What is the recommended management for a reproductive‑age woman with ongoing abnormal uterine bleeding while using the Nexplanon (etonogestrel) implant?

Management of Ongoing Bleeding with Nexplanon

Start with mefenamic acid 500 mg three times daily for 5 days during bleeding episodes—this is the most effective first-line treatment, achieving significant bleeding cessation within 7 days compared to placebo. 1, 2

Initial Evaluation Before Treatment

Before attributing bleeding to Nexplanon, systematically exclude other causes:

• Rule out pregnancy first in all cases, as this could indicate contraceptive failure or ectopic pregnancy 2, 3
• Screen for sexually transmitted infections (chlamydia and gonorrhea), as unscheduled bleeding can indicate STI, particularly in adolescents 2, 3
• Evaluate for new uterine pathology such as polyps, fibroids, or structural abnormalities that could explain irregular bleeding 1, 2
• Review concomitant medications for drug interactions that may affect bleeding patterns, especially anticoagulants 2, 3

Understanding Expected Bleeding Patterns

Counseling about normal bleeding patterns is critical:

• 22% of Nexplanon users experience amenorrhea and 34% have infrequent spotting during the first year 1, 2
• 18% report prolonged bleeding and 7% experience frequent bleeding episodes 1, 2
• These patterns are not harmful and do not indicate contraceptive failure 1, 2
• Bleeding patterns in the first 3 months may predict future patterns, though individual variation is high 2

Pharmacologic Treatment Algorithm

First-Line: NSAIDs (5-7 days during bleeding episodes)

Mefenamic acid is superior to other NSAIDs:

• Mefenamic acid 500 mg three times daily for 5 days achieves significant bleeding cessation within 7 days compared to placebo 1, 2
• Celecoxib 200 mg once daily for 5 days is an alternative NSAID with demonstrated efficacy 1, 2
• Ibuprofen has inconsistent results and should not be relied upon—one study showed reduction in bleeding days while another found no significant difference versus placebo 1, 2

Second-Line: Hormonal Treatment (10-20 days during bleeding episodes)

When NSAIDs fail or are contraindicated:

• Low-dose combined oral contraceptives (COCs) for 10-20 days are highly effective—one trial showed 76.2% of women stopped bleeding within 7 days versus only 35.7% with NSAIDs 1, 2, 4
• Estrogen-only therapy for 10-20 days can reduce bleeding days when COCs are unsuitable 1, 2
• Screen for cardiovascular contraindications before prescribing estrogen, particularly history of spontaneous coronary artery dissection 2

Emerging Evidence: Norethisterone

A 2025 randomized controlled trial demonstrated:

• Norethisterone acetate 10 mg daily until 2 consecutive bleeding-free days (maximum 30 days) achieved 86.7% bleeding cessation within 7 pills versus 48.9% with placebo 5
• Treatment failure was significantly lower (2.2% versus 17.8% with placebo) 5
• However, bleeding recurrence occurs sooner (5 days versus 10.5 days with placebo), so this does not prevent future episodes 5

Treatments to Avoid

• Doxycycline alone does NOT improve bleeding cessation in Nexplanon users and should not be used as sole intervention 1, 2
• Avoid tranexamic acid in patients with cardiovascular risk factors due to thrombotic event risk 2
• Aspirin showed no significant difference in median length of bleeding episodes 1

When Bleeding Persists Despite Treatment

If irregular bleeding persists and the woman finds it unacceptable:

• Counsel on alternative contraceptive methods and offer another method if desired 1
• The levonorgestrel-releasing intrauterine system (20 µg/day) is the most effective alternative, reducing menstrual blood loss by 71-95% 2
• Consider implant removal if bleeding remains unacceptable despite treatment attempts or if hemodynamic instability develops 3

Management of Amenorrhea

If bleeding pattern changes to amenorrhea:

• Amenorrhea does not require medical treatment—provide reassurance only 1, 2, 6
• If regular bleeding pattern abruptly changes to amenorrhea, rule out pregnancy if clinically indicated 1, 6
• Explain that amenorrhea affects approximately 1 in 5 users and is not harmful 6

Critical Pitfalls to Avoid

• Do not assume all bleeding is benign—always exclude pregnancy, STIs, and structural pathology first 2, 3
• Do not prescribe estrogen without cardiovascular screening, as this can precipitate serious adverse events 2
• Do not use doxycycline as it has been proven ineffective for this indication 1, 2
• Enhanced pre-insertion counseling about expected bleeding patterns reduces discontinuation rates in clinical trials, so invest time in counseling before insertion 1, 3