BACKGROUND: The placebo response of sham acupuncture in patients with primary dysmenorrhea is a substantial factor associated with analgesia. However, the magnitude of the placebo response is unclear. OBJECTIVE: This meta-analysis assessed the effects of sham acupuncture in patients with primary dysmenorrhea and the factors contributing to these effects. SEARCH STRATEGY: PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were searched from inception up to August 20, 2022. INCLUSION CRITERIA: Randomized controlled trials (RCTs) using sham acupuncture as a control for female patients of reproductive age with primary dysmenorrhea were included. DATA EXTRACTION AND ANALYSIS: Pain intensity, retrospective symptom scale, and health-related quality of life were outcome measures used in these trials. Placebo response was defined as the change in the outcome of interest from baseline to endpoint. We used standardized mean difference (SMD) to estimate the effect size of the placebo response. RESULTS: Thirteen RCTs were included. The pooled placebo response size for pain intensity was the largest (SMD = -0.99; 95% confidence interval [CI], -1.31 to -0.68), followed by the retrospective symptom scale (Total frequency rating score: SMD = -0.20; 95% CI, -0.80 to -0.39. Average severity score: SMD = -0.35; 95% CI, -0.90 to -0.20) and physical component of SF-36 (SMD = 0.27; 95% CI, -0.17 to 0.72). Studies using blunt-tip needles, single-center trials, studies with a low risk of bias, studies in which patients had a longer disease course, studies in which clinicians had < 5 years of experience, and trials conducted outside Asia were more likely to have a lower placebo response. CONCLUSION Strong placebo response and some relative factors were found in patients with primary dysmenorrhea. PROSPERO registration number: CRD42022304215. Please cite this article as: Sun CY, Xiong ZY, Sun CY, Ma PH, Liu XY, Sun CY, Xin ZY, Liu BY, Liu CZ, Yan SY. Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis. J Integr Med. 2023; 21(5): 455-463.
Female ; Humans ; Dysmenorrhea/therapy* ; Acupuncture Therapy ; Pain Management ; Needles ; Placebo Effect

OBJECTIVE: To observe the skin surface microcirculation of acupoints of conception vessel, governor vessel and thoroughfare vessel in patients with primary dysmenorrhea using laser speckle contrast imaging (LSCI), and provide acupoint selection basis of acupuncture-moxibustion for primary dysmenorrhea. METHODS: Ninety-nine healthy female college students with regular menstrual cycles (normal group) and 94 female college students with primary dysmenorrhea (dysmenorrhea group) were recruited. Before menstrual period, on the first day of menstruation, and on the third day after menstruation, LSCI was used to observe the surface microcirculation at the abdominal acupoints of conception vessel, i. e. Yinjiao (CV 7), Qihai (CV 6), Shimen (CV 5), Guanyuan (CV 4), Zhongji (CV 3) and Qugou (CV 2), acupoints of thoroughfare vessel, i. e. Huangshu (KI 16), Zhongzhu (KI 15), Siman (KI 14), Qixue (KI 13), Dahe (KI 12), Henggu (KI 11) and acupoints of lumbosacral region of governor vessel, i. e. Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3), Yaoshu (GV 2) as well as two non-acupoints. RESULTS: Before menstrual period, there was no significant difference in the surface blood perfusion of the acupoints between the dysmenorrhea group and the normal group (P>0.05). On the first day of menstruation, the surface blood perfusion of Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3) and right Huangshu (KI 16) in the dysmenorrhea group was higher than that in the normal group (P<0.05, P<0.01). On the third day after menstruation, the surface blood perfusion of the right Henggu (KI 11) in the dysmenorrhea group was lower than that in the normal group (P<0.05). CONCLUSION In patients with primary dysmenorrhea, on the first day of menstruation, the surface blood perfusion of Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3) of governor vessel, and the right Huangshu (KI 16) of thoroughfare vessel is increased, while on the third day after menstruation, the surface blood perfusion of the right Henggu (KI 11) of thoroughfare vessel is decreased. These findings might provide a basis for acupoint selection in the acupuncture-moxibustion treatment of primary dysmenorrhea.
Humans ; Female ; Microcirculation ; Dysmenorrhea/therapy* ; Menstrual Cycle ; Acupuncture Points ; Acupuncture Therapy

Objective: To investigate the relationship between magnetic resonance imaging (MRI) imaging characteristics and clinical symptoms and therapeutic efficacy in adenomyosis patients. Methods: The clinical characteristics of the adenomyosis questionnaire was self-designed. This was a retrospective study. From September 2015 to September 2020, totally 459 patients were diagnosed with adenomyosis and underwent pelvic MRI examination at Peking University Third Hospital. Clinical characteristics and treatment were collected, MRI was used to determine the lesion location, and to measure the maximum lesion thickness, the maximum myometrium thickness, uterine cavity length, uterine volume, the minimum distance between the lesion and serosa or endometrium, and whether combined with ovarian endometrioma. The difference of MRI imaging characteristics in patients with adenomyosis and its relationship with clinical symptoms and therapeutic efficacy were analyzed. Results: (1) Among the 459 patients, the age was (39.1±6.4) years. There were 376 patients (81.9%, 376/459) with dysmenorrhea. Whether patients had dysmenorrhea were related to uterine cavity length, uterine volume, ratio of the maximum lesion thickness to the maximum myometrium thickness, and whether patients had ovarian endometrioma (all P<0.001). Multivariate analysis suggested that ovarian endometrioma was the risk factor for dysmenorrhea (OR=0.438, 95%CI: 0.226-0.850, P=0.015). There were 195 patients (42.5%, 195/459) with menorrhagia. Whether patients had menorrhagia were related to age, whether patients had ovarian endometrioma, uterine cavity length, the minimum distance between lesion and endometrium or serosa, uterine volume, ratio of the maximum lesion thickness to the maximum myometrium thickness (all P<0.001). Multivariate analysis suggested that ratio of the maximum lesion thickness to the maximum myometrium thickness was the risk factor for menorrhagia (OR=774.791, 95%CI: 3.500-1.715×10⁵, P=0.016). There were 145 patients (31.6%, 145/459) with infertility. Whether the patients had infertility were related to age, the minimum distance between lesion and endometrium or serosa, and whether patients had ovarian endometrioma (all P<0.01). Multivariate analysis suggested that young and large uterine volume were risk factors for infertility (OR=0.845, 95%CI: 0.809-0.882, P<0.001; OR=1.001, 95%CI: 1.000-1.002, P=0.009). (2) The success rate of in vitro fertilization-embryo transfer (IVF-ET) was 39.2% (20/51). Dysmenorrhea, high maximum visual analogue scale score and large uterine volume affected the success rate of IVF-ET (all P<0.05). The smaller the maximum lesion thickness, the smaller the distance between the lesion and serosa, the larger the distance between the lesion and endometrium, the smaller the uterine volume, and the smaller the ratio of the maximum lesion thickness to the maximum myometrium thickness, the better the therapeutic efficacy of progesterones (all P<0.05). Conclusions: Concomitant ovarian endometrioma increases the risk of dysmenorrhea in patients with adenomyosis. The ratio of the maximum lesion thickness to the maximum myometrium thickness is an independent risk factor for menorrhagia. Young and large uterine volume may increase the risk of infertility. Severe dysmenorrhea and large uterine volume affect the success rate of IVF-ET. The therapeutic efficacy of progesterones is relatively better when the lesion is small and far away from the endometrium.
Female ; Humans ; Adult ; Middle Aged ; Adenomyosis/pathology* ; Dysmenorrhea/therapy* ; Menorrhagia/pathology* ; Endometriosis/therapy* ; Retrospective Studies ; Infertility/complications* ; Magnetic Resonance Imaging

BACKGROUND: Primary dysmenorrhea (PD) is the most common complaint associated with menstruation and affects up to three-quarters of women at some stage of their reproductive life. In Chinese medicine, navel therapy, treatment provided at Shenque (CV 8), is used as a treatment option for PD. OBJECTIVE: To evaluate the effect of navel therapy on pain relief and quality of life in women with PD, compared with Western medicine (WM). METHODS: China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), SinoMed and Wanfang Database, MEDLINE, the Cochrane Library, Embase, Web of Science, and the International Clinical Trial Registry of the U.S. National Institutes of Health were searched from their inceptions to April 1, 2021. Randomized controlled trials (RCTs) assessing therapeutic effects of navel therapy on PD were eligible for inclusion. RevMan 5.4 software was used for data analyses. The certainty of the evidence was assessed using the online GRADEpro tool. RESULTS: Totally 24 RCTs involving 2,614 participants were identified. Interventions applied to acupuncture point CV 8 included: herbal patching, moxibustion or combined navel therapy (using at least 2 types of stimulation). Compared to placebo, there was a significant effect in favor of navel therapy on reducing overall menstrual symptom scores at the end of treatment [mean difference: -0.82, 95% confidence interval (CI): -1.00 to -0.64, n=90; 1 RCT]. As compared with Western medicine, navel therapy had a superior effect on pain intensity as assessed by Visual Analogue Scale at the end of treatment [standardized mean difference (SMD): -0.64, 95% CI: -1.22 to -0.06, I²=80%, n=262; 3 RCTs]; on symptom resolution rate at 3-month follow-up (risk ratio: 1.94, 95% CI: 1.47 to 2.56, n=1527, I²=38%; 13 RCTs); and on global menstrual symptoms score at the end of treatment (SMD: -0.67, 95% CI: -0.90 to -0.45, I²=63%, n=990; 12 RCTs). Subgroup analyses showed either a better or an equivalent effect comparing navel therapy with Western medicine. No major adverse events were reported. The methodological quality of included trials was poor overall. CONCLUSIONS Navel therapy appears to be more effective than Western medicine in decreasing menstrual pain and improving overall symptoms of PD. However, these findings need to be confirmed by well-designed clinical trials with adequate sample size (Systematic review registration at PROSPERO, No. CRD42021240350).
United States ; Female ; Humans ; Dysmenorrhea/drug therapy* ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic ; Moxibustion ; Pain Management

OBJECTIVE: To assess the efficacy of a curcumin supplementation on cognitive abilities in women suffering from premenstrual syndrome (PMS) and dysmenorrhea. METHODS: A randomized, triple-blind, placebo-controlled trial was conducted from December 2019 to March 2020. A total of 124 women who had both PMS and dysmenorrhea were enrolled, and were equally and randomly assigned to the curcumin group or placebo group, 62 cases in each. Each subject received either a capsule containing 500 mg of curcuminoid, or a placebo daily, for 10 days (7 days before and until 3 days after the onset of menstrual bleeding) over 3 menstrual cycles. The cognitive abilities questionnaire was used to measures cognitive functions in 7 specific areas. Adverse reactions were monitored during and after the trial in both groups. RESULTS: Administration of curcumin was associated with a significant increase in memory score (P=0.002), inhibitory control and selective attention (P=0.020), and total cognitive ability task (P=0.024). In addition, significant increments were found in scores of memory (3.5±3.1 vs. 0.4±3.8 in the curcumin and placebo groups, respectively; P=0.035), inhibitory control and selective attention (3.0±3.7 vs. 0.4±3.7; P=0.027) and total cognitive abilities (8.3±12.3 vs. 2.2±12.4; P=0.025) in the curcumin group versus placebo groups. Curcumin was safe and well-tolerable in current clinical trial. CONCLUSION Curcumin has a beneficial efficacy on cognitive function scores in women with PMS and dysmenorrhea, with improvements in memory, inhibitory control and selective attention. (Registration No. IRCT20191112045424N1, available at: https://www.irct.ir ).
Humans ; Female ; Curcumin/therapeutic use* ; Dysmenorrhea/drug therapy* ; Premenstrual Syndrome/psychology* ; Cognition ; Double-Blind Method

Based on the data mining technology, the main indications and compatibility rules of Ciliao (BL 32) were analyzed and summarized. The relevant literature was retrieved from the databases of CNKI, Wanfang, VIP, Cochrane Library, SinoMed, Scopus, Web of Science, EMbase and PubMed, from the date of establishment to September 8, 2021. Using the software of SPSS Modeler 18.0 and Gephi0.9.2, the included literature was analyzed by data mining. A total of 218 articles were included, of them, there were 36 articles using single-acupoint prescriptions and 182 articles using compound prescriptions. Acupuncture was the most frequently used intervention of Ciliao (BL 32), followed by electroacupuncture. Dysmenorrhea and labor analgesia were the dominant indications of single-acupoint prescriptions of Ciliao (BL 32), and 9 diseases i.e. dysmenorrhea, urinary incontinence, urinary retention, chronic pelvic inflammatory disease, chronic prostatitis and lumbar disc herniation were the dominant indications of compound prescriptions. The main indications of Ciliao (BL 32) involved diseases of reproductive system, urinary system and waist. There were 92 acupoints in compatibility with Ciliao (BL 32), which were main belonged to the bladder meridian, the conception vessel and the spleen meridian, the most frequently used acupoints were Sanyinjiao (SP 6), Guanyuan (CV 4), Shenshu (BL 23) and Zhongji (CV 3).
Acupuncture Points ; Acupuncture Therapy ; Data Mining ; Dysmenorrhea ; Female ; Humans ; Male ; Meridians

OBJECTIVE: To investigate the effect of acupuncture on the brain functional activities of the patients with primary dysmenorrhea based on the resting-state functional magnetic resonance imaging (rs-fMRI), and to provide visual evidence for the central mechanism of acupuncture in treatment of primary dysmenorrhea. METHODS: Forty-two patients of primary dysmenorrhea were enrolled and randomly divided into an observation group (21 cases, 1 case dropped off) and a control group (21 cases, 2 cases dropped off, 3 cases withdrawal). In the observation group, acupuncture was exerted at Sanyinjiao (SP 6) and Guanyuan (CV 4), started 5-7 days before menstrual flow, once a day till menstrual onset, for a total of 3 menstrual cycles. No intervention was applied in the control group. The scores of visual analogue scale (VAS) and Cox menstrual symptom scale (CMSS) were observed in both groups before and after treatment. Based on rs-fMRI, the data of resting-state functional magnetic resonance were collected from two groups before and after treatment. Combined with functional connectivity strength (FCS) and functional connectivity (FC) analysis, the differences of brain regions before and after treatment were compared between the two groups and the correlation was analyzed between their functional connectivity changes and the improvements in VAS and CMSS scores of the patients in the observation group. RESULTS: In the observation group, the scores of VAS and CMSS were all decreased after treatment (P<0.05), while the scores related to the symptom time in CMSS was reduced in comparison with that before treatment in the control group (P<0.05). The score reducing ranges of VAS and CMSS in the observation group were larger than the control group (P<0.05). Compared before treatment, FCS of the right middle cingulate cortex and the left cuneus was increased, while FCS of the left inferior parietal lobule was decreased after treatment in the observation group. In the control group, FCS of the left orbital frontal cortex was increased after treatment. Compared with the control group, FCS of the left anterior insula was increased in the observation group after treatment. FC analysis was performed using the left anterior insula as the seed point. In comparison with the control group, FC of the left anterior insula was increased either with the inferior temporal gyrus or with the right hippocampus; and was decreased either with the middle occipital lobe or with the right dorsolateral prefrontal cortex in the observation group after treatment. In the observation group, FC between the left anterior insula and the right hippocampus was positively correlated with the improvements in symptom severity (r =0.385, P<0.05) and symptom time (r =0.510, P<0.05) of CMSS, and FC between the right dorsolateral prefrontal cortex and the left anterior insula was negatively correlated with the improvement in symptom severity of CMSS after treatment (r =-0.373, P<0.05). CONCLUSION The anterior insula may be the key brain region in treatment of primary dysmenorrhea with acupuncture. Acupuncture may relieve dysmenorrhea and the related symptoms through strengthening the functional connectivity of anterior insula-limbic system and anterior insula-control network.
Acupuncture Therapy ; Brain/diagnostic imaging* ; Dysmenorrhea/therapy* ; Female ; Humans ; Magnetic Resonance Imaging/methods*

OBJECTIVE: To prove the therapeutic effect of auricular intradermal needling and auricular point sticking on primary dysmenorrhea (PD), and to explore its mechanism. METHODS: A total of 90 patients with PD were randomized into an auricular intradermal needling group, an auricular point sticking group and a placebo group, 30 cases in each one. Neishengzhiqi (TF RESULTS: Compared before treatment, the scores of CMSS, VAS and SAS were decreased at each time point of treatment in the auricular intradermal needling group, 2, 3 courses into treatment and at follow-up in the auricular point sticking group and 3 courses into treatment in the placebo group ( CONCLUSION Auricular intradermal needling and auricular point sticking can both improve the clinical symptom of primary dysmenorrhea, relieve the pain and anxiety, their mechanism may be related to regulating the serum levels of PGF
Acupuncture Points ; Acupuncture, Ear ; Anxiety Disorders ; Dysmenorrhea/therapy* ; Female ; Humans ; Treatment Outcome

This study aimed to explore the characteristic role of Puerariae Lobatae Radix(PLR) in Gegen Decoction for the treatment of primary dysmenorrhea(PD). Estrogen(E_2) was combined with oxytocin to establish a mouse model of PD. The mice were randomly divided into a normal group, a model group, a Gegen Decoction group, a PLR-free Gegen Decoction group, a PLR group, and a positive drug group(ibuprofen). Writhing response times and writhing incubation of mice in each group were tested by behavio-ral assessment, and the serum levels of prostaglandin F_(2α)(PGF_(2α)), prostaglandin E_2(PGE_2), E_2, and progesterone(PROG) were detected by ELISA kits. Western blot method was adopted to detect cyclooxygenase-2(COX-2) and estrogen receptor alpha(ER_α) expression levels in uterine tissues. Doppler ultrasound was employed to detect changes in uterine artery blood flow in mice, including peak systolic blood flow velocity(maximum velocity), end-diastolic velocity(minimum velocity), peak systolic blood flow velocity/end-diastolic velocity(S/D), pulsatility index(PI), and resistive index(RI). Histopathological changes in the uterus were detected by HE staining. Based on the oxytocin-induced isolated uterine contraction model, the effects of Gegen Decoction, PLR-free Gegen Decoction, and PLR on the amplitude, frequency, and activity of isolated uterine contraction were compared to investigate the role of PLR in Gegen Decoction for the treatment of PD. The results showed that compared with the Gegen Decoction group, the PLR-free Gegen Decoction improved the indicators of PD except for E_2 content, ER_α expression, and uterine artery blood flow. PLR could significantly down-regulate the serum content of E_2 and the protein expression of uterine ER_α, and improve the uterine artery blood flow. The data suggested that PLR, as the sovereign drug of Gegen Decoction, might function in Gegen Decoction for the treatment of PD by mediating E_(2 )and improving the uterine artery blood flow.
Animals ; Drugs, Chinese Herbal ; Dysmenorrhea/drug therapy* ; Humans ; Mice ; Plant Roots ; Pueraria ; Uterus

OBJECTIVE: To observe the clinical efficacy of thunder-fire moxibustion combined with mifepristone for ovarian chocolate cyst dysmenorrhea with kidney deficiency and blood stasis. METHODS: Seventy patients were randomly divided into an observation group and a control group, 35 cases in each group. The patients in the the control group were treated with oral administration of mifepristone, 10 mg each time, once a day; based on the treatment of the control group, the patients in the observation group were treated with thunder-fire moxibustion at Guanyuan (CV 4), Zigong (EX-CA 1), Xuehai (SP 10), once every other day. Both the groups were treated for 3 months. The Cox menstrual symptom scale (CMSS) score, the maximum cross-sectional area of ectopic cyst, and the serum levels of transforming growth factor-β1 (TGF-β1) and interleukin-17 (IL-17) were observed before and after treatment in the two groups. The clinical efficacy was evaluated. RESULTS: Compared before treatment, the severity scores and duration scores of CMSS as well as the serum levels of TGF-β1 were reduced after treatment in the two groups ( CONCLUSION Thunder-fire moxibustion combined with mifepristone could significantly improve dysmenorrhea symptoms, shorten dysmenorrhea time and promote atrophy of ovarian heterotopic cyst in patients with ovarian chocolate cyst dysmenorrhea of kidney deficiency and blood stasis, and the mechanism may be related to the reduction of serum levels of TGF-β1 and IL-17.
Acupuncture Points ; Chocolate ; Cysts ; Dysmenorrhea/drug therapy* ; Female ; Humans ; Kidney ; Mifepristone ; Moxibustion