By Rebecca H. Allen, MD, MPH, Editor
SYNOPSIS: In this prospective cohort study, 362 participants started year 6 of the device and 223 women completed eight years of 52-mg levonorgestrel intrauterine device use. For years 6-8, the three-year Pearl Index (95% confidence interval) was 0.28 (0.03-1.00), with a three-year cumulative failure rate of 0.68% (0.17-2.71).
SOURCE: Jensen JT, Lukkari-Lax E, Schulze A, et al. Contraceptive efficacy and safety of 52 mg LNG-IUS for up to 8 years: Findings from the Mirena Extension Trial. Am J Obstet Gynecol 2022; Sep 9:S0002-9378(22)00729-3.doi: 10.1016/j.ajog.2022.09.007. [Online ahead of print].
The 52-mg levonorgestrel intrauterine device (LNG-IUD), brand name Mirena, was approved for up to five years of use for contraception and the treatment of heavy menstrual bleeding when this study began. An equivalent competing device, brand name Liletta, was approved for up to six years of use. Mirena since has been approved for up to six years of use, and then, in 2021, for seven years of use. Both companies have been conducting trials to ascertain whether use could be extended up to eight years.
This was a prospective, multicenter study conducted in 54 sites across the United States between December 2016 and May 2021 to assess the contraceptive efficacy of the 52-mg LNG-IUD, brand name Mirena, from six to eight years of use. Those who enrolled were fertile women aged 18 to 35 years who already were using the LNG-IUD for contraception or contraception plus the treatment of abnormal uterine bleeding and who were willing to continue to use it for up to eight years. Exclusion criteria included known or suspected pregnancy, abnormal cervical Pap smear, menopausal symptoms and follicle-stimulating hormone (FSH) > 30 mIU/mL, unexplained uterine bleeding or anomaly, acute infection, malignancy, immune deficiency, organic disease, substance abuse, or inability to cooperate with the study procedures. Follow-up visits were scheduled every six months, where the presence of the IUD was confirmed by visualization of the strings, or if strings were not visible, then transvaginal ultrasound. Pregnancy tests were performed at each visit, and participants also were given pregnancy tests to use at home if needed. The primary outcome of the study was the occurrence of pregnancies within years 6-8 of 52-mg LNG-IUD use, analyzed by the Pearl Index (PI) and the cumulative failure rate. The PI was calculated as the number of pregnancies per 100 women-years, i.e., the number of pregnancies that occurred divided by the time the women were at risk of getting pregnant. There was a subgroup analysis of women who also were using the device for heavy menstrual bleeding, where menstrual blood loss was measured by the alkaline hematin method at the baseline visit and then annually.
A total of 362 participants started at year 6 of LNG-IUD use; 266 entered the study and 223 completed eight years of use. Only 26 subjects (7.2%) were lost to follow-up and most were using the device for contraception only (98.3%). The mean age was 29.4 (standard deviation 3.1) years, approximately half the sample was parous (52.8%), and the majority were white (75.4%). There were two pregnancies, one in year 6 and one in year 7, during the study. For years 6 through 8, the three-year PI (95% confidence interval [CI]) was 0.28 (0.03-1.00) and the three-year cumulative failure rate was 0.68% (0.17-2.71). There were five expulsions (1.4%) and four perforations (1.1%) discovered through the course of the study. There were not enough participants in the heavy menstrual bleeding subgroup for analysis. However, among all participants, the mean number of bleeding/spotting days decreased from the first (n = 9.8, ± 9.5 days) to the 12th (n = 6.7, ± 8.9 days) 90-day reference period. The proportion of women reporting amenorrhea increased from 18.3% to 33.6% through the study.
COMMENTARY
This study demonstrated that the 52-mg LNG-IUD, brand name Mirena, remains highly effective for contraception during years 6 through 8. There is minimal information, however, on its efficacy for the treatment of heavy menstrual bleeding for this extended duration, since the trial was unable to recruit enough participants for this analysis. A similar device on the market, brand name Liletta, also was studied through eight years of use with the results published in May 2022.1
In this larger trial of the device, 576 individuals aged 16 to 35 years started year 7, 478 completed year 7, and 343 completed year 8. Two pregnancies happened in year 7 of the trial and zero in year 8. The PI for year 7 was 0.46 (95% CI, 0.06-1.66 pregnancies per 100 women-years). The cumulative failure rate for the entire eight years of the study was 1.32% (95% CI, 0.69-2.51). The rates of amenorrhea ranged from 37% to 42% from years 3 through 8. In this study, there were no perforations discovered in years 7 and 8, with only two (0.1%) throughout the entire course of the eight years. The rate of expulsion for the entire eight years was 4.1%, which is consistent with previous studies.
The strength of these studies combined indicates that patients can feel comfortable using the device for up to eight years if desired for contraception, with a failure rate of roughly 1%. Based on its study, Mirena already has obtained approval for eight years of use as of August 2022, and the company that manufactures Liletta likely will follow suit. Perforations and expulsions were rare in these studies, demonstrating safety of the device. If bleeding patterns worsen after year 5, then the patient can always opt for removal and replacement.
The recent study indicating that the LNG-IUD is as effective for emergency contraception as the copper IUD opens up a new indication for the LNG-IUD with the possibility that patients can use the device long-term if desired.2 The copper T 380A IUD (brand name Paragard) currently is approved for up to 10 years of use; however, there are data indicating efficacy through 12 years of use.3 Similarly, there are data supporting the extended use of the etonogestrel contraceptive implant (brand name Nexplanon) up to five years of use.4
Whether the companies that manufacture Nexplanon and Paragard will pursue efficacy studies and Food and Drug Administration approval for an extended duration is unknown. However, physicians are permitted to use devices off-label if there is evidence to support other indications and different durations of use.
REFERENCES
- Creinin MD, Schreiber CA, Turok DK, et al. Levonorgestrel 52 mg intrauterine system efficacy and safety through 8 years of use. Am J Obstet Gynecol 2022; May 13:S0002-9378(22)00366-0.doi: 10.1016/j.ajog.2022.05.022. [Online ahead of print].
- Turok DK, Gero A, Simmons RG, et al. Levonorgestrel vs. copper intrauterine devices for emergency contraception. N Engl J Med 2021;384:335-344.
- Kaneshiro B, Aeby T. Long-term safety, efficacy, and patient acceptability of the intrauterine copper T-380A contraceptive device. Int J Womens Health 2010;2:211-220.
- Ali M, Akin A, Bahamondes L, et al. Extended use up to 5 years of the etonogestrel-releasing subdermal contraceptive implant: Comparison to levonorgestrel-releasing subdermal implant. Human Reprod 2016;31:2491-2498.
