Intervention Review

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Acupuncture for menopausal hot flushes

  1. Sylvie Dodin1,*,
  2. Claudine Blanchet1,
  3. Isabelle Marc2,
  4. Edzard Ernst3,
  5. Taixiang Wu4,
  6. Caroline Vaillancourt5,
  7. Joalee Paquette6,
  8. Elizabeth Maunsell7

Editorial Group: Cochrane Gynaecology and Fertility Group

Published Online: 30 JUL 2013

Assessed as up-to-date: 15 JAN 2013

DOI: 10.1002/14651858.CD007410.pub2


How to Cite

Dodin S, Blanchet C, Marc I, Ernst E, Wu T, Vaillancourt C, Paquette J, Maunsell E. Acupuncture for menopausal hot flushes. Cochrane Database of Systematic Reviews 2013, Issue 7. Art. No.: CD007410. DOI: 10.1002/14651858.CD007410.pub2.

Author Information

  1. 1

    Université Laval, Department of Obstetrics and Gynecology, Quebec, Canada

  2. 2

    Centre Hospitalier Universitaire de Québec, Département de pédiatrie, Université Laval, Québec, Québec, Canada

  3. 3

    Peninsula Medical School, University of Exeter, Complementary Medicine Department, Exeter, UK

  4. 4

    West China Hospital, Sichuan University, Chinese Clinical Trial Registry, Chinese Ethics Committee of Registering Clinical Trials, Chengdu, Sichuan, China

  5. 5

    Université Laval, Québec, Québec, Canada

  6. 6

    Institut des nutraceutiques et des aliments fonctionnels, Québec, Canada

  7. 7

    Hopital du Saint-Sacrement, Centre de recherche, Quebec, QC, Canada

*Sylvie Dodin, Department of Obstetrics and Gynecology, Université Laval, 45, Leclerc - Room D6-723, Quebec, G1L 2G1, Canada. sylvie.dodin@ogy.ulaval.ca.

Publication History

  1. Publication Status: New
  2. Published Online: 30 JUL 2013

SEARCH

 
Characteristics of included studies [ordered by study ID]
Avis 2008

Methods2-site clinical trial using 3-arm prospective, randomized, single-blind, sham-control design; UC, SA, and TA


Participants37 perimenopausal or postmenopausal women aged 42-55 years experiencing at least 4 moderate-to-severe hot flushes per day and not having used HT, a selective oestrogen-receptor modulator, an aromatase inhibitor, clonidine, Bellergal, antidepressant therapy, or gabapentin in the past 12 weeks; not having received chemotherapy; not having used acupuncture for any reason within the past 4 weeks; not having any previous acupuncture treatment for hot flushes; having no significant psychiatric disorder and untreated thyroid disease; not having been diagnosed with bleeding or clotting problem other than heavy periods; not currently taking any prescribed medications that increase the risk of bleeding (warfarin, enoxaparin, or clopidogrel)

Setting: Massachusetts General Hospital and University of North Carolina. Women were recruited through newspaper advertisements, radio announcements, and hospital postings


InterventionsTA:

30-minutes, standardized and individualized treatment according to TCM designed to tone or reinforce the kidney essence, balance yin/yang, and control hot flushes and night sweats, 2 times per week for 8 weeks. Treatments were given by experienced acupuncturists trained in TCM. No more than 16 acupuncture points were needled during any treatment. The 'De Qui' sensation was the elicited response. Type of needle used: Vinco 34-gauge, 1-inch (0.22 x 25 mm) and 30-gauge, 1.5-inch (0.30 x 40 m). Acupuncture points for the standardized treatment were CV 4, KI 3 (bilateral), SP 6(bilateral), BL 23(bilateral), HT 6 (bilateral), and KI 7 (bilateral), and the possible additional points (based on a person’s TCM diagnostic category or based on acupuncturist clinical judgement were KI 6, KI 10, GV 4, GV 20, CV 6, CV 15, BL 15, BL 18, BL 52, LR 3, LR 8, GB 13, GB 20, PC 7, HT 7, HT 8, yintang and taiyang

SA:

30-minutes treatment 2 times per week for 8 weeks were given by experienced acupuncturists trained in TCM. Non-acupuncture points sites (sites where minimal effects on hot flushes) were needled shallowly, without attempting to elicit the 'De Qui' sensation. 12 needles were inserted, 6 on both side of the body (right and left). Point locations were: 3.5 cun below GB-34; mid-way between GB and BL channels; 2 cun above the lateral malleolus; 3 cun lateral to the navel; in the depression proximal to the metacarpal-phalangeal joint between the index and middle fingers; approximately 1-1.5 inches above or proximal to the third and fourth toe web space between the third and fourth metatarsals; and 3 cun lateral to the lower border of the spinous process of the fourth lumbar vertebra

UC:

There had been no initiation of treatment for their hot flushes for 2 months, but participants could continue with any non-pharmacological treatment they were currently using


OutcomesPrimary outcomes:

  • frequency of hot flushes using a daily diary
  • severity of hot flushes using a daily diary
  • times of assessment of the main outcomes: at baseline, every week during the 8-week treatment, and at the end of treatment (week 8)


Secondary outcomes:

  • hot flushes interference using the 10-item Hot Flash Related Daily Interference Scale
  • sleep quality using the Women's Health Initiative Insomnia Rating Scale (6-item scale)
  • how bothersome symptoms were using the Menopause-specific Quality of Life Questionnaire
  • mood using the Psychological General Well-Being Index
  • health-related quality of life using a 100-mm VAS (from 0 to 100) and the Medical Outcomes Study 36-Item Short Form Health Survey


Source of fundingNational Cancer Institute, Massachusetts General Hospital, National Institutes of Health, National Center for Research Resources, General Clinical Research Centers Program, University of North Carolina at the Verne S. Caviness General Clinical Research Center at UNC School of Medicine


NotesFollow-up: 8 weeks (after completion of treatment)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Treatment assignment was generated using a randomisation computer program and a computer file was kept at each clinic with their respective randomisation list. The acupuncturist accessed it from his/her PC and a paper copy of the randomisation assignments was kept at each clinical centre and by the Biostatistics and Data Management group at Wake Forest University for easy access in case of computer malfunction" (from the author)

Allocation concealment (selection bias)Low risk"The study coordinator and/or other personnel administering the questionnaires did not have access to the randomisation list to remain masked"

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "Study staff who administered questionnaires were blinded to which form of acupuncture that the women received"

"The acupuncturists were blinded to the participant's treatment group until after making the TCM diagnosis"

Incomplete outcome data (attrition bias)
All outcomes
High riskQuote: "Study retention was excellent with all women remaining in the study. However, not all women completed all study procedures. Eight (42%) of the women in the TA group and 10 (56%) in the SA group completed at least (80%) of the 16 treatments. Furthermore, two women in the UC group did not complete any follow-up diaries, one in the SA group, and three in the TA group"

Nothing reported about reasons for treatment withdrawal/not completing all study procedures

Analyses were conducted with an ITT approach

Nothing mentioned about imputation method

Selective reporting (reporting bias)Low riskThe published report included all expected outcomes

Other biasLow riskThe study appeared free of other sources of bias

Bokmand 2013

MethodsRandomized, subject-blinded trial. 3 groups: true acupuncture, SA and no treatment


Participants94 women in the postoperative period from 6 months to 5 years

Perimenopausal or postmenopausal women aged 43-76 years, treated for breast cancer, experiencing hot flushes and disturbed night sleep. Not having HT treatment or known metastatic disease

Setting: Vejle Hospital and Herlev Hospital, Copenhagen University Hospital. Women were recruited through advertisement at the breast centre waiting room for mammography control and in the outpatient clinics


Interventions2 experienced acupuncturists gave either acupuncture in the selected acupuncture points or in the sham points

True acupuncture:

Predetermined bilateral points for 15-20 minutes once a week for 5 consecutive weeks

4 acupuncture points were needled; Hc6, Ki3, Sp6, and Lr3. These points are located on the wrist, ankle, and foot

SA:

4 predetermined bilateral non-acupuncture points outside the meridians, but in the same region as the true points

No treatment:

Received no acupuncture

To our knowledge none of the participants had acupuncture before


OutcomesPrimary outcomes:

  • a subjective VAS from 0 to 10. The logbook was filled 2 weeks before entering the study and in 3 days after each treatment


Secondary outcomes:

  • sleep disturbances were rated at the same time points
  • plasma oestradiol level were done at the same time points


Source of funding"The study funds have no role in the study."

The authors were supported by funds from Vejle Hospital: “Udviklingsfonden” and “Forskningsrådet”.


NotesThe study appeared free of other sources of bias


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "The randomization was done by the acupuncturist. The participant personally drew a sealed envelope from a plastic bag and was randomly allocated to either of the three groups." No further details reported

Allocation concealment (selection bias)Unclear riskQuote: "The randomization was done by the acupuncturist. The participant personally drew a sealed envelope from a plastic bag and was randomly allocated to either of the three groups." No further details reported

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "Group acupuncture and sham-acupuncture were both patient - and investigator blinded"

"Participants of no treatment group were not blinded"

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo dropout

Selective reporting (reporting bias)Low riskThe published report included all expected outcomes

Other biasUnclear riskDuring the project period, some women received other type of treatment, which had no effect on neither the treatment nor acupuncture according to the authors. These women were divided in the 3 groups

Borud 2009

MethodsMulticentre, randomized, controlled trial with 2 parallel arms; TA + self care advice, self care only


Participants267 postmenopausal women experiencing on average, 7 or more hot flushes per 24 h for 7 consecutive days within the 2-week qualifying period

They were excluded if they had surgical menopause, history of cancer within the past 5 years (including use of tamoxifen), heart valve disease, poorly controlled hypertension, poorly controlled diabetes mellitus, organ transplant, mental disease, drug or alcohol dependency; used anticoagulant medication, and had inability to complete study forms. Women were recruited by newspaper advertisements and media coverage

Setting: Oslo, Bergen and Tromso in Sweden


InterventionsTA + self-care advice (1 page information):

10 individualized TCM acupuncture treatments were given for 12 consecutive weeks by 10 different acupuncturists having at least 2500 h of training and at least 3 years of clinical experience. The intervention could be extended 2 weeks if needed. The minimum number of session accepted as 'per protocol' was 6. Acupuncturist was instructed to see the participant within 1 week. Participants were treated according to the syndrome diagnosis. Point location was not standardized in the study but was left to the acupuncturists to decide. The 'De Qui' sensation was the elicited response. Moxibustion (heated needles) could be added if indicated in co-intervention. They also received the 1-page leaflet with information about self care strategies to relieve menopausal symptoms, and they were free to use any of these. Advice about sufficient sleep and rest, reduction in physical and psychological stress, regular exercise, healthy food, limited tobacco smoking and limited alcohol intake. There was a washout period for participants who had already taken HT: for systemic HT and SSRIs/SNRIs an 8-week washout period was required; for local prescription HT 4-week washout period was required.

Self care advice only:

Participants were not prescribed any medical treatment for menopausal symptoms but they were free to use any over-the-counter medication and self provided non-pharmaceutical interventions, guided by the self-care information leaflet (the same than in the acupuncture group). The intervention lasted 12 consecutive weeks. There was a washout period for participants who had already taken HT: for systemic HT and SSRIs/SNRIs an 8-week washout period was required; for local prescription HT 4-week washout period was required


OutcomesPrimary outcomes:

  • frequency of hot flushes per 24 h using a daily diary
  • change in mean hot flushes frequency per 24 h
  • severity of hot flushes using a daily diary and VAS (0-10 scale)
  • hours of sleep per night recorded in a daily diary
  • times of assessment of the main outcomes: 2 weeks before study, at the baseline, and for 1 week of weeks 4, 8 and 12 of the intervention period


Secondary outcomes:

  • health-related quality of life (depressed mood, somatic symptoms, memory/concentration, vasomotor symptoms, sexual behaviour, menstrual symptoms, anxiety/fears, sleep problems, and attractiveness) using the Women's Health Questionnaire (0-1 scale)


Source of fundingThe Research Council of Norway and University Hospital of North Norway


NotesFollow-up: 12 months (after the beginning of the study)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomization lists were computer generated (blocked randomization, random block size) and stratified by centre

Allocation concealment (selection bias)Low riskQuote: "After enrolment, the local coordinator telephoned the central randomization unit at the University Hospital of North Norway (UNN) to obtain group allocation"

Blinding (performance bias and detection bias)
All outcomes
High riskQuote: "All researchers remained blinded throughout the study. A person blinded to group allocation entered data on hot flashes and sleep into the database. The randomization code was broken only after the analyses of the primary outcomes were completed"

"Participants were not blinded because they had acupuncture or a one page information of self-care menopausal symptoms" 

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "Missing data were handled by single imputation of missing values. Missing data on hot flash frequency and intensity of sleep at 12 weeks were substituted with the mean value of the entries in the diary of at least 3 days data had been recorded. If less than 3 days’ data were recorded, the data were considered missing. Single imputation is considered fairly accurate if the proportion of missing values is small (<5%). and replacing the missing values by the mean value is considered a valid strategy"

"Missing data on hot flash frequency and intensity or sleep were found in a total of 16 hot flash diaries at week 12. The rate of missing information was 1.5%. Missing values for 1 day were substituted with the mean of the reported data in 10 diaries, for 2 days in two diaries, for 3 days in 2 diaries, and 4 days in 2 diaries"

Few dropouts and reasons for withdrawal are reported. No serious adverse effects were reported

Selective reporting (reporting bias)Low riskThe published report included all expected outcomes

Other biasLow riskThis study appeared free of other sources of bias

Deng 2007

MethodsRandomized, controlled, subject-blinded trial. 2 groups: true acupuncture and SA


Participants71 women undergoing treatment for breast cancer at Memorial Sloan-Kettering Cancer Center having a Karnofsky's performance score > 60 and experiencing an average of 3 or more hot flushes per day for 1-week period with baseline diary

Women planning surgery, chemotherapy, radiotherapy, immunotherapy; having initiated or ceased HT during the trial or within 3 weeks before the trial; using pharmacological treatment of hot flushes or SSRIs (unless dose remained stable for 4 weeks prior to study); having skin infection; having received acupuncture treatment in the 6 weeks prior to study or acupuncture given specifically for the treatment of hot flushes in the previous 6 months were excluded

Setting: Memorial Sloan-Kettering Cancer Center, New York, USA


InterventionsTrue acupuncture:

Treatment given 2 times per week for 4 weeks by several licensed acupuncturists having 3 years of normal postgraduate training and 3 to 25 years of continuous practice

Needles (stainless-steel filiform 0.20 x 30 mm manufactured by Seiring Corp, Shizuoka, Japan) were inserted 0.25 to 0.5 inches into the skin at 19 acupuncture points (DU14, GB20, BL13, PC7, H6, K7, ST36, SP6, ear shen men, ear sympathetic point) for 20 minutes, and were manually stimulated. The 'De Qui' sensation was the elicited response

SA:

Treatment given 2 times per week for 4 weeks by several licensed acupuncturists having 3 years of normal postgraduate training and 3 to 25 years of continuous practice

Needles (Streitberger sham needles 0.30 x 30 mm manufactured by Asjamed, Pullach, Germany) were applied a few centimetres away from the true acupuncture points for 20 minutes. Rather than penetrating the skin, the needle retracted inside its handle after insertion through an adhesive tape placed on a plastic supporting ring


OutcomesFrequency of hot flushes per day using a diary


Source of fundingNational Cancer Institute


NotesFollow-up: 6 months after initiation of treatment


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Random assignment of participants was accomplished using a secure, password-protected, institutional computer system that stratified by using permuted blocks of random length"

Allocation concealment (selection bias)Low riskQuote: "The system is designed to ensure that allocation cannot be guessed before a patient is registered and cannot be changed afterwards, thus ensuring full allocation concealment.” "After participant registration and random assignment, a research assistant who was otherwise unconnected with the trial accessed allocation and telephoned the acupuncturist with the details of allocation"

Blinding (performance bias and detection bias)
All outcomes
Low risk"Patients, researchers, and others involved in patient care were blind to study group; only acupuncturists and the designated research assistant were aware of which patients received true and which received placebo treatment"

Incomplete outcome data (attrition bias)
All outcomes
Low riskFew dropouts and lost of follow-up (true acupuncture, 2%; SA, 7%). Reason for missing outcome data unlikely to be related to true outcome. No ITT analysis

Selective reporting (reporting bias)Low riskThe published report included all expected outcomes

Other biasLow riskThe study appeared free of other sources of bias

Frisk 2008

MethodsRandomized, controlled study, part of the multicentre study HABITS (Hormonal replacement therapy After Breast cancer - is IT Safe?). 2 groups: EA and HT


Participants45 postmenopausal women having previously completed treatment for breast cancer in situ, T1 and T2 tumours with 4 or fewer lymph nodes positive for metastasis, T3 tumours without metastasis; having no clinical or mammographic signs of recurrence; having vasomotor symptoms needing treatment according to the woman herself

Women planning surgery, chemotherapy, radiotherapy, immunotherapy; having initiated or ceased HT during the trial or within 3 weeks before the trial; taking pharmacological treatment of hot flushes; using of SSRIs (unless dose remained stable for 4 weeks prior to study); having skin infection; having received acupuncture treatment in the 6 weeks prior to study; and having received acupuncture specifically for the treatment of hot flushes in the previous 6 months were excluded

"The women were referred from breast surgeons or oncologists because they suffered from breast cancer and vasomotor symptoms severe enough to merit therapy"

Setting: this study was part of an international, multicentre study, HABITS, involving women from 3 centres in Sweden (Kalmar, Linkoping, Norrkoping). EA treatments were given both at hospitals and private practices


InterventionsEA:

30-minute treatment given by 6 different physiotherapists educated and experienced in acupuncture for 12 weeks (twice per week for the first 2 weeks and once a week for 10 other weeks). Physiotherapists were instructed orally and in writing about the acupuncture points. Participants received EA at 2 Hz in 4 and 'classical acupuncture' in 8 of the acupuncture points: UB 15, 23, 32 (bilateral) and GV 20, H7, P6, LIV 3, SP6, SP9 (unilateral). The needles were inserted and rotated to elicit the sensation Teh Chi. At depths of 1.25-2.5 cm this sensation was usually obtained. The procedure used was according to TCM acupuncture

HT:

There were 3 options for this treatment: women less than 2 years after menopause were given a sequential oestrogen/progestogen combination; women more than 2 years after menopause were given continuous combined oestrogen/progestogen; and post-hysterectomy women received unopposed oestrogen. The treatment was given over 24 months


Outcomes
  • Number of hot flushes during day and night using logbook
  • Times of assessment of the main outcomes: at baseline, at the 12th week of treatment, and 1 week at 6, 9, 12, 18 and 24 months after start of treatment
  • Climacteric symptoms using modified version of the Kupperman's Index


Source of fundingThe country Council of Ostergotland


NotesFollow-up (for EA): 24 months (after start of treatment)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "The computerized randomization in blocks of eight for the HABITS study occurred at the University of Uppsala"

"In all, 27 women were randomised to non-hormonal and 18 to hormonal treatment; the groups were uneven because the three centres did not filled each of their block"

Allocation concealment (selection bias)Unclear riskMethod not reported

Blinding (performance bias and detection bias)
All outcomes
High riskQuote of author: "So, the patients knew which treatment (pills of HT or acupuncture) they were getting. All women, no matter if they were offered HT or acupuncture, chose to start the treatment they were randomized to"

Incomplete outcome data (attrition bias)
All outcomes
High riskQuote: "Missing data were completed in the log books and for the KI, by taking the mean of the previous and the following measurements for that specific patient (logbook data in 8 cases (3%), when including women with another period of acupuncture in 12 cases (5%), KI data in 3 cases (1%), when including women with another period of acupuncture in 6 cases (3%))"

Quote: "By the end of the study, 12/23 (52%) had asked for no other treatment than EA for 24 months." Therefore, 47.8% dropout for the EA group at 24 months

Quote: "Eleven out of 18 women completed 24 months of HT." Therefore, 38.9% of dropouts for the HT

An ITT approach was used to conducted the analyses

High dropout rate during treatment

Reasons for dropouts are reported

Selective reporting (reporting bias)Low riskThe published report included all expected outcomes. However, the number of hot flushes per 24 h, as well as the Kupperman index score, was reported as mean changes and medians. The author provided the data for the 12 weeks for hot flushes frequency and severity for both groups

No table for distress and not much detail for HT group (distress, number...)

Other biasLow riskThe study appeared free of other sources of bias

Hervik 2009

MethodsRandomized, single-blind study of women following a breast cancer surgery. 2 groups: TA and SA


Participants59 postmenopausal women (no menstruation for at least 3 months) having finished treatment for breast cancer (chemotherapy or radiotherapy), treated with oestrogen antagonist, tamoxifen, for at least 3 months after chemotherapy or radiotherapy, and complaining of hot flushes (no severity limits)

Women taking medication for hot flushes either prior to, or during the treatment and follow-up period; having received previous acupuncture treatment; being treated with other complementary or alternative therapies simultaneously; having serious endocrine or vascular disorders; suffering from psychological problems; and having hypertension (diastolic blood pressure over 95 mm Hg) were excluded

Setting: The Breast Centre at Vestfold Central Hospital in Norway


InterventionsTA:

30-minute treatment were given for 10 consecutive weeks (twice per week the 5 first weeks and once per week the remaining 5 weeks) by a physiotherapist (the same for both TA and SA groups) having 3 years' certified training course and 15 years' practice. 8 needles (0.30 mm) were inserted 0.5-3 cm deep at 8 points along meridians in TCM (LIV3, GB20, LU7, KI3, Sp6, REN4, P7 and LIV8, unilateral) and manually stimulated. The 'De qui' sensation was the elicited response

SA:

30-minute treatment were given for 10 consecutive weeks (twice per week the 5 first weeks and once per week the remaining 5 weeks) by a physiotherapist (the same for both TA and SA group) having 3 years' certified training course and 15 years' practice. 8 needles (identical to TA group) were inserted 2-3 mm deep at 8 points well away from acupuncture and trigger points (bilateral)


Outcomes
  • Hot flushes frequency at day and night (data assessment tool not reported). Timing of assessment: each week for a period of 4 weeks prior to treatment, during the treatment (10 weeks) and for the 12 weeks following treatment
  • Menopausal symptoms using the Kupperman index. Timing of assessment: at baseline, at the end of the treatment, and 12 weeks after treatment


Source of fundingThe Norwegian Acupuncture Association (NAFO), University of Tromso (NAFKAM), and Vestfold Central Hospital


NotesFollow-up: 12 weeks (after completion of treatment). Additional data obtained from author by personal communication


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "Patients were randomized, using a sealed envelope technique, to receive either TA or SA"

Comment: does not mention the randomization method

Allocation concealment (selection bias)Unclear riskQuote: "Patients were randomized, using a sealed envelope technique, to receive either TA or SA"

Comments: not mentioned whether the envelopes were sequentially numbered and opaque

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "Patients were blinded to the type of acupuncture received"

"A neutral attitude towards the patients and potential treatment effects was attempted, and all data was handled by a secretary blinded to the treatment group"

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "All patients completed treatment"; "Number of hot flashes was recorded in all but one patient (SA group), the KI was obtained from all patients throughout the study period"

No dropout

Use of ITT approach or imputation method not mentioned

Comments: unclear about what have been done with the missing data

Selective reporting (reporting bias)Low riskThe published report included all expected outcomes

Other biasLow riskThe study appeared free of other sources of bias

Kim 2011

MethodsRandomized, single-blind study of perimenopausal or postmenopausal women with moderate or severe hot flushes. 2 groups: TKM acupuncture and SA


Participants54 perimenopausal and postmenopausal women (no menstruation for at least 3 months) having desired to receive treatment for hot flushes and complaining of moderate (able to continue activities) and severe hot flushes (not able to continue activities)

Women taking medication for hot flushes within the 8 weeks prior to the study; history of cancer within 5 years; having total hysterectomy and serious endocrine or vascular disorders; suffering from psychological problems; and having medical conditions such as uncontrolled hypertension, diabetes mellitus or vaginal bleeding of unknown origin within 6 weeks were excluded

Setting: The Dongguk University Ilsan Korean Medicine Hospital in South Korea


InterventionsTKM acupuncture:

20-minute treatments were given for 7 consecutive weeks (twice per week the 4 first weeks and once per week the remaining 3 weeks) by a traditional Korean medicine doctor (the same for both TA and SA group) having more than 4 years of clinical experience and certified by the Korean Ministry of Health and Welfare. 13 needles (0.30 mm) were inserted 0.2-10 mm deep at 7 points and manually stimulated. The 'de qi' sensation was the elicited response

SA:

20-minute treatments were given for 7 consecutive weeks (twice per week the 4 first weeks and once per week the remaining 3 weeks) by a TKM doctor (the same for both TA and SA group) having more than 4 years of clinical experience and certified by the Korean Ministry of Health and Welfare. 12 needles (identical to TA group) were inserted on 7 predefined non-acupuncture points without stimulation, to not elicit the 'de qi' sensation

For both groups, all participants were in a separate room with an eye bandage and no patient-practitioner communication was allowed


Outcomes
  • Changes in hot flushes scores at week 7 from the start of treatment. Hot flushes scores = hot flushes frequency at day and night (data assessment by diary) x hot flushes severity (data assessment by VAS, 0 to 10). Timing of assessment: each week for a period of 4 weeks prior to treatment, during the treatment (7 weeks) and for the 8 weeks following treatment
  • Frequency and severity of hot flushes
  • Vasomotor symptoms using the MRS, which consists of 11 questions divided into 3 subscales: psychological, somatic, and urogenital. Timing of assessment: at screening (week -4), at baseline (week 0), at the end of the treatment (week 7), and follow-up (week 15)


Source of fundingThe Korean Institute of Oriental Medicine


NotesFollow-up: 15 weeks (8 weeks after completion of treatment)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Random allocation software V1.0 (Department of Anaesthesia, Isfanhan University of Medical Science) was used to randomise patients into two groups. A block size of 4 was used"

Allocation concealment (selection bias)Unclear riskQuote: "The allocation of each patient was concealed by placing each random code in an opaque, sealed envelope. These envelopes were opened after the enrolment of the patient"

Comments: not mentioned if the envelopes were sequentially numbered

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "Patients were blinded to the type of acupuncture received. All participants were in a separate room with an eye bandage and no-patient-practitioner communication was allowed"

"All data was collected by a blinded assessor"

Incomplete outcome data (attrition bias)
All outcomes
Low riskFew dropouts and lost of follow-up (TA, 2 women; SA, 4 women). An ITT approach was used to conduct the analyses

Selective reporting (reporting bias)Low riskThe published report included all expected outcomes

Other biasLow riskThe study appeared free of other sources of bias

Kim 2010

MethodsMulticentre, randomized, controlled trial. 2 groups: acupuncture plus UC and UC alone


Participants175 peri- and postmenopausal women aged 45-60 years having a mean daily hot flush scores (daily frequency x severity) of 10 or higher for 1 week before screening visit

Perimenopausal was defined as menstrual irregularity or amenorrhoea of 3-11 months and postmenopausal as 1 of the following: 12 months of spontaneous amenorrhoea; 6 months of spontaneous amenorrhoea with FSH levels > 40 mIU/mL; 6 weeks' postsurgical bilateral oophorectomy with or without hysterectomy; or hysterectomy with at least 1 intact ovary

Women were excluded if they had uncontrolled hypertension, diabetes mellitus, required insulin injections, any type of thyroid dysfunction, past or present malignant tumours, severe dyslipidaemia, other infectious diseases, or systemic diseases, and if they were using hormones, antidepressants, gabapentin, SSRIs, or sedatives

Women were recruited through local newspaper advertisements, hospital postings, and notification in the community meeting

Setting: Kang-nam Kyung Hee Oriental Medical Center (Seoul), Dongguk International Hospital (Ilsan), Semyung University Hospital (Jecheon), Dong-Eui Medical Center (Busan), Korea


InterventionsAcupuncture plus UC:

Treatments were given by TKM physicians registered by the government with 3 years of clinical experience, 3 times per week for 4 consecutive weeks. Acupuncture points were selected according to recommendations of TKM clinical experts and are ST36, SP6, LI4, PC6, HT7, HT8, and CV4 and the 'De Qui' sensation were the elicited response. Needles were inserted 3-15 mm depending on the point selected, remained in place for 20 minutes, and were manipulated manually (intermittently). Needles used were 40 x 0.25 mm. Participants and physicians could communicate freely about participant's symptoms and general conditions

Follow-up at weeks 6 and 8. UC consisted of the use of non-prescription drugs for episodic or minor symptoms that were not related to hot flushes or supplements (including evening primrose oil, phyto-oestrogens, omega-3 fatty acids, calcium, and vitamins.

UC:

UC alone group received no acupuncture treatment for the 4-week study period and could use non-prescription drugs for episodic or minor symptoms that were not related to hot flushes or supplements (including evening primrose oil, phyto-oestrogens, omega-3 fatty acids, calcium, and vitamins

Additional acupuncture treatment, herb prescriptions, or therapeutic interventions by another TKM physician were not allowed during the treatment period for both groups

Follow-up at weeks 6 and 8


OutcomesPrimary outcome:

  • mean reduction in mean 24-h hot flush score using a self report diary from baseline to week 4


Secondary outcome:

  • mean reduction in menopause-related symptoms using the MRS


Timing of assessment of the main outcome: at baseline, and at week 1, 2, 3, 4, 6, and 8 after randomization


Source of fundingAcupuncture, Moxibustion, and Meridian Research Project (K09050) of the Korean Institute of Oriental Medicine


NotesFollow-up: 2 weeks (after completion of treatment, i.e. weeks 6 and 8)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "A separate randomization sequence was computer generated at the central coordinating centre and provided for each local treatment centre"

Allocation concealment (selection bias)Unclear riskMethod not reported

Blinding (performance bias and detection bias)
All outcomes
High riskQuote: "This was an open trial, so patient blinding was unavailable. We failed to blind the assessor to assignment of patient. Instead, all outcomes were self-administered by patients, and the researcher who was separated from the treatment procedure collected the data. Data were sent to the central research centre, and personal who were independent of this study entered the data"

Incomplete outcome data (attrition bias)
All outcomes
Low riskMissing outcome data are not balanced across intervention groups (acupuncture plus UC, dropouts 7%; UC, dropouts 19%) and reasons for missing data differ

Analyses were conducted with an ITT approach

Missing data were replaced with the last observation value

Selective reporting (reporting bias)Low riskThis study appeared free from selective reporting

Other biasLow riskThis study appeared free from other bias

Nedstrand 2006

MethodsRandomized, controlled trial in women treated for breast cancer. 2 groups: AR and EA


Participants38 women treated for breast cancer aged 30-64 years, with treatment-induced or spontaneous menopause, that had last menstruation at least 6 months prior, experiencing at least 2 flushes per 24 h and regarding the flushes severe enough to require treatment, and wishing to receive treatment for vasomotor symptoms

Women that took HT in the last 6 months; had severe metabolic, endocrine, or thromboembolic disease; had uncontrolled hypertension and used sedatives daily; and taken anxiolytic or antidepressant medication were excluded

Study setting: the outpatient clinics at the Departments of Oncology and Breast Surgery at the Linköping University Hospital in Sweden


InterventionsAR:

Weekly 60-minute group sessions (5-6 in each group) for a 12-week period given by a physician familiar with AR having undergone training but not having formal education in behaviour therapy. This instructor was self trained to use technique of AR, and was supervised by a certified clinical psychologist. Participants were asked to train at home twice daily, to discuss the results of training each week at the group session and were given information about menopause and theories of hot flushes. The following components were explored during the AR programme: progressive relaxation, cue-controlled relaxation, differential relaxation, and rapid relaxation.

EA:

30-minutes treatment given twice per week the first 2 weeks and once a week for another 10 weeks by a physiotherapist experienced and skilled in acupuncture treatment. 12 sterile stainless-steel needles were inserted 5-20 mm into the skin and were twirled to elicit the 'De qui' sensation. 4 of them were in the lower back, BL23 and 32 bilaterally, and were attached to an electrical stimulator giving a low burst frequency of 2 Hz alternating current stimulation. A non-painful local muscle stimulation.


Outcomes
  • General mood using the Mood Scale (measuring 3 subscales; from 1 to 4)
  • General psychological well-being using The Symptom Checklist, (measuring 9 subscales; from 0 to 4, the lower score the better)
  • Climacteric symptoms intensity using a VAS (from 0 to 10)
  • Climacteric symptoms using the Kupperman index (from 0 to 3)
  • Frequency of hot flushes per 24 h using a logbook


Timing of assessment: at baseline; after 4, 8, and 12 weeks of therapy; and at 3 and 6 months after completion of therapy for the first 4 outcomes cited above; 2 weeks prior to treatment, daily for the 12-week treatment period, and for the 6-month follow-up in daily every fourth week for hot flushes frequency


Source of fundingThe Swedish Medical Research Council, The Swedish Foundation for Health Care Sciences and Allergy Center, Cancer and Trafikskadades Förbund, and The Lions Foundation


NotesFollow-up: 6 month (after completion of treatment)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of generating random sequence not reported

Allocation concealment (selection bias)Unclear riskQuote: "Randomization to AR or EA was performed using identical, opaque, sealed envelopes containing a label naming the treatment." Not reported whether envelopes were sequentially numbered

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants and therapists were not blinded because of 2 different therapies applied

Comments: not reported if the others involved in the research were blinded

Incomplete outcome data (attrition bias)
All outcomes
High riskHigh dropout rate (AR, 26%; EA, 11%)

Reasons for withdrawal mentioned

Quote: "Missing values were compensated for by the mean of the score from the time before and after in each case"

No mention of ITT approach

Number of women analysed at week 12 and at the end of the 6-month follow-up is unclear

Selective reporting (reporting bias)Low riskThis study appeared free from selective reporting

Other biasUnclear riskFew information about characteristics of participants at baseline

Nir 2007

MethodsRandomized, placebo-controlled pilot study. 2 groups: active acupuncture and SA


Participants29 postmenopausal women aged 45-65 having: no menstrual period for at least 6 months or at least 6 weeks post-bilateral oophorectomy; a baseline oestradiol concentration of less than 50 pg/mL and normal TSH level; a mean of at least 7 moderate-to-severe hot flushes/24 h or a mean of at least 70 hot flushes per week during the screening/baseline phase

Women having endocrine disorders, including unstable thyroid disease, known or suspected oestrogen-dependent neoplasia, known psychiatric disorders, abnormal results on a laboratory TSH test, a baseline oestrogen level higher than 50 pg/mL; having received any treatment for hot flushes, including black cohosh, phyto-oestrogens, or acupuncture for 6 weeks before the study; having any unstable medical conditions; using any medication known to affect vasomotor symptoms (e.g. clonidine, veralipride, SSRIs); and having received acupuncture within the past year were excluded

Women were recruited through advertisements at community clinics

Setting: community clinics of San Francisco Bay Area, US


InterventionsActive acupuncture:

9 acupuncture sessions, twice weekly for the first 2 weeks and once weekly for the remaining 5 weeks. Disposable, stainless-steel filiform needles (appearing identical to placebo) were inserted for 20 minutes at 5-7 active treatment points (3-6 points according to participant's primary TCM-defined pattern for hot flushes, and 1 or 2 points according to secondary TCM-defined pattern). Stimulation was manual and the 'De qui' sensation was the elicited response. 5 licensed acupuncturists provided both active and placebo treatments. They received training to maintain a standardized interaction with all participants. Follow-up: 1 month

SA:

9 acupuncture sessions, twice weekly for the first 2 weeks and once weekly for the remaining 5 weeks. Disposable, stainless-steel filiform needles (appearing identical to active needles and having blunt tips that touch the skin before retracting up into a hollow shaft handle) were used at 5-7 sham points among 10 non-valid points located off any acupuncture channels. There was no skin penetration and stimulation was manual. Follow-up: 1 month


OutcomesPrimary:

  • severity of hot flushes per 24 h using daily logs
  • frequency of hot flushes per 24 h using daily logs


Timing of assessment of the main outcome: at baseline, every week for the 7-week treatment, at the end of treatment, at the end of the 1-month follow-up

Secondary:

  • quality of life using the Menopausal Specific Quality of Life questionnaire


Source of fundingNot reported


NotesFollow-up: 1 month (after completion of treatment)

There were no significant differences between groups at baseline in severity, frequency, body mass index, age at menopause, years since last menstrual period, history of or time on HT but there was a significant difference in age


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "In order to balance the number of placebo and active treatments among the acupuncturists, we created a separate randomization table for each acupuncturist by generating a random string of permutations of two elements (blocked randomization)"

Allocation concealment (selection bias)Unclear riskQuote(from the author): "The subjects underwent the same protocol for the first acupuncture visit (anamnesis, questions regarding the hot flashes etc.) nature which determined which points would be used and only after this session they were divided to the treatment and placebo group using a sealed envelope with allocation. Not reported whether envelopes opaque, sealed and sequentially numbered"

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote (from the report): "To minimize the potential confounding effect of the acupuncturist’s awareness of which treatment participants were receiving, acupuncturists were trained to maintain a standardized interaction with all participants. All sessions were audio-taped, of which five percent were randomly selected and reviewed for adherence to the standardized protocol by an independent rater who remained blind to the type of treatment received"

Quote (from the author): "Placebo treatment included none acupuncture points but to the inexperienced patient these are very similar (proximal) to actual points and similar in number to the treatment group. The acupuncturists were instructed on how to verbally conduct the session, to avoid any conversation other than the pre determined protocol. This included length of the session and wording. Investigators were not aware of the allocation of the patients to treatment or placebo group during the study when meeting with the patients in the first session as well as when reviewing hot flash log data"

Incomplete outcome data (attrition bias)
All outcomes
High riskHigh dropout rate (active acupuncture, 17%; SA, 24%)

Reasons mentioned but some are likely to be related to true outcome (dissatisfied with treatment). The total number of women analyzed was 12 in the active acupuncture group and 17 in the SA (according to the participant flow diagram).

ITT approach and imputation method not reported

Selective reporting (reporting bias)Low riskThe published report included all expected outcomes

Other biasHigh riskThere was a significant difference in age between the 2 groups at baseline

Source of funding not mentioned

Painovich 2012

MethodsPilot, randomized, single-blind, placebo-controlled trial. 3 groups: TA, SA, and waiting list control


Participants21 women older than 40 years with menopause-related vasomotor symptoms.

Inclusion criteria included at least 7 hot flushes per day and at least 1 missed menstrual cycle or spontaneous or medically induced menopause.

Exclusion criteria included concomitant illness with reasonable likelihood of limiting survival to less than 1 year; current substance abuse; known, suspected, or planned pregnancy in the next year; other concomitant menopause treatment; participating in acupuncture treatment or formal psychological stress management programme within the last year; participating in another treatment of vasomotor symptoms, unless willing to stop it 4 weeks in advance of participation; human immunodeficiency virus infection; chronic or active hepatitis; or other blood-borne illness

Setting: Cedars-Sinai Heart Institute, Los Angeles, CA, US


InterventionsIntervention period was 3 months; participants received treatment 3 times per week for a maximum total of 36 treatments. Data and specimen collections were carried out at weeks 0, 5, and 12

TA:

11 front points, which were placed with the women lying supine, and 7 back points, which were accessed in prone position. The needles were inserted 0.5-1.5 inches and then manually stimulated to reach 'de-qi' and then retained for 30 minutes. The needles were secure with adhesive tape

SA:

The sham points were selected by the team to be proximate to the TA site. The disposable acupuncture needle and plastic needle tube were placed on the sham points, manipulated without skin penetration and secure with adhesive tape

Waiting list control:

The women received no treatment for 3 months, underwent exit testing, and subsequently had the option of 1 month of complimentary TA


Outcomes
  • Frequency of hot flushes in a 7-day diary
  • Severity of hot flushes in a 7-day diary
  • Severity score was computed as the mean severity-weighted number of vasomotor symptoms per day
  • Menopause Specific Quality of Life Questionnaire (MENQOL)
  • Sleep quality: Pittsburgh Sleep Quality Index
  • Depression: Beck Depression Inventory II
  • Anxiety: State-Trait Anxiety Inventory
  • Hypothalamic-pituitary-adrenal measurements


Source of fundingNational Institutes of Health - National Center for Alternative and Complementary Medicine and General Clinical Research Center grant from the National Center for Research Resources


NotesStudy approved by the Cedars-Sinai Institutional Review Board


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskParticipants were allocated to 1 of 3 study arms with equal probability using a randomized block design after signing the consent form

Allocation concealment (selection bias)Unclear riskMethod not reported

Blinding (performance bias and detection bias)
All outcomes
Low riskThe participants were blinded as to the randomization status, the waiting list control group necessarily knew their randomization status. Both TA and SA groups were required to wear eye covers throughout the treatment

The treating acupuncturists were unblinded, to know whether to deliver TA or SA

Comments: nothing mentioned concerning the blinding of the outcome assessors

Incomplete outcome data (attrition bias)
All outcomes
Low risk27 dropped out, 16 before treatment began, 8 in each acupuncture group and 11 from the waiting control despite being offered free acupuncture after the 3-month waiting period

Selective reporting (reporting bias)Low riskThe published report included all expected outcomes

Other biasLow riskThe study appeared free from other bias

Park 2009

MethodsRandomized, clinical trial. 3 groups: moxibustion 1, moxibustion 2, and waiting list


Participants28 perimenopausal or postmenopausal women aged 45-60 years experiencing at least 5 moderate (warm sensation with a transient and insignificant impact on the participant's activity) to severe (hot sensation with sweating that caused significant disruption to a participant's daily activity) hot flushes every 24 h and had natural or surgical menopause

Women having uncontrolled hypertension, diabetes mellitus requiring insulin injections, any type of thyroid dysfunction, past or current malignant tumours, severe dyslipidaemia, other infectious diseases or systemic diseases; using hormones, antidepressants, gabapentin, SSRIs, or sedatives; using transdermal HT within 4 weeks or oral hormone medication within 8 weeks were excluded

Women were recruited from Daejeon, South Korea using local newspaper advertisements and notices posted at various clinics

Setting: South Korea


InterventionsMoxibustion 1:

Moxibustion capsules formulated as a disposable adhesive, and were composed of a moxa pillar attached to the base of the device. Total length of the moxibustion device was 25 mm, of which 18 mm constituted the moxa pillar. Acupoints used were consistent with evidence from clinical practice. There were 4 acupoints: CV12, CV4, bilateral ST36, SP6. 5 moxibustion capsules used at each point in a single session. Treatment procedures were identical in Moxa 1 and Moxa 2. Treatments were given for 4 weeks (4 times per week for the first 2 weeks and 3 times per week for the 2 remaining weeks) by a qualified acupuncture doctor licensed in the Republic of Korea having had 6 years of training in acupuncture and moxibustion

Moxibustion 2:

The same moxibustion capsules were used in Moxa 1 and Moxa 2. Acupoints used were consistent with evidence in published literature. 5 moxibustion capsules were used at each point in a single session. There were 4 acupoints: GV4, CV3, CV6, bilateral UB23. Participants received this type of acupuncture 4 times per week for the first 2 weeks and 3 times per week for the 2 remaining weeks. Treatments were given for 4 weeks (4 times per week for the first 2 weeks and 3 times per week for the 2 remaining weeks) by a qualified acupuncture doctor licensed in the Republic of Korea having had 6 years of training in acupuncture and moxibustion

Waiting list:

The 10 participants in this group did not received any treatment for 5 weeks (including the 1-week follow-up period)


OutcomesPrimary outcomes:

  • frequency of hot flushes for 1 week using VAS
  • intensity of hot flushes for 1 week using VAS


Time of assessment of the main outcomes: at baseline, during treatment (at 1, 2, and 3 weeks), at the end of treatment (week 4), and for a 2-week follow-up period (week 6)

Secondary outcomes:

  • quality of life using the Menopausal-Specific Quality of Life Scale
  • climatic symptoms using the MR


Source of fundingKorea Institute of Oriental Medicine (K08010)


NotesFollow-up: 2 weeks (after completion of treatment); and 1 week for the waiting list group


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Randomization was performed by the study coordinator using a computerized list with an assignment ratio of 2:2:1 (Moxa 1/Moxa 2/control)”

Allocation concealment (selection bias)Unclear riskMethod not reported

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "All analyses were conducted blind to group allocation”

"[The participants] were not told which treatment they would received. In addition, to eliminate observation bias, the two assessors were blind to the intervention group before analysis of data"

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "Analyses were performed with the ''intention to treat'' population for which all participants were randomised at least once after moxibustion treatment (missing data were replaced with the last observation value)''

Moderate dropout rate (10% for both moxibustion group 1 and 2; 0% for the waiting list)

Reasons for dropouts are mentioned

Selective reporting (reporting bias)Low riskThe published report included all expected outcomes

Other biasLow riskThis study appeared to be free of other sources of bias

Venzke 2010

MethodsRandomized, single-blind, controlled clinical trial. 2 groups: TCM acupuncture and SA


Participants51 postmenopausal women having vasomotor symptoms (hot flushes, night sweats) more than 14 events of any severity per week, or more than 5 moderate-to-severe events (waking up soaked, needed to change clothing); having no menstrual period for at least 12 months; having natural menopause; not using ET/HT or herbal treatment for menopausal symptoms for at least 3 months before enrolment; and not having received acupuncture treatments within the last 6 months; able to keep regular appointment

Women having artificial menopause (due to surgery, radiotherapy, or medication), a pacemaker, an history of heart disease, an history of active alcohol or drug abuse within the last year before enrolment; human immunodeficiency virus disease, fibromyalgia, uncontrolled thyroid disease, uncontrolled hypertension and any systematic illness, condition, or personal situation (such as an unstable living situation) that might render the person unable to complete the study, fulfil the demands of the study, interfere with data interpretation, or create undue risk were excluded

Women were recruited through advertisements in the local newspaper, brochures displayed in local physician's surgery, and by word of mouth

Setting: Sky Lake Medical Center in a small city, Klamath Falls, in rural area of Eastern Oregon, US


InterventionsTCM acupuncture:

25-minute treatment given for 12 weeks twice a week for 4 weeks and once a week for 8 weeks) by a licensed acupuncturist trained in TCM-style acupuncture and having expertise in hot flushes with menopausal women and women with breast cancer. TCM pattern differentiation and selection of acupuncture points were based on several TCM sources. Stimulations received were manual and electrical. Hwato needles (1 inch/34 gauge and 1.1/2 inch/32 gauge) without tubes were used. During each treatment, 6-12 acupuncture points were selected among the following: UB23-20-15-17, Du9-4-24, Sp9-6, right Lu7, left Ki6, Ki3-7, H6-7, Liv3, and GB20. The 'De Qui' sensation was the response elicited. For electrical stimulation, acupuncturist used 4 needles (bilateral UB23 and SP6) connected to an EA device (ITO, model IC 1107) and stimulated at a frequency of 2 Hz. For manual stimulation, the remaining needles were stimulated again manually after 15 minutes. The needle retention time was 25 minutes. Advice regarding diet and exercise was also given to women

SA:

25-minute treatment given for 12 weeks (twice a week for 4 weeks and once a week for 8 weeks) by a licensed acupuncturist trained in TCM-style acupuncture and having expertise in hot flushes with menopausal women and women with breast cancer. Streitberger and Kleinhenz needles as well as small plastic rings for no penetration of the skin were used (2 on the back, 2 on the lower legs, and 2 on the forearms). 4 of the placebo needles were connected to a disabled acupuncture device (ITO, model IC 1107). The other 2 placebo needles had manual stimulation. The specific points were away any acupuncture meridians. The acupuncturist had expertise in hot flushes with menopausal women and women with breast cancer. Advice regarding diet and exercise were also given to women


OutcomesPrimary outcomes:

  • hot flush scores using diary
  • numeric scores on the following scales: Greene Climacteric Scale, Beck Depression Inventory, and Beck Anxiety Scale


Timing of assessment of the main outcome: at baseline, at week 4 during treatment, and at week 13 and 24 after treatment


Source of fundingMerle West Center for Medical Research (Klamath Falls, Oregon)


NotesFollow-up: 12 weeks (after completion of treatment)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "At the start of the study, randomization was then accomplished by asking study subjects to draw an envelope. In each envelope there was a small piece of paper with the typed letter A or B. Subjects who drew an A were randomised to the PA [placebo acupuncture] group; subjects who drew B were randomised to RA [real acupuncture] group"

Allocation concealment (selection bias)Unclear riskQuote: "At the start of the study, randomization was then accomplished by asking study subjects to draw an envelope. In each envelope there was a small piece of paper with the typed letter A or B. Subjects who drew an A were randomised to the PA [placebo acupuncture] group; subjects who drew B were randomised to RA [real acupuncture] group"

Rationale for judgement: unclear whether allocation might be predictable as envelopes ran out

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "This study was designed as a single-blind, randomised, controlled clinical trial"

"During the final visit study subjects were asked to guess whether they had received placebo or real acupuncture, and at what stage they came to that conclusion. This helped us assess how successful our blinding was"

Comments: participants blinding only

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "A total of 56 subjects were randomised and 51 of these completed the study." "RA was given to 27 and PA to 24 of the 51 subjects who completed the study." (Total dropout rate was 9%)

Reasons for dropouts are not reported

Imputation method and use of an ITT approach to conduct analyses are not reported

Selective reporting (reporting bias)Low riskThe published report included all expected outcomes

Other biasLow riskThe study appeared free of other sources of bias

Vincent 2007

MethodsProspective, randomized, single-blind, sham-controlled trial. 2 groups: medical acupuncture and SA


Participants103 perimenopausal (3 or more months of self reported menstrual irregularity or amenorrhoea) and postmenopausal (amenorrhoea for 12 or more months) women aged 45-59 years and experiencing a mean of 5 or more hot flushes per day. Women using oestrogen, soy, progesterone, vitamin E, or black cohosh; using non-prescription drugs, gabapentin, or antidepressants specifically for the treatment of hot flushes within the previous month; using warfarin; having skin disorders with skin breakdown such as eczema or psoriasis; having a pacemaker or prosthetic joints; having active chemotherapy; and suffering of diabetic neuropathy were excluded

Setting: Mayo Clinic General Clinical Research Center, US


InterventionsMedical acupuncture:

Treatments were given twice per week for 5 weeks by an acupuncturist (the same for both medical and SA) licensed by the Minnesota Board of Medical Practice and having 5000 h of experience. The needling was administered in 12 acupuncture points (SP4 unilateral, SP6 bilateral, He7 bilateral, Ll11 bilateral, Liv2 bilateral, Ki6 unilateral, LU7 unilateral right, PC6 unilateral left, GB34 bilateral, Liv3 bilateral, Ren4, GB20 bilateral). Needles were inserted 0.5-3 cm into the skin, and the 'De qui' sensation was the elicited response

Follow-up: 7 weeks

SA:

Needling administered in non-acupuncture, non-meridian areas, whenever possible 5 cm or more away from the actual acupuncture point. Treatments were given twice a week for 5 weeks

Follow-up: 7 weeks


OutcomesPrimary: daily hot flush score (frequency x severity) using a diary

Timing of assessment: at baseline, and every week for the 5-week treatment and for the 7-week follow-up period


Source of fundingMayo Foundation Award


NotesFollow-up: 7 weeks (after completion of treatment)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Participants were randomized to medical or sham acupuncture using a stratified randomization schedule. Stratification was done using menopausal status to ensure equal distribution of peri- and postmenopausal women among the two groups. A blocked size of four was used"

Allocation concealment (selection bias)Unclear riskMethod not reported

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote (from the author): "Patients were blinded to the group assignment. We also did not include any patients who had previous acupuncture so they would not know if it was actual or sham acupuncture. We did not blind the investigators"

Incomplete outcome data (attrition bias)
All outcomes
Low riskDropout rate was about 10% (SA: 13%; medical acupuncture: 10%)

Reasons for attrition were reported (not related to true outcome)

Quote: "The last observation carried forward was used for imputing missing data per an intention-to-treat model"

Selective reporting (reporting bias)Low riskThe published report included all expected outcomes

Other biasLow riskThe study appeared free of other sources of bias

Wyon 2004

MethodsRandomized controlled trial. 3 groups: EA, SNI, and ET


Participants28 postmenopausal women aged 48-63 years with vasomotor symptoms and a spontaneous menopause at least 6 months previously. Women were excluded if they had a severe metabolic, thromboembolic, or endocrine disease; they had uncontrolled hypertension (> 95 mmHg diastolic); they were using sedative, anxiolytic, or antidepressant medication; if they were using narcotics; they were doing regular exercise more than once per week

Setting: gynaecological outpatient clinic of the Linköping University Hospital in Sweden


InterventionsEA:

30-minute treatment given by an experienced physiotherapist skilled in acupuncture for 12 weeks (twice per week for the first 2 weeks and once a week for the next 10 weeks). 12 needles (stainless-steel, Hwato 0.25 mm diameter, 15 mm long, and 0.30 mm diameter and 30 mm long) were inserted 5-20 mm into the skin at different point locations (bilaterally, B15-23-32; unilaterally, HT7, SP6-9, LR3, PC6, GV20). 4 needles in lower back were attached to an electrical stimulator (IC-1107, Ito Co., Ltd, Japan) with a burst frequency of 2 Hz alternating current stimulation. The 'De qui' and a non-painful local muscle contractions were the elicited responses

Follow-up: once a week for the next 6 month after treatment

SNI:

30-minute treatment given by an experienced physiotherapist skilled in acupuncture for 12 weeks (twice per week for the first 2 weeks and once a week for the next 10 weeks). Small-dimension needles (Hwato, 0.25 mm diameter, 15 mm long) were inserted parallel to the skin 1-5 cm away from EA points. 3 needles (BL15-23-32) were moved laterally on the back about 10-15 cm. No additional stimulation after insertion was elicited

Follow-up: once a week for the next 6 months after treatment

ET:

Women were given oral 2 mg 17β-oestradiol for 12 weeks. They were suggested to continue their ET with additional sequential progestogens given monthly

Follow-up: once a week for the next 6 month after treatment


OutcomesPrimary:

  • frequency of hot flushes using a logbook


Timing of assessment of the main outcome: before treatment; after 4, 8, and 12 weeks of treatment; and 12 and 24 weeks after the end of therapy

Secondary:

  • menopausal symptoms using a slightly modified Kupperman index
  • general climacteric symptoms using a general summary of the climacteric symptom intensity scale


Source of fundingThe Swedish Medical Research Council grant to K2001-72x-12651-O4B, The Swedish Foundation for Health Care Sciences and Allergy Research and Cancer and Trafikskadades Förbund, The Lions Foundation


NotesNo significant difference of groups at baseline except that women in the oestrogen group were slightly younger

Follow-up: 6 month (after completion of treatment)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod not reported

Allocation concealment (selection bias)Unclear riskQuote: "Randomization was performed by the use of identical, opaque, sealed envelopes, containing label to determine the treatment." Not reported whether envelopes sequentially numbered

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "The gynaecologists and nurses evaluating the patients were blind to treatments, i.e. at evaluation, the physician and research nurse did not know which acupuncture treatment each women had and not until after analysis of the results did we unveil the treatment modalities. Furthermore, the patients were only informed that two different modalities were used but not that we expected one to be more efficient"

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "All women randomized to electro-acupuncture and estradiol therapy completed the 12 weeks of treatment"

At 6 months, few dropouts and exclusions (EA :4, SNI :1, ET:6)

Reasons for withdrawals reported

No ITT analysis

Selective reporting (reporting bias)Low riskThe published report included all expected outcomes

Other biasLow riskThe study appeared free of other sources of bias

Zhou 2011

MethodsRandomized controlled trial. 2 groups: acupuncture, auricular acupressure, and HT


ParticipantsBilaterally ovariectomized Chinese women suffering from menopausal hot flushes presenting a normal TSH level and oestradiol concentration < 50 pg/mL. They were excluded if they were under other medical treatment during the research period, had metabolic, renal, anaphylactic, or endocrine disease, or suffered from primary hypertension, primary hypotension, chronic anaemia, tuberculosis, a mental disorder, or a chronic condition; body mass index more than 24, or cigarette smoker. Women were recruited by advertisement.

Setting: Zhejiang University, University of Chinese Medicine, Liaoning University of Chinese and Colorado School of Traditional Chinese Medicine


InterventionsAcupuncture:

40-minute treatment given twice a week for 12 weeks. 8 points were selected: SP6, GB20, LI4, LI11, CV4, GV14, KI7, and EX-CA1. The needles were manipulated twice during the treatment using a twirling technique in a small range. The manipulation lasted 30 seconds for each acupoint. Sterilized disposable needles (0.35 mm x 40 mm) were inserted using the double hand-needle insertion technique. The depth of insertion was adjusted based on the woman's body size and the permissible depth of insertion of the specific acupoint

Auricular acupressure:

Height auricular acupoints were selected: AH6a, TF4, TG2p, AT4, CO18, CO10, CO15, and Co12. Pieces of plaster with magnetic beads of proper size and good quality were stuck to the acupoints, which were then pressed slightly until the person had an aching pain, numbness, distension, and a warm sensation. The participants were asked to press the acupoints by themselves 6 times a day for a 3-minute duration each time. The auricular acupressure was alternatively conducted on both ears every 2 days. The plaster was changed once a week

HT:

The participants were prescribed with oral Livial (tibolone) of 1 tablet a day (2.5 mg/tablet) for 12 consecutive weeks


OutcomesPrimary outcomes:

  • number of hot flushes occurred during 24 h
  • severity of hot flushes per 24 h using a severity score


Time of assessment: at baseline, at the end of treatment, and after a 4-week follow-up period

Secondary outcomes:

  • serum levels of FSH, LH, and oestradiol


Source of fundingNatural Medicine Research UK, China Postdoctoral Science Foundation, Zhejiang Traditional Chinese Medicine Foundation, Zhejiang Provincial Postdoctoral Science Foundation, Outstanding Young Medical Scientist Foundation of Zhejiang Province


NotesFollow-up: 4 weeks (after completion of treatment)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Subjects were randomized to either the acupuncture and auricular acupressure group or the HT group with the use of a randomization chart constructed in Microsoft Excel that randomized numbers into two groups"

Allocation concealment (selection bias)Unclear riskMethod not reported

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants knew which treatment (acupuncture + auricular acupressure or HT) they were getting. The acupuncturist was not blinded to the treatment

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "Three subjects were considered missing cases during the study and were excluded from analysis"

Reasons for withdrawals reported

No ITT analysis

Selective reporting (reporting bias)Low riskThe published report included all expected outcomes

Other biasLow riskThis study appeared free from other bias

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Azizi 2011Combination of treatments

Borud 2010Not an RCT

Castelo Branco 2011No washout period between interventions

Cohen 2003Data on vasomotor symptoms

Cummins 2000Not an RCT

Davies 2001Not an RCT

De Valois 2003Not an RCT

De Valois 2010Not an RCT

Facchinetti 1989Data on acupuncture techniques

Frisk 2012Data on vasomotor symptoms were the same presented in Frisk's study in 2008

Grilli 1989Data on acupuncture techniques

Gui-e 2000The trial does not include perimenopausal, menopausal, or postmenopausal women who experiencing hot flushes at baseline

Guévin 2009Not an RCT

Harris 2002Not an RCT

Hervik 2010Not an RCT

Hu 2005Not an RCT

Huang 2006Data are identical to Nir's study in 2006

Huazhang 2008There is no comparison between acupuncture intervention and placebo, control or other treatment

Huo 2004No data on menopausal hot flushes or on other menopausal symptoms

Ji 1998Not an RCT

Jin 2007Data on vasomotor symptoms

Kao 2012No data on hot flushes

Lesi 2012Meeting abstract. Uncontrolled experimental pilot study

Li 2005Data on vasomotor symptoms

Mingling 1991Not an RCT

Nedstrand 2005Data are identical to Nedstrand's study in 2006

O'Brien 2010Data on vasomotor symptoms

Otte 2011Not an RCT

Perez 2005Meeting abstract

Porzio 2002Not an RCT

Sandberg 2002No assessment of hot flushes

Spetz Holm 2012Not an RCT

Sunay 2011Not an RCT

Towlerton 1999Not an RCT

Tukmachi 2000Not an RCT

Walker 2007Not an RCT

Walker 2008Meeting abstract. Data are identical to Walker's study in 2010

Walker 2010Data on vasomotor symptoms

Wyon 1995Data on vasomotor symptoms

Xia 2008Data on vasomotor symptoms

Xiaoming 2005Not an RCT

Xu 2004Complex therapy included acupuncture, traditional Chinese medicine drug, and Nieji were used in treatment group

Zaborowska 2007Duplicate of Wyon's study in 2004

Zhang 2006Not an RCT

Zhenya 2001Not an RCT

Zhou 2006Not an RCT

 
Comparison 1. Acupuncture versus sham acupuncture

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Hot flush frequency (number/day)8414Mean Difference (IV, Random, 95% CI)-1.13 [-2.55, 0.29]

    1.1 Traditional vs. sham acupuncture
6332Mean Difference (IV, Random, 95% CI)-1.65 [-3.62, 0.32]

    1.2 Electroacupuncture vs. sham acupuncture
128Mean Difference (IV, Random, 95% CI)-0.30 [-3.60, 3.00]

    1.3 Changes in frequency of hot flushes from baseline to end of study
154Mean Difference (IV, Random, 95% CI)-0.20 [-1.68, 1.28]

 2 Hot flush severity6297Std. Mean Difference (IV, Random, 95% CI)-0.45 [-0.84, -0.05]

    2.1 Traditional vs. sham acupuncture
4215Std. Mean Difference (IV, Random, 95% CI)-0.44 [-0.98, 0.10]

    2.2 Electroacupuncture vs. sham acupuncture
128Std. Mean Difference (IV, Random, 95% CI)-0.09 [-0.83, 0.66]

    2.3 Changes in severity of hot flushes from baseline to end of study
154Std. Mean Difference (IV, Random, 95% CI)-0.77 [-1.33, -0.22]

 3 Hot flush frequency in trials less than 12 weeks6335Mean Difference (IV, Random, 95% CI)-1.68 [-3.61, 0.24]

    3.1 Traditional vs. sham acupuncture
5281Mean Difference (IV, Random, 95% CI)-2.29 [-4.88, 0.31]

    3.2 Changes in frequency of hot flushes from baseline to end of study
154Mean Difference (IV, Random, 95% CI)-0.20 [-1.68, 1.28]

 4 Hot flush frequency in trials of 12 weeks and more3103Mean Difference (IV, Random, 95% CI)0.15 [-1.11, 1.40]

    4.1 Traditional vs. sham acupuncture
151Mean Difference (IV, Random, 95% CI)0.10 [-1.47, 1.67]

    4.2 Electroacupuncture vs. sham acupuncture
128Mean Difference (IV, Random, 95% CI)-0.30 [-3.60, 3.00]

    4.3 Changes in frequency of hot flushes from baseline to end of study
124Mean Difference (IV, Random, 95% CI)0.60 [-2.13, 3.33]

 5 Hot flush frequency in cancer trials2126Mean Difference (IV, Random, 95% CI)-6.20 [-16.03, 3.64]

    5.1 Traditional vs. sham acupuncture
2126Mean Difference (IV, Random, 95% CI)-6.20 [-16.03, 3.64]

 6 Hot flush severity in cancer trials160Mean Difference (IV, Fixed, 95% CI)-2.40 [-3.50, -1.30]

 7 Hot flush severity in trials less than 12 weeks5269Std. Mean Difference (IV, Random, 95% CI)-0.50 [-0.95, -0.06]

    7.1 Traditional vs. sham acupuncture
4215Std. Mean Difference (IV, Random, 95% CI)-0.44 [-0.98, 0.10]

    7.2 Changes in severity of hot flushes from baseline to end of study
154Std. Mean Difference (IV, Random, 95% CI)-0.77 [-1.33, -0.22]

 8 Hot flush severity in trials of 12 weeks and more252Std. Mean Difference (IV, Random, 95% CI)-0.09 [-0.63, 0.46]

    8.1 Electroacupuncture vs. sham acupuncture
128Std. Mean Difference (IV, Random, 95% CI)-0.09 [-0.83, 0.66]

    8.2 Changes in severity of hot flushes from baseline to end of study
124Std. Mean Difference (IV, Random, 95% CI)-0.09 [-0.89, 0.72]

 9 Quality of life3104Std. Mean Difference (IV, Random, 95% CI)0.12 [-0.26, 0.51]

    9.1 Traditional vs. sham acupuncture
280Std. Mean Difference (IV, Random, 95% CI)0.11 [-0.33, 0.55]

    9.2 Changes in quality of life from baseline to end of study
124Std. Mean Difference (IV, Random, 95% CI)0.16 [-0.64, 0.96]

 10 Quality of life in trials less than 12 weeks129Std. Mean Difference (IV, Random, 95% CI)0.13 [-0.61, 0.87]

    10.1 Traditional vs. sham acupuncture
129Std. Mean Difference (IV, Random, 95% CI)0.13 [-0.61, 0.87]

 11 Quality of life in trials of 12 weeks and more151Std. Mean Difference (IV, Random, 95% CI)0.10 [-0.45, 0.66]

    11.1 Traditional acupuncture vs. sham acupuncture
151Std. Mean Difference (IV, Random, 95% CI)0.10 [-0.45, 0.66]

 
Comparison 2. Acupuncture versus hormone therapy

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Hot flush frequency (number/day)3114Mean Difference (IV, Random, 95% CI)3.18 [2.06, 4.29]

    1.1 Electroacupuncture vs. HT
271Mean Difference (IV, Random, 95% CI)3.40 [1.96, 4.84]

    1.2 Acupuncture + auricular acupressure vs. HT
143Mean Difference (IV, Random, 95% CI)2.84 [1.07, 4.61]

 2 Hot flush severity284Std. Mean Difference (IV, Random, 95% CI)0.53 [-0.14, 1.20]

    2.1 Electroacupuncture vs. HT
141Std. Mean Difference (IV, Random, 95% CI)0.89 [0.24, 1.53]

    2.2 Acupuncture + auricular acupressure vs. HT
143Std. Mean Difference (IV, Random, 95% CI)0.20 [-0.40, 0.80]

 3 Hot flush severity in cancer trials141Std. Mean Difference (IV, Random, 95% CI)0.89 [0.24, 1.53]

    3.1 Electroacupuncture vs. HT
141Std. Mean Difference (IV, Random, 95% CI)0.89 [0.24, 1.53]

 4 Quality of life141Mean Difference (IV, Random, 95% CI)0.11 [0.01, 0.21]

    4.1 Electroacupuncture vs. HT
141Mean Difference (IV, Random, 95% CI)0.11 [0.01, 0.21]

 
Comparison 3. Electroacupuncture versus relaxation

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Hot flush frequency (number/day)138Mean Difference (IV, Random, 95% CI)-0.40 [-2.18, 1.38]

    1.1 Electroacupuncture vs. relaxation
138Mean Difference (IV, Random, 95% CI)-0.40 [-2.18, 1.38]

 2 Hot flush frequency in cancer trials138Std. Mean Difference (IV, Random, 95% CI)-0.14 [-0.78, 0.50]

    2.1 Electroacupuncture vs. relaxation
138Std. Mean Difference (IV, Random, 95% CI)-0.14 [-0.78, 0.50]

 3 Hot flush severity1Mean Difference (IV, Random, 95% CI)Subtotals only

    3.1 Electroacupuncture vs. relaxation
138Mean Difference (IV, Random, 95% CI)0.20 [-0.85, 1.25]

 4 Quality of life1Mean Difference (IV, Random, 95% CI)Subtotals only

    4.1 Electroacupuncture vs. relaxation
138Mean Difference (IV, Random, 95% CI)8.3 [-4.23, 20.83]

 
Comparison 4. Acupuncture versus waiting list or no intervention

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Change in frequency of hot flushes from baseline to end of study3463Std. Mean Difference (IV, Random, 95% CI)-0.50 [-0.69, -0.31]

    1.1 Traditional acupuncture vs. waiting list/no intervention
3463Std. Mean Difference (IV, Random, 95% CI)-0.50 [-0.69, -0.31]

 2 Hot flush frequency128Mean Difference (IV, Random, 95% CI)-5.27 [-8.06, -2.48]

    2.1 Moxibustion vs. waiting list/no intervention
128Mean Difference (IV, Random, 95% CI)-5.27 [-8.06, -2.48]

 3 Change in hot flush severity from baseline to end of study3463Std. Mean Difference (IV, Random, 95% CI)-0.54 [-0.73, -0.35]

    3.1 Traditional acupuncture vs. waiting list/no intervention
3463Std. Mean Difference (IV, Random, 95% CI)-0.54 [-0.73, -0.35]

 4 Hot flush severity (end score)293Std. Mean Difference (IV, Random, 95% CI)-1.35 [-1.81, -0.89]

    4.1 Acupuncture vs. waiting list/no treatment
165Std. Mean Difference (IV, Random, 95% CI)-1.27 [-1.81, -0.74]

    4.2 Moxibustion vs. waiting list/no treatment
128Std. Mean Difference (IV, Random, 95% CI)-1.55 [-2.43, -0.66]

 5 Quality of life - change from baseline to end of study3463Std. Mean Difference (IV, Random, 95% CI)-0.93 [-1.20, -0.67]

    5.1 Traditional acupuncture vs. waiting list/no intervention
3463Std. Mean Difference (IV, Random, 95% CI)-0.93 [-1.20, -0.67]

 6 Quality of life (end score)130Mean Difference (IV, Random, 95% CI)-0.46 [-5.98, 5.06]

    6.1 Moxibustion vs. waiting list/no intervention
130Mean Difference (IV, Random, 95% CI)-0.46 [-5.98, 5.06]

 
Summary of findings for the main comparison. Acupuncture versus sham acupuncture for menopausal hot flushes

Acupuncture versus sham acupuncture for menopausal hot flushes

Population: women with menopausal hot flushes
Intervention: acupuncture versus sham acupuncture

OutcomesIllustrative comparative risks* (95% CI)No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Acupuncture versus sham acupuncture

Hot flush frequency (number/day)The mean hot flush frequency in the intervention groups was
1.13 flushes per day lower
(2.55 lower to 0.29 higher)
414
(8 studies)
⊕⊕⊝⊝
low1,2
There was no significant difference between the groups in the mean number of hot flushes per day

Hot flush severityThe mean hot flush severity in the intervention groups was
0.45 standard deviations lower
(0.84 to 0.05 lower)
297
(6 studies)
⊕⊝⊝⊝
very low3,4
Hot flushes were significantly less severe in the acupuncture group. The size of the effect was small.

SMD -0.45 (-0.84 to -0.05)

*The basis for the assumed risk is the median control group risk across studies. 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; SMD: standardized mean difference.

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.

 1 Only 2/8 studies described appropriate methods of randomization and allocation concealment, one of which had very high attrition.
2 Heterogeneity 70%.
3 Heterogeneity 68%.
4 Small total sample (n = 297).
 
Summary of findings 2. Acupuncture compared to hormone therapy for menopausal hot flushes

Acupuncture versus hormone therapy for menopausal hot flushes

Population: women with menopausal hot flushes
Intervention: acupuncture
Comparison: hormone therapy

OutcomesIllustrative comparative risks* (95% CI)No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Acupuncture versus hormone therapy

Hot flush frequency (number/day)The mean hot flush frequency in the intervention groups was
3.18 flushes per day higher
(2.06 to 4.29 higher)
114
(3 studies)
⊕⊕⊝⊝
low1,2
Hot flushes were significantly more common in the acupuncture group than in the hormone therapy group

Hot flush severity The mean hot flush severity in the intervention groups was
0.53 standard deviations higher
(0.14 lower to 1.2 higher)
84
(2 studies)
⊕⊕⊝⊝
low1,2
There was no significant difference between the groups in the mean severity of hot flushes

SMD 0.53 (-0.14 to 1.2)

*The basis for the assumed risk is the median control group risk across studies. 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; SMD: standardized mean difference.

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.

 1 None of studies described method of allocation concealment.
2 Total sample only 114 women.
 
Summary of findings 3. Electroacupuncture versus relaxation for menopausal hot flushes

Electroacupuncture versus relaxation for menopausal hot flushes

Population: women with menopausal hot flushes
Intervention: electroacupuncture versus relaxation

OutcomesIllustrative comparative risks* (95% CI)No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Electroacupuncture versus relaxation

Hot flush frequency (number/day)The mean hot flush frequency in the intervention groups was
0.4 flushes per day lower
(2.18 lower to 1.38 higher)
38
(1 study)
⊕⊝⊝⊝
very low1,2,3
There was no significant difference between the groups in the frequency or severity of hot flushes

Hot flush severity The mean hot flush severity in the intervention groups was
0.2 higher
(0.85 lower to 1.25 higher)
38
(1 study)
⊕⊝⊝⊝
very low1,2,3

*The basis for the assumed risk is the median control group risk across studies. 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.

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.

 1 Methods of randomization and allocation concealment not described in sufficient detail.
2 Single study conducted in women treated for breast cancer.
3 Very small sample (n = 38).
 
Summary of findings 4. Acupuncture versus waitlist or no intervention for menopausal hot flushes

Acupuncture versus waitlist or no intervention for menopausal hot flushes

Population: women with menopausal hot flushes
Intervention: acupuncture versus waiting list or no intervention

OutcomesIllustrative comparative risks* (95% CI)No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Acupuncture versus wait listing or no intervention

Change in frequency of hot flushes from baseline to end of studyThe mean change in frequency of hot flushes from baseline to end of study in the intervention groups was
0.5 standard deviations lower
(0.69 to 0.31 lower)
463
(3 studies)
⊕⊕⊝⊝
low1
Acupuncture significantly reduced the frequency and severity of hot flushes compared to waiting list or no intervention

The effect size was moderate in both cases

Frequency: SMD -0.5 (-0.69 to -0.31)

Severity: SMD -0.54 (-0.73 to -0.35)

Change in hot flush severity from baseline to end of studyThe mean change in hot flush severity from baseline to end of study in the intervention groups was
0.54 standard deviations lower
(0.73 to 0.35 lower)
463
(3 studies)
⊕⊕⊝⊝
low1

*The basis for the assumed risk is the median control group risk across studies. 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; SMD: standardized mean difference.

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.

 1 Only 1/3 studies described satisfactory methods of randomization and allocation concealment; 2/3 unblinded.