Drug · FAERS side-effect profile with label screen

Levonorgestrel and Ethinyl Estradiol side effects: what 8,325 FDA adverse event reports show

Levonorgestrel / Ethinyl Estradiol · 13 reaction terms · 73 drug–reaction co-reports · data 2026-09-14

Drug class

Progestin, Progestin-containing Intrauterine System

FDA label (Established Pharmacologic Class) of the closest related product

Label matched

Levonorgestrel (Liletta)

closest FDA label found for this product string; brand list suppressed because the label is a related product, not an exact match

Who reports

8,325 reports · 79% serious · 212 with death outcome · 99% female

openFDA FAERS counts, all years, deduplication not applied

Used for

LILETTA is a progestin-containing intrauterine system indicated for: Prevention of pregnancy for up to 8 years ( 1.1 ) Treatment of heavy menstrual bleeding for up to 5 years in patients who choose intrauterine contraception as their method of contraception ( 1.2 ) 1.1 Contraception LILETTA is indicated for prevention of pregnancy for up to 8 years.

FDA label, Indications and Usage

What it is

the following structural formula: Levonorgestrel USP, (-)-13-ethyl-17-hydroxy-18,19-dinor-17-pregn-4-en-20-yn-3-one, the active ingredient in LILETTA, is the levorotatory form of norgestrel, which consists of a racemic mixture of D-(–)-norgestrel (levonorgestrel) and L-(+)-norgestrel (dextronorgestrel).

FDA label, Description section

Boxed warning

None in the current 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

Labeled adverse reaction 1Likely indication confounding 1Not in label — unassessed 5

What the badges mean

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.
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.
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. 6 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
Unintended pregnancy	7	33.7 16.1–70.2ROR 34.2 · χ² 190 / p 1e-43	30.8 EB05 15.6 · IC025 +2.1 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	–	no trial data cached
Metrorrhagia	11	32.0 17.9–57.3ROR 32.8 · χ² 300 / p 2e-67	30.4 EB05 18.1 · IC025 +2.7 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Vaginal discharge	5	25.0 10.5–59.9ROR 25.3 · χ² 93 / p 3e-22	20.9 EB05 6.9 · IC025 +1.4 3/3 methods agree	Labeled adverse reaction exact term	–	no trial data cached
Gallbladder disorder	8	22.5 11.3–44.6ROR 22.9 · χ² 143 / p 2e-33	20.7 EB05 10.1 · IC025 +2.1 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Amenorrhoea (missed periods)	6	18.1 8.2–40.0ROR 18.3 · χ² 81 / p 1e-19	14.8 EB05 5.4 · IC025 +1.6 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Vaginal haemorrhage	11	13.0 7.3–23.3ROR 13.3 · χ² 110 / p 4e-26	11.3 EB05 5.9 · IC025 +2.1 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Menorrhagia (heavy periods)	5	12.6 5.3–30.2ROR 12.8 · χ² 43 / p 3e-11	8.3 EB05 3.2 · IC025 +1.1 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
Vaginal haemorrhage	11	13.0 7.3–23.3ROR 13.3 · χ² 110 / p 4e-26	11.3 EB05 5.9 · IC025 +2.1 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Metrorrhagia	11	32.0 17.9–57.3ROR 32.8 · χ² 300 / p 2e-67	30.4 EB05 18.1 · IC025 +2.7 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Gallbladder disorder	8	22.5 11.3–44.6ROR 22.9 · χ² 143 / p 2e-33	20.7 EB05 10.1 · IC025 +2.1 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Unintended pregnancy	7	33.7 16.1–70.2ROR 34.2 · χ² 190 / p 1e-43	30.8 EB05 15.6 · IC025 +2.1 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	–	no trial data cached
Amenorrhoea (missed periods)	6	18.1 8.2–40.0ROR 18.3 · χ² 81 / p 1e-19	14.8 EB05 5.4 · IC025 +1.6 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Menorrhagia (heavy periods)	5	12.6 5.3–30.2ROR 12.8 · χ² 43 / p 3e-11	8.3 EB05 3.2 · IC025 +1.1 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Vaginal discharge	5	25.0 10.5–59.9ROR 25.3 · χ² 93 / p 3e-22	20.9 EB05 6.9 · IC025 +1.4 3/3 methods agree	Labeled adverse reaction exact term	–	no trial data cached
Drug exposure during pregnancy	4	5.8 2.2–15.5ROR 5.9 · χ² 12 / p 3e-4	3.8 EB05 1.7 · IC025 +0.2	Reporting / coding artifact	–	no trial data cached
Cholecystectomy	4	17.7 6.7–47.0ROR 17.9 · χ² 47 / p 3e-12	11.8 EB05 3.4 · IC025 +0.9 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Premature delivery	3	9.4 3.1–29.1ROR 9.5 · χ² 15 / p 5e-5	4.9 EB05 1.7 · IC025 +0.0	Labeled adverse reaction exact term	–	no trial data cached
Dysmenorrhoea	3	11.5 3.7–35.6ROR 11.6 · χ² 19 / p 6e-6	5.8 EB05 1.9 · IC025 +0.1	Not in label — unassessed	–	no trial data cached
Caesarean section	3	12.8 4.2–39.6ROR 12.9 · χ² 22 / p 1e-6	6.5 EB05 2.0 · IC025 +0.2 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Grand mal convulsion	3	16.1 5.2–49.8ROR 16.2 · χ² 29 / p 4e-8	8.5 EB05 2.3 · IC025 +0.3 3/3 methods agree	Not in label — unassessed	–	no trial data cached

Unlabeled candidate signals

Every screened signal with n ≥ 20 was either labeled, an indication term, or an artifact pattern — no unlabeled candidate stood out in the top signals.

✓ 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 Levonorgestrel and Ethinyl Estradiol?

In FDA FAERS, the most frequently co-reported reaction terms for Levonorgestrel and Ethinyl Estradiol are vaginal haemorrhage, metrorrhagia, gallbladder disorder, unintended pregnancy, amenorrhoea, menorrhagia. 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 Levonorgestrel and Ethinyl Estradiol have an FDA boxed warning?

No. The FDA label retrieved for Levonorgestrel and Ethinyl Estradiol has no boxed warning; see the label's Warnings and Precautions for the recognised risks.

Do FAERS signals prove that Levonorgestrel and Ethinyl 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 aaf0eb2a-f88a-4f26-a445-0fd30176c326, effective 20230629; matched on openfda.generic_name.exact:"LEVONORGESTREL" AND openfda.product_type:"HUMAN PRESCRIPTION DRUG")
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, 13 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.