NIHR Signal A hormone-releasing coil is best for relieving heavy periods

Published on 28 September 2015

This Cochrane systematic review of trials found that a progesterone releasing coil device (mainly Mirena®) inserted in the womb was more effective at reducing heavy periods than taking oral tablets. The coil led to more minor side effects, but improved quality of life, compared with tablets. Surgical removal of the womb, hysterectomy, was more effective than the coil, but is more invasive and costly. A second surgical option - removing the womb lining – was similar at reducing heavy bleeding and improving quality of life as the coil. The findings are in line with 2007 NICE guidance saying the coil should be the first treatment considered.

Share your views on the research.

Why was this study needed?

Heavy menstrual bleeding does not necessarily mean there is anything seriously wrong, but it can affect a woman physically, emotionally and socially, and can disrupt everyday life. It is not clear how common it is in the UK, but around 1 in 10 of all gynaecology referrals includes heavy menstrual bleeding. If treatment is needed, medication is most commonly used first. If this doesn’t work surgery is a later option. This can include removal of the womb (hysterectomy), or womb lining. Both operations carry risks associated with having major surgery and hysterectomy removes the ability to have children. This Cochrane systematic review aimed to find the most effective treatments for heavy menstrual bleeding by looking at all relevant trials. It updated a 2005 review with more recent studies.

What did this study do?

The study was a systematic review of randomised controlled trials. It included 21 trials involving 2,082 women of reproductive age who had heavy menstrual bleeding that was not due to a disease. Most trials excluded women with fibroids. The review compared the progesterone-releasing coil with a placebo or taking tablets, or surgical options. Only the coil device containing the hormone levonorgestrel remain on the market, so the researchers drew conclusions based on this hormone alone. Cochrane systematic reviews follow a rigorous process so are considered reliable.

What did it find?

  • The progesterone-releasing coil reduced blood loss by an average of 67ml (95% confidence interval 43 to 91ml) more than taking tablets, such as hormone treatment or mefenamic acid. This was linked to a slightly higher chance of side effects using the coil including pelvic pain, breast tenderness and benign ovarian cysts. Despite this, the coil was more effective at improving quality of life, and women were more likely to continue using the coil after two years of treatment, compared with tablets.
  • However, almost half (46%) of women using the coil eventually needed surgical removal of the womb to control bleeding within 10 years.
  • There were no differences in patient satisfaction for any of the treatments.
  • Removing the womb was most effective at reducing heavy menstrual bleeding but was the most expensive option, even over ten years.
  • The findings are consistent with the 2005 Cochrane review. But their strength has increased as 12 more trials were included with more comparisons against no treatment.

What does current guidance say on this issue?

2007 NICE guidance recommends offering the progesterone-releasing coil as the first choice treatment for women who do not have underlying disease such as large fibroids, non-cancerous growths in or around the womb. The second choice is oral medication using tranexamic acid or non-steroidal anti-inflammatory drugs, or combined oral contraceptives. This guidance is due to be updated but a specific date has not been given.

What are the implications?

The findings are in line with existing 2007 NICE guideline treatment recommendations. This review strengthens the evidence on effectiveness and acceptability of the progesterone-releasing coil and so adds further weight behind its place as the first-line treatment option, before other medication or surgery. However, research evidence was incomplete on women’s satisfaction with the full range of treatments, so services should offer women information and choice on the options.

Citation

Lethaby A, Hussain M, Rishworth JR, Rees MC. Progesterone or progestogen‐releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst Rev. 2015;(4):CD002126.

Bibliography

Clegg J, King E. Estimation of haemoglobin by the alkaline haematin method. BMJ. 1942;2(4263):329.

Higham JM. O’Brien PM, Shaw RM. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol. 1990; 8: 734–739.

NHS Choices. Heavy periods (menorrhagia). [internet] London: NHS Choices; updated 2014.

NICE. Heavy menstrual bleeding. CG44. London: National Institute for Health and Care Excellence; 2007.

Why was this study needed?

Heavy menstrual bleeding does not necessarily mean there is anything seriously wrong, but it can affect a woman physically, emotionally and socially, and can disrupt everyday life. It is not clear how common it is in the UK, but around 1 in 10 of all gynaecology referrals includes heavy menstrual bleeding. If treatment is needed, medication is most commonly used first. If this doesn’t work surgery is a later option. This can include removal of the womb (hysterectomy), or womb lining. Both operations carry risks associated with having major surgery and hysterectomy removes the ability to have children. This Cochrane systematic review aimed to find the most effective treatments for heavy menstrual bleeding by looking at all relevant trials. It updated a 2005 review with more recent studies.

What did this study do?

The study was a systematic review of randomised controlled trials. It included 21 trials involving 2,082 women of reproductive age who had heavy menstrual bleeding that was not due to a disease. Most trials excluded women with fibroids. The review compared the progesterone-releasing coil with a placebo or taking tablets, or surgical options. Only the coil device containing the hormone levonorgestrel remain on the market, so the researchers drew conclusions based on this hormone alone. Cochrane systematic reviews follow a rigorous process so are considered reliable.

What did it find?

  • The progesterone-releasing coil reduced blood loss by an average of 67ml (95% confidence interval 43 to 91ml) more than taking tablets, such as hormone treatment or mefenamic acid. This was linked to a slightly higher chance of side effects using the coil including pelvic pain, breast tenderness and benign ovarian cysts. Despite this, the coil was more effective at improving quality of life, and women were more likely to continue using the coil after two years of treatment, compared with tablets.
  • However, almost half (46%) of women using the coil eventually needed surgical removal of the womb to control bleeding within 10 years.
  • There were no differences in patient satisfaction for any of the treatments.
  • Removing the womb was most effective at reducing heavy menstrual bleeding but was the most expensive option, even over ten years.
  • The findings are consistent with the 2005 Cochrane review. But their strength has increased as 12 more trials were included with more comparisons against no treatment.

What does current guidance say on this issue?

2007 NICE guidance recommends offering the progesterone-releasing coil as the first choice treatment for women who do not have underlying disease such as large fibroids, non-cancerous growths in or around the womb. The second choice is oral medication using tranexamic acid or non-steroidal anti-inflammatory drugs, or combined oral contraceptives. This guidance is due to be updated but a specific date has not been given.

What are the implications?

The findings are in line with existing 2007 NICE guideline treatment recommendations. This review strengthens the evidence on effectiveness and acceptability of the progesterone-releasing coil and so adds further weight behind its place as the first-line treatment option, before other medication or surgery. However, research evidence was incomplete on women’s satisfaction with the full range of treatments, so services should offer women information and choice on the options.

Citation

Lethaby A, Hussain M, Rishworth JR, Rees MC. Progesterone or progestogen‐releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst Rev. 2015;(4):CD002126.

Bibliography

Clegg J, King E. Estimation of haemoglobin by the alkaline haematin method. BMJ. 1942;2(4263):329.

Higham JM. O’Brien PM, Shaw RM. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol. 1990; 8: 734–739.

NHS Choices. Heavy periods (menorrhagia). [internet] London: NHS Choices; updated 2014.

NICE. Heavy menstrual bleeding. CG44. London: National Institute for Health and Care Excellence; 2007.

Progesterone or progestogen-releasing intrauterine systems for heavy menstrual bleeding

Published on 1 May 2015

Lethaby, A.,Hussain, M.,Rishworth, J. R.,Rees, M. C.

Cochrane Database Syst Rev Volume 4 , 2015

BACKGROUND: 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. OBJECTIVES: To determine the effectiveness, acceptability and safety of progesterone or progestogen-releasing intrauterine devices in achieving a reduction in heavy menstrual bleeding. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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; I(2) = 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; I(2) = 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. AUTHORS' CONCLUSIONS: 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 is defined as excessive menstrual blood loss that interferes with a woman's physical, social, emotional, or material quality of life. The clinical definition is blood loss of at least 80 ml per menstrual cycle, but some women feel their blood loss is excessive when it is less than this.

The two main ways of measuring menstrual blood loss are the alkaline haematin test, a laboratory test and the Pictorial Bleeding Assessment Chart, a more subjective score filled out by the woman herself. Although the laboratory test is more accurate, it is impractical to organise, so the self‑completed chart is more commonly used.

Expert commentary

The practical implications of this Cochrane review and the impact on policy and practice in the UK in general and the NHS in particular, is that the levonorgestrel-releasing intrauterine device is more effective than oral medication as a treatment for heavy menstrual bleeding in the short and long term. It has similar satisfaction rates and improvements in quality of life compared to endometrial ablation and hysterectomy. It is less effective than hysterectomy in reducing bleeding. The device is more cost-effective compared to both surgical options. This review confirms that a levonorgestrel-releasing intrauterine device should be used as first line treatment for women with heavy menstrual bleeding. Its use in primary care should be promoted.

Professor Janesh Gupta, Professor of Obstetrics and Gynaecology, University of Birmingham, Birmingham Women’s Hospital