Drug · FAERS side-effect profile with label screen

Etonogestrel and Ethinyl Estradiol side effects: what 22,047 FDA adverse event reports show

Etonogestrel And Ethinyl Estradiol · 1,146 reaction terms · 80,403 drug–reaction co-reports · data 2026-09-14

Drug class

Progestin

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

Label matched

Etonogestrel (Nexplanon)

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

Who reports

22,047 reports · 48% serious · 280 with death outcome · 99% female

openFDA FAERS counts, all years, deduplication not applied

Used for

NEXPLANON ® is indicated for prevention of pregnancy in women of reproductive potential for up to 5 years. NEXPLANON is a progestin indicated for prevention of pregnancy in women of reproductive potential for up to 5 years. ( 1 )

FDA label, Indications and Usage

What it is

NEXPLANON is a radiopaque, progestin-only, soft, flexible implant preloaded in a sterile, disposable applicator for subdermal use. The implant is white/off-white, non-biodegradable and 4 cm in length with a diameter of 2 mm (see Figure 19 ).

FDA label, Description section

Boxed warning

RISK OF COMPLICATIONS DUE TO IMPROPER INSERTION and REMOVAL Improper insertion of NEXPLANON increases the risk of complications [see Warnings and Precautions (5.1) ] . Proper training prior to first use of NEXPLANON can minimize the risk of improper NEXPLANON insertion [see Warnings and Precautions (5.1) ] .

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 40 strongest signals

Labeled — boxed warning 1Labeled (related wording) 6Reporting / coding artifact 3Lab value / disease marker 4Not in label — unassessed 26

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 (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.
Lab value / disease marker A laboratory result, investigation or disease-activity marker (antibody positive, CRP abnormal, swollen joint count) not described in the label. These usually mirror the monitored disease or testing protocol rather than a drug effect; not screened further.
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. 1,106 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
Vaginal mycosis	116	929.6 719.3–1,201.3ROR 934.5 · χ² 53,564 / p <1e-300	433.7 EB05 371.4 · IC025 +7.0 3/3 methods agree	Not in label — unassessed	–	not reported in cached trials
Contraceptive device complication	16	833.4 425.0–1,634.1ROR 834.0 · χ² 6,608 / p <1e-300	289.1 EB05 188.7 · IC025 +4.1 3/3 methods agree	Reporting / coding artifact	serious n=12	not reported in cached trials
Vena cava filter removal	15	781.3 393.8–1,550.1ROR 781.8 · χ² 5,957 / p <1e-300	276.4 EB05 177.8 · IC025 +4.0 3/3 methods agree	Not in label — unassessed	serious n=15	not reported in cached trials
Vena cava filter insertion	137	721.6 577.7–901.3ROR 726.1 · χ² 55,304 / p <1e-300	386.1 EB05 334.8 · IC025 +7.1 3/3 methods agree	Not in label — unassessed	serious n=137	not reported in cached trials
Venous stent insertion	28	656.3 405.0–1,063.6ROR 657.1 · χ² 10,394 / p <1e-300	305.7 EB05 222.0 · IC025 +5.0 3/3 methods agree	Labeled (related wording) related wording	serious n=28	not reported in cached trials
Abnormal withdrawal bleeding	249	360.3 311.5–416.7ROR 364.4 · χ² 64,189 / p <1e-300	255.4 EB05 229.9 · IC025 +7.2 3/3 methods agree	Not in label — unassessed	serious n=49 · 71% consumer	not reported in cached trials
Medical device site discomfort	154	289.4 241.6–346.5ROR 291.4 · χ² 33,597 / p <1e-300	215.5 EB05 188.4 · IC025 +6.7 3/3 methods agree	Not in label — unassessed	serious n=29	not reported in cached trials
Colposcopy	13	283.5 152.4–527.0ROR 283.6 · χ² 2,597 / p <1e-300	165.4 EB05 102.9 · IC025 +3.7 3/3 methods agree	Not in label — unassessed	serious n=10	not reported in cached trials
May-thurner syndrome	40	279.9 196.7–398.3ROR 280.4 · χ² 8,346 / p <1e-300	195.7 EB05 149.9 · IC025 +5.4 3/3 methods agree	Not in label — unassessed	serious n=39 · 73% consumer	not reported in cached trials
Ectropion of cervix	10	275.8 136.3–558.1ROR 275.9 · χ² 1,908 / p <1e-300	152.1 EB05 88.3 · IC025 +3.2 3/3 methods agree	Not in label — unassessed	–	not reported in cached trials
Withdrawal bleed	151	249.2 208.4–298.1ROR 251.0 · χ² 29,299 / p <1e-300	192.3 EB05 167.9 · IC025 +6.6 3/3 methods agree	Not in label — unassessed	serious n=48 · 71% consumer	not reported in cached trials
Thrombolysis	45	239.7 172.8–332.5ROR 240.2 · χ² 8,330 / p <1e-300	176.9 EB05 137.6 · IC025 +5.5 3/3 methods agree	Not in label — unassessed	serious n=44 · 74% consumer	not reported in cached trials
Thrombectomy	64	231.7 176.3–304.5ROR 232.3 · χ² 11,603 / p <1e-300	176.3 EB05 142.9 · IC025 +5.8 3/3 methods agree	Not in label — unassessed	serious n=62	not reported in cached trials
Protein s deficiency	35	203.8 141.4–293.7ROR 204.1 · χ² 5,637 / p <1e-300	153.7 EB05 115.5 · IC025 +5.1 3/3 methods agree	Not in label — unassessed	serious n=34	not reported in cached trials
Intentional medical device removal by patient	173	202.0 171.5–237.9ROR 203.6 · χ² 28,303 / p <1e-300	163.4 EB05 144.0 · IC025 +6.6 3/3 methods agree	Labeled (related wording) related wording	serious n=12	not reported in cached trials
Hypercoagulation	321	191.8 170.2–216.1ROR 194.6 · χ² 50,430 / p <1e-300	157.9 EB05 143.9 · IC025 +6.8 3/3 methods agree	Not in label — unassessed	serious n=319	not reported in cached trials
Protein c deficiency	20	175.2 108.7–282.4ROR 175.4 · χ² 2,774 / p <1e-300	129.8 EB05 88.7 · IC025 +4.3 3/3 methods agree	Not in label — unassessed	serious n=19	not reported in cached trials
Pulmonary infarction	338	157.2 140.2–176.3ROR 159.6 · χ² 44,796 / p <1e-300	133.8 EB05 122.2 · IC025 +6.6 3/3 methods agree	Labeled (related wording) related wording	serious n=338 · 73% consumer	not reported in cached trials
Loop electrosurgical excision procedure	20	155.0 96.6–248.7ROR 155.1 · χ² 2,495 / p <1e-300	118.4 EB05 80.9 · IC025 +4.2 3/3 methods agree	Reporting / coding artifact	serious n=20	not reported in cached trials
Transverse sinus thrombosis	68	139.8 108.4–180.3ROR 140.2 · χ² 8,035 / p <1e-300	117.8 EB05 96.2 · IC025 +5.6 3/3 methods agree	Not in label — unassessed	serious n=67	not reported in cached trials
Thromboembolectomy	12	137.2 74.9–251.4ROR 137.3 · χ² 1,299 / p 9e-285	101.0 EB05 61.6 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	serious n=12	not reported in cached trials
Intracranial venous sinus thrombosis	136	136.4 114.0–163.2ROR 137.2 · χ² 15,838 / p <1e-300	117.3 EB05 101.6 · IC025 +6.1 3/3 methods agree	Not in label — unassessed	serious n=135	not reported in cached trials
Antiphospholipid antibodies positive	72	134.7 105.3–172.4ROR 135.2 · χ² 8,240 / p <1e-300	114.4 EB05 93.9 · IC025 +5.6 3/3 methods agree	Lab value / disease marker	serious n=72 · 72% consumer	not reported in cached trials
Protein s decreased	18	130.8 79.9–214.2ROR 130.9 · χ² 1,923 / p <1e-300	102.7 EB05 68.7 · IC025 +4.0 3/3 methods agree	Lab value / disease marker	serious n=17	not reported in cached trials
Post thrombotic syndrome	53	126.1 94.7–168.0ROR 126.4 · χ² 5,689 / p <1e-300	107.1 EB05 85.0 · IC025 +5.3 3/3 methods agree	Labeled (related wording) related wording	serious n=51	not reported in cached trials
Coagulation factor viii level increased	17	122.6 74.0–203.2ROR 122.7 · χ² 1,707 / p <1e-300	97.0 EB05 64.2 · IC025 +3.9 3/3 methods agree	Lab value / disease marker	serious n=17	not reported in cached trials
Breast prosthesis implantation	11	121.3 64.8–227.3ROR 121.4 · χ² 1,058 / p 2e-232	91.0 EB05 54.3 · IC025 +3.2 3/3 methods agree	Not in label — unassessed	serious n=11	not reported in cached trials
Chlamydial infection	84	118.6 94.6–148.8ROR 119.1 · χ² 8,592 / p <1e-300	103.0 EB05 85.8 · IC025 +5.7 3/3 methods agree	Not in label — unassessed	serious n=68	not reported in cached trials
Ovarian cystectomy	19	112.0 69.6–180.3ROR 112.1 · χ² 1,770 / p <1e-300	91.3 EB05 61.7 · IC025 +4.1 3/3 methods agree	Not in label — unassessed	serious n=18	not reported in cached trials
Chlamydia test positive	12	111.4 61.2–202.6ROR 111.5 · χ² 1,077 / p 2e-236	86.4 EB05 52.7 · IC025 +3.4 3/3 methods agree	Lab value / disease marker	serious n=9	not reported in cached trials
Medical device discomfort	321	111.1 99.0–124.6ROR 112.7 · χ² 31,219 / p <1e-300	98.9 EB05 90.1 · IC025 +6.2 3/3 methods agree	Not in label — unassessed	serious n=24	not reported in cached trials
Genital pruritus female	34	109.5 76.8–156.2ROR 109.7 · χ² 3,178 / p <1e-300	93.2 EB05 69.7 · IC025 +4.8 3/3 methods agree	Labeled (related wording) related wording	–	not reported in cached trials
Endometrial ablation	35	104.2 73.5–147.7ROR 104.3 · χ² 3,127 / p <1e-300	89.4 EB05 67.2 · IC025 +4.8 3/3 methods agree	Not in label — unassessed	serious n=34	not reported in cached trials
Vaginitis bacterial	63	103.6 79.9–134.4ROR 103.9 · χ² 5,674 / p <1e-300	90.9 EB05 73.6 · IC025 +5.3 3/3 methods agree	Not in label — unassessed	serious n=51	not reported in cached trials
Withdrawal bleeding irregular	24	101.8 66.8–155.1ROR 101.9 · χ² 2,071 / p <1e-300	85.9 EB05 60.7 · IC025 +4.3 3/3 methods agree	Labeled (related wording) related wording	–	not reported in cached trials
Female sterilisation	49	100.1 74.6–134.3ROR 100.3 · χ² 4,254 / p <1e-300	87.5 EB05 68.8 · IC025 +5.1 3/3 methods agree	Not in label — unassessed	serious n=48	not reported in cached trials
Menstruation normal	30	98.7 67.8–143.7ROR 98.8 · χ² 2,537 / p <1e-300	84.7 EB05 62.2 · IC025 +4.6 3/3 methods agree	Reporting / coding artifact	–	not reported in cached trials
Unintended pregnancy	951	95.1 89.1–101.5ROR 99.4 · χ² 80,362 / p <1e-300	86.3 EB05 81.8 · IC025 +6.3 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 82.4	not reported in cached trials
Trichomoniasis	13	93.8 53.0–165.8ROR 93.8 · χ² 1,002 / p 4e-220	76.1 EB05 47.4 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	serious n=12	not reported in cached trials
Superior sagittal sinus thrombosis	68	87.3 68.1–111.9ROR 87.6 · χ² 5,230 / p <1e-300	78.3 EB05 63.9 · IC025 +5.3 3/3 methods agree	Not in label — unassessed	serious n=67	not reported in cached trials

Trial evidence (ClinicalTrials.gov)

✓ Trial adverse-event data found on ClinicalTrials.gov

Largest completed trials with posted results that list Etonogestrel and Ethinyl Estradiol as a study intervention. The right-hand column of the signal table shows whether each FAERS term was also recorded in these trials, with a real denominator (0 of 40 signal terms matched).

NCT02616146 — Efficacy and Safety of Etonogestrel + 17β-Estradiol Vaginal Ring and Levonorgestrel-Ethinyl Estradiol Combined (N=2016, PHASE3; 13 AE terms posted; arms: ENG-E2 125 μg/300 μg; LNG-EE 150 μg/30 μg)

Caveats: trial populations, doses and follow-up differ from the reporting population; AE terms are sponsor-coded and matched here by wording; absence from a trial list means the term was not reported above the sponsor's frequency threshold, not that it cannot occur.

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
Pulmonary embolism (lung blood clot)	3,951	41.0 39.9–42.2ROR 49.8 · χ² 148,511 / p <1e-300	39.4 EB05 38.3 · IC025 +5.2 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 47.7	NCT02616146: 1/492 (0.2%) on Etonogestrel and Ethinyl Estradiol (serious AE)
Deep vein thrombosis (leg blood clot)	2,663	40.4 39.0–41.9ROR 45.8 · χ² 98,379 / p <1e-300	38.8 EB05 37.5 · IC025 +5.2 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 42.5 · 70% consumer	NCT02616146: 1/492 (0.2%) on Etonogestrel and Ethinyl Estradiol (serious AE)
Inappropriate schedule of drug administration	2,230	30.3 29.1–31.5ROR 33.6 · χ² 61,406 / p <1e-300	29.4 EB05 28.4 · IC025 +4.8 3/3 methods agree	Reporting / coding artifact	serious PRR 9.0	not reported in cached trials
No adverse event	1,589	8.6 8.2–9.0ROR 9.2 · χ² 10,642 / p <1e-300	8.5 EB05 8.2 · IC025 +3.0 3/3 methods agree	Reporting / coding artifact	serious PRR 2.1	not reported in cached trials
Device expulsion	1,377	20.5 19.5–21.6ROR 21.8 · χ² 25,053 / p <1e-300	20.1 EB05 19.2 · IC025 +4.2 3/3 methods agree	Reporting / coding artifact	serious PRR 20.0	not reported in cached trials
Headache	1,177	1.8 1.7–1.9ROR 1.8 · χ² 421 / p 8e-94	1.8 EB05 1.7 · IC025 +0.7	Labeled adverse reaction exact term	serious PRR 3.1	NCT02616146: 116/1,504 (7.7%) on Etonogestrel and Ethinyl Estradiol
Metrorrhagia	1,140	67.1 63.3–71.2ROR 70.7 · χ² 69,268 / p <1e-300	62.6 EB05 59.6 · IC025 +5.8 3/3 methods agree	Not in label — unassessed	serious n=222	not reported in cached trials
Nausea	1,031	1.2 1.2–1.3ROR 1.3 · χ² 51 / p 5e-13	1.2 EB05 1.2 · IC025 +0.2	Labeled adverse reaction exact term	serious PRR 1.7	not reported in cached trials
Incorrect drug administration duration	1,017	35.1 33.1–37.4ROR 36.8 · χ² 32,522 / p <1e-300	33.9 EB05 32.2 · IC025 +5.0 3/3 methods agree	Reporting / coding artifact	serious PRR 20.5	not reported in cached trials
Unintended pregnancy	951	95.1 89.1–101.5ROR 99.4 · χ² 80,362 / p <1e-300	86.3 EB05 81.8 · IC025 +6.3 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 82.4	not reported in cached trials
Depression	926	3.9 3.6–4.1ROR 4.0 · χ² 1,978 / p <1e-300	3.8 EB05 3.6 · IC025 +1.8 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 5.5	not reported in cached trials
Anxiety	879	2.9 2.8–3.1ROR 3.0 · χ² 1,133 / p 1e-248	2.9 EB05 2.8 · IC025 +1.4 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 4.5	not reported in cached trials
Device breakage	826	20.4 19.1–21.8ROR 21.2 · χ² 14,931 / p <1e-300	20.0 EB05 18.9 · IC025 +4.2 3/3 methods agree	Reporting / coding artifact	serious PRR 5.7	not reported in cached trials
Migraine	821	8.3 7.8–8.9ROR 8.6 · χ² 5,237 / p <1e-300	8.2 EB05 7.7 · IC025 +2.9 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 15.5	not reported in cached trials
Off label use (used outside approved label)	724	0.8 0.7–0.9ROR 0.8 · χ² 40 / p 1e-10	0.8 EB05 0.7 · IC025 -0.5 PRR-only: not supported by EBGM or IC	Reporting / coding artifact	serious PRR 1.5	not reported in cached trials

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.

Vaginal mycosis — n=116, PRR 929.6
Vena cava filter insertion — n=137, PRR 721.6
Abnormal withdrawal bleeding — n=249, PRR 360.3
Medical device site discomfort — n=154, PRR 289.4
May-thurner syndrome — n=40, PRR 279.9
Withdrawal bleed — n=151, PRR 249.2
Thrombolysis — n=45, PRR 239.7
Thrombectomy — n=64, PRR 231.7
Protein s deficiency — n=35, PRR 203.8
Hypercoagulation — n=321, PRR 191.8

✓ 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 Etonogestrel and Ethinyl Estradiol?

In FDA FAERS, the most frequently co-reported reaction terms for Etonogestrel and Ethinyl Estradiol are pulmonary embolism, deep vein thrombosis, headache, metrorrhagia, nausea, unintended pregnancy. 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 Etonogestrel and Ethinyl Estradiol have an FDA boxed warning?

Yes. The current FDA label carries a boxed warning: RISK OF COMPLICATIONS DUE TO IMPROPER INSERTION and REMOVAL Improper insertion of NEXPLANON increases the risk of complications [see Warnings and Precautions (5.1) ] . Proper training prior to first use of NEXPLANON can minimize the risk of improper NEXPLANON insertion [see Warnings and Precautions (5.1) ] .

Do FAERS signals prove that Etonogestrel 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 487f8a62-e142-457c-97cc-2e398fde7594, effective 20260528; matched on openfda.generic_name.exact:"ETONOGESTREL")
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, 1,146 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
ClinicalTrials.gov API v2 (query ETONOGESTREL, results-bearing studies sorted by enrollment)

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.