A levonorgestrel-releasing intrauterine system was more effective than usual medical treatments in alleviating the adverse effects of menorrhagia on women's lives, a 2-year primary care–based study has found.
The results were published in the January 10 issue of the New England Journal of Medicine by Janesh Gupta, MD, from the School of Clinical and Experimental Medicine, University of Birmingham, United Kingdom, and colleagues.
Initially developed as a contraceptive, the levonorgestrel-releasing intrauterine system (levonorgestrel-IUS; Mirena, Bayer HealthCare) also reduces menstrual blood loss and has been available for that use since 2009 in the United States, and earlier in Europe.
A previous meta-analysis of 9 small randomized trials involving a total of 783 women showed that the levonorgestrel-IUS produced a greater reduction in menstrual blood loss than did other hormonal and nonhormonal treatments, but those studies were mostly short-term (3 - 12 months) and did not investigate the effect of the treatments on bleeding-related quality of life.
The study enrolled a total of 571 women aged between 25 and 50 years (mean age, 42 years) who had consulted their primary care physician for menorrhagia. They were randomly assigned to receive either levonorgestrel-IUS or usual medical treatment, which could include mefenamic acid, tranexamic acid, norethindrone, a combined estrogen-progestogen or any progesterone-only oral contraceptive pill, or medroxyprogesterone acetate injection.
The choice of particular usual treatment decision was made by the physician and patient based on individual needs and desires and was specified before randomization. The study design allowed changes in all treatments, including the levonorgestrel-IUS, for any reason.
At 2 years, 64% of the women assigned to levonorgestrel-IUS were still receiving it compared with 38% who were still receiving their assigned usual treatment (P < .001). Reasons for discontinuing levonorgestrel-IUS included lack of effectiveness and irregular/prolonged bleeding (37% and 28%, respectively); lack of effectiveness was the most common reason for discontinuing usual therapy (53%).
Of the 163 women who discontinued usual treatment, 49% switched to levonorgestrel-IUS.
Serious adverse event rates did not differ between the 2 groups.
The primary outcome measure was the condition-specific Menorrhagia Multi-Attribute Scale (MMAS), which assesses the condition's effect in 6 daily life domains: practical difficulties, social life, psychological health, physical health, work/daily routine, and family life/relationships. Scores range from 0 (severe effect of menorrhagia) to 100 (no effect).
Total MMAS scores were improved significantly from baseline in both groups at 6 months, 1 year, and 2 years. However, improvements were greater in the levonorgestrel-IUS group, with a mean difference of 13.4 points at 2 years (95% confidence interval [CI], 9.9 - 16.9; P < .001). The levonorgestrel-IUS Improvements were significantly greater in all 6 domains at all 3 times (P for trend < .001).
Secondary outcomes included measures of health-related quality of life and sexual activity. On the Medical Outcomes Study 36-Item Short-Form Health Survey version 2, scores were significantly improved at all points for both groups, but were improved to a greater degree for the levonorgestrel-IUS group in all domains except mental health.
Between-group differences were not seen for other measures, including the pleasure, discomfort, and frequency domains of the Sexual Activity Questionnaire.
Rates of surgical interventions for heavy menstrual bleeding were similar between the groups. Hysterectomies were performed in 6% of each group, and endometrial ablations in 4% of the women treated with levonorgestrel-IUS vs 6% of the usual-treatment group (P = .44).
The authors note that they plan to conduct additional intention-to-treat analyses at 5 and 10 years.
Etiology Is Important
Sarah L. Berga, MD, told Medscape Medical News that levonorgestrel-IUS is an effective treatment for heavy menstrual bleeding in women who have age-related ovarian dysfunction, but faulted the study for failing to adequately eliminate other possible causes of excessive bleeding before initiating treatment.
"They never delineated truly the cause of the menorrhagia. I think that's one of the study's weaknesses," said Dr. Berga, professor and chair of the Department of Obstetrics and Gynecology and associate dean of Women's Health Research at Wake Forest School of Medicine and vice president of Women's Health Services at Wake Health Baptist Medical Center, Winston-Salem, North Carolina.
The study did exclude women who had bleeding between periods and those who had "findings suggestive of fibroids (abdominally palpable uterus equivalent in size to that at 10 to 12 weeks' gestation)."
However, Dr. Berga pointed out, neither of those exclusions eliminates the possibility of small polyps or fibroids that can lead to excessive bleeding.
"They did look for palpable fibroids, but the kind of fibroids that cause heavy bleeding at the expected time are typically ones that are small and intrude on the uterine cavity, and you wouldn't really expect to palpate them.... They don't have to be very big to interfere with the vascular bed."
In addition, even large fibroids can be missed by palpation alone in heavier women with large uteri, she added.
"We like to do ultrasound to see the uterine architecture. I don't know why they didn't in the study. From my point of view as a gynecologist, they skipped a step," Dr. Berga told Medscape Medical News.
However, she noted that one reassuring "clue" in the study was that 90% of the women were aged 35 years or older, suggesting that for the majority, the heavy bleeding was probably a result of age-related ovarian dysfunction. That condition, she said, is "a perfect use" of the levonorgestrel-IUS.
In fact, Dr. Berga believes levonorgestrel-IUS is "very underappreciated" as a treatment for heavy bleeding resulting from age-related changes in ovarian function. Although it is used widely for contraception, there is still hesitation about using intrauterine devices for menorrhagia, she noted.
"Let's assume these women have age-related changes in ovarian function leading to heavy periods.... If they're still sexually active there's still a small risk of pregnancy. Here's a wonderful treatment because it provides contraception and a hormonal signal to the uterus to reduce bleeding. I think it's a perfect first choice."
The study was supported by the National Institute of Health Research–Health Technology Assessment Programme. Dr. Gupta has reported receiving royalties from Hodder Arnold Publishing and lecture fees from Ethicon Gynecare, being an employee of Femcare-Nikomed, and receiving payment for expert testimony for clinical negligence cases in the United Kingdom National Health Service regarding vaginal hysterectomy and uterine rupture and for expert testimony on behalf of the Lincolnshire Police Force in a criminal case regarding the death of an unborn baby in utero. The other authors have disclosed no relevant financial relationships. Dr. Berga has disclosed serving on medical advisory boards for Agile Therapeutics, Noven Pharmaceutical, Watson Pharmaceutical, Teva Pharmaceutical Industries, Pfizer, and Shionogi and as a consultant for AHC Media LLC and Shionogi.
N Engl J Med. 2013;368:128-137.
Medscape Medical News © 2013 WebMD, LLC
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Cite this: Levonorgestrel System Eases Effects of Menorrhagia - Medscape - Jan 09, 2013.