Norelgestromin and Ethinyl Estradiol side effects: what 1,833 FDA adverse event reports show

Norelgestromin And Ethinyl Estradiol · 38 reaction terms · 2,296 drug–reaction co-reports · data 2026-09-14

Drug class

Progestin, Estrogen

FDA label (Established Pharmacologic Class) · compare the class

Who reports

1,833 reports · 15% serious · 5 with death outcome · 100% female

openFDA FAERS counts, all years, deduplication not applied

Used for

Norelgestromin and ethinyl estradiol transdermal system is indicated for the prevention of pregnancy in women with a body mass index (BMI) < 30 kg/m 2 for whom a combined hormonal contraceptive is appropriate. Limitations of Use: Norelgestromin and ethinyl estradiol transdermal system may be less effective in preventing pregnancy in women who weigh 198 lbs (90 kg) or more.

FDA label, Indications and Usage

What it is

Norelgestromin and ethinyl estradiol transdermal system is a transdermal system with a contact surface area of 15.75 cm 2 . It contains 4.678 mg norelgestromin, USP (NGMN) and 0.53 mg ethinyl estradiol, USP (EE), and its delivery rate is approximately 150 mcg of NGMN and 35 mcg of EE per day.

FDA label, Description section

Boxed warning

CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS and CONTRAINDICATED IN WOMEN WITH A BMI |GTE 30 kg/m2 • Cigarette Smoking and Serious Cardiovascular Events Cigarette smoking increases the risk of serious cardiovascular events from hormonal contraceptive use.

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 23 strongest signals

Labeled adverse reaction 3Labeled (related wording) 6Reporting / coding artifact 9Not 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.
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.
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. 15 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
Product adhesion issue	691	227.1 213.9–241.1ROR 363.5 · χ² 152,480 / p <1e-300	221.2 EB05 207.7 · IC025 +7.5 3/3 methods agree	Reporting / coding artifact	serious n=25 · 94% consumer	no trial data cached
Application site rash	118	98.5 82.7–117.4ROR 105.2 · χ² 11,201 / p <1e-300	96.2 EB05 82.5 · IC025 +5.8 3/3 methods agree	Labeled (related wording) related wording	serious n=7 · 75% consumer	no trial data cached
Application site irritation	104	96.2 79.8–116.1ROR 102.0 · χ² 9,632 / p <1e-300	93.8 EB05 79.7 · IC025 +5.7 3/3 methods agree	Labeled (related wording) related wording	serious n=7 · 87% consumer	no trial data cached
Application site pruritus	166	84.1 72.7–97.3ROR 92.4 · χ² 13,468 / p <1e-300	82.8 EB05 72.7 · IC025 +5.8 3/3 methods agree	Labeled (related wording) related wording	serious n=10 · 90% consumer	no trial data cached
Metrorrhagia	111	73.8 61.6–88.4ROR 78.4 · χ² 7,850 / p <1e-300	72.4 EB05 61.8 · IC025 +5.5 3/3 methods agree	Not in label — unassessed	serious n=3 · 89% consumer	no trial data cached
Application site erythema	120	52.3 44.0–62.2ROR 55.9 · χ² 5,968 / p <1e-300	51.7 EB05 44.4 · IC025 +5.1 3/3 methods agree	Labeled (related wording) related wording	serious n=2 · 84% consumer	no trial data cached
Application site pain	73	38.0 30.3–47.6ROR 39.5 · χ² 2,586 / p <1e-300	37.5 EB05 30.8 · IC025 +4.5 3/3 methods agree	Labeled (related wording) related wording	serious n=8 · 90% consumer	no trial data cached
Product packaging quantity issue	26	27.3 18.6–40.0ROR 27.6 · χ² 631 / p 2e-139	26.7 EB05 19.2 · IC025 +3.5 3/3 methods agree	Reporting / coding artifact	serious n=1 · 88% consumer	no trial data cached
Dysmenorrhoea	23	20.1 13.4–30.2ROR 20.4 · χ² 399 / p 6e-89	19.7 EB05 13.8 · IC025 +3.1 3/3 methods agree	Not in label — unassessed	serious n=3 · 91% consumer	no trial data cached
Wrong technique in product usage process	340	19.3 17.5–21.2ROR 23.4 · χ² 5,914 / p <1e-300	19.2 EB05 17.6 · IC025 +4.0 3/3 methods agree	Reporting / coding artifact	serious PRR 6.5 · 92% consumer	no trial data cached
Menorrhagia (heavy periods)	27	15.5 10.7–22.5ROR 15.7 · χ² 352 / p 9e-79	15.1 EB05 10.7 · IC025 +3.0 3/3 methods agree	Not in label — unassessed	serious PRR 19.6 · 92% consumer	no trial data cached
Menstruation irregular	32	13.8 9.8–19.4ROR 14.0 · χ² 367 / p 5e-82	13.4 EB05 9.7 · IC025 +2.9 3/3 methods agree	Not in label — unassessed	91% consumer	no trial data cached
Dermatitis contact	12	12.1 6.9–21.2ROR 12.2 · χ² 111 / p 3e-26	10.4 EB05 5.7 · IC025 +2.1 3/3 methods agree	Labeled adverse reaction exact term	serious n=3	no trial data cached
Vaginal haemorrhage	37	9.9 7.2–13.7ROR 10.1 · χ² 289 / p 5e-65	9.4 EB05 7.0 · IC025 +2.6 3/3 methods agree	Labeled (related wording) related wording	serious PRR 17.2 · 89% consumer	no trial data cached
Mood swings	25	9.0 6.1–13.2ROR 9.1 · χ² 169 / p 6e-39	8.1 EB05 5.6 · IC025 +2.3 3/3 methods agree	Not in label — unassessed	serious PRR 9.5 · 91% consumer	no trial data cached
Product quality issue	98	8.3 6.9–10.1ROR 8.7 · χ² 626 / p 2e-138	8.1 EB05 6.8 · IC025 +2.7 3/3 methods agree	Reporting / coding artifact	serious PRR 9.4 · 92% consumer	no trial data cached
Product substitution issue	37	7.3 5.3–10.1ROR 7.5 · χ² 197 / p 5e-45	6.8 EB05 5.1 · IC025 +2.2 3/3 methods agree	Reporting / coding artifact	serious PRR 28.8 · 75% consumer	no trial data cached
Incorrect drug administration duration	11	4.4 2.4–7.9ROR 4.4 · χ² 26 / p 2e-7	3.8 EB05 2.3 · IC025 +0.9 3/3 methods agree	Reporting / coding artifact	serious PRR 4.3	no trial data cached
Product dose omission	25	4.3 2.9–6.4ROR 4.4 · χ² 61 / p 4e-15	4.0 EB05 2.9 · IC025 +1.3 3/3 methods agree	Reporting / coding artifact	96% consumer	no trial data cached
Skin irritation	14	3.5 2.1–5.9ROR 3.5 · χ² 22 / p 1e-6	3.2 EB05 2.0 · IC025 +0.8 3/3 methods agree	Labeled adverse reaction exact term	serious n=1	no trial data cached
Inappropriate schedule of drug administration	21	3.3 2.2–5.1ROR 3.4 · χ² 32 / p 8e-9	3.1 EB05 2.2 · IC025 +0.9 3/3 methods agree	Reporting / coding artifact	serious PRR 2.1 · 95% consumer	no trial data cached
No adverse event	45	2.9 2.2–3.9ROR 2.9 · χ² 55 / p 8e-14	2.8 EB05 2.2 · IC025 +1.0 3/3 methods agree	Reporting / coding artifact	84% consumer	no trial data cached
Acne	17	2.5 1.6–4.1ROR 2.6 · χ² 15 / p 7e-5	2.4 EB05 1.6 · IC025 +0.5	Labeled adverse reaction exact term	serious PRR 5.6	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 adhesion issue	691	227.1 213.9–241.1ROR 363.5 · χ² 152,480 / p <1e-300	221.2 EB05 207.7 · IC025 +7.5 3/3 methods agree	Reporting / coding artifact	serious n=25 · 94% consumer	no trial data cached
Wrong technique in product usage process	340	19.3 17.5–21.2ROR 23.4 · χ² 5,914 / p <1e-300	19.2 EB05 17.6 · IC025 +4.0 3/3 methods agree	Reporting / coding artifact	serious PRR 6.5 · 92% consumer	no trial data cached
Application site pruritus	166	84.1 72.7–97.3ROR 92.4 · χ² 13,468 / p <1e-300	82.8 EB05 72.7 · IC025 +5.8 3/3 methods agree	Labeled (related wording) related wording	serious n=10 · 90% consumer	no trial data cached
Application site erythema	120	52.3 44.0–62.2ROR 55.9 · χ² 5,968 / p <1e-300	51.7 EB05 44.4 · IC025 +5.1 3/3 methods agree	Labeled (related wording) related wording	serious n=2 · 84% consumer	no trial data cached
Application site rash	118	98.5 82.7–117.4ROR 105.2 · χ² 11,201 / p <1e-300	96.2 EB05 82.5 · IC025 +5.8 3/3 methods agree	Labeled (related wording) related wording	serious n=7 · 75% consumer	no trial data cached
Metrorrhagia	111	73.8 61.6–88.4ROR 78.4 · χ² 7,850 / p <1e-300	72.4 EB05 61.8 · IC025 +5.5 3/3 methods agree	Not in label — unassessed	serious n=3 · 89% consumer	no trial data cached
Application site irritation	104	96.2 79.8–116.1ROR 102.0 · χ² 9,632 / p <1e-300	93.8 EB05 79.7 · IC025 +5.7 3/3 methods agree	Labeled (related wording) related wording	serious n=7 · 87% consumer	no trial data cached
Product quality issue	98	8.3 6.9–10.1ROR 8.7 · χ² 626 / p 2e-138	8.1 EB05 6.8 · IC025 +2.7 3/3 methods agree	Reporting / coding artifact	serious PRR 9.4 · 92% consumer	no trial data cached
Application site pain	73	38.0 30.3–47.6ROR 39.5 · χ² 2,586 / p <1e-300	37.5 EB05 30.8 · IC025 +4.5 3/3 methods agree	Labeled (related wording) related wording	serious n=8 · 90% consumer	no trial data cached
No adverse event	45	2.9 2.2–3.9ROR 2.9 · χ² 55 / p 8e-14	2.8 EB05 2.2 · IC025 +1.0 3/3 methods agree	Reporting / coding artifact	84% consumer	no trial data cached
Product substitution issue	37	7.3 5.3–10.1ROR 7.5 · χ² 197 / p 5e-45	6.8 EB05 5.1 · IC025 +2.2 3/3 methods agree	Reporting / coding artifact	serious PRR 28.8 · 75% consumer	no trial data cached
Vaginal haemorrhage	37	9.9 7.2–13.7ROR 10.1 · χ² 289 / p 5e-65	9.4 EB05 7.0 · IC025 +2.6 3/3 methods agree	Labeled (related wording) related wording	serious PRR 17.2 · 89% consumer	no trial data cached
Menstruation irregular	32	13.8 9.8–19.4ROR 14.0 · χ² 367 / p 5e-82	13.4 EB05 9.7 · IC025 +2.9 3/3 methods agree	Not in label — unassessed	91% consumer	no trial data cached
Drug dose omission	28	1.9 1.3–2.8ROR 1.9 · χ² 11 / p 4e-4	1.9 EB05 1.4 · IC025 +0.3	Reporting / coding artifact	serious PRR 1.1 · 89% consumer	no trial data cached
Menorrhagia (heavy periods)	27	15.5 10.7–22.5ROR 15.7 · χ² 352 / p 9e-79	15.1 EB05 10.7 · IC025 +3.0 3/3 methods agree	Not in label — unassessed	serious PRR 19.6 · 92% 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=111, PRR 73.8
Dysmenorrhoea — n=23, PRR 20.1
Menorrhagia — n=27, PRR 15.5
Menstruation irregular — n=32, PRR 13.8
Mood swings — n=25, PRR 9.0

✓ 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 Norelgestromin and Ethinyl Estradiol?

In FDA FAERS, the most frequently co-reported reaction terms for Norelgestromin and Ethinyl Estradiol are application site pruritus, application site erythema, application site rash, metrorrhagia, application site irritation, application site pain. 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 Norelgestromin and Ethinyl Estradiol have an FDA boxed warning?

Yes. The current FDA label carries a boxed warning: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS and CONTRAINDICATED IN WOMEN WITH A BMI |GTE 30 kg/m2 • Cigarette Smoking and Serious Cardiovascular Events Cigarette smoking increases the risk of serious cardiovascular events from hormonal contraceptive use.

Do FAERS signals prove that Norelgestromin 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 10fa1458-c8ed-4197-922a-1ba7271d2b02, effective 20260416; matched on openfda.generic_name.exact:"NORELGESTROMIN 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, field patient.drug.openfda.generic_name.exact, 38 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.