg P.O. daily for 25 days of a 31-day cycle.

Pharmacodynamics
Estrogenic action: Estropipate mimics the action of endogenous estrogen in treating female hypogonadism, menopausal symptoms, and atrophic vaginitis.

Pharmacokinetics
Absorption: After oral administration, estropipate and other synthetic derivatives of the natural estrogens are rapidly absorbed.
Distribution: About 50% to 80% bound to plasma protein. Distribution occurs throughout the body, with highest levels appearing in fat.
Metabolism: Steroidal estrogens are metabolized primarily in the liver, where they are conjugated with sulfate and glucuronide. Because of the rapid metabolism, many forms of estrogen must be administered daily.
Excretion: Mostly eliminated through the kidneys in the form of sulfate or glucuronide conjugates.

Contraindications and precautions
Contraindicated in patients with thrombophlebitis or thromboembolic disorders, estrogen-dependent neoplasia, breast or reproductive organ cancer (except for palliative treatment), or undiagnosed abnormal genital bleeding and during pregnancy.
 Use cautiously in patients with cerebrovascular or coronary artery disease, gallbladder disease, hypertension, asthma, bone diseases, mental depression, migraine, seizures, or cardiac, hepatic, or renal dysfunction. Also use cautiously in women with family history (mother, grandmother, sister) of breast or genital tract cancer or who have breast nodules, fibrocystic disease, or abnormal mammographic findings.

Interactions
Drug-drug. Drugs that induce hepatic metabolism, such as barbiturates, carbamazepine, phenytoin, primidone, rifampin: May result in decreased estrogenic effects from a given dose. These drugs are known to accelerate the metabolism of certain other agents. Use together cautiously.
Insulin, oral antidiabetics: May alter blood glucose level. Adjust dosage as needed.
Tamoxifen: Decreases tamoxifen effects. Monitor patient closely.
Warfarin-type anticoagulants: Decreases anticoagulant effect. Dosage adjustment may be needed.
Drug-herb. Red clover: May interfere with hormonal therapies. Discourage use together.
Drug-food. Caffeine: May increase serum caffeine levels. Discourage caffeine use.
Drug-lifestyle. Smoking: Increases risk of adverse CV effects. Discourage smoking.

Adverse reactions
CNS: headache, dizziness, depression, migraine, seizures, CVA.
CV: pulmonary embolism, MI, thromboembolism, thrombophlebitis, edema.
EENT: worsening of myopia or astigmatism, intolerance of contact lenses.
GI: vomiting, abdominal cramps, bloating, gallbladder disease.
GU: breakthrough bleeding, increased size of uterine fibromas, dysmenorrhea, amenorrhea, vaginal candidiasis, endometrial cancer, altered menstrual flow, cervical erosion, altered cervical secretions, cystitis-like syndrome (which resembles premenstrual syndrome), testicular atrophy.
Hepatic: cholestatic jaundice, hepatic adenoma.
Metabolic: hyperglycemia, hypercalcemia, weight changes.
Skin: erythema multiforme, erythema nodosum, hair loss, hemorrhagic eruption, hirsutism, melasma.
Other: libido changes; in women, breast cancer, aggravation of porphyria, breast changes (tenderness, enlargement, secretion); gynecomastia in men.

Effects on lab test results
• May increase levels of glucose; calcium; clotting factors VII, VIII, IX, and X; total T₄; thyroid-binding globulin; phospholipid; and triglyceride. May decrease serum folate, pyridoxine, and antithrombin III levels.
• May increase PT and norepinephrine-induced platelet aggregation.

Overdose and treatment
Serious toxicity caused by overdose of this drug hasn’t been reported. Nausea may occur.
 Provide appropriate supportive care.

Special considerations
• Therapy with estrogens increases sulfobromophthalein retention. Thyroid-binding globulin levels may increase, resulting in increased total thyroid levels (measured by protein-bound iodine or total T₄) and decreased uptake of free T₃ resin. Glucose tolerance may be impaired. Pregnanediol excretion may decrease.
• When used for progressive, inoperable prostate cancer, remission should be apparent within 3 weeks of therapy.
• When submitting specimens to pathologist for evaluation, note that patient is taking estrogens.
Pregnant patients
• Drug is contraindicated during pregnancy.
Breast-feeding patients
• Drug is contraindicated in breast-feeding women.
Geriatric patients
• Frequent physical examinations are recommended for postmenopausal women taking estrogens.

Patient education
• Tell patient to read package insert describing adverse estrogen effects; also give verbal explanation.
• Tell diabetic patient to report elevated glucose levels.
• Stress importance of regular physical examinations. Postmenopausal women who use estrogen replacement for longer than 5 years may have increased risk of endometrial cancer. Using cyclic therapy and lowest possible estrogen dosage reduces risk. Adding progestins to regimen decreases risk of endometrial hyperplasia; however, it isn’t known whether progestins affect risk of endometrial cancer.
 ALERT Warn patient to immediately report abdominal pain; pain, stiffness, or numbness in legs or buttocks; pressure or pain in chest; shortness of breath; severe headaches; visual disturbances, such as blind spots or flashing lights; vaginal bleeding or discharge; breast lumps; swelling of hands or feet; yellow skin or sclera; dark urine; and light-colored stools.
• Teach woman how to perform routine breast self-examination.
• Advise patient not to become pregnant while on estrogen therapy.
• Advise woman of childbearing age to call immediately if she becomes pregnant.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use