Ethinylestradiol + Levonorgestrel

Combined oral contraceptives (COC), second generation

ATC code: G03AA07(Levonorgestrel and estrogen)

Updated 24 Sep 2026 · Methodology

Indications

Contraception

First line

Regular contraception for women of reproductive age. Per MEC 2015 and SEGO 2023, the preferred COC without VTE risk factors (smoking after 35, migraine with aura, thrombophilia, BMI ≥35, uncontrolled hypertension). One tablet at the same time daily for 21 days, then 7-day break with withdrawal bleed. Efficacy – Pearl Index 0.3 perfect-use. A missed dose >24 h reduces protection – use backup barrier for 7 days.

Sources

ICD-10: Z30.0 · ICD-11: QA21

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Contraception during breastfeeding

Not recommended

Ethinylestradiol + Levonorgestrel during breastfeeding. MEC 2015 and SEGO 2023 classify combined COCs with estrogen as category 4 (contraindicated) in the first 6 weeks postpartum due to elevated VTE risk. From week 6 to 24 with established lactation – category 2 (acceptable). Estrogen lowers milk supply, especially before lactation stabilizes. Alternatives are progestin-only methods (Cerazette, desogestrel or levonorgestrel mini-pills, implant, LNG-IUS) from day 1 postpartum. If breastfeeding matters and you have a choice, consider a second opinion.

Sources

ICD-10: Z30.0 · ICD-11: QA21

Pill-free interval for “detox”

Not recommended

Blogs and forums advise pausing COCs for 3–6 months so «the body rests from hormones». Committee Opinion 2017 and SEGO 2023 do not support this. Ethinylestradiol and Levonorgestrel clear within days. Ovulation returns in 1–3 cycles in most women. A break does not improve fertility and raises unintended pregnancy risk. When planning pregnancy, stop the COC and start trying immediately – no «detox» needed. If a clinician recommends a mandatory break without medical reason, consider a second opinion.

Sources

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

Suppresses ovulation by lowering pituitary FSH and LH. Ethinylestradiol is a synthetic estrogen; levonorgestrel is a second-generation progestin with mild androgenic activity. Thickens cervical mucus and thins endometrium, reducing implantation. Pearl Index 0.3 perfect-use, 7 typical-use. Levonorgestrel is cheaper and has the lowest VTE risk among progestins (5–7 per 10,000 woman-years vs 9–12 with drospirenone).

Safety

Contraindications

History or current venous thromboembolism
Known thrombophilia (Leiden, prothrombin G20210A)
Smoking after 35 (≥15 cigarettes/day)
Migraine with aura
Uncontrolled hypertension (≥160/100)
Ischemic heart disease, stroke
Diabetes with complications
History of breast cancer
Severe cirrhosis, active hepatitis, liver tumors
First 6 weeks postpartum
Pregnancy

Serious adverse effects

Venous thromboembolism (5–7 per 10,000 woman-years)
Ischemic stroke in smokers ≥35
Hypertension
Cholestatic jaundice
Benign liver tumors (rare)

Common adverse effects

Nausea
Breast tenderness
Breakthrough bleeding in first 1–3 months
Headache
Mood changes
Decreased libido
Weight gain 1–2 kg

Pregnancy: can you take Ethinylestradiol + Levonorgestrel?

Contraindicated in pregnancy. Accidental use in early pregnancy is not linked to birth defects – continuing pregnancy is safe. Once pregnancy is confirmed, stop the COC immediately.

Breastfeeding: can you take Ethinylestradiol + Levonorgestrel?

Hale L3 · Probably compatible, limited data

Ethinylestradiol reduces milk supply. WHO MEC 2015: first 6 weeks postpartum – category 4 (contraindicated); weeks 6–24 with stable lactation – category 2 (acceptable). Levonorgestrel transfers to milk in small amounts (RID about 1–2%) and is considered compatible per Hale L2. The estrogen is the main issue. If breastfeeding matters, progestin-only methods are preferred.

RID, infant dose via milk: 1.3%
Maternal half-life: 26.0 h
Maternal peak time: 2 h
Peak milk concentration: 0 mg/L
Milk-to-plasma ratio: 0.28

Calculate RID Safe feeding window Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

One tablet at the same time daily for 21 days, then 7-day break. If missed <24 h – take the missed dose immediately. If >24 h in week 1 – backup barrier for 7 days. In week 3 – skip the break and start a new pack immediately.

Drug interactions

Strong CYP3A4 inducers reduce efficacy: rifampicin, phenytoin, carbamazepine, oxcarbazepine, phenobarbital, topiramate >200 mg/day, St John's wort. COCs lower lamotrigine levels – check with epileptologist. Broad-spectrum antibiotics (amoxi, doxycycline) do not clinically reduce COC efficacy – no backup needed.

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Frequently asked

What is Ethinylestradiol + Levonorgestrel used for?

Ethinylestradiol + Levonorgestrel is evaluated for the following indications with varying evidence strength: Contraception (evidence tier A), Contraception during breastfeeding (evidence tier D), Pill-free interval for “detox” (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Ethinylestradiol + Levonorgestrel?

Common side effects of Ethinylestradiol + Levonorgestrel (≥ 1 in 100): Nausea, Breast tenderness, Breakthrough bleeding in first 1–3 months, Headache, Mood changes, Decreased libido. See the Safety section for uncommon and serious reactions.

Is Ethinylestradiol + Levonorgestrel safe during pregnancy?

Contraindicated in pregnancy. Accidental use in early pregnancy is not linked to birth defects – continuing pregnancy is safe. Once pregnancy is confirmed, stop the COC immediately.

Is Ethinylestradiol + Levonorgestrel compatible with breastfeeding?

Who should not take Ethinylestradiol + Levonorgestrel?

Ethinylestradiol + Levonorgestrel is contraindicated in: History or current venous thromboembolism; Known thrombophilia (Leiden, prothrombin G20210A); Smoking after 35 (≥15 cigarettes/day); Migraine with aura; Uncontrolled hypertension (≥160/100). Full list in the Safety section.

Other drugs in this group

Ethinylestradiol + Norgestimate, Etonogestrel (implant), Follitropin alfa, Levonorgestrel, Medroxyprogesterone acetate depot, Red clover (Trifolium pratense), Cyproterone acetate + Ethinylestradiol, Estradiol + Nomegestrol acetate