Version July 2025
Estrogens increase the risk of endometrial cancer. Close clinical surveillance of all women taking estrogens is important. Adequate diagnostic measures, including endometrial sampling when indicated, to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. There is no evidence that the use of "natural" estrogens results in a different endometrial risk profile than synthetic estrogens at equivalent estrogen doses.
Estrogens with and without progestins should not be used for the prevention of cardiovascular disease. The Women's Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5 years of treatment with oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone (2.5 mg), relative to placebo.
The Women's Health Initiative (WHI) study reported increased risks of invasive breast cancer in postmenopausal women (50 to 79 years of age) during 5 years of treatment with oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone (2.5 mg) relative to placebo.
The Women's Health Initiative Memory Study (WHIMS) a substudy of WHI, reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with oral conjugated estrogens plus medroxyprogesterone acetate relative to placebo. It is unknown whether this finding applies to younger postmenopausal women or to women taking estrogen alone therapy.
Other doses of conjugated estrogens with medroxyprogesterone acetate, and other combinations and dosage forms of estrogens and progestins were not studied in the WHI clinical trials and, in the absence of comparable data, these risks should be assumed to be similar. Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
Breast cancer, metastatic (appropriately selected patients): Males and postmenopausal females: Oral: 10 mg 3 times/day for at least 3 months.
Prostate cancer, advanced: Oral: 1.25 to 2.5 mg 3 times/day.
Secondary amenorrhea, hypoestrogenism (alternative agent):
Manufacturer’s labeling: Oral: 1.25 mg/day cyclically (3 weeks on and 1 week off). Adjust dosage upward or downward, according to the severity of symptoms and patient response. For maintenance, adjust dosage to lowest level that will provide effective control. Estrogen is given with a progestogen (ie, a natural progesterone or synthetic progestin) in a patient with a uterus.
Vasomotor symptoms associated with menopause (alternative agent): Note: For use in symptomatic patients who are <60 years of age or within 10 years of menopause who do not have contraindications to hormone therapy (eg, breast cancer) (Ref). Nonoral estrogen preparations are preferred in patients with hypertriglyceridemia, risk factors for venous thromboembolic disease, active gallbladder disease, and/or migraine headache with aura (Ref). Initiate at the lowest dose and increase approximately every 4 weeks as needed to relieve symptoms (Ref). Evaluate routinely to minimize drug exposure and optimize administration route. Younger patients (eg, bilateral oophorectomy) may require higher doses. In patients with a uterus, give estrogen with a progestogen (ie, a natural progesterone or synthetic progestin), dosed either cyclically (preferred in late menopausal transition or early postmenopause) or continuously (preferred if >2 to 3 years postmenopause) (Ref).
Oral: Initial: 0.3 mg once daily. Dosage range: 0.3 to 1.25 mg once daily; dosed either cyclically or continuously (Ref).
Duration of therapy: Not clearly established; continued use may be appropriate in patients ≥60 years of age or >10 years after menopause with a low risk of cardiovascular disease and breast cancer and with persistent vasomotor symptoms after attempted taper/discontinuation of estrogen and trial of alternative therapies. Evaluate routinely for comorbidities and appropriateness of lower doses, nonoral routes of administration (preferred in patients ≥60 years of age), choice of progestogen, and discontinuation of therapy (Ref).
Vulvar and vaginal atrophy associated with menopause: Oral: 0.3 to ≥1.25 mg/day, initiate at the lowest dose and adjust based on patient response. Administer cyclically (3 weeks on and 1 week off).
No dosage adjustment provided in manufacturer's labeling; use with caution.
No dosage adjustment provided in manufacturer's labeling; use is contraindicated with hepatic impairment or dysfunction.
Note: The Beers Criteria recommends avoiding systemic estrogen therapy in postmenopausal patients ≥65 years of age (independent of diagnosis or condition). In older postmenopausal patients already taking systemic estrogens, consider deprescribing (Ref). Duration of use is not clearly established; continued use may be appropriate in patients ≥60 years of age or >10 years after menopause with a low risk of cardiovascular disease and breast cancer with persistent vasomotor symptoms after attempted taper/discontinuation of estrogen and trial of alternative therapies. Evaluate routinely for comorbidities and appropriateness of lower doses, nonoral routes of administration (preferred in patients ≥60 years of age), choice of progestogen, and discontinuation of therapy (Ref).
Refer to adult dosing.
The following adverse drug reactions are derived from product labeling unless otherwise specified. Adverse reactions may be reported with estrogens and progestin therapy.
Postmarketing:
Cardiovascular: Acute myocardial infarction, deep vein thrombosis, edema, increased blood pressure, pulmonary embolism, thrombophlebitis, venous thromboembolism (including superficial venous thromboembolism)
Dermatologic: Chloasma, erythema multiforme, erythema nodosum, hemorrhagic eruption of the skin, loss of scalp hair, pruritus, skin rash, urticaria
Endocrine & metabolic: Amenorrhea, change in libido, exacerbation of porphyria, galactorrhea not associated with childbirth, hirsutism, hypocalcemia, impaired glucose tolerance, increased serum triglycerides, menstrual disease (abnormal withdrawal bleeding, alterations in menstrual patterns, change in menstrual flow, spotting), premenstrual-like syndrome, weight gain, weight loss
Gastrointestinal: Abdominal cramps, bloating, gallbladder disease, nausea, pancreatitis, vomiting
Genitourinary: Breakthrough bleeding, breast hypertrophy, breast tenderness, change in cervical ectropion, change in cervical secretions, cystitis-like syndrome, dysmenorrhea, endometrial carcinoma, endometrial hyperplasia, fibrocystic breast changes, malignant neoplasm of breast, mastalgia, nipple discharge, ovarian carcinoma, uterine fibroids (increased size), vaginitis, vulvovaginal candidiasis
Hepatic: Cholestatic jaundice, exacerbation of hepatic hemangioma (enlargement)
Hypersensitivity: Anaphylaxis, angioedema, nonimmune anaphylaxis
Nervous system: Cerebrovascular accident, chorea, dementia, depression, dizziness, exacerbation of epilepsy, headache, irritability, migraine, mood disorder, nervousness
Neuromuscular & skeletal: Arthralgia, lower limb cramp
Ophthalmic: Change in corneal curvature (steepening), contact lens intolerance, retinal thrombosis
Respiratory: Exacerbation of asthma
Hypersensitivity to estrogens or any component of the formulation; undiagnosed abnormal genital bleeding; DVT or PE (current or history of); active or recent (within 1 year) arterial thromboembolic disease (eg, stroke, MI); breast cancer (known, suspected or history of), except in appropriately selected patients being treated for metastatic disease; known or suspected estrogen-dependent tumor; hepatic dysfunction or disease; known or suspected pregnancy
Concerns related to adverse effects:
• Breast cancer: Estrogen with or without progestogen for the management of menopausal symptoms may be associated with an increased risk of breast cancer. The risk of breast cancer in patients who are postmenopausal on hormone therapy may depend upon type of estrogen and/or progestogen, dose, timing of therapy initiation, duration of therapy, route of administration, and individual patient characteristics (AACE/ACE [Cobin 2017]; NAMS 2022). Hormone therapy may be associated with increased breast density (NAMS 2022); an increase in abnormal mammogram findings requiring further evaluation has been reported with estrogen alone or in combination with progestogen therapy. Estrogen use may lead to severe hypercalcemia in patients with breast cancer and bone metastases; discontinue estrogen if hypercalcemia occurs.
• Dementia: Do not use estrogens with or without progestogen to prevent dementia. In the Women’s Health Initiative Memory Study (WHIMS), an increased incidence of dementia was observed in women ≥65 years of age taking conjugated estrogens (CE) alone or in combination with MPA. Because the Women’s Health Initiative (WHI) memory studies were conducted in patients ≥65 years of age, it is unknown if these findings apply to younger patients who are postmenopausal. However, hormone therapy is not recommended at any age to prevent or treat cognitive decline or dementia (NAMS 2022).
• Endometrial cancer: The use of unopposed estrogen in patients with a uterus is associated with an increased risk of endometrial cancer. The addition of a progestogen to estrogen therapy may decrease the risk of endometrial hyperplasia, a precursor to endometrial cancer. Perform adequate diagnostic measures, including endometrial sampling if indicated, to rule out malignancy in patients who are postmenopausal with undiagnosed abnormal vaginal bleeding. There is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens at equivalent estrogen doses. The risk of endometrial cancer appears to be dose and duration dependent, greatest with use ≥5 years, and may persist following discontinuation of therapy. The use of a progestogen is not generally required when low doses of estrogen are used locally for vaginal atrophy, although long term data (>1 year) supporting this recommendation are lacking (NAMS 2022).
• Endometriosis: Estrogens may exacerbate endometriosis. Malignant transformation of residual endometrial implants has been reported posthysterectomy with unopposed estrogen therapy. Consider adding a progestogen in patients with residual endometriosis posthysterectomy.
• Inherited thrombophilia: Patients with inherited thrombophilias (eg, protein C or S deficiency) may have increased risk of venous thromboembolism (DeSancho 2010; van Vlijmen 2011).
• Lipid effects: Estrogen compounds are generally associated with lipid effects such as increased HDL-cholesterol and decreased LDL-cholesterol. Triglycerides may also be increased in patients with preexisting hypertriglyceridemia; discontinue if pancreatitis occurs.
• Ovarian cancer: Available information related to the use of menopausal estrogen or estrogen/progestogen therapy and risk of ovarian cancer is inconsistent. If an association is present, the absolute risk is likely rare and may be influenced by duration of therapy (ES [Stuenkel 2015]; NAMS 2022).
• 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.
Disease-related concerns:
• Asthma: Use caution in patients with asthma; may exacerbate disease.
• Cardiovascular disease: Do not use estrogens with or without progestogen to prevent cardiovascular disease. The WHI studies reported an increased risk of deep vein thrombosis (DVT) and stroke with CE and an increased risk of DVT, stroke, pulmonary emboli (PE) and myocardial infarction (MI) with CE with MPA in patients who are postmenopausal and 50 to 79 years of age. Additional risk factors include diabetes mellitus, hypercholesterolemia, hypertension, SLE, obesity, tobacco use, and/or history of venous thromboembolism (VTE). Adverse cardiovascular events have also been reported in patients taking estrogens for prostate cancer. Manage risk factors appropriately; discontinue use immediately if adverse cardiovascular events occur or are suspected. Due to possible lower risk of thrombotic events, transdermal administration may be preferred for treating vasomotor symptoms of menopause in patients with risk factors for cardiovascular disease (AACE/ACE [Cobin 2017]; ACOG 556 2013; ES [Stuenkel 2015]).
• Diabetes mellitus: May impair glucose tolerance; use caution in patients with diabetes mellitus. Prior to therapy, consider age, cardiovascular, and metabolic risk factors in patients previously diagnosed with diabetes (AACE/ACE [Cobin 2017]).
• Diseases exacerbated by fluid retention: Use with caution in patients with diseases which may be exacerbated by fluid retention, including cardiac or renal dysfunction.
• Epilepsy: Use caution with epilepsy; may exacerbate disease.
• Gallbladder disease: Use of postmenopausal estrogen may be associated with an increased risk of gallbladder disease requiring surgery.
• Hepatic dysfunction: Estrogens are poorly metabolized in patients with hepatic dysfunction. Use caution with a history of cholestatic jaundice associated with prior estrogen use or pregnancy. Discontinue if jaundice develops or if acute or chronic hepatic disturbances occur.
• Hepatic hemangiomas: Use with caution in patients with hepatic hemangiomas; may exacerbate disease.
• Hereditary angioedema: Exogenous estrogens may exacerbate angioedema symptoms in patients with hereditary angioedema.
• Hypocalcemia: Use with caution in patients with severe hypocalcemia.
• Migraine: Use caution with migraine; may exacerbate disease.
• Porphyria: Use with caution in patients with porphyria; may exacerbate disease.
• SLE: Use with caution in patients with SLE; may exacerbate disease.
Special populations:
• Surgery: Whenever possible, discontinue estrogens at least 4 to 6 weeks prior to elective surgery associated with an increased risk of thromboembolism or during periods of prolonged immobilization.
Other warnings/precautions:
• Duration of use: Not clearly established; continued use may be appropriate in patients ≥60 years of age or >10 years after menopause with a low risk of cardiovascular disease and breast cancer with persistent vasomotor symptoms after attempted taper/discontinuation of estrogen and trial of alternative therapies. Evaluate routinely for comorbidities and appropriateness of lower doses, nonoral routes of administration (preferred in patients ≥60 years of age), choice of progestogen, and discontinuation of therapy (NAMS 2022).
• Genitourinary syndrome of menopause: Low-dose vaginal estrogen is preferred over systemic therapy for genitourinary syndrome of menopause in the absence of vasomotor symptoms due to increased efficacy and decreased systemic effects (eg, cardiovascular effects, cancer risk) (Crandall 2018; NAMS 2022).
• Risks vs benefits: When used for the relief of menopausal symptoms, the benefit-risk of hormone therapy is most favorable if started in patients who have no contraindications to therapy, are <60 years of age, within 10 years of menopause onset, have a favorable lipid profile, and do not have the factor V Leiden genotype or metabolic syndrome. Consider cardiovascular disease risk factors when evaluating therapy and route of administration (AACE/ACE [Cobin 2017]; NAMS 2022). Use for the shortest duration possible at the lowest effective dose consistent with treatment goals. Reevaluate patients as clinically appropriate to determine if treatment is still necessary. Available data related to treatment risks are from WHI studies, which evaluated oral CE 0.625 mg with or without MPA 2.5 mg relative to placebo in patients who were postmenopausal. Other combinations and dosage forms of estrogens and progestins were not studied. Assume outcomes reported from clinical trials using CE with or without MPA to be similar for other doses and other dosage forms of estrogens and progestogens until comparable data becomes available.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Menest: 0.3 mg, 0.625 mg, 1.25 mg, 2.5 mg
No
Tablets (Menest Oral)
0.3 mg (per each): $2.27
0.625 mg (per each): $3.22
1.25 mg (per each): $4.50
2.5 mg (per each): $6.39
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Hazardous agent (NIOSH 2024 [table 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Breast cancer, metastatic: Treatment of metastatic breast cancer (palliation) in appropriately selected males and postmenopausal females.
Prostate cancer: Palliative therapy of advanced prostatic carcinoma.
Secondary amenorrhea, hypoestrogenism: Treatment of hypoestrogenism due to hypogonadism, castration, or primary ovarian failure.
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 symptoms of vulvar and vaginal atrophy associated with menopause.
Limitations of use: When used solely for the treatment of vulvar and vaginal atrophy, consider topical vaginal products.
Note: The International Society for the Study of Women’s Sexual Health and The North American Menopause Society have endorsed the term genitourinary syndrome of menopause (GSM) as new terminology for vulvovaginal atrophy. The term GSM encompasses all genital and urinary signs and symptoms associated with a loss of estrogen due to menopause (Portman 2014).
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (contraindicated in pregnancy) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).
Beers Criteria: Estrogens (oral or topical patch products only), with or without progestins, are identified in the Beers Criteria as potentially inappropriate medications to be avoided in postmenopausal patients ≥65 years of age (independent of diagnosis or condition) due to their carcinogenic potential (breast and endometrium) and lack of cardioprotection or cognitive protection. Starting therapy in postmenopausal patients ≥60 years of age has greater risks (eg, heart disease, stroke, blood clots, dementia) than benefits. In postmenopausal patients already taking systemic estrogens, consider deprescribing (Beers Criteria [AGS 2023]).
Estragyn: Brand name for estrone vaginal [Canada] and estrogens esterified oral [Canada]
Substrate of CYP1A2 (Minor), CYP2B6 (Minor), CYP2C9 (Minor), CYP2E1 (Minor), CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Ajmaline: Estrogen Derivatives may increase adverse/toxic effects of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor
Anastrozole: Estrogen Derivatives may decrease therapeutic effects of Anastrozole. Risk X: Avoid
Anthrax Immune Globulin (Human): Estrogen Derivatives may increase thrombogenic effects of Anthrax Immune Globulin (Human). Risk C: Monitor
Antidiabetic Agents: Hyperglycemia-Associated Agents may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
C1 Inhibitors: Estrogen Derivatives may increase thrombogenic effects of C1 Inhibitors. Risk C: Monitor
Chenodiol: Estrogen Derivatives may decrease therapeutic effects of Chenodiol. Risk C: Monitor
Chlorprothixene: Estrogen Derivatives may increase adverse/toxic effects of Chlorprothixene. Estrogen Derivatives may increase therapeutic effects of Chlorprothixene. Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
Corticosteroids (Systemic): Estrogen Derivatives may increase serum concentration of Corticosteroids (Systemic). Risk C: Monitor
Cosyntropin: Coadministration of Estrogen Derivatives and Cosyntropin may alter diagnostic results. Management: Discontinue estrogen containing drugs 4 to 6 weeks prior to cosyntropin (ACTH) testing. Risk D: Consider Therapy Modification
CYP3A4 Inducers (Moderate): May decrease serum concentration of Estrogen Derivatives. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Estrogen Derivatives. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of Estrogen Derivatives. Risk C: Monitor
Dantrolene: Estrogen Derivatives may increase hepatotoxic effects of Dantrolene. Risk C: Monitor
Exemestane: Estrogen Derivatives may decrease therapeutic effects of Exemestane. Risk X: Avoid
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Growth Hormone Analogs: Estrogen Derivatives may decrease therapeutic effects of Growth Hormone Analogs. Management: Initiate somapacitan at 2 mg once weekly in patients receiving oral estrogens. Monitor for reduced efficacy of growth hormone analogs; increased doses may be required. Risk D: Consider Therapy Modification
Hemin: Estrogen Derivatives may decrease therapeutic effects of Hemin. Risk X: Avoid
Hyaluronidase: Estrogen Derivatives may decrease therapeutic effects of Hyaluronidase. Risk C: Monitor
Hydrocortisone (Systemic): Estrogen Derivatives may increase serum concentration of Hydrocortisone (Systemic). Estrogen Derivatives may decrease serum concentration of Hydrocortisone (Systemic). Risk C: Monitor
Immune Globulin: Estrogen Derivatives may increase thrombogenic effects of Immune Globulin. Management: Use the lowest dose of immune globulin and minimum infusion rate practicable during coadministration with estrogen derivatives. Risk D: Consider Therapy Modification
Indium 111 Capromab Pendetide: Coadministration of Estrogen Derivatives and Indium 111 Capromab Pendetide may alter diagnostic results. Risk X: Avoid
LamoTRIgine: Estrogen Derivatives may decrease serum concentration of LamoTRIgine. Risk C: Monitor
Lenalidomide: Estrogen Derivatives may increase thrombogenic effects of Lenalidomide. Risk C: Monitor
Melatonin: Estrogen Derivatives may increase serum concentration of Melatonin. Risk C: Monitor
MetyraPONE: Coadministration of Estrogen Derivatives and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking estrogen derivatives. Risk D: Consider Therapy Modification
Mivacurium: Estrogen Derivatives may increase serum concentration of Mivacurium. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May increase thrombogenic effects of Estrogen Derivatives. Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may increase serum concentration of Estrogen Derivatives. Risk C: Monitor
Ospemifene: Estrogen Derivatives may increase adverse/toxic effects of Ospemifene. Risk X: Avoid
Pomalidomide: Estrogen Derivatives may increase thrombogenic effects of Pomalidomide. Risk C: Monitor
Protease Inhibitors: May decrease serum concentration of Estrogen Derivatives. Protease Inhibitors may increase serum concentration of Estrogen Derivatives. Risk C: Monitor
Raloxifene: Estrogen Derivatives may increase adverse/toxic effects of Raloxifene. Risk X: Avoid
ROPINIRole: Estrogen Derivatives may increase serum concentration of ROPINIRole. Risk C: Monitor
Succinylcholine: Estrogen Derivatives may increase serum concentration of Succinylcholine. Risk C: Monitor
Tacrolimus (Systemic): Estrogen Derivatives may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Thalidomide: Estrogen Derivatives may increase thrombogenic effects of Thalidomide. Risk C: Monitor
Thyroid Products: Estrogen Derivatives may decrease therapeutic effects of Thyroid Products. Risk C: Monitor
Tranexamic Acid: Estrogen Derivatives may increase thrombogenic effects of Tranexamic Acid. Risk X: Avoid
Ursodiol: Estrogen Derivatives may decrease therapeutic effects of Ursodiol. Risk C: Monitor
Folic acid absorption may be decreased.
Estrogens esterified are contraindicated for use during pregnancy.
In general, the use of estrogen and progestogen as in combination hormonal contraceptives have not been associated with teratogenic effects when inadvertently taken early in pregnancy.
Estrogens are present in breast milk.
Estrogen has been shown to decrease the quantity and quality of human milk. The manufacturer recommends caution be used if administered to a patient who is breastfeeding.
Prior to therapy, baseline risk for breast cancer and CVD. During therapy, age appropriate breast and pelvic exams; blood pressure; unscheduled bleeding lasting >6 months for endometrial pathology (sooner in patients with obesity, diabetes, or a history of endometrial cancer); serum triglycerides (2 weeks after starting therapy in patients with baseline level >200 mg/dL); TSH (6 to 12 weeks after starting oral therapy in patients taking thyroid replacement) (ES [Stuenkel 2015]).
Menopausal symptoms: Efficacy beginning 1 to 3 months after starting therapy, then every 6 to 12 months as appropriate. Duration of treatment should be evaluated at least annually (ES [Stuenkel 2015]).
Note: Monitoring of FSH and serum estradiol is not useful when managing vasomotor symptoms or genitourinary symptoms of menopause.
Esterified estrogens contain a mixture of estrogenic substances; the principle component is estrone. Preparations contain 75% to 85% sodium estrone sulfate and 6% to 15% sodium equilin sulfate such that the total is not <90%. Estrogens are responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Estradiol is the principle intracellular human estrogen and is more potent than estrone and estriol at the receptor level; it is the primary estrogen secreted prior to menopause. In males and following menopause in females, estrone and estrone sulfate are more highly produced. Estrogens modulate the pituitary secretion of gonadotropins, luteinizing hormone, and follicle-stimulating hormone through a negative feedback system; estrogen replacement reduces elevated levels of these hormones.
Absorption: Readily
Distribution: Widely distributed; high concentrations in the sex hormone target organs
Protein binding: Bound to sex hormone-binding globulin and albumin
Metabolism: Hepatic; partial metabolism via CYP3A4 enzymes; estradiol is reversibly converted to estrone and estriol; oral estradiol also undergoes enterohepatic recirculation by conjugation in the liver, followed by excretion of sulfate and glucuronide conjugates into the bile, then hydrolysis in the intestine and estrogen reabsorption. Sulfate conjugates are the primary form found in patients who are postmenopausal.
Excretion: Primarily urine (as estradiol, estrone, estriol, and their glucuronide and sulfate conjugates)
