Premenstrual syndrome (PMS) is characterized by repeated emotional, behavioral, and physical disorders during the luteal phase and is alleviated by the onset of menstruation [
Numerous clinical randomized controlled trials and several meta-analyses [
It is well known that the onset of premenstrual syndrome is periodic. Modern experiments have confirmed that time affects the efficacy of acupuncture [
This meta-analysis compared the efficacy of acupuncture group and control group (including drugs, placebo acupuncture, or no treatment) in patients with PMS. It further compared the effectiveness of different intervention times in the acupuncture group to determine the best acupuncture treatment intervention time. The frequency of acupoints used to treat PMS in the included studies was also counted in this meta-analysis.
Studies published on the Pubmed, Embase, Cochrane Library, Web of science, Chinese National Knowledge Infrastructure (CNKI), VIP, Wanfang, China Biomedical Literature Database (CBM), and Chinese Clinical Trial Registry System were searched since their time of establishment to September 2018. The search keywords used were “Premenstrual syndrome”, “Premenstrual Tensions”, “Premenstrual”, “Acupuncture”, “Acupoints”, as well as “random” and there was no restriction on language. More details have been provided on the “PROSPERO” website, and the registration number is
Types of study: The studies included were RCTs which is stated by the “randomization” phrase, and blinding was not restricted. Case reports, animal mechanism studies, self pre- and postcontrol studies, or non-RCTs were excluded.
Types of participants: Patients with clinically diagnosed premenstrual syndrome were included. Patients who experienced single symptoms such as dysmenorrhea before menstruation were excluded. There was no limitation on age or nation. Patients with severe medical conditions were excluded.
Types of interventions: RCT using acupuncture, acupuncture catgut embedding or acupoint injection with drugs, placebo acupuncture, or no treatment (waiting-listed) for comparison. This review is restricted to acupuncture manipulation, emphasis on penetrating into skin, and manipulating to deqi. Trial on auricular point, acupressure, and laser acupuncture were excluded.
Types of outcome measures: The primary outcomes were effective rate after treatment, effective rate after one month of follow-up, and effective rate of acupuncture treatment with different intervention time. Most of the included studies calculated the effective rate using the reduced symptom scores. The secondary outcome is frequency of acupoints used in the prescription and adverse events including fainting, broken needle, hematoma, and pneumothorax.
Articles that were not available after contacting their authors were excluded. For articles that were repeatedly published, the one with the highest quality was chosen. Articles published for different indicators in the same study were merged.
Literature screening, study selection, and data extraction were performed by two reviewers (Jiayuan Zhang, Liu Cao). The data extraction was conducted in a standard form, which included characteristics of the study type, patient, intervention details, outcomes, and adverse events. Disagreements were solved by discussion until a consensus was reached.
Data analysis was performed using Review Manager 5. 3 software provided by the Cochrane Collaboration. Effective rate was calculated by odds risk while heterogeneity was considered to be significant when I2 ≥ 50%. A fixed-effect model was performed when there was no significant heterogeneity; otherwise, a random-effect model was performed. Public bias was estimated by symmetry of the funnel plot when the number of the included studies was more than 10.
After searching 9 databases, 151 related articles were collected, and 40 duplicate articles were excluded. A total of 56 articles were excluded because they did not meet the inclusion criteria after reading the title and abstract. The full text of the remaining papers was obtained from the databases, and 40 articles were excluded after full reading and the details are presented in Figure
Flow of literature screening.
Twelve studies were conducted in China [
Characteristics of the included studies.
Study | Sample | Experiment | control | Acupoints | Intervention time | Outcomes | AE |
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Liu 2006 [ | 44/44 | ACE | Medicine | PC6, SP6, CV4, CV17, LR3 | 15 days before MS | IR | NR |
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Xu 2005 [ | 54/48 | AI+AT | Medicine | AI in SP6, ST36 and AT in L14, LR6, RN4, RN6, EX-HN5 | 10 days before MS | IR | NR |
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Fang 2008 [ | 47/43 | AT | Medicine | DU24, LR3+L14, SP6 | 14-16 days before MS | IR, symptom score, HAMA score | NR |
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Li 2011 [ | 15/15 | AT | Medicine | RN12, RN10, RN4, RN6, SP15, ST29 | 7 days before MS | symptom score, SCL-90 scores, IR | NR |
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Yu 2006 [ | 33/32 | AT | sham AT | DU20, EX-HN3, EX-HN5, SP6, SP10 | 7 days before MS | symptom score | hypomenorrhea |
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Zhang 2017 [ | 30/30/30 | AT | Medicine/ACE+Auricular points | LR3, SP6, PC6, LA14, BL18 | 14 days before MS | symptom score | NR |
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Hong 2002 [ | 35/31 | EA | Medicine | Scalp acupuncture: Frontal line, middle line of vertex | three times per week | symptom score, IR | NR |
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Xu 2006 [ | 30/30 | AT | Medicine | DU8, DU6, DU4, BL18, BL20, BL22, BL47, BL49, BL51 | 14 days before MS | IR | NR |
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Sun 2004 [ | 30/31 | AT | Medicine | D20, RN17, RN4, SP6, PC6, LR3 | 14 days before MS | symptom score, IR | NR |
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Xu 2008 [ | 100/100 | AT | Medicine | GB20, DU15 | When the symptoms occurred | IR | NR |
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Zhang 2016 [ | 35/35/35 | AT+Intradermal needle | non acupoint superficial AT | AT:DU8, EX-HN3, RN12, RN10, BL24, RN4, EX-CA1, SP6, KI6, LI4, LR3 | AT:3 per week | HAMA/WHOQOL-BREF/DRSP scale | Hematoma, pain;redness, itching, in the skin, pain |
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Zeng 2013 [ | 80/80 | AT+Medicine | Medicine | LR3, K13, RN6, BL18, RN17, SP6 | 10 days before MS | IR | NR |
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Habek 2002 [ | 18/17 | AT | sham AT | DU20, L14, LR3, RN3, RN4, RN6, PC6, GB34, BL23 | Luteal phase | IR | Hematoma |
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Shin 2009 [ | 10/10/10 | Korea hand AT | no treatment | A5, A6, A8, A12, A16, A18, N18, F6 | 1 per 3 days | symptom score | None |
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Kim 2005 [ | 10/10 | AT | sham AT | SP6, RN9 | 2 per week | symptom score | NR |
(ACE: acupuncture catgut embedding, A/C: acupuncture group versus control group, AE: adverse events, AI: acupoint injection, AT: acupuncture, DRSP score: Daily record of severity of problems scale, E2: estradiol, ET: electroacupuncture, HAMA: Hamilton anxiety scale, IR: effective rate, MS: menstruation, NR: not reported, P: progesterone, SCL-90: SymptomChecklist90, WHOQOL-BREF scale:WHO Quality of Life-BREF scale)
As shown in Figure
Risks of bias assessment.
Ten studies [
Funnel plot of AT vs medicine.
Forest plot of AT vs medicine.
Three studies [
Forest plot of AT vs sham AT.
Effective rate after follow-up for one month was reported in 2 trails [
Forest plot of AT vs control after 1 month of follow-up.
To analyze the difference in clinical curative effect of acupuncture on PMS at different intervention times, subgroup analysis was conducted for the outcome of effective rate after acupuncture therapy at two weeks, 10 days, 7 days before menstruation, or at the symptom onset time. Even with continuous therapy at a fixed-frequency, there was no significant difference between acupuncture group and control group in terms of improving the effective rate for PMS (P = 0.61) (Figure
Forest plot of subgroup analysis of different intervention time.
Shin [
Three trails reported mild adverse events that did not require treatment. Yu [
This systematic review shows that the overall effectiveness of acupuncture treatment of premenstrual syndrome is superior to that of sham acupuncture and related medications, which is consistent with previous systematic review reports [
As early as 2006, the complex and close interactions between metabolism and immunity were considered to be key mechanisms for the body to maintain homeostasis [
The intervention time of acupuncture treatment for PMS in the included studies varied across intermenstrual, premenstrual, and entire menstrual cycles. 6 of the 15 clinical studies began treatment of PMS about 2 weeks before menstruation, 2 were 10 days before menstruation, 2 were 7 days before menstruation, while 1 started acupuncture treatment when the symptoms of PMS appeared. Four of the 15 clinical studies employed continuous treatment for premenstrual syndrome. It was found that, after acupuncture treatment at different times before the menstrual treatment, the difference in efficacy was not statistically significant based on subgroup analysis. An authoritative standard for the intervention time of Chinese medicine treatment for PMS has not been setup.
It has been reported that the brain responded differently to the immediate and sustained stimulation of acupuncture [
Furthermore, considering the small sample size, short follow-up duration, and little observation time points of the included trials, the cumulative effect of early acupuncture on PMS may not be apparent. Consequently, studies on the timing of acupuncture intervention in patients with PMS are indispensable, but the sample size should be expanded, the follow-up time should be prolonged, and the time point of efficacy observation should be increased.
SP6 was the most frequently used acupuncture point in this review. TCM theory states that SP6 is the intersection of the three yin meridians of the liver, the spleen, and the kidney. The occurrence of gynecological diseases is closely related to these three internal organs; SP6 is thus the key point for the treatment of gynecological diseases. Presently, studies on acupuncture at SP6 for PMS mainly focus on the nervous system. Modern research shows that the incidence of PMS may be related to abnormal neural activity in the brain’s default mode network (DMN) [
Three of the 15 studies reported adverse reactions of acupuncture (hypomenorrhea, subcutaneous hematoma, and pain), while the other 12 studies did not mention the adverse reactions. Therefore, the safety of acupuncture could not be judged comprehensively in this review. However, it can preliminarily be inferred that acupuncture is safe to some extent according to the results of this study.
The methodological quality of the literature included in this study is poor, and the sample size of each study is small. There is no standard guideline for the acupuncture treatment and the evaluation system of its efficacy. Due to the particularity of TCM- (traditional Chinese medicine-) related research, most of the literatures included in this review were conducted in China, which presents a possible language bias. Therefore, the findings of this study should be interpreted cautiously. Large-scale, case-control studies with rigorous designs are necessary to provide accurate evidence.
In conclusion, acupuncture treatment leads to higher effective rate for PMS. There is no significant difference of effective rate in intervention time of acupuncture treating PMS. The most used acupoints for PMS treatment are SP6, LR3, and RN4. However, considering the methodological limitation of the studies, caution needs to be taken in applying the conclusions of this review. Thus, further studies with high methodological quality are required to validate the conclusions of this review.
The authors declare that they have no conflicts of interest.