NSAIDs for heavy menstrual bleeding

Clinical question

In premenopausal heavy menstrual bleeding without pathologic cause, do nonsteroidal anti-inflammatory drugs (NSAIDs) improve patient outcomes?

Bottom line

Based on low-quality evidence, NSAIDs reduce relative mean menstrual blood loss by about 30%, and about 20% to 50% fewer sanitary products are used than with placebo. Effects on bleeding duration are inconsistent.

Evidence

Evidence was focused on placebo-controlled RCTs. Menorrhagia, when defined, was more than 80 mL per cycle.

• Naproxen: In 2 crossover RCTs (N = 4 each), baseline blood loss was about 140 mL. After 2 cycles of each treatment, mean blood loss decreased about 30% over placebo¹ and 79% felt naproxen was better than placebo.² There was no effect on bleeding duration.²

• Ibuprofen: In 1 crossover RCT (N = 13),³ baseline blood loss was not stated. After 1 cycle of each treatment, mean blood loss decreased about 25% over placebo (1200 mg/d) and was not different from placebo (600 mg/d). There was no effect on bleeding duration.

• Mefenamic acid: Evidence was 5 RCTs.

  • - The largest RCT (N = 80) followed 3 consecutive cycles.⁴

    • — “Relief” of menorrhagia (not defined): 86% versus 20%, number needed to treat (NNT) = 2.

    • — Pads per day: 15 at baseline, 7 with mefenamic acid (placebo not stated).

    • — Bleeding days: 10 at baseline, 4 with mefenamic acid (placebo not stated).

  • - In 3 RCTs (2 crossover; N = 49), mefenamic acid was better than placebo.

    • —Mean blood loss was about 10% to 40% lower than placebo.¹

    • —“ Responded” (undefined): 79% versus 18% (placebo), NNT = 2.^5,6

  • - In 1 crossover RCT (N = 15), there was no difference in blood loss.⁷

• Mefenamic acid versus diclofenac: In 1 RCT of 68 women, only 1 completed all study follow-up.⁸

  • - Median number of pads used (baseline unknown) was 21 versus 10 (diclofenac).

  • - Number of bleeding days (baseline unknown) was 6 versus 4 (diclofenac).

• Naproxen versus mefenamic acid: In 1 crossover RCT (N = 35),⁹ both groups improved similarly compared with baseline. Blood loss decreased by about 47%, there were 0.8 fewer days of bleeding, and tampon number decreased from about 31 to 24.

Context

• Blood loss does not correlate with patient experience.¹

• The NSAIDs were used just before and during menses.

• Mefenamic acid costs about $20 per cycle; naproxen and ibuprofen are approximately $4 each per cycle.¹

Implementation

The NSAIDs are well tolerated.⁶ Discontinuations due to adverse effects are similar between mefenamic acid and naproxen.⁹ The NSAIDs may be less effective in reducing menstrual blood loss than levonorgestrel intrauterine systems (LNG-IUS)¹⁰; guidelines recommend LNG-IUS over combined oral contraceptives, luteal-phase progestins, antifibrinolytics, and NSAIDs.¹¹ However, nonhormonal methods may be more appropriate for some patients, (eg, when contraception or hormonal treatments are not desired). Antifibrinolytics are another nonhormonal option. Based on 2 small RCTs, 87% of those taking tranexamic acid may “improve” compared with 61% taking NSAIDs.¹²

Tools for Practice articles in Canadian Family Physician are adapted from articles published on the Alberta College of Family Physicians (ACFP) website, summarizing medical evidence with a focus on topical issues and practice-modifying information. The ACFP summaries and the series in Canadian Family Physician are coordinated by Dr G. Michael Allan, and the summaries are co-authored by at least 1 practising family physician and are peer reviewed. Feedback is welcome and can be sent to toolsforpractice@cfpc.ca. Archived articles are available on the ACFP website: www.acfp.ca.