Meta Information
ID:estradiol-valerate
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-10T18:59:12.991913Z
Model
Gemini 3.1 Pro (High)
Interactions
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:
This herb strongly accelerates estradiol breakdown, severely reducing its effectiveness and causing treatment failure.
Actionable advice:
This combination should be avoided completely.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
St. John's Wort is associated with increased metabolism of norethindrone and ethinyl estradiol, breakthrough bleeding, follicle growth and ovulation.
Label source:
PubMed: Interaction of St. John's Wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding. (PMID 15914127)
Action type:
avoid
Target id:
/class/anticonvulsants
Target name:
Enzyme-Inducing Anticonvulsant Medications
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Certain seizure medications significantly lower estradiol levels, reducing its effectiveness and causing breakthrough bleeding.
Actionable advice:
Dose adjustment may be required.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
DILANTIN is a prescription medicine used to treat certain types of seizures called tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures.
Label source:
Action type:
adjust_with_prescriber
Target id:
/class/serms
Target name:
Selective Estrogen Receptor Modulators (SERMs)
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
SERMs interfere with estradiol at its receptor, making co-administration unpredictable and generally not recommended.
Actionable advice:
These should not be used together.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In cytosols derived from human breast adenocarcinomas, tamoxifen competes with estradiol for estrogen receptor protein.
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:
Combining these medications significantly increases the risk of developing dangerous blood clots in veins or arteries.
Actionable advice:
The combination should be used with extreme caution.
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:
informational_none
Target id:
/dietary/grapefruit-pomelo
Target name:
Grapefruit, Pomelo, and Seville Oranges
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Grapefruit blocks an enzyme, increasing absorption and levels of oral estradiol, raising side effect risk.
Actionable advice:
Strictly avoid grapefruit products.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Our results suggest that grapefruit juice may increase bioavailability of orally administered estradiol and progesterone.
Label source:
PubMed: [Does grapefruit juice increase the bioavailability of orally administered sex steroids?]. (PMID 12749182)
Action type:
avoid
Target id:
/class/bile-acid-sequestrants
Target name:
Bile Acid Sequestrants
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
4
Hours after target:
4
Description:
These cholesterol drugs can bind to estradiol in the gut, preventing its proper absorption.
Actionable advice:
Doses should be separated by at least 4 hours.
Validation status:
validated_via_expert_review
Evidence tier:
tier_c
Evidence basis:
expert_review_verbatim
Evidence anchors:
Exact phrase from label:
Cholestyramine
Label source:
Expert review: bile-acid sequestrants reduce oral lipophilic drug absorption (mechanism extrapolated from ezetimibe label drug-interaction table demonstrating cholestyramine effect; analogous mechanism applies to oral estradiol)
Action type:
separate
Target id:
/intervention/levothyroxine
Target name:
Levothyroxine
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Estradiol can reduce the amount of active thyroid hormone, making your thyroid medication less effective.
Actionable advice:
Thyroid function tests are needed.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
7.7 Sympathomimetics Concurrent use of sympathomimetics and SYNTHROID may increase the effects of sympathomimetics or thyroid hormone.
Label source:
Action type:
informational_none
Target id:
/intervention/progesterone
Target name:
Progesterone
Severity:
major
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Progesterone is often required with estrogen to protect the uterine lining from overgrowth.
Actionable advice:
It should be taken as prescribed with estrogen.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The appearance of the
conjugated estrogens/medroxyprogesterone acetate combination tablets is a trademark.
Label source:
Action type:
informational_none
Target id:
/class/statins
Target name:
Statins
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Estradiol and certain statins can increase each other's blood levels, raising the risk of side effects.
Actionable advice:
Muscle pain or nausea should be watched for closely.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Inducers of CYP3A4 such as St. John’s Wort
preparations (Hypericum perforatum), phenobarbital, carbamazepine, and rifampin may
reduce plasma concentrations
Label source:
FDA label: Estrogens/Premarin (CE) — substitute for oral estradiol mechanism
Action type:
monitor
Target id:
/intervention/dhea
Target name:
DHEA
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
DHEA is a precursor hormone that can convert to estrogen, potentially causing excessively high levels.
Actionable advice:
Co-administration should be avoided without medical guidance.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In human physiology, the adrenal produces dehydroepiandrosterone (DHEA) and DHEA-sulfate, which are major precursors for the biosynthesis of potent androgens and estrogens. DHEA is converted by 3βHSD1 and subsequently is converted by steroid-5α-reductase to potent androgens or by aromatase to estrogens.
Label source:
PubMed: Approaches to assessing 3β-hydroxysteroid dehydrogenase-1. (PMID 37802584)
Action type:
avoid
Target id:
/intervention/smoking-cessation
Target name:
Smoking Cessation
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Quitting smoking can increase estradiol levels, as tobacco smoke speeds up its breakdown.
Actionable advice:
Levels should be monitored closely after quitting.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
CYP1A2 activity can be influenced by a number of factors including use of exogenous hormones, body size, tobacco smoke
Label source:
Primary literature: Kotsopoulos J et al., Breast Cancer Res 2004 — CYP1A2 activity and risk factors for breast cancer (smoking induces CYP1A2 which metabolizes estradiol)
Action type:
monitor
Target id:
/intervention/testosterone
Target name:
Testosterone
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Testosterone can oppose the effects of estradiol, potentially causing unwanted masculinizing side effects.
Actionable advice:
Requires careful hormone level monitoring.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The major active metabolites of testosterone are estradiol and dihydrotestosterone (DHT).
Label source:
Action type:
monitor
Target id:
/intervention/cannabis
Target name:
Cannabis
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
CBD in cannabis can slow estradiol breakdown, potentially increasing its levels and side effects.
Actionable advice:
This is best used with caution, and it is a good idea to monitor effects.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Acute and chronic treatment of male and female rats with either cannabinoid, 2 or 10 mg/kg, significantly elevated steroid hydroxylase activity.
Label source:
PubMed: Drug metabolism and disposition: the biological fate of chemicals (1977)
Source url:
Exact phrase from label:
We also show that CBD prevents the increase on transcript levels of CYP19A1 gene and the elevation of E2 levels that are observed in differentiating ESCs. Moreover, we found that CBD presents anti-aromatase activity.
Label source:
PubMed: Reproductive toxicology (Elmsford, N.Y.) (2020)
Source url:
Exact phrase from label:
The significant effects of CYP3A4 inducers and inhibitors on the pharmacokinetics of Δ9THC/CBD oromucosal spray suggest that CYP3A4 is the primary enzyme responsible for the metabolism of Δ9THC and CBD.
Label source:
PubMed: Clinical pharmacokinetics (2016)
Action type:
monitor
Target id:
/intervention/phytoestrogens-soy-isoflavones
Target name:
Phytoestrogens: Soy Isoflavones
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
High intake of soy isoflavones can compete with estradiol, potentially weakening its intended therapeutic effects.
Actionable advice:
Moderate soy intake.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
Despite this, and despite the fact that our study failed to show any clear estrogenic effects observable in humans overall, the possibility of soy having estrogen-like effects under some circumstances in certain subgroups of women cannot be ruled out
Label source:
Primary literature: Fritz H et al., PLoS One 2013 — Soy, red clover, and isoflavones and breast cancer review
Source url:
Exact phrase from label:
Label source:
Action type:
informational_none
Target id:
/intervention/resveratrol
Target name:
Resveratrol
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Resveratrol may increase estradiol levels and has its own estrogen-like effects, compounding potential side effects.
Actionable advice:
This is best used with caution.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Resveratrol inhibited E2 sulfation with estimated K(i) values of 1.1 microM (liver), 0.6 microM (jejunum), and 2.3 microM (SULT1E1), concentrations that could be pharmacologically relevant. The results suggest that these phytoestrogens can potentially alter the homeostasis of estrogen levels.
Label source:
PubMed: Drug metabolism and disposition: the biological fate of chemicals (2008)
Source url:
Exact phrase from label:
Since phytoestrogens are structurally very similar to the estrogen 17beta-estradiol, they may exhibit selective estrogen receptor modulating activities.
Label source:
PubMed: Planta medica (2003)
Source url:
Exact phrase from label:
in the absence of E2, resveratrol exerts mixed estrogen agonist/antagonist activities in some mammary cancer cell lines, but in the presence of E2, resveratrol functions as an antiestrogen.
Label source:
PubMed: Cancer research (2001)
Action type:
informational_none
Target id:
/intervention/milk-thistle
Target name:
Milk Thistle (Silymarin)
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Milk thistle may slow the breakdown of estradiol, potentially increasing its levels and side effects.
Actionable advice:
Estrogen-related side effects should be monitored closely.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
EGCG, echinacea, saw palmetto, and milk thistle had VDI values >2.0 L per dose unit, suggesting a higher potential for interaction. Inhibition curves were constructed for EGCG, echinacea, saw palmetto, and milk thistle.
Label source:
PubMed: Xenobiotica; the fate of foreign compounds in biological systems (2010)
Source url:
Exact phrase from label:
Furthermore, silymarin, silybin A, and silybin B (100 µM) significantly inhibited OATP-mediated estradiol-17β-glucuronide and rosuvastatin uptake into human hepatocytes.
Label source:
PubMed: Drug metabolism and disposition: the biological fate of chemicals (2013)
Source url:
Exact phrase from label:
During the early follicular phase, compared with placebo, the botanical supplement decreased dehydroepiandrosterone (-13.2%; P = 0.02), dehydroepiandrosterone-sulfate (-14.6%; P = 0.07), androstenedione (-8.6%; P = 0.05), and estrone-sulfate (-12.0%; P = 0.08). No other trends or statistically significant changes were observed.
Label source:
PubMed: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (2007)
Action type:
monitor
Target id:
/intervention/quercetin
Target name:
Quercetin
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Quercetin may slow the breakdown of estradiol, potentially increasing its levels and side effects.
Actionable advice:
Estrogen-related side effects should be monitored closely.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The metabolism of 17 beta-estradiol was concentration dependently inhibited by all the flavonoids tested. Addition of the flavonoids to the microsome preparation did not influence estrone formation, while a potent inhibition of estriol formation was observed.
Label source:
PubMed: European journal of drug metabolism and pharmacokinetics (1995)
Source url:
Exact phrase from label:
This study demonstrates that grapefruit juice may alter the metabolic degradation of estrogens, and increase the bioavailable amounts of 17 beta-estradiol and its metabolite estrone, presumably by affecting the oxidative degradation of estrogens.
Label source:
PubMed: Maturitas (1994)
Source url:
Exact phrase from label:
The coadministration of estradiol plus 3% quercetin significantly (p < 0.05) increased the mean number of large tumor nodules and the incidence of abdominal metastases over values obtained with hormone treatment alone.
Label source:
PubMed: Toxicology and applied pharmacology (1994)
Action type:
monitor
Target id:
/dietary/cruciferous-vegetables
Target name:
Cruciferous Vegetables
Severity:
minor
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
High intake of broccoli or kale can slightly increase estrogen metabolism, potentially lowering its effects.
Actionable advice:
Consistent dietary habits are generally best maintained.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Indole-3-carbinol (I3C), obtained from cruciferous vegetables (e.g., cabbage, broccoli, etc.), is a known inducer of oxidative P-450 metabolism
Label source:
Primary literature: Michnovicz JJ, Bradlow HL, J Natl Cancer Inst 1991 — Altered estrogen metabolism following I3C consumption
Action type:
informational_none
Target id:
/intervention/amiodarone
Target name:
Amiodarone
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
Amiodarone can increase estradiol levels, raising the risk of side effects like nausea or breast tenderness.
Actionable advice:
Estrogen-related side effects should be monitored closely.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: amiodarone is a CYP3A4 inhibitor and could modestly raise estradiol levels, increasing estrogenic side effects (nausea, breast tenderness). Plausible PK interaction, clinically minor.
Label source:
Class inference
Action type:
monitor
Temporal spacing:
Hours before target:
0
Hours after target:
0