Data support the LNG 52-mg IUD for HMB in nulliparous and obese patients
Creinin MD, Barnhart KT, Gawron LM, et al. Heavy menstrual bleeding treatment with a levonorgestrel 52-mg intrauterine device. Obstet Gynecol. 2023;141:971-978. doi:10.1097AOG.0000000000005137
Creinin and colleagues conducted a study for US regulatory product approval of the LNG 52-mg IUD (Liletta) for HMB. This multicenter phase 3 open-label clinical trial recruited nonpregnant participants aged 18 to 50 years with HMB at 29 clinical sites in the United States. No BMI cutoff was used.
Baseline menstrual flow data were obtained over 2 to 3 screening cycles by collection of menstrual products and quantification of blood loss using alkaline hematin measurement. Patients with 2 cycles with a blood loss exceeding 80 mL had an IUD placement, with similar flow evaluations during the third and sixth postplacement cycles.
Treatment success was defined as a reduction in blood loss by more than 50% as compared with baseline (during screening) and measured blood loss of less than 80 mL. The enrolled population (n=105) included 28% nulliparous users, with 49% and 28% of participants having a BMI of 30 kg/m2 or higher and higher than 35 kg/m2, respectively.
Treatment highly successful in reducing blood loss
Participants in this trial had a 93% and a 98% reduction in blood loss at the third and sixth cycles of use, respectively. Additionally, during the sixth cycle of use, 19% of users had no bleeding. Treatment success occurred in about 80% of participants overall and occurred regardless of parity or BMI.
To assess a subjective measure of success, participants were asked to evaluate their menstrual bleeding and dysmenorrhea severity, acceptability, and overall impact on quality of life at 3 time points: during prior typical menses, cycle 3, and cycle 6. At cycle 6, all participants reported significantly improved acceptability of bleeding and uterine pain and, importantly, decreased overall menstrual interference with the ability to complete daily activities (TABLE 3).
IUD expulsion and replacement rates
Although bleeding greatly decreased in all participants, 13% (n=14) discontinued before cycle 6 due to expulsion or IUD-related symptoms, with the majority citing bleeding irregularities. Expulsion occurred in 9% (n=5) of users, with the majority (2/3) occurring in the first 3 months of use and more commonly in obese and/or parous users. About half of participants with expulsion had the IUD replaced during the study. ●
WHAT THIS EVIDENCE MEANS FOR PRACTICE
Interestingly, both LNG 52-mg IUDs have been approved in most countries throughout the world for HMB treatment, and only in the United States was one of the products (Liletta) not approved until this past year. The FDA required more stringent trials than had been previously performed for approval outside of the United States. However, a benefit for clinicians is that this phase 3 study provided data in a contemporary US population. Clinicians can feel confident in counseling and offering the LNG 52-mg IUD as a first-line treatment option for patients with HMB, including those who have never been pregnant or have a BMI greater than 35 kg/m2.
Importantly, though, clinicians should be realistic with all patients that this treatment, although highly effective, is not successful for about 20% of patients by about 6 months of use. For those in whom the treatment is beneficial, the quality-of-life improvement is dramatic. Additionally, this study reminds us that expulsion risk in a population primarily using the IUD for HMB, especially if also obese and/or parous, is higher in the first 6 months of use than patients using the method for contraception. Expulsion occurs in 1.6% of contraception users through 6 months of use.12 These data highlight that IUD expulsion risk is not a fixed number, but instead is modified by patient characteristics. Patients should be counseled regarding the appropriate expulsion risk and that the IUD can be safely replaced should expulsion occur.