In the first of a new series on evidence-based practice, Dr Kirsten Duckitt explains why tranexamic acid should be used to treat menorragia rather than progestogens

The Effective Health Care Bulletin on menorrhagia,1 published in 1995, was probably the first widely distributed synopsis of evidence which showed that tranexamic acid and mefenamic acid were effective in reducing regular heavy menstrual blood loss (menorrhagia), whereas the commonlyVused treatment of a progestogen in the luteal phase of the cycle was ineffective.

This evidence came mainly from a meta-analysis of randomised controlled trials (RCTs) and a survey of GP prescribing habits.2 This showed that less than 2% of the sampled GPs prescribed tranexamic acid, while the majority of GPs used oral progestogens such as norethisterone.

Since then two national guidelines have reinforced the recommendations that tranexamic acid and mefenamic mcid are effective treatments for menorrhagia and should be used in preference to a luteal phase progestogen.3,4

A more recent GP survey did show an increased awareness of the effectiveness of tranexamic acid, although progestogens were still commonly prescribed.5

Dhe problem is not confined to primary care. In New Zealand, where the use of tranexamic acid is restricted to secondary care, 50% of gynaecologists still use luteal phase progestogens for menorrhagia, and less than 10% use tranexamic acid.6

Two systematic reviews of RCTs have found that tranexamic acid significantly reduces menstrual blood loss compared with placebo (weighted mean difference –94 ml, 95% CI –151ml to –37ml).2,7 One of the reviews also found that tranexamic acid significantly reduces menstrual blood loss compared with luteal phase oral progestogens, mefenamic acid and ethamsylate.7

Small individual RCTs found that tranexamic acid was significantly more effective than mefenamic acid, ethamsylate, flurbiprofen, diclofenac, and norethisterone.

Nausea and leg cramps occur in a third of women taking tranexamic acid, but there was no increase in gastrointestinal adverse effects compared with either placebo or other drugs.8

Long-term follow-up studies have found no evidence to confirm the possibility of an increased risk of thromboembolism.8 Unlike non-steroidal anti-inflammatory drugs (NSAIDs), tranexamic acid has no effect on dysmenorrhoea.

One systematic review of RCTs found that NSAIDs, with the exception of ibuprofen, significantly reduced menstrual blood loss compared with placebo.4 Medication was taken only during menstruation, but doses varied depending on the drug. The mean reduction in menstrual blood loss compared with placebo ranged from 23ml (mefenamic acid) to 74ml (diclofenac).

When all the NSAIDs were combined, the difference compared with placebo was a reduced blood loss of 35ml (weighted mean difference –35ml, 95% CI –43 to –27ml).

Another systematic review of RCTs found no evidence of a difference in effectiveness between mefenamic acid and naproxen and no evidence of a difference between NSAIDs and other medical treatments.9 NSAIDs, especially naproxen, ibuprofen and mefenamic acid, have the additional advantage of relieving dysmenorrhoea in three-quarters of women.10,11

Commonly reported adverse effects were headaches and gastrointestinal disturbances, including indigestion, nausea, vomiting and diarrhoea. They occurred in at least half of the women taking NSAIDs in the RCTs that reported data on adverse effects, but similar levels of adverse effects were found in placebo cycles.4,9

Ñhere are no RCTs that compare oral progestogens with placebo. Two systematic reviews of comparative RCTs have found little benefit from oral progestogens given in the luteal phase, although oral progestogen treatment for 21 days of the cycle 2,12 and intrauterine progestogens13 significantly reduce menstrual blood loss from baseline.

In the trial of the longer treatment cycle, only 44% of women said they liked the treatment "well" or "very well", and only 22% elected to continue with treatment after the 3 months study period.13

Intrauterine progestogens have not, as yet, been compared with either tranexamic acid or mefenamic acid.

A recent RCT studied the effect of an education package on the management of menorrhagia in primary care in East Anglia.14 One hundred GP practices were recruited and randomised to either intervention or control.

The educational package was based on the principles of 'academic detailing' with independent academics. It was given in small practice-based interactive groups with a visual presentation, a printed evidence-based summary, a graphic management flow chart, and a follow-up meeting at 6 months.

The intervention package clearly highlighted the evidence for effective and ineffective treatments of menorrhagia. Treatments offered and referral rates to secondary care in women with menorrhagia were the main outcome measures.

The results of the trial show that women with menorrhagia in the intervention practices were 2.4 times as likely to be prescribed tranexamic acid compared with women in the control practices (odds ratio [OR] 2.38, 95%CI 1.61–3.49).

Interestingly, prescribing rates of mefenamic acid (29% vs 39%) and norethisterone (22% vs 24%) did not differ between intervention and control practices respectively. However, referral rates were significantly lower in the intervention group (20% vs 29%, OR 0.64, 95% CI 0.41–0.99), suggesting that the increased use of tranexamic acid in the intervention practices could have been responsible for the decreased rates of referral, presumably because the women received an effective treatment and were satisfied.

This is important as other studies have shown that surgical intervention is highly likely after referral to hospital, with 60% of women undergoing hysterectomy after referral in one study.15

Even when good evidence on effective treatments for a particular condition exists, there is no guarantee that doctors will change the way they manage that condition.

There is little evidence that traditional lectures, direct mailings or mere distribution of guidelines result in a sustained change in doctors prescribing and referral practice without specific dissemination and implementation strategies.16,17 There are many barriers to change18 and the current challenge is to find out which strategies for changing practice work best.

Specific interventions that can be used to promote change in practice include:

Use of clinical guidelines and computerised decision support systems

Developing educational programmes (such as the example described above)

Communicating research findings to patients
Developing strategies for organisational change.18

Compendiums, such as Clinical Evidence,19 that collate all the best evidence and are updated regularly, especially when they are available electronically, may become increasingly useful as the number of systematic reviews of evidence increases.

  1. Nuffield Institute for Health, University of Leeds, NHS Centre for Reviews and Dissemination, University of York, Royal College of Physicians. The management of menorrhagia. Effective Health Care 1995; 9.
  2. Coulter A, Kelland J, Peto V, Rees MC. Treating menorrhagia in primary care. An overview of drug trials and a survey of prescribing practice. Int J Technol Assess Health Care 1995; 11: 456-71.
  3. Royal College of Obstetricians and Gynaecologists. The Initial Management of Menorrhagia. Evidence-based Clinical Guidelines No.1. RCOG: London, 1998.
  4. Working Party for Guidelines for the Management of Heavy Menstrual Bleeding. An evidence-based guideline for the management of heavy menstrual bleeding. NZ Med J 1999; 112: 174-7.
  5. Taskforce to Improve the Management of Menorrhagia. GP Survey on Menorrhagia. London: Meditex, 1997. (Available from the Secretariat to the Taskforce to Improve the Management of Menorrhagia, 35 Findon Road, London W12 9PP)
  6. Farquhar CM, Kimble R. How do NZ gynaecologists treat menorrhagia? Aust NZ J Obstet Gynaecol 1996; 36: 444-7.
  7. Cooke I, Lethaby A, Farquhar C. Antifibrinolytics for heavy menstrual bleeding (Review). In: The Cochrane Library, Issue 4, 1999. Oxford: Update Software.
  8. Rybo G. Tranexamic acid therapy is effective treatment in heavy menstrual bleeding: clinical update on safety. Ther Adv 1991; 4:1-8.
  9. Lethaby A, Augood C, Duckitt K. Nonsteroidal anti-inflammatory drugs vs either placebo or any other medical treatment for heavy menstrual bleeding (Review). In: The Cochrane Library, Issue 4, 1999. Oxford: Update Software.
  10. Owen PR. Prostaglandin synthetase inhibitors in the treatment of primary dysmenorrhoea. Am J Obstet Gynecol 1984; 148: 96-103.
  11. Zhang WY, Li Wan Po A. Efficacy of minor analgesics in primary dysmenorrhoea: a systematic review. Br J Obstet Gynaecol 1998; 105: 780-9.
  12. Lethaby A, Irvine G, Cameron I. Cyclical progestogens for heavy menstrual bleeding. In: The Cochrane Library. Issue 3, 1999. Oxford: Update Software.
  13. Irvine GA, Campbell-Brown MB, Lumsden MA, Heikkila A, Walker JJ, Cameron IT. Randomised comparative study of the levonorgestrel intrauterine system and norethisterone for the treatment of idiopathic menorrhagia. Br J Obstet Gynaecol 1998; 105: 592-8.
  14. Fender GRK, Prentice A, Gorst T et al. Randomised controlled trial of educational package on management of menorrhagia in primary care: the Anglia menorrhagia education study. Br Med J 1999; 318: 1246-50.
  15. Coulter A, Bradlow J, Agass M, Martin-Bates C, Tulloch A. Outcomes of referrals to gynaecology outpatient clinics for menstrual problems: an audit of general practice records. Br J Obstet Gynaecol 1991; 98: 789-96.
  16. Davis DA, Thomson MA, Oxman AD, Haynes RB. Changing physician performance: a systematic review of continuing medical education strategies. JAMA 1995; 274: 700-5.
  17. NHS Centre for Reviews and Dissemination. Implementing clinical guidelines. Effective Health Care 1994; 8.
  18. Haines A, Donald A. Getting research findings into practice: making better use of research findings. Br Med J 1998; 317: 72-5.
  19. Clinical Evidence Issue 2. BMJ Publishing Group and the American College of Physicians-American Society of Internal Medicine, December 1999.

Guidelines in Practice, January/February 2000, Volume 3
© 2000 MGP Ltd
further information | subscribe