In a reproductive‑age woman seeking emergency contraception, is ulipristal acetate more effective than levonorgestrel, and how do timing, BMI, and alternatives (e.g., copper IUD) affect the choice?

Ulipristal Acetate vs Levonorgestrel for Emergency Contraception

Ulipristal acetate (UPA) 30 mg is superior to levonorgestrel 1.5 mg for emergency contraception, particularly when taken 3-5 days after intercourse or in women with higher BMI, though the copper IUD remains the most effective option overall. 1

Efficacy Comparison by Timing

Within 72 Hours (0-3 Days)

• UPA and levonorgestrel have similar effectiveness when taken within 3 days of unprotected intercourse, though emerging evidence suggests UPA may have an advantage even in this early window. 1
• A meta-analysis demonstrates that UPA reduces pregnancy risk by 42% compared to levonorgestrel when taken within 72 hours, and by 65% when taken within the first 24 hours. 2, 3, 4
• Levonorgestrel achieves maximum effectiveness within 72 hours, with pregnancy rates remaining low when administered within 4 days. 1, 5

Beyond 72 Hours (3-5 Days)

• UPA is significantly more effective than levonorgestrel when taken 3-5 days after intercourse, maintaining consistent efficacy throughout the full 120-hour window. 1, 6
• Levonorgestrel effectiveness decreases markedly after 72 hours, with pregnancy rates increasing substantially at 4-5 days post-intercourse. 1, 7, 5
• In women presenting between 72-120 hours, UPA prevented significantly more pregnancies than levonorgestrel in randomized trials. 8, 4

BMI and Weight Considerations

• Levonorgestrel may be less effective in obese women regardless of dose, making UPA the preferred option in this population. 1, 7
• For women weighing >165 pounds (75 kg), UPA is more effective than levonorgestrel even when taken within 72 hours. 7
• The mechanism of levonorgestrel (delaying ovulation) has biological limits that cannot be overcome by increasing the dose, supporting standard 1.5 mg dosing rather than higher doses. 7

Mechanism of Action Differences

• UPA can delay or inhibit ovulation even when taken 24-48 hours before expected ovulation, a critical window when levonorgestrel is no longer effective. 2, 8
• UPA maintains efficacy on larger follicles (up to 18 mm) compared to levonorgestrel (up to 14 mm), explaining its superior performance near ovulation. 9
• Both medications work primarily by delaying ovulation, not by preventing implantation. 8, 9

Copper IUD as Gold Standard

• The copper IUD is the most effective emergency contraception method with <1% failure rate, far exceeding both oral options. 6, 7
• The copper IUD can be inserted within 5 days of unprotected intercourse (or up to 5 days after ovulation if timing is known). 1, 6
• The copper IUD provides ongoing long-term contraception after insertion, making it both an emergency and continuing contraceptive method. 1, 6

Clinical Algorithm for Selection

First-Line Choice

• Copper IUD if patient is appropriate candidate and provider is available - highest efficacy regardless of timing or BMI. 6, 7

Oral Emergency Contraception Selection

• Within 72 hours + normal weight (<165 lbs): Either UPA or levonorgestrel acceptable, though UPA may have slight advantage. 1, 7
• Within 72 hours + weight >165 lbs: UPA 30 mg preferred. 7
• Between 72-120 hours (any weight): UPA 30 mg is the only effective oral option. 1, 6, 7
• Do not use levonorgestrel at 5 days due to significantly reduced effectiveness at this timepoint. 7

Critical Post-Administration Instructions

After Levonorgestrel

• Resume or start regular contraception immediately. 6, 7
• Use barrier method or abstain for 7 consecutive days after restarting hormonal contraception. 6
• Pregnancy test if menstrual bleeding delayed >1 week. 7

After UPA

• Start regular contraception immediately but use barrier method or abstain for 14 consecutive days (or until next menses, whichever comes first). 6, 7
• This longer barrier period is essential because UPA may interfere with hormonal contraception effectiveness. 6
• Pregnancy test if no withdrawal bleed within 3 weeks. 7

Common Pitfalls to Avoid

• Do not withhold emergency contraception based on perceived low pregnancy risk - patient autonomy justifies provision even after condom use without ejaculation. 7
• Do not assume levonorgestrel can be made more effective by increasing the dose - standard 1.5 mg is appropriate, and higher doses do not overcome biological limitations. 7
• Do not forget the 14-day barrier requirement after UPA - this is longer than the 7-day requirement after levonorgestrel and is frequently missed. 6, 7
• Do not dismiss the copper IUD option - many patients are unaware this is available and it provides the highest efficacy. 6, 7

Safety and Tolerability

• Both UPA and levonorgestrel are generally well tolerated with similar side effect profiles. 8, 4
• The most frequent adverse event for both is headache (approximately 19% for both medications). 4
• Menses onset is typically delayed by 2-3 days following treatment with either medication. 8