Popular Levonorgestrel/Ethinyl Estradiol Combinations
The most commonly used levonorgestrel/ethinyl estradiol combinations are low-dose formulations containing 20 mcg ethinyl estradiol with 100 mcg levonorgestrel (monophasic) or 30-35 mcg ethinyl estradiol with levonorgestrel, which are recommended as first-line options for adolescents and adults. 1
Standard Contraceptive Formulations
Low-Dose Monophasic Combinations
- 20 mcg ethinyl estradiol + 100 mcg levonorgestrel is one of the most widely studied and prescribed low-dose combinations, demonstrating a Pearl index of 0.88 (less than 1 pregnancy per 100 woman-years) with excellent tolerability 2, 3
- This formulation provides effective cycle control with breakthrough bleeding occurring in 12.9% of cycles and spotting in 10.1%, with both decreasing over time 3
- The 20 mcg/100 mcg combination shows minimal effects on lipid and glucose metabolism and is associated with low venous thromboembolism risk 4
Continuous-Use Formulations
- 20 mcg ethinyl estradiol + 90 mcg levonorgestrel in continuous-use regimen (without placebo weeks) is available for extended cycle control 5
- This formulation demonstrated a Pearl index of 1.26 per 100 women-years with increasing amenorrhea rates over extended use 5
- Adverse menstrual cycle-related symptoms were significantly improved with continuous administration compared to cyclical regimens 5
Standard-Dose Combinations
- 30-35 mcg ethinyl estradiol with levonorgestrel formulations are recommended by adolescent medicine experts as appropriate starting options for healthy patients 1
- These "low-dose" pills (≤35 mcg ethinyl estradiol) can be initiated with same-day "quick start" protocols 1
Emergency Contraception Formulation
Combined Estrogen-Progestin Emergency Contraceptive
- 100 mcg ethinyl estradiol + 0.50 mg (500 mcg) levonorgestrel given as two doses 12 hours apart is an available emergency contraception option 1
- However, this combined regimen is less effective than ulipristal acetate or levonorgestrel-only emergency contraception and causes more side effects (nausea and vomiting) 1
- This formulation should be taken as soon as possible within 5 days of unprotected intercourse, though efficacy decreases after 3 days 1
Alternative Delivery System
- Transdermal contraceptive delivery system (TCDS) containing ethinyl estradiol/levonorgestrel maintains stable serum levels with efficacy similar to combination oral contraceptives 6
- This system demonstrates lower ethinyl estradiol exposure compared to the norelgestromin-containing patch, potentially reducing thromboembolism risk 6
Clinical Considerations
Contraindications Apply to All Formulations
- Absolute contraindications include: history of venous thromboembolism, uncontrolled severe hypertension (≥160/100 mmHg), migraines with aura, active liver disease, thrombophilia, and estrogen-sensitive cancers 1, 7
- Smoking is not a contraindication in women under 35 years old, though it should be discouraged 1
Risk-Benefit Profile
- The venous thromboembolism risk increases from 1 per 10,000 to 3-4 per 10,000 woman-years with combined oral contraceptive use 1
- This risk is substantially lower than pregnancy-associated thromboembolism (10-20 per 10,000 woman-years) 1
- Lower estrogen doses (20 mcg) may increase breakthrough bleeding risk but potentially reduce thrombotic complications 7
Prescribing Practices
- The CDC recommends prescribing up to 1 year of combined oral contraceptives at a time 1
- A follow-up visit 1-3 months after initiation is useful for addressing adverse effects or adherence issues 1
- Backup contraception (condoms or abstinence) should be used for the first 7 days when starting combined oral contraceptives 1