By Katherine Rivlin, MD, MSc
Assistant Professor, Obstetrics and Gynecology, The Ohio State University Medical Center, Columbus, OH
SYNOPSIS: In this multicenter, randomized, noninferiority trial among patients aged 34 years and older with heavy menstrual bleeding, the levonorgestrel-releasing intrauterine system did not meet the noninferiority threshold when compared to endometrial ablation for mean blood loss at 24 months following intervention. Both interventions did lead to large decreases in blood loss and comparable satisfaction and quality-of-life scores.
SOURCE: Beelen P, van den Brink MJ, Herman MC, et al. Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding. Am J Obstet Gynecol 2021;224:187.e1-187.e10.
Heavy menstrual bleeding is common and can affect a patient’s health and quality of life dramatically. Two commonly used management options for heavy menstrual bleeding are the levonorgestrel-releasing intrauterine system (LNG-IUS) and endometrial ablation (EA). When compared to oral medications, the LNG-IUS reduces heavy menstrual bleeding more effectively and improves quality of life.1,2 EA is a surgical intervention intended for patients who no longer desire pregnancy. Like the LNG-IUS, EA is a minimally invasive alternative to hysterectomy, but unlike the LNG-IUS, it is permanent. Although EA can be performed in the office, it is more commonly performed in an operating room by an OB/GYN. Direct comparisons of these two interventions have produced inconclusive and, at times, contradictory results, since most studies published previously have been limited by small sample sizes, high attrition, or short follow-up.
This multicenter trial occurred from 2012 to 2016 in the Netherlands. Participants were eligible for enrollment if they had heavy menstrual bleeding, defined as a score of 150 points or higher on the Pictorial Blood Loss Assessment Chart (PBAC). Participants were excluded if they were younger than 34 years of age; desired pregnancy; had abnormal cervical cytology in last five years; had intracavitary fibroids, polyps, or large intramural fibroids; had a uterine length greater than 10 cm; or had a uterine size greater than 10 weeks on ultrasound or bimanual exam. Consenting participants were randomized in a 1:1 ratio to an LNG-IUS insertion (performed in the office), or an EA procedure (performed either in the office under local anesthesia or conscious sedation, or in the operating room under general anesthesia or spinal anesthesia). Neither the participants nor the treating clinicians were blinded, given the nature of both interventions.
Participants completed PBAC scores prior to enrollment, and again at three, six, 12, and 24 months after randomization. This score is calculated by adding together the total number of tampons or pads used over the course of a month, with each product assigned a score of 1-20, depending on degree of saturation. The primary outcome was PBAC at 24 months. Secondary outcomes included controlled bleeding (PBAC < 75 points), complications and reinterventions, amenorrhea, spotting, dysmenorrhea, presence of clots, duration of blood loss, satisfaction with treatment (calculated on a five-point Likert scale), and quality of life.
Of 645 eligible participants, 270 consented to the study. Of the 132 participants randomized to the LNG-IUS, 122 (92%) had the Mirena intrauterine device inserted, with a median time to insertion of seven days. Of the 138 participants randomized to EA, 130 (94%) underwent the Novasure procedure, although in seven (5.4%) cases, the procedure could not be completed. The median time to EA was 27 days. Both groups had similar baseline characteristics. The mean PBAC at 24 months was 64.8 points in the LNG-IUS group compared to 14 points in the EA group (mean difference 50.5; 95% confidence interval [CI], 4.3-96.7). Since the upper limit of the 95% CI exceeded the predetermined noninferiority margin of 25 points, this study did not demonstrate noninferiority of the LNG-IUS to EA.
In both intervention groups, significant declines in mean PBAC were observed from the baseline score to the three-month follow-up score, with most below 75 in both groups. By 24 months, 87% of participants in the LNG-IUS group and 94% of participants in the EA group had PBAC scores below 75. Amenorrhea, duration of blood loss, spotting, presence of clots, and dysmenorrhea were the same between both groups. LNG-IUS removal occurred in 49 (39%) cases, and the LNG-IUS group was more likely than the EA group to receive additional surgical or drug reintervention within 24 months (35% vs. 27%; relative risk [RR], 1.77; 95% CI, 1.17-2.68). Until 12 months, satisfaction was higher in the EA group compared to the LNG-IUS group. At 24 months, satisfaction was comparable between groups, with 74% of participants in the LNG-IUS group and 84% in the EA group satisfied with their method (RR, 0.88; 95% CI, 0.76-1.01).
COMMENTARY
This randomized controlled trial does not demonstrate that the LNG-IUS is noninferior to EA when comparing mean PBAC scores at 24 months among people with heavy menstrual bleeding. However, both interventions led to a significant decrease in blood loss among participants, comparable quality-of-life and satisfaction scores. Most participants in both groups ended the study with PBAC scores under 75, which indicates controlled bleeding. Although the removal rate of the LNG-IUS was high (39%) and participants in the LNG-IUS group were twice as likely to require an additional drug or surgical intervention, hysterectomy rates were similar between the two groups. Participants in the EA group achieved satisfaction more quickly than those in the LNG-IUS group, likely because the EA works immediately, while the LNG-IUS can take a three to six months to reach its desired effects, with the potential for irregular or prolonged bleeding patterns in the interim.
This study benefits from a large sample size and a low loss to follow-up rate. Participant recruitment from both OB/GYN and primary care providers reflects real-life clinical practice. However, as with many studies conducted outside of the United States, the results may be of limited generalizability. For example, the average body mass index (BMI) in both groups is 27 kg/m2, which is lower than the average BMI in the United States (29 kg/m2). Not included in the results are participant medical comorbidities, such as rates of diabetes or hypertension. Was this study population at risk of endometrial pathology? What about anesthetic complications? In some clinical scenarios, a provider may encourage an LNG-IUS over EA given the protective effect of progestin on the endometrium. In others, medical comorbidities may put patients at higher risk of anesthetic complications, making the operating room a less desirable option.
The shorter median time to LNG-IUS insertion (seven days) compared to EA provision (27 days) in this study highlights the ease and convenience of an LNG-IUS insertion, both for providers and patients. Additionally, while in practice and in this study most EAs were performed by OB/GYNs, primary care providers also can insert an LNG-IUS, which expands access. Finally, although no data are included on rates of insurance coverage in the study population, insurance coverage is an important predictor of healthcare access. Without health insurance, a same-day LNG-IUS insertion may be more feasible and affordable compared to a trip to the operating room for an EA.
This study highlights the pros and cons of two commonly used management options for heavy menstrual bleeding. Both the LNG-IUS and EA are highly effective and minimally invasive alternatives to hysterectomy. The EA offers a quicker, more robust reduction in blood loss with lower chances of requiring surgical reintervention (with the exception of hysterectomy) compared to the LNG-IUS. In contrast, the LNG-IUS is a reversible, convenient option that can be placed immediately in the office without the need for anesthesia, and it provides endometrial protection.
REFERENCES
- Gupta J, Kai J, Middleton L, et al. Levonorgestrel intrauterine system versus medical therapy for menorrhagia. N Engl J Med 2013;368:128-137.
- Daud S, Ewies AA. Levonorgestrel-releasing intrauterine system: Why do some women dislike it? Gynecol Endocrinol 2008;24:686-690.
