Non‐steroidal anti‐inflammatory drugs for heavy menstrual bleeding

Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Analysis 1.1

Comparison 1 NSAIDs versus placebo, Outcome 1 Menstrual blood loss (MBL) (mL/cycle).

Analysis 1.2

Comparison 1 NSAIDs versus placebo, Outcome 2 Proportion with no subjective improvement in MBL.

Analysis 1.3

Comparison 1 NSAIDs versus placebo, Outcome 3 Adverse events.


Study
Mefenamic acid vs placebo
Fraser 1981	Mean menstrual blood loss (standard deviation (SD)) on placebo: 70.7 (24.9) mL Mean menstrual blood loss (SD) on mefenamic acid: 47.3 (21.7) mL P < 0.001, n = 28, paired t test, t = 6.56 Other outcomes were not given for this subgroup.
Muggeridge 1983	Mean menstrual blood loss (SD) on placebo: 161 (78.5) mL Mean menstrual blood loss (SD) on mefenamic acid: 128.3 (78.1) mL No significant difference between placebo and mefenamic acid (MFA) cycles, n = 15, Wilcoxon Sum Rank Test Mean score of dysmenorrhoea symptoms (SD) in 2nd placebo cycle: 2.1 (2.1) Mean score of dysmenorrhoea symptoms (SD) in 2nd MFA cycle: 1.3 (1.6) No significant difference between placebo and MFA cycles, n = 15, Wilcoxon Sum Rank Test
Tsang 1987	Mean menstrual blood loss (SD) on placebo: 156.5 (105.9) Mean menstrual blood loss (SD) on MFA: 140.0 (109) P < 0.05, n = 10, t test comparing MFA cycles with combined placebo and control cycles
Naproxen vs placebo
Rybo 1981	Mean menstrual blood loss (standard deviation (SD)) on placebo: 144 (26) mL Mean menstrual blood loss (SD) on naproxen: 107 (154) mL P < 0.02, n = 4, statistical method not given
Ylikorkala 1986	Mean menstrual blood loss (SD) on placebo: 150.7 (34) mL Mean menstrual blood loss (SD) on naproxen: 96.8 (27.3) mL P < 0.001, n = 14, paired t test Proportion of women with adverse effects on placebo: 7% Proportion of women with adverse effects on naproxen: 0% Not tested
Ibuprofen vs placebo
Makarainen 1986	Median menstrual blood loss (range) on placebo: 146 (71–374) mL Median menstrual blood loss (range) on ibuprofen 600 mg: 123 (23–319) mL Median menstrual blood loss (range) on ibuprofen 1200 mg: 110 (30–288) mL P < 0.01, n = 13, Wilcoxon paired test, ibuprofen 1200 vs placebo

Analysis 1.4

Comparison 1 NSAIDs versus placebo, Outcome 4 MBL and other outcomes (descriptive results).

Analysis 2.1

Comparison 2 NSAIDs versus tranexamic acid, Outcome 1 Menstrual blood loss (MBL) (mL/cycle).

Analysis 2.2

Comparison 2 NSAIDs versus tranexamic acid, Outcome 2 Proportion with no subjective improvement in MBL.

Analysis 2.3

Comparison 2 NSAIDs versus tranexamic acid, Outcome 3 Number of days' bleeding.

Analysis 2.4

Comparison 2 NSAIDs versus tranexamic acid, Outcome 4 Proportion with no improvement in quality of life or dysmenorrhoea (or both).

Analysis 2.5

Comparison 2 NSAIDs versus tranexamic acid, Outcome 5 Proportion who found treatment unacceptable.

Study

Andersch 1988

Mean menstrual blood loss (standard deviation (SD)) on tranexamic acid: 154.8 (127.8) mL
Mean menstrual blood loss (SD) on flurbiprofen: 223 (168.5) mL
P < 0.01, n = 15, student's t test

Proportion of women with adverse effects on tranexamic acid: 47%
Proportion of women with adverse effects on flurbiprofen: 27%
DIfference not tested

Analysis 2.6

Comparison 2 NSAIDs versus tranexamic acid, Outcome 6 MBL and other outcomes (descriptive results).

Analysis 3.1

Comparison 3 NSAIDs versus ethamsylate, Outcome 1 Menstrual blood loss after treatment (mL/cycle).

Analysis 3.2

Comparison 3 NSAIDs versus ethamsylate, Outcome 2 Menstrual blood loss 1–6 months after treatment (mL/cycle).

Analysis 3.3

Comparison 3 NSAIDs versus ethamsylate, Outcome 3 Proportion with no subjective improvement in MBL.

Analysis 3.4

Comparison 3 NSAIDs versus ethamsylate, Outcome 4 Proportion with no improvement in quality of life or dysmenorrhoea (or both).

Analysis 3.5

Comparison 3 NSAIDs versus ethamsylate, Outcome 5 Number of days' bleeding.

Analysis 3.6

Comparison 3 NSAIDs versus ethamsylate, Outcome 6 Proportion who found treatment unacceptable.

Analysis 4.1

Comparison 4 NSAIDs versus danazol, Outcome 1 Menstrual blood loss (MBL) (mL/cycle).

Analysis 4.2

Comparison 4 NSAIDs versus danazol, Outcome 2 Proportion with no improvement in quality of life or dysmenorrhoea (or both).

Analysis 4.3

Comparison 4 NSAIDs versus danazol, Outcome 3 Number of days' bleeding.

Analysis 4.4

Comparison 4 NSAIDs versus danazol, Outcome 4 Proportion who found treatment unacceptable.

Analysis 4.5

Comparison 4 NSAIDs versus danazol, Outcome 5 Adverse events.

Analysis 5.1

Comparison 5 NSAIDs versus oral progestogens, Outcome 1 Menstrual blood loss (MBL) (mL/cycle).

Analysis 5.2

Comparison 5 NSAIDs versus oral progestogens, Outcome 2 Number of days' bleeding.

Analysis 5.3

Comparison 5 NSAIDs versus oral progestogens, Outcome 3 Proportion with non‐adherence.

Analysis 5.4

Comparison 5 NSAIDs versus oral progestogens, Outcome 4 Total adverse events.

Analysis 5.5

Comparison 5 NSAIDs versus oral progestogens, Outcome 5 Adverse events – headache.

Analysis 5.6

Comparison 5 NSAIDs versus oral progestogens, Outcome 6 Adverse events – abdominal pain.

Analysis 5.7

Comparison 5 NSAIDs versus oral progestogens, Outcome 7 Adverse events – nausea.

Analysis 6.1

Comparison 6 NSAIDs versus progesterone‐releasing intrauterine system (IUS), Outcome 1 Menstrual blood loss (MBL) (mL/cycle).


Study	Outcomes	Results (NSAIDs)	Results (LNG IUS)	Significance test	Comment
Reid 2005	Menstrual blood loss (alkaline haematin method): Total menstrual fluid loss: PBAC score:	3 months: Median (range): 94 (29–219) mL 6 months: Median (range): 100 (46–168) mL 3 months: Median (range): 151 (57–280) mL 6 months: Median (range): 157 (76–319) 3 months: Median (range): 161 (77–262) 6 months: Median (range): 159 (50–307)	3 months: Median (range): 12 (0‐240) mL 6 months: Median (range): 5 (0–45) mL 3 months: Median (range): 53 (0–459) mL 6 months: Median (range): 27 (0–156) mL 3 months: Median (range): 49 (0–286) 6 months: Median (range): 25 (0–402)	Wilcoxon rank sum test: P < 0.001 for all comparisons	—

Analysis 6.2

Comparison 6 NSAIDs versus progesterone‐releasing intrauterine system (IUS), Outcome 2 MBL and other outcomes (descriptive results).

Analysis 6.3

Comparison 6 NSAIDs versus progesterone‐releasing intrauterine system (IUS), Outcome 3 Number of days' bleeding.

Analysis 6.4

Comparison 6 NSAIDs versus progesterone‐releasing intrauterine system (IUS), Outcome 4 Adverse events.

Analysis 7.1

Comparison 7 NSAIDs versus oral contraceptive pill (OCP), Outcome 1 Menstrual blood loss (mL/cycle).

Analysis 8.1

Comparison 8 Mefenamic acid versus naproxen, Outcome 1 Menstrual blood loss (mL/cycle).

Analysis 8.2

Comparison 8 Mefenamic acid versus naproxen, Outcome 2 Number of days' bleeding.

Analysis 8.3

Comparison 8 Mefenamic acid versus naproxen, Outcome 3 Total adverse events.

Analysis 8.4

Comparison 8 Mefenamic acid versus naproxen, Outcome 4 Gastrointestinal adverse events.

Analysis 8.5

Comparison 8 Mefenamic acid versus naproxen, Outcome 5 Central nervous system adverse events.


Study	Group	n	Baseline mean PBAC score	Baseline standard deviation (SD)	PBAC score at 6 months	SD at 6 months	Test
Najam 2010	Tranexamic acid + mefenamic acid	55	246 points	Not reported	100 points	Not reported	Significant change from baseline, P < 0.01
Najam 2010	Tranexamic acid	55	250 points	Not reported	125 points	Not reported	Not significant change from baseline, P > 0.05

Analysis 9.1

Comparison 9 Tranexamic acid and mefenamic acid versus tranexamic acid, Outcome 1 Pictorial blood loss assessment chart (PBAC) score at 6 months' follow‐up.

Summary of findings for the main comparison. NSAIDs versus placebo (control)

NSAIDs versus placebo (control)
Patient or population: women with heavy menstrual bleeding Intervention: NSAIDs Comparison: placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	NSAIDs
MBL (mL/cycle)	—	The mean MBL (mL/cycle) in the intervention groups was 124 lower (186.36 to 61.64 lower)	—	11 (1 study)	⊕⊕⊝⊝ Low^a	—
Proportion of women with no subjective improvement in MBL	Study population		OR 0.08 (0.03 to 0.18)	80 (1 study)	⊕⊕⊝⊝ Low^b,c	—
	800 per 1000	242 per 1000 (107 to 419)
	Moderate
	800 per 1000	242 per 1000 (107 to 419)
Quality of life	No study reported this outcome
Number of days' bleeding	No study reported this outcome
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MBL: menstrual blood loss; NSAID: non‐steroidal anti‐inflammatory drug; OR: odds ratio.
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate.
^aDowngraded two levels for imprecision (very small trial). ^bDowngraded one level for imprecision (single trial). ^cDowngraded one level for risk of bias (no explanation was provided).

Summary of findings for the main comparison. NSAIDs versus placebo (control)

Summary of findings 2. NSAIDs versus tranexamic acid (control)

NSAIDs versus tranexamic acid (control)
Patient or population: women with heavy menstrual bleeding Intervention: NSAIDs Comparison: tranexamic acid
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	NSAIDs
MBL (mL/cycle) alkaline haematin method	—	The mean MBL (mL/cycle) in the intervention groups was 73 higher (21.66 to 124.34 higher)	—	48 (1 study)	⊕⊕⊝⊝ Low^a,b	—
Proportion of women with no subjective improvement in MBL	Study population		OR 1.44 (0.45 to 4.61)	49 (1 study)	⊕⊕⊝⊝ Low^a,b	—
	308 per 1000	390 per 1000 (167 to 672)
	Moderate
	308 per 1000	391 per 1000 (167 to 672)
Number of days' bleeding	—	The mean duration of menstruation (days) in the intervention groups was 0.4 higher (0.47 lower to 1.27 higher)	—	49 (1 study)	⊕⊕⊝⊝ Low^a,b	—
Quality of life	No study reported this outcome
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MBL: menstrual blood loss; NSAID: non‐steroidal anti‐inflammatory drug; OR: odds ratio.
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate.
^aDowngraded one level for risk of bias (allocation concealment not stated). ^bDowngraded one level for imprecision (single trial).

Summary of findings 2. NSAIDs versus tranexamic acid (control)

Summary of findings 3. NSAIDs versus ethamsylate (control)

NSAIDs versus ethamsylate (control)
Patient or population: women with heavy menstrual bleeding Intervention: NSAIDs Comparison: ethamsylate
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	NSAIDs
MBL at Rx (mL/cycle)	—	The mean MBL at Rx (mL/cycle) in the intervention groups was 42.88 lower (86.25 lower to 0.5 higher)	—	82 (2 studies)	⊕⊕⊕⊝ Moderate^a	—
Proportion of women with no subjective improvement in MBL	Study population		OR 0.7 (0.23 to 2.12)	50 (1 study)	⊕⊕⊝⊝ Low^a,b
	481 per 1000	394 per 1000 (176 to 663)
	Moderate
	482 per 1000	394 per 1000 (176 to 664)
Number of days' bleeding	—	The mean duration of menstruation (days) in the intervention groups was 0.4 lower (1.56 lower to 0.76 higher)	—	46 (1 study)	⊕⊕⊝⊝ Low^a,b	—
Quality of life	No study reported this outcome
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MBL: menstrual blood loss; NSAID: non‐steroidal anti‐inflammatory drug; OR: odds ratio; Rx: treatment
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate.
^aDowngraded one level for risk of bias (allocation concealment not stated). ^bDowngraded one level for imprecision (one small study).

Summary of findings 3. NSAIDs versus ethamsylate (control)

Summary of findings 4. NSAIDs versus danazol (control)

NSAIDs versus danazol (control)
Patient or population: women with heavy menstrual bleeding Intervention: NSAIDs Comparison: danazol
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	NSAIDs
MBL (mL/cycle)	—	The mean MBL (mL/cycle) in the intervention groups was 45.06 higher (18.73 to 71.39 higher)	—	79 (3 studies)	⊕⊕⊕⊝ Moderate^a	—
Number of days' bleeding	—	The mean duration of menstruation (days) in the intervention groups was 1.03 higher (0.26 to 1.8 higher)	—	53 (2 studies)	⊕⊕⊕⊝ Moderate^a	—
Quality of life	No study reported this outcome
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MBL: menstrual blood loss; NSAID: non‐steroidal anti‐inflammatory drug.
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate.
^aDowngraded one level for risk of bias (allocation concealment not stated).

Summary of findings 4. NSAIDs versus danazol (control)

Summary of findings 5. NSAIDs versus oral progestogens (control)

NSAIDs vs oral progestogens (control)
Patient or population: women with heavy menstrual bleeding Intervention: NSAIDs Comparison: oral progestogens
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	NSAIDs vs oral progestogens
MBL (mL/cycle)	—	The mean MBL (mL/cycle) in the intervention groups was 22.97 lower (46.57 lower to 0.62 higher)	—	48 (2 studies)	⊕⊕⊝⊝ Low^a,b	—
Number of days' bleeding	—	The mean duration of bleeding (days) in the intervention groups was 0.41 lower (0.95 lower to 0.13 higher)	—	48 (2 studies)	⊕⊕⊕⊝ Moderate^a	—
Quality of life	No study reported this outcome
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MBL: menstrual blood loss; NSAID: non‐steroidal anti‐inflammatory drug.
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate.
^aDowngraded one level for risk of bias (allocation concealment not reported). ^bDowngraded one level for substantial heterogeneity.

Summary of findings 5. NSAIDs versus oral progestogens (control)

Summary of findings 6. NSAIDs versus progesterone‐releasing intrauterine system (control)

NSAIDs versus progesterone‐releasing intrauterine system (control)
Patient or population: women with heavy menstrual bleeding Intervention: NSAIDs Comparison: progesterone‐releasing intrauterine system
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	NSAIDs
MBL (mL/cycle)	—	The mean MBL (mL/cycle) in the intervention groups was 4 lower (31.23 lower to 23.23 higher)	—	16 (1 study)	⊕⊕⊝⊝ Low^a,b	—
Number of days' bleeding	—	The mean duration of menstruation (days) in the intervention groups was 5 lower (6.08 to 3.92 lower)	—	16 (1 study)	⊕⊕⊝⊝ Low^a,b	—
Quality of life	No study reported this outcome
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MBL: menstrual blood loss; NSAID: non‐steroidal anti‐inflammatory drug.
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate.
^aDowngraded one level for risk of bias (randomisation method and allocation concealment not reported). ^bDowngraded one level for imprecision (one small trial).

Summary of findings 6. NSAIDs versus progesterone‐releasing intrauterine system (control)

Summary of findings 7. NSAIDs versus oral contraceptive pill (control)

NSAIDs versus oral contraceptive pill (control)
Patient or population: women with heavy menstrual bleeding Intervention: NSAIDs Comparison: oral contraceptive pill
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	NSAIDs
MBL (mL/cycle)	—	The mean MBL (mL/cycle) in the intervention groups was 25.25 higher (22.34 lower to 72.84 higher)	—	26 (1 study)	⊕⊕⊝⊝ Low^a,b	—
Quality of life	No study reported this outcome
Days of bleeding	No study reported this outcome
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MBL: menstrual blood loss; NSAID: non‐steroidal anti‐inflammatory drug.
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate.
^aDowngraded one level for risk of bias (randomisation method and allocation concealment not reported). ^bDowngraded one level for imprecision (one small study).

Summary of findings 7. NSAIDs versus oral contraceptive pill (control)

Summary of findings 8. Mefenamic acid compared to naproxen for heavy menstrual bleeding

Mefenamic acid compared to naproxen for heavy menstrual bleeding
Patient or population: women with heavy menstrual bleeding Intervention: mefenamic acid Comparison: naproxen
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Naproxen	Mefenamic acid
MBL (mL/cycle)	—	The mean MBL (mL/cycle) in the intervention groups was 21 higher (5.85 lower to 47.85 higher)	—	61 (2 studies)	⊕⊕⊝⊝ Low^a,b	—
Number of days' bleeding	—	The mean duration of menstruation (days) in the intervention groups was 0.4 lower (1.59 lower to 0.79 higher)	—	35 (1 study)	⊕⊕⊝⊝ Low^b,c	—
Quality of life	No study reported this outcome
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MBL: menstrual blood loss; NSAID: non‐steroidal anti‐inflammatory drug.
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate.
^aDowngraded one level for risk of bias (lack of blinding). ^bDowngraded one level for imprecision (one or two small studies). ^cDowngraded one level for risk of bias (attrition bias).

Summary of findings 8. Mefenamic acid compared to naproxen for heavy menstrual bleeding

Comparison 1. NSAIDs versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Menstrual blood loss (MBL) (mL/cycle) Show forest plot	1	11	Mean Difference (IV, Fixed, 95% CI)	‐124.0 [‐186.36, ‐61.64]

1.1 Mefenamic acid vs placebo	1	11	Mean Difference (IV, Fixed, 95% CI)	‐124.0 [‐186.36, ‐61.64]
2 Proportion with no subjective improvement in MBL Show forest plot	1	80	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.08 [0.03, 0.18]

2.1 Mefenamic acid vs placebo	1	80	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.08 [0.03, 0.18]
3 Adverse events Show forest plot	1	11	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.77 [0.07, 8.09]

3.1 Mefenamic acid vs placebo	1	11	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.77 [0.07, 8.09]
4 MBL and other outcomes (descriptive results) Show forest plot			Other data	No numeric data

4.1 Mefenamic acid vs placebo			Other data	No numeric data
4.2 Naproxen vs placebo			Other data	No numeric data
4.3 Ibuprofen vs placebo			Other data	No numeric data

Comparison 1. NSAIDs versus placebo

Comparison 2. NSAIDs versus tranexamic acid

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Menstrual blood loss (MBL) (mL/cycle) Show forest plot	1	48	Mean Difference (IV, Fixed, 95% CI)	73.0 [21.66, 124.34]

2 Proportion with no subjective improvement in MBL Show forest plot	1	49	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.44 [0.45, 4.61]

3 Number of days' bleeding Show forest plot	1	49	Mean Difference (IV, Fixed, 95% CI)	0.40 [‐0.47, 1.27]

4 Proportion with no improvement in quality of life or dysmenorrhoea (or both) Show forest plot	1	49	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.13 [0.27, 4.73]

5 Proportion who found treatment unacceptable Show forest plot	1	49	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.17 [0.32, 4.27]

6 MBL and other outcomes (descriptive results) Show forest plot			Other data	No numeric data

Comparison 2. NSAIDs versus tranexamic acid

Comparison 3. NSAIDs versus ethamsylate

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Menstrual blood loss after treatment (mL/cycle) Show forest plot	2	82	Mean Difference (IV, Fixed, 95% CI)	‐42.88 [‐86.25, 0.50]

2 Menstrual blood loss 1–6 months after treatment (mL/cycle) Show forest plot	1	31	Mean Difference (IV, Fixed, 95% CI)	‐70.3 [‐158.88, 18.28]

3 Proportion with no subjective improvement in MBL Show forest plot	1	50	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.70 [0.23, 2.12]

4 Proportion with no improvement in quality of life or dysmenorrhoea (or both) Show forest plot	1	50	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.83 [0.18, 3.72]

5 Number of days' bleeding Show forest plot	1	46	Mean Difference (IV, Fixed, 95% CI)	‐0.40 [‐1.56, 0.76]

6 Proportion who found treatment unacceptable Show forest plot	1	50	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.20 [0.07, 0.61]

Comparison 3. NSAIDs versus ethamsylate

Comparison 4. NSAIDs versus danazol

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Menstrual blood loss (MBL) (mL/cycle) Show forest plot	3	79	Mean Difference (IV, Fixed, 95% CI)	45.06 [18.73, 71.39]

2 Proportion with no improvement in quality of life or dysmenorrhoea (or both) Show forest plot	1	28	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.19 [0.20, 7.05]

3 Number of days' bleeding Show forest plot	2	53	Mean Difference (IV, Fixed, 95% CI)	1.03 [0.26, 1.80]

4 Proportion who found treatment unacceptable Show forest plot	1	40	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.82 [0.24, 2.80]

5 Adverse events Show forest plot	1	40	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.17 [0.05, 0.59]

Comparison 4. NSAIDs versus danazol

Comparison 5. NSAIDs versus oral progestogens

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Menstrual blood loss (MBL) (mL/cycle) Show forest plot	2	48	Mean Difference (IV, Fixed, 95% CI)	‐22.97 [‐46.57, 0.62]

2 Number of days' bleeding Show forest plot	2	48	Mean Difference (IV, Fixed, 95% CI)	‐0.41 [‐0.95, 0.13]

3 Proportion with non‐adherence Show forest plot	1	32	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.88 [0.05, 14.78]

4 Total adverse events Show forest plot	1	32	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.54 [0.13, 2.26]

5 Adverse events – headache Show forest plot	1	32	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.63 [0.14, 2.86]

6 Adverse events – abdominal pain Show forest plot	1	32	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.86 [0.15, 4.96]

7 Adverse events – nausea Show forest plot	1	32	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.79 [0.17, 18.65]

Comparison 5. NSAIDs versus oral progestogens

Comparison 6. NSAIDs versus progesterone‐releasing intrauterine system (IUS)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Menstrual blood loss (MBL) (mL/cycle) Show forest plot	1	16	Mean Difference (IV, Fixed, 95% CI)	‐4.0 [‐31.23, 23.23]

2 MBL and other outcomes (descriptive results) Show forest plot			Other data	No numeric data

3 Number of days' bleeding Show forest plot	1	16	Mean Difference (IV, Fixed, 95% CI)	‐5.0 [‐6.08, ‐3.92]

4 Adverse events Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

4.1 Headache	1	51	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.94 [0.31, 2.86]
4.2 Abdominal pain	1	51	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.22 [0.06, 0.87]
4.3 Ovarian cyst	1	51	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.43 [0.10, 1.80]
4.4 Breast pain	1	51	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.30 [0.07, 1.33]
4.5 Nausea	1	51	Peto Odds Ratio (Peto, Fixed, 95% CI)	2.01 [0.37, 10.86]
4.6 Diarrhoea	1	51	Peto Odds Ratio (Peto, Fixed, 95% CI)	3.53 [0.57, 21.98]
4.7 Upper respiratory infection	1	51	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.95 [0.24, 3.75]

Comparison 6. NSAIDs versus progesterone‐releasing intrauterine system (IUS)

Comparison 7. NSAIDs versus oral contraceptive pill (OCP)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Menstrual blood loss (mL/cycle) Show forest plot	1	26	Mean Difference (IV, Fixed, 95% CI)	25.25 [‐22.34, 72.84]

Comparison 7. NSAIDs versus oral contraceptive pill (OCP)

Comparison 8. Mefenamic acid versus naproxen

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Menstrual blood loss (mL/cycle) Show forest plot	2	61	Mean Difference (IV, Fixed, 95% CI)	21.00 [‐5.85, 47.85]

2 Number of days' bleeding Show forest plot	1	35	Mean Difference (IV, Fixed, 95% CI)	‐0.40 [‐1.59, 0.79]

3 Total adverse events Show forest plot	1	35	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.12 [0.01, 2.00]

4 Gastrointestinal adverse events Show forest plot	1	35	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.24 [0.06, 0.87]

5 Central nervous system adverse events Show forest plot	1	35	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.40 [0.34, 5.73]

Comparison 8. Mefenamic acid versus naproxen

Comparison 9. Tranexamic acid and mefenamic acid versus tranexamic acid

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Pictorial blood loss assessment chart (PBAC) score at 6 months' follow‐up Show forest plot			Other data	No numeric data

Comparison 9. Tranexamic acid and mefenamic acid versus tranexamic acid