By Rebecca H. Allen, MD, MPH, Editor
SYNOPSIS: This randomized controlled trial among 62 individuals compared the 52-mg levonorgestrel intrauterine device to combined oral contraceptives for heavy menstrual bleeding and found that, in the intention-to-treat analyses, there was no significant difference in Menstrual Bleeding Questionnaire scores at six months or 12 months (mean difference, 2.5; 95% confidence interval [CI], -10.0, 5.0; and mean difference, -1.1; 95% CI, -8.7, 6.5, respectively).
SOURCE: Matteson KA, Valcin J, Raker CA, Clark MA. A randomized trial comparing the 52-mg levonorgestrel system with combination oral contraceptives for treatment of heavy menstrual bleeding. Am J Obstet Gynecol 2023;229:532.e1-532.e13.
The medical treatment of heavy menstrual bleeding (HMB) includes progestins in the form of pills; injectable, implant, and intrauterine device (IUD); combined hormonal contraceptives; and tranexamic acid. There are few comparative trials between these methods; therefore, the authors of this study sought to estimate the relative effectiveness of combined oral contraceptives (COCs) and the 52-mg levonorgestrel (LNG) IUD. This was a pragmatic randomized clinical trial that included individuals with self-reported HMB caused by endometrial or ovulatory disorders recruited from obstetrics and gynecology practices. Participants were between 18 and 51 years of age, English- or Spanish-speaking, nonpregnant, had not had an endometrial ablation or delivery in the past six months, did not have a copper IUD in place, had no contraindications to COCs or the LNG-IUD, and were not planning pregnancy for 12 months. Participants then were randomly assigned to the LNG-IUD or a monophasic 30 mcg or 35 mcg ethinyl estradiol COC to be taken cyclically.
Patients completed questionnaires at baseline, six weeks, three months, six months, and 12 months that included the Menstrual Bleeding Questionnaire (MBQ), the 36-Item Short Form Survey (SF-36), the EuroQol (EQ-5D), and the Work Productivity and Activity Impairment Questionnaire. The primary outcome was the mean change in the score on the MBQ between baseline and six and 12 months. The MBQ includes 20 questions regarding bleeding amount, bleeding irregularity, pain, and effect on quality of life, with scores ranging from 0 (best) to 75 (worst). Twenty-four subjects per group were required to detect a 10-point difference in change in the MBQ score with an alpha of 0.05 and 80% power. Both the intention-to-treat and per-protocol analyses were performed with missing MBQ scores computed.
Out of 16,143 patients screened, 95 were determined to be eligible for the study and 62 were randomized to treatment (n = 29: LNG-IUD and n = 33: COCs). Out of these, seven patients withdrew or were lost to follow-up prior to treatment, leaving 24 patients in the LNG-IUD arm and 31 patients in the COC arm. However, only 19 of 24 patients actually received the LNG-IUD and 31 of 31 patients received COCs. All 62 participants were included in the intention-to-treat analysis, and 42 patients completed all study visits. The median age was 31 years, and the median body mass index was 29.3.
Adherence to the randomized treatment declined over the 12 months; 8.3% of LNG-IUD users crossed over to COCs and 6.5% of COCs users crossed over to the LNG-IUD. Overall, MBQ scores dropped by half in both groups from baseline to 12 months (LNG-IUD, 33.2 vs. 14.3, and COCs, 32.9 vs. 15.8). In the intention-to-treat analysis, there was no significant difference in MBQ scores at six months or 12 months (mean difference, -2.5; 95% confidence interval [CI], -10.0, 5.0 and mean difference, -1.1; 95% CI, -8.7, 6.5, respectively). In the per-protocol analysis (n = 47), there was a greater decrease in MBQ scores in the LNG-IUD group (n = 18) at six months (mean difference -7.0; 95% CI, -13.8 to -0.2) but not at 12 months (difference, -4.8; 95% CI, -11.8 to 2.3) when compared with the COC arm (n = 29). There was no major difference between the two groups in the SF-36 or EQ-5D scores. In the LNG-IUD group, there were no adverse events. In the COC group, one participant developed new-onset migraine headaches and one participant had deep vein thrombosis.
COMMENTARY
Both the LNG-IUD and COCs have been studied individually for the treatment of HMB, but they rarely have been compared to each other. The 52-mg LNG-IUD is Food and Drug Administration (FDA)-approved for the treatment of HMB and drastically decreases blood loss with menses.1 There is only one FDA-approved COC for the treatment of HMB, and it contains estradiol valerate and dienogest (brand name: Natazia). Nevertheless, other COCs have been studied and show the same effect on reducing menstrual blood loss.2 Typically, both are first-line medical options for the treatment of HMB.
The authors of this study had difficulties with recruitment and retention, with 18 participants actually using the LNG-IUD and 29 users in the COC group in the per-protocol analysis. The hypothesis was that the LNG-IUD would be superior to the COC in improving menstrual bleeding-related quality of life. However, at 12 months, in both the intention-to-treat analysis and the per-protocol analysis, there was no significant difference between the two groups in bleeding-related quality-of-life scores. The authors deliberately measured bleeding-related quality of life as the variable most important to patients based on prior studies. They found that in both groups, the effect of HMB on quality-of-life measures was reduced by about half, with improvements starting as soon as six weeks.
Ultimately, it is up to patients to choose which treatment method they prefer. The LNG-IUD requires a procedure for insertion, whereas COCs need only a prescription. Nevertheless, remembering to take a pill every day often is more challenging than using an IUD for patients. Furthermore, because of their estrogen content, COCs have more contraindications to use than the LNG-IUD. This study shows that both options are reasonable and effective treatments for patients.
REFERENCES
- Matteson KA, Anderson BL, Pinto SB, et al. Practice patterns and attitudes about treating abnormal uterine bleeding: A national survey of obstetricians and gynecologists. Am J Obstet Gynecol 2011;205:321.e1-8.
- American College of Obstetricians and Gynecologists. Practice Bulletin No. 136. Management of abnormal uterine bleeding associated with ovulatory dysfunction. Published July 2013. https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2013/07/management-of-abnormal-uterine-bleeding-associated-with-ovulatory-dysfunction
