Version July 2025
There is an increased risk of endometrial cancer in a patient with a uterus who uses unopposed estrogens. Conjugated estrogens/bazedoxifene has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Perform adequate diagnostic measures, including directed or random endometrial sampling when indicated, to rule out malignancy in postmenopausal patients with undiagnosed persistent or recurring abnormal genital bleeding.
Estrogen therapy should not be used for the prevention of cardiovascular disease.
The Women's Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (0.625 mg) alone, relative to placebo.
Estrogen therapy should not be used for the prevention of dementia. The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older during 5.2 years of treatment with daily conjugated estrogens (0.625 mg) alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.
Women taking conjugated estrogens/bazedoxifene should not take additional estrogens. Only daily oral conjugated estrogen (0.625 mg) was studied in the estrogen-alone substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events and dementia to lower conjugated estrogen doses, other routes of administration, or other estrogen-alone products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risk of estrogen-alone therapy, taking into account her individual risk profile. Estrogens should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
Osteoporosis, postmenopausal, prevention (alternative agent):
Note: May be used as an alternative to first-line therapies to prevent bone loss in patients with a uterus who have moderate to severe vasomotor symptoms of menopause (Ref). In patients without menopausal vasomotor symptoms who require fracture risk reduction, other first-line therapies are preferred. Avoid use in patients >60 years of age or who are >10 years beyond menopause (Ref). Ensure adequate calcium and vitamin D intake during therapy.
Oral: Conjugated estrogens 0.45 mg and bazedoxifene 20 mg once daily.
Duration of therapy: The optimal duration of therapy has not been established. Estrogens should be used for the shortest duration possible consistent with treatment goals (Ref). Extended use may be considered in patients in whom alternative therapies are not appropriate and when benefits of therapy are expected to outweigh risks (Ref).
Discontinuation of therapy: If continued osteoporosis preventive therapy is necessary, switch to antiresorptive therapy (eg, with a bisphosphonate) following discontinuation (Ref).
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 (Ref). Combination products are only indicated for patients with a uterus; the selective estrogen receptor modulator component prevents estrogen therapy-associated endometrial hyperplasia. Generally reserved for patients unable to tolerate oral progestogens or patients who experience breast tenderness with standard hormone therapy (Ref).
Oral: Conjugated estrogens 0.45 mg/bazedoxifene 20 mg once daily.
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), and discontinuation of therapy (Ref).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Use is not recommended.
Use is contraindicated with hepatic dysfunction or disease.
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. Use in females >75 years of age is not recommended (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Percentages as reported with combination product.
1% to 10%:
Central nervous system: Dizziness (5%)
Gastrointestinal: Diarrhea (8%), nausea (8%), dyspepsia (7%), upper abdominal pain (7%)
Neuromuscular & skeletal: Muscle spasm (9%), neck pain (5%)
Respiratory: Oropharyngeal pain (7%)
Hypersensitivity to estrogens, bazedoxifene, or any component of the formulation; undiagnosed abnormal uterine bleeding; active or past history of venous thromboembolism (VTE) (eg, PE, DVT); active or history of arterial thromboembolic disease (eg, stroke, MI); carcinoma of the breast (known, suspected or history of); estrogen-dependent tumor (known or suspected); hepatic impairment or disease; known protein C, protein S, or antithrombin deficiency or other known thrombophilic disorders; pregnancy.
Canadian labeling: Additional contraindications (not in US labeling): Active thrombophlebitis; endometrial hyperplasia; partial or complete loss of vision due to ophthalmic vascular disease.
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 receiving 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: Because the WHI memory studies were conducted in females ≥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 (AACE [Goodman 2011]; NAMS 2022).
• 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: 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 (AACE [Goodman 2011]; ES [Stuenkel 2015]; NAMS 2022).
• Retinal vascular thrombosis: Estrogens may cause retinal vascular thrombosis; discontinue pending examination 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.
• Carbohydrate intolerance: May impair glucose tolerance; use caution in patients with diabetes. Prior to therapy, consider age, cardiovascular and metabolic risk factors in patients previously diagnosed with diabetes (AACE/ACE [Cobin 2017]).
• Cardiovascular disease: Estrogens and bazedoxifene are known to increase the risk of venous thromboembolism (VTE). Additional risk factors include diabetes mellitus, hypercholesterolemia, hypertension, SLE, obesity, tobacco use, and/or history of VTE. 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]).
• Diseases exacerbated by fluid retention: Use with caution in patients with diseases which may be exacerbated by fluid retention, including cardiac or renal dysfunction.
• Endometrial hyperplasia: Risk may be increased in patients taking combination estrogens.
• 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 females with hereditary angioedema.
• Hypoparathyroidism: Use caution in patients with hypoparathyroidism; estrogen-induced hypocalcemia may occur.
• 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.
Concurrent drug therapy issues:
• Thyroid replacement therapy: Estrogens may increase thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels. Females on thyroid replacement therapy may require higher doses of thyroid hormone while receiving estrogens.
Special populations:
• Overweight/Obese: Bazedoxifene exposure is decreased in females with a BMI >27 kg/m2 which may be associated with an increased risk of endometrial hyperplasia. Females with a BMI >34 kg/m2 or >32.2 kg/m2 were excluded from some initial vasomotor or osteoporosis studies, respectively (Lindsay 2009; Pinkerton 2009). Regardless of BMI, monitor to rule out malignancy in patients who are postmenopausal with undiagnosed persistent or recurrent abnormal genital bleeding.
• 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).
• Laboratory changes: The use of estrogens and/or progestogens may change the results of some laboratory tests (eg, coagulation factors, lipids, glucose tolerance, binding proteins). The dose, route, and the specific estrogen/progestogen influences these changes.
• Osteoporosis use: In patients with premature menopause, hormone therapy to prevent bone loss may be used unless otherwise contraindicated; reassess therapy when the average age of menopause is reached. It is also an appropriate bone-active therapy for females with vasomotor symptoms who are <60 years of age or within 10 years of menopause onset. Use may be considered for patients at high risk of fractures who are not candidates for other osteoporosis therapies (NAMS 2022).
• Risks vs benefits: When used for the relief of menopausal symptoms or increased risk of bone fracture/loss, 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 risk factors for cardiovascular disease when evaluating therapy and route of administration (AACE/ACE [Cobin 2017]; NAMS 2022). Do not take progestogens or additional estrogen agonists/antagonists. Reevaluate patients as clinically appropriate to determine if treatment is still necessary. Available data related to treatment risks are from Women’s Health Initiative (WHI) studies, which evaluated oral CE 0.625 mg relative to placebo in females who were postmenopausal.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Duavee: Conjugated estrogens 0.45 mg and bazedoxifene acetate 20 mg
No
Tablets (Duavee Oral)
0.45-20 mg (per each): $8.11
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Extended Release, Oral:
Duavive: Conjugated estrogens 0.45 mg and bazedoxifene 20 mg
Administer without regard to meals; swallow tablets whole.
Estrogens (conjugated) is a 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.
Osteoporosis, postmenopausal, prevention: Prevention of postmenopausal osteoporosis in patients with a uterus.
Limitations of use: For use only in patients at significant risk of postmenopausal osteoporosis; consider use of nonestrogen medications.
Vasomotor symptoms: Treatment of moderate to severe vasomotor symptoms associated with menopause in patients with a uterus.
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]).
Refer to individual components.
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
Atazanavir: May increase serum concentration of UGT1A1 Substrates. Management: Do not use UGT1A1 substrates for which small increases in exposure can cause serious adverse effects together with atazanavir, and use caution with any UGT1A1 substrate, even when small changes in exposure are less likely to cause serious adverse effects. Risk D: Consider Therapy Modification
Belumosudil: May increase serum concentration of UGT1A1 Substrates. Management: Avoid coadministration of belumosudil with substrates of UGT1A1 for which minimal concentration increases can cause serious adverse effects. If coadministration is required, dose reductions of the UGT1A1 substrate may be required. Risk D: Consider Therapy Modification
C1 Inhibitors: Estrogen Derivatives may increase thrombogenic effects of C1 Inhibitors. Risk C: Monitor
CarBAMazepine: May decrease serum concentration of Bazedoxifene. This may lead to loss of efficacy or, if bazedoxifene is combined with estrogen therapy, an increased risk of endometrial hyperplasia. 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
CloZAPine: CYP1A2 Inhibitors (Weak) may increase serum concentration of CloZAPine. 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
Fezolinetant: CYP1A2 Inhibitors (Weak) may increase serum concentration of Fezolinetant. Risk X: Avoid
Fluoroestradiol F18: Coadministration of Selective Estrogen Receptor Modulators and Fluoroestradiol F18 may alter diagnostic results. Risk X: Avoid
Fosphenytoin-Phenytoin: May decrease serum concentration of Bazedoxifene. Risk C: Monitor
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
Mitapivat: May decrease serum concentration of UGT1A1 Substrates. Risk C: Monitor
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
Ospemifene: Selective Estrogen Receptor Modulators may increase adverse/toxic effects of Ospemifene. Ospemifene may also enhance adverse/toxic effects of other Selective Estrogen Receptor Modulators. Risk X: Avoid
PHENobarbital: May decrease serum concentration of Bazedoxifene. This may lead to loss of efficacy or, if bazedoxifene is combined with estrogen therapy, an increased risk of endometrial hyperplasia. Risk C: Monitor
Pomalidomide: Estrogen Derivatives may increase thrombogenic effects of Pomalidomide. Risk C: Monitor
Primidone: May decrease serum concentration of Bazedoxifene. This may lead to loss of efficacy or, if bazedoxifene is combined with estrogen therapy, an increased risk of endometrial hyperplasia. 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
RifAMPin: May decrease serum concentration of Bazedoxifene. This may lead to loss of efficacy or, if bazedoxifene is combined with estrogen therapy, an increased risk of endometrial hyperplasia. Risk C: Monitor
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
Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase serum concentration of Theophylline Derivatives. Risk C: Monitor
Thyroid Products: Estrogen Derivatives may decrease therapeutic effects of Thyroid Products. Risk C: Monitor
TiZANidine: CYP1A2 Inhibitors (Weak) may increase serum concentration of TiZANidine. Management: Avoid the use of tizanidine with weak CYP1A2 inhibitors when possible. If combined, monitor closely for increased tizanidine toxicities (eg, hypotension, bradycardia, drowsiness). Tizanidine dose reduction or discontinuation may be necessary. Risk D: Consider Therapy Modification
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
This combination product is approved for use in postmenopausal patients only. Use is contraindicated during pregnancy.
Estrogens are present in breast milk; excretion of bazedoxifene is not known.
Also refer to the Estrogens (Conjugated/Equine) monograph for additional information.
Ensure adequate calcium and vitamin D intake when used for the prevention of osteoporosis.
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 who are obese, diabetic, or have 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]).
Osteoporosis, prevention: Bone density measurement
Vasomotor symptoms: Efficacy beginning 1 to 3 months after starting therapy, then every 6 to 12 months as appropriate. Evaluate duration of treatment at least annually (ES [Stuenkel 2015]).
Note: Monitoring of FSH and serum estradiol is not useful when managing vasomotor symptoms of menopause
Conjugated estrogens contain a mixture of estrone sulfate, equilin sulfate, 17 alpha-dihydroequilin, 17 alpha-estradiol and 17 beta-dihydroequilin. Bazedoxifene is a selective estrogen receptor modulator (SERM). Conjugated estrogens act as an estrogen agonist and bazedoxifene acts as an estrogen agonist/antagonist depending on the specific tissue. The combination of a SERM and estrogen [referred to as a tissue-selective estrogen complex (TSEC)] provides relief of vasomotor symptoms and maintenance of bone mineral density in postmenopausal females with a uterus, while reducing the risk of endometrial hyperplasia observed with estrogen use alone (Pickar 2009).
Onset:
Relief of vasomotor symptoms: A significant reduction in the number and severity of moderate/severe hot flashes was observed after 4 weeks of therapy (Pinkerton, 2009).
Osteoporosis: A significant increase in BMD measured at the lumbar spine and hip was observed at 12 months of therapy (Lindsay, 2009).
Absorption: Conjugated estrogens: Well-absorbed from the gastrointestinal tract.
Distribution: Bazedoxifene: Vd: ~15 L/kg.
Protein binding:
Bazedoxifene: 98% to 99%; does not bind to sex-hormone binding globulin.
Conjugated estrogens: Binds to sex-hormone-binding globulin and albumin.
Metabolism:
Bazedoxifene: Metabolized via glucuronidation; forms metabolites; little or no CYP mediated metabolism; undergoes hepatic recirculation.
Conjugated estrogens: Hepatic via CYP3A4; estradiol is converted to estrone and estriol; also undergoes enterohepatic recirculation; estrone sulfate is the main metabolite in females who are postmenopausal.
Bioavailability: Bazedoxifene: ~6%.
Half-life elimination: Bazedoxifene: ~30 hours; Total estrone: ~17 hours.
Time to peak: Bazedoxifene: ~2.5 hours; Total estrone: ~6.5 hours.
Excretion:
Conjugated estrogens: Urine (primarily estriol, also as estradiol, estrone, and conjugates).
Bazedoxifene: Biliary; feces (~85%); urine (<1%).
