Norgestimate and Ethinyl Estradiol side effects: what 4,549 FDA adverse event reports show
Drug class
Not stated in label
Who reports
4,549 reports · 41% serious · 43 with death outcome · 99% female
Used for
Norgestimate and ethinyl estradiol tablets USP are estrogen/progestin COCs, indicated for use by women to prevent pregnancy. ( 1.1 ) 1.1 Oral Contraceptive Norgestimate and ethinyl estradiol tablets USP are indicated for use by females of reproductive potential to prevent pregnancy .
What it is
Each of the following products is a combination oral contraceptive containing the progestational compound Norgestimate and the estrogenic compound ethinyl estradiol. Norgestimate is designated.
Boxed warning
CIGARETTE SMOKING and SERIOUS CARDIOVASCULAR EVENTS See full prescribing information for complete boxed warning. Norgestimate and Ethinyl Estradiol Tablets USP is contraindicated in women over 35 years old who smoke. (4) Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives (COC) use. (4)
Causality screen of the 40 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.
- 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. 173 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 |
|---|---|---|---|---|---|---|
| Metrorrhagia | 86 | 23.0 18.6–28.4ROR 23.4 · χ² 1,779 / p <1e-300 | 22.8 EB05 19.0 · IC025 +4.0 3/3 methods agree | Labeled adverse reaction exact term | serious n=33 | no trial data cached |
| Menstruation irregular | 100 | 17.4 14.3–21.1ROR 17.8 · χ² 1,526 / p <1e-300 | 17.3 EB05 14.6 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious n=22 · 80% consumer | no trial data cached |
| Dysmenorrhoea | 47 | 16.6 12.5–22.1ROR 16.8 · χ² 671 / p 3e-148 | 16.4 EB05 12.8 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious n=13 | no trial data cached |
| Menorrhagia (heavy periods) | 68 | 15.8 12.4–20.0ROR 16.0 · χ² 923 / p 6e-203 | 15.6 EB05 12.7 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious PRR 20.6 | no trial data cached |
| Menstruation delayed | 31 | 13.8 9.7–19.6ROR 13.9 · χ² 354 / p 4e-79 | 13.4 EB05 9.6 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious n=2 · 93% consumer | no trial data cached |
| Vaginal haemorrhage | 102 | 11.0 9.1–13.4ROR 11.3 · χ² 922 / p 9e-203 | 10.9 EB05 9.2 · IC025 +3.1 3/3 methods agree | Labeled (related wording) related wording | serious PRR 8.4 · 82% consumer | no trial data cached |
| Coeliac disease | 23 | 10.8 7.2–16.2ROR 10.9 · χ² 195 / p 2e-44 | 9.9 EB05 6.7 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious PRR 17.4 · 86% consumer | no trial data cached |
| Ovarian cyst | 21 | 9.6 6.3–14.8ROR 9.7 · χ² 154 / p 1e-35 | 8.6 EB05 5.7 · IC025 +2.3 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 12.9 | no trial data cached |
| Product substitution issue | 116 | 9.3 7.8–11.1ROR 9.5 · χ² 851 / p 3e-187 | 9.1 EB05 7.8 · IC025 +2.9 3/3 methods agree | Reporting / coding artifact | serious PRR 10.6 | no trial data cached |
| Unintended pregnancy | 21 | 9.3 6.0–14.2ROR 9.3 · χ² 146 / p 6e-34 | 8.2 EB05 5.5 · IC025 +2.2 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious PRR 13.5 | no trial data cached |
| Mood swings | 52 | 7.5 5.7–9.8ROR 7.6 · χ² 287 / p 1e-64 | 7.1 EB05 5.6 · IC025 +2.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 8.6 | no trial data cached |
| Gallbladder disorder | 29 | 7.5 5.2–10.7ROR 7.5 · χ² 156 / p 5e-36 | 6.8 EB05 4.9 · IC025 +2.1 3/3 methods agree | Labeled (related wording) related wording | serious PRR 11.6 | no trial data cached |
| Breast pain | 17 | 7.3 4.6–11.8ROR 7.4 · χ² 87 / p 6e-21 | 6.3 EB05 4.1 · IC025 +1.8 3/3 methods agree | Labeled adverse reaction exact term | serious n=4 | no trial data cached |
| Pelvic pain | 28 | 7.1 4.9–10.3ROR 7.1 · χ² 140 / p 1e-32 | 6.4 EB05 4.6 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 8.5 | no trial data cached |
| Cholelithiasis | 50 | 7.0 5.3–9.3ROR 7.1 · χ² 252 / p 4e-57 | 6.6 EB05 5.2 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious PRR 10.5 | no trial data cached |
| Product packaging issue | 14 | 7.0 4.1–11.7ROR 7.0 · χ² 65 / p 3e-16 | 5.8 EB05 3.6 · IC025 +1.6 3/3 methods agree | Reporting / coding artifact | – | no trial data cached |
| Cholecystectomy | 17 | 6.9 4.3–11.1ROR 6.9 · χ² 80 / p 2e-19 | 5.9 EB05 3.9 · IC025 +1.7 3/3 methods agree | Not in label — unassessed | serious PRR 10.1 | no trial data cached |
| Dermatitis atopic | 74 | 6.8 5.4–8.6ROR 6.9 · χ² 362 / p 4e-81 | 6.6 EB05 5.4 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | – | no trial data cached |
| Complication of device insertion | 26 | 6.5 4.4–9.5ROR 6.5 · χ² 114 / p 5e-27 | 5.9 EB05 4.2 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious n=2 · 92% clinician | no trial data cached |
| Vaginal discharge | 14 | 6.4 3.8–10.8ROR 6.4 · χ² 59 / p 9e-15 | 5.4 EB05 3.4 · IC025 +1.5 3/3 methods agree | Labeled (related wording) related wording | serious n=3 | no trial data cached |
| Amenorrhoea (missed periods) | 23 | 6.3 4.2–9.5ROR 6.4 · χ² 98 / p 2e-23 | 5.7 EB05 4.0 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious PRR 8.0 · 86% consumer | no trial data cached |
| Initial insomnia | 14 | 6.3 3.7–10.7ROR 6.3 · χ² 57 / p 2e-14 | 5.3 EB05 3.4 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious n=2 | no trial data cached |
| Affect lability | 13 | 6.2 3.6–10.7ROR 6.2 · χ² 51 / p 4e-13 | 5.2 EB05 3.2 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious PRR 5.6 | no trial data cached |
| Abortion induced | 12 | 5.9 3.3–10.3ROR 5.9 · χ² 44 / p 2e-11 | 4.9 EB05 3.0 · IC025 +1.3 3/3 methods agree | Not in label — unassessed | serious PRR 8.7 | no trial data cached |
| Cholecystitis | 15 | 5.8 3.5–9.6ROR 5.8 · χ² 55 / p 6e-14 | 5.0 EB05 3.2 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 8.3 | no trial data cached |
| Abdominal pain lower | 31 | 5.6 4.0–8.0ROR 5.7 · χ² 113 / p 9e-27 | 5.2 EB05 3.8 · IC025 +1.8 3/3 methods agree | Labeled (related wording) related wording | serious PRR 8.1 | no trial data cached |
| Mood altered | 33 | 5.6 4.0–7.9ROR 5.6 · χ² 120 / p 3e-28 | 5.2 EB05 3.9 · IC025 +1.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 8.1 | no trial data cached |
| Panic attack | 41 | 5.2 3.8–7.0ROR 5.2 · χ² 134 / p 3e-31 | 4.9 EB05 3.8 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious PRR 6.2 | no trial data cached |
| Injury | 79 | 5.1 4.1–6.4ROR 5.2 · χ² 261 / p 6e-59 | 5.0 EB05 4.1 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 8.8 | no trial data cached |
| Sleep disorder due to a general medical condition | 18 | 5.1 3.2–8.1ROR 5.1 · χ² 56 / p 4e-14 | 4.6 EB05 3.1 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | – | no trial data cached |
| Pulmonary embolism (lung blood clot) | 106 | 5.1 4.2–6.2ROR 5.2 · χ² 348 / p 6e-78 | 5.0 EB05 4.3 · IC025 +2.0 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 7.2 | no trial data cached |
| Product dose omission | 71 | 4.9 3.9–6.2ROR 5.0 · χ² 219 / p 6e-50 | 4.8 EB05 3.9 · IC025 +1.9 3/3 methods agree | Reporting / coding artifact | serious PRR 1.6 · 80% consumer | no trial data cached |
| Impaired work ability | 21 | 4.5 2.9–6.9ROR 4.5 · χ² 54 / p 1e-13 | 4.1 EB05 2.9 · IC025 +1.3 3/3 methods agree | Labeled (related wording) related wording | serious PRR 5.8 | no trial data cached |
| Deep vein thrombosis (leg blood clot) | 62 | 4.4 3.4–5.6ROR 4.4 · χ² 158 / p 1e-36 | 4.2 EB05 3.4 · IC025 +1.7 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 6.3 | no trial data cached |
| Genital haemorrhage | 12 | 4.3 2.4–7.5ROR 4.3 · χ² 27 / p 1e-7 | 3.7 EB05 2.3 · IC025 +0.9 3/3 methods agree | Labeled (related wording) related wording | serious PRR 6.9 | no trial data cached |
| Pharmaceutical product complaint | 24 | 4.2 2.8–6.3ROR 4.2 · χ² 55 / p 5e-14 | 3.9 EB05 2.8 · IC025 +1.3 3/3 methods agree | Not in label — unassessed | serious PRR 8.4 | no trial data cached |
| Pregnancy | 18 | 4.1 2.6–6.5ROR 4.1 · χ² 39 / p 2e-10 | 3.7 EB05 2.5 · IC025 +1.1 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 5.2 | no trial data cached |
| Maternal exposure during pregnancy | 78 | 4.1 3.3–5.1ROR 4.1 · χ² 178 / p 6e-41 | 4.0 EB05 3.3 · IC025 +1.6 3/3 methods agree | Reporting / coding artifact | serious PRR 5.6 | no trial data cached |
| Mydriasis | 11 | 4.0 2.2–7.1ROR 4.0 · χ² 21 / p 2e-6 | 3.5 EB05 2.1 · IC025 +0.8 3/3 methods agree | Not in label — unassessed | serious PRR 5.9 | no trial data cached |
| Acne | 65 | 3.9 3.1–5.0ROR 4.0 · χ² 139 / p 2e-32 | 3.8 EB05 3.1 · IC025 +1.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 7.2 · 72% consumer | 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 |
|---|---|---|---|---|---|---|
| Nausea | 417 | 2.4 2.2–2.7ROR 2.6 · χ² 364 / p 2e-81 | 2.4 EB05 2.2 · IC025 +1.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.4 · 70% consumer | no trial data cached |
| Headache | 282 | 2.1 1.9–2.3ROR 2.1 · χ² 160 / p 5e-37 | 2.1 EB05 1.9 · IC025 +0.9 | Labeled — boxed warning exact term | serious PRR 2.1 | no trial data cached |
| Anxiety | 209 | 3.4 3.0–3.9ROR 3.5 · χ² 351 / p 1e-78 | 3.3 EB05 3.0 · IC025 +1.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.2 | no trial data cached |
| Depression | 177 | 3.6 3.1–4.1ROR 3.7 · χ² 328 / p 2e-73 | 3.5 EB05 3.1 · IC025 +1.6 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.8 | no trial data cached |
| Product dose omission issue | 118 | 1.9 1.6–2.3ROR 1.9 · χ² 51 / p 5e-13 | 1.9 EB05 1.6 · IC025 +0.6 | Reporting / coding artifact | serious PRR 2.8 | no trial data cached |
| Product substitution issue | 116 | 9.3 7.8–11.1ROR 9.5 · χ² 851 / p 3e-187 | 9.1 EB05 7.8 · IC025 +2.9 3/3 methods agree | Reporting / coding artifact | serious PRR 10.6 | no trial data cached |
| Abdominal pain upper | 114 | 2.6 2.1–3.1ROR 2.6 · χ² 107 / p 2e-25 | 2.5 EB05 2.2 · IC025 +1.0 3/3 methods agree | Labeled (related wording) related wording | serious PRR 3.6 · 78% consumer | no trial data cached |
| Pulmonary embolism (lung blood clot) | 106 | 5.1 4.2–6.2ROR 5.2 · χ² 348 / p 6e-78 | 5.0 EB05 4.3 · IC025 +2.0 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 7.2 | no trial data cached |
| Injection site pain (pain where injected) | 104 | 1.6 1.3–1.9ROR 1.6 · χ² 22 / p 2e-6 | 1.6 EB05 1.3 · IC025 +0.3 | Labeled (related wording) related wording | serious PRR 1.8 | no trial data cached |
| Vaginal haemorrhage | 102 | 11.0 9.1–13.4ROR 11.3 · χ² 922 / p 9e-203 | 10.9 EB05 9.2 · IC025 +3.1 3/3 methods agree | Labeled (related wording) related wording | serious PRR 8.4 · 82% consumer | no trial data cached |
| Menstruation irregular | 100 | 17.4 14.3–21.1ROR 17.8 · χ² 1,526 / p <1e-300 | 17.3 EB05 14.6 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious n=22 · 80% consumer | no trial data cached |
| Feeling abnormal | 91 | 1.7 1.4–2.1ROR 1.8 · χ² 28 / p 5e-8 | 1.7 EB05 1.5 · IC025 +0.4 | Not in label — unassessed | serious PRR 2.2 · 81% consumer | no trial data cached |
| Drug dose omission | 89 | 2.4 2.0–3.0ROR 2.5 · χ² 75 / p 2e-18 | 2.4 EB05 2.0 · IC025 +0.9 3/3 methods agree | Reporting / coding artifact | serious PRR 1.7 · 90% consumer | no trial data cached |
| Metrorrhagia | 86 | 23.0 18.6–28.4ROR 23.4 · χ² 1,779 / p <1e-300 | 22.8 EB05 19.0 · IC025 +4.0 3/3 methods agree | Labeled adverse reaction exact term | serious n=33 | no trial data cached |
| Urticaria (hives) | 81 | 2.2 1.8–2.8ROR 2.3 · χ² 55 / p 7e-14 | 2.2 EB05 1.8 · IC025 +0.8 | Labeled adverse reaction exact term | serious PRR 2.0 · 71% 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.
- Menstruation irregular — n=100, PRR 17.4
- Dysmenorrhoea — n=47, PRR 16.6
- Menorrhagia — n=68, PRR 15.8
- Menstruation delayed — n=31, PRR 13.8
- Coeliac disease — n=23, PRR 10.8
- Pelvic pain — n=28, PRR 7.1
- Cholelithiasis — n=50, PRR 7.0
- Dermatitis atopic — n=74, PRR 6.8
- Complication of device insertion — n=26, PRR 6.5
- Amenorrhoea — n=23, PRR 6.3
✓ 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 Norgestimate and Ethinyl Estradiol?
In FDA FAERS, the most frequently co-reported reaction terms for Norgestimate and Ethinyl Estradiol are nausea, headache, anxiety, depression, abdominal pain upper, pulmonary embolism. 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 Norgestimate and Ethinyl Estradiol have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: CIGARETTE SMOKING and SERIOUS CARDIOVASCULAR EVENTS See full prescribing information for complete boxed warning. Norgestimate and Ethinyl Estradiol Tablets USP is contraindicated in women over 35 years old who smoke. (4) Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives (COC) use. (4)
Do FAERS signals prove that Norgestimate 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 03de435b-b8fb-4faa-a0ec-01e48b5aaae4, effective 20240423; matched on
openfda.generic_name.exact:"NORGESTIMATE AND ETHINYL 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, 213 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.