What are the indications, dosing regimens, contraindications, and side effects of levonorgestrel for emergency contraception and routine hormonal birth control?

Levonorgestrel: Indications, Dosing, Contraindications, and Side Effects

Emergency Contraception Indications

Levonorgestrel 1.5 mg is the first-line oral emergency contraceptive for patients presenting within 72 hours of unprotected intercourse, and should be offered to any patient requesting it regardless of perceived pregnancy risk. 1

• The CDC recommends providing emergency contraception even after low-risk intercourse (e.g., condom use without ejaculation), prioritizing patient autonomy over theoretical risk calculations. 1
• Emergency contraception is appropriate even when patients are already using combined oral contraceptives or depot medroxyprogesterone acetate if unprotected intercourse or contraceptive failure has occurred. 2
• Specific scenarios warranting levonorgestrel include: missed or late doses of regular contraception during the first week of a pill pack, or DMPA injection delayed ≥2 weeks (≥15 weeks after previous injection). 2

Dosing Regimens for Emergency Contraception

The standard dose is levonorgestrel 1.5 mg as a single dose, which can be given as one 1.5 mg tablet or two 0.75 mg tablets taken simultaneously. 1

• Maximum effectiveness occurs when administered as soon as possible within 72 hours of intercourse, with efficacy declining markedly after this window. 1
• The medication remains usable up to 120 hours (5 days) after intercourse, though effectiveness is substantially reduced at 96-120 hours compared to earlier administration. 1
• The two-dose regimen (0.75 mg taken twice, 12 hours apart) is FDA-approved but offers no advantage over single-dose administration; the second dose can be taken 12-24 hours after the first without compromising efficacy. 3

Clinical Algorithm for Emergency Contraception Selection

Within 72 hours for normal-weight patients (≤165 lbs): Levonorgestrel 1.5 mg single dose is appropriate, though ulipristal acetate may have a slight efficacy advantage. 1

Within 72 hours for patients >165 lbs: Ulipristal acetate 30 mg is preferred over levonorgestrel due to reduced efficacy of levonorgestrel in obese women regardless of dose. 1, 2

Between 72-120 hours: Ulipristal acetate 30 mg is significantly more effective than levonorgestrel, which shows sharply declining efficacy after 72 hours with substantially higher pregnancy rates at 4-5 days. 1, 2

Highest efficacy at any timepoint: The copper IUD inserted within 5 days provides <1% failure rate and offers ongoing contraception, making it the most effective emergency contraception method regardless of timing or patient weight. 1, 2

Mechanism of Action

Levonorgestrel works primarily by delaying or inhibiting ovulation when given before the preovulatory LH surge begins. 4, 5

• Once LH has started to increase, levonorgestrel cannot prevent ovulation and does not prevent fertilization. 4
• The medication has no effect on endometrial development, fallopian tube function, or blastocyst implantation—it does not act as an abortifacient. 4
• The biological mechanism has inherent limits that cannot be overcome by increasing the dose, which is why standard 1.5 mg dosing is maintained. 1

Post-Emergency Contraception Management

After levonorgestrel use: Resume or start regular contraception immediately, but use barrier method or abstain for 7 consecutive days after restarting hormonal contraception. 1, 2

After ulipristal acetate use: Start any contraceptive method immediately, but barrier contraception or abstinence is mandatory for 14 consecutive days (or until next menses, whichever occurs first). 1, 2

• Perform a pregnancy test if withdrawal bleeding does not occur within 3 weeks after levonorgestrel administration. 1, 6
• After ulipristal acetate, obtain a pregnancy test if no withdrawal bleed occurs within 3 weeks. 1
• Patients already on combined oral contraceptives should continue their pill pack as scheduled after emergency contraception use. 2

Contraindications and Limitations

Known or suspected pregnancy is the primary contraindication, though levonorgestrel will not harm an existing pregnancy. 7

• Prior use of combined hormonal contraceptives does not contraindicate emergency contraception provision. 1
• Existing hormonal contraception (COC or DMPA) does not interfere with emergency contraception effectiveness. 2
• Levonorgestrel should not be used as an ongoing contraceptive method—it is a backup option, not a substitute for regular contraception. 7

Side Effects and Adverse Events

Common adverse effects (not serious): Nausea, vomiting, headache, breast tenderness, and transient alteration of menstrual bleeding pattern. 7, 8

Uncommon adverse reactions: Anorexia, exanthema, chloasma, weight gain. 8

Rare serious adverse events reported: Ectopic pregnancy (when treatment fails), convulsion, stroke, anaphylaxis, ovarian cyst rupture, febrile neutropenia, serious infections. 8

• The prevalence of adverse events is not statistically different between the 0.75 mg two-dose regimen and the 1.5 mg single-dose regimen. 8
• Tolerance is similar to or better than other oral emergency contraceptives. 7
• It is unknown whether levonorgestrel increases the risk of ectopic pregnancy when treatment fails, though ectopic pregnancy has been reported. 7, 8

Important Clinical Caveats

Timing is critical: Counsel patients that efficacy diminishes with time, reinforcing the importance of prompt administration within 72 hours. 1

Weight considerations: In obese women, levonorgestrel efficacy is reduced regardless of dose; ulipristal acetate or copper IUD should be strongly considered. 1, 6

Pre-ejaculate concerns: While condom use without ejaculation carries very low pregnancy risk, pre-ejaculate can theoretically contain sperm, justifying emergency contraception provision when patients request it. 1

Repeated use: Data regarding adverse reactions from repeated levonorgestrel use are scarce, and further studies are needed to ensure safety with multiple uses. 8