Estradiol Valerate side effects: what 752 FDA adverse event reports show
Drug class
Not stated in label
Who reports
752 reports · 68% serious · 19 with death outcome · 89% female
Used for
Estradiol Valerate Injection, USP is 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.
What it is
DESCRIPTION Estradiol Valerate Injection, USP contains estradiol valerate, a long-acting estrogen in sterile oil solutions for intramuscular use. These solutions are clear, colorless to pale yellow.
Boxed warning
ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER Close clinical surveillance of all women taking estrogens is important. Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding.
Causality screen of the 28 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. 19 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 |
|---|---|---|---|---|---|---|
| Dizziness postural | 15 | 43.6 26.4–72.0ROR 44.5 · χ² 582 / p 7e-129 | 41.4 EB05 26.7 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious n=15 | no trial data cached |
| Ligament sprain | 13 | 36.8 21.5–63.1ROR 37.4 · χ² 417 / p 5e-93 | 35.0 EB05 21.8 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=13 | no trial data cached |
| Bursitis | 14 | 32.4 19.3–54.4ROR 33.0 · χ² 395 / p 4e-88 | 31.1 EB05 19.7 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious PRR 32.3 | no trial data cached |
| Eye haemorrhage | 15 | 31.3 19.0–51.7ROR 31.9 · χ² 410 / p 2e-91 | 30.2 EB05 19.4 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious PRR 29.7 | no trial data cached |
| Drug level decreased | 10 | 27.3 14.7–50.5ROR 27.6 · χ² 228 / p 1e-51 | 25.9 EB05 14.8 · IC025 +2.5 3/3 methods agree | Reporting / coding artifact | serious PRR 28.5 | no trial data cached |
| Thyroid disorder | 15 | 27.2 16.5–44.8ROR 27.7 · χ² 352 / p 7e-79 | 26.3 EB05 16.9 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious PRR 31.9 | no trial data cached |
| Sensory disturbance | 15 | 26.0 15.7–42.8ROR 26.5 · χ² 335 / p 3e-75 | 25.2 EB05 16.1 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious PRR 33.9 | no trial data cached |
| Lymphocyte count decreased | 15 | 23.7 14.3–39.1ROR 24.1 · χ² 303 / p 3e-68 | 23.0 EB05 14.6 · IC025 +2.9 3/3 methods agree | Lab value / disease marker | serious PRR 24.5 | no trial data cached |
| Diabetes mellitus inadequate control | 15 | 23.6 14.3–39.0ROR 24.1 · χ² 303 / p 4e-68 | 22.9 EB05 14.6 · IC025 +2.9 3/3 methods agree | Labeled (related wording) related wording | serious PRR 23.5 | no trial data cached |
| Musculoskeletal chest pain | 13 | 23.4 13.7–40.1ROR 23.8 · χ² 257 / p 4e-58 | 22.6 EB05 13.8 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 28.2 | no trial data cached |
| Sciatica | 13 | 22.9 13.3–39.2ROR 23.3 · χ² 250 / p 1e-56 | 22.1 EB05 13.5 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 26.0 | no trial data cached |
| Bacterial infection | 14 | 21.0 12.5–35.3ROR 21.4 · χ² 248 / p 5e-56 | 20.3 EB05 12.6 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 20.6 | no trial data cached |
| Oral herpes | 14 | 20.1 12.0–33.8ROR 20.4 · χ² 235 / p 2e-53 | 19.4 EB05 11.9 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 39.9 | no trial data cached |
| Gamma-glutamyltransferase increased | 15 | 18.9 11.4–31.1ROR 19.2 · χ² 236 / p 1e-53 | 18.2 EB05 11.3 · IC025 +2.7 3/3 methods agree | Lab value / disease marker | serious PRR 16.7 | no trial data cached |
| Blood pressure fluctuation | 13 | 15.1 8.8–25.8ROR 15.3 · χ² 157 / p 2e-36 | 14.0 EB05 7.8 · IC025 +2.4 3/3 methods agree | Lab value / disease marker | serious PRR 16.1 | no trial data cached |
| Breast cancer female | 14 | 14.5 8.6–24.4ROR 14.8 · χ² 163 / p 1e-37 | 13.5 EB05 7.8 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 11.5 | no trial data cached |
| Fungal infection | 16 | 13.4 8.3–21.8ROR 13.7 · χ² 172 / p 2e-39 | 12.4 EB05 7.5 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 20.8 | no trial data cached |
| Migraine | 45 | 13.2 10.0–17.6ROR 14.0 · χ² 499 / p 9e-111 | 13.0 EB05 10.0 · IC025 +3.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 20.0 | no trial data cached |
| Skin cancer | 10 | 12.9 7.0–24.0ROR 13.1 · χ² 99 / p 1e-23 | 11.0 EB05 5.5 · IC025 +2.0 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 11.2 | no trial data cached |
| Hyperkalaemia (high potassium) | 16 | 12.8 7.9–20.8ROR 13.0 · χ² 162 / p 2e-37 | 11.7 EB05 7.0 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 11.1 | no trial data cached |
| Burning sensation | 27 | 10.7 7.4–15.6ROR 11.1 · χ² 230 / p 4e-52 | 10.0 EB05 7.0 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious PRR 16.3 | no trial data cached |
| Abortion spontaneous | 15 | 10.4 6.3–17.2ROR 10.6 · χ² 118 / p 7e-28 | 9.0 EB05 5.4 · IC025 +2.1 3/3 methods agree | Labeled (related wording) related wording | serious PRR 8.9 | no trial data cached |
| Cardiac failure congestive | 26 | 8.9 6.1–13.0ROR 9.2 · χ² 176 / p 2e-40 | 8.1 EB05 5.7 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious PRR 7.6 | no trial data cached |
| Exposure during pregnancy | 17 | 7.6 4.8–12.2ROR 7.8 · χ² 92 / p 5e-22 | 6.5 EB05 4.2 · IC025 +1.9 3/3 methods agree | Reporting / coding artifact | serious PRR 8.0 | no trial data cached |
| Maternal exposure during pregnancy | 23 | 7.3 4.9–10.9ROR 7.5 · χ² 119 / p 6e-28 | 6.5 EB05 4.5 · IC025 +2.0 3/3 methods agree | Reporting / coding artifact | serious PRR 7.2 | no trial data cached |
| Product quality issue | 30 | 6.2 4.4–8.8ROR 6.4 · χ² 127 / p 1e-29 | 5.7 EB05 4.2 · IC025 +1.9 3/3 methods agree | Reporting / coding artifact | serious PRR 2.9 | no trial data cached |
| Skin burning sensation | 15 | 5.9 3.6–9.7ROR 6.0 · χ² 56 / p 3e-14 | 5.1 EB05 3.2 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 38.5 | no trial data cached |
| Breast cancer | 18 | 5.3 3.4–8.4ROR 5.4 · χ² 59 / p 6e-15 | 4.7 EB05 3.2 · IC025 +1.5 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 4.3 | 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 |
|---|---|---|---|---|---|---|
| Migraine | 45 | 13.2 10.0–17.6ROR 14.0 · χ² 499 / p 9e-111 | 13.0 EB05 10.0 · IC025 +3.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 20.0 | no trial data cached |
| Product quality issue | 30 | 6.2 4.4–8.8ROR 6.4 · χ² 127 / p 1e-29 | 5.7 EB05 4.2 · IC025 +1.9 3/3 methods agree | Reporting / coding artifact | serious PRR 2.9 | no trial data cached |
| Burning sensation | 27 | 10.7 7.4–15.6ROR 11.1 · χ² 230 / p 4e-52 | 10.0 EB05 7.0 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious PRR 16.3 | no trial data cached |
| Cardiac failure congestive | 26 | 8.9 6.1–13.0ROR 9.2 · χ² 176 / p 2e-40 | 8.1 EB05 5.7 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious PRR 7.6 | no trial data cached |
| Maternal exposure during pregnancy | 23 | 7.3 4.9–10.9ROR 7.5 · χ² 119 / p 6e-28 | 6.5 EB05 4.5 · IC025 +2.0 3/3 methods agree | Reporting / coding artifact | serious PRR 7.2 | no trial data cached |
| Breast cancer | 18 | 5.3 3.4–8.4ROR 5.4 · χ² 59 / p 6e-15 | 4.7 EB05 3.2 · IC025 +1.5 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 4.3 | no trial data cached |
| Exposure during pregnancy | 17 | 7.6 4.8–12.2ROR 7.8 · χ² 92 / p 5e-22 | 6.5 EB05 4.2 · IC025 +1.9 3/3 methods agree | Reporting / coding artifact | serious PRR 8.0 | no trial data cached |
| Hyperkalaemia (high potassium) | 16 | 12.8 7.9–20.8ROR 13.0 · χ² 162 / p 2e-37 | 11.7 EB05 7.0 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 11.1 | no trial data cached |
| Fungal infection | 16 | 13.4 8.3–21.8ROR 13.7 · χ² 172 / p 2e-39 | 12.4 EB05 7.5 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 20.8 | no trial data cached |
| Skin burning sensation | 15 | 5.9 3.6–9.7ROR 6.0 · χ² 56 / p 3e-14 | 5.1 EB05 3.2 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 38.5 | no trial data cached |
| Abortion spontaneous | 15 | 10.4 6.3–17.2ROR 10.6 · χ² 118 / p 7e-28 | 9.0 EB05 5.4 · IC025 +2.1 3/3 methods agree | Labeled (related wording) related wording | serious PRR 8.9 | no trial data cached |
| Gamma-glutamyltransferase increased | 15 | 18.9 11.4–31.1ROR 19.2 · χ² 236 / p 1e-53 | 18.2 EB05 11.3 · IC025 +2.7 3/3 methods agree | Lab value / disease marker | serious PRR 16.7 | no trial data cached |
| Diabetes mellitus inadequate control | 15 | 23.6 14.3–39.0ROR 24.1 · χ² 303 / p 4e-68 | 22.9 EB05 14.6 · IC025 +2.9 3/3 methods agree | Labeled (related wording) related wording | serious PRR 23.5 | no trial data cached |
| Lymphocyte count decreased | 15 | 23.7 14.3–39.1ROR 24.1 · χ² 303 / p 3e-68 | 23.0 EB05 14.6 · IC025 +2.9 3/3 methods agree | Lab value / disease marker | serious PRR 24.5 | no trial data cached |
| Sensory disturbance | 15 | 26.0 15.7–42.8ROR 26.5 · χ² 335 / p 3e-75 | 25.2 EB05 16.1 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious PRR 33.9 | 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.
- Burning sensation — n=27, PRR 10.7
- Cardiac failure congestive — n=26, PRR 8.9
✓ 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 Valerate?
In FDA FAERS, the most frequently co-reported reaction terms for Estradiol Valerate are migraine, burning sensation, cardiac failure congestive, breast cancer, hyperkalaemia, fungal infection. 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 Valerate have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER Close clinical surveillance of all women taking estrogens is important. Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding.
Do FAERS signals prove that Estradiol Valerate 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 66f40ab0-4432-4e85-b709-a0bc076868c6, effective 20251110; matched on
openfda.generic_name.exact:"ESTRADIOL VALERATE") - 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, 47 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.