Which medications work best for menorrhagia?

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doi:10.12788/jfp.0054

Clinical Inquiries

Which medications work best for menorrhagia?

J Fam Pract. 2020 September;69(7):E11-E13 | 10.12788/jfp.0054

By

Allison Lale, MD, MPH

Elise Halajian, DO

Rick Guthmann, MD, MPH

Joan Nashelsky, MLS

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EVIDENCE-BASED ANSWER:

Four medications have been shown to reduce menstrual blood loss (MBL) significantly in placebo-controlled randomized controlled trials (RCTs): the levonorgestrel-releasing intrauterine system (LNG-IUS), tranexamic acid, nonsteroidal anti-inflammatory drugs (NSAIDs), and danazol, a synthetic steroid (strength of recommendation: A, meta-analyses of RCTs).

A single trial showed that the LNG-IUS reduced MBL by about 100 mL, compared with placebo. In a meta-analysis of 4 placebo-controlled RCTs, tranexamic acid reduced MBL by about 53 mL, roughly a 40% to 50% decrease. The 8 NSAID trials (5 mefenamic acid, 2 naproxen, 1 ibuprofen) demonstrated effectiveness, but the effect size is difficult to quantify. The single danazol RCT used a subjective scoring system without reporting MBL.

No studies compared all effective medical therapies against one another. In head-to-head comparisons, women were more likely to experience improvement with the LNG-IUS than with tranexamic acid (number needed to treat [NNT] = 2 to 6). Both treatments are superior to NSAIDs. Danazol is also more efficacious than NSAIDs, but its use is limited by its adverse effects, including teratogenicity.

No placebo-controlled trials have studied oral contraceptive pills (OCPs) or oral progesterone to treat menorrhagia. However, multiple comparative RCTs have demonstrated that these commonly prescribed medications significantly decrease MBL. Trials have shown the reduction to be inferior to LNG-IUS and danazol and equivalent to NSAIDs.

References

1. Lethaby A, Hussain M, Rishworth JR, et al. Progesterone or progesterone-releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst Rev. 2015;(4):CD002126.

2. Gupta J, Kai J, Middleton L, et al. Levonorgestrel intrauterine system versus medical therapy for menorrhagia N Engl J Med. 2013;368:128-137.

3. Farquhar C, Brown J. Oral contraceptive pill for heavy menstrual bleeding. Cochrane Database Syst Rev. 2009;(4):CD000154.

4. Bryant-Smith AC, Lethaby A, Farquhar C, et al. Antifibrinolytics for heavy menstrual bleeding. Cochrane Database Syst Rev. 2018;(4):CD000249.

5. Lethaby A, Duckitt K, Farquhar C. Non-steroidal anti-inflammatory drugs for heavy menstrual bleeding. Cochrane Database Syst Rev. 2013;(1):CD000400.

6. Beaumont HH, Augood C, Duckitt K, et al. Danazol for heavy menstrual bleeding. Cochrane Database Syst Rev. 2010;(1):CD00107.

7. Hartmann KE, Jerome RN, Lindegren ML, et al. Primary Care Management of Abnormal Uterine Bleeding. Comparative Effectiveness Review No. 96 (AHRQ Publication No. 13-EHC025-EF). Rockville, MD: Agency for Healthcare Research and Quality; 2013. https://effectivehealthcare.ahrq.gov/topics/abnormal-uterine-bleeding. Accessed August 25, 2020.

8. National Institute for Health Care and Excellence (NICE). Heavy menstrual bleeding: assessment and management. NICE Guideline NG88; 2018. www.nice.org.uk/guidance/ng88. Accessed August 25, 2020.

EVIDENCE SUMMARY

A 2015 Cochrane review of the LNG-IUS for menorrhagia included 1 placebo-controlled RCT; most of the remaining 21 RCTs compared the LNG-IUS to invasive procedures such as endometrial ablation or hysterectomy.¹The placebo-controlled trial compared the LNG-IUS with placebo in 40 women on anticoagulation therapy and found a mean beneficial difference of 100 mL (95% confidence interval [CI], –116 to –83) using a subjective pictorial blood assessment chart.

Women are less likely to withdraw from LNG-IUS treatment

Four trials (379 patients) included in the Cochrane review compared LNG-IUS with combination or progesterone-only pills. All of the trials excluded women with palpable or large (> 5 cm) fibroids. In 3 trials (2 against OCPs and 1 against a 10-day course of oral progesterone), the LNG-IUS decreased MBL more than OCPs did. A fourth trial found LNG-IUS comparable to oral progesterone dosed 3 times a day from Day 5 to Day 26 of each menstrual cycle.

A recent large RCT (571 patients) that compared LNG-IUS with usual medical treatment (mefenamic acid [MFA], tranexamic acid, norethindrone, OCPs, progesterone-only pill, medroxyprogesterone acetate injection) found women significantly less likely to withdraw from LNG-IUS at 2 years (relative risk [RR] = 0.58; 95% CI, 0.49-0.70).²

Estrogen and progestin contraceptives significantly reduce bleeding

In addition to the trials in the 2015 Cochrane review comparing OCPs with LNG-IUS, a 2009 Cochrane review included a single 2-month crossover trial of 45 patients.³ This RCT compared OCPs with naproxen, MFA, and danazol to treat heavy menstrual bleeding (assessed using the alkaline haematin method).

Researchers didn’t analyze the data using intention-to-treat. No group was found to be superior. The OCP group (6 women) had a 43% reduction in MBL over baseline (no P value reported).

Tranexamic acid outperforms oral progesterone and NSAIDs but not ...

A 2018 Cochrane meta-analysis of 13 RCTs (1312 patients) of antifibrinolytics for reproductive-age women with regular heavy periods and no known underlying pathology included 4 RCTs (565 patients) that used placebo as a comparator.⁴Therapy with tranexamic acid decreased blood loss by53 mL per cycle (95% CI, 44-63 mL), a 40% to 50% improvement compared with placebo. Three of the RCTs (271 patients) reported the percent of women improving on tranexamic acid as 43% to 63%, compared with 11% for placebo, resulting in an NNT of 2 to 3.

In head-to-head comparisons, women were more likely to improve with the LNG-IUS than tranexamic acid for reducing menstrual blood loss.

One trial (46 patients) found tranexamic acid superior to luteal phase oral progesterone, and another study (48 patients) demonstrated superiority to NSAIDs, with a mean decrease in MBL of 86 mL compared with 43 mL (P < .0027).

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Evidence-based answers from the Family Physicians Inquiries Network

Which medications work best for menorrhagia?

EVIDENCE-BASED ANSWER:

References

EVIDENCE SUMMARY

Women are less likely to withdraw from LNG-IUS treatment

Estrogen and progestin contraceptives significantly reduce bleeding

Tranexamic acid outperforms oral progesterone and NSAIDs but not ...

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