Table 13Primary outcomes of NSAIDs for abnormal cyclic uterine bleeding

Author, Year
Country
Quality
Comparison Groups (n)Key Outcomes
Vargyas et al., 198772
United States
Good
G1a: Meclofenamate, 100 mg 3 times daily for 2 cycles followed by placebo for 2 cycles (15)
G2: Placebo for 2 cycles, followed by meclofenamate for 2 cycles (17)
  • Mean MBL during meclofenamate cycles (69.0 ± 6.3 ml) was significantly less than baseline (141.6 ± 15.9 ml) and during placebo cycles (135.6 ± 11.3 ml) (p<0.0001).
  • Mean number of bleeding days was shorter during meclofenamate cycles (4.8 ± 0.2) than during placebo cycles (5.4 ± 0.18) (p<0.0003).
  • Median hemoglobin, hematocrit, and serum ferritin levels did not change during the study.
Van Elijkeren et al., 199267
Netherlands
Fair
G1: Mefenamic acid, 500 mg 3 times daily (6)
G2: Placebo (5)
  • Mean MBL decreased 40% in G1 from baseline mean 108 ml to 65 ml (p=0.01) compared with increase in G2 from 151 ml to 189 ml (p=0.46).
  • Patients were scheduled for hysterectomy.
Hall et al., 198775
United Kingdom
Fair
G1: Mefenamic acid 500 mg every 8 hrs. in phase 1 and naproxen in phase 2 (19)a
G2: Naproxen 550 mg loading dose followed by 275 mg every 6 hrs. in phase 1 followed by mefenamic acid in phase 2 (19)a
  • Treatment with mefenamic acid and naproxen reduced bleeding by average of 47 and 46% respectively.
Fraser et al., 1981, 198476 ,93
Australia
Fair
G1: Mefenamic acid, 500 mg 3 times daily for 2 cycles followed by placebo for 2 cycles (38)a
G2: Placebo for 2 cycles followed by mefenamic acid (31)a
  • Mefenamic acid significantly reduced mean MBL (28%) compared with placebo (p<0.001).
  • Reductions were greater (30%) among women with MBL >80 ml at baseline (p<0.001).
  • Only 30 out of 69 women had measured blood loss >80 ml during placebo cycles.
Najam et al., 201077
India
Poor
G1: TXA, 500 mg and mefenamic acid, 250 mg 3 times daily (55)
G2: TXA, 500 mg 3 times daily (55)
  • The mean PBLAC score in G1 declined from 246 to 100 at 6 months (p<0.01) and in G2 from 250 to 125 (p=NS).
  • Hemoglobin levels significantly increased in both groups, from 8.6 to 12.3 in G1 (p=0.016) and from 9.5 to 12.0 in G2 (p=0.04).
Reid and Virtanen-Kari, 200563
United Kingdom
Poor
G1: LNG-IUS (25)
G2: Mefenamic acid 500 mg 3 times daily for first 4 days of cycle (26)
  • MBL significantly reduced in both groups from baseline but after 6 months median MBL was 5 ml in G1 compared with 100 ml in G2 (p<0.001).
Bonnar and Sheppard, 199666
Ireland
Poor
G1: Mefenamic acid, 500 mg (25)
G2: TXA, 1 g (27)
G3: Ethamsylate, 500 mg (29)
  • TXA reduced MBL by 54% (mean decreased from 164 ml to 75 ml) and mefenamic acid reduced MBL by 20% (from 186 ml to 148 ml). Ethamsylate did not reduce MBL.
  • Mean MBL for women in G1 remained >80 ml after 3 treatment cycles (148 ml; range, 138 to 168 ml).
  • 77% in G2 and 74% in G1 wished to continue treatment.
  • Improvement in dysmenorrheal was reported by 19% in G1, 13% in G2 and 4% in G3.
Fraser and McCarron, 199168
Australia
Poor
G1: Mefenamic acid, 500 mg every 6 to 8 hrs. for 2 cycles; naproxen, 500 mg at onset followed by 250 mg every 6 to 8 hrs. for 2 cycles (15)a
G2: Mefenamic acid, 500 mg every 6 to 8 hrs. for 2 cycles; low-dose COC (ethinyl estradiol 30 mcg and levonorgestrel 150 mcg) for 2 cycles (15)a
  • Mefenamic acid reduced MBL by 38% in G2 (p=0.002) and by 20% in G1 (p=0.198).
  • Women treated with low-dose COC had 43% reduction in MBL (p<0.001).
  • Naproxen resulted in a 12% reduction in MBL (p=0.079).
Grover et al., 199069
India
Poor
G1: Mefenamic acid, 500 mg, every 8 hours (40)a
G2: Placebo (40)a
  • 86% of women in G1 reported relief of menorrhagia compared with 20% in G2 (p<0.001).
  • Mean bleeding days in G1 reduced from 9.7 ± 3.1 to 4.1 ± 0.6.
Cameron et al., 199070
Scotland
Poor
G1: Mefenamic acid, 500 mg 3 times daily (17)
G2: Norethisterone, 5 mg twice daily (15)
  • Median blood loss was significantly reduced in both groups from 123 ml to 81 ml in G1 (p<0.001) and from 109 ml to 92 in G2 (p<0.002).
  • Median percentage reduction in blood loss was 24% for G1 and 20% for G2 (p>0.1).
  • 52% of women in G1 and 67% in G2 still had menorrhagia after 2 months of treatment.
Andersch et al., 198871
Sweden
Poor
G1: Flurbiprofen, 100 mg twice daily for 2 cycles followed by TXA for 2 cycles (15)a
G2: TXA, 1.5 g 3 times daily on days 1 to 3 and 1 g twice daily on days 4 to 5 for 2 cycles followed by flurbiprofen for 2 cycles (15)a
  • Both treatments significantly reduced MBL (p<0.01).
  • Reduction in MBL was 53% with TXA compared with 24% for flurbiprofen (p<0.01).
  • Mean MBL reduced to 155 ± 33 ml with TXA and 223 ± 44 ml for flurbiprofen (baseline MBL was 295 ± 52 ml).
  • Hemoglobin did not change with either treatment.
Tsang et al., 198773
Canada
Poor
G1: Mefenamic acid, 500 mg at onset followed by 250 mg every 6 hrs. for 3 to 5 days for 2 cycles followed by placebo (14)a
G2: Placebo for 2 cycles followed by mefenamic acid for 2 cycles (14)a
  • 8/10 women experienced reduction in MBL while taking mefenamic acid compared with placebo (p<0.05).
Cameron et al., 198774
United Kingdom
Poor
G1: Mefenamic acid, 500 mg 3 times daily (8)
G2: Norethisterone, 5 mg twice daily (8)
G3: Progesterone-impregnated intrauterine coil releasing 65 mcg daily (8)
  • Median MBL reduced in G1 from 68 to 47 ml (p=0.05) and in G3 from 71 to 45 ml (p<0.05).
  • Median MBL was unchanged in G2 (94 to 110 ml).

COC = combined oral contraceptive; LNG-IUS = levonorgestrel-releasing intrauterine system; MBL = menstrual blood loss; NS = not significant; PBLAC = pictorial blood assessment chart; TXA = tranexamic acid

a

Crossover study.

From: Results

Cover of Primary Care Management of Abnormal Uterine Bleeding
Primary Care Management of Abnormal Uterine Bleeding [Internet].
Comparative Effectiveness Reviews, No. 96.
Hartmann KE, Jerome RN, Lindegren ML, et al.

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