Estradiol is a hormone (oestrogen) used in hormone replacement therapy to relieve menopausal symptoms such as hot flushes. It is available as tablets, patches, gels and creams.
Also known as: Estrace, Evorel
DailyMed/FDA (NIH/NLM) — approved Estradiol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5718f042-e8c0-b721-e063-6294a90a5bef ; EMC-UK (MHRA) — approved SmPC (estradiol+drospirenone): https://www.medicines.org.uk/emc/product/101678/smpc — with additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Do not use estradiol (or other oestrogens) during anastrozole treatment — oestrogen counteracts the medicine's effect in breast cancer.
Anastrozole acts by inhibiting aromatase, reducing peripheral oestrogen production. Concomitant administration of exogenous oestrogens (hormone replacement therapy, hormonal contraception) replenishes the oestrogen the drug aims to suppress, abolishing or diminishing the antitumour effect. The approved label and the EMC-UK SmPC for anastrozole state that combination with oestrogen-containing therapies should be avoided.
Oestrogen-containing products (including hormone replacement therapy) diminish the activity of anastrozole (aromatase inhibitor). Avoid the combination; HRT is not recommended during adjuvant breast cancer therapy.
Direct pharmacological antagonism: exogenous oestrogen cancels oestrogen suppression.
Signs/symptoms of recurrence; vasomotor symptoms and quality of life.
Vaginal bleeding, new bone pain, breast lump — oncology assessment.
Do not combine oestrogens with anastrozole; discuss non-hormonal options for vasomotor symptoms with the oncologist.
EMC-UK (MHRA) — approved Anastrozole SmPC: https://www.medicines.org.uk/emc/product/100971/smpc ; DailyMed/FDA (NIH/NLM) — approved Estradiol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5718f042-e8c0-b721-e063-6294a90a5bef ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Carbamazepine can reduce the effect of estradiol (hormone therapy), lowering effectiveness and changing the bleeding pattern. Tell your doctor.
The approved estradiol label (DailyMed) documents that oestrogens are partially metabolised by CYP3A4 and that inducers of this enzyme — such as carbamazepine, phenytoin, barbiturates and rifampicin — can reduce plasma concentrations, decreasing the therapeutic effect and changing the uterine bleeding pattern. In hormone replacement therapy, a dose adjustment or another route may be needed; in hormonal contraceptives, contraceptive effectiveness may be compromised.
CYP3A4 inducers (carbamazepine, phenytoin, rifampicin) reduce oestrogen concentrations, decreasing the therapeutic effect and changing the bleeding pattern. Consider a dose adjustment or an alternative.
CYP3A4 induction, accelerating oestrogen metabolism.
Vasomotor symptoms, bleeding pattern and contraceptive effectiveness.
Irregular bleeding, return of menopausal symptoms, unplanned pregnancy.
Monitor the therapeutic effect; consider an estradiol dose adjustment or non-hormonal contraception when applicable.
DailyMed/FDA (NIH/NLM) — approved Estradiol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5718f042-e8c0-b721-e063-6294a90a5bef ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2 ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Rifampicin can reduce the effect of estradiol, lowering the effectiveness of hormone therapy. Tell your doctor if you are going to take rifampicin.
The approved estradiol label (DailyMed) cites rifampicin among the CYP3A4 inducers that reduce plasma oestrogen concentrations, with possible decreased therapeutic effect and changes in the bleeding pattern. In patients taking rifampicin (e.g. tuberculosis), hormone replacement therapy may be insufficient and hormonal contraceptive effectiveness is compromised.
Rifampicin (a potent CYP3A4 inducer) reduces oestrogen concentrations; monitor the effect and consider a dose adjustment during the antibiotic.
CYP3A4 induction by rifampicin, accelerating oestrogen elimination.
Vasomotor symptoms and bleeding pattern.
Return of symptoms, irregular bleeding.
Watch for return of menopausal symptoms and consider a dose adjustment; use non-hormonal contraception if applicable.
DailyMed/FDA (NIH/NLM) — approved Estradiol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5718f042-e8c0-b721-e063-6294a90a5bef ; approved Rifampicin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b389b1a3-672f-47e3-916c-4a9c044b211b ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Clarithromycin can increase estradiol levels in the blood, with more side effects. Tell your doctor if you notice anything unusual.
The approved estradiol label (DailyMed) documents that CYP3A4 inhibitors — erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice — can increase plasma oestrogen concentrations and cause side effects. Clarithromycin is a macrolide and potent CYP3A4 inhibitor; during the combination, nausea, breast tenderness, fluid retention and changes in the bleeding pattern may occur.
CYP3A4 inhibitors (clarithromycin, erythromycin, ketoconazole, itraconazole, grapefruit juice) increase oestrogen concentrations, with a risk of dose-dependent adverse effects. Monitor.
CYP3A4 inhibition by clarithromycin, reducing oestrogen metabolism.
Symptoms of oestrogen excess: nausea, breast pain, oedema, irregular bleeding.
Severe breast pain, oedema, abnormal bleeding — medical evaluation.
Watch for dose-dependent adverse effects during the antibiotic; consider an estradiol dose adjustment if symptoms are relevant.
DailyMed/FDA (NIH/NLM) — approved Estradiol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5718f042-e8c0-b721-e063-6294a90a5bef ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Ketoconazole can increase estradiol levels and its side effects. Watch for signs such as nausea, breast tenderness or swelling.
The approved estradiol label (DailyMed) lists ketoconazole among the CYP3A4 inhibitors that increase plasma oestrogen concentrations. Systemic ketoconazole is now restricted, but the combination can occur with highly absorbed topical antifungals or in older regimens. Signs of oestrogen excess should be watched during treatment.
Ketoconazole (a potent CYP3A4 inhibitor) increases oestrogen concentrations; monitor dose-dependent effects during the combination.
CYP3A4 inhibition, reducing oestrogen metabolism.
Symptoms of oestrogen excess.
Breast pain, oedema, irregular bleeding.
Watch for adverse effects during the antifungal; adjust the estradiol dose if needed.
DailyMed/FDA (NIH/NLM) — approved Estradiol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5718f042-e8c0-b721-e063-6294a90a5bef ; approved Ketoconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f162e616-21b4-49b1-b437-15e21001a6f0 ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Grapefruit juice inhibits CYP3A4 and can increase plasma oestrogen concentrations, with a risk of dose-dependent adverse effects.
Avoid large amounts of grapefruit juice during oestrogen therapy.
DailyMed/FDA (NIH/NLM) — approved Estradiol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5718f042-e8c0-b721-e063-6294a90a5bef
Oestrogens increase the risk of VTE; previous or current deep vein thrombosis or pulmonary embolism is a contraindication.
Do not use oestrogens in patients with previous or current VTE; assess thrombotic risk factors before starting.
DailyMed/FDA (NIH/NLM) — approved Estradiol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5718f042-e8c0-b721-e063-6294a90a5bef ; EMC-UK (MHRA) — approved Estradiol SmPC: https://www.medicines.org.uk/emc/product/101678/smpc
Oestrogens are contraindicated in known, suspected or historical breast cancer (except selected patients with metastatic disease).
Do not use oestrogens in patients with breast cancer; rule out breast disease before starting hormone therapy.
DailyMed/FDA (NIH/NLM) — approved Estradiol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5718f042-e8c0-b721-e063-6294a90a5bef
Acute liver disease or a history of liver disease while liver tests have not normalised is a contraindication to oestrogens.
Do not use oestrogens in patients with active liver disease; stop if jaundice or deterioration of liver function occurs.
EMC-UK (MHRA) — approved Estradiol SmPC: https://www.medicines.org.uk/emc/product/101678/smpc
Estradiol is not indicated in pregnancy; epidemiological studies have not indicated a teratogenic effect with inadvertent exposure, but the drug must not be used.
Stop immediately if pregnancy occurs during treatment; do not use in any trimester.
Oestrogens reduce milk production; hormone therapy is not indicated during breastfeeding.
In women of childbearing age, use effective contraception if hormone therapy is started (usually premenopause is excluded).
DailyMed/FDA (NIH/NLM) — approved Estradiol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5718f042-e8c0-b721-e063-6294a90a5bef
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Steroid hormone essential for the development and maintenance of the female reproductive system and secondary sexual characteristics. In postmenopausal hormone therapy it prevents vertebral bone loss; after discontinuation, bone loss resumes at a rate comparable to the immediate postmenopausal period.
Oestrogens bind to nuclear receptors in responsive tissues, modulating gene transcription. Oestradiol modulates pituitary secretion of LH and FSH through negative feedback, reducing the elevated levels of these hormones in postmenopause.
Oestrogens circulate largely bound to sex hormone binding globulin (SHBG) and albumin, distributing widely through the body with higher concentrations in the sex hormone target organs.
Exogenous oestrogens are metabolised like endogenous ones, mainly in the liver: oestradiol is reversibly converted to oestrone and both to oestriol; they undergo sulfate and glucuronide conjugation and enterohepatic recirculation. CYP3A4 partially participates in metabolism; inducers and inhibitors of this isoenzyme may alter concentrations.
The approved label does not report half-life values; oestradiol, oestrone and oestriol are excreted in urine as conjugates (glucuronides and sulfates), with oestrone sulfate serving as a circulating reservoir of more active oestrogens.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
