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


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

BOTTOM LINE
RÉSULTAT FINAL
 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
DONNÉES PROBANTES
 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

Michel Cauchon April 17, 2021

what is the exact posologia for ibuprofen and napproxen?

Annie Josee Le Bouthillier April 17, 2021

confirm my thoughts and knowledge

Momir Pantelic April 22, 2021

My biggest question would have been the proper dosing and the actual podcast ending discussed this and helped with that so thanks!

E Douglas Gat May 10, 2021

cost reference important

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Author(s)
Auteur(s)
  • Jennifer Potter MD CCFP
  • Zainab Sari
  • Adrienne J Lindblad BSP ACPR PharmD

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.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.