Estradiol Valerate, Estradiol Valerate and Dienogest side effects: what 316 FDA adverse event reports show

Estradiol Valerate And Estradiol Valerate/Dienogest · 9 reaction terms · 128 drug–reaction co-reports · data 2026-09-14

Drug class

Not stated in label

Who reports

316 reports · 20% serious · 0 with death outcome · 100% female

openFDA FAERS counts, all years, deduplication not applied

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.

FDA label, Indications and Usage

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.

FDA label, Description section

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.

FDA label

How to read this page. FAERS is a spontaneous-reporting system: counts are not incidence rates and a signal is not proof of causation. Each reaction below is run through an automated screen — is the term in the FDA label (known), in the indications (the disease being treated), an administrative/coding term, or none of these (unlabeled)? That screen is mechanical text matching, not a causality assessment. The 30 hand-written Bradford Hill assessments are on the causality assessment page. Not medical advice.

Causality screen of the 7 strongest signals

Likely indication confounding 1Reporting / coding artifact 1Not in label — unassessed 5

What the badges mean

Likely indication confounding The term appears in the label's indications: reports probably describe the disease being treated (or its progression), not a drug effect. Classic confounding by indication.
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.
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. 2 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.

Show: hide coding/lab/outcome terms hide indication terms unlabeled only hide PRR-only

Reaction	Reports	PRR 95% CI · ROR · χ²/p	EBGM EB05 · IC025	Label screen	Serious-only & strata	Trial cross-check
Metrorrhagia	35	134.5 98.4–184.0ROR 151.2 · χ² 4,501 / p <1e-300	125.2 EB05 94.1 · IC025 +5.0 3/3 methods agree	Not in label — unassessed	serious n=2 · 91% consumer	no trial data cached
Menstruation delayed	12	76.7 44.0–133.7ROR 79.7 · χ² 822 / p 4e-181	68.6 EB05 41.8 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious n=1	no trial data cached
Amenorrhoea (missed periods)	10	39.8 21.6–73.2ROR 41.0 · χ² 340 / p 3e-76	37.2 EB05 21.5 · IC025 +2.7 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Menorrhagia (heavy periods)	8	26.7 13.4–52.8ROR 27.3 · χ² 173 / p 9e-40	24.8 EB05 12.8 · IC025 +2.2 3/3 methods agree	Not in label — unassessed	serious PRR 44.1	no trial data cached
Vaginal haemorrhage	15	23.4 14.3–38.3ROR 24.5 · χ² 300 / p 2e-67	22.7 EB05 14.5 · IC025 +2.9 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious PRR 67.6	no trial data cached
Drug dose omission	34	13.5 9.8–18.5ROR 15.0 · χ² 383 / p 2e-85	13.1 EB05 9.6 · IC025 +2.9 3/3 methods agree	Reporting / coding artifact	serious PRR 10.0 · 91% consumer	no trial data cached
Extra dose administered	7	11.6 5.6–24.2ROR 11.9 · χ² 58 / p 1e-14	8.6 EB05 3.9 · IC025 +1.5 3/3 methods agree	Not in label — unassessed	–	no trial data cached

Trial evidence (ClinicalTrials.gov)

Trial cross-check not yet run for this drug (ClinicalTrials.gov pull covers the 800 most-reported drugs first).

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
Metrorrhagia	35	134.5 98.4–184.0ROR 151.2 · χ² 4,501 / p <1e-300	125.2 EB05 94.1 · IC025 +5.0 3/3 methods agree	Not in label — unassessed	serious n=2 · 91% consumer	no trial data cached
Drug dose omission	34	13.5 9.8–18.5ROR 15.0 · χ² 383 / p 2e-85	13.1 EB05 9.6 · IC025 +2.9 3/3 methods agree	Reporting / coding artifact	serious PRR 10.0 · 91% consumer	no trial data cached
Vaginal haemorrhage	15	23.4 14.3–38.3ROR 24.5 · χ² 300 / p 2e-67	22.7 EB05 14.5 · IC025 +2.9 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious PRR 67.6	no trial data cached
Menstruation delayed	12	76.7 44.0–133.7ROR 79.7 · χ² 822 / p 4e-181	68.6 EB05 41.8 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious n=1	no trial data cached
Amenorrhoea (missed periods)	10	39.8 21.6–73.2ROR 41.0 · χ² 340 / p 3e-76	37.2 EB05 21.5 · IC025 +2.7 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Menorrhagia (heavy periods)	8	26.7 13.4–52.8ROR 27.3 · χ² 173 / p 9e-40	24.8 EB05 12.8 · IC025 +2.2 3/3 methods agree	Not in label — unassessed	serious PRR 44.1	no trial data cached
Extra dose administered	7	11.6 5.6–24.2ROR 11.9 · χ² 58 / p 1e-14	8.6 EB05 3.9 · IC025 +1.5 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Genital haemorrhage	4	20.5 7.7–54.3ROR 20.8 · χ² 56 / p 4e-14	14.5 EB05 3.9 · IC025 +0.9 3/3 methods agree	Not in label — unassessed	serious PRR 75.1	no trial data cached
Menstruation irregular	3	7.5 2.4–23.1ROR 7.6 · χ² 11 / p 4e-4	4.1 EB05 1.6 · IC025 -0.1 PRR-only: not supported by EBGM or IC	Not in label — unassessed	–	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.

Metrorrhagia — n=35, PRR 134.5

✓ 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 Valerate?

In FDA FAERS, the most frequently co-reported reaction terms for Estradiol Valerate are metrorrhagia, vaginal haemorrhage, menstruation delayed, amenorrhoea, menorrhagia, extra dose administered. 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, field patient.drug.openfda.generic_name.exact, 9 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.