Estrogen Medication Monograph

Indications: Vasomotor symptoms associated with menopause: Treatment of moderate to severe vasomotor symptoms associated with menopause Vulvar and vaginal atrophy associated with menopause: Treatment of moderate to severe vaginal dryness and pain with intercourse, symptoms of vulvar and vaginal atrophy

Dosing (Adults): Varies by indication, dosage form, type and severity of symptoms

Renal Dosing: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied)

Hepatic Impairment: Use is contraindicated with hepatic dysfunction or disease

Contraindications: Angioedema, anaphylactic reaction or hypersensitivity to conjugated estrogens or any component of the formulation; undiagnosed abnormal genital bleeding; DVT or PE; active or history of arterial thromboembolic disease (eg, stroke, MI); breast cancer; estrogen-dependent tumor; hepatic dysfunction or disease; known protein C, protein S, antithrombin deficiency or other known thrombophilic disorders; pregnancy

Warnings/Precautions:

Anaphylaxis: Anaphylaxis requiring emergency medical management has been reported and may develop at any time during therapy. Angioedema involving the face, feet, hands, larynx, and tongue has also been reported

Breast cancer: [US Boxed Warning]: An increased risk of invasive breast cancer was observed in postmenopausal women using conjugated estrogens (CE) in combination with medroxyprogesterone acetate (MPA). This risk may be associated with duration of use and declines once combined therapy is discontinued. An increase in abnormal mammogram findings has also been reported. Estrogen use may lead to severe hypercalcemia in patients with breast cancer and bone metastases. Use is contraindicated in patients with known or suspected breast cancer

Cardiovascular disease: [US Boxed Warning]: Progestin plus estrogen should not be used for the prevention of cardiovascular disease. In the WHI studies, an increased risk of DVT, PE, stroke, and myocardial infarction was observed in women ≥65 years with daily conjugated estrogens combined with medroxyprogesterone. Additional risk factors include diabetes mellitus, hypercholesterolemia, hypertension, SLE, obesity, tobacco use, and/or history of venous thromboembolism (VTE). Discontinue use if adverse cardiovascular events occur or are suspected

Dementia: [US Boxed Warning]: Estrogens with or without progestin should not be used to prevent dementia. In the Women’s Health Initiative Memory Study (WHIMS), an increased incidence of probable dementia was observed in women ≥65 years of age taking CE alone or in combination with MPA

Endometrial cancer: [US Boxed Warning]: The use of unopposed estrogen in women with a uterus is associated with an increased risk of endometrial cancer. The addition of a progestin to estrogen therapy may decrease the risk of endometrial hyperplasia, a precursor to endometrial cancer. The risk of endometrial cancer is dose and duration dependent; risk appears to be greatest with use ≥5 years and may persist following discontinuation of therapy. The use of a progestin is not generally required when low doses of estrogen are used locally for vaginal atrophy

Endometriosis: Estrogens may exacerbate endometriosis. Consider adding a progestin in women with residual endometriosis post-hysterectomy

Inherited thrombophilia: Women with inherited thrombophilias (eg, protein C or S deficiency) may have increased risk of venous thromboembolism (DeSancho 2010; van Vlijmen 2011). Use is contraindicated in women with protein C, protein S, antithrombin deficiency, or other known thrombophilic disorders

Lipid effects: Estrogen compounds are generally associated with lipid effects such as increased HDL-cholesterol and decreased LDL-cholesterol. Triglycerides may also be increased; discontinue if pancreatitis occurs

Ovarian cancer: Postmenopausal estrogens with or without progestins may increase the risk of ovarian cancer; however, the absolute risk to an individual woman is small

Retinal vascular thrombosis: Estrogens may cause retinal vascular thrombosis; discontinue if migraine, loss of vision, proptosis, diplopia, or other visual disturbances occur; discontinue permanently if papilledema or retinal vascular lesions are observed on examination

Diseases exacerbated by fluid retention: Use with caution in patients with diseases which may be exacerbated by fluid retention, including cardiac or renal dysfunction

Surgical patients: Whenever possible, estrogens should be discontinued at least 4 to 6 weeks prior to elective surgery associated with an increased risk of thromboembolism or during periods of prolonged immobilization

[US Boxed Warning]: Progestin with estrogens should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. Before prescribing estrogen therapy to postmenopausal women, the risks and benefits must be weighed for each patient. Patients should be reevaluated as clinically appropriate to determine if treatment is still necessary

Drug Interactions: Anastrozole: Estrogen Derivatives may diminish the therapeutic effect of Anastrozole. Anticoagulants: Estrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. Exemestane: Estrogen Derivatives may diminish the therapeutic effect of Exemestane. Ospemifene: Estrogen Derivatives may enhance the adverse/toxic effect of Ospemifene. TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Thyroid replacement therapy: Estrogens may increase thyroid-binding globulin levels leading to increased circulating total thyroid hormone levels. Women on thyroid replacement therapy may require higher doses of thyroid hormone while receiving estrogens

Please speak with your doctor or pharmacist about other possible drug interactions as this list is not all-inclusive

Adverse Reactions: Headache, breast tenderness, irregular vaginal bleeding or spotting, stomach or abdominal cramps, bloating, nausea and vomiting, hair loss, fluid retention

Patient Education:

What should I tell my doctor about before taking this medication?

Bleeding disorders, blood clots, a higher risk of having a blood clot, breast cancer, liver problems or liver tumor, heart attack, stroke, or a tumor where estrogen makes it grow, unexplained vaginal bleeding, if you are pregnant or may be pregnant, other medications you take including those that are over-the-counter

When and how do I take this medication?

This medication is usually used once daily, without regard to time of day. If you have a uterus, talk with your healthcare provider about whether the addition of a progestin is right for you

What side effects should I call my doctor about right away?

Vaginal bleeding; pelvic pain or breast pain; a lump in the breast or nipple discharge; signs of a stroke such as confusion, weakness on one side of the body, trouble speaking or thinking; signs of a blood clot such as pain, swelling, warmth, or numbness in your arm or leg; signs of a heart attack such as chest pain or pressure, sudden shoulder pain; swollen lips, tongue or face