Manual Therapy in Primary Dysmenorrhea: A Systematic Review and Meta-Analysis

Figures & data

Figure 1 PRISMA flowchart. Adapted from Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. J Clin Epidemiol. 2021;134:178–189. Creative Commons.¹¹

Table 1 Summary of Included Trials Basic Information

Study	Country	Study Design	Number of Participants		Age, Mean (SD)/Range		Intervention	Control
			Intervention	Control	Intervention	Control
Atrian 2013^Citation36	Iran	RCT	27	32	21.40 (2.45)	21.95 (3.01)	Acupressure	No treatment
Azima 2015^Citation37	Iran	RCT	34	34	21.41 (0.95)	21.08 (1.21)	Massage	No treatment
Barassi 2018^Citation38	Italy	RCT	30	30	31.56 (7.44)		Neuromuscular therapy	NSAIDs
Bazarganipour 2017^Citation39	Iran	RCT	30	30	22 (1.71)	21.76 (1.73)	Acupressure	Placebo
Behbahani 2016^Citation40	Iran	RCT	40	40	20.02 (1.44)	20.37 (1.54)	Acupressure	NSAIDs
Chen 2004^Citation41	Taiwan	RCT	35	34	17.78 (1.43)		Acupressure	No treatment
Chen 2010^Citation42	Taiwan	RCT	36	35	16.75 (1.36)	16.77 (1.19)	Acupressure	No treatment
Chen 2011^Citation18	China	RCT	30	30	22.47 (4.58)	23.70 (4.56)	Massage	NSAIDs
Chen 2015^Citation43	Taiwan	RCT	65	64	18.75 (1.74)	18.73 (0.63)	Acupressure	No treatment
Chen 2016^Citation19	China	RCT	25	25	20.44 (1.54)	20.44 (1.8)	Massage	No treatment
Guo 2015^Citation20	China	RCT	34	34	14–30	14–30	Acupressure	NSAIDs
Hondras 1999^Citation44	America	RCT	69	69	31.1	29.7	Spinal manipulative therapy	Placebo
Hu 2015^Citation21	China	RCT	40	40	22.61 (1.63)	22.83 (1.72)	Massage	NSAIDs
Jia 2011^Citation22	China	RCT	16	16	21–27	21–27	Holographic therapy	No treatment
Lin 2010^Citation23	China	RCT	20	20	14–41		Massage	NSAIDs
Lin 2017^Citation24	China	RCT	20	20	17.45 (1.13)		Massage	NSAIDs
Lin 2018^Citation25	China	RCT	20	20	20.2 (1.43)	20.93 (1.53)	Massage	NSAIDs
Liu 2012^Citation26	China	RCT	55	55	22.46 (7.21)	23.51 (6.98)	Massage	NSAIDs
Ru 2015^Citation27	China	RCT	50	50	26.62 (2.14)	26.77 (2.21)	Massage	NSAIDs
Susanne 2018^Citation45	Germany	RCT	111	110	24.4 (3.3)	23.7 (3.9)	Acupressure	No treatment
Tang 2012^Citation28	China	RCT	30	30	21.41 (1.58)	21.39 (1.03)	Spinal manipulative therapy	NSAIDs
Vagedes 2019^Citation46	Germany	RCT	23	17	30.22 (7.72)	26.65 (8.4)	Massage	NSAIDs
Valiani 2010^Citation47	Iran	RCT	32	36	21.6 (1.79)		Foot reflexology	NSAIDs
Wang 2003^Citation29	China	RCT	62	30	17–35	15–32	Massage	NSAIDs
Wong 2010^Citation48	Hong Kong	RCT	19	21	22	21.57	Acupressure	No treatment
Wu 2017^Citation30	China	RCT	12	12	22.41 (1.56)	22.6 (1.72)	Massage	No treatment
Xu 2008^Citation31	China	RCT	62	47	20.3		Holographic therapy	NSAIDs
Yilmaz 2019^Citation49	Turkey	RCT	29	29	20.3	19.7	Foot reflexology	Placebo
Zhao 2015^Citation32	China	RCT	30	30	22 (3.6)	21 (4.1)	Massage	NSAIDs
Zhou 2016^Citation33	China	RCT	34	30	26.2 (2.59)	25.3 (3.1)	Massage	NSAIDs
Zhu 2012^Citation34	China	RCT	50	46	–	–	Massage	NSAIDs
Zhu 2015^Citation35	China	RCT	125	125	18–27	18–27	Acupressure	NSAIDs

Table 2 Summary of Included Trials’ Outcome Measures and Follow-Up Period

Study	Outcomes	Course of Disease, Range/Mean±SD		Intervention Period (Menstrual Cycle)	Follow-Up Period (Menstrual Cycle)
		Intervention	Control
Atrian 2013^Citation36	VAS	–		3	3
Azima 2015^Citation37	VAS, Anxiety Level	–		3	3
Barassi 2018^Citation38	VAS, Number of days with pain	–		4	4
Bazarganipour 2017^Citation39	Wong-Baker faces pain scale, SF12	–		3	3
Behbahani 2016^Citation40	MPQ	–		2	2
Chen 2004^Citation41	VAS, VASA, MDQ	–		3	6
Chen 2010^Citation42	VAS, VASA, MDQ	–		3	6
Chen 2011^Citation18	VAS, PGF2a, UHD, PGE2	4.46±3.44 year	5.51±3.38 year	3	3
Chen 2015^Citation43	VAS, MDQ	–		4	12
Chen 2016^Citation19	Traditional Chinese Medicine Symptom Score, Effective Rate	–		2	2
Guo 2015^Citation20	Effective Rate	6 month-5 year		3	3
Hondras 1999^Citation44	VAS, PGF2a	-		4	4
Hu 2015^Citation21	NRS	5.63±2.51 year	6.21 ±1.89 year	3	3
Jia 2011^Citation22	Effective Rate, Pain score, UHD	2–6 year		3	3
Lin 2010^Citation23	Effective Rate	0.5–5 year		3	6
Lin 2017^Citation24	VAS, Effective Rate, Clinical Symptom Scoring for Dysmenorrhea	3.75±0.67 year		2	5
Lin 2018^Citation25	Pain score, Hormone levels, emotional factors	3.7±0.62 year		3	3
Liu 2012^Citation26	Effective Rate, Pain score	0.5–10 year		3	3
Ru 2015^Citation27	Effective Rate	7.26±3.15 month	7.13±3.04 month	3	3
Susanne 2018^Citation45	NRS, Number of days with pain	-		3	6
Tang 2012^Citation28	VAS	63.89±30.36 month	68.32±15.58 month	3	3
Vagedes 2019^Citation46	NRS, SF12	–		3	3
Valiani 2010^Citation47	VAS, MPQ, PRI	–		3	3
Wang 2003^Citation29	Effective Rate	3 month-5 year		3	3
Wong 2010^Citation48	VAS, MDQ	–		3	3
Wu 2017^Citation30	VAS, Effective Rate, Pain score, PPI, Traditional Chinese Medicine Symptom Score	6.33±2.05 year	6.25±1.76 year	3	3
Xu 2008^Citation31	Effective Rate	0.7–4.3 year		3	3
Yilmaz 2019^Citation49	VAS	–		2	4
Zhao 2015^Citation32	Effective Rate	3±2.4 year	3±2.4 year	3	3
Zhou 2016^Citation33	VAS, Effective Rate	2.7±2.03 year	2.6±1.66 year	3	3
Zhu 2012^Citation34	Effective Rate	–		3	3
Zhu 2015^Citation35	Effective Rate	2–8 year		3	3

Abbreviations: VASA, Visual Analog Scale for Anxiety; SF12, Short Form 12-Item Health Survey; PRI, Pain Rating Index; PPI, Pain Pressure Threshold; PGF2a, Prostaglandin F2 alpha; UHD, Uterine hemodynamics; PGE2, Prostaglandin E2.

Figure 2 Risk of bias graph: review of the authors’ judgments regarding each risk of bias item presented as percentages across all included studies.

Figure 3 Risk of bias summary: review of the authors’ judgments regarding each risk of bias item in each included study.

Figure 4 Overall and different follow-up times subgroup forest plot of weighted mean difference (95% CI) for pain intensity for manual therapy versus no treatment.

Figure 5 Overall and various manual therapies subgroup forest plot of weighted mean difference (95% CI) for pain intensity for manual therapy versus no treatment.

Figure 6 Overall and various manual therapies subgroup forest plot of weighted OR (95% CI) for effective rate for manual therapy versus no treatment.

Figure 7 Overall and different follow-up times subgroup forest plot of weighted mean difference (95% CI) for MDQ for manual therapy versus no treatment.

Figure 8 Forest plot of weighted mean difference (95% CI) for pain intensity for manual therapy versus place control.

Figure 9 Overall and various manual therapies subgroup forest plot of weighted mean difference (95% CI) for pain intensity for manual therapy versus NSAIDs.

Figure 10 Overall and different follow-up times subgroup forest plot of weighted mean difference (95% CI) for pain intensity for manual therapy versus versus NSAIDs.

Figure 11 Overall and various manual therapies subgroup forest plot of weighted OR (95% CI) for effective rate for manual therapy versus NSAIDs.

Figure 12 Overall and different follow-up times subgroup forest plot of weighted OR (95% CI) for effective rate for manual therapy versus NSAIDs.

Table 3 Summery of Finding

Outcome No of Participants (Studies)	Relative Effect (95% CI)	Anticipated Absolute Effects (95% CI)			Certainty
		Without Manual Therapy	With Manual Therapy	Difference
Manual therapy compared to no treatment for PD
Pain intensity № of participants: 629 (8 RCTs)	–	–	–	MD 0.81 higher (0.35 higher to 1.28 higher)	⨁◯◯◯ Very low^a,b,c
Effective rate № of participants: 106 (3 RCTs)	OR 8.73 (3.03 to 25.19)	50.9%	90.1% (86.1 to 97.6)	39.1% more (24.9 more to 45.4 more)	⨁⨁◯◯ Low^d
MDQ № of participants: 309 (3 RCTs)	–	–	–	MD 3.84 higher (2.27 higher to 5.4 higher)	⨁◯◯◯ Very low^a,d
Manual therapy compared to placebo control for PD
Pain intensity № of participants: 507 (9 RCTs)	–	–	–	MD 0.10 higher (0.37 lower to 0.58 higher)	⨁◯◯◯ Very low^a,b,c
Manual therapy compared to NSAIDs for PD
Pain intensity № of participants: 507 (9 RCTs)	–	–	–	MD 3.01 higher (1.08 higher to 4.94 higher)	⨁◯◯◯ Very low^a,b,c
Effective rate № of participants: 1029 (11 RCTs)	OR 4.87 (3.29 to 7.20)	73.3%	93.0% (90 to 95.2)	19.7% more (16.7 more to 21.9 more)	⨁⨁◯◯ Low^a,c

Notes: The risk in the intervention group (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). GRADE Working Group grades of evidence: High certainty: we are very confident that the true effect lies close to that of the estimate of the effect; Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different; Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect; Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. ^aDownload one level for serious risk of bias: included studies did not conduct the blinding method, and unclear risk of bias in one or two domains. ^bDowngraded one level for serious inconsistent: interventions of included studies inconsistent, or the outcome indicators exist statistical heterogeneous. ^cDowngraded one level for wide confidence intervals. ^dDowngraded two level for serious imprecision: very small sample size.

Abbreviations: CI, confidence interval; MD, mean difference; OR, odds ratio.

Figure 13 Funnel plot of effective rate for manual therapy versus NSAIDs.

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