What is the comparative effectiveness of Intrauterine Device (IUD) versus Nexplanon (Etonogestrel)?

From the Guidelines

In patients requiring contraception, particularly those with antiphospholipid antibody-positive status, an Intrauterine Device (IUD) is recommended over Nexplanon (Etonogestrel) due to its proven safety profile regarding thrombosis risk. When considering the comparative effectiveness of IUDs versus Nexplanon, it's crucial to prioritize the patient's medical history and potential risks associated with each method. According to the 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases 1, IUDs (levonorgestrel or copper) are strongly recommended in women with positive antiphospholipid antibodies (aPL) because they do not increase the risk of thromboembolism, unlike estrogen-containing contraceptives.

Key Considerations

• The risk of venous thromboembolism (VTE) is significantly higher with combined estrogen-progestin contraceptives compared to progestin-only methods or IUDs 1.
• Progestin-only methods, including IUDs, are considered lower-risk options for patients with contraindications to estrogen, such as those with positive aPL 1.
• Nexplanon, containing etonogestrel, lacks comprehensive data on VTE risk, particularly in patients with increased thrombosis risk, making it a less favorable choice in these scenarios 1.
• IUDs, especially those releasing progestin (like levonorgestrel), have been shown not to increase thrombosis risk in healthy women or those with non-aPL associated increased thrombosis risk 1.

Patient-Specific Factors

• Medical history, including the presence of antiphospholipid antibodies or other thrombosis risk factors, plays a critical role in choosing between IUDs and Nexplanon.
• Patient preferences regarding menstrual bleeding patterns, contraceptive duration, and hormone sensitivity should also be considered.
• The potential for increased menstrual bleeding and cramping with the copper IUD, which may be mitigated by progestin IUDs, is an important factor for patients receiving anticoagulation therapy 1.

Conclusion Drawn from Evidence

Given the emphasis on minimizing thrombosis risk and the proven safety of IUDs in this context, IUDs are the preferred choice over Nexplanon for patients requiring effective contraception with a low risk of thromboembolic events. This recommendation is based on the most recent and highest quality evidence available, prioritizing patient safety and outcomes 1.

From the Research

Comparative Effectiveness of IUD and Nexplanon (Etonogestrel)

• The comparative effectiveness of Intrauterine Device (IUD) versus Nexplanon (Etonogestrel) can be evaluated based on various studies 2, 3, 4, 5, 6.
• A study published in 2015 compared the contraceptive effectiveness of levonorgestrel-releasing intrauterine systems (LNG IUSs) and copper intrauterine devices (IUDs) 2. The results showed that both types of IUD were highly effective, with overall Pearl indices of 0.06 and 0.52 for LNG IUS and copper IUDs, respectively.
• Another study published in 2022 reviewed the evidence supporting the use of the copper intrauterine device, levonorgestrel intrauterine devices, and etonogestrel subdermal implant beyond the Food and Drug Administration approved duration of use for contraception 3.
• A study published in 2015 identified factors associated with the choice of highly effective, long-acting, progestin-only contraceptive methods after abortion, including the levonorgestrel intrauterine device (IUD), the progestin implant, and the progestin injection (depot medroxyprogesterone acetate or DMPA) 4.
• A systematic review published in 2001 assessed the contraceptive efficacy, tolerability, and acceptability of hormonally impregnated intrauterine systems (IUSs) in comparison to other reversible contraceptive methods 5.
• A randomized controlled trial published in 2015 compared the clinical performance of the 3-year one-rod etonogestrel (ENG)- and the 5-year two-rod levonorgestrel (LNG)-releasing contraceptive implants during 3 years of insertion, and between implant and intrauterine device (IUD) contraception 6.

Key Findings

• The ENG- and LNG-releasing implants had the same 3-year cumulative pregnancy rate of 0.4 per 100 W-Y 6.
• The method continuation rates for ENG and LNG implants at 2.5 years were 69.8 and 71.8 per 100 W-Y, respectively 6.
• Bleeding disturbances were the most frequent reason for method discontinuation, and were significantly more common in the ENG group than in the LNG group 6.
• The 3-year cumulative loss to follow-up was lower in the ENG- than in the LNG-implant group 6.
• The median duration of implant removal was 50 s shorter among women with ENG than among women with LNG implant 6.
• The 3-year relative risk for pregnancy in IUD group compared with the combined implant group was 5.7 per 100 W-Y 6.

Comparison of IUD and Nexplanon

• The study published in 2015 found that the copper IUD cohort contained more than 30 different types, and the validated 1-year follow-up information for 58,324 users showed that the LNG IUS was associated with a significantly lower risk of pregnancy, including ectopic pregnancy, than the copper IUDs 2.
• The randomized controlled trial published in 2015 found that the 3-year cumulative pregnancy rate was significantly lower in the implant group (0.4 per 100 W-Y) compared to the IUD group (5.7 per 100 W-Y) 6.
• The study published in 2001 found that the LNG-20 IUS users were no more or less likely to have unwanted pregnancies than IUD >250mm2 and Norplant-2 users 5.