Levonorgestrel IUD Users Report Low Rates of Hormonal Side Effects, Study Finds

The researchers revealed that using combined hormonal contraception before the placement of the levonorgestrel 52 mg intrauterine device is weakly associated with the reporting of hormonally related side effects, such as acne. They also found that only a small percentage of levonorgestrel 52 mg intrauterine device users experienced hormone-related side effects during the first six months of use, and these side effects led to discontinuation in some cases.

Contraceptive trials require enrollment of heterosexually active participants, many of whom may stop using prior contraceptive methods before the study. Some early side effects could stem from this cessation rather than the IUD itself. Hormonal IUDs have low systemic hormone exposure, but some participants report hormone-related side effects linked to stopping combined hormonal contraception.

Although the levonorgestrel 52 mg intrauterine device is locally active with low systemic hormone exposure, some users report hormone-related side effects. Considering this, Mitchell D. Creinin, Department of Obstetrics and Gynecology, University of California, Davis, Sacramento, CA, and colleagues aimed to assess the rates of hormone-related adverse events among all participants and compare these rates between those who used combined hormonal contraception or no hormonal contraception before enrollment.

For this purpose, the researchers analyzed data from 1,714 women aged 16 to 45 who received a levonorgestrel 52 mg intrauterine device in a multicenter phase 3 trial assessing contraceptive efficacy and safety for up to 10 years. This analysis focused on a subset of participants who used combined hormonal contraception or no hormonal contraception in the month before device placement. They evaluated all nonexpulsion, nonbleeding-related events with an incidence of ≥1% at 180 days, with weight increase included regardless of incidence, while excluding nonhormonal events.

The researchers calculated 180-day side effect frequency rates based on the number of days a side effect was reported during the study period. A multivariable model was developed to assess side effect incidence at 180 days, factoring in age, race, ethnicity, body mass index at enrollment, parity, and prior contraception use. For side effects with a P value < 0.2 in univariate comparisons between combined hormonal and no-hormonal contraception users, the researchers further analyzed 360-day event rates.

The study revealed the following findings:

• A total of 644 participants used combined hormonal contraception (primarily oral [n=499, 77.5%]) before intrauterine device placement, while 855 used no hormonal method.
• Side effect rates during the first 180 days did not differ significantly between combined hormonal contraception users and non-hormonal users, except for acne:
  • 13.0% of participants in the combined hormonal group reported acne compared to 8.5% in the no-hormonal group.
  • The odds ratio was 1.61.
  • After adjusting for age, race, ethnicity, obesity, and parity, the association weakened (adjusted odds ratio 1.40).
• At 360 days, prior combined hormonal contraception users were more likely to report:
  • Acne: 15.7% of participants compared to 10.6% in the non-hormonal group.
  • Orgasm/libido problems: 3.1% of participants in the combined hormonal group compared to 1.4% in the non-hormonal group.
• Over the first 180 days, all side effects other than acne were reported on less than 3% of days.
• Acne was reported an average of 13 days (7.4%) per combined hormonal contraception user and 9 days (5.0%) per non-hormonal user.
• Discontinuation due to side effects occurred in 5.5% of participants, with no significant difference between groups:
  • Combined hormonal group: 5.6% participants.
  • Non-hormonal group: 5.5% participants.

"Overall, the levonorgestrel 52-mg IUD remains a safe and effective contraceptive choice for most users, with hormonal side effects being rare and manageable. With continued research and patient education, these findings can ensure better experiences for women opting for this long-term, reversible contraceptive option," the researchers concluded.

Reference:

Kerns, J. L., Keder, L. M., Cwiak, C. A., Westhoff, C. L., & Creinin, M. D. (2024). Hormone-related side effects in new users of a levonorgestrel 52-mg intrauterine device. American Journal of Obstetrics and Gynecology, 231(6), 628.e1-628.e10. https://doi.org/10.1016/j.ajog.2024.06.049