Is the levonorgestrel-releasing intrauterine system (Mirena) safe and effective for reducing heavy menstrual bleeding?
The levonorgestrel-releasing intrauterine system is more effective than other medical therapies at reducing menstrual bleeding volume (mean difference [MD] = 67 mL; 95% CI, 43 to 91 mL), with similar rates of adverse effects. The effectiveness of the levonorgestrel-releasing intrauterine system compared with endometrial ablation and hysterectomy has been inadequately studied.1 (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)
Heavy menstrual bleeding is defined by the perception of excessive bleeding affecting a patient's quality of life and is common among those of reproductive age. Numerous medical and surgical therapeutic options exist for heavy menstrual bleeding. The authors of this Cochrane review sought to evaluate the effectiveness and safety of the levonorgestrel-releasing intrauterine system compared with other therapeutic options for heavy menstrual bleeding.1
This Cochrane review included 25 randomized controlled trials and 2,511 patients, with studies comparing the levonorgestrel-releasing intrauterine system with no treatment, placebo, medical therapies (including nonsteroidal anti-inflammatory drugs, antifibrinolytic drugs, and hormone-containing medications), endometrial ablation, and hysterectomy.1 Participants were of reproductive age with regular heavy periods. The study locations and durations were heterogeneous, spanning multiple countries and ranging in length from three months to 10 years. The primary outcomes were effectiveness (reduction in blood loss measured objectively, semi-objectively, or subjectively) and patient satisfaction (measured on a five-point Likert scale). Secondary outcomes were quality of life, adverse effects, withdrawal from treatment, treatment failure, need for subsequent surgery, and cost.
The levonorgestrel-releasing intrauterine system consistently reduced heavy menstrual bleeding compared with other medical therapies. The intrauterine system was associated with greater reduction of bleeding volume from baseline compared with an oral contraceptive measured by objective methods (MD = 67 mL; 95% CI, 43 to 91 mL; two studies; 170 women) and a separate analysis of semi-objective methods (MD = 55 mL; 95% CI, 28 to 82 mL; three studies; 335 women; duration of six to 12 months). Most of the remaining six randomized controlled trials also noted reduction in heavy menstrual bleeding volume with the levonorgestrel-releasing intrauterine system compared with other medical therapies, although treatment outcomes could not be pooled because of clinical heterogeneity.
Bleeding outcomes were mixed when comparing the levonorgestrel-releasing intrauterine system and endometrial ablation, with two studies showing improvement of bleeding with endometrial ablation, two showing improvement with the levonorgestrel-releasing intrauterine system, and four with no clear difference. Data were insufficient to compare the effectiveness between the levonorgestrel-releasing intrauterine system and hysterectomy.
The authors note that the quality of all studies was limited by low participant numbers, and confidence in the findings was also low. The levonorgestrel-releasing intrauterine system caused similar rates of adverse effects and lower rates of treatment failure compared with other medical therapies. The intrauterine system had higher treatment failure rates and more adverse effects, especially progestin-related effects, including mastalgia, weight gain, and acne, compared with endometrial ablation. The authors were unable to adequately compare the levonorgestrel-releasing intrauterine system and hysterectomy.
These findings reflect conclusions of previous reviews demonstrating that the levonorgestrel-releasing intrauterine system is likely the most effective medical therapy for heavy menstrual bleeding.2 The National Institute for Health and Care Excellence guidelines for heavy menstrual bleeding recommend considering the levonorgestrel-releasing intrauterine system as first-line treatment for patients with heavy menstrual bleeding with no identified pathology.3
The practice recommendations in this activity are available at http://www.cochrane.org/CD002126.