Tools for Practice


#287 How to Slow the Flow: NSAIDs for Heavy Menstrual Bleeding


CLINICAL QUESTION
In premenopausal heavy menstrual bleeding without pathological 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 ~30%, and ~20-50% fewer sanitary products used than placebo. Effects on bleeding duration are inconsistent.


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EVIDENCE
Focused on randomized, placebo-controlled trials (RCTs). Menorrhagia, when defined: >80ml/cycle. Naproxen: 2 cross-over RCTs, 4 patients each. Baseline blood loss ~140ml. After 2 menstrual cycles of each treatment:1-3
  • Mean blood loss decreased ~30% over placebo.1-3
  • In 1 RCT, 79% felt naproxen better than placebo.3
  • No effect on bleeding duration.3
Ibuprofen: 1 cross-over RCT, 13 patients.4 Baseline blood loss not stated. After 1 cycle of each treatment:
  • Ibuprofen 1200mg/day decreased mean blood loss ~25% over placebo.
  • Ibuprofen 600mg/day: not different from placebo.
  • No effect bleeding duration.
Mefenamic acid: 5 RCTs
  • Largest RCT: 80 women, 3 consecutive cycles.5
    • “Relief” of menorrhagia (not defined): 86% versus 20%, number needed to treat=2.
    • Number of pads per day: 15 at baseline, 7 on mefenamic acid (placebo not stated).
    • Number of bleeding days: 10 at baseline, 4 on mefenamic acid (placebo not stated).
  • 3 RCTs (2 cross-over, total 49 patients): mefenamic acid better than placebo.
    • Mean blood loss ~10-40% lower than placebo.6-8
    • “Responded” (not defined): 79% versus 18% (placebo).6,9
  • 1 cross-over RCT, 15 patients: no difference in blood loss.10
Mefenamic acid versus diclofenac:
  • 1 RCT, 68 women, only 1 completed all study follow-up.11
    • Median number of pads used (baseline unknown): 21 versus 10 (diclofenac).
    • Number of bleeding days (baseline unknown): 6 versus 4 (diclofenac).
Naproxen versus mefenamic acid:
  • 1 cross-over RCT, 35 women.12
    • Both groups decreased mean blood loss ~47% from baseline.
    • Days of bleeding in both groups decreased 0.8.
    • Number of tampons decreased from ~31 at baseline to ~24.
Context:
  • Volume of blood loss does not correlate with patient experience.13
  • NSAIDs are used immediately before and during menses (example: mefenamic acid 500mg TID from menstruation onset to end6).
  • Mefenamic acid costs ~$20/cycle; naproxen and ibuprofen ~$4 each.14-16
April 6, 2021

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Author(s):

  • Adrienne J Lindblad BSP ACPR PharmD
  • Jennifer Potter MD CCFP
  • Zainab Sari

1. Nygren GK, Rybo G. Acta Obstet Gynecol Scand Suppl. 1983; 113:101-3.

2. Rybo G, Nilsson S, Sikstrom B, Nygren KG. Lancet. 1981 Mar 14; 1(8220 Pt 1):608-9.

3. Ylikorkala O, Pekonen F. Obstet Gynecol. 1986; 10:10-12.

4. Mäkäräinen L, Ylikorkala O. Br J Obstet Gynaecol. 1986; 93:974-8.

5. Grover V, Usha R, Gupta U, et al. Asia-Oceania J Obstet Gynaecol. 1990; 16(3):255-9.

6. Fraser IS, Pearse C, Shearman RP, et al. Obstet Gynecol. 1981; 58:543-51.

7. Tsang BK, Domingo MT, Spence EH, et al. Can J Physiol Pharmacol. 1987; 65:2081-4.

8. Van Eijkeren MA, Christiaens GCML, Geuze HJ, et al. Am J Obstet Gynecol. 1992; 166:1419-28.

9. Bofill Rodriguez M, Lethaby A, Farquhar C. Cochrane Database Syst Rev. 2019; 9: CD000400.

10. Muggeridge J, Elder MG. Res Clin Forums. 1983; 5:83-8.

11. Kumar S, Tekur U, Singh B, et al. IJBCP. 2018; 7(10):1905-11.

12. Hall P, MacLachlan N, Thorn N, et al. Br J Obstet Gynaecol. 1987; 94:554-8.

13. Warner PE, Critchley HO, Lumsden MA et al. Am J Obstet Gynecol. 2004; 190:1224-1229.

14. Alberta Interactive Drug Benefit List. Available at: https://idbl.ab.bluecross.ca/idbl/load.do. Accessed October 5, 2020.

15. Well.ca online pharmacy. Available at: https://well.ca/products/rexall-extra-strength-ibuprofen_167575.html. Accessed October 2, 2020.

16. Well.ca online pharmacy. Available at: https://well.ca/products/rexall-naproxen-sodium-tablets-220_190531.html. Accessed October 2, 2020.

Authors do not have any conflicts of interest to declare.