Meta Information
ID:estradiol
Name:Estradiol
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/condition/history-of-breast-cancer
Target name:
History of Estrogen-Sensitive Breast Cancer
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Estradiol can stimulate the growth of any remaining hormone-receptor-positive cancer cells, significantly increasing the risk of cancer recurrence.
Actionable advice:
This should be strictly avoided with a personal history of estrogen-sensitive breast cancer.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
These include an increased risk of breast cancer.
Label source:
Action type:
avoid
Target id:
/condition/history-of-endometrial-cancer
Target name:
History of Endometrial Cancer
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Estradiol can promote the growth of endometrial tissue, potentially increasing the risk of recurrence for hormone-sensitive uterine cancers.
Actionable advice:
This should be strictly avoided with a personal history of endometrial cancer.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Endometrial hyperplasia may be a precursor to endometrial cancer.
Label source:
Action type:
avoid
Target id:
/condition/history-of-vte
Target name:
History of Blood Clots (VTE, DVT, PE)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Estradiol increases the production of clotting factors, which elevates the risk of forming new, potentially life-threatening blood clots in the veins.
Actionable advice:
This should be strictly avoided with a personal history of deep vein thrombosis or pulmonary embolism.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Norelgestromin and ethinyl estradiol transdermal system may increase your risk of blood clots after surgery.
Label source:
Action type:
avoid
Target id:
/condition/history-of-stroke-or-mi
Target name:
History of Stroke or Heart Attack
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Due to its effects on blood clotting, estradiol may increase the risk of arterial thrombotic events in susceptible individuals.
Actionable advice:
This should be strictly avoided with a personal history of stroke or heart attack.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The Women’s Health Initiative (WHI) study reported increased risks of myocardial
infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in
postmenopausal women
Label source:
FDA label: Estrogens/Premarin (CE) — Boxed Warning section
Action type:
avoid
Target id:
/condition/undiagnosed-vaginal-bleeding
Target name:
Undiagnosed Abnormal Vaginal Bleeding
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Abnormal bleeding must be investigated before starting therapy, as it could be a symptom of endometrial hyperplasia or cancer, which would be worsened by estradiol.
Actionable advice:
This should not be used until the cause of any abnormal vaginal bleeding has been diagnosed by a doctor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
● have unexplained vaginal bleeding ● are pregnant or think you may be pregnant.
Label source:
Action type:
avoid
Target id:
/condition/hepatic-impairment
Target name:
Severe Liver Disease
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
A severely impaired liver cannot properly metabolize and clear estradiol, leading to dangerously high hormone levels and an increased risk of side effects.
Actionable advice:
This should be strictly avoided with severe or active liver disease.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
5.10 Hepatic Impairment and/or Past History of Cholestatic Jaundice Estrogens may be poorly metabolized in women with hepatic impairment.
Label source:
Action type:
avoid
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Exogenous estradiol is not indicated during pregnancy and may cause harm to the developing fetus.
Actionable advice:
This should not be used during pregnancy or when planning to become pregnant.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
However, norelgestromin and ethinyl estradiol transdermal system is not known to cause birth defects when used by accident during pregnancy.
Label source:
Action type:
avoid
Target id:
/intervention/progesterone
Target name:
Progesterone or Progestin
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
In women with a uterus, unopposed estradiol stimulates endometrial growth, which significantly increases the risk of uterine cancer. Progesterone opposes this effect, protecting the uterine lining.
Actionable advice:
If you have a uterus, you must take progesterone or a progestin concurrently with estradiol.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The dose proportionality of estrogens and medroxyprogesterone acetate was assessed by
combining pharmacokinetic data across another two studies totaling 61 healthy, postmenopausal
women.
Label source:
Action type:
informational_none
Target id:
/class/broad-spectrum-inducers
Target name:
Strong Metabolic Enzyme Inducers
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Certain drugs (like rifampin, carbamazepine, phenytoin) and supplements (St. John's Wort) strongly accelerate the breakdown of estradiol in the liver, drastically reducing its blood levels and effectiveness.
Actionable advice:
These inducers should not be used with estradiol, or significant dose adjustments should be discussed with a doctor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
John's wort ( Hypericum perforatum ) preparations, phenobarbital, carbamazepine and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile.
Label source:
Action type:
avoid
Target id:
/intervention/saint-johns-wort
Target name:
Saint John's Wort
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
St. John's Wort is a potent inducer of the CYP3A4 enzyme, which significantly speeds up the breakdown of estradiol, reducing its effectiveness.
Actionable advice:
St. John's Wort should not be taken with estradiol.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
CONCLUSION: St John's wort causes an induction of ethinyl estradiol-norethindrone metabolism consistent with increased CYP3A activity.
Label source:
PubMed: The interaction between St John's wort and an oral contraceptive. (PMID 14663455)
Action type:
avoid
Target id:
/class/cyp3a4-strong-inhibitors
Target name:
Strong CYP3A4 Inhibitors
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Potent inhibitors (like ketoconazole, clarithromycin, ritonavir) block the enzyme that breaks down estradiol, leading to higher blood levels and an increased risk of side effects.
Actionable advice:
Concurrent use of strong CYP3A4 inhibitors with oral estradiol should be avoided.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and grapefruit juice may increase plasma concentrations of estrogens and may result in adverse reactions.
Label source:
Action type:
avoid
Target id:
/intervention/tranexamic-acid
Target name:
Tranexamic Acid
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both tranexamic acid and estradiol independently increase the risk of blood clots; using them together significantly elevates this risk.
Actionable advice:
Concurrent use should be avoided unless specifically approved and monitored by a physician.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Tranexamic acid, however, at blood concentrations of 1 and 10 mg/mL prolongs the thrombin time.
Label source:
Action type:
avoid
Target id:
/intervention/lamotrigine
Target name:
Lamotrigine
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Oral estradiol significantly accelerates the elimination of lamotrigine, which can drastically lower its levels and lead to a loss of seizure control or mood stabilization.
Actionable advice:
Concurrent use should be avoided, or significant lamotrigine dose adjustments and close monitoring should be planned for.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Some medicines and grapefruit juice may increase your level of the hormone ethinyl estradiol if used together, including: ● acetaminophen ● ascorbic acid ● medicines that affect how your liver breaks down other medicines (itraconazole, ketoconazole, voriconazole, and fluconazole) ● certain HIV medicines (atazanavir, indinavir) ● atorvastatin ● rosuvastatin ● etravirine Hormonal birth control methods may interact with lamotrigine, an anti-seizure medicine used for epilepsy.
Label source:
Action type:
avoid
Target id:
/class/serms
Target name:
SERMs (e.g., Tamoxifen, Raloxifene)
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
SERMs work by blocking or modulating estrogen receptors; taking them with estradiol is pharmacologically contradictory and negates the intended therapeutic action of one or both drugs.
Actionable advice:
Estradiol should not be taken concurrently with SERMs.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In this rat model, tamoxifen appears to exert its antitumor effects by binding the estrogen receptors.
Label source:
Action type:
avoid
Target id:
/class/aromatase-inhibitors
Target name:
Aromatase Inhibitors (e.g., Anastrozole)
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Aromatase inhibitors work by blocking the body's production of estrogen; taking supplemental estradiol is directly counter to the goal of this therapy.
Actionable advice:
Estradiol should not be taken concurrently with aromatase inhibitors.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
It contains two female hormones, an estrogen called ethinyl estradiol, and a progestin called norelgestromin.
Label source:
Action type:
avoid
Target id:
/condition/smoking
Target name:
Smoking Tobacco
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Smoking is a major independent risk factor for blood clots, stroke, and heart attack, and it compounds the thrombotic risk associated with estrogen therapy.
Actionable advice:
Smoking should be strictly avoided while on estradiol therapy.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Smoking increases your risk of serious cardiovascular side effects from hormonal birth control methods, including death from heart attack, blood clots or stroke.
Label source:
Action type:
avoid
Target id:
/biomarker/comprehensive-sex-hormone-panel
Target name:
Hormone Level Monitoring
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Regular monitoring of estradiol and other hormone levels is essential to ensure the dose is safe and effective, and to guide adjustments over time.
Actionable advice:
Schedule regular blood tests as recommended by your doctor to monitor hormone levels.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
General information about the safe and effective use of norelgestromin and ethinyl estradiol transdermal system.
Label source:
Action type:
monitor
Target id:
/intervention/levothyroxine
Target name:
Levothyroxine (Thyroid Hormone)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Estradiol increases levels of thyroid-binding globulin (TBG), which binds to thyroid hormone and reduces the amount of free, active hormone, potentially causing hypothyroidism symptoms.
Actionable advice:
Thyroid function (TSH, free T4) should be monitored 6-8 weeks after starting estradiol, and the levothyroxine dose may need adjustment.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Inform patients that agents such as iron and calcium supplements and antacids can decrease the absorption of levothyroxine.
Label source:
FDA label: Levothyroxine (Synthroid)
Action type:
adjust_with_prescriber
Target id:
/class/corticosteroids
Target name:
Corticosteroids
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Estradiol can slow the metabolic clearance of corticosteroids, potentially increasing their levels and the risk of side effects like fluid retention or high blood pressure.
Actionable advice:
Your doctor may need to monitor you closely or adjust the corticosteroid dose if used together long-term.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients.
Label source:
Action type:
adjust_with_prescriber
Target id:
/dietary/grapefruit-pomelo
Target name:
Grapefruit and Grapefruit Juice
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Grapefruit inhibits the CYP3A4 enzyme in the gut, which can increase the absorption and blood levels of oral estradiol, raising the risk of side effects.
Actionable advice:
Grapefruit or grapefruit juice is best avoided while taking oral estradiol.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and grapefruit juice may increase plasma concentrations of estrogens and may result in adverse reactions.
Label source:
Action type:
avoid
Target id:
/intervention/somatropin
Target name:
Somatropin (Growth Hormone)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Oral estradiol can reduce the liver's production of IGF-1 in response to growth hormone therapy, potentially blunting its effects. This interaction is less significant with transdermal estradiol.
Actionable advice:
If using growth hormone, prefer transdermal estradiol and monitor IGF-1 levels to guide dosing.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
By contrast, transdermal E2 administration, which restored circulating E2 concentrations to the midfollicular range, increased circulating IGF-I
Label source:
Primary literature: Weissberger AJ et al., J Clin Endocrinol Metab 1991 — Contrasting effects of oral and transdermal estrogen on GH/IGF-I axis
Action type:
monitor
Target id:
/condition/alcohol-chronic
Target name:
Chronic Alcohol Use (Alcohol Use Disorder)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Chronic heavy alcohol consumption can impair liver function and may alter estrogen metabolism, potentially increasing circulating hormone levels and the risk of side effects.
Actionable advice:
Alcohol intake is best limited to moderate levels (e.g., no more than 1 drink per day) while on estradiol therapy.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
a single large dose of alcohol
Label source:
Primary literature: Weisberg E, Alcohol Health Res World 1996 (PMC review) — Alcohol, Hormones, and Postmenopausal Women
Action type:
informational_none
Target id:
/class/antibiotics-long-term
Target name:
Broad-Spectrum Antibiotics
Severity:
minor
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Some antibiotics may disrupt gut bacteria involved in the reabsorption of oral estrogens (enterohepatic circulation), theoretically leading to slightly lower estradiol levels. The clinical significance is low.
Actionable advice:
Symptoms may change during antibiotic use; dose adjustments are rarely needed.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide
conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis
in the gut followed by reabsorption.
Label source:
FDA label: Estrogens/Premarin (CE) — Drug Interactions
Action type:
adjust_with_prescriber
Target id:
/class/antidiabetic-medications
Target name:
Diabetes Medications
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Estradiol can influence insulin sensitivity and blood glucose control, which may require minor adjustments to the doses of diabetes medications.
Actionable advice:
It is a good idea to check blood glucose levels when starting, stopping, or changing the dose of estradiol.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Less common side effects are: ● acne ● less sexual desire ● bloating or fluid retention ● blotchy darkening of your skin, especially your face ● high blood sugar, especially in women with diabetes ● high fat (cholesterol, triglycerides) levels in the blood ● depression, especially if you have had depression in the past.
Label source:
Action type:
monitor
Target id:
/intervention/vitamin-c
Target name:
Vitamin C (High Dose)
Severity:
minor
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
0.5
Hours after target:
0.5
Description:
Taking high doses of Vitamin C (1g or more) at the same time as oral estradiol may increase estradiol absorption and blood levels, potentially increasing side effects.
Actionable advice:
High-dose Vitamin C and the oral estradiol dose are best separated by at least 2 hours.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
Oral ascorbic acid increases plasma oestradiol
Label source:
Primary literature: Isaksson B et al., Maturitas 2002 — Oral ascorbic acid increases plasma oestradiol during oestradiol therapy
Action type:
separate
Target id:
/condition/estrogen-dependent-cancer
Target name:
History of Estrogen-Dependent Cancer
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Estradiol can promote the growth of hormone-sensitive cancers, such as certain types of breast cancer (ER+) or endometrial cancer. It is contraindicated in individuals with a history of these conditions.
Actionable advice:
Systemic estradiol should be avoided with a current or past history of breast, uterine, or other estrogen-sensitive cancers.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER
Label source:
FDA label: Estradiol tablets (Estrace) — Boxed Warning
Action type:
avoid
Target id:
/lifestyle/tobacco-smoking
Target name:
Tobacco Smoking (Cardiovascular Risk)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Smoking significantly increases the risk of serious cardiovascular events, such as blood clots, stroke, and heart attack, when used with estrogens, especially in women over 35.
Actionable advice:
Smoking should not be done while using systemic estradiol due to a greatly increased risk of blood clots.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Risk factors for arterial vascular disease (e.g., hypertension, diabetes mellitus,
tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism
Label source:
FDA label: Estradiol tablets (Estrace)
Action type:
informational_none
Target id:
/condition/hypertriglyceridemia
Target name:
High Triglycerides (Hypertriglyceridemia)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Oral estradiol can significantly increase triglyceride levels, which in individuals with pre-existing high levels can increase the risk of pancreatitis.
Actionable advice:
Triglyceride levels should be monitored closely; transdermal estradiol is preferred as it has less impact on lipids.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
5.9 Exacerbation of Hypertriglyceridemia In women with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis.
Label source:
Action type:
monitor
Target id:
/biomarker/estradiol
Target name:
Estradiol Blood Test
Severity:
major
Interaction type:
assay_interference
Nature:
temporal
Temporal spacing:
Hours before target:
72
Hours after target:
0
Description:
High doses of supplemental biotin (>5 mg/day) can interfere with the laboratory assays used to measure estradiol, leading to falsely high or low results.
Actionable advice:
Biotin supplements should be stopped for at least 72 hours before estradiol levels are tested.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Some studies have reported that women who use norelgestromin and ethinyl estradiol transdermal system have a higher risk of getting a blood clot.
Label source:
Action type:
separate
Target id:
/class/thyroid-hormones
Target name:
Thyroid Hormones (e.g., Levothyroxine)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Oral estradiol increases levels of thyroxine-binding globulin (TBG), which binds to thyroid hormone, reducing the amount of free, active hormone available and potentially requiring a higher dose of thyroid medication.
Actionable advice:
If you take thyroid medication, your dose may need adjustment after starting oral estradiol; monitor thyroid function tests (TSH).
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Monitor thyroid function in these women during treatment with LYLLANA to maintain their free thyroid hormone levels in an acceptable range.
Label source:
Action type:
separate
Target id:
/class/bile-acid-sequestrants
Target name:
Bile Acid Sequestrants (e.g., Cholestyramine)
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
4
Hours after target:
1
Description:
Bile acid sequestrants can bind to oral estradiol in the gut, significantly reducing its absorption and effectiveness.
Actionable advice:
Oral estradiol is best taken at least 1 hour before or 4 hours after a bile acid sequestrant.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Interference with the
absorption of oral phosphate supplements has been observed with another positively-charged
bile acid sequestrant.
Label source:
Action type:
separate
Target id:
/class/anticoagulants-antiplatelets
Target name:
Anticoagulants and Antiplatelets
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
While not a direct drug interaction, estrogens increase the baseline risk of blood clots, complicating the risk-benefit assessment when used with medications that affect blood clotting.
Actionable advice:
This is best used with caution and under strict medical supervision, as the underlying risk of thrombosis is increased.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Perform adequate diagnostic measures, including directed or random endometrial sampling when indicated, to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding with unknown etiology.
Label source:
Action type:
informational_none
Target id:
/dietary/alcohol-acute
Target name:
Alcohol (Acute Consumption)
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Acute alcohol intake can temporarily increase estradiol levels, while chronic heavy use may also alter estrogen metabolism, potentially increasing exposure and side effect risk.
Actionable advice:
Moderate alcohol consumption, as excessive intake may alter estradiol levels and increase side effect risk.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Acute alcohol ingestion may lead to significant and sustained elevations in circulating estradiol to levels 300% higher than those targeted in clinical use of ERT.
Label source:
Primary literature: Ginsburg ES et al., JAMA 1996 — Effects of alcohol ingestion on estrogens in postmenopausal women
Action type:
informational_none
Derived From
estradiol_systemic_healthspan
Provenance Note
Interactions duplicated from 'estradiol_systemic_healthspan'. Systemic estradiol (scope-suffix reconciliation).
Merged From
- estradiol_systemic_disease