This page shows what was measured, who it was measured in, and what that does not settle.
What Estradiol does in the body
Symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered
From the FDA-approved label: Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level.
What happened in people
RNAWiki has not yet published a reviewed conclusion for this use.
§ A fixed RNAWiki sentence
Where this came from
Wording RNAWiki always uses, not a finding about this substance.
No reviewed claim names a result for any goal on this record.
No source is stored against this line.
The limit that matters most
Not recorded.
Where it acts
Not recorded.
Kind of result
No result is published, so no kind of result applies yet
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
What the registries record it as
Its recorded molecular formula is C18H24O2, weighing 272.39.
US prescribing information · 0e927450-3f02-4d2f-9235-a255357e8d93 · read 2026-08-30
Where each sentence above came from
The recorded explanation names an amount, so it does not open this page. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
No statement of the main limit is recorded.
The four opening statements run to 81 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Stand-in result
A stand-in result is a number measured because the real result takes too long.
A picture of it, and where the picture fails
It is like judging a journey by the speedometer rather than by arriving.
Where that stops being true. Speed does predict arrival. Many stand-in results do not predict the real one.
What people get wrong. A stand-in result is often reported as the result itself.
A surrogate endpoint substituted for a clinical endpoint, valid only where the substitution has been shown to hold.
Enzyme
An enzyme is a protein that speeds up one chemical change.
A picture of it, and where the picture fails
An enzyme is like a machine on a production line doing one cut.
Where that stops being true. A machine is switched on and off by a person. Enzymes are controlled by the cell.
What people get wrong. Enzymes are thought to be used up. They are not; they work again and again.
A catalytic protein that lowers the activation energy of a specific reaction.
Receptor
A receptor is a part of a cell that a signal fits into.
A picture of it, and where the picture fails
A receptor is like a lock waiting for one key.
Where that stops being true. A lock either opens or does not. A receptor can be half-triggered, or worn out.
What people get wrong. Fitting a receptor is read as causing a benefit. It causes a step, and nothing more.
A protein that binds a specific ligand and converts that binding into a cellular response.
Pathway
A pathway is a chain of steps inside a cell, each one setting off the next.
A picture of it, and where the picture fails
A pathway is like a row of dominoes.
Where that stops being true. Dominoes fall one way. Pathways loop back and can switch themselves off.
What people get wrong. Changing one step is read as changing the outcome. Other steps often absorb it.
An ordered series of molecular interactions producing a defined cellular change.
What happened in people◇Read from sources, not yet reviewed
What was measured, goal by goal
One row for each goal a registered study measured something for. One column for each kind of thing that could be measured.
Registered studies list 40 outcome measures that RNAWiki could read. A registered study says what someone planned to measure. It does not say what they found. 0 of the matched studies tested this substance, and 0 posted a result.
There is no single score. A strong test result and a weak life result are different facts.
Goals down the side, kinds of measurement across the top. Each cell says what kind of thing was registered, not what was found.
Goal
Life outcome
What a body can do
How a person feels
A test result
A step in the body
Harms
How long
Who was studied
Focus
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Mood
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
…Waiting for a reviewer3 registered symptom measure.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Energy
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Fertility and sexual health
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
…Waiting for a reviewer1 registered symptom measure.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Which registered measures put each goal on this table
Focus
cognitive test scores at months 1 3 vs baseline; memory for emotionally valent words and neutral words; verbal memory immediate recall; verbal memory delayed recall
Mood
beck depression inventory; edinburgh postnatal depression scale mean total; center for epidemiologic studies depression scale
Energy
bones evaluated by dual energy x ray absorptiometry scan; resting energy expenditure
Fertility and sexual health
mccoy s sexual questionnaire
Sorted by fixed word lists, version v1. A name the rules do not recognise stays unsorted rather than moving to the nearest column.
What each mark on this table means
∅ Nothing in the sources checked
No registered study lists a life outcome for this goal.
— Not recorded
Harms were not a registered measure for this goal.
… Waiting for a reviewer
Who was studied is listed further down the page.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Percentage of Participants With Local Reactions Within 7 Days After Dose 1: Phase 1
✗ The study did not show it
Who was studied
NCT04368728
How many people
46969
Study design
Phase 2/Phase 3
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Result not recorded on this page
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Injection
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
openFDA Drugs@FDA · a recorded source, not a stored snapshot
openFDA NDC Directory · a recorded source, not a stored snapshot
openFDA SPL label · a recorded source, not a stored snapshot
PubChem PUG-REST · a recorded source, not a stored snapshot
Overall survival
✗ The study did not show it
Who was studied
NCT00268476
How many people
11992
Study design
Phase 2/Phase 3
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
Result not recorded on this page
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Injection
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
openFDA Drugs@FDA · a recorded source, not a stored snapshot
openFDA NDC Directory · a recorded source, not a stored snapshot
openFDA SPL label · a recorded source, not a stored snapshot
PubChem PUG-REST · a recorded source, not a stored snapshot
Evidence of disease progression for mild cases
✗ The study did not show it
Who was studied
NCT05774405
How many people
9169
Study design
Phase 2
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Result not recorded on this page
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Injection
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
openFDA Drugs@FDA · a recorded source, not a stored snapshot
openFDA NDC Directory · a recorded source, not a stored snapshot
openFDA SPL label · a recorded source, not a stored snapshot
PubChem PUG-REST · a recorded source, not a stored snapshot
Hormonal Birth Control and the Risk of Acquiring HIV
✗ The study did not show it
Who was studied
NCT00006324
How many people
6360
Study design
Not applicable
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Result not recorded on this page
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Injection
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
openFDA Drugs@FDA · a recorded source, not a stored snapshot
openFDA NDC Directory · a recorded source, not a stored snapshot
openFDA SPL label · a recorded source, not a stored snapshot
PubChem PUG-REST · a recorded source, not a stored snapshot
Change in cognitive function
✗ The study did not show it
Who was studied
NCT06294431
How many people
4794
Study design
Not applicable
Compared against
Not recorded for this study
Kind of result
What a body can do day to day
What was found
Result not recorded on this page
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Injection
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
openFDA Drugs@FDA · a recorded source, not a stored snapshot
openFDA NDC Directory · a recorded source, not a stored snapshot
openFDA SPL label · a recorded source, not a stored snapshot
PubChem PUG-REST · a recorded source, not a stored snapshot
Change in GI (Gastrointestinal) Health (1)
✗ The study did not show it
Who was studied
NCT06376695
How many people
4607
Study design
Not applicable
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Result not recorded on this page
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Injection
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
openFDA Drugs@FDA · a recorded source, not a stored snapshot
openFDA NDC Directory · a recorded source, not a stored snapshot
openFDA SPL label · a recorded source, not a stored snapshot
PubChem PUG-REST · a recorded source, not a stored snapshot
What we know
RNAWiki holds 6 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What happened in people◇Read from sources, not yet reviewed
How close this is to real life
The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.
■Living longer, or avoiding a major eventEvidence recorded. Death, a heart attack, a stroke, a hospital stay.2 registered measures of this kind. 2 written-up studies measured this and did not show a benefit.
□What a body can do day to dayNo evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
□Measured performanceNo evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
■Symptoms and quality of lifeEvidence recorded. Pain, tiredness, mood, sleep, as the person rated it.6 registered measures of this kind.
■A number that stands in for healthEvidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.2 registered measures of this kind.
■A step measured inside a personEvidence recorded. Something measured in human tissue or human cells.2 registered measures inside human tissue.
■AnimalsEvidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.Stored records in C. elegans (roundworm), Mouse, Rat, Non-human primate. A result in animals says what to test next. It does not say what happens in people.
■Cells in a dishEvidence recorded. Cells or chemistry on a bench, far from a whole body.Stored mechanism abstracts describe steps measured in cells or tissue.
□A guess from softwareNo evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.
Higher on these steps means closer to something a person would feel. It does not mean better done.
What it would be like to take◇Read from sources, not yet reviewed
Felt, measured, or meaningful
Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.
Felt
Things a person could notice without a test.
beck depression inventory
edinburgh postnatal depression scale mean total
center for epidemiologic studies depression scale
positive and negative syndrome scale
time to first symptom of urinary tract infection
mccoy s sexual questionnaire
Measured
Things only a test, a scale or a device shows.
size of the uterus evaluated by magnetic resonance scan
molecular assessment of gene expression
bone mineral density at the lumbar spine
bone mineral density
Meaningful
Things that change how a life goes, not only a number.
progression free survival
overall survival
A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.
Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.
Measured, but not felt. A number moves. The person notices nothing. Both can be true.
Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.
Matters, but takes years. The result that counts may take longer than anyone would keep watching.
Names that fit none of the three (28)
clinical symptoms
progression of subclinical atherosclerosis
bones evaluated by dual energy x ray absorptiometry scan
cognitive test scores at months 1 3 vs baseline
clinical benefit rate
daily moderate to severe hot flushes
daily hot flush severity
vulvovaginal atrophy symptoms
complete wound closure of skin graft donor site
regional lipolysis assessed by microdialysis
lipoprotein lipase activity
adrenergic receptor mrna expression
relief of vaginal symptoms
bleeding or spotting days
that had an increase in myocardial fatty acid utilization
response
vascular function
resting energy expenditure
cortisol response to crh under dex suppression
effects of sex steroids on adipocytes
These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.
What it would be like to take◇Read from sources, not yet reviewed
How long anything takes
Nine different lengths of time that get confused with each other. None of them is worked out from another.
Before anything is noticed.RNAWiki does not store this separately, and never works it out from another figure on this page.
Before a test result moves.RNAWiki does not store this separately, and never works it out from another figure on this page.
Before performance moves.RNAWiki does not store this separately, and never works it out from another figure on this page.
How long the result was watched.No finished study window is recorded for a study that tested this substance.
How long people took it.How long people actually took it is not stored. The study window is not the same thing.
How long people were followed.Follow-up length is not stored separately. It is never read off the study window, which would be a different thing.
How fast the body clears it. 10 hours hours
Read from the label, which states: “The apparent terminal half-life for estradiol was about 10 hours following administration of estradiol gel.”
How long effects linger.RNAWiki does not store this separately, and never works it out from another figure on this page.
Beyond the studies. Nothing is recorded about the long term.
The longest finished study sets the edge of what anyone measured.
A study window is not how long people took it, and neither is how long they were followed. Where RNAWiki holds only one of the three, it shows one.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Estradiol tablets are indicated in the: Treatment of moderate to severe vasomotor symptoms associated with the menopause. Treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with the menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “Estradiol gel is not indicated for use in pediatric patients.”
US prescribing information · 0e927450-3f02-4d2f-9235-a255357e8d93 · read 2026-08-30
On older people, the label states: “There have not been sufficient numbers of geriatric women involved in studies utilizing estradiol gel to determine whether those over 65 years of age differ from younger subjects in their response to estradiol gel.”
US prescribing information · 0e927450-3f02-4d2f-9235-a255357e8d93 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary Estradiol gel is not indicated for use in pregnant women.”
US prescribing information · 0e927450-3f02-4d2f-9235-a255357e8d93 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary Estrogens are present in human milk and can reduce milk production in breast-feeding women.”
US prescribing information · 0e927450-3f02-4d2f-9235-a255357e8d93 · read 2026-08-30
Where the result stopped carrying
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied for a different goal
The studies measured something else entirely.
On this record: Some registered studies measured things that match no goal on this page.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (10)
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Injection
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Suppression classes recorded: S3, S6.
No source is stored against this line.
What is in the pack
Sold as injectable, film, extended release, tablet, gel, metered, given by the injection, transdermal, oral route.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take∅Nothing found in the sources checked
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
∅Nothing found in the sources checked
No harm is recorded against this substance in the sources RNAWiki checked. Finding nothing is not the same as showing there is nothing.
The sources listed were searched and held nothing. That is not the same as nothing existing.
Reports sent to a regulator
These are reports people sent to a regulator. They do not show the medicine caused the reaction.
Nobody counted how many people took the medicine and reported nothing.
The same event can be reported more than once, and many reports are incomplete.
News coverage, lawsuits and new warnings change how often people report.
A count is not a rate and not a risk.
Estradiol appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 4342 reaction mentions were counted. One report can name several reactions.
The recorded terms (10)
pulmonary embolism — 997 reaction mentions
hot flush — 657 reaction mentions
deep vein thrombosis — 568 reaction mentions
metrorrhagia — 397 reaction mentions
unintended pregnancy — 330 reaction mentions
wrong technique in product usage process — 330 reaction mentions
application site rash — 302 reaction mentions
vaginal haemorrhage — 289 reaction mentions
migraine — 249 reaction mentions
menorrhagia — 223 reaction mentions
open-targets-adr · recorded 2026-06-24 · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Injection
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
Nothing further is recorded about which forms are sold.
No source is stored against this line.
What is recorded as being sold
355 products list this as an active ingredient in the United States drug directory. 302 of them contain it and nothing else.
FDA National Drug Code directory · 72162-2036 · read 2026-08-29
They are sold as capsule, cream, film, extended release, gel, gel, metered and implant, taken oral, topical, transdermal and vaginal.
FDA National Drug Code directory · 72162-2036 · read 2026-08-29
The regulator's established pharmacologic class for it is estradiol congeners [cs], estrogen receptor agonists [moa] and estrogen [epc].
FDA National Drug Code directory · 72162-2036 · read 2026-08-29
178 published labels name it as an active ingredient. 139 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 8b6077c2-ecab-441a-8196-fcf736643fc6 · read 2026-08-29
Those labels are classed as human otc drug and human prescription drug.
US prescribing information · 8b6077c2-ecab-441a-8196-fcf736643fc6 · read 2026-08-29
17 marketed supplement labels list this ingredient, classed as botanical with nutrients and other combinations.
Those labels carry all other, nutrient and structure/function claims. A claim of that kind is written by the manufacturer and is not assessed by any regulator, so its presence says nothing about whether it is true.
ESTRADIOL is topical at 3 DOSAGE FORMS AND STRENGTHS Estradiol gel is available in five doses of 0.25, 0.5, 0.75, 1.0, and 1.25 grams for transdermal application (corresponding to 0.25, 0.5, 0.75, 1.0, and 1.25 mg estradiol, respectively)., recorded as fda label in effect 2024-04-30 in the United States.
US prescribing information · 0e927450-3f02-4d2f-9235-a255357e8d93 · read 2026-08-30
Recorded price in US: 0.0608–12.47858 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 136 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Recorded price in US: 0.42567–3.41443 USD per one gram, across 22 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Estradiol studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
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What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
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RNAWiki has not yet published a reviewed conclusion for this use.
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What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Estradiol are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
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Check any of this yourself
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134 documents were read for this substance.
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How this medicine reached us
Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.
What the approval register records
86 approved applications cover products containing this substance. The earliest was ANDA084500, approved 19750723 to BRISTOL MYERS SQUIBB.
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5 questions this page could not answer
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Recorded evidence blocks (14)
Q2
What did Estradiol's largest trial (500000 people) and its longest (28 years) measure?
500000 people in Estradiol's largest registered study, 28 years in its longest registered window, measuring Functional Magnetic Resonance Imaging (fMRI) Changes in Response to Estrogen and Aging - Dorsolateral Pre-frontal Cortex (DLPFC). ClinicalTrials.gov · 2026-09-01
63 na, 60 phase4, 51 phase2, 44 phase3, 20 phase1, 13 na or unstated, 9 early phase1; NCT00001481; 2024-10-25. Last human test completed 2026, NCT07727863.
Interpretation These counts include studies where Estradiol was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.
Show the evidence
na
63
phase4
60
phase2
51
phase3
44
phase1
20
na or unstated
13
2 more recorded rows
early phase1
9
Last recorded human testNCT07727863
2026-06-21
recorded 2026-09-01 · last checked 2026-09-04
Q3
From C. elegans to human: where has Estradiol shown lifespan?
Interpretation Functional Magnetic Resonance Imaging (fMRI) Changes in Response to Estrogen and Aging - Dorsolateral Pre-frontal Cortex (DLPFC) — the recorded outcome words.
Show the evidence
C. elegans
lifespan
NHP
mechanism-only
mouse
lifespan
rat
mechanism-only
humanNCT01268046
mechanism-only; Functional Magnetic Resonance Imaging (fMRI) Changes in Response to Estrogen and Aging - Dorsolateral Pre-frontal Cortex (DLPFC); 252
Horvath: "We analyzed the relationship between estradiol, dehydroepiandrosterone sulfate (DHEAS) and the Free Androgen Index with DNAmAA estimators from 6 epigenetic clocks (Horvath's, Hannum's, 7-CpG clock, PhenoAge, GrimAge, DunedinPACE) in 1 404 participants of the Berlin Aging Study II (BASE-II, mean age at baseline 68.7 ±…" Europe PMC · epigenetic clock search · 2025-06-01
7 recorded sentences; 2025, 2024; biomarker
Show the evidence
HorvathPMID 40342106
2025; "We analyzed the relationship between estradiol, dehydroepiandrosterone sulfate (DHEAS) and the Free Androgen Index with DNAmAA estimators from 6 epigenetic clocks (Horvath's, Hannum's, 7-CpG clock, PhenoAge, GrimAge, DunedinPACE) in 1 404 participants of the Berlin Aging Study II (BASE-II, mean age at baseline 68.7 ± 3.7 years, 48% women)."
GrimAgePMID 40342106
2025; "In women, we found an inverse association between estradiol and DunedinPACE (baseline) and a positive association with GrimAge (follow-up)."
HorvathPMID 38890131
2024; "Increased epigenetic age acceleration of follicular fluid using the Horvath clock, but not other epigenetic clocks (GrimAge and Granulosa Cell), was associated with lower peak estradiol levels and decreased number of total and mature oocytes."
epigenetic agePMID 38890131
2024; "The association between epigenetic age acceleration and ovarian response outcomes (peak estradiol levels, follicle stimulation hormone, number of total, and mature oocytes) was assessed using linear and Poisson regression adjusted for chronological age, three surrogate variables (to account for cellular heterogeneity), race, smoking status, initial infertility diagnosis, and stimulation protocol."
Horvath
PMID 38890131
2024; "Age acceleration based on the Horvath clock was associated with lower peak estradiol levels (-819.4 unit decrease in peak estradiol levels per standard deviation increase; 95% CI: -1265.7, -373.1) and fewer total (% change in total oocytes retrieved per standard deviation increase: -21.8%; 95% CI: -37.1%, -2.8%) and mature oocytes retrieved (% change in mature oocytes retrieved per standard…"
2024; "We analysed the relationship between estradiol, dehydroepiandrosterone sulfate (DHEAS) and the Free Androgen Index (FAI) with DNAmAA estimators from six epigenetic clocks (Horvath’s, Hannum’s, 7-CpG clock, PhenoAge, GrimAge, DunedinPACE) in 1,404 participants of the Berlin Aging Study II (BASE-II, mean age at baseline 68.7 ±3.7 years, 48% women)."
GrimAge
2024; "In women we found an inverse association between estradiol and DunedinPACE (baseline) and a positive association with GrimAge (follow-up)."
"A U-shaped biphasic association was observed between estradiol levels and scoliosis risk (non-linear P <0.05)."
PMID 41548307
"Elevated Cd exposure was significantly associated with lower serum estradiol levels and an inverted U-shaped relationship with anti-Müllerian hormone levels, suggesting diminished ovarian reserve."
PMID 41083018
"RCS results demonstrated an inverted U-shaped relationship between 2-OHFLU and estradiol (F=2.8, P = 0.019), a non-linear negative association between MIBP and estradiol (F=3.3, P = 0.002), and an inverted U-shaped relationship between MEOHP and estradiol (F=4.4, P = 0.005)."
PMID 41310874
"Cross-sectional assessments showed that in males, testosterone levels, SHBG, and T/E2 ratio were negatively correlated with obesity, while estradiol displayed a non-linear, inverted U-shaped relationship."
PMID 40797168
"1500 ≤ E2-hCG ≤ 4000 pg/mL increased 30% BPR (OR 1.30, 95%CI 1.07 ~ 1.56, p-value = 0.007) and 28% CPR (OR 1.28, 95%CI 1.07 ~ 1.54, p-value = 0.008) compared to E2-hCG < 1500 pg/mL. However, E2-hCG > 4000 pg/mL did not significantly increase BPR (OR 1.13, 95%CI 0.80 ~ 1.60, p-value = 0.50) and CPR (OR 1.07, 95%CI 0.76 ~ 1.50, p-value = 0.71) compared to E2-hCG < 1500 pg/mL. CONCLUSIONS: For fresh…"
recorded 2026-04-02 · last checked 2026-09-04
Q8
Estradiol's half-life is 10 hours — which schedules were studied?
10 hours, the half-life Estradiol's label states. openfda-label · e84ad638-6768-41aa-b2b8-e2514ef63881 · 2026-08-30
Show the evidence
half life
10 hours hours; The apparent terminal half-life for estradiol was about 10 hours following administration of estradiol gel.
metabolism
Although the clinical significance has not been determined , estradiol from estradiol gel does not undergo first pass metabolism and provides estradiol to estrone ratios at steady state in the range of 0.42 to 0.65.
recorded 2026-08-30 · last checked 2026-09-04
Q9
Which of adrenergic receptor mrna expression, beck depression inventory and bleeding and spotting days did Estradiol's trials measure?
adrenergic receptor mrna expression, beck depression inventory and bleeding and spotting days lead 40 outcome terms across Estradiol's trials. ClinicalTrials.gov · 2026-09-01
clinical symptoms, progression of subclinical atherosclerosis, size of the uterus evaluated by magnetic resonance scan, bones evaluated by dual energy x ray absorptiometry scan, cognitive test scores at months 1 3 vs baseline and molecular assessment of gene expression follow.
Show the evidence
beck depression inventory
1
edinburgh postnatal depression scale mean total
1
center for epidemiologic studies depression scale
1
clinical symptoms
1
progression of subclinical atherosclerosis
1
size of the uterus evaluated by magnetic resonance scan
1
14 more recorded rows
bones evaluated by dual energy x ray absorptiometry scan
1
cognitive test scores at months 1 3 vs baseline
1
molecular assessment of gene expression
1
progression free survival
1
overall survival
1
bone mineral density at the lumbar spine
1
clinical benefit rate
1
positive and negative syndrome scale
1
daily moderate to severe hot flushes
1
daily hot flush severity
1
vulvovaginal atrophy symptoms
1
complete wound closure of skin graft donor site
1
regional lipolysis assessed by microdialysis
1
lipoprotein lipase activity
1
recorded 2026-09-01 · last checked 2026-09-04
Q10
Which of Estradiol's 34 ongoing trials reports first?
What is the number of participants that show improvement of symptoms using vaginal estrogen as compared to the control.; To assess changes in breast cancer proliferation after a 7-14 day trial of estradiol in newly diagnosed estrogen receptor positive post-menopausal breast cancer patients prior to…; latest 2033-03-01
Show the evidence
Trial
NCT01984138
"REVIVE: Replens Versus Intra-Vaginal Estrogen for the Treatment of Vaginal Dryness on Aromatase Inhibitor Therapy"; n 33; "What is the number of participants that show improvement of symptoms using vaginal estrogen as compared to the control."; 2026-06
NCT02238808
"A Study to See Whether Estrogen Can Slow the Growth of Some ER Positive Breast Cancers"; n 19; "To assess changes in breast cancer proliferation after a 7-14 day trial of estradiol in newly diagnosed estrogen receptor positive post-menopausal breast cancer patients prior to surgery."; 2028-06
NCT03401047
"Study to Assess Potential Impairments in Estradiol Augmentation of Gonadotropin Secretion in Polycystic Ovary Syndrome"; n 37; "Estradiol-induced change in 24-hour urinary LH excretion"; 2025-12-01
NCT03941730
"Estradiol in Treating Patients With ER Beta Positive, Triple Negative Locally Advanced or Metastatic Breast Cancer"; n 8; "Clinical Benefit Rate"; 2026-12-31
NCT04255160
"Impact of Estradiol on Endothelial Function in Peri-Menopausal Women"; n 80; "Vascular Endothelial Function (Flow mediated dilation or FMD)"; 2026-10-31
NCT05221021
"Vaginal Estradiol vs Oral Beta-3 Agonist for Overactive Bladder Syndrome"; n 152; "OAB-q short form (SF) symptom bother scores"; 2027-01-30
14 further recorded trials
NCT05282277
"Examining the Effects of Estradiol on Neural and Molecular Response to Reward"; n 103; "Changes in Striatal Activation Between Groups during the MID task"; 2026-12-31
NCT05283421
"Improving Diagnostics in Cervical Dysplasia"; n 150; "Scoring of the visibility of the Squamous columnar junction (SCJ)"; 2026-08-16
NCT05457972
"Postpartum Vaginal Estrogen for Breastfeeding Patients"; n 100; "Total Female Sexual Function Index (FSFI) score"; 2026-12-31
NCT05473273
"Descriptive Analysis of Serum Immunological Markers During an Euploid Frozen Embryo Transfer in a Natural Cycle."; n 40; "Blood levels of IL-4 (Interleukin 4) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)"; 2026-12-30
NCT05663892
"Drug-Drug Interaction Study in Trans Women Living With HIV"; n 45; "BIC, FTC, and TAF minimum plasma concentrations."; 2025-01
NCT05704036
"Estrogen Supplementation and Bone Health in Women With CF"; n 75; "Change in lumbar spine bone mineral density assessed by dual-energy x-ray absorptiometry (DXA)"; 2027-01
NCT05716516
"STUDY02001740;22SCH740: Estradiol For ER+ Advanced Breast Cancer (ESTHER)"; n 36; "Clinical Benefit Rate"; 2027-05
NCT05723601
"Preference of Women With Recurrent Urinary Tract Infection for Vaginal Estradiol Tablet vs Cream"; n 21; "Patient preference rate for vaginal estradiol cream versus tablet"; 2027-01
NCT05900895
"Estradiol Plus Olaparib for Breast Cancer (PHOEBE)"; n 6; "Determine the Phase II dose of olaparib in combination with 17b-estradiol"; 2028-12
NCT06179303
"Functional Imaging in Prediction of Response to Abemaciclib for Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer"; n 60; "Response to abemaciclib + endocrine therapy"; 2028-06-01
NCT06247267
"The Effect of Sex Steroid Replacement Therapy in the Hypogonadism and Transgender Active-Duty Population"; n 75; "Effects of sex steroid hormone replacement therapy on body composition"; 2025-08
NCT06353269
"Adherence to Vaginal Estrogen Therapy in Hypoestrogenic Women With Recurrent Urinary Tract Infections"; n 111; "Adherence to vaginal estrogen treatment"; 2027-09
NCT06369363
"Estrogen Deficiency on Cardiovascular Risk"; n 20; "Red blood cell flux"; 2028-11
NCT06544473
"Determining Dose Equivalence Between Oral and Transdermal Estrogen Treatment in Women With Turner Syndrome"; n 50; "Equipotency"; 2026-12-31
recorded 2026-09-01 · last checked 2026-09-04
Q11
Which 70 trials of Estradiol posted no result?
Posted no result
70 of 70 completed trials
Registrations
NCT00465192, NCT00464971, NCT00000559, NCT00005108, NCT00206570 and NCT00220454, and 64 more
Completion dates
oldest 1995-11-30; newest 2024-03-15
Show the evidence
Trial
NCT00465192
1995-11-30
NCT00464971
1996-11-30
NCT00000559
2001-08
NCT00005108
2002-01
NCT00206570
2004-12
NCT00220454
2005-03
14 further recorded trials
NCT00294463
2005-03
NCT01553773
2005-03
NCT00391417
2005-04
NCT00727129
2005-08
NCT00160173
2005-09-06
NCT00206622
2006-02
NCT00435175
2006-07
NCT00185237
2006-11
NCT01507454
2006-11
NCT00860964
2006-12
NCT00108849
2007-05
NCT01486979
2007-05
NCT00310531
2007-06
NCT00227942
2007-11
Q12
At the median, Estradiol's trials enrolled 63 people — anything larger?
Median enrolment
63
Largest enrolment
500000
Registered trials counted
251
Q13
What do 4342 spontaneous reports say about Estradiol — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Estradiol appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 4342 reaction mentions were counted: pulmonary embolism 997; hot flush 657; deep vein thrombosis 568; metrorrhagia 397. open-targets-adr · CHEMBL135 · 2026-06-24
Show the evidence
pulmonary embolism
997
hot flush
657
deep vein thrombosis
568
metrorrhagia
397
unintended pregnancy
330
wrong technique in product usage process
330
4 more recorded rows
application site rash
302
vaginal haemorrhage
289
migraine
249
menorrhagia
223
recorded 2026-06-24 · last checked 2026-09-04
Q14
Estradiol and CYP3A4 and cytochrome P450: shared by which compounds?
CYP3A4 and cytochrome P450 appear in Estradiol's recorded interaction sentences, 5 in all. openfda-label+europepmc · 2026-08-21
Interpretation drug_interactions
Show the evidence
cytochrome P450drug_interactions
7 DRUG INTERACTIONS In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4).
CYP3A4
drug_interactions
Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism.
drug_interactions
Inducers of CYP3A4, such as St. 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.
drug_interactions
Inhibitors of CYP3A4, such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and grapefruit juice, may increase plasma concentrations of estrogens and result in adverse reactions.
drug_interactions
Inducers and inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration ( 7 ).
recorded 2026-08-21 · last checked 2026-09-04
Q15
What is recorded about Estradiol and sirtuin?
"The introduction of estradiol mitigated high-fat diet-induced muscle dysfunction by enhancing expression of SIRT1 and inhibiting the acetylation of NAMPT, reducing upper airway collapse (81.7 vs. 96.7 pixels, p = 0.06)." — where Estradiol and sirtuin appear together. Europe PMC · pathway abstract search · 2026-02-26
"The introduction of estradiol mitigated high-fat diet-induced muscle dysfunction by enhancing expression of SIRT1 and inhibiting the acetylation of NAMPT, reducing upper airway collapse (81.7 vs. 96.7 pixels, p = 0.06)."
NAD+PMID 39901373
"The introduction of estradiol mitigated high-fat diet-induced muscle dysfunction by enhancing expression of SIRT1 and inhibiting the acetylation of NAMPT, reducing upper airway collapse (81.7 vs. 96.7 pixels, p = 0.06)."
sirtuin
"We show that NAD + levels and SIRT3 activity are upregulated by RANKL and inhibited by 17β-estradiol (E 2 ) in mouse and human osteoclast precursors."
NAD+
"We show that NAD + levels and SIRT3 activity are upregulated by RANKL and inhibited by 17β-estradiol (E 2 ) in mouse and human osteoclast precursors."
sirtuinPMID 41525905
"The in vitro steroid hormone immature egg culture experiment showed that estradiol significantly inhibited the expression of sirt1, sirt2, sirt4, sirt5, sirt6 genes."
mTORPMID 41490658
"Network pharmacology identified key molecular targets involved in estradiol-mediated pathways and mTOR-regulated autophagy."
1 more recorded row
autophagyPMID 41490658
"Network pharmacology identified key molecular targets involved in estradiol-mediated pathways and mTOR-regulated autophagy."
mTOR
PMID 41744685
"These findings are consistent with evidence that estradiol enhances mTOR activation via estrogen receptor α (ERα) signaling, suggesting coordinated regulation between estrogen and mTOR signaling in B cells."
PMID 41744685
"We show that estradiol in females regulates B cell metabolism to promote the maturation and metabolic activation of antibody-secreting B cells, thereby enhancing humoral immunity and protection following vaccination. mTOR signaling in B cells was greater in adult females than males after vaccination, which was diminished with aging or depletion of estradiol."
autophagyPMID 40624227
"In conclusion, the present study demonstrated that 17β-estradiol attenuates homocysteine-induced inflammatory injury in HUVECs through the activation of autophagy via the PI3K/Akt/mTOR signalling axis."
AMPKPMID 34711685
"This study aimed to assess whether the up-regulation of SIRT1 induced by 17beta-estradiol (17β-E2) could promote autophagy and inhibit apoptosis in osteoblasts via the AMPK-mTOR and FOXO3a pathways, respectively."
autophagyPMID 34711685
"This study aimed to assess whether the up-regulation of SIRT1 induced by 17beta-estradiol (17β-E2) could promote autophagy and inhibit apoptosis in osteoblasts via the AMPK-mTOR and FOXO3a pathways, respectively."
recorded 2026-02-26 · last checked 2026-09-04
Where it is registeredIdentifiers, relations and other names
ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Europe PMC — metadata only, under the recorded legal gate · Open Targets 26.06 — CC0 · derived from this page's own recorded fields; no external licence · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
✗ required summary fields resolved: 5 required field(s) not terminal: Why people use it, Best-supported result, Most important common problem, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 12 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.