This page shows what was measured, who it was measured in, and what that does not settle.
What Diethylstilbestrol does in the body
Formerly given during pregnancy to prevent miscarriage.
DES is not a steroid but it fits the oestrogen receptor and switches it on. In an adult that produces ordinary oestrogen effects. In a female fetus, the tissue that will become the vagina, cervix and uterus is being laid down, and a strong oestrogen signal at that moment permanently rewires it — leaving misplaced glandular tissue that can become cancer twenty years later, and a uterus shaped wrongly enough to make pregnancies fail.
What happened in people
It did not prevent miscarriage and later caused rare cancers and reproductive problems in exposed children.
✓ Reviewed first-read answer
Where this came from
A person wrote this and a reviewer approved it against this exact record. It carries no effect size.
A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.
No source is stored against this line.
The limit that matters most
Millions received it before a controlled study showed the intended benefit was absent.
Where it acts
Estrogen receptors throughout the body; the injury site is the Müllerian duct of the developing female fetus
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. It is a prescription or clinician-administered medicine where it is approved.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · 731DCA35BT · read 2026-08-29
Its recorded molecular formula is C18H20O2, weighing 268.3.
PubChem record · 448537 · read 2026-08-29
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
The limit a reviewer approved as the one that matters most here.
The four opening statements run to 98 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.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
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 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.
Pregnancy complications and losses on diethylstilbestrol versus placebo — "Does the administration of diethylstilbestrol during pregnancy have therapeutic value?"
✗ The study did not show it
Who was studied
Dieckmann et al. Chicago Lying-In Hospital controlled trial (1953)
How many people
0
Study design
Blinded placebo-controlled trial in pregnancy
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
The trial found no therapeutic value; its records were durable enough to establish maternal exposure status in the later Titus-Ernstoff cancer follow-up
Repeated elsewhere
Replicated
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 adverse outcome then known could have been detected, because the injury appeared in the offspring roughly two decades after the trial ended.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet; also an injectable diphosphate form for prostate cancer
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Cumulative risk of twelve adverse outcomes to age 45 (reproductive) and age 55 (other) in 4,653 exposed women versus 1,927 unexposed controls
✓ The study showed what it set out to show
Who was studied
NCI Combined DES Cohort Follow-up (Hoover et al.)
How many people
6580
Study design
Combined prospective cohort study with 40 years of follow-up
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Hazard ratios from 1.42 for pre-eclampsia to 4.68 for preterm delivery, all with confidence intervals excluding 1
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Risk was higher in exposed women with baseline vaginal epithelial changes, a marker of higher dose and earlier exposure — an internal dose-response gradient.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet; also an injectable diphosphate form for prostate cancer
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 3 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 eventNo evidence recorded. Death, a heart attack, a stroke, a hospital stay.No registered study measures this.
□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 lifeNo evidence recorded. Pain, tiredness, mood, sleep, as the person rated it.No registered study measures this.
□A number that stands in for healthNo evidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.No registered study measures this.
■A step measured inside a personEvidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
■AnimalsEvidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.Stored records in Mouse, Rat. 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 changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Diethylstilbestrol
What a person takes: Oral tablet; also an injectable diphosphate form for prostate cancer.
The measurement behind this step
Orally active because its non-steroidal stilbene skeleton escapes the first-pass inactivation that limits natural estradiol. It was never patented, so it was made cheaply by many manufacturers, which is part of why exposure reached the scale it did.
Getting in
Taken orally, and it survives the first pass
Unlike the body's own oestrogen, this one works well as a tablet, which is a large part of why it was used so widely.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Non-steroidal stilbene structure gives good oral bioavailability where natural estradiol is largely inactivated on first pass. It was never patented, so it was manufactured cheaply by many companies at once.
It passes from the mother's bloodstream into the developing baby, which is where the lasting damage happened.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Freely transplacental. The exposure window that matters is Müllerian duct differentiation in the first trimester, which is why outcome severity in the cohort data tracks with earlier exposure.
It fits the same receptor the body's own oestrogen uses and switches it on, in tissue that was never meant to receive that signal yet.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Binds ER-alpha and ER-beta with affinity comparable to or exceeding estradiol; the ligand-receptor complex acts as a transcription factor at estrogen response elements throughout the genome.
The developing reproductive tract is permanently rewired
The tissue that becomes the vagina, cervix and uterus takes its instructions during a narrow window. A strong oestrogen signal in that window changes those instructions for life.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Disrupted HOX gene expression along the Müllerian duct alters regional identity, producing vaginal adenosis — glandular epithelium where squamous epithelium belongs — cervical and uterine structural abnormalities including the T-shaped uterus, and persistently altered epithelial differentiation. The change is developmental and permanent, not pharmacological and reversible.
Cancer at twenty, and a lifetime of reproductive failure
Around one in a thousand exposed daughters developed a rare vaginal cancer. Far more had infertility, premature births, ectopic pregnancies and second-trimester losses.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Measured endpoints: about 40-fold relative risk of clear cell adenocarcinoma at an absolute risk near 1 in 1,000; infertility 33.3% versus 15.5%; preterm delivery 53.3% versus 17.8%; ectopic pregnancy 14.6% versus 2.9%; second-trimester loss 16.4% versus 1.7%; breast cancer at 40 or older 3.9% versus 2.2%.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
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.
Nobody, in pregnancy or otherwise, in the United States. The population that matters now is the DES daughters and sons still under surveillance, and the third generation.
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.
Where the result stopped carrying
The 1953 randomised trial found no therapeutic value and prescribing continued for eighteen more years
The FDA acted in 1971 on the cancer report, not on the 1953 efficacy failure
An estimated 5 to 10 million Americans were exposed between 1940 and 1971
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
Withdrawn
❝ 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
Oral tablet; also an injectable diphosphate form for prostate cancer
✎ 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. It is a prescription or clinician-administered medicine where it is approved.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
A register records the withdrawal of an approval.
No source is stored against this line.
What is in the pack
Orally active because its non-steroidal stilbene skeleton escapes the first-pass inactivation that limits natural estradiol. It was never patented, so it was made cheaply by many manufacturers, which is part of why exposure reached the scale it did.
✎ 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◇Read from sources, not yet reviewed
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.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Contraindicated in pregnancy since 1971. The measured harms in daughters exposed in utero are an approximately 40-fold relative risk of clear cell adenocarcinoma of the lower genital tract, and cumulative risks of infertility, preterm delivery, ectopic pregnancy, second-trimester loss, pre-eclampsia, stillbirth, early menopause, high-grade cervical intraepithelial neoplasia and breast cancer after 40, all significantly raised. In the mothers, breast cancer relative risk was 1.27. High-dose oestrogen also carries substantial thromboembolic and cardiovascular risk, which is why it was displaced in prostate cancer.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
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.
Diethylstilbestrol appears in spontaneous reports to regulators. Across the 2 most-reported reaction terms, 6 reaction mentions were counted. One report can name several reactions.
The recorded terms (2)
embolism — 4 reaction mentions
desmoid tumour — 2 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
Oral tablet; also an injectable diphosphate form for prostate cancer
✎ 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
It was never patented, so it was made cheaply by many manufacturers, which is part of why exposure reached the scale it did.
✎ 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 which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
3 products list this as an active ingredient in the United States drug directory. 1 of them contain it and nothing else.
FDA National Drug Code directory · 43742-2222 · read 2026-08-29
They are sold as liquid and powder, taken oral.
FDA National Drug Code directory · 43742-2222 · read 2026-08-29
2 published labels name it as an active ingredient. None of them describes this substance alone, so no label text on this page can be attributed to it rather than to a combination.
US prescribing information · 7f79058a-c35a-429a-be3c-4cff1d657087 · read 2026-08-29
Those labels are classed as human otc drug.
US prescribing information · 7f79058a-c35a-429a-be3c-4cff1d657087 · read 2026-08-29
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, withdrawn medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Diethylstilbestrol 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?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That supplementing oestrogen prevents miscarriage, because miscarriage is associated with lower oestrogen
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That a drug shown to be safe in the woman taking it is safe for the fetus she is carrying — DES is the case that established transplacental carcinogenesis as a category
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
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.
How much did people take in the studies?
The sources RNAWiki checked hold nothing for this field.
Why it matters. A result belongs to an amount. Without the amount the result floats free.
What would answer it
A stored source that records 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.
How fast does the body clear it?
The sources RNAWiki checked hold nothing for this field.
Why it matters. Without this, nothing on this page can say how long anything lasts.
What would answer it
A stored source that records 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 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.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
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 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 Diethylstilbestrol 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.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
The 1953 randomised trial asked whether it worked, and the answer was no
In plain words
A double-blind placebo-controlled trial published in 1953 tested whether DES prevented pregnancy complications. It did not. The drug went on being prescribed for another eighteen years.
What was measured
Pregnancy outcomes on diethylstilbestrol versus placebo in a blinded controlled trial
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Dieckmann, Davis, Rynkiewicz and Pottinger reported a controlled trial at the Chicago Lying-In Hospital under the title "Does the administration of diethylstilbestrol during pregnancy have therapeutic value?" — and concluded that it did not. The study is unusual for its era in being placebo-controlled and blinded, and its trial records were durable enough that the Titus-Ernstoff cancer follow-up later used them to establish exposure status for the mothers. The finding did not change prescribing. DES continued to be given to pregnant women in the United States until the FDA notified prescribers against it in 1971, following the cancer report rather than the efficacy failure.
Written into the record, not signed off as a reviewed claim
Herbst 1971: clear-cell adenocarcinoma of the vagina in the daughters
In plain words
A cluster of a cancer that essentially never occurs in young women turned out to trace back to what their mothers had taken while pregnant with them, twenty years earlier.
What was measured
Association between maternal stilbestrol exposure and vaginal adenocarcinoma in young women
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Herbst, Ulfelder and Poskanzer reported the association between maternal stilbestrol therapy and the appearance of adenocarcinoma of the vagina in young women. Clear-cell adenocarcinoma of the vagina in adolescents and women in their early twenties was, before this, close to unheard of, and it was the improbability of the tumour type in that age group that made a small case series decisive. This is the first established example of a transplacental carcinogen in humans: exposure in one generation, malignancy in the next, with a latency of two decades. The FDA notified prescribers soon afterwards that DES should not be given to pregnant women.
Written into the record, not signed off as a reviewed claim
About 40 times the risk of clear-cell adenocarcinoma, at about 1 in 1,000
In plain words
Daughters exposed before birth have roughly forty times the usual risk of this cancer. In absolute terms, about one in a thousand developed it.
What was measured
Relative and absolute risk of clear cell adenocarcinoma of the lower genital tract in DES daughters
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The National Cancer Institute states that DES daughters have about 40 times the risk of developing clear cell adenocarcinoma of the lower genital tract as unexposed women, while noting that the cancer remains rare: approximately 1 in 1,000 DES daughters developed it. Both numbers belong on the page. The relative risk is what identified the drug as a carcinogen; the absolute risk is what an individual DES daughter is actually facing, and the two answer different questions. NCI estimates that 5 to 10 million Americans — pregnant women and the children born to them — were exposed between 1940 and 1971.
Source
National Cancer Institute, Diethylstilbestrol (DES) and Cancer fact sheet
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Twelve adverse outcomes measured in 4,653 exposed women over four decades
In plain words
The cancer was the headline and it was not the biggest burden. Infertility, preterm delivery, ectopic pregnancy and second-trimester loss were all several times more common in exposed daughters.
What was measured
Cumulative risk of twelve adverse outcomes to ages 45 and 55, exposed versus unexposed
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Hoover and colleagues combined three cohorts begun in the 1970s: 4,653 women exposed in utero to DES and 1,927 unexposed controls, with cumulative risks calculated to age 45 for reproductive outcomes and to age 55 for others. Exposed versus unexposed cumulative risks were: infertility 33.3% versus 15.5% (HR 2.37, 95% CI 2.05 to 2.75); spontaneous abortion 50.3% versus 38.6% (HR 1.64, 1.42 to 1.88); preterm delivery 53.3% versus 17.8% (HR 4.68, 3.74 to 5.86); loss of second-trimester pregnancy 16.4% versus 1.7% (HR 3.77, 2.56 to 5.54); ectopic pregnancy 14.6% versus 2.9% (HR 3.72, 2.58 to 5.38); pre-eclampsia 26.4% versus 13.7% (HR 1.42, 1.07 to 1.89); stillbirth 8.9% versus 2.6% (HR 2.45, 1.33 to 4.54); early menopause 5.1% versus 1.7% (HR 2.35, 1.67 to 3.31); CIN grade 2 or higher 6.9% versus 3.4% (HR 2.28, 1.59 to 3.27); and breast cancer at age 40 or older 3.9% versus 2.2% (HR 1.82, 1.04 to 3.18). For most outcomes risk was higher in those with baseline vaginal epithelial changes, which correlate with higher dose and earlier exposure.
Written into the record, not signed off as a reviewed claim
A dose-response gradient inside the exposed cohort
In plain words
Within the exposed group, the women whose tissue showed the most evidence of early high-dose exposure had the highest risk of nearly every outcome. That gradient is what makes the association causal rather than coincidental.
What was measured
Outcome risk stratified by baseline vaginal epithelial changes within the exposed cohort
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Hoover et al. stratified by the baseline presence or absence of vaginal epithelial changes, a marker correlated with higher dose of, and earlier exposure to, DES in utero. For most of the twelve outcomes, risks among exposed women were higher for those with vaginal epithelial changes than for those without. An internal dose-response gradient of this kind is among the strongest observational evidence available for causation, because it cannot easily be produced by confounding between exposed and unexposed groups — the comparison is entirely within the exposed cohort.
Written into the record, not signed off as a reviewed claim
The mothers were harmed too, at a modest relative risk
In plain words
The women who took the drug, not just their daughters, had a slightly raised risk of breast cancer — about 27% higher.
What was measured
Relative risk of breast cancer in women given DES during pregnancy
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Titus-Ernstoff and colleagues combined two cohorts of women exposed to DES during pregnancy, with exposure status established from medical records of the Mothers Study cohort or from the clinical trial records of the Dieckmann Study. Poisson regression gave a relative risk for breast cancer of 1.27 (95% CI 1.07 to 1.52). The increase was not exacerbated by family history of breast cancer, oral contraceptive use or hormone replacement therapy. No association was found with ovarian, endometrial or other cancers. The size of this effect is worth keeping in proportion: it is a modest excess in the mothers, against a 40-fold relative risk of a specific rare cancer and a broad spectrum of reproductive harm in the daughters.
Written into the record, not signed off as a reviewed claim
The whole indication was an inference from endocrinology that was never tested first
In plain words
The reasoning was that miscarriage follows low hormone levels, so giving a strong hormone should prevent it. The reasoning came first, the prescribing came second, and the trial came eleven years after that.
What was measured
That supplementing oestrogen would prevent miscarriage, because miscarriage is associated with lower oestrogen levels
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
DES was licensed in 1941 and promoted for the prevention of miscarriage on a physiological argument: pregnancy loss was associated with low oestrogen, therefore supplementing oestrogen should reduce loss. The argument moved from mechanism to prescription without an intervening controlled trial. When the trial was finally run and published in 1953 it found no therapeutic value, and prescribing continued regardless for a further eighteen years. Two distinct failures are stacked here — an untested causal inference, and then the failure of a negative trial to change practice — and it is the second that turned a useless drug into a generational injury.
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What is not here
6 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What was measured, goal by goal — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A synthetic oestrogen given to millions of pregnant women for an effect a 1953 randomised trial had already failed to find, which turned out to be a transplacental carcinogen and to raise the lifetime risk of infertility, preterm delivery, ectopic pregnancy and breast cancer in the daughters exposed in the womb.
Recorded evidence blocks (7)
Q1
What did Diethylstilbestrol's largest trial (260 people) and its longest (4.3 years) measure?
260 people in Diethylstilbestrol's largest registered study, 4.3 years in its longest registered window, measuring Prostate-specific antigen (PSA) response. ClinicalTrials.gov · 2026-09-01
1 phase3; NCT00316927; 2007-04; no ageing endpoint recorded. Last human test completed 2007, NCT00316927.
Interpretation These counts include studies where Diethylstilbestrol 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
phase3
1
Last recorded human testNCT00316927
2007-04
recorded 2026-09-01 · last checked 2026-09-04
Q2
From mouse to human: where has Diethylstilbestrol shown lifespan?
Could one person measure Diethylstilbestrol's effect on prostate specific antigen response?
Prostate specific antigen response: measured in Diethylstilbestrol's trials.
Interpretation prostate specific antigen response is the recorded endpoint.
Show the evidence
biomarkers
prostate specific antigen response; 2026-09-01
Not recorded for this substance
a recorded half-life; a small human trial reporting an effect
Q4
Which one trial of Diethylstilbestrol posted no result?
Posted no result
1 of 1 completed trials
Registrations
NCT00316927
Completion dates
oldest 2007-04
Show the evidence
TrialNCT00316927
2007-04
Q5
At the median, Diethylstilbestrol's trials enrolled 260 people — anything larger?
Median enrolment
260
Largest enrolment
260
Registered trials counted
1
Q6
What do 6 spontaneous reports say about Diethylstilbestrol — 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.
Diethylstilbestrol appears in spontaneous reports to regulators. Across the 2 most-reported reaction terms, 6 reaction mentions were counted: embolism 4; desmoid tumour 2. open-targets-adr · CHEMBL411 · 2026-06-24
Show the evidence
embolism
4
desmoid tumour
2
recorded 2026-06-24 · last checked 2026-09-04
Q7
What is recorded about Diethylstilbestrol and sirtuin?
"Neither activators of estrogen receptors (diethylstilbestrol [18 μM] and raloxifene [8 μM]) nor activator of SIRT1 (SRT1720 [2.4-3.2 μM]) caused morphological and molecular alterations that are comparable to trans-resveratrol (10 μM)." — where Diethylstilbestrol and sirtuin appear together. Europe PMC · pathway abstract search · 2018-07-07
"Neither activators of estrogen receptors (diethylstilbestrol [18 μM] and raloxifene [8 μM]) nor activator of SIRT1 (SRT1720 [2.4-3.2 μM]) caused morphological and molecular alterations that are comparable to trans-resveratrol (10 μM)."
IGF-1PMID 27760898
"In contrast, diethylstilbestrol, which is known to selectively activate nuclear ERs but not membrane ERs, inhibited IGF-1-induced proliferation and modulated mRNA expression of estrogen-responsive genes to a similar degree as E2."
NAD+PMID 11306031
"It is proposed that quercetin inhibits the enzyme by binding competitively in both the aldehyde substrate binding-pocket and the NAD(+)-binding site, whereas resveratrol and diethylstilbestrol can only bind in the aldehyde site."
IGF-1PMID 15387438
"In a human serum matrix the MELN system was able to detect the transcriptional activity of estradiol, growth factors (epidermal growth factor (EGF), insulin at insulin-like growth factor 1 (IGF-1)-like concentrations), xeno-estrogens (diethylstilbestrol, phytoestrogens) and tamoxifen in a dose-dependent manner."
recorded 2018-07-07 · 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
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