or migraine; if examination reveals papilledema or retinal vascular lesions, estrogens should be permanently discontinued May cause fluid retention; women with conditions that might be influenced by this factor, such as cardiac or renal dysfunction, warrant careful observation when estrogen-alone prescribed A few cases of malignant transformation of residual endometrial implants reported in women treated post-hysterectomy with estrogen-alone therapy; for women known to have residual endometriosis post-hysterectomy, addition of progestin should be considered Estrogen therapy should be used with caution in women with hypoparathyroidism as estrogen-induced hypocalcemia may occur Rare cases of anaphylaxis and angioedema reported; may exacerbate symptoms of hereditary angioedema May cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas Premarin cream may weaken latex condoms; the potential for the vaginal cream to weaken and contribute to the failure of condoms, diaphragms, or cervical caps made of latex or rubber should be considered Hypothyroidism Estrogen administration leads to increased thyroid-binding globulin (TBG) levels; women with normal thyroid function can compensate for increased TBG by making more thyroid hormone, thus maintaining free T4 and T3 serum concentrations in the normal range Women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy; these women should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range Venous Thromboembolism Manage appropriately risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) (for example, personal history or family history of VTE, obesity, and systemic lupus erythematosus) Should VTE occur or be suspected, estrogen-alone therapy should be discontinued immediately Pregnancy Category: X Lactation: Distributed in human breast milk; caution when breast feeding, estrogens may decrease the quantity and quality of milkPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Estrogens act through binding to nuclear receptors in estrogen-responsive tissues Absorption Peak plasma concentration: 42 pg/mL (estrone); 12.8 pg/mL (estradiol) Peak plasma time: 7.4 hr (estrone); 8.5 hr (estradiol) AUC: 826 pg•hr/mL (estrone); 231 pg•hr/mL (estradiol) Distribution Protein binding: Largely bound to sex hormone binding globulin (SHBG) and albumin Widely distributed throughout body, higher concentration in sex hormone target organs Metabolism Liver Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is a major urinary metabolite Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the intestine followed by reabsorption Elimination Excretion: Estradiol, estrone, and estriol are excreted in the urine along with glucuronide and sulfate conjugates No images available for this drug. No images available for this drug.A Patient Handout is not currently available for this monograph.Print FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.Create Your List of PlansAdding plans allows you to:View the formulary and any restrictions for each plan.Manage and view all your plans together – even plans in different states.Compare formulary status to other drugs in the same class.Access your plan list on any device – mobile or desktop. The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. View explanations for tiers and restrictions Tier Description 1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs. 2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs. 3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs. 4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. NC NOT COVERED – Drugs that are not covered by the plan. Code Definition PA Prior Authorization Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription. 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