Intrauterine System Eases Heavy Menstrual Bleeding

For women presenting to their primary care providers with menorrhagia, the levonorgestrel-releasing intrauterine system (IUS) leads to greater improvement in alleviating the adverse effects on daily life of heavy menstrual bleeding compared with usual medical treatments, according to results of the 2-year ECLIPSE (Effectiveness and Cost-Effectiveness of Levonorgestrel-Containing Intrauterine System in Primary Care against Standard Treatment for Menorrhagia) trial. Trial results were reported in the New England Journal of Medicine [2013;368(2):128-137].

In an updated meta-analysis from 9 small randomized trials involving 783 women, the levonorgestrel-IUS showed a greater reduction in menstrual blood loss than other nonhormonal and hormonal treatments. However, it is not clear whether these benefits continue because the studies were short-term (3-12 months) and did not investigate the effects of this therapy on bleeding-related quality of life.

The ECLIPSE trial was a pragmatic, multicenter, randomized trial that compared the clinical effectiveness of the levonorgestrel-IUS with usual medical treatment in the primary care setting. The study enrolled 571 women 25 to 50 years of age (mean age 42) from 63 United Kingdom centers who presented to the primary care physicians with menorrhagia involving at least 3 consecutive cycles. Exclusion criteria included women who intended to become pregnant in the next 5 years, were taking hormone-replacement therapy or tamoxifen, had intermenstrual bleeding or postcoital bleeding or fibroids or other disorders, or had contraindications to, or a preference for, either the levonorgestrel-IUS or usual medical treatments.

The participants were randomly assigned to levonorgestrel-IUS (n=285) or usual medical treatment (n=286). Usual medical treatment included mefenamic acid, tranexamic acid, norethindrone, a combined estrogen-progestogen or progesterone-only oral contraceptive pill, or medroxyprogesterone acetate injection. The choice of usual medical treatment was determined by the physician and patient based on individual needs or the desire to avoid hormonal treatment and was specified before randomization. The study design also allowed changes in all treatments for any reason.

The primary outcome measure was the condition-specific Menorrhagia Multi-Attribute Scale (MMAS), which evaluated the condition’s effect on 6 quality-of-life domains: (1) practical difficulties, (2) social life, (3) psychological health, (4) physical health, (5) work and daily routines, and (6) family life and relationships. Scores ranged from 0 (severely affected) to 100 (not affected). Secondary outcome measures included general health-related quality of life, sexual activity, and surgical interventions.

Total MMAS scores improved significantly from baseline to 6 months in both the levonorgestrel-IUS group and the usual-treatment group (mean increase, 32.7 and 21.4 points, respectively; P<.001 for both). The improvements were sustained through 2 years with a significantly greater benefit in the levonorgestrel-IUS group compared with the usual-treatment group (mean between-group difference, 13.4 points; 95% confidence interval, 9.9-16.9; P<.001). Improvement in all 6 MMAS domains was significantly greater in levonorgestrel-IUS, and this was also true for 7 of the 8 quality-of-life domains. The study results showed no major difference between the 2 groups in the rates of sexual activity scores or surgical interventions.

At 2 years, more women assigned to the levonorgestrel-IUS group were still receiving it than those undergoing usual treatment (64% vs 38%; P<.001). The most common reasons for discontinuing levonorgestrel-IUS included lack of effectiveness (37%) and irregular or prolonged bleeding (28%). Lack of effectiveness was the most common reason for discontinuing usual therapy (53%). Of the 163 women who discontinued usual medical treatment, 49% switched to the levonorgestrel-IUS. There were no significant differences in serious adverse events between groups.

“Our study showed that both the levonorgestrel-IUS and usual medical treatments reduced the adverse effect of menorrhagia on women’s lives over the course of 2 years, but the levonorgestrel-IUS was the more effective first choice, as assessed by the impact of bleeding on the women’s quality of life,” concluded the researchers.