Estrogens. Natural and semisynthetic estrogens, plain
ATC code: G03CA01 (Ethinylestradiol)
Brand names
Yasmin (combination), Loestrin (combination), Ortho Tri-Cyclen (combination), Yaz (combination)
A synthetic estrogen, the primary estrogen component of most combined oral contraceptives. Binds estrogen receptors in the hypothalamus and pituitary, suppressing FSH and LH secretion. This prevents ovulation and maintains a stable hormonal background when combined with a progestin. Additional effects: increased hepatic synthesis of transport proteins (including sex hormone–binding globulin), favorable lipid effects, mineralocorticoid effects at some doses.
First line
Ethinylestradiol is the main estrogen component of most combined hormonal contraceptives. The dose ranges from 15 to 35 mcg depending on the product. With perfect use, the Pearl Index is less than 1. Modern formulations with 20–30 mcg ethinylestradiol balance efficacy and safety. Alternatives include COCs with natural estradiol or estradiol valerate for patients with thromboembolism risk factors.
Before prescribing, assess the CDC USMEC 2016 category: age, smoking, blood pressure, migraine with aura, history of thromboembolism, BMI and comorbidities.
Second line
Selected COCs with ethinylestradiol (combined with drospirenone, norgestimate, cyproterone) are -approved for moderate acne in women of reproductive age who also need contraception. The effect develops over 3–6 months. Prescribed only when contraindications to combined hormonal contraception are absent and after discussion of risk-benefit balance with the patient (thromboembolism risk versus added benefit over standard anti-acne therapy).
Second line
As a component of menopausal hormone therapy, ethinylestradiol is rarely used – current international guidelines ( NG23, NAMS 2022) prefer transdermal natural estradiol due to a better safety profile. Ethinylestradiol has stronger effects on hepatic coagulation factor synthesis and raises venous thromboembolism risk. Used only in selected clinical situations when modern MHT preparations are unavailable.
Not recommended
In women over 35 who smoke more than 15 cigarettes per day, combined hormonal contraception with ethinylestradiol is contraindicated (CDC USMEC 2016 category 4). The combination of nicotine toxicity and estrogen effects on coagulation raises risks of myocardial infarction, stroke and venous thromboembolism to unacceptable levels. Alternatives: progestin-only methods (levonorgestrel IUD, progestin-only pill, implant), barrier methods.
Not recommended
In women with migraine with aura, combined hormonal contraception with ethinylestradiol is contraindicated (CDC USMEC 2016 category 4) due to increased ischemic stroke risk. Alternatives: progestin-only methods, barrier methods, copper IUD. In migraine without aura, the decision is individualized based on age and other risk factors (USMEC categories 2–3).
Long-term combined oral contraceptive use moderately lowers erythrocyte folate. Women planning pregnancy immediately after COC withdrawal are advised to take 400 mcg folic acid daily starting at least 1 month before conception. Some COCs (Yaz Plus, Yasmin Plus) include metafolin as an additional component.
COCs moderately reduce plasma pyridoxine. Clinical significance for most patients is limited; with pronounced mood symptoms and insufficient dietary intake, dietary adjustment or 25 mg pyridoxine daily is discussed.
2 pairs found. Sorted from critical to minor.
Mechanism
Индукция CYP3A4 ускоряет метаболизм этинилэстрадиола, эффективность КОК снижается. Описаны случаи беременности на КОК + карбамазепин.
Management
Использовать барьерные методы дополнительно или ВМС/инъекционные прогестагены. КОК как монометод не рекомендованы.
Mechanism
Рифампицин – мощнейший индуктор CYP3A4, снижает концентрацию этинилэстрадиола на 40–60%. Эффективность КОК резко падает.
Management
Использовать барьерные методы или ВМС на весь курс и 4 недели после. КОК как монометод противопоказаны.
Boxed warning
FDA boxed warning: smoking significantly increases the risk of serious cardiovascular events on combined hormonal contraception. Risk increases with age, particularly after 35, and with smoking intensity. Combined ethinylestradiol-containing contraceptives are contraindicated in women over 35 who smoke.
FDA category X. If pregnancy occurs on COC, the drug is discontinued immediately. Accumulated data do not show increased congenital malformation risk, but pregnancy is not routinely continued on hormonal contraception.
Within 6 weeks postpartum, ethinylestradiol-containing COCs are contraindicated (USMEC category 4) due to thromboembolism risk. After 6 weeks with stable lactation – USMEC category 2. Ethinylestradiol may reduce milk supply, especially in the early months. Progestin-only methods are preferred in breastfeeding mothers.
Ethinylestradiol is evaluated for the following indications with varying evidence strength: Combined oral contraception (evidence tier A), Menopausal hormone therapy (evidence tier B), Hormonal acne in women (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of Ethinylestradiol (≥ 1 in 100): Nausea, especially in early cycles, Breast tenderness, Breakthrough bleeding, Headache, Decreased libido, Mood changes. See the Safety section for uncommon and serious reactions.
FDA category X. FDA category X. If pregnancy occurs on COC, the drug is discontinued immediately. Accumulated data do not show increased congenital malformation risk, but pregnancy is not routinely continued on hormonal contraception.
Within 6 weeks postpartum, ethinylestradiol-containing COCs are contraindicated (USMEC category 4) due to thromboembolism risk. After 6 weeks with stable lactation – USMEC category 2. Ethinylestradiol may reduce milk supply, especially in the early months. Progestin-only methods are preferred in breastfeeding mothers.
Ethinylestradiol is contraindicated in: Active venous thromboembolism, history of VTE; Active ischemic heart disease, history of stroke; More than 15 cigarettes per day in women over 35; Migraine with aura; Uncontrolled hypertension (BP ≥ 160/100). Full list in the Safety section.
FDA boxed warning: smoking significantly increases the risk of serious cardiovascular events on combined hormonal contraception. Risk increases with age, particularly after 35, and with smoking intensity. Combined ethinylestradiol-containing contraceptives are contraindicated in women over 35 who smoke.
systematic reviews show no clinically significant weight gain with modern low-dose COCs. Individual variation exists.
ovulation usually resumes within 1–3 months of withdrawal; fertility is not affected.
they increase venous thromboembolism risk and slightly raise breast and cervical cancer risk. They simultaneously reduce ovarian and endometrial cancer risk by 30–50% with long-term use.
routine breaks are not needed and do not improve safety; they raise risk of unplanned pregnancy.