Chronic constipation is a common gastrointestinal disorder manifested with infrequent bowel movements, excessive straining, hard stools, and/or incomplete evacuation feelings [
Conventional treatments of chronic constipation include stimulant and osmotic medications, yet, due to concerns for efficacy and safety, nearly 50% of patients with chronic constipation were not satisfied with these pharmacological treatments [
The primary findings of the original multicenter randomized controlled trial on acupuncture for chronic severe functional constipation demonstrated that electroacupuncture increased mean weekly CSBMs during weeks 1 to 8 [
In order to extend the findings of the previous trial, a subgroup analysis of data was performed to specifically evaluate the efficacy and safety of electroacupuncture (EA) in women with chronic severe functional constipation.
The acupuncture constipation study [
The study protocol was performed in accordance with Declaration of Helsinki and approved by the ethics committees of each responsible site. The study protocol complied with Standards for Reporting Interventions in Clinical Trials of Acupuncture guidelines. The trial was registered at ClinicalTrials.gov (identifier
In this study, efficacy of EA on only female patients (76%) with chronic severe functional constipation was assessed. The European Medicines Agency (EMA) guideline [
The primary outcome was analyzed by fitting a generalized linear model for a binomial distribution, adjusted for baseline value and sites. The same approach was used for overall responders, participants who met the responder criteria for ≥ 9 of the 12 weeks of the follow-up period, and patients using other measures. The changes from baseline in mean CSBMs per week, mean SBMs per week, mean stool consistency, and mean straining scores and PAC-QOL score were assessed using a general linear model. Wilcoxon rank-sum test was used to compare the frequency of other treatments used per week. The proportions of weekly responders from weeks 1 to 20 were plotted and compared with a generalized linear model between groups.
Analyses were based on the intention-to-treat principle, with all randomly assigned participants included. Patients were considered nonresponders if they withdrew from study without providing data for CSBMs during the intervention or follow-up period. Descriptive statistics were used for demographics, baseline characteristics, and safety variables. All statistical analyses were performed using SAS version 9.4 (SAS Institute Inc.) with a 2-sided P value of less than .05 considered significant.
Details of participant flow through the acupuncture constipation study have been described elsewhere [
Baseline characteristics of the randomized participants.
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Age, mean (SD), y | 45.60 (15.69) | 45.49 (15.11) |
Participants with age <65 y | 371 (89.40) | 369 (90.66) |
Participants with age ≥65 y | 44 (10.60) | 38 (9.34) |
Race | ||
Han | 401 (96.63) | 396 (97.30) |
Minorities | 14 (3.37) | 11(2.70) |
BMI, mean (SD), kg/m2 | 22.12 (3.04) | 22.49 (3.11) |
Constipation duration, mean (SD), mo. | 135.80 (122.26) | 145.00 (130.29) |
Coexisting illness | 83 (20.00) | 77 (18.92) |
Others | 55 (13.25) | 56 (13.76) |
Hypertension | 28 (6.75) | 21 (5.16) |
Digestive system diseases | 6 (1.45) | 10 (2.46) |
Diabetes mellitus | 8 (1.93) | 3 (0.74) |
CSBMs/week, mean (SD) | 0.40 (0.63) | 0.40 (0.62) |
SBMs/week, mean (SD) | 1.89 (1.32) | 2.03 (1.41) |
Mean stool consistency of SBMs, mean |
2.58 (1.13) | 2.59 (1.10) |
Mean straining of SBMs, mean |
1.65 (0.66) | 1.69 (0.61) |
PAC-QOL score, mean (SD) | 2.75 (0.69) | 2.69 (0.69) |
Patients using other treatments | ||
Rescue medicine | 126 (30.36%) | 103 (25.30%) |
Others | 14 (3.37%) | 13 (3.19%) |
Weekly frequency of other treatments used, median (IQR) † | ||
Rescue medicine | 1.25 (0.50-2.00) | 1.00 (1.00-2.00) |
Others | 1.25 (0.50-4.00) | 1.00 (0.50-3.00) |
Data are n (%) unless otherwise stated.
Abbreviations: EA, electro-acupuncture; SA, sham acupuncture; CSBMs, complete spontaneous bowel movements; SBMs, spontaneous bowel movements; BMI, body mass index; PAC-QOL, Patient Assessment of Constipation Quality of Life Questionnaire; SD, standard deviation; IQR, interquartile range. Coexisting illness with different types occurring in a single participant were defined as independent coexisting illness.
† The weekly frequency of other treatments was assessed in the patients who used other treatments for constipation.
For the primary outcome, the proportion of sustained responders were statistically significantly higher in the EA group (24.3%) than the SA group (8.1%) with a difference of 13.1% (95%CI, 6.5% to 19.7%; P<0.001) (Table
Outcome measures of intention-to-treat population.
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Sustained responders (%) |
101 (24.34) | 33 (8.11) | 13.10% (6.50% - 19.70%) | <0.001 |
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Overall responders (%) † | 103 (24.82) | 35 (8.60) | 12.45% (7.26% -17.64%) | <0.001 |
Responders at week 8 (%) ‡ | 212 (51.08) | 80 (19.65) | 28.31% (21.86% - 34.73%) | <0.001 |
Responders for ≥ 9 of 12 weeks of follow-up weeks § | 158 (38.07) | 46 (11.30) | 23.90% (18.02% - 29.78%) | <0.001 |
Change in mean CSBMs/week from baseline, mean (95%CI) | ||||
Weeks 1-8 | 1.73 (1.40 - 2.06) | 0.80 (0.47 - 1.13) | 0.93 (0.52 - 1.33) | <0.001 |
Weeks 9-20 | 1.92 (1.59 - 2.25) | 0.80 (0.47 - 1.13) | 1.13 (0.73 - 1.53) | <0.001 |
Change in mean SBMs/week during weeks 1-8, mean (95% CI)
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2.29 (2.13 - 2.45) | 1.31 (1.15 - 1.47) | 0.98 (0.75 - 1.20) | <0.001 |
Change in stool consistency of SBMs during weeks 1-8, mean (95% CI)
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0.85 (0.77 - 0.93) | 0.64 (0.56 - 0.71) | 0.21 (0.11 - 0.33) | <0.001 |
Change in straining of SBMs during weeks 1-8 mean (95% CI)
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-0.71 (-0.76 to -0.66) | -0.48 (-0.53 to -0.43) | -0.22 (-0.29 to -0.16) | <0.001 |
Change in PAC-QOL score, mean (95% CI) | ||||
Week 4 | -0.50 (-0.54 to -0.45) | -0.35 (-0.40 to -0.30) | -0.15 (-0.21 to -0.08) | <0.001 |
Week 8 | -0.87 (-0.93 to -0.82) | -0.56 (-0.62 to -0.51) | -0.31 (-0.38 to -0.24) | <0.001 |
Patients using other treatments | ||||
Weeks 1-8 | ||||
Rescue medicine | 121 (29.20) | 137 (33.70) | -5.50% (-11.90% - 0.90%) | 0.09 |
Others | 12 (2.90) | 12 (3.00) | 0.80% (-6.90% - 8.50%) | 0.83 |
Weeks 9-20 | ||||
Rescue medicine | 77 (18.60%) | 88 (21.60%) | -3.3% (-10.20% - 3.60%) | 0.35 |
Others | 9 (2.20%) | 12 (3.00%) | -0.4% (-8.70% - 8.00%) | 0.93 |
Weekly frequency of other treatments used, median (IQR) | ||||
Weeks 1-8 | ||||
Rescue medicine | 0.63 (0.25 - 1.25) | 0.75 (0.38 - 1.50) | NA | 0.12 |
Others | 0.44 (0.19 - 1.00) | 0.19 (0.13 - 0.69) | NA | 0.23 |
Weeks 9-20 | ||||
Rescue medicine | 0.75 (0.33 - 1.42) | 0.75 (0.33 - 1.67) | NA | 0.50 |
Others | 0.25 (0.17 - 0.42) | 0.42 (0.83 - 1.63) | NA | 0.83 |
Data are n (%) unless otherwise stated.
Abbreviations: EA, electro-acupuncture; SA, sham acupuncture; CSBMs, complete spontaneous bowel movements; SBMs, spontaneous bowel movements; BMI, body mass index; PAC-QOL, Patient Assessment of Constipation Quality of Life questionnaire; SD, standard deviation; IQR, interquartile range, NA, not applicable.
† Overall responders were defined as responders for treatment for ≥ 6 of 8 treatment weeks according to the guideline of European Medicines Agency [
‡ Responders were defined as patients achieving at least 3 CSBMs/week and, at the same time, an increase of at least 1 CSBM/week compared to baseline according to the guideline of European Medicines Agency [
§ 15 participants in the EA group and 27 in the SA group were treated as non-responders.
The increases in the mean CSBMs per week from baseline to weeks 1-8 and weeks 9-20 were significantly higher in the EA group than the SA group with between-group differences of 0.9 (95%CI, 0.5 to 1.3; P<0.001) and 1.1 (95%CI, 0.7 to 1.5; P <0.001) during the treatment and follow-up periods, respectively. The EA group also showed significantly greater increases in mean weekly SBMs than the SA group during weeks 1-8 with a between-group difference of 1.0 (95%CI, 0.8 to 1.2; P<0.001). Mean score change of stool consistency and straining from baseline were statistically better in the EA group than the SA group during weeks 1-8 (P <0.001 for both) with between-group differences of 0.2 (95%CI, 0.1 to 0.3; P<0.001) and -0.2 (95%CI, -0.3 to -0.2; P<0.001), respectively.
The improvements of PAC-QOL overall score were significantly greater in the EA group than the SA group with between-group differences of -0.2 (95%CI, -0.2 to -0.1; P<0.001) and -0.3 (95%CI, -0.4 to -0.2; P<0.001) at week 4 and week 8, respectively. No differences were found between groups in the proportion or frequency of patients using other treatments during weeks 1-8 or weeks 9-20 (P > 0.05 for all).
Throughout the trial, 16 participants (3.9%) in the EA group and 11 participants (2.7%) in the SA group had adverse events (AEs) related to acupuncture with local hematoma as the most common in both groups (Table
Adverse events related to treatment.
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Total adverse events | 23 (5.55) | 16 (3.94) |
Hematoma around the site of needling | 13 (3.14) | 11 (2.71) |
Severe sharp pain (VAS ≥ 7) | 2 (0.48) | 4 (0.98) |
Sharp pain lasting more than 0.5 hour | 2 (0.48) | 1 (0.25) |
Fever | 1 (0.25) | 0 (0.00) |
Fever with abdominal pain | 1 (0.25) | 0 (0.00) |
Fatigue | 1 (0.25) | 0 (0.00) |
Insomnia | 1 (0.25) | 0 (0.00) |
Other discomforts | 3 (0.72) | 0 (0.00) |
Adverse events were analyzed in all participants who received treatment. Adverse events were counted by type rather than frequency in the same participant. Adverse events with different types occurring in a single participant were defined as independent adverse events. An adverse event with multiple occurrences in a single participant was defined as 1 adverse event.
† Data on safety evaluation for 2 participants were not available (1 in EA group and 1 in SA group).
This study demonstrated that 8 weeks’ EA treatment has many positive effects for relieving symptoms in women with chronic severe functional constipation as evidenced by a higher proportion of sustained responders (24.3% in the EA group versus 8.1% in the SA group) in regaining CSBMs. Moreover, the proportion of weekly responders for more than 9 weeks of 12 weeks’ follow-up period was 38.1% in the EA group and 11.3% in the SA group with the difference of 23.9% between two groups. EA may thus be an effective alternative for the management of chronic constipation in women and the effectiveness could last for 12 weeks without treatment.
To the best of our knowledge, this is the first study assessing the effectiveness of acupuncture for women with chronic constipation. Responder analyses were frequently used in pharmaceutical trials for chronic constipation. In the study including 1346 patients (80.8% female patients), the percentages of sustained responders were 21% and 19.5% after 12 weeks of 3mg and 6mg plecanatide treatment as compared to 10.2% in the group treated with placebo [
An integrated analysis of 4 double-blind, placebo-controlled, phase III studies of Asian and non-Asian women showed that after 2 mg prucalopride at week 12, the percentage of responders who have at least 3 CSBMs a week was approximately 25% to 34% [
Additionally, in this analysis, EA was also found effective in increasing weekly CSBMs and improving quality of life in female patients with chronic severe functional constipation. The change of mean weekly CSBMs from baseline in the EA group was 1.7 during weeks of 1-8 and 1.9 during weeks of 9-20 which was consistent with the results in the original trial (1.76 and 1.96). The consistency of results may show the stability of acupuncture effect. In previous pharmaceutical trials, the change from baseline in mean weekly CSBMs after 12-week treatment of prucalopride 2mg ranged from 1.6 to 2.6 [
The change of overall PAC-QOL score in the present study was 0.9 and 0.6 in the EA and the SA groups, respectively. A multicenter, randomized, placebo-controlled trial [
Acupuncture effects may result from both biological and psychological influences of acupuncture on the human body [
The decision for patients to accept and healthcare providers to recommend a treatment usually depends on not only the effectiveness of the treatment but also economic costs. Although the total cost for 28 sessions ($80 USD each session) of EA seems far more expensive than pharmaceutical interventions [
This subgroup analysis has some limitations. First, only Chinese female patients were included in this secondary analysis which may limit the generalizability of the findings to other countries. Second, the subgroup analysis was not prespecified in the original trial.
8-week treatment of EA significantly improved the spontaneity and the completeness of the bowel movement in women with severe functional constipation and the effect could sustain for 12 weeks after stopping treatment. EA is safe and could be a promising alternative for the treatment of women with chronic severe functional constipation.
Electroacupuncture
Complete spontaneous bowel movements
European Medicines Agency
Spontaneous bowel movements
Bristol Stool Form Scale
Patient Assessment of Constipation Quality of Life Questionnaire
Sham-acupuncture
Adverse events.
The data used to support the findings of this study are included within the article.
The authors have no conflicts of interest to declare.
Zhishun Liu, Yan Liu, and Jing Zhou contributed to the conception and design of this study and critical revision of the manuscript. Jing Zhou and Yan Liu contributed to the interpretation of the data and manuscript writing. Yan Liu contributed to statistical analysis and critical revision. Kehua Zhou contributed to modifying the language and critical revision. Baoyan Liu contributed to acquisition of the data and trial supervision. Tongsheng Su and Weiming Wang contributed to the interpretation of the data. All authors approved the final manuscript. Jing Zhou and Yan Liu contributed equally to this work.
The authors thank the patients who participated in this study and the clinicians who contributed their untiring efforts to the conduction of the study. This study is supported by the Ministry of Science and Technology of the People's Republic of China through the Twelfth Five-Year National Science and Technology Pillar Program (2012BAI24B01).
Supplementary Table 1. The difference in weekly responders between groups Supplementary Table 2. Adverse events unrelated to treatment Supplementary File. CONSORT checklist Supplementary File. Ethics committee approval.