Estradiol, Folliculinum and Oophorinum (Suis) side effects: what 2,170 FDA adverse event reports show
Who reports
2,170 reports · 60% serious · 81 with death outcome · 97% female
Used for
Estradiol transdermal system is indicated for: Estradiol transdermal system is an estrogen indicated for: Treatment of moderate to severe vasomotor symptoms due to menopause (1.1) Treatment of moderate to severe symptoms of vulvar and vaginal atrophy d.
What it is
Estradiol transdermal system, USP contains estradiol, USP in a multipolymeric adhesive. The system is designed to release estradiol, USP continuously upon application to intact skin. Five dosa.
Boxed warning
ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, and BREAST CANCER Estrogen-Alone Therapy Endometrial Cancer There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens.
Causality screen of the 37 strongest signals
What the badges mean
- Labeled — boxed warning The term (or its clinical synonym) appears in the FDA boxed warning: causality is regulator-recognised and considered serious.
- Labeled adverse reaction The exact term appears in the label's warnings or adverse-reactions sections: a known, expected effect. The FAERS signal confirms the label rather than discovering anything.
- Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
- Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
- Lab value / disease marker A laboratory result, investigation or disease-activity marker (antibody positive, CRP abnormal, swollen joint count) not described in the label. These usually mirror the monitored disease or testing protocol rather than a drug effect; not screened further.
- Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.
Strongest disproportionality signals
Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only and flags pairs whose reports are unusually skewed by sex or come mostly from consumers rather than clinicians. 101 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Breast cancer female | 113 | 40.7 34.0–48.7ROR 42.8 · χ² 4,320 / p <1e-300 | 40.2 EB05 34.4 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | serious PRR 39.0 | no trial data cached |
| Breast cancer metastatic | 28 | 25.2 17.4–36.5ROR 25.5 · χ² 626 / p 2e-138 | 24.8 EB05 18.0 · IC025 +3.5 3/3 methods agree | Labeled (related wording) related wording | serious PRR 24.6 | no trial data cached |
| Product odour abnormal | 16 | 14.9 9.1–24.3ROR 15.0 · χ² 193 / p 3e-44 | 14.0 EB05 8.5 · IC025 +2.5 3/3 methods agree | Reporting / coding artifact | – | no trial data cached |
| Breast cancer | 94 | 9.6 7.9–11.8ROR 10.0 · χ² 722 / p 2e-159 | 9.4 EB05 7.9 · IC025 +2.9 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 9.1 · 97% consumer | no trial data cached |
| Middle insomnia | 16 | 8.3 5.1–13.5ROR 8.4 · χ² 96 / p 7e-23 | 7.1 EB05 4.5 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 2.2 | no trial data cached |
| Disease recurrence | 37 | 7.5 5.4–10.3ROR 7.6 · χ² 202 / p 5e-46 | 7.0 EB05 5.2 · IC025 +2.2 3/3 methods agree | Reporting / coding artifact | serious PRR 2.3 | no trial data cached |
| Migraine | 63 | 6.4 5.0–8.2ROR 6.6 · χ² 283 / p 8e-64 | 6.1 EB05 5.0 · IC025 +2.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 9.1 | no trial data cached |
| Hot flush (hot flashes) | 50 | 6.4 4.9–8.4ROR 6.5 · χ² 223 / p 1e-50 | 6.1 EB05 4.8 · IC025 +2.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 7.5 | no trial data cached |
| Vaginal haemorrhage | 27 | 6.1 4.2–8.9ROR 6.2 · χ² 111 / p 4e-26 | 5.6 EB05 4.0 · IC025 +1.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.9 | no trial data cached |
| Abscess | 10 | 6.0 3.3–11.2ROR 6.1 · χ² 37 / p 5e-10 | 4.9 EB05 2.8 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 6.4 | no trial data cached |
| Poor quality sleep | 13 | 5.9 3.4–10.1ROR 5.9 · χ² 48 / p 3e-12 | 4.9 EB05 3.1 · IC025 +1.4 3/3 methods agree | Reporting / coding artifact | serious PRR 6.4 | no trial data cached |
| Product availability issue | 13 | 5.6 3.3–9.6ROR 5.6 · χ² 45 / p 1e-11 | 4.7 EB05 3.0 · IC025 +1.3 3/3 methods agree | Reporting / coding artifact | serious PRR 7.7 | no trial data cached |
| Diverticulitis | 16 | 5.6 3.4–9.1ROR 5.6 · χ² 56 / p 4e-14 | 4.9 EB05 3.2 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 5.7 | no trial data cached |
| Abnormal dreams | 16 | 5.6 3.4–9.0ROR 5.6 · χ² 55 / p 5e-14 | 4.8 EB05 3.2 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious PRR 4.8 | no trial data cached |
| Muscle twitching | 13 | 5.4 3.2–9.3ROR 5.5 · χ² 43 / p 3e-11 | 4.6 EB05 2.9 · IC025 +1.3 3/3 methods agree | Not in label — unassessed | serious PRR 7.5 | no trial data cached |
| Blood pressure systolic increased | 11 | 5.4 3.0–9.8ROR 5.4 · χ² 35 / p 1e-9 | 4.5 EB05 2.7 · IC025 +1.2 3/3 methods agree | Lab value / disease marker | serious PRR 5.7 | no trial data cached |
| Night sweats | 17 | 5.1 3.2–8.2ROR 5.1 · χ² 52 / p 3e-13 | 4.5 EB05 3.0 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious PRR 2.5 | no trial data cached |
| Intentional dose omission | 12 | 4.2 2.4–7.4ROR 4.2 · χ² 26 / p 1e-7 | 3.7 EB05 2.3 · IC025 +0.9 3/3 methods agree | Reporting / coding artifact | serious PRR 4.9 | no trial data cached |
| Sedation | 11 | 4.1 2.3–7.3ROR 4.1 · χ² 23 / p 1e-6 | 3.5 EB05 2.1 · IC025 +0.8 3/3 methods agree | Not in label — unassessed | serious PRR 2.4 | no trial data cached |
| Dry eye | 20 | 4.0 2.6–6.2ROR 4.0 · χ² 42 / p 5e-11 | 3.7 EB05 2.5 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious PRR 6.2 · 70% consumer | no trial data cached |
| Crying | 15 | 4.0 2.4–6.6ROR 4.0 · χ² 30 / p 2e-8 | 3.6 EB05 2.3 · IC025 +1.0 3/3 methods agree | Not in label — unassessed | serious PRR 5.2 | no trial data cached |
| Blood creatine phosphokinase increased | 12 | 4.0 2.2–7.0ROR 4.0 · χ² 24 / p 6e-7 | 3.5 EB05 2.2 · IC025 +0.8 3/3 methods agree | Lab value / disease marker | serious PRR 3.9 | no trial data cached |
| Covid-19 | 72 | 3.9 3.1–4.9ROR 4.0 · χ² 155 / p 6e-36 | 3.8 EB05 3.2 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious PRR 2.9 | no trial data cached |
| Flatulence (gas) | 23 | 3.9 2.6–5.9ROR 3.9 · χ² 47 / p 3e-12 | 3.7 EB05 2.6 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 4.2 · 78% consumer | no trial data cached |
| Needle issue | 11 | 3.7 2.1–6.7ROR 3.7 · χ² 19 / p 6e-6 | 3.3 EB05 2.0 · IC025 +0.7 | Not in label — unassessed | serious n=8 | no trial data cached |
| Withdrawal syndrome | 16 | 3.7 2.2–6.0ROR 3.7 · χ² 28 / p 5e-8 | 3.4 EB05 2.2 · IC025 +0.9 3/3 methods agree | Labeled (related wording) related wording | serious PRR 4.1 | no trial data cached |
| Mood swings | 12 | 3.6 2.1–6.4ROR 3.6 · χ² 20 / p 3e-6 | 3.3 EB05 2.0 · IC025 +0.7 3/3 methods agree | Not in label — unassessed | serious PRR 3.0 | no trial data cached |
| Dysgeusia (altered taste) | 27 | 3.5 2.4–5.1ROR 3.5 · χ² 46 / p 7e-12 | 3.3 EB05 2.4 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious PRR 2.1 · 81% consumer | no trial data cached |
| Product substitution issue | 19 | 3.2 2.0–5.0ROR 3.2 · χ² 26 / p 1e-7 | 3.0 EB05 2.0 · IC025 +0.8 3/3 methods agree | Reporting / coding artifact | serious PRR 2.7 | no trial data cached |
| Influenza like illness (flu-like illness) | 25 | 2.9 2.0–4.3ROR 2.9 · χ² 30 / p 3e-8 | 2.8 EB05 2.0 · IC025 +0.8 3/3 methods agree | Labeled (related wording) related wording | serious PRR 3.6 · 76% consumer | no trial data cached |
| Anger | 10 | 2.8 1.5–5.3ROR 2.8 · χ² 10 / p 7e-4 | 2.6 EB05 1.5 · IC025 +0.3 | Not in label — unassessed | serious PRR 2.7 | no trial data cached |
| Colitis ulcerative | 13 | 2.8 1.6–4.8ROR 2.8 · χ² 13 / p 1e-4 | 2.6 EB05 1.7 · IC025 +0.5 | Not in label — unassessed | serious PRR 2.9 | no trial data cached |
| Eye irritation | 15 | 2.6 1.6–4.3ROR 2.6 · χ² 13 / p 1e-4 | 2.5 EB05 1.6 · IC025 +0.4 | Labeled (related wording) related wording | serious PRR 4.1 | no trial data cached |
| Suicidal ideation (thoughts of suicide) | 24 | 2.5 1.7–3.8ROR 2.5 · χ² 21 / p 3e-6 | 2.4 EB05 1.7 · IC025 +0.6 | Not in label — unassessed | serious PRR 2.5 · 83% consumer | no trial data cached |
| Drug dose omission by device | 18 | 2.3 1.4–3.6ROR 2.3 · χ² 12 / p 3e-4 | 2.2 EB05 1.5 · IC025 +0.3 | Not in label — unassessed | serious n=3 | no trial data cached |
| Wrong technique in device usage process | 10 | 2.1 1.1–3.9ROR 2.1 · χ² 5 / p 0.014 | 2.0 EB05 1.2 · IC025 -0.1 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | serious n=4 | no trial data cached |
| Injection site haemorrhage | 17 | 2.1 1.3–3.3ROR 2.1 · χ² 8 / p 0.002 | 2.0 EB05 1.3 · IC025 +0.2 | Labeled (related wording) related wording | serious PRR 7.8 | no trial data cached |
Trial evidence (ClinicalTrials.gov)
Most frequently reported reactions
By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Breast cancer female | 113 | 40.7 34.0–48.7ROR 42.8 · χ² 4,320 / p <1e-300 | 40.2 EB05 34.4 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | serious PRR 39.0 | no trial data cached |
| Breast cancer | 94 | 9.6 7.9–11.8ROR 10.0 · χ² 722 / p 2e-159 | 9.4 EB05 7.9 · IC025 +2.9 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 9.1 · 97% consumer | no trial data cached |
| Covid-19 | 72 | 3.9 3.1–4.9ROR 4.0 · χ² 155 / p 6e-36 | 3.8 EB05 3.2 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious PRR 2.9 | no trial data cached |
| Migraine | 63 | 6.4 5.0–8.2ROR 6.6 · χ² 283 / p 8e-64 | 6.1 EB05 5.0 · IC025 +2.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 9.1 | no trial data cached |
| Hot flush (hot flashes) | 50 | 6.4 4.9–8.4ROR 6.5 · χ² 223 / p 1e-50 | 6.1 EB05 4.8 · IC025 +2.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 7.5 | no trial data cached |
| Injection site pain (pain where injected) | 43 | 1.4 1.0–1.8ROR 1.4 · χ² 4 / p 0.024 | 1.4 EB05 1.1 · IC025 -0.1 PRR-only: not supported by EBGM or IC | Labeled (related wording) related wording | serious PRR 4.5 | no trial data cached |
| Disease recurrence | 37 | 7.5 5.4–10.3ROR 7.6 · χ² 202 / p 5e-46 | 7.0 EB05 5.2 · IC025 +2.2 3/3 methods agree | Reporting / coding artifact | serious PRR 2.3 | no trial data cached |
| Breast cancer metastatic | 28 | 25.2 17.4–36.5ROR 25.5 · χ² 626 / p 2e-138 | 24.8 EB05 18.0 · IC025 +3.5 3/3 methods agree | Labeled (related wording) related wording | serious PRR 24.6 | no trial data cached |
| Dysgeusia (altered taste) | 27 | 3.5 2.4–5.1ROR 3.5 · χ² 46 / p 7e-12 | 3.3 EB05 2.4 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious PRR 2.1 · 81% consumer | no trial data cached |
| Vaginal haemorrhage | 27 | 6.1 4.2–8.9ROR 6.2 · χ² 111 / p 4e-26 | 5.6 EB05 4.0 · IC025 +1.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.9 | no trial data cached |
| Influenza like illness (flu-like illness) | 25 | 2.9 2.0–4.3ROR 2.9 · χ² 30 / p 3e-8 | 2.8 EB05 2.0 · IC025 +0.8 3/3 methods agree | Labeled (related wording) related wording | serious PRR 3.6 · 76% consumer | no trial data cached |
| Suicidal ideation (thoughts of suicide) | 24 | 2.5 1.7–3.8ROR 2.5 · χ² 21 / p 3e-6 | 2.4 EB05 1.7 · IC025 +0.6 | Not in label — unassessed | serious PRR 2.5 · 83% consumer | no trial data cached |
| Flatulence (gas) | 23 | 3.9 2.6–5.9ROR 3.9 · χ² 47 / p 3e-12 | 3.7 EB05 2.6 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 4.2 · 78% consumer | no trial data cached |
| Dry eye | 20 | 4.0 2.6–6.2ROR 4.0 · χ² 42 / p 5e-11 | 3.7 EB05 2.5 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious PRR 6.2 · 70% consumer | no trial data cached |
| Product substitution issue | 19 | 3.2 2.0–5.0ROR 3.2 · χ² 26 / p 1e-7 | 3.0 EB05 2.0 · IC025 +0.8 3/3 methods agree | Reporting / coding artifact | serious PRR 2.7 | no trial data cached |
Unlabeled candidate signals
These flagged terms were not found in the FDA label text and do not match an artifact pattern. They are the pairs that would merit a structured assessment (temporality, dose-response, biological plausibility, consistency across databases, trial or cohort evidence). The screen has not done that; string-matching misses label wording, and a strong PRR can still be stimulated reporting, co-medication, or the disease itself.
- Breast cancer female — n=113, PRR 40.7
- Dry eye — n=20, PRR 4.0
- Covid-19 — n=72, PRR 3.9
- Flatulence — n=23, PRR 3.9
- Dysgeusia — n=27, PRR 3.5
- Suicidal ideation — n=24, PRR 2.5
✓ A hand-written Bradford Hill causality assessment exists for this drug: Drospirenone/ethinyl estradiol ↔ Pulmonary embolism (venous thromboembolism).
Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.
Common questions
What are the most reported side effects of Estradiol?
In FDA FAERS, the most frequently co-reported reaction terms for Estradiol are breast cancer female, breast cancer, covid-19, migraine, hot flush, injection site pain. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.
Does Estradiol have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, and BREAST CANCER Estrogen-Alone Therapy Endometrial Cancer There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens.
Do FAERS signals prove that Estradiol causes these side effects?
No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.
Sources & methods
- FDA label via openFDA (set ID 0500ee9b-bf4a-4432-9afe-20a7d60a6fe5, effective 20240514; matched on
openfda.generic_name.exact:"ESTRADIOL") - Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
- FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA
count=aggregation, fieldpatient.drug.openfda.generic_name.exact, 138 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction - Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
- Seriousness and sex counts from openFDA
count=serious,patient.patientsex,seriousnessdeath
Page generated 2026-10-08. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.