Drug · FAERS side-effect profile with label screen
Norethindrone and Ethinyl Estradiol side effects: what 2,250 FDA adverse event reports show
Drug class
Progestin
FDA label (Established Pharmacologic Class) of the closest related product
Label matched
Norethindrone (Norethindrone)
closest FDA label found for this product string; brand list suppressed because the label is a related product, not an exact match
Who reports
2,250 reports · 34% serious · 16 with death outcome · 100% female
openFDA FAERS counts, all years, deduplication not applied
Used for
1. Indications Progestin-only oral contraceptives are indicated for the prevention of pregnancy. 2. Efficacy If used perfectly, the first-year failure rate for progestin-only oral contraceptives is 0.3%. However, the typical failure rate is estimated to be closer to 9%, due to late or omitted pills. Table 1 lists the pregnancy rates for users of all major methods of contraception.
FDA label, Indications and Usage
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 40 strongest signals
Labeled adverse reaction 4Labeled (related wording) 2Likely indication confounding 1Reporting / coding artifact 8Not in label — unassessed 25
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.
- Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
- 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. 74 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
Show:
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Metrorrhagia | 31 | 16.7 11.8–23.7ROR 16.9 · χ² 442 / p 2e-98 | 16.4 EB05 12.0 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=4 · 90% consumer | no trial data cached |
| Menstruation irregular | 37 | 13.0 9.4–17.9ROR 13.2 · χ² 398 / p 9e-89 | 12.6 EB05 9.4 · IC025 +2.9 3/3 methods agree | Labeled (related wording) related wording | serious n=8 · 86% consumer | no trial data cached |
| Coeliac disease | 13 | 12.3 7.2–21.2ROR 12.4 · χ² 124 / p 4e-29 | 10.9 EB05 6.1 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 26.1 | no trial data cached |
| Menstruation delayed | 13 | 11.7 6.8–20.1ROR 11.7 · χ² 116 / p 2e-27 | 10.1 EB05 5.7 · IC025 +2.1 3/3 methods agree | Labeled adverse reaction exact term | serious n=1 | no trial data cached |
| Dermatitis atopic | 57 | 10.6 8.2–13.7ROR 10.9 · χ² 488 / p 2e-108 | 10.3 EB05 8.1 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious n=1 | no trial data cached |
| Sleep disorder due to a general medical condition | 17 | 9.8 6.1–15.7ROR 9.9 · χ² 126 / p 2e-29 | 8.6 EB05 5.4 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 5.8 | no trial data cached |
| Menorrhagia (heavy periods) | 20 | 9.4 6.0–14.5ROR 9.4 · χ² 141 / p 8e-33 | 8.3 EB05 5.5 · IC025 +2.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 12.5 | no trial data cached |
| Dysmenorrhoea | 12 | 8.5 4.9–15.0ROR 8.6 · χ² 73 / p 8e-18 | 6.9 EB05 4.1 · IC025 +1.7 3/3 methods agree | Not in label — unassessed | serious n=1 | no trial data cached |
| Bursitis | 11 | 8.5 4.7–15.3ROR 8.5 · χ² 65 / p 3e-16 | 6.8 EB05 3.9 · IC025 +1.7 3/3 methods agree | Not in label — unassessed | serious PRR 17.0 | no trial data cached |
| Vaginal haemorrhage | 38 | 8.3 6.1–11.4ROR 8.4 · χ² 237 / p 7e-54 | 7.8 EB05 5.8 · IC025 +2.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 5.5 · 89% consumer | no trial data cached |
| Amenorrhoea (missed periods) | 13 | 7.3 4.2–12.5ROR 7.3 · χ² 64 / p 6e-16 | 6.0 EB05 3.7 · IC025 +1.6 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious PRR 8.7 | no trial data cached |
| Injection site urticaria | 18 | 6.9 4.4–10.9ROR 7.0 · χ² 85 / p 1e-20 | 6.0 EB05 4.0 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious n=2 | no trial data cached |
| Product substitution issue | 39 | 6.3 4.6–8.6ROR 6.4 · χ² 169 / p 5e-39 | 5.9 EB05 4.5 · IC025 +2.0 3/3 methods agree | Reporting / coding artifact | serious PRR 7.6 · 74% consumer | no trial data cached |
| Ear infection | 17 | 6.0 3.7–9.6ROR 6.0 · χ² 65 / p 3e-16 | 5.2 EB05 3.4 · IC025 +1.6 3/3 methods agree | Labeled (related wording) related wording | serious PRR 12.0 | no trial data cached |
| Poor quality sleep | 13 | 5.7 3.3–9.7ROR 5.7 · χ² 45 / p 8e-12 | 4.8 EB05 3.0 · IC025 +1.3 3/3 methods agree | Reporting / coding artifact | serious PRR 13.6 | no trial data cached |
| Product dose omission in error | 16 | 5.5 3.4–9.0ROR 5.6 · χ² 55 / p 5e-14 | 4.8 EB05 3.2 · IC025 +1.4 3/3 methods agree | Reporting / coding artifact | serious PRR 13.9 | no trial data cached |
| Middle insomnia | 11 | 5.5 3.1–9.9ROR 5.5 · χ² 36 / p 9e-10 | 4.6 EB05 2.7 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 9.3 | no trial data cached |
| Migraine | 52 | 5.1 3.9–6.7ROR 5.2 · χ² 168 / p 9e-39 | 4.9 EB05 3.9 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious PRR 9.5 | no trial data cached |
| Night sweats | 17 | 4.9 3.1–7.9ROR 4.9 · χ² 49 / p 1e-12 | 4.4 EB05 2.9 · IC025 +1.3 3/3 methods agree | Not in label — unassessed | serious PRR 3.4 | no trial data cached |
| Intentional dose omission | 14 | 4.8 2.8–8.0ROR 4.8 · χ² 38 / p 4e-10 | 4.2 EB05 2.7 · IC025 +1.2 3/3 methods agree | Reporting / coding artifact | serious PRR 3.6 | no trial data cached |
| Mood swings | 16 | 4.7 2.9–7.6ROR 4.7 · χ² 43 / p 3e-11 | 4.2 EB05 2.7 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 3.5 | no trial data cached |
| Disease recurrence | 21 | 4.1 2.7–6.3ROR 4.1 · χ² 46 / p 5e-12 | 3.8 EB05 2.6 · IC025 +1.2 3/3 methods agree | Reporting / coding artifact | serious PRR 1.3 | no trial data cached |
| Eczema | 21 | 3.9 2.5–5.9ROR 3.9 · χ² 42 / p 4e-11 | 3.6 EB05 2.5 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious PRR 1.8 | no trial data cached |
| Injection site pruritus | 27 | 3.8 2.6–5.5ROR 3.8 · χ² 53 / p 2e-13 | 3.6 EB05 2.6 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 1.7 · 77% consumer | no trial data cached |
| Mood altered | 11 | 3.8 2.1–6.8ROR 3.8 · χ² 20 / p 5e-6 | 3.3 EB05 2.0 · IC025 +0.7 3/3 methods agree | Not in label — unassessed | serious PRR 6.2 | no trial data cached |
| Hot flush (hot flashes) | 29 | 3.6 2.5–5.1ROR 3.6 · χ² 52 / p 3e-13 | 3.4 EB05 2.5 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 5.9 · 81% consumer | no trial data cached |
| Injection site swelling | 29 | 3.6 2.5–5.1ROR 3.6 · χ² 51 / p 4e-13 | 3.4 EB05 2.5 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 4.0 | no trial data cached |
| Injury | 27 | 3.6 2.4–5.2ROR 3.6 · χ² 47 / p 3e-12 | 3.4 EB05 2.4 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious PRR 7.5 | no trial data cached |
| Injection site bruising | 29 | 3.4 2.4–4.9ROR 3.5 · χ² 48 / p 3e-12 | 3.3 EB05 2.4 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious PRR 1.2 · 76% consumer | no trial data cached |
| Emotional disorder | 11 | 3.3 1.8–6.0ROR 3.3 · χ² 15 / p 4e-5 | 3.0 EB05 1.8 · IC025 +0.6 | Not in label — unassessed | serious PRR 5.6 | no trial data cached |
| Injection site reaction | 24 | 3.3 2.2–4.8ROR 3.3 · χ² 35 / p 1e-9 | 3.1 EB05 2.2 · IC025 +1.0 3/3 methods agree | Not in label — unassessed | serious PRR 1.2 | no trial data cached |
| Product dose omission | 23 | 3.2 2.2–4.9ROR 3.3 · χ² 33 / p 4e-9 | 3.1 EB05 2.2 · IC025 +0.9 3/3 methods agree | Reporting / coding artifact | 74% consumer | no trial data cached |
| Injection site erythema (redness where injected) | 41 | 3.1 2.3–4.2ROR 3.1 · χ² 56 / p 3e-14 | 3.0 EB05 2.3 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious PRR 1.6 | no trial data cached |
| Crying | 12 | 3.1 1.7–5.4ROR 3.1 · χ² 15 / p 6e-5 | 2.8 EB05 1.7 · IC025 +0.5 | Not in label — unassessed | serious PRR 5.9 | no trial data cached |
| Suicidal ideation (thoughts of suicide) | 30 | 3.0 2.1–4.3ROR 3.1 · χ² 39 / p 2e-10 | 2.9 EB05 2.2 · IC025 +1.0 3/3 methods agree | Not in label — unassessed | serious PRR 5.2 | no trial data cached |
| Product dose omission issue | 93 | 3.0 2.5–3.7ROR 3.1 · χ² 127 / p 9e-30 | 3.0 EB05 2.5 · IC025 +1.2 3/3 methods agree | Reporting / coding artifact | serious PRR 4.6 | no trial data cached |
| Colitis ulcerative | 14 | 2.9 1.7–4.9ROR 2.9 · χ² 16 / p 3e-5 | 2.7 EB05 1.7 · IC025 +0.6 | Not in label — unassessed | serious PRR 4.6 | no trial data cached |
| Acne | 23 | 2.8 1.9–4.2ROR 2.8 · χ² 25 / p 3e-7 | 2.7 EB05 1.9 · IC025 +0.7 | Labeled adverse reaction exact term | serious PRR 12.2 · 76% consumer | no trial data cached |
| Irritability | 18 | 2.8 1.8–4.4ROR 2.8 · χ² 19 / p 7e-6 | 2.6 EB05 1.8 · IC025 +0.6 | Not in label — unassessed | serious PRR 3.2 | no trial data cached |
| No adverse event | 53 | 2.8 2.1–3.6ROR 2.8 · χ² 59 / p 7e-15 | 2.7 EB05 2.2 · IC025 +1.0 3/3 methods agree | Reporting / coding artifact | 87% consumer | 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 |
|---|---|---|---|---|---|---|
| Product dose omission issue | 93 | 3.0 2.5–3.7ROR 3.1 · χ² 127 / p 9e-30 | 3.0 EB05 2.5 · IC025 +1.2 3/3 methods agree | Reporting / coding artifact | serious PRR 4.6 | no trial data cached |
| Injection site pain (pain where injected) | 68 | 2.1 1.7–2.6ROR 2.1 · χ² 38 / p 4e-10 | 2.1 EB05 1.7 · IC025 +0.6 | Labeled (related wording) related wording | serious PRR 2.3 · 71% consumer | no trial data cached |
| Dermatitis atopic | 57 | 10.6 8.2–13.7ROR 10.9 · χ² 488 / p 2e-108 | 10.3 EB05 8.1 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious n=1 | no trial data cached |
| No adverse event | 53 | 2.8 2.1–3.6ROR 2.8 · χ² 59 / p 7e-15 | 2.7 EB05 2.2 · IC025 +1.0 3/3 methods agree | Reporting / coding artifact | 87% consumer | no trial data cached |
| Migraine | 52 | 5.1 3.9–6.7ROR 5.2 · χ² 168 / p 9e-39 | 4.9 EB05 3.9 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious PRR 9.5 | no trial data cached |
| Injection site erythema (redness where injected) | 41 | 3.1 2.3–4.2ROR 3.1 · χ² 56 / p 3e-14 | 3.0 EB05 2.3 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious PRR 1.6 | no trial data cached |
| Product substitution issue | 39 | 6.3 4.6–8.6ROR 6.4 · χ² 169 / p 5e-39 | 5.9 EB05 4.5 · IC025 +2.0 3/3 methods agree | Reporting / coding artifact | serious PRR 7.6 · 74% consumer | no trial data cached |
| Vaginal haemorrhage | 38 | 8.3 6.1–11.4ROR 8.4 · χ² 237 / p 7e-54 | 7.8 EB05 5.8 · IC025 +2.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 5.5 · 89% consumer | no trial data cached |
| Menstruation irregular | 37 | 13.0 9.4–17.9ROR 13.2 · χ² 398 / p 9e-89 | 12.6 EB05 9.4 · IC025 +2.9 3/3 methods agree | Labeled (related wording) related wording | serious n=8 · 86% consumer | no trial data cached |
| Dry skin | 35 | 2.5 1.8–3.4ROR 2.5 · χ² 30 / p 3e-8 | 2.4 EB05 1.8 · IC025 +0.7 | Labeled (related wording) related wording | serious PRR 2.6 | no trial data cached |
| Metrorrhagia | 31 | 16.7 11.8–23.7ROR 16.9 · χ² 442 / p 2e-98 | 16.4 EB05 12.0 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=4 · 90% consumer | no trial data cached |
| Suicidal ideation (thoughts of suicide) | 30 | 3.0 2.1–4.3ROR 3.1 · χ² 39 / p 2e-10 | 2.9 EB05 2.2 · IC025 +1.0 3/3 methods agree | Not in label — unassessed | serious PRR 5.2 | no trial data cached |
| Injection site bruising | 29 | 3.4 2.4–4.9ROR 3.5 · χ² 48 / p 3e-12 | 3.3 EB05 2.4 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious PRR 1.2 · 76% consumer | no trial data cached |
| Injection site swelling | 29 | 3.6 2.5–5.1ROR 3.6 · χ² 51 / p 4e-13 | 3.4 EB05 2.5 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 4.0 | no trial data cached |
| Hot flush (hot flashes) | 29 | 3.6 2.5–5.1ROR 3.6 · χ² 52 / p 3e-13 | 3.4 EB05 2.5 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 5.9 · 81% consumer | 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=31, PRR 16.7
- Dermatitis atopic — n=57, PRR 10.6
- Migraine — n=52, PRR 5.1
- Eczema — n=21, PRR 3.9
- Injection site pruritus — n=27, PRR 3.8
- Hot flush — n=29, PRR 3.6
- Injection site swelling — n=29, PRR 3.6
- Injury — n=27, PRR 3.6
- Injection site bruising — n=29, PRR 3.4
- Injection site reaction — n=24, PRR 3.3
✓ A hand-written Bradford Hill causality assessment exists for this drug: Medroxyprogesterone acetate ↔ Meningioma.
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 Norethindrone and Ethinyl Estradiol?
In FDA FAERS, the most frequently co-reported reaction terms for Norethindrone and Ethinyl Estradiol are injection site pain, dermatitis atopic, migraine, injection site erythema, vaginal haemorrhage, menstruation irregular. 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 Norethindrone and Ethinyl Estradiol have an FDA boxed warning?
No. The FDA label retrieved for Norethindrone and Ethinyl Estradiol has no boxed warning; see the label's Warnings and Precautions for the recognised risks.
Do FAERS signals prove that Norethindrone 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 0d2f8fea-3675-40d2-afd9-9fcb148dbd4b, effective 20260131; matched on
openfda.generic_name.exact:"NORETHINDRONE") - 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, 114 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.