Hormonal contraceptive levonorgestrel at different doses increases ectopic pregnancy risk: JAMA

A countrywide Danish research found that each of the three dosages of the hormonal contraceptive levonorgestrel-releasing intrauterine systems (13.5 mg, 19.5 mg, and 52 mg levonorgestrel IUSs) were associated with a greater risk of ectopic pregnancy when compared to other hormonal contraceptives. The findings of this study were published in the Journal of American Medical Association. 

This study conducted by Amani Meaidi and team, used Danish national databases from 2001 to 2021 to track 963,964 nulliparous women without a history of ectopic pregnancy for 7.8 million person-years. The primary finding of this study was the diagnosis of ectopic pregnancy in the hospital registration upon discharge.

The major findings of this study were:

In comparison to other hormonal contraceptives, all 3 doses of levonorgestrel intrauterine systems (IUSs) had a greater absolute rate of ectopic pregnancy per 10,000 person-years: 51 mg: 7.7 (95% CI, 4.7-11.9), 52 mg: 7.7 (95% CI, 4.7-11.9), 13.5 mg: 15.7 (95% CI, 11.4-21.2), and 19.5 mg: 7.1 (95% CI, 4.3-11.2). 2.4 (95% CI, 2.1-2.6) for both hormonal contraceptives and other forms. 

The 19.5 mg dosage of levonorgestrel IUS is not appreciably higher than the 52 mg dose: adjusted incidence rate ratio for ectopic pregnancy at 13.5 mg is 2.3 (95% confidence interval [CI], 1.6-3.5). 1.2 (95% CI, 0.7-1.9) is the adjusted incidence rate ratio for 19.5 mg, which is not significantly higher than the baseline rate.

In conclusion, The 19.5 mg dosage of levonorgestrel IUS is not linked to a higher risk for ectopic pregnancy when compared to the other two doses. In order to lower the chance of an ectopic pregnancy, the authors state that the 19.5 mg dose "should be preferable" above the 13.5 mg dose.

Reference: 

Meaidi, A., Torp-Pedersen, C., Lidegaard, Ø., & Mørch, L. S. (2023). Ectopic Pregnancy Risk in Users of Levonorgestrel-Releasing Intrauterine Systems With 52, 19.5, and 13.5 mg of Hormone. In JAMA (Vol. 329, Issue 11, p. 935). American Medical Association (AMA). https://doi.org/10.1001/jama.2023.0380