Levonorgestrel-Releasing Intrauterine System May Improve Quality of Life Compared to Usual Medical Treatments for Women with Menorrhagia
Resident Focus - Volume 10, Issue 2
Heavy menstrual bleeding affects approximately 25% of women of childbearing age and accounts for over 18% of gynecologic visits (Br J Gen Pract 2004;54(502):359). Menorrhagia can be detrimental to ones work and daily routine, psychological well being, and physical health, and can ultimately reduce quality of life. In the past, menorrhagia was defined as menstrual blood loss of >80mL; however, around half of women presenting with menorrhagia do not meet that criteria. Therefore, using a patient-oriented approach measuring quality of life provides a more clinically meaningful goal for intervention. The levonorgestrel-releasing intrauterine system (LNG-IUS), oral contraceptive pills, nonsteroidal anti-inflammatory drugs, antifibrinolytics, and surgical procedures such as myomectomy or hysterectomy have traditionally been used for menorrhagia. What is the treatment of choice for sustained improvement in quality of life measures in menorrhagia?
In the ECLIPSE trial, 571 women with menorrhagia who met eligibility criteria (i.e. no pregnancy intention for 5 years and no fibroids) from 63 United Kingdom medical centers were randomly assigned to receive treatment with LNG-IUS or usual medical treatment such as tranexamic acid, oral contraceptives, or depo-provera. Baseline characteristics, including age, BMI, race, menorrhagia duration, menstrual pain, and contraceptive requirement were similar between the two groups. The primary outcome was assessed over two years with the Menorrhagia Multi-Attribute Scale (MMAS), a well-validated scale with a high degree of internal consistency and construct validity. The MMAS focuses on six quality of life measures: practical difficulties, social life, family life, work and daily routine, psychological well being and physical health. Summary scores ranging from 0 (severely affected) to 100 (not affected) were assessed at 6, 12, and 24 months; the minimal clinically important difference for this scale was not reported. Secondary outcome measures included rates of surgical intervention, health-related quality of life and a sexual activity questionnaire.
478 women (83.7%) completed the two-year study (247 in the LNG-IUS group and 231 in the usual medical treatment group). Both groups showed improvements in the primary outcome (MMAS score) over two years. However, the LNG-IUS group showed significantly greater improvement in total MMAS score at 6 months through 24 months, and this improvement was maintained through two years (between-group difference 13.4 points, 95% CI 9.9 to 16.9, P <0.001). An increase in 10 to 17 points on the MMAS would mean that someone who was substantially affected before treatment would now only be minimally-to-unaffected by menorrhagia post treatment with LNG-IUS. There was an overall between-group difference of 18.7 points favoring LNG-IUS for menorrhagia treatment when women who switched treatment or ceased taking treatment were excluded (14.8 to 22.6, p < 0.001). Women using LNG-IUS were almost twice as likely to be using their assigned treatment at the end of the study (64% vs 38%, P <0.001). Of the 163 women (62%) who discontinued usual medical treatment, 80 (49%) switched to LNG-IUS, citing lack of effectiveness as the most common reason. Of the 36% who discontinued LNG-IUS, 33 (37%) cited lack of efficacy and 25 (28%) cited irregular or prolonged bleeding. The crossover rates were accounted for in further subgroup analyses. It is noteworthy that at the end of two years, women in the LNG-IUS group were nearly twice as likely to be receiving their assigned treatment as the women in the usual treatment group (64% vs. 38%, p<0.001).
In a subgroup analysis, women in the LNG-IUS group with BMI > 25 (-16.5 MMAS points) benefited more than women with BMI < 25 (-5.4 points) (p = 0.004). The LNG-IUS group also showed greater improvement in secondary outcome measures of physical role, energy and vitality, pain and social functioning (P< 0.001 for trend). There was no significant between-group difference in 2 of the 3 quality of life assessment tools, sexual activity secondary outcomes, or surgical intervention frequency (hysterectomy, endometrial ablations). There was also no significant difference in frequency of adverse effects between the two groups (58 in usual treatment group, 49 in LNG-IUS group, P=0.59) during the two year study period.
While both LNG-IUS and usual medical treatments improved MMAS quality of life measures, such as effects on social life, work routine, and family life, the improvements were significantly greater in the LNG-IUS group. This multicenter randomized controlled trial showed that LNG-IUS decreased the impact of heavy menstrual bleeding on women’s quality of life more than usual medical treatments over the two-year study period.
For more information, see the Heavy menstrual bleeding topic in DynaMed.