Review question: This Cochrane review has evaluated whether the levonorgestrel–releasing intrauterine system (LNG IUS) reduces heavy menstrual bleeding and whether it is safe and acceptable.
Background: Heavy or excessive menstrual bleeding is a common problem in women before they reach the menopause. Women who feel that their menstrual bleeding is excessive will have reduced quality of life and are likely to seek medical help. A wide variety of treatments, of variable effectiveness, are available for women with heavy bleeding. These include oral tablets, such as non steroidal anti-inflammatory drugs, anti-fibrinolytic drugs, the contraceptive pill and drugs containing progestogen. Surgery, either hysterectomy (removal of the womb) or endometrial ablation (removal of the inner lining of the womb) are also commonly used, often when drug treatments are ineffective. A less invasive alternative to these options is the progestogen-releasing intrauterine system, a device placed inside the womb, which regularly delivers small amounts of progestogen and can also be used for contraception.
Study characteristics: This review contains 21 RCTs conducted up to July 2014 that included 2082 participants with heavy menstrual bleeding. Evidence obtained is current to January 2015.
Key results: Almost all the studies assessed the effects of the LNG IUS and conclusions refer only to this device. The LNG IUS was more effective in reducing heavy menstrual bleeding and improving quality of life than oral medication. Satisfaction with treatment was not assessed in enough trials to know whether this was better with LNG IUS. The evidence suggested that the LNG IUS and techniques used to remove the inner lining of the womb were similarly effective at reducing heavy menstrual bleeding and improving quality of life and satisfaction and the two treatments had similar failure rates. The LNG IUS caused higher rates of some side effects, such as breast tenderness, bloating, weight gain and ovarian cysts, but this did not seem to cause women to stop taking their treatment. The LNG IUS was not as effective as hysterectomy in reducing menstrual blood loss but improvements in quality of life were similar. Although many women trying the LNG IUS eventually went on to have a hysterectomy for their heavy menstrual bleeding, the LNG IUS appeared to have lower overall costs than either endometrial ablation or hysterectomy.
Quality of the evidence: Many of the trials in this review were small (<100 participants) and some were at high risk of bias. Ratings for the overall quality of the evidence for each comparison ranged from very low to high. Limitations in the evidence included inadequate reporting of study methods and inconsistency. One large trial compared the LNG IUS with hysterectomy over a 10-year period and a number of other trials made assessments two years after starting treatment, so we have some information on the long-term effects of treatments. Future research needs to measure satisfaction.
The levonorgestrel-releasing intrauterine device (LNG IUS) is more effective than oral medication as a treatment for heavy menstrual bleeding (HMB). It is associated with a greater reduction in HMB, improved quality of life and appears to be more acceptable long term but is associated with more minor adverse effects than oral therapy.
When compared to endometrial ablation, it is not clear whether the LNG IUS offers any benefits with regard to reduced HMB and satisfaction rates and quality of life measures were similar. Some minor adverse effects were more common with the LNG IUS but it appeared to be more cost effective than endometrial ablation techniques.
The LNG IUS was less effective than hysterectomy in reducing HMB. Both treatments improved quality of life but the LNG IUS appeared more cost effective than hysterectomy for up to 10 years after treatment.
Heavy menstrual bleeding (HMB) is an important cause of ill health in women and it accounts for 12% of all gynaecology referrals in the UK. Heavy menstrual bleeding is clinically defined as greater than or equal to 80 mL of blood loss per menstrual cycle. However, women may complain of excessive bleeding when their blood loss is less than 80 mL. Hysterectomy is often used to treat women with this complaint but medical therapy may be a successful alternative.
The intrauterine device was originally developed as a contraceptive but the addition of progestogens to these devices resulted in a large reduction in menstrual blood loss. Case studies of two types of progesterone or progestogen-releasing systems, Progestasert and Mirena, reported reductions of up to 90% and improvements in dysmenorrhoea (pain or cramps during menstruation). Insertion, however, may be regarded as invasive by some women, which affects its acceptability as a treatment. Frequent intermenstrual bleeding and spotting is also likely during the first few months after commencing treatment.
To determine the effectiveness, acceptability and safety of progesterone or progestogen-releasing intrauterine devices in achieving a reduction in heavy menstrual bleeding.
All randomised controlled trials of progesterone or progestogen-releasing intrauterine devices for the treatment of heavy menstrual bleeding were obtained by electronic searches of The Cochrane Library, the specialised register of MDSG, MEDLINE (1966 to January 2015), EMBASE (1980 to January 2015), CINAHL (inception to December 2014) and PsycINFO (inception to January 2015). Additional searches were undertaken for grey literature and for unpublished trials in trial registers. Companies producing progestogen-releasing intrauterine devices and experts in the field were contacted for information on published and unpublished trials.
Randomised controlled trials in women of reproductive age treated with progesterone or progestogen-releasing intrauterine devices versus no treatment, placebo, or other medical or surgical therapy for heavy menstrual bleeding within primary care, family planning or specialist clinic settings were eligible for inclusion. Women with postmenopausal bleeding, intermenstrual or irregular bleeding, or pathological causes of heavy menstrual bleeding were excluded.
Potential trials were independently assessed by at least two review authors. The review authors extracted the data independently and data were pooled where appropriate. Risk ratios (RRs) were estimated from the data for dichotomous outcomes and mean differences (MD) for continuous outcomes. The primary outcomes were reduction in menstrual blood loss and satisfaction; in addition, rate of adverse effects, changes in quality of life, failure of treatment and withdrawal from treatment were also assessed.
We included 21 RCTs (2082 women). The included trials mostly assessed the levonorgestrel-releasing intrauterine device (LNG IUS) (no conclusions could be reached from one small study assessing Progestasert which was discontinued in 2001) and so conclusions are based only on LNG IUS. Comparisons were made with placebo, oral medical treatment, endometrial destruction techniques and hysterectomy. Ratings for the overall quality of the evidence for each comparison ranged from very low to high. Limitations in the evidence included inadequate reporting of study methods and inconsistency.
Seven studies compared the LNG IUS with oral medical therapy: either norethisterone acetate (NET) administered over most of the menstrual cycle, medroxyprogesterone acetate (MPA) (administered for 10 days), the oral contraceptive pill, mefenamic acid or usual medical treatment where participants could choose the oral treatment that was most suitable. The LNG IUS was more effective at reducing HMB as measured by the alkaline haematin method (MD 66.91 mL, 95% CI 42.61 to 91.20; two studies, 170 women; I2 = 81%, low quality evidence) or by Pictorial Bleeding Assessment Chart (PBAC) scores (MD 55.05, 95% CI 27.83 to 82.28; three studies, 335 women; I2 = 79%, low quality evidence), improving quality of life and a greater number of women continued with their treatment at two years when compared with oral treatment. Although substantial heterogeneity was identified for the bleeding outcomes, the direction of effect consistently favoured the LNG IUS. There was insufficient evidence to reach conclusions on satisfaction. Minor adverse effects (such as pelvic pain, breast tenderness and ovarian cysts) were more common with the LNG IUS.
Ten studies compared the LNG IUS with endometrial destruction techniques: three with transcervical resection, one with rollerball ablation and six with thermal balloon ablation. Evidence was inconsistent and very low quality with respect to reduction in bleeding outcomes and satisfaction was comparable between treatments (low and moderate quality evidence). Improvements in quality of life were experienced with both types of treatment. Minor adverse events were more common with the LNG IUS overall, but it appeared more cost effective compared to thermal ablation within a two-year time frame in one study.
Three studies compared the LNG IUS with hysterectomy. The LNG IUS was not as successful at reducing HMB as hysterectomy (high quality evidence). The women in these studies reported improved quality of life, regardless of treatment. In spite of the high rate of surgical treatment in those having LNG IUS within 10 years, the LNG IUS was more cost effective than hysterectomy.