4

July 2016

Prepared for:

Department of Veterans Affairs

Veterans Health Administration

Quality Enhancement Research Initiative

Health Services Research & Development Service

Washington, DC 20420 

Prepared by:

Evidence-based Synthesis Program (ESP) Center

Durham VA Healthcare System

Durham, NC 

John W. Williams, Jr., MD, MHSc, Director 

Department of Veterans Affairs

Health Services Research & Development Service Evidence-based Synthesis Program

Nonpharmacologic 

Treatments for 

Menopause-associated 

Vasomotor Symptoms

Investigators:

Principal Investigators: 

Karen M. Goldstein, MD, MSPH 

Remy R. Coeytaux, MD, PhD 

John W. Williams, Jr. MD, MHSc 

Co-investigators: 

Megan Shepherd-Banigan, PhD 

Adam P. Goode, DPT, PhD 

Jennifer R. McDuffie, PhD 

Deanna Befus, BSN 

Soheir Adam, MD 

Varsha Masilamani, MBBS

Megan Van Noord, MSIS 

Research Associates: 

Avishek Nagi, MS 

Liz Wing, MA 

4
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program 

Vasomotor Symptoms

i

PREFACE

The VA Evidence-based Synthesis Program (ESP) was established in 2007 to provide timely and 

accurate syntheses of targeted healthcare topics of particular importance to clinicians, managers, and 

policymakers as they work to improve the health and healthcare of Veterans. QUERI provides funding 

for four ESP Centers, and each Center has an active University affiliation. Center Directors are 

recognized leaders in the field of evidence synthesis with close ties to the AHRQ Evidence-based 

Practice Centers. The ESP is governed by a Steering Committee comprised of participants from VHA 

Policy, Program, and Operations Offices, VISN leadership, field-based investigators, and others as 

designated appropriate by QUERI/HSR&D.

The ESP Centers generate evidence syntheses on important clinical practice topics. These reports help: 

Develop clinical policies informed by evidence;

Implement effective services to improve patient outcomes and to support VA clinical practice

guidelines and performance measures; and

Set the direction for future research to address gaps in clinical knowledge.

The ESP disseminates these reports throughout VA and in the published literature; some evidence 

syntheses have informed the clinical guidelines of large professional organizations. 

The ESP Coordinating Center (ESP CC), located in Portland, Oregon, was created in 2009 to expand the 

capacity of QUERI/HSR&D and is charged with oversight of national ESP program operations, program 

development and evaluation, and dissemination efforts. The ESP CC establishes standard operating 

procedures for the production of evidence synthesis reports; facilitates a national topic nomination, 

prioritization, and selection process; manages the research portfolio of each Center; facilitates editorial 

review processes; ensures methodological consistency and quality of products; produces “rapid response 

evidence briefs” at the request of VHA senior leadership; collaborates with HSR&D Center for 

Information Dissemination and Education Resources (CIDER) to develop a national dissemination 

strategy for all ESP products; and interfaces with stakeholders to effectively engage the program. 

Comments on this evidence report are welcome and can be sent to Nicole Floyd, ESP CC Program 

Manager, at Nicole.Floyd@va.gov. 

Recommended citation: Goldstein KM, Coeytaux RR, Williams Jr JW, Shepherd-Banigan M, Goode 

AP, McDuffie JR, Befus D, Adam S, Masilamani V, Van Noord MG. Nonpharmacologic Treatments for 

Menopause-Associated Vasomotor Symptoms. VA ESP Project #09-009; 2016.

This report is based on research conducted by the Evidence-based Synthesis Program (ESP) Center located at 

the Durham VA Medical Center, Durham, NC, funded by the Department of Veterans Affairs, Veterans Health 

Administration, Office of Research and Development, Quality Enhancement Research Initiative. The findings and 

conclusions in this document are those of the author(s) who are responsible for its contents; the findings and 

conclusions do not necessarily represent the views of the Department of Veterans Affairs or the United States 

government. Therefore, no statement in this article should be construed as an official position of the Department 

of Veterans Affairs. No investigators have any affiliations or financial involvement (eg, employment, consultancies, 

honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties) that 

conflict with material presented in the report.
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

ii

TABLE OF CONTENTS 

ABSTRACT ................................................................................................................................... 1

Introduction ................................................................................................................................. 1

Methods ...................................................................................................................................... 1

Results ......................................................................................................................................... 1

Conclusion .................................................................................................................................. 4

Abbreviations Table .................................................................................................................... 5

INTRODUCTION......................................................................................................................... 6

METHODS .................................................................................................................................... 7

Topic Development ..................................................................................................................... 7

Search Strategy ........................................................................................................................... 8

Study Selection ........................................................................................................................... 9

Data Abstraction ....................................................................................................................... 10

Quality Assessment ................................................................................................................... 10

Data Synthesis ........................................................................................................................... 10

Rating the Body of Evidence .................................................................................................... 12

Peer Review .............................................................................................................................. 12

RESULTS .................................................................................................................................... 13

Literature Flow ......................................................................................................................... 13

Characteristics of Included Studies ........................................................................................... 14

KEY QUESTION: In women with vasomotor symptoms (VMS) that are 

associated with perimenopause or postmenopause, what are the effects on 

VMS, health-related quality of life, and adverse events of the following 

nonpharmacologic, nonhormonal interventions? .......................................................................... 15

Acupuncture .............................................................................................................................. 15

Yoga, Tai Chi, and Qigong ....................................................................................................... 28

Structured Exercise ................................................................................................................... 34

Meditation, Mindfulness, Hypnosis, and Relaxation ................................................................ 43

Secondary Outcomes Across All Interventions ........................................................................ 54

SUMMARY AND DISCUSSION .............................................................................................. 57

Limitations ................................................................................................................................ 57
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

iii

Summary of Evidence ............................................................................................................... 58

Clinical Implications ................................................................................................................. 59

Research Gaps/Future Research ............................................................................................... 59

Conclusions ............................................................................................................................... 60

REFERENCES ............................................................................................................................ 61

TABLES

Table 1. Eligible Interventions and Definitions .......................................................................... 7

Table 2. Inclusion and Exclusion Criteria .................................................................................. 9

Table 3. Study Characteristics: Dodin et al 201340 ................................................................... 17

Table 4. Study Characteristics of New RCTs ........................................................................... 20

Table 5. Study Characteristics: Cramer et al 201243 ................................................................. 29

Table 6. Study Characteristics of New RCTs ........................................................................... 31

Table 7. Study Characteristics: Daley et al 201444 ................................................................... 36

Table 8. Study Characteristics of New RCTs ........................................................................... 39

Table 9. Study Characteristics: Saensak et al 201445 ................................................................ 45

Table 10. Study Characteristics: Cramer et al 201549 ............................................................... 46

Table 11. Study Characteristics of New RCTs ......................................................................... 48

Table 12. Strength of Evidence for Effects of Interventions on VMS ..................................... 59

FIGURES

Figure 1. Literature Flow Chart ................................................................................................ 14

Figure 2. Risk of Bias Ratings for New Acupuncture RCTsa ................................................... 22

Figure 3. Forest Plot of Acupuncture versus No Acupuncture on Change 

in Hot Flash Frequency at End of Treatment ............................................................................ 23

Figure 4. Forest Plot of Acupuncture versus No Acupuncture on Change in 

Hot Flash Severity at End of Treatment ................................................................................... 23

Figure 5. Forest Plot of Acupuncture versus Sham Acupuncture on Change 

in Hot Flash Frequency at End of Treatment ............................................................................ 25

Figure 6. Forest Plot of Acupuncture versus Sham Acupuncture on Change 

in Hot Flash Severity at End of Treatment ............................................................................... 26

Figure 7. Forest Plot of Acupuncture versus Sham Acupuncture on Change 

in Quality of Life at End of Treatment ..................................................................................... 27
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

iv

Figure 8. Risk of Bias Ratings for New Yoga RCTs ................................................................ 32

Figure 9. Forest Plot of Yoga versus Control on Change in 

Hot Flash Severity at End of Treatment ................................................................................... 33

Figure 10. Risk of Bias Ratings for New Structured Exercise RCTsa ...................................... 40

Figure 11. Forest Plot of Exercise versus Control on Change in 

Hot Flash Frequency at End of Treatment. ............................................................................... 41

Figure 12. Forest Plot of Exercise versus Control on Change in Hot Flash Severity ............... 42

Figure 13. Risk of Bias Ratings for Meditation, Mindfulness, 

Hypnosis, and Relaxation New RCTsa ..................................................................................... 50

Figure 14. Forest Plot of Paced Respiration versus Control on 

Change in Hot Flash Frequency ................................................................................................ 53

Figure 15. Forest Plot of Paced Respiration versus Control on 

Change in Hot Flash Severity at End-of-Treatment ................................................................. 54

APPENDIX A. Search Strategy ................................................................................................. 69

APPENDIX B. Criteria Used in Quality Assessment .............................................................. 75

APPENDIX C. Quality Assessment Ratings ............................................................................ 85

APPENDIX D. Measurement Scales for Menopause .............................................................. 88

APPENDIX E. Peer Review Comments/Author Responses ................................................... 90
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

1

ABSTRACT

INTRODUCTION 

Vasomotor symptoms (VMS), which include hot flashes and night sweats, are the most common 

symptoms reported during the menopausal transition and are experienced by as many as 80% of 

women. VMS can lead to increased healthcare encounters for symptom relief and reductions in 

quality of life. The degree to which VMS is bothersome is determined not only by how 

frequently it occurs but also by other factors such as duration of VMS, coexisting sleep 

problems, and the extent to which VMS interferes with daily activities or job-related activities. 

Hormone therapy (HT) is an effective treatment for reducing VMS, but use of this therapeutic 

approach must be individualized through weighing benefits with known risks, such as 

cardiovascular events or uterine and breast cancers. Based on age (> 45 years), currently half of 

the approximately 360,000 women Veterans who use Veterans Health Administration healthcare 

are perimenopausal or postmenopausal. Due in part to concerns about possible harms from longterm hormone therapy and in part to uncertain efficacy and safety of pharmacologic treatments, 

many women with VMS seek nonhormonal, nonpharmacologic treatment options. 

METHODS

We developed the following research question in consultation with our stakeholders and a panel 

of technical experts: 

In women with vasomotor symptoms (VMS) that are associated with perimenopause or 

postmenopause, what are the effects on VMS, health-related quality of life, and adverse 

effects of the following nonpharmacologic, nonhormonal interventions: acupuncture; yoga, 

tai chi, and qigong; structured exercise; and meditation, mindfulness, hypnosis, and 

relaxation?

Given the multiple high-quality systematic reviews (SRs) in this topic area, we chose a method 

commonly known as an umbrella review, or review of reviews. We supplemented this approach 

by also evaluating randomized controlled trials (RCTs) published after the most recent goodquality SR for each of the eligible interventions. We grouped SRs and RCTs by intervention 

category. We graded the quality of SRs and new RCTs and prioritized the highest-quality SRs. 

Good-quality reviews had no important limitations and fair reviews had at least some important 

limitations. We reported intervention effects separately for inactive and active comparators and 

examined SRs for relevant subgroup analyses. When a new meta-analysis was indicated and 

feasible, we computed summary estimates of effect for each intervention. We explored the 2 

primary outcomes: VMS and health-related quality of life. We assessed strength of evidence 

using the approach described in the Agency for Healthcare Research and Quality’s Methods 

Guide for Effectiveness and Comparative Effectiveness Reviews. 

RESULTS

We identified 239 unique SR citations; of these, 37 were retrieved for full-text review, and 10 

were retained for data abstraction. We also identified 1135 unique RCTs; of these, 67 were 

retrieved for full-text review, and 14 articles plus 2 companion papers were retained for data 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

2

abstraction. The 10 SRs addressed acupuncture (n = 3), yoga (n = 1), structured exercise (n = 1), 

and meditation, mindfulness, hypnosis, relaxation, or mixed interventions (n = 5). The 14 new 

RCTs evaluated acupuncture (n = 4), yoga (n = 2), structured exercise (n = 3), and meditation, 

mindfulness, hypnosis, relaxation, or mixed interventions (n = 6). All studies reported the effects 

of interventions on VMS; quality of life and other outcomes were reported less frequently.

Acupuncture 

We identified one good-quality SR published in 2013 that included women with VMS from any 

cause and 2 fair-quality SRs that included only women with any type of cancer. The good-quality 

SR included 15 relevant RCTs comprising 1127 participants. Comparison groups were no 

acupuncture, sham acupuncture, hormone therapy, or relaxation. Duration of acupuncture 

treatments ranged from 4 to 12 weeks across the RCTs. Traditional acupuncture was 

administered in 11 trials, electroacupuncture in 3 trials, and a combination of acupuncture and 

auricular acupuncture in a single trial. Twelve RCTs reported daily VMS by a self-report 

symptom diary. The remaining 3 assessed daily VMS frequency and severity as a hot flash score. 

Three RCTs assessed menopause-related symptoms considered by the authors of the SR to 

reflect quality of life. Applying the Cochrane guidance for overall risk of bias, 2 RCTs were 

rated as low risk and 11 were rated as high risk. This SR did not address durability of effect. 

We identified 4 relevant RCTs with low risk of bias published since 2012 that were not included 

in the eligible SRs. Three examined the effect of acupuncture on VMS in perimenopausal and 

postmenopausal women, and one examined the effects of electroacupuncture in breast cancer 

survivors compared with the drug gabapentin, a placebo pill, or sham acupuncture. All 4 of these 

RCTs examined durability of effect. Three of the 4 new RCTS found that reductions in Hot Flash 

Composite Score and hot flash frequency were maintained at 12, 16, and 24 weeks 

posttreatment, respectively.

Our updated meta-analyses suggest that acupuncture is effective at reducing VMS frequency 

(SMD -0.66, 95% CI -1.06 to -0.26, I2

= 61.7%, 5 trials) and VMS severity (SMD -0.49, 95% CI 

-0.85 to -0.13, I2= 18.1%, 4 trials), and improving quality of life (SMD 0.93, 95% CI -1.20 

to -0.67, I2

= 0.0%, 3 trials) when compared with no acupuncture, but not when compared with 

sham acupuncture. This translates to an average of 3 fewer hot flashes daily. Two of 4 trials 

reported that treatment benefit was maintained 16 to 24 weeks after end of treatment. The other 2 

trials did not show sustained effects. Meta-analysis also suggests that acupuncture is associated 

with higher daily VMS frequency compared with hormone therapy (SMD 3.18, 95% CI 2.06 to 

4.29, I2= 0%, 3 trials). Acupuncture and hormone therapy, however, are associated with similar 

changes in VMS severity (SMD 0.53, 95% CI -0.14 to 1.20, 2 trials). 

Yoga, Tai Chi, and Qigong

We identified a single good-quality SR published in 2012 that included 5 RCTs (582 

participants) evaluating the effect of yoga on VMS when compared with both inactive and/or 

active comparators. Yoga interventions were delivered in 34 to 40 sessions over 8 weeks to 4 

months. All 5 interventions included yoga postures and meditation; 4 included breathing 

exercises, and 2 included lifestyle lectures. Risk of bias was determined to be low risk for 2 

RCTs and high risk for 3 RCTs. Only one study included in the SR examined durability of effect 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

3

at 12 weeks post-treatment. We did not identify any eligible SRs that evaluated the effectiveness 

of tai chi or qigong. 

We also identified 2 new relevant RCTs that assessed the impact of yoga on hot flash frequency 

and severity and quality of life among 102 perimenopausal or postmenopausal women, but both 

were judged to be of high risk of bias. In these, integral yoga or a Rusie Dutton course lasting 10 

or 13 weeks was compared with inactive controls. Sessions were held weekly for 90 minutes. 

Outcomes were assessed using the Daily Hot Flash Diary and the Global Quality of Life Scale at 

5 and 10 weeks in one RCT and subscales from the Menopause-specific Quality of Life 

instrument at 12 weeks in the other RCT. Neither of the new RCTs examined durability of 

treatment effects beyond the end of treatment. We did not identify any new RCTs that evaluated 

the effectiveness of tai chi or qigong.

The authors of the SR did not find an association between yoga and a reduction in VMS. We 

conducted an updated meta-analysis examining the effect of yoga compared with active and 

inactive controls on hot flash severity change scores using data from 2 new RCTs and 2 RCTs 

included in the SR. Results suggest that yoga is significantly associated with a reduction in hot 

flash severity (SMD -0.36, 95% CI -0.65 to -0.07, I2

= 0.0%, 4 trials). Quality of life was not 

examined frequently. The single, small RCT that suggested some improvement in quality of life 

was statistically inconclusive.

Structured Exercise

We identified one good-quality and one fair-quality SR, both published in 2014, that included 

comparative evaluations of exercise, mindfulness, and relaxation. The good-quality SR included 

5 RCTs that involved 762 sedentary, perimenopausal or postmenopausal women with VMS. In 

the majority of studies (n = 4), exercise was conducted with supervision or in a group session. 

The number and length of planned sessions ranged from 12 to 96 sessions over 12 to 36 weeks. 

The risk of bias was judged by the authors of the SR to be high risk for 4 RCTs and low risk for 

one RCT. The authors of the SR concluded there was no evidence that exercise reduced hot flash 

frequency or severity compared with inactive control (n = 4), yoga (n = 2), or hormone therapy 

(n = 1). Our updated meta-analyses did not find significant effects of structured exercise for 

either VMS frequency (SMD -0.08, 95% CI -0.33 to 0.16, I2= 0.0%, 4 trials) or severity (SMD -

0.06, 95% CI -0.21 to 0.10, I2

= 0.0%, 5 trials) compared with inactive control.

We identified 2 new RCTs that examined the effect of exercise compared with inactive control 

for VMS among perimenopausal or postmenopausal women. Both trials were judged to be low 

risk of bias. One studied women after breast cancer treatment exclusively. Exercise interventions 

were individually tailored programs focusing on aerobic exercise sessions lasting 40 to 90 

minutes for 12 to 24 weeks. VMS was assessed using the Hot Flash Rating Scale in both trials. 

One RCT reported menopause-specific quality of life and found significantly lower sleep 

problem scores at 6 months’ follow-up. The other trial found moderate benefit from structured 

exercise on health-related quality of life at end of treatment (effect size 0.46) and 12 weeks later 

(effect size 0.41). 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

4

Meditation, Mindfulness, Hypnosis, and Relaxation

We identified 5 SRs (2 good-quality, 3 fair-quality) that met eligibility criteria. One SR 

examined relaxation and mindfulness, one examined hypnosis exclusively, and 3 reported on 

mixed interventions. Of the RCTs included in the SRs, only one evaluated mindfulness-based 

stress reduction, and none assessed the effects of meditation. We focused on both the goodquality 2014 Cochrane Collaboration SR that addressed relaxation and paced respiration in 281 

women with VMS and the fair-quality 2015 SR examining hypnosis in 274 women with breast 

cancer.

In the good-quality SR, 4 RCTs assessed VMS frequency, Kupperman Index scores, and mood. 

No studies reported on quality of life or adverse effects. Time of final follow-up assessment 

varied across RCTs from 4 weeks to 24 weeks with only one trial completing a follow-up 

assessment after completion of the intervention. No significant difference in reduction of hot 

flash frequency was found between any type of relaxation or mindfulness interventions 

compared with control groups for the primary outcomes of VMS frequency or quality of life. 

Authors of the SR did not report an overall risk of bias rating for individual studies but noted that 

the overall quality of evidence was “very low.” 

In the fair-quality SR, 3 RCTs included the comparators of attention control, no treatment, and 

gabapentin. Outcomes measured included VMS frequency, health-related quality of life, mood, 

and adverse effects. The timing of outcome assessments was unclear for these trials. This SR 

presented qualitative findings only and found a significant decrease in hot flashes among women 

treated with hypnosis compared with no treatment; however, there was no difference when 

compared with gabapentin. Authors reported an overall low risk of bias in the included studies 

using the Cochrane Risk of Bias tool. 

We identified 6 new RCTs that were not included in existing SRs. Three examined paced 

respiration and 3 examined effects of applied relaxation on VMS or quality of life among 

perimenopausal or postmenopausal women. Of the 3 new relaxation RCTs, one was low risk of 

bias, one was unclear risk, and one was high risk. We conducted a new meta-analysis comparing 

paced respiration with a control group. We found that paced respiration is not associated with a 

statistically significant decrease in hot flash frequency (SMD 0.04, 95% CI -0.73 to 0.82, I2

= 

56.6%) or severity (SMD 0.06, 95% CI -0.69 to 0.80, I2

= 65.1%). 

In general, our secondary outcomes of interest—sleep quality, depression, anxiety, and adverse 

effects—were rarely reported in the SRs addressing relaxation, and the results were mixed when 

they were reported.

CONCLUSION

Compared with waitlist controls, RCTs support acupuncture and yoga for reducing VMS and the 

impact of such symptoms on women’s activities and health-related quality life. The strength of 

evidence, however, is low to moderate. Moderately good evidence shows no benefit from 

structured exercise for VMS. The evidence in support of the effectiveness of mindfulness or 

relaxation is mixed, with some promising evidence that needs replication for hypnosis. There is 

insufficient evidence to draw conclusions about the effectiveness of these nonpharmacologic 

therapies for improving sleep, depression, or anxiety. The safety of the nonpharmacologic, 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

5

nonhormonal approaches evaluated in this report has not been rigorously examined, but there is 

no clear signal for a significant potential for harm. Overall, most of the data included in this 

report comes from smaller studies with homogenous participant populations. Larger trials of 

populations more reflective of the diversity of women experiencing VMS will be necessary to 

discern the effectiveness of nonpharmacologic interventions in symptomatic menopausal women. 

ABBREVIATIONS TABLE

AHRQ Agency for Healthcare Research and Quality

CI Confidence interval

CINAHL Cumulative Index to Nursing and Allied Health Literature

ESP Evidence-based Synthesis Program

MD Mean difference

MeSH Medical Subject Heading

PICOTS Population, intervention, comparator, outcome, timing, setting

RCT Randomized controlled trial

SMD Standardized mean difference

SOE Strength of evidence

SR Systematic review

VA Veterans Affairs

VMS Vasomotor symptoms

VHA Veterans Health Administration
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

6

EVIDENCE REPORT

INTRODUCTION

Hot flashes and night sweats (or vasomotor symptoms) are 2 of the most common symptoms 

reported during the menopausal transition and are experienced by as many as 80% of women.

1

The mean age at onset of vasomotor symptoms (VMS) is 51 years,2 and recent longitudinal 

studies of the menopausal transition revealed the median total duration can last more than 7 

years.3 Women’s experience of VMS can vary based on personal characteristics. For example, 

more African-American women can expect to experience VMS than women from other 

racial/ethnic groups,3 and those who gain weight in midlife are more likely to report hot flashes 

than those who do not.4

Prevalence and duration of VMS in perimenopausal and postmenopausal women are important 

women’s health issues. VMS can lead to increased healthcare encounters for symptom relief5 and 

reductions in quality of life.

6,7 The impact of VMS on quality of life can be worse for certain 

populations of women, such as those who undergo surgical rather than natural menopause.8

Moreover, the degree to which VMS is bothersome is determined not only by how frequently it 

occurs but also by other factors such as duration of VMS, coexisting sleep problems,

9 and the 

extent to which VMS interferes with daily activities or job-related activities. For some defined 

populations of women, VMS exerts an especially strong, negative impact on quality of life; this 

appears to be the case for women Veterans.

6

Hormone therapy (HT) is an effective treatment for reducing moderate to severe VMS, but use of 

this therapeutic approach must be individualized through weighing benefits with known risks, 

such as cardiovascular events or uterine and breast cancers.10-12 FDA guidance defines moderate 

symptoms as “the sensation of heat with sweating, able to continue activity” and severe 

symptoms as those that cause “cessation of activity.”13 A common recommended strategy is to 

use HT with the “lowest effective dose for the shortest duration that is needed”.14,15 Additionally, 

HT is contraindicated for some women due to comorbid health conditions such as a history of 

breast cancer or being high risk for development of breast cancer, liver disease, or a history of 

blood clots. Based on age (> 45 years), currently half of the approximately 360,000 women 

Veterans who use Veterans Health Administration (VHA) healthcare are perimenopausal or 

postmenopausal. Many are at increased risk for complications of hormone therapy, such as 

cardiovascular disease, due to highly prevalent, known risk factors like obesity,

16 smoking,17 and 

depression.18 Despite this, recent evidence indicates that, compared with the general population 

of women in the United States, women Veterans using VHA are twice as likely to use hormone 

therapy for relief of menopausal symptoms.19

Due to the restriction on long-term hormone therapy use and the extended duration of expected 

VMS, many women with VMS are left in need of nonhormonal treatment options for many

years. Thus, identifying effective nonhormonal interventions for improving quality of life among 

women Veterans with VMS is an important step to finding safe alternatives to hormone therapy 

and improved options for Veteran-centered care. Many perimenopausal and postmenopausal 

women are already using nonpharmacologic agents to manage VMS.20-22 Nonpharmacologic 

treatments for VMS include herbal remedies (eg, black cohosh), mind and body practices (eg, 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

7

yoga, tai chi), structured exercise programs, and complementary and alternative medicine 

interventions (eg, acupuncture).23 

In 2015, an Agency for Healthcare Research and Quality (AHRQ) systematic review24 examined 

the comparative effectiveness of estrogens, isoflavones, selective serotonin reuptake 

inhibitors/serotonin-norepinephrine reuptake inhibitors, gabapentin, black cohosh, and ginseng 

for menopausal symptoms, including VMS. However, the AHRQ review did not address 

nonpharmacologic interventions such as mind and body practices, structured exercise programs, 

or complementary and alternative medicine interventions. Also in 2015, the North America 

Menopause Society released a position statement providing recommendations for many such 

intervention types and graded the level of evidence for their recommendations; however, this was 

not a formal systematic review of the literature.25

Our goal with this report is to summarize and update the evidence from systematic reviews 

(hereafter referred to as SRs) on selected nonpharmacologic approaches for the treatment of 

menopause-associated VMS and health-related quality of life. 

METHODS 

Given the multiple high-quality SRs in this topic area, we chose a method commonly known as 

an umbrella review, or review of reviews. We supplemented this approach by also evaluating 

randomized controlled trials (RCTs) published after the most recent good-quality SR for each of 

the eligible interventions. We followed methodological guidance from the Cochrane 

Collaboration26 and AHRQ’s Evidence-based Practice Centers.27

TOPIC DEVELOPMENT

Numerous interventions could be considered nonpharmacologic treatments for VMS in 

perimenopausal and postmenopausal women, particularly variations of complementary and 

alternative medicine approaches to symptom control.20 To focus the selection of interventions for 

this review, we invited individuals with expertise in the field of menopause management both 

from within the Veterans Health Administration (VHA) and outside the VHA to participate in a 

technical expert panel. This panel provided consultation during the process of reviewing and 

organizing a list of potential interventions originally generated by the primary review team based 

on published literature and clinical practice. Table 1 lists the eligible nonpharmacologic 

interventions and definitions for this umbrella review. 

Table 1. Eligible Interventions and Definitions

Intervention category Definitions and examples

Acupuncture, acupressure Acupuncture from any tradition was considered, including 

auricular acupuncture, electroacupuncture, acupressure, and 

laser acupuncture. Excluded were studies where acupuncture 

was administered in conjunction with Chinese herbal therapies. 

Cupping therapy was excluded unless it was a component of an 

acupuncture intervention.
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

8

Intervention category Definitions and examples

Yoga, tai chi, qigong (as defined 

by study investigators) 

Yoga typically involves combinations of physical exercises and 

bodily positions or postures, breath control practices, and 

meditation.

Tai chi typically involves a series of movements performed in a 

slow, focused manner accompanied by deep breathing.

Qigong typically involves a combination of coordinated body 

postures and movement, breathing, and meditation.

Structured exercise, physical 

activity

Structured exercise is defined as regular physical activity done 

with the intention of improving or maintaining physical fitness or 

health, or performed as part of a class or with support from a 

health professional.

Meditation, mindfulness, relaxation Practices include:

• Alexander technique

• Benson's relaxation response

• Bernstein and Borkovec's progressive relaxation

• Everly and Rosenfeld's passive relaxation

• Guided imagery-based approaches

• Hypnosis

• Madder's release

• Mindfulness-based stress reduction

• Mitchell method

• Osts's applied relaxation

• Paced respiration

• Poppen's behavioral relaxation training

• Progressive relaxation

• Roll breathing

• 4-7-8 breath technique

• Other approaches that focus on diaphragmatic breathing

The final key question (KQ), developed in consultation with stakeholders, was: 

In women with vasomotor symptoms (VMS) that are associated with perimenopause or 

postmenopause, what are the effects on VMS, health-related quality of life, and adverse

events of the following nonpharmacologic, nonhormonal interventions? 

Acupuncture 

Yoga, tai chi, and qigong 

Structured exercise

Meditation, mindfulness, hypnosis, and relaxation

We followed a standard protocol for this review,28 and each step was pilot-tested to train and 

calibrate study investigators. The PROSPERO registration number is CRD42016029335.29

SEARCH STRATEGY 

In consultation with an expert librarian, we conducted searches of MEDLINE (via PubMed) and 

the Cochrane Database of Systematic Reviews from January 2010 through November 2015 for 

SRs, as well as searches of PubMed, EMBASE, CINAHL, and the Allied and Complementary 

Medicine Database from January 2012 through February 2016 for RCTs. We used MeSH 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

9

keywords and selected free-text terms for the interventions and health conditions of interest as 

well as terms for SRs and RCTs. The exact search strategies used are in Appendix A. All eligible 

SRs along with relevant umbrella and narrative reviews identified during citation screening were 

reviewed for additional relevant RCTs. All citations were imported into 2 electronic databases 

(for referencing, EndNote® Version X7, Thomson Reuters, Philadelphia, PA; for data 

abstraction, DistillerSR; Evidence Partners Inc., Manotick, ON, Canada). 

STUDY SELECTION

Using prespecified inclusion/exclusion criteria (Table 2), titles and abstracts of SRs and RCTs 

identified through our primary search were reviewed by 2 reviewers for potential relevance to the 

key question. Articles included by either reviewer underwent full-text screening. At the full-text 

screening stage, 2 independent reviewers were required to agree on a final inclusion/exclusion 

decision. Disagreements were resolved by discussion or by a third investigator. Articles meeting 

eligibility criteria were included for data abstraction.

Table 2. Inclusion and Exclusion Criteria

Study Characteristic Inclusion/Exclusion Criteria

Population Perimenopausal and postmenopausal women who are experiencing 

bothersome VMS. Perimenopause is defined as amenorrhea for > 60 

days in the past 12 months; postmenopause is defined as being without 

a menstrual cycle due to spontaneous or surgical reasons for the 

preceding 12 months. 

Bothersome VMS is defined as any of the following: 

 Self-identified “bothersome” hot flashes 

 Moderate to severe VMS as defined by the FDA13 

 Hot flashes that occur at least 6 days in the previous 2 weeks3

 Hot flashes associated with functional impairment (eg, impairment in 

role, social, emotional, or physical functioning)

Interventionsa Acupuncture, acupressure

Yoga, tai chi, qigong (as defined by study investigators) 

Structured exercise, physical activity 

Meditation, mindfulness, hypnosis, relaxation

Comparators Any inactive control (waitlist, attention, sham acupuncture, information 

control, or unenhanced usual care) or active comparator (including 

hormone treatments, antidepressants or other pharmacotherapies, 

dietary supplements, health education, and alternative forms of 

exercise)

Outcomes Primary:

Frequency and severity of VMS

Overall and condition-specific health-related quality of life

Secondary: 

Psychological well-being (ie, depressive or anxiety symptoms) and 

sleep quality, prioritizing validated scales over unvalidated scales or 

single-symptom measures

Serious adverse effects and adverse effects
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

10

Study Characteristic Inclusion/Exclusion Criteria

Timing For SRs, timing of outcome assessments as specified by the review

For RCTs, outcomes assessed at > 60 days after treatment 

assignment

Setting Outpatient or community settings (and mixed settings inclusive of 

outpatient/community settings)

Study design Included: SRs and RCTs that evaluate an eligible intervention for VMS 

that is associated with perimenopause or postmenopause

Excluded: SRs of complementary and alternative therapies in general 

without a specific focus on the interventions of interest, and umbrella 

reviews

Publication type Included: Full articles published in peer-reviewed journals from January 

2010 to November 2015 for SRs, or from January 2012 to February 

2016 for RCTs 

Excluded: Abstracts and dissertations a Intervention definitions are in Table 1. 

Abbreviations: RCT = randomized controlled trial; SR = systematic review; VMS = vasomotor symptoms

DATA ABSTRACTION

Data from published fair- or good-quality SRs and newly identified RCTs were abstracted into a 

customized DistillerSR database by one reviewer and overread by a second reviewer. 

Disagreements were resolved by discussion or by a third investigator. Data elements include 

descriptors to characterize the type of study, study population, intervention, comparator, 

outcomes reported, study quality, and author conclusions. 

QUALITY ASSESSMENT

Two reviewers assessed the quality of SRs and RCTs (Appendix B). Disagreements were 

resolved by discussion or by a third investigator. For SRs, we used the following key quality 

criteria, adapted from ROBIS30 and AMSTAR7

: search methods adequate for replication and 

comprehensive; selection bias avoided; data abstracted reliably; characteristics of primary 

literature reported and quality assessed appropriately; results synthesized using appropriate 

methods; publication bias assessed; conflict of interest reported; and conclusions supported by 

results. Based on these criteria, SRs were categorized as good, fair, or poor quality. Good- and 

fair-quality SRs should provide sufficient information to assess the strength of the body of 

evidence using the GRADE criteria.

31,32 Poor-quality reviews were excluded from our review. 

For newly identified RCTs, we used the Cochrane Collaboration’s risk of bias (ROB) tool,33

which categorizes biases by 6 domains (selection bias, performance bias, detection bias, attrition 

bias, reporting bias, and other bias) and makes a summary assessment. For each item, a summary 

rating (high, low, or unclear ROB) was made (Appendix C). 

DATA SYNTHESIS

We grouped the SRs and RCTs by intervention. We prioritized SRs that are the highest quality 

and most relevant to the study question.34 Relevance was assessed using the PICOTS 

(population, intervention, comparator, outcome, timing, setting) framework along with the search 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

11

date, review methods, and completeness of reporting. For each intervention, tables or graphical 

displays describe the studies included, study quality, and treatment effects. We report 

intervention effects separately for inactive and active comparators. We examined SRs for 

relevant subgroup analyses, including concurrent use of hormone therapy, effects in women with 

and without breast cancer, perimenopausal and postmenopausal women, and women with 

surgical versus natural menopause. 

Although umbrella reviews typically do not search for new primary studies, our review 

incorporated this step in order to identify important new data. As a framework for determining 

whether a new quantitative synthesis is needed, we considered the number of new studies, the 

sample size, and the strength of evidence (SOE) domains.31 When an updated or new metaanalysis was indicated and feasible, we computed summary estimates of effect for each 

intervention using end-of-treatment outcomes. When means and measures of dispersion were not 

reported in the text, they were approximated from figures with the use of Engauge Digitizer.35

We imputed missing control group standard deviations (SDs) in one study (and for 2 outcome 

measures) by using the maximum of all available SDs from other arms in the same study, which 

were measured on the same scale. 

One difficulty in performing new meta-analyses for the quality of life outcome was the large 

variation in the types of scales used to measure this variable. For example, a scale could have 

separate subscales labeled VMS, physical, and somatic, all of which we considered part 

of physical domain but not address the social, occupational or functional aspects, whereas other 

scales contained occupational, social, and emotional subscales, but did not address the physical 

domain. 

We devised a working definition for health-related quality of life in order to bring some degree 

of homogeneity to our analyses. To be included, a scale must have had at least 2 of the following 

5 domains that were determined to be major: emotional, functional, occupational, physical, 

and/or social. These 5 domains were found in 50% or more of all the scales represented in the 

studies that examined quality of life. Of the eight scales used in the studies included in our metaanalyses, only one scale, the MENQOL, contained only 2 of the 5 domains and only one scale, 

the SF-36, contained all 5 domains. All others contained at least 3 of the 5 major domains used in 

our working definition. 

We used R version 3.1.2 (R Foundation for Statistical Computing, Vienna, Austria) with the 

metafor package36 to calculate random-effects model summary estimates of effect with Knapp 

and Hartung adjustment of standard errors of the estimated coefficients.

37,38 Because outcomes 

were measured across the trials using different instruments, outcome measures were combined 

using standardized mean differences (SMDs) in a random-effects model. The SMD was 

calculated by dividing the difference in mean values by the pooled SDs of the 2 groups. SMDs of 

0.2 can be considered small treatment effects; 0.5, moderate effects; and ≥0.8, large effects.39 For 

hot flash frequency, we transformed the pooled SMD26 into hot flashes/day by multiplying the 

SMD by the standard deviation of the original scale from a representative study. Consistency of 

findings across individual studies was assessed by standard chi-square tests and the I2 statistic. 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

12

RATING THE BODY OF EVIDENCE

SOE was assessed using the approach described in the Agency for Healthcare Research and 

Quality (AHRQ)’s Methods Guide for Effectiveness and Comparative Effectiveness Reviews.

27

We focused on the 2 primary outcomes of impact on VMS and health-related quality of life. The 

AHRQ approach requires assessment of 4 domains: risk of bias, consistency, directness, and 

precision. Additional domains are used when appropriate: coherence, dose-response association, 

impact of plausible residual confounders, strength of association (magnitude of effect), and 

publication bias. These domains were considered qualitatively, and a summary rating of high, 

moderate, or low SOE was assigned after discussion by 2 investigators. In some cases, a rating of 

high, moderate, or low was impossible or imprudent to make. In these situations, a rating of 

insufficient was assigned. This 4-level rating scale consists of the following definitions:

High—We are confident that the true effect lies close to the estimate of effect. 

Moderate—We are moderately confident of the effect estimate. The true effect is likely to 

be close to the estimate of effect, but there is a possibility that it is substantially different. 

Low—Our confidence in the effect estimate is limited: The true effect may be 

substantially different from the estimate of effect.

Insufficient—We have very little confidence in the effect estimate. The true effect is 

likely to be substantially different from the estimate of effect. 

PEER REVIEW

This report was reviewed by technical experts and clinical leadership. A transcript of their 

comments and our responses is provided in Appendix E. 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

13

RESULTS

LITERATURE FLOW

Figure 1 shows the flow of articles through the literature search and screening process. The 

literature search for SRs identified 239 unique citations from a combined search of PubMed and 

the Cochrane Database of Systematic Reviews. After applying inclusion and exclusion criteria at 

the title-and-abstract screening level, 37 full texts were retrieved for further review. Of these, 10 

were retained for data abstraction.

A separate literature search for RCTs published after January 2012 identified 1135 unique 

citations from a combined search of PubMed, EMBASE, CINAHL, and the Allied and 

Complementary Medicine Database. One additional citation was identified by review of study 

bibliographies or contact with authors. After applying inclusion and exclusion criteria at the titleand-abstract screening level, 68 full texts were retrieved for further review. After eliminating 

studies included in eligible reviews and applying eligibility criteria at the full-text review level, 

14 were retained for data abstraction, and 2 were identified as companion papers (ie, secondary 

analyses to studies included in an eligible review).
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

14

Figure 1. Literature Flow Chart

CHARACTERISTICS OF INCLUDED STUDIES

Systematic Reviews

We identified 10 eligible SRs (5 good quality and 5 fair quality): 3 addressed acupuncture;40-42 1 

addressed yoga;

43 1 addressed structured exercise;44 and 5 addressed meditation, mindfulnessbased practices, hypnosis, relaxation, or mixed interventions.45-49 All SRs evaluated interventions 

in women who were perimenopausal or postmenopausal and 5 required women to report

bothersome frequency of VMS. Four restricted their focus to women with a history of breast 

cancer. Seven SRs included only RCTs. Four reported summary estimates of treatment effect 

from meta-analyses, while 6 synthesized results qualitatively. 

New Randomized Controlled Trials

We identified 14 eligible RCTs published after the SRs (hereafter described as “new RCTs”) that 

evaluated a range of interventions: 4 addressed acupuncture;50-53 2 addressed yoga;54,55 6 

addressed relaxation, paced respiration, or hypnosis;56-61 and 2 addressed structured exercise.62,63

All new RCTs enrolled perimenopausal or postmenopausal women with VMS. Three RCTs 

focused on breast cancer survivors. Trials randomized 40 to 327 (median = 63 patients and 

reported outcomes at 5 to 24 (median = 11) weeks. All RCTs reported the effects of interventions 

on VMS; however, quality of life and other outcomes were reported less frequently. 

Search results:

239 (SR) 

references

Pulled for fulltext review: 37 

(SR) references

Excluded at title screening = 202 

(SR) references

Excluded at full text review = 27 

(SR) references

Not full publications, meeting 

abstracts: 7

SR published prior to year 

2010: 5

Not an SR: 10

Not condition of interest: 1

Not outcome of interest: 1

Poor-quality SR: 3

10 SRs and 14 RCTs

Included studies:

10 SR references

Search results:

1135 (RCT) + 2 

manual 

references

Pulled for fulltext review: 68

(RCT) 

references

Included studies:

14 RCTs 

(plus 2 companion

references)

Excluded at title screening = 

1069 (RCT) references

Excluded at full text review = 

54 (RCT) references

Not English/not full

publication: 11

Not an RCT: 12

Not population of interest: 20

Not relevant outcomes: 8

Not intervention of interest: 2

Not setting of interest: 1
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

15

For each of the 4 intervention categories, we focus our discussion on the SR(s) having the 

highest quality and most relevance to the primary outcomes of interest: VMS symptoms and 

health-related quality of life. Results from other SRs are described when they provided unique 

information. We then discuss results from the new RCTs and our updated syntheses (quantitative 

or qualitative) that included these additional studies. Results are further organized by inactive 

and active comparators. Last, we describe the findings for the secondary outcomes across all 4 

intervention categories, which include adverse effects as well as effects on sleep, depression, and 

anxiety.

KQ: In women with vasomotor symptoms (VMS) that are 

associated with perimenopause or postmenopause, what are 

the effects on VMS, health-related quality of life, and adverse 

events of the following nonpharmacologic, nonhormonal 

interventions?

• Acupuncture

• Yoga, tai chi, and qigong

• Structured exercise

• Meditation, mindfulness, hypnosis, and relaxation

ACUPUNCTURE

Key Points

We identified one good-quality SR published in 2013 and 2 fair-quality SRs published in 

2013 and 2015 that met eligibility criteria. The good-quality review included women with 

menopausal VMS from any cause, and the 2 fair-quality reviews included only women 

with any type of cancer. All 3 SRs included RCTs that compared acupuncture with no 

acupuncture, sham acupuncture, hormone therapy, or relaxation.

The Dodin et al meta-analysis suggests that acupuncture is effective at reducing VMS 

frequency (SMD -0.66, 95% CI -1.06 to -0.26, I

2

= 61.7%, 5 trials) and VMS severity 

(SMD -0.49, 95% CI -0.85 to -0.13, I

2

= 18.1%, 4 trials) and improving quality of life 

(SMD -0.93, 95% CI -1.20 to -0.67, I

2

= 0.0%, 3 trials) when compared with no 

acupuncture. This translates to an average of 3 fewer hot flashes daily.

Updated meta-analysis suggests that acupuncture is not effective at reducing VMS 

frequency (SMD -0.21, 95% CI -0.49 to 0.07, I2

= 53.5%, 10 trials) compared with sham 

acupuncture, but there is a modest, positive effect associated with acupuncture for 

reducing VMS severity compared with sham acupuncture (SMD -0.35, 95% CI -0.70 to 

0.01, I2= 66.5%, 8 trials). Acupuncture does not appear to be more effective than sham 

acupuncture in improving quality of life as assessed by symptom inventories (SMD -0.23, 

95% CI -1.40 to 0.95, I2

= 77.0%, 5 trials).
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

16

Meta-analysis suggests that acupuncture is associated with much higher daily VMS 

frequency compared with hormone therapy (SMD 3.18, 95% CI 2.06 to 4.29, I

2

= 0%, 3

trials). This translates to 13 more hot flashes daily. Acupuncture and hormone therapy, 

however, did not differ in effects on VMS severity (SMD 0.53, 95% CI -0.14 to 1.20, 2 

trials), but trials were small and 95% CI wide. 

We identified 4 relevant, low risk of bias RCTs published since 2012 that were not 

included in the eligible SRs. Two RCTs compared 8- or 12-week courses of acupuncture 

with sham acupuncture among 327 and 20 women with VMS; one compared 6 months of 

acupuncture with a waitlist control among 209 women with VMS; and one 4-arm trial 

randomized 120 breast cancer survivors to 8 weeks of electroacupuncture versus 

gabapentin versus sham acupuncture versus placebo gabapentin.

Systematic Reviews

Study characteristics

We identified 3 eligible SRs evaluating the effectiveness of acupuncture for VMS and quality of 

life. One was a good-quality Cochrane Collaboration SR by Dodin et al40 published in 2013, and 

2 were fair-quality SRs that were qualitative summaries of RCTs published in 201364 and 201541

evaluating acupuncture among women with cancer (primarily breast cancer) who reported VMS. 

The Dodin et al SR included all but 3 of the individual RCTs that were also included in the 2 

fair-quality SRs. Dodin et al excluded one RCT because of insufficient information provided 

about VMS experienced by the participants,65 and 2 RCTs were indexed in the literature 

databases after the search date of January 15, 2013.

66,67

For the purposes of this report, we focus on the SR by Dodin et al40 because it did not limit 

inclusion to trials of women with a history of cancer, it included all but 3 RCTs also included in 

the other 2 SRs, it conducted meta-analyses pertinent to this report, and it was judged to be of 

higher quality than the other 2 SRs. Additionally, the other SRs did not provide a quantitative 

synthesis of findings.

Dodin et al included 16 RCTs68-83 comparing any type of acupuncture with no acupuncture, sham 

acupuncture, or other treatments for reducing menopausal hot flashes and improving the quality 

of life of symptomatic perimenopausal and postmenopausal women. Of the 16 RCTs, one is not 

pertinent to our report because the study intervention was moxibustion alone,

70 which is not 

technically acupuncture. Collectively, the 15 relevant RCTs included 1127 women. The 

minimum number of daily VMS for inclusion in the trials was 2 to 7 in the 8 RCTs that reported 

this inclusion criterion. All RCTs included perimenopausal or postmenopausal women. Five 

exclusively enrolled women who had recently completed treatment for breast cancer, and one 

included only women who had undergone bilateral oophorectomy.

Duration of acupuncture treatments ranged from 4 to 12 weeks across the RCTs. Traditional 

acupuncture was administered in 11 trials, electroacupuncture in 3, and a combination of 

acupuncture and acupressure in one RCT. Standardized or semistandardized acupuncture 

treatment protocols were employed in 12 RCTs, with the number of acupuncture points needled 

at each treatment session ranging from 4 to 13. Individualized treatments were administered in 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

17

the other 3 RCTs. Although 6 of the 15 applicable trials reported durability of effect at 3 to 12 

months, the SR by Dodin et al40 did not address durability of treatment effect. 

Twelve RCTs reported daily VMS as assessed by a self-report symptom diary. The remaining 3 

also assessed daily VMS frequency but reported the findings as a Hot Flash Score, calculated by 

multiplying the number of VMS per day by self-reported VMS severity. Three RCTs assessed 

health-related quality of life using the Menopause-specific Quality of Life (MENQOL) 

instrument, SF-36, or a visual analog scale. Sleep quality or quantity was assessed in 4 RCTs 

using the Women’s Health Initiative Insomnia Rating Scale, Pittsburgh Sleep Quality Index, or 

number of hours of sleep per night. The Kupperman Index was used in 3 RCTs to assess 

menopause-related symptoms. Two RCTs assessed symptoms of depression using the Beck 

Depression Inventory, 2 assessed symptoms of anxiety, one used the Greene Climacteric Scale, 

and one used the Women’s Health Questionnaire. Authors of the SR considered the MENQOL, 

the Kupperman Index, the Greene Climacteric Scale, and the Women’s Health Questionnaire as 

measures of quality of life. 

Characteristics of the SR and included RCTs are summarized in Table 3. 

Table 3. Study Characteristics: Dodin et al 201340

Characteristic Value

Systematic review

Number of included trials 15a

Number of patients 1127

Date of SR literature search January 2013

Age range, years 40-76 

RCTs included in the SR

Study years 2006-2013

Countries

USA

Sweden

South Korea

Norway

China

Denmark

6 

3 

2 

2 

1 

1

Population

Perimenopausal or postmenopausal

Women who had completed treatment for breast cancer

Women who had ovaries surgically removed

13 

1 

1

Acupuncture interventions

Traditional acupuncture

Electroacupuncture

Acupuncture plus acupressure

11

3 

1

Planned number of acupuncture treatments 5-36

Length of intervention period 4-12 weeks

Training of persons administering acupuncture

Licensed acupuncturist

Physiotherapist

Traditional Korean medical doctor

Not reported

7 

4 

2 

2
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

18

Characteristic Value

Comparisonsb

No acupuncture or usual care only

Sham acupuncture

Hormone therapy

Relaxation

5 

10

3 

1

Outcomes

Daily VMS diary

VMS frequency

VMS severity

Hot flash score (frequency times severity)

Kupperman Index

MENQOL

Sleep quality (various measures)

15

12

5 

3 

3 

2 

4

Timing of last outcome assessment after randomization

3 days after each treatment

8-24 weeks

6-24 months

1 

10

4 a We excluded one of the 16 RCTs because the study intervention was moxibustion, which is not technically 

acupuncture.

b Some RCTs included 3 arms and thus had 2 comparators.

Risk of bias—Systematic review

In the SR, authors assessed each included RCT using the Cochrane Risk of Bias Tool across 6

domains (2 selection bias domains, detection bias, attrition bias, reporting bias, and other). Of the 

12 trials that contributed data to meta-analyses reported in the SR, 10 were judged by the authors 

to have 4 or more low risk of bias domains (out of 6) and 2 were judged to have 3 low risk of 

bias domains. Applying the Cochrane guidance for assessing overall risk of bias, 2 RCTs would 

be rated as low risk and 10 would be rated as high risk. 

New Randomized Controlled Trials

Study characteristics

We identified 4 relevant RCTs published after 2012 that assessed the impact of acupuncture on 

VMS or quality of life among perimenopausal or postmenopausal women.50-53 Avis et al52

compared acupuncture with no acupuncture for the treatment of VMS. In this RCT, 209 

perimenopausal or postmenopausal women who reported an average of 4 or more VMS per day 

were randomized to receive up to 20 acupuncture treatments within 6 weeks or to a waitlist 

control. In a 4-arm trial, Mao et al51 compared acupuncture with sham acupuncture and 

randomized 120 breast cancer survivors experiencing bothersome hot flashes to gabapentin 

versus placebo versus 10 treatments (8 weeks) of electroacupuncture, compared with sham 

acupuncture. Ee et al50 randomized 327 perimenopausal and postmenopausal women 

experiencing bothersome hot flashes to 10 treatments (8 weeks) of acupuncture or sham 

acupuncture. Nedeljkovic et al randomized 40 postmenopausal women with at least 20 hot 

flashes per week to 12-weeks of acupuncture, sham acupuncture, Chinese herbal medicine, or 

placebo. 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

19

Outcome measures

In Avis et al52 primary outcomes were daily hot flash frequency and severity, as measured by a 

daily hot flash diary. Secondary outcomes were hot flash interference with daily life, sleep 

quality, depressive symptoms, somatic and other symptoms, anxiety, and quality of life assessed 

at end of treatment and 6 months post-treatment. In Mao et al51 the primary outcome was the 

once per week average hot flash composite score as measured by a daily hot flash diary. 

Participants documented their hot flash frequency and severity each day starting from baseline 

until end of intervention and then for 1 week at 12 and 24 weeks (16 weeks post-treatment). In 

Ee et al,

50 the primary outcome was a hot flash score reflecting frequency and severity at the end 

of treatment. Secondary outcomes included quality of life, anxiety, depression, and adverse 

events. Participants recorded the number of daily mild, moderate, severe, and very severe hot 

flashes for 7 days using a validated hot flash diary. Participants were assessed for secondary 

outcomes at 4 weeks, the end of treatment, and then 3 and 6 months after the end of treatment.

Hot flash frequency and severity, measured with a daily diary at 12 and 24 weeks, were the 

primary outcomes in the study by Nedeljkovic et al. Menopause-related quality of life was 

assessed using the Menopause Rating Scale-II.

Characteristics of the 4 new RCTs are summarized in Table 4.
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

20

Table 4. Study Characteristics of New RCTs

Study

Country

Population

# Women randomized

Type of menopause

# Hot flashes

Mean age in years (range)

Intervention

Category/type

Session frequency/duration

Comparator 

Category/type

Session frequency/duration

General Outcomes 

Instrumentsa

Ee 201650

Australia

327 

Perimenopausal and 

postmenopausal

≥7 moderate per day

Intervention: 55.2 (4.3) 

Comparator: 54.8 (4.2)

Acupuncture

10 treatments over 8 weeks

Sham acupuncture (Park 

Sham device)

10 sessions over 8 weeks

8 and 24 weeks:

Hot flash frequency

Hot flash severity

Hot flash score

Menopause QOL

Hospital Anxiety and 

Depression Scale 

Adverse events

Avis 201652

USA 

209 

Perimenopausal and 

postmenopausal

≥4 per day

53.8 (3.5)

Acupuncture

Up to 20 treatments over 24 

weeks

Waitlist control: usual care 

for 6 months followed by 6-

month course of 

acupuncture treatments

Several time points up to 26 

weeks: 

 Hot flash frequency

 Hot flash severity

 Hot flash Daily Interference

Pittsburgh Sleep Quality Index 

and PROMIS short form Sleep 

Disturbance

Women’s Health 

Questionnaire

Center for Epidemiologic 

Studies Depression Scale

General Anxiety Disorder 

Scale and PROMIS short form 

Anxiety

Perceived Stress Scale

Medical Outcomes Study short 

form, Physical and Mental 

Health Component scores 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

21

Study

Country

Population

# Women randomized

Type of menopause

# Hot flashes

Mean age in years (range)

Intervention

Category/type

Session frequency/duration

Comparator 

Category/type

Session frequency/duration

General Outcomes 

Instrumentsa

Mao 201551

USA 

120 

Breast cancer survivors

≥2 per day of bothersome 

severity

53.4 (3.4)

Electroacupuncture

10 treatments over 8 weeks

(1) Sham acupuncture

10 sessions over 8 weeks

(2) Gabapentin

900 mg/day for 8 weeks

(3) Placebo pill

Gelatin capsules filled with 

lactose monohydrate

8 and 24 weeks:

 Hot flash composite score

Adverse events

Nedeljkovic 

201453

Switzerland

40

Postmenopausal

≥20 per week

53.1 (3.5)

Acupuncture

12 weekly treatments

(1) Sham acupuncture, 12 

weekly sessions

(2) Chinese herbal medicine, 

3 capsules twice daily and 4 

clinic visits

(3) Placebo, 3 capsules 

twice daily and 4 clinic visits

12 and 24 weeks:

Hot flash frequency

Hot flash severity

Menopause Rating Scale-II

a Menopause instruments and scales are described in Appendix D.
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

22

Risk of bias—New RCTs

All 4 new RCTs were judged to be low risk of bias. Risk of bias domains for the 4 RCTs are

reported in Figure 2. 

Figure 2. Risk of Bias Ratings for New Acupuncture RCTsa

a A white bar indicates that the outcome was not reported.

Synthesis of Findings: Primary Outcomes

Vasomotor symptoms

Acupuncture versus no acupuncture or usual care 

In the SR, Dodin et al40 conducted a meta-analysis of 3 trials that compared acupuncture with no 

acupuncture, the results of which demonstrated a statistically significant effect associated with 

acupuncture for both VMS frequency (SMD -0.50, 95% CI -0.69 to -0.31, I2

= 0.0%) and 

severity (SMD -0.54, 95% CI -0.73 to -0.35, I2= 0.0%) compared with no acupuncture. 

Subgroup and sensitivity analysis were not performed. A meta-analysis reported in the review 

also suggests that quality of life, as assessed by the Women’s Health Questionnaire, Menopausal 

Rating Scale, or the Menopause Specific Quality of Life Questionnaire, is improved with 

acupuncture (SMD -0.93, 95% CI -1.20 to -0.67, I2= 32%, 3 trials) compared with no 

acupuncture. Each of the 3 trials included in these meta-analyses was judged by the authors of 

the SR to have low risk of bias for 5 of the 6 Cochrane Collaboration’s Risk of Bias domains 

assessed. However, confidence intervals reported for pooled estimates of effect in this review are 

likely overly precise because Dodin et al did not use methods to account for small sample

effects.84
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

23

We updated the meta-analysis reported in the SR by adding both the results at the end of 

treatment from Avis et al52 and the results of the waitlist control group at the end of treatment 

from the 3-arm RCT by Avis et al80 in the SR by Dodin (which was not included in the metaanalyses of acupuncture versus no acupuncture in that SR). Our updated meta-analysis generated 

an estimate of the SMD of -0.66 (95% CI -1.06 to -0.26; I2

= 61.7%, 5 trials) for reduction in 

VMS frequency (Figure 3) and SMD -0.49 (95% CI -0.85 to -0.13, I2= 18.1%, 4 trials) for 

reduction in VMS severity (Figure 4). This translates to an average of 3 fewer hot flashes daily.

Acupuncture resulted in a statistically significant decrease in hot flash frequency at 6 months that 

was maintained until 12 months after baseline.52 

Figure 3. Forest Plot of Acupuncture versus No Acupuncture on Change in Hot Flash 

Frequency at End of Treatment

Figure 4. Forest Plot of Acupuncture versus No Acupuncture on Change in Hot Flash

Severity at End of Treatment
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

24

Acupuncture versus sham acupuncture 

Several different procedures designed to simulate the subjective experience of receiving an 

acupuncture treatment have been used as semi-inert comparisons to true acupuncture in the 

context of clinical trials. Dodin et al40 conducted meta-analyses using data from 8

trials68,69,72,74,76,77,80,83 that compared acupuncture to a sham control and reported daily VMS 

frequency or severity. These meta-analyses revealed no significant difference for daily VMS

frequency (SMD -1.13, 95% CI -2.55 to 0.29; I2

= 70%) but significantly improved severity of 

hot flashes (SMD -0.45, 95% CI -0.84 to -0.05, I2 = 62%) compared with sham acupuncture. 

Subgroup analyses demonstrated that heterogeneity was partially explained by the trials 

involving women with breast cancer and trials with duration of treatment less than or greater 

than 12 weeks. Collectively, the 8 trials included in the meta-analyses had 37 low-risk, 3 highrisk, and 8 unclear risk of bias domains, as judged by the authors of the SR. 

In the new RCT by Mao et al,

51 electroacupuncture (which involves administering low-dose 

electrical current through some of the acupuncture needles) reduced the hot flash composite 

score at 24 weeks by 7.4 units, compared with 5.9 with sham electroacupuncture, 5.2 with 

gabapentin, and 3.4 with the placebo medication (p<0.001). In the new RCT by Ee et al,

50 hot 

flash scores decreased in both groups by approximately 40% from baseline to end of treatment 

and were sustained for 6 months. There was no evidence of an advantage of electroacupuncture 

over sham acupuncture on quality of life. In the new RCT by Nedeljkovic et al,53 acupuncture 

was more effective than sham acupuncture in reducing hot flash frequency and severity, and in 

improving menopause-related quality of life.

We updated the meta-analysis reported in the SR by adding findings from these 3 new 

RCTs.50,51,53 Our updated meta-analysis generated an estimate of the SMD of -0.21 (95% CI -

0.49 to 0.07, I2= 53.5%, 10 trials) for reduction in VMS frequency (Figure 5) and -0.35 (95% CI 

-0.70 to 0.01, I2

= 66.5%, 8 trials) for reduction in VMS severity (Figure 6). 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

25

Figure 5. Forest Plot of Acupuncture versus Sham Acupuncture on Change in Hot Flash

Frequency at End of Treatment 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

26

Figure 6. Forest Plot of Acupuncture versus Sham Acupuncture on Change in Hot Flash

Severity at End of Treatment

In the 2 RCTs that assessed quality of life in the SR,69,72 no significant difference in quality of 

life (as assessed by the Menopausal Specific Quality of Life questionnaire or the Greene 

Climacteric Scale) was found between acupuncture and sham acupuncture (SMD 0.11, 95% 

CI -0.33 to 0.55). Our updated meta-analysis that included results of changes in the Menopause 

Specific Quality of Life questionnaire in 2 of the new RCTs

50,53 generated an estimate of the 

SMD of -0.23 (95% CI -1.40 to 0.95, I2= 77.0%, 5 trials) for change in quality of life (Figure 7). 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

27

Figure 7. Forest Plot of Acupuncture versus Sham Acupuncture on Change in Quality of 

Life at End of Treatment 

Acupuncture versus hormone therapy 

We did not identify new RCTs that compared acupuncture with hormone therapy. The SR, 

however, included 3 RCTs that compared acupuncture with hormone therapy.81-83 Among these, 

acupuncture was associated with significantly higher daily VMS frequency compared with

hormone therapy (SMD 3.18, 95% CI 2.06 to 4.29, I2 = 0%, 3 trials). There was no statistically 

significant difference in VMS severity between acupuncture and hormone therapy (SMD 0.53, 

95% CI -0.14 to 1.20, 2 trials). Two of these RCTs were judged to be of low risk for 4 of 6 

domains, and one was judged to have 3 low-risk, 2 high-risk, and 1 unclear risk of bias domains. 

Quality of life as assessed by the Kupperman Index was significantly greater in the hormone 

therapy group than in the acupuncture group (MD 0.11, 95% CI 0.01 to 0.21, 1 trial) in the single 

study included in the review that reported this outcome.82

Acupuncture versus relaxation 

We did not identify any new RCTs that compared acupuncture with relaxation. However, a

single RCT73 included in the SR compared electroacupuncture with relaxation, finding no 

significant between-group differences for either daily VMS frequency (MD -0.40, 95% CI -2.18 

to 1.38) or severity (MD 0.20, 95% CI -0.85 to 1.25). This RCT is discussed in greater detail in 

the Meditation, Relaxation, and Mindfulness section of this report. 

Summary of Findings for Acupuncture

We found evidence that a course of acupuncture improves VMS and quality of life compared 

with no acupuncture, but not more than sham acupuncture. This suggests that acupuncture may 

be useful as an adjunct therapy and that the observed clinical benefits associated with 

acupuncture in the context of clinical trials may be attributable in part or in whole to nonspecific 

effects. We also found evidence that acupuncture may improve sleep quality, with one of the 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

28

new RCTs demonstrating significant improvement in sleep compared with a waitlist control on 2

of 3 sleep outcome measures. There is inconclusive evidence of acupuncture’s effectiveness in 

alleviating symptoms of depression or anxiety among women who experience menopause-related 

VMS. The only RCT included in our review that systematically assessed the safety of 

acupuncture relative to no acupuncture or medical management found that acupuncture was 

associated with significantly fewer adverse effects than gabapentin. To make these 

determinations, we drew from an existing, good-quality SR that included 15 pertinent trials and 4 

new low risk of bias RCTs. Three of the 4 new RCTS found that reductions in Hot Flash 

Composite Score and hot flash frequency were maintained at 12, 16, and 24 weeks posttreatment, respectively.51-53

YOGA, TAI CHI, AND QIGONG

Key Points

We identified one eligible good-quality SR, published in 2012, that included 5 RCTs 

comparing yoga with inactive (waitlist) and/or active (exercise, stretching) comparators, and 

2 new RCTs published since 2012 that assessed the impact of yoga on hot flash frequency, 

severity, and quality of life. We did not identify any eligible SRs or new RCTs that evaluated 

the effectiveness of tai chi or qigong.

We conducted a meta-analysis examining the effect of yoga compared with active and 

inactive comparators on hot flash severity change scores using 2 new RCTs and 2 RCTs 

included in the SR. Meta-analysis results suggest that yoga is significantly associated with a 

reduction in hot flash severity (SMD -0.36, 95% CI -0.65 to -0.07, I2= 0.0%).

One RCT examined the effect of yoga versus control on quality of life; results were 

inconclusive due to the small study sample, but suggest that yoga may improve some 

measures of quality of life. Adverse effects were reported as an outcome in only one RCT

and were infrequent. 

Systematic Review

Study characteristics

We identified one good-quality SR by Cramer et al43 published in 2012 that included 5 RCTs85-89

(582 total participants) evaluating the effectiveness of yoga for bothersome menopause 

symptoms. Yoga interventions were delivered in 34 to 40 sessions over 8 weeks to 4 months. 

Outcomes included overall menopause symptoms and quality of life;85-87 VMS;

85,88,89

psychological symptoms;85-89 and the adverse effects of yoga.87 Only one study88 examined the 

durability of treatment effects beyond end of treatment (at 12 weeks post intervention); this study 

only reported findings related to VMS using a daily diary (total score of hot flash frequency and 

severity) and not menopause symptoms or quality of life.

Authors of the SR43 conducted a meta-analysis for outcomes reported by more than 2 RCTs. 

Meta-analyses evaluated the effect of yoga compared with an active comparator and yoga 

compared with no treatment on (1) total menopause symptoms, (2) psychological symptoms, and 

(3) VMS. Subgroup meta-analyses also considered the effect of yoga versus an attention control 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

29

and yoga versus no treatment separately on those 5 outcomes. One RCT was not included 

because it did not report sufficient data for quantitative analysis;88 all RCTs were included in the 

qualitative analysis.

Characteristics of the SR and included RCTs are summarized in Table 5.

Table 5. Study Characteristics: Cramer et al 201243

Characteristic Value

Systematic review

Number of included trials 5

Number of patients 582

Date of SR literature search April 2012

Mean age range in years (median) 45.6 to 54.9 (49.0) 

RCTs included in the SR

Study years 2007-2011

Countries

USA

India

Brazil

2 

2 

1

Population

Perimenopausal or postmenopausal

Women who had completed treatment for breast cancer

4 

1

Yoga interventions

Yoga postures

Breathing

Meditation

Lifestyle lectures

5 

4 

5 

2

Planned number of yoga treatments 34-40

Length of intervention period 8 weeks to 4 months

Training of yoga instructors

Certified and experienced

Not reported

2 

3

Comparisons

Inactive—waitlist

Active—walking, stretching, lifestyle lectures

Inactive and active (3-arm trial)

4 

3 

2

Outcomes

Total menopause symptoms

Vasomotor symptoms

Psychological symptoms

Sleep/insomnia

Adverse effects of yoga

3 

3 

5 

0 

1

Timing of last outcome assessment after randomization

Short-term (taken closest to 12 weeks after randomization)

Long-term (taken closest to 12 months after randomization)

5 

1

Risk of bias—Systematic review 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

30

In the SR,43 risk of bias was assessed for each included RCT using the 12 criteria recommended 

by the Cochrane Back and Neck Review Group. RCTs that met 6 of the 12 criteria were rated as 

having low risk of bias. Of the 5 included RCTs, 2 were rated as low risk of bias86,88 and 3 as 

high risk of bias.85,87,89 Key issues included lack of blinding of participants or providers, 

inadequate intention-to-treat analysis, and inadequate disclosure of the full study protocol.

New Randomized Controlled Trials

Study characteristics

We identified 2 new RCTs published after 2012 that assessed the impact of yoga on VMS or 

quality of life among perimenopausal or postmenopausal women. Avis et al54 conducted a 3-arm

trial comparing the effects of 10 weeks of integral yoga versus health-and-wellness education 

and waitlist control on frequency and severity of hot flashes. Ngowsiri et al55 conducted a trial

comparing a 13-week Rusie Dutton course (which we determined to have similar components to 

yoga) with a waitlist control on menopause symptoms, including VMS. Outcomes examined 

among the 2 RCTs included VMS,54,55 health-related quality of life,54 psychological 

symptoms,

54,55 and sleep disturbance.54,55 Yoga was compared with an attention health-andwellness education control in one RCT54 and with an inactive waitlist control in both RCTs.

Sample sizes were 5454 and 48.55 All participants were perimenopausal or postmenopausal. One 

RCT did not report cause of menopause or breast cancer history.

55 Mean participant age ranged 

from 50.7 to 53.5 years. Yoga interventions included a combination of postures and breathing. 

One RCT included relaxation/meditation techniques in addition to yoga.

54 The duration of yoga 

treatment ranged from 10 weeks to 13 weeks; sessions were held weekly for 90 minutes in both 

trials and all participants were encouraged to practice at home.

Outcome measures

In the 2 new RCTs, VMS was assessed using the Daily Hot Flash Diary (DHFD) at 5 and 10 

weeks post-randomization54 and subscales from the MENQOL (Thai version) at 12 weeks postrandomization.

55 Quality of life was measured using the Global Quality of Life scale at 5 and 10 

weeks post-randomization and the Hot Flash Related Daily Interference Scale at 5 and 10 weeks 

post-randomization.

54 Psychological symptoms were examined using the CESD-10 at 5 and 10 

weeks post-randomization54 (Avis 2014) and subscales from the MENQOL at 12 weeks postrandomization (Ngowsiri 2014).55 Persistence of treatment effects beyond end of treatment was 

not examined in either study. Characteristics of the 2 new RCTs are summarized in Table 6.
Nonpharmacologic Treatments for Menopause-Associated 

Vasomotor Symptoms Evidence-based Synthesis Program

31

Table 6. Study Characteristics of New RCTs

Study

Country

Population

# Women randomized

Type of menopause

# Hot flashes

Mean age (range)

Intervention

Category/type

Session frequency/duration

Comparator

Category/type

Session frequency/duration

General Outcomes 

Instrumentsa

Avis 201454

USA

Yoga: 18 

Health and wellness: 19 

Waitlist: 17 

Natural; surgical; and women 

treated for breast cancer (not 

currently receiving treatment) 

≥4 hot flashes per day on 

average for ≥4 weeks and ≥2 

months since last menses

Yoga: 53.5 (0.7)

Health and wellness: 52.8

(0.7)

Waitlist: 53.5(0.7)

Yoga: integral yoga, adapted 

from Satchidananda, with

breathing, relaxation, and 

postures

1 group session per week for 

10 weeks; 2-3 home practice

per week for 15 minutes

90 minutes duration

Attention: health and 

wellness education

10 weekly educational 

classes; materials to read at 

home (to match time spent in 

home practice among 

individuals in intervention 

group)

90 minutes duration

Inactive comparator: Waitlist; 

no initiation of new therapies 

for hot flashes or participation

in classes for 10 weeks

Frequency/severity of hot 

flashes (DDHF)

Sleep quality (Global Sleep 

Quality index)

Anxiety (HSCL)

Depressive symptoms 

(CESD)

Global quality of life (SF36)

Ngowsiri 

201455 

Thailand

Rusie Dutton: 24

Waitlist: 26 

Type of menopause NR

Mild to moderate menopause 

symptoms per SelfAssessment for Menopause 

Symptoms (developed from 

MRS)

Yoga: 52.9 (4.3)

Waitlist: 50.7 (3.6)

Yoga: Rusie Dutton

1 group class per week for 13 

weeks; 2 home practice per

week

90 minutes duration

Inactive comparator: Waitlist;

offered class 13 weeks after 

post-test assessment was 

completed

Menopause specific quality of 

life subscales (Thai version of 

MENQOL subscales: 

vasomotor, psychological)

a Menopause instruments and scales are described in Appendix D.
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

32

Risk of bias—New RCTs 

Both new RCTs were judged to be high risk of bias. Of primary concern was the use of a weak 

control (waitlist). Also, the study methods were not clearly described, including the method for 

random sequence generation, allocation concealment, and participant, provider, and assessor 

blinding (Figure 8).

Figure 8. Risk of Bias Ratings for New Yoga RCTs

Synthesis of Findings: Primary Outcomes

Vasomotor symptoms

Yoga versus inactive control 

In the SR by Cramer et al, 2 studies examined the effect of yoga versus a waitlist control on 

VMS.

85,88 The study by Carson et al was not included in the quantitative analysis because of 

incomplete reporting; therefore the SR did not conduct a meta-analysis that examined the effect 

of yoga compared with a waitlist control only on VMS. The Carson et al study was the only trial 

in the SR that examined the durability of treatment effect comparing yoga versus a waitlist 

control on VMS88; qualitative results suggest that the positive effects of yoga on VMS persisted 

at 12 weeks after the end of treatment (20 weeks post-randomization). 

Our updated meta-analysis included data from the SR and both new RCTs. We summarized the 

findings of 3 RCTs that examined the effect of yoga compared with a waitlist control on changes 

in hot flash severity.54,55,85 These trials included the 3-armed trial85 identified in the SR, a newly 

identified 3-armed RCT that also included inactive and attention control arms,54 and another 

newly identified RCT that compared yoga with a waitlist control.

55 We pooled the 3-arm trial 

samples and, unlike the SR, analyzed them as part of the inactive control comparator subgroup 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

33

analysis. In our meta-analysis, we found no effect of yoga (3 trials; SMD -0.34, 95% CI -0.92 to 

0.25, I2= 0.0%) (Figure 9).

Figure 9. Forest Plot of Yoga versus Control on Change in Hot Flash Severity at End of 

Treatment

Yoga versus attention control 

Authors of the SR conducted a meta-analysis of 2 RCTs; one compared yoga with an attention 

control89 and the other, a 3-armed trial, included an attention and inactive control.85 Only data 

from the attention control arm was used; the analysis examined yoga versus an attention control 

and found that, compared with exercise, stretching, and lifestyle discussions, yoga was not 

associated with a reduction in VMS (2 trials, SMD -0.13, 95% CI -0.58 to 0.33, I2

= 67%).85,89 

For one of the new RCTs54 – a 3-arm trial (yoga vs waitlist control vs health-and-wellness 

education attention control) – the data from the 2 control arms were pooled and analyzed as part 

of the inactive comparator subgroup analysis. In this trial,

89 yoga was more effective than the 

waitlist and attention control arms combined (SMD -0.40, 95% CI -0.78 to -0.02) (Figure 9). 

Overall effect of yoga versus all controls 

Of the 2 new RCTs, one found significant differences in vasomotor pre/post scores on the 

MENQOL Thai version subscale (p = 0.04).55 The other RCT did not find any statistically 

significant effects of yoga on VMS (Table 6).54 We updated the meta-analysis in the SR by 

adding data reported in the 2 new RCTs54,55 to assess the effect of yoga on changes in hot flash 

severity. We included inactive (waitlist)54,55,85 and attention (health-and-wellness education and 

exercise) controls;54,89 attention and inactive controls were pooled. We found that yoga was 

associated with an overall statistically significant decrease in hot flash severity (4 trials, 

SMD -0.36, 95% CI -0.65 to -0.07, I2= 0.0%) (Figure 9). 

In the SR,43 authors conducted a meta-analysis of 2 RCTs85,89 and found that yoga compared 

with exercise89 and waitlist control85 was not associated with short-term benefits for VMS (2 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

34

trials, SMD -0.04, 95% CI -0.68 to 0.60, I2= 81%). The effects were inconsistent across the 2 

RCTs: one showed a small benefit and the other showed a small harm, but in both, the effect size 

was not statistically significant. However, in one RCT that included a longer-term follow-up (20 

weeks) for yoga compared with no treatment, significant effects were found for VMS.

88

Health-related quality of life

Of the 5 RCTs identified by the SR, only one RCT used a scale (the Greene Climacteric Scale) 

that by our judgment assessed the concept of health-related quality of life,85 which was 

conceptualized as total menopause symptoms in the SR. The other 2 RCTs that assessed total 

menopause symptoms used the Kupperman Index87 and the Menopause Rating Scale.86 In an 

RCT comparing yoga with a walking attention control and a waitlist control,85 yoga was not 

found to have an impact on quality of life. Of the 2 new RCTs, one did not assess quality of life55

and the other used the SF-36 and found no effect of yoga on quality of life.54

Summary of Findings for Yoga

We identified 1 good-quality SR and 2 new RCTs that examined the effect of yoga on 

bothersome menopause symptoms and quality of life. In general, RCTs demonstrated 

inconsistent effects of yoga for reducing VMS and increasing quality of life. Meta-analysis 

results from the SR suggest that short-term effects of yoga are not significantly associated with 

changes in VMS. However, results from our meta-analysis suggest that yoga is associated with a 

decrease in hot flash severity. Our results likely differ from those in the SR because of the 

addition of the 2 new RCTs and because we used a treatment effect that adjusted for baseline 

differences in symptom severity.85 Yoga demonstrated no impact on quality of life.

STRUCTURED EXERCISE

Key Points

We identified 2 SRs (1 good quality and 1 fair quality) that met our eligibility criteria. 

One SR focused exclusively on exercise for the frequency and severity of hot flashes 

among perimenopausal and postmenopausal women, and the other SR included 

evaluations of exercise and mindfulness and relaxation. All of the studies in the goodquality SR were included in the fair-quality SR. 

In the good-quality SR, no statistical evidence was found to support exercise versus 

control (n = 4 studies) or exercise versus yoga (n = 2 studies). One RCT (n = 14) included 

in this SR found hormone therapy to be statistically superior to exercise. 

We identified 2 new RCTs that examined exercise for VMS frequency and severity of hot 

flashes among perimenopausal or postmenopausal women. One of these included only 

women after breast cancer treatment. Both RCTs were judged to be low risk of bias.

Our new meta-analysis compared exercise as an intervention for hot flash frequency and 

severity. We found that exercise did not produce a significant effect on either hot flash 

frequency (SMD -0.08, 95% CI -0.33 to 0.16, I2

= 0.0%, 4 trials) or severity (SMD -0.06, 

95% CI -0.21 to 0.10, I2= 0.0%, 5 trials).
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

35

One new RCT reported on the outcome of menopause-specific quality of life and found

significantly lower sleep problem scores at the 6-month follow-up. The other new RCT 

measured overall health-related quality of life and reported moderate benefit on shortterm (effect size 0.46) and long-term (effect size 0.41) physical function outcomes. A 

companion study reported that exercise significantly improved sleep quality and 

decreased hot flashes during sleep.

One RCT reported on adverse events, finding no serious adverse events and no 

differential incident adverse events between the exercise and control groups.

Systematic Reviews

Study characteristics

We identified 2 eligible SRs evaluating the effectiveness of structured exercise for VMS and 

quality of life.44,46 The good-quality SR by Daley et al44 published in 2014 included 5 RCTs 

evaluating the effectiveness of structured exercise for menopausal hot flashes.85,90-93 The fairquality SR by Woods et al46 published in 2014 included 4 RCTs that were not included in the SR 

by Daley et al. Of those, 3 were excluded by Daley et al because women were not symptomatic 

at baseline, and one was excluded because participants were taking hormone therapy at baseline.

Two RCTs85,92 were included in both SRs. 

For the purposes of this report, we focus only on the good-quality Cochrane Collaboration SR by 

Daley et al44 because it included more studies, employed more inclusive eligibility criteria, 

contained a meta-analysis of studies, and was of higher quality. In this SR, sample sizes of the 5 

included RCTs ranged from 37 to 355. The population was middle-aged women with VMS. 

Most studies required women to be sedentary or at low activity levels at baseline. Hormone 

therapy was restricted in most studies (n = 3) to the previous 2 months to 6 months. The 

comparator in most studies was an inactive control (n = 4) or yoga (n = 2).

A total of 762 women were enrolled across the 5 RCTs with an age range of 40 to 63 years. 

Three of the 5 RCTs were 3-arm trials resulting in a total of 8 comparators. Comparisons in most 

studies were made between inactive controls (n = 4) or yoga (n = 2). The outcome was VMS 

frequency and severity for all 5 RCTs with only one study reporting adverse effects. The 

majority of the RCTs included symptomatic perimenopausal or postmenopausal women (n = 4), 

with one RCT including women with surgically removed ovaries. In the majority of studies (n = 

4) exercise was conducted with supervision or in a group session. The number of planned 

sessions and length of the intervention period varied greatly from 12 to 96 weeks and 12 to 36 

weeks, respectively. Only 2 RCTs used a certified or trained exercise instructor during the 

exercise sessions. The majority of studies were short-term (≤12 weeks). 

Authors of the SR44 conducted a meta-analysis using random-effects models when 2 or more 

RCTs reported the same outcomes. The primary outcome was frequency and severity of VMS

and the secondary outcome was adverse effects of the intervention. For the primary outcome,

summary estimates were generated for exercise compared with no treatment or control (n = 3

studies)

85,90,91 and exercise compared with yoga (n = 2 studies).85,91 Qualitative analysis was 

conducted for one RCT93 that compared structured exercise with hormone therapy and for one 

RCT in which the authors determined that insufficient data were provided to be included in the 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

36

meta-analysis. For the secondary outcome, qualitative analyses were provided for one RCT that 

included data on adverse events of the intervention. 

Characteristics of the SR and included RCTs are summarized in Table 7. 

Table 7. Study Characteristics: Daley et al 201444 

Characteristic Value

Systematic review

Number of included trials 5

Number of patients 762

Date of SR literature search March 2014

Mean age range in years (median) 40-63

RCTs included in the SR

Study years 2002-2011

Countries

Iran

Finland

Sweden

USA

1 

1 

1 

2

Population

Perimenopausal or postmenopausal

Women who had completed treatment for breast cancer

Women who had ovaries surgically removed

4 

0 

1

Exercise interventions

Exercise unsupervised

Exercise with supervision

Exercise in a group

1 

2 

2

Planned number of exercise treatments 12 to 96

Length of intervention period in weeks 12 to 36

Training of exercise instructors

No instructor or supervision

Certified and trained

Not reported

2 

2 

1

Comparisons

Inactive control

Active (yoga or hormone therapy)

5 

3

Outcomes

 Hot flash frequency and severity

 Adverse effects

5 

1

Timing of last outcome assessment after randomization

3 months

6 to 9 months

3 

2 (6 and 9 months)

Risk of bias—Systematic review

In the SR,44 risk of bias was assessed for each included RCT using the Cochrane Risk of Bias 

Tool. The risk of bias was judged to be high among 4 RCTs85,90,92,93 and low in one.91 Key issues 

included unclear specification of sequence generation (n = 2 studies), unclear outcome 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

37

assessment blinding (n = 3 studies), high attrition rate (n = 1 study), and incomplete data 

reporting (n = 2 studies).

New Randomized Controlled Trials 

Study characteristics

We identified 2 relevant RCTs that were not included in the SR by Daley et al.

62,63 Both 

compared exercise with an inactive control. One RCT62 was published in 2015 after the SR, and 

the other,63 published in 2012, was not included in the SR because it evaluated only women who 

had primary breast cancer. The new RCT by Daley et al62 was a 3-arm trial randomizing 

participants to (1) exercise and DVD support, (2) exercise and community-based social support,

or (3) inactive control. The outcomes were measured at both 6 months (immediately following 

completion of the intervention) as well as at 12 months’ post-randomization. The 2 exercise 

intervention groups consisted of face-to-face consultations with a physical activity facilitator, 

with one of the groups additionally receiving a DVD of menopause education and written 

materials to encourage regular exercise. 

The RCT by Duijts et al63 was a 4-arm trial randomizing participants to (1) exercise alone, (2)

exercise plus cognitive behavioral therapy, (3) cognitive behavioral therapy alone, or (4) a 

waitlist control group. The exercise program was a 12-week, individually tailored, home-based, 

self-directed exercise program of 2.5 to 3 hours per week. A primary outcome for both of these 

studies was hot flash frequency and severity. Outcomes were measured at both 12 weeks 

(immediately following completion of the intervention) as well as at 6 months postrandomization.

Among both RCTs, there were 576 participants; all were perimenopausal or postmenopausal. 

One RCT63 included only women with primary breast cancer not currently on cancer treatment 

but experiencing VMS. The other62 included women with VMS who were not receiving hormone 

therapy in the past 3 months. Mean participant age ranged from 47.7 to 57.7 years. Exercise 

interventions were group sessions63 and individually tailored programs,

62 with both studies 

focusing on aerobic exercise. The intervention in one RCT63 included one treatment arm with 

cognitive behavioral therapy and a treatment arm with combined cognitive behavioral therapy 

and exercises; for the purposes of this review, it was excluded from the meta-analysis. The

exercise intervention in the other RCT62 included supplemental DVD education in one arm and 

social support in the other arm. We combined these 2 arms and compared them against the 

control group in our updated meta-analysis because we were primarily concerned with the 

efficacy of exercise. From both RCTs, the duration of exercise interventions ranged from 12

weeks to 24 weeks; sessions were held weekly for 40 to 90 minutes, and all participants were 

encouraged to exercise at home on their own.

Outcome measures

In both new RCTs, VMS was assessed using the Hot Flush Rating Scale. Outcomes were 

assessed at 6 and 12 months post-randomization62 and at 12 weeks and 6 months follow-up.

63

One RCT included generic health-related quality of life measured with the SF-36 Short Health 

Assessment Form as a secondary outcome63 and the other RCT included menopause-specific 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

38

quality of life using subscales from the Women’s Health Questionnaire as a secondary 

outcome.62

Characteristics of the 2 new RCTs are summarized in Table 8.
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

39

Table 8. Study Characteristics of New RCTs

Study

Country

Population

# Women randomized

Type of menopause

# Hot flashes

Mean age (range)

Intervention

Category/type

Session frequency/duration

Comparator

Category/type

Session frequency/duration

General Outcomes 

Instrumentsa

Duijts 

201263

Netherlands

Exercise + CBT: 106 

Exercise: 104 

Waitlist: 103 

Primary breast cancer and 

not currently on treatment

2 or 3 VMS symptoms 

“sometimes” or 1 “often” in 

previous 2 weeks 

Exercise + CBT: 49.0

Exercise: 47.7

Control: 47.8

Cognitive behavioral therapy; 6

weekly group sessions of 90 

minutes, including relaxation 

exercises

Physical exercise: 12 weeks, 

individually tailored, home-based, 

self-directed program of 2.5 to 3 

hours per week

Waitlist control with no 

instructions

Hot flashes and night 

sweats measured 

using Hot Flush Rating 

Scale

Generic quality of life 

measured using SF-36 

Short Form Health 

Survey

Daley 

201562 

Thailand

Exercise + DVD: 87

Exercise + social support: 87

Control: 87

Perimenopausal and 

postmenopausal women 

experiencing ≥ 5 hot 

flashes/night sweats per day 

and have not taken hormone 

therapy in previous 3 months

Exercise + DVD: 52.3 (2.4)

Exercise + social support: 

52.7 (2.5)

Control: 52.0 (2.4)

Both intervention groups: 2 face-toface consultations with a physical 

activity facilitator to support 

engagement in regular exercise 

Exercise + DVD group received a 

menopause-specific information

DVD and written materials to 

encourage regular exercise 

Exercise + support group offered 

opportunity to attend exercise social 

support groups in their communities

Inactive comparator (control) 

offered the opportunity to 

have an exercise 

consultation and were given 

a pedometer at the end of 

their involvement in the 

study

Hot flashes and night 

sweat frequency 

measured using Hot 

Flush Rating Scale

Menopause-specific 

quality of life 

subscales from the 

Women’s Health 

Questionnaire 

a Menopause instruments and scales are described in Appendix D.
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

40

Risk of bias—New RCTs

Both new RCTs were judged to be low risk of bias. Of primary concern in one RCT was the use 

of a weak control and poor compliance with the intervention.62 Both studies had high or unclear 

risk of bias for items related to blinding of the intervener or the participant. However, studies 

using exercise as an intervention are commonly unable to implement blinding and therefore 

comments and ratings should be interpreted in light of these constraints (Figure 10). 

Figure 10. Risk of Bias Ratings for New Structured Exercise RCTsa

a A white bar indicates that the outcome was not reported.

Synthesis of Findings: Primary Outcomes

Vasomotor symptoms

Structured exercise versus inactive control

In the SR, 4 RCTs were evaluated that compared structured exercise with an inactive 

control.85,90,91,93 Three of the these were included in a meta-analysis; one93 was excluded due to 

inadequate reporting of the control group. The random-effects meta-analysis of the other 3 RCTs 

demonstrated no significant effect of exercise on the outcome of frequency or severity of VMS 

when compared with no treatment or control. The RCT excluded in this meta-analysis93 included 

37 women and reported a significant decrease (p<0.05) in hot flash scores in the exercise plus 

soy milk group compared with control. 

Our updated meta-analysis provided separate pooled estimates for hot flash frequency and 

severity. We summarized 3 RCTs85,90,91 from the SR examining a change in hot flash frequency 

plus one new RCT62 assessing a follow-up for hot flash frequency. Effects were fairly consistent 

and studies were homogeneous; however, we found no statistical evidence that exercise 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

41

decreased hot flash frequency when compared with no treatment or control (SMD -0.08, 95% CI 

-0.33 to 0.16, I2= 0.0%, 4 trials) (Figure 11). Only one study, the new RCT by Daley et al,

62

measured hot flash frequency at 12 months, 6 months following end of treatment, finding no 

significant difference between the intervention arm and control arm. For hot flash severity, we 

summarized 3 RCTs62,63,85 on follow-up in hot flash severity and 2 RCTs90,91 on a change in hot 

flash severity. Again, effects were fairly consistent and studies were homogeneous; however, we 

found no statistical evidence that exercise decreased hot flash severity when compared to no 

treatment or control (SMD -0.07, 95% CI -0.26 to 0.13, I2

= 1.8%, 3 trials) (Figure 12). Both 

Duijts et al and Daley et al followed participants after the end of treatment, showing no 

significant durability of effect for exercise as an intervention for hot flash severity. 

Figure 11. Forest Plot of Exercise versus Control on Change in Hot Flash Frequency at 

End of Treatment.
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

42

Figure 12. Forest Plot of Exercise versus Control on Change in Hot Flash Severity

Structured exercise versus yoga

Authors of the SR44 identified 2 RCTs that compared structured exercise with yoga.85,91 In a 

random-effects meta-analysis no evidence was found that structured exercise was significantly 

better than yoga for reducing a combined frequency or severity score for hot flashes (SMD 0.03, 

95% CI -0.45 to 0.38, I2= 61%, 2 trials).

Structured exercise versus hormone therapy 

Only one RCT was identified in the SR evaluating structured exercise compared with hormone 

therapy.92 This RCT reported a larger reduction in the frequency of hot flashes per 24 hours in 

the hormone treatment group than in the exercise group (mean difference 5.80, 95% CI 3.17 to 

8.43) among 14 participants at a 12-week follow-up. 

Sensitivity analyses

Authors of the SR44 found that exclusion of the single low risk of bias RCT did not affect the 

overall findings for any outcome.

Summary of Findings for Exercise

Overall, there were 7 RCTs evaluating exercise as an intervention among perimenopausal or 

postmenopausal women experiencing hot flashes. Five of these were identified in one goodquality SR with a meta-analysis examining the effect of exercise on the frequency and severity of 

hot flashes among perimenopausal or postmenopausal women.44 We also identified 2 new RCTs 

and conducted a new meta-analysis separating the outcomes of hot flash frequency and 

severity.62,63 The meta-analysis conducted in the SR along with our meta-analysis indicated no 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

43

significant effect of exercise for decreasing hot flash frequency or severity. Statistically 

significant findings were shown in 2 new RCTs for the secondary outcomes of generic healthrelated quality of life63 and menopause-specific quality of life.

62 A companion follow-up paper 

indicated that exercise significantly improved sleep quality and decreased hot flashes during 

sleep. Only one RCT reported adverse events, finding no serious or differential adverse events 

between exercise and control groups.91 The sample sizes of included studies in the SR were 

small, many of the primary studies included in the SR were judged to be of low quality, and few 

studies addressed long-term outcomes. The new RCTs were of greater sample size and judged by 

our group to be low risk of bias63 and unclear risk of bias.62 We conclude that the there is no 

evidence that structured exercise is beneficial over an inactive control for the outcomes of VMS 

frequency or severity, and limited evidence suggests that exercise is not beneficial over an active 

comparator or hormone therapy. 

MEDITATION, MINDFULNESS, HYPNOSIS, AND RELAXATION

Key Points

We identified 5 SRs (2 good quality, 3 fair quality) that met eligibility criteria. Four SRs 

examined relaxation and mindfulness. Three of these reported on trials of multiple types 

of interventions. One examined hypnosis exclusively.

No significant difference in reduction of hot flash frequency was found between any 

types of relaxation or mindfulness interventions compared with control groups for the 

primary outcomes of VMS frequency or quality of life. One small RCT found that 

severity of hot flashes decreased more in a modified applied relaxation training group

compared with traditional applied relaxation. One trial of mindfulness-based stress 

reduction compared with a waitlist control found significant improvements in anxiety and 

sleep quality. However, the quality of evidence overall was poor. 

One fair-quality SR included 3 RCTs examining the impacts of hypnosis on breast 

cancer-related symptoms, including hot flashes, and found a significant decrease in hot 

flashes compared with no treatment (effect size ranged from 0.479 to 1.25), but no 

difference with hypnosis when compared to an active control (gabapentin). 

We identified 6 new RCTs that were not included in existing SRs. Three RCTs examined 

paced respiration and 3 examined applied relaxation. Overall, the quality of these new 

studies was mixed. 

We conducted 2 new meta-analyses examining 4 RCTs comparing paced respiration with 

a control group. We found that paced respiration is not associated with a statistically 

significant decrease in hot flash frequency (SMD 0.04, 95% CI -0.73 to 0.82, I2

= 56.6%, 

3 trials) or severity (SMD 0.06, 95% CI -0.69 to 0.80; I2

= 65.1% 3 trials).
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

44

Systematic Reviews

Study characteristics

We identified 5 eligible SRs evaluating the effectiveness of meditation, mindfulness, or 

relaxation interventions for bothersome menopause symptoms.45-49 Of these, one good-quality 

SR focused solely on relaxation,45 and one fair-quality SR focused solely on hypnosis,49 while 

the other 3 evaluated multiple interventions.46-48 Of the latter SRs, one was good quality48 and 2 

were fair quality.46,47 

For the purposes of this report, we focus on the 2014 Cochrane Collaboration SR by Saensak et 

al45 addressing relaxation, and on the 2015 SR by Cramer et al,

49 which presented qualitative 

findings only of studies that examined hypnosis. We include findings from the latter primarily 

because it was the only SR available on this intervention type. The other fair-quality SRs 

evaluated additional studies that were not included in our 2 prioritized SRs, but the individual 

studies were generally of poor quality. One unique RCT evaluating relaxation94 was included in 

the good-quality SR48 of multiple interventions and is noted in our synthesis. Only one RCT 

evaluating mindfulness-based stress reduction95 was identified and it was described in 2 of the 

fair-quality SRs. 

The good-quality SR from 201445 by Saensak et al included 4 RCTs96-99 comparing relaxationbased interventions and either nontreatment or other nonhormonal treatments. The authors 

focused on identifying relaxation techniques that were based on physiological principles of either 

somatic or cognitive relaxation, or both. These included more commonly known types of 

relaxation techniques such as paced respiration and muscle relaxation, though the authors also 

looked for a wide variety of relaxation approaches. Six databases and the grey literature were 

searched through February 19, 2014. The 4 RCTs included 281 menopausal women ranging in 

age from 30 to 77 years. Women were included if their last menstrual period was at least 6 

months ago,98 and one RCT was limited women to those whose last menstrual period was at least 

12 months ago.97 Menopausal status was confirmed with labs including follicle-stimulating 

hormone and estradiol levels in 2 RCTs.98,99 Two RCTs targeted women with primary breast 

cancer who were bothered by hot flashes, one of which specified that women taking aromatase 

inhibitors or hormone therapies other than tamoxifen were included.96,98 The reason for 

menopause onset (spontaneous versus surgical) was not specified in one study.99 

VMS status in these RCTs was described as follows: one trial specified hot flashes that were 

troublesome,96 one trial required at least 5 hot flashes per day,97 one trial required at least 2 hot 

flashes per 24 hour period,98 and one trial required hot flashes severe enough to request 

treatment.99 Outcomes studied included VMS frequency per 24 hours (n = 3),97-99 Kupperman 

Index (n = 2),96,98 and mood (n = 1)96; no studies reported on quality of life or adverse effects. 

Two RCTs included in the SR reported duration of treatment sessions and number of sessions 

planned.98,99 In both of those, the applied relaxation arms received 12 weekly training sessions of 

60 minutes per session. Duration and frequency of relaxation treatments in the other 2 RCTs 

were not reported. Only one of the 4 trials included in the SR assessed the durability of treatment 

effects, reporting outcomes 12 weeks after completion of the intervention.98 Final follow-up visit 

data from this trial and that from a second trial of relaxation99 were pooled despite differences in 

time since baseline. 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

45

Characteristics of this SR and included RCTs are summarized in Table 9.

Table 9. Study Characteristics: Saensak et al 201445

Characteristic Value

Systematic review

 Number of included trials 4

 Number of patients 281

 Date of SR literature search February 2014

 Age range in years 30 to 77

RCTs included in the SR

 Study years 1992-2008

 Country, number of studies

 Sweden

 United Kingdom

 United States

2 

1 

1

 Population

 Excluded women who had stopped hormone therapy within 6 

months 

 Surgical menopause allowed

 Breast cancer patients

2 

3 

2

 Interventions

 Paced respiration

 Applied relaxation

1 

3

 Planned number of sessions

 12 sessions of 60 minutes

 Not reported

2 

2

 Duration of intervention

 4 weeks

 12 weeks

1 

3

 Training of instructors

 Not reported 4a

 Comparisons

 Control

 Electro acupuncture

Superficial needle insertion/electroacupuncture/oral 

estrogen

 Alpha-wave biofeedback

1 

1 

1 

1

 Outcomes

 VMS frequency per 24 hours

 Quality of life

 Menopause-related quality of life

 Mood

 Adverse effects

3 

0 

2 

1 

0

 Timing of last outcomeb

 4 weeks

 6 months

2 

1 a No restriction was placed on training type of person delivering intervention.

b Timing of outcomes for one RCT was not reported.

The fair-quality SR from 201549 included 13 RCTs examining hypnosis among women with 

breast cancer, women who were survivors of breast cancer, women undergoing diagnostic breast 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

46

biopsy, and postmenopausal women without a history of breast cancer. Five databases were 

searched from inception through February 25, 2014, as well as a review of bibliographies. Of the 

13 RCTs, 3 were relevant to our review and included a total of 274 women.100-102 One RCT 

compared hypnosis with attention control among 187 postmenopausal women.100 One compared 

hypnosis with no treatment among breast cancer survivors (n = 60)101; and one compared 

hypnosis with moderate-dose gabapentin in breast cancer survivors and women at increased risk 

of developing breast cancer (n = 27).102 Outcomes measured by these RCTs included VMS 

frequency (n = 2),100,102 health-related quality of life (n = 3),100-102 mood (n = 1),101 and adverse 

effects (n = 2).100,102 Timing of follow-up assessments during these RCTs was not clearly stated.

Characteristics of this SR and included RCTs are summarized in Table 10. 

Table 10. Study Characteristics: Cramer et al 201549

Characteristic Value

Systematic review

 Number of included trials 3

 Number of patients 274

 Date of SR literature search February 2014

 Age range in years 54.5 to 58.2a

RCTs included in the SR

 Study years 2008-2013

 Country, number of studies

 United States 3

 Population

 Breast cancer survivors

 Postmenopausal women without a breast cancer history

2 

1

 Interventions

 Hypnosis 3 

 Planned number of sessions

 5 weekly sessions

 3 weekly sessions

2 

1

 Duration of intervention

 3 to 5 weeks 3

 Training of instructors

 Not reported 3b

 Comparisons

 No treatment

 Attention control

 Gabapentin

1 

1 

1

 Outcomes

 VMS frequency

 Health-related quality of life

 Mood

 Adverse effects

2 

3 

1 

2

 Timing of last outcome 

 Not reported 3 a One study did not report mean age of participants.

b No restriction was placed on training type of person delivering intervention.
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

47

Saensak at al45 pooled the data from 2 RCTs for a meta-analysis comparing the effectiveness of 

relaxation versus acupuncture.98,99 Too few studies were identified for additional sensitivity 

analysis. Cramer et al49 presented only qualitative descriptions of included studies. None of the 

other SRs conducted any meta-analyses; instead, results of comparisons were described 

qualitatively.

Risk of bias—Systematic reviews

In the SR by Saensak et al,

45 authors did not report an overall risk of bias rating for individual 

studies. They noted that the overall quality of the evidence was “very low,” implying high risk of 

bias. Concerns included lack of data, imprecision, failure to report methods adequately, and 2

RCTs whose data were not suitable for meta-analysis. They also noted that the included RCTs 

did not report important outcomes of interest including adverse events, night sweats, and sleep 

disturbances.

The SR by Cramer et al49 reported that, overall, the studies they included had a low risk of bias 

using the Cochrane Risk of Bias tool.33 However, in the risk of bias assessment for the 3 relevant 

studies for our review, one was noted to be at high risk for performance, detection, attrition, and 

other biases.102 The second RCT was at unclear risk of performance and detection bias and high 

risk of reporting bias.101 The third RCT was at unclear risk of selection, performance, and 

detection bias.100

New Randomized Controlled Trials

Study characteristics

We identified 6 relevant RCTs not included in the previous SRs that assessed the impact of 

meditation, mindfulness, hypnosis, or relaxation interventions on VMS or quality of life among 

perimenopausal or postmenopausal women.

56-61 Of the 6 RCTs, 3 examined paced 

respiration56,57,60 and 3 examined applied relaxation.58,59,61 We did not find any new RCTs on 

hypnosis. There was a total of 650 participants across the 6 RCTs, 446 for comparisons of paced 

respiration and 177 for relaxation. 

Characteristics of the 6 new RCTs are summarized in Table 11.
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

48

Table 11. Study Characteristics of New RCTs

Study

Country

Population

# Women randomized

Type of menopause

# Hot flashes

Mean age in years (range)

Intervention

Category/type

Session frequency/duration

Comparator

Category/type

Session frequency/duration

General Outcomes 

Instrumentsa

Paced respiration

Carpenter 201356

USA 

218

Mixed populationa

≥2 hot flashes per day of 

moderate or greater 

severity

53.44 (6.84)

Paced respiration

Home-based practice

15 minutes twice daily

Attention control: fast 

shallow breathing 

Twice daily

Usual care: waitlist

 Hot flash frequency

Hot flash severity

Profile of Mood Statesshort form

Pittsburgh Sleep Quality 

Index

Adverse events

Huang 201557

USA 

123

Perimenopausal or 

postmenopausal

≥4 per day

53.4 (3.4)

Paced respiration

Brief, in-person instruction 

(<15 minutes); ≥15 minutes 

per day home practice

Attention control: music 

listening

Brief, in-person instruction 

(<15 minutes); ≥15 minutes 

per day home practice

 Hot flash frequency

Hot flash severity

Menopause quality of life

Insomnia Severity Index

Beck Depression Inventory

Hospital Anxiety and 

Depression Scale

Sood 201360

USA 

105

Mixed populationb

≥14 per week, at least 1 

month prior to enrollment

51 

Paced breathing (2 arms)

Initial in-person instruction: 

(1) 15 minutes once daily

and (2) 15 minutes twice 

daily

Attention control: usual 

breathing

Initial in-person instruction; 

10 minutes per day

Hot flash frequency

Hot flash severity

Profile of Mood States

Pittsburgh Sleep Quality 

Index

Adverse effects 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

49

Study

Country

Population

# Women randomized

Type of menopause

# Hot flashes

Mean age in years (range)

Intervention

Category/type

Session frequency/duration

Comparator

Category/type

Session frequency/duration

General Outcomes 

Instrumentsa

Applied relaxation

Lindh-Astrand

201561

Sweden

46 

Postmenopausal

≥7 moderate/severe per 24 

hours

Mean age: NR

Applied relaxation,

internet-delivered

10 weeks; 9 weekly modules 

via group sessions

Instructional CD

Untreated control 10 weeks:

Hot flash frequency

Lindh-Astrand

201358

Sweden

60 

Postmenopausal

≥7 moderate to severe per 

24 hours

Applied relaxation: 54.0 

(5.7)

Control: 56.0 (5.1)

Applied relaxation

10 therapist-led group 

sessions over 12 weeks; 

60 minutes per session

Home practice

Untreated control:

waitlist control

12 weeks:

Hot flash frequency

Women’s Health 

Questionnaire: 

 Sleep subscale

Adverse events

Saensak 201359

Thailand

71 

Perimenopausal and 

postmenopausal womenc

≥ Hot flash severity score

Modified relaxation: 49.8 

(3.8)

Applied relaxation: 52.5 

(5.1)

Applied relaxation,

modified relaxation version 

One 60-minute session of 

therapist-led training; daily 

home practice of 15-20 

minutes per day at least 5 

days per week

Weekly phone contact with 

therapist

Applied relaxation:

Conventional

12 weekly sessions of 

therapist-led training; 60 

minutes per session; daily 

home practice; weekly 

phone contact with 

therapists

12 weeks: 

Hot flash frequency

Hot flash severity

Sleep disturbance

a Menopause instruments and scales are described in Appendix D.

b Mixed population includes those with and without a history of breast cancer. c Surgical or natural.
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

50

Risk of bias—New RCTs

Of the 6 new RCTs that we identified, one was judged to be at high risk of bias,61 2 at unclear 

risk of bias,58,60 and 3 at low risk of bias56,57,59 (Figure 13). For the new RCTs of paced 

respiration, there were 2 low risk56,57 and one at unclear risk.60 Of the 3 new relaxation RCTs, 

one was low risk,59 one was unclear risk,58 and one was high risk.61 The one study at high risk 

was stopped prematurely due to an unacceptably high dropout rate (>60%). There were concerns 

regarding blinding of participants in all new RCTs except for one,59 which was comparing 2 

versions of applied relaxation. Similar to other types of interventions considered in this review, it 

is not uncommon to be unable to fully blind participants in relaxation, mindfulness, or hypnosis 

interventions. Another common concern among these trials was the measurement of self-reported 

outcomes among participants who were unblinded or incompletely blinded. Again, this concern 

is shared across all the intervention types included in this review. 

Figure 13. Risk of Bias Ratings for Meditation, Mindfulness, Hypnosis, and Relaxation 

New RCTsa

a A white bar indicates that the outcome was not reported.

Synthesis of Findings: Primary Outcomes

For the primary outcomes of VMS and quality of life, we have organized the findings by 

intervention type (ie, meditation, mindfulness, hypnosis, and relaxation). We focus on findings 

from the good-quality SRs – Saensak et al45 and Rada et al48 – and supplement by using results 

from the new RCTs as applicable.

Meditation

We did not find an SR that addressed meditation, nor did we identify any recently published 

RCTs on this intervention type for treatment of VMS in perimenopausal or postmenopausal 

women. 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

51

Mindfulness

We did not find an SR that addressed mindfulness specifically, nor did we identify any recently 

published RCTs on this intervention type. One RCT95 included in the fair-quality SR by Woods 

et al46 compared mindfulness-based stress reduction with a waitlist control. In this trial of 110 

women (mean age 53.1 years), there was no difference between groups in hot flash frequency or 

intensity. This same study noted that women in the mindfulness-based stress reduction group did 

experience significant improvements (p<0.01) in sleep quality and anxiety compared with a 

waitlist control at 9 weeks.

Hypnosis

Based on one fair-quality SR by Cramer et al49 that included 3 trials of hypnosis on women with 

a history of breast cancer and those with hot flashes in the setting of menopause, there is 

evidence of a significant decrease in hot flashes compared with no treatment (effect size ranged 

from 0.479 to 1.25), though no difference for hypnosis was found compared with treatment with 

gabapentin.100-102 

Active comparators 

One RCT (n = 27) in Cramer et al102 compared hypnosis with 900mg daily of gabapentin among 

breast cancer survivors and those at increased risk for breast cancer. Authors found that the 

median number of hot flashes decreased in both arms (80% versus 33.3% respectively), though 

the between-group difference was not statistically different. A similar reduction in hot flash 

severity as reported by the Hot Flash Severity Score in both arms was similarly not significant 

between groups. 

Inactive comparators 

The 2 RCTs

100,101 comparing hypnosis with no treatment/attention control in Cramer et al49

found that hypnosis led to a larger decrease in hot flashes than no treatment/attention control, 

with effect sizes of 0.479 (p < 0.001) in one RCT of breast cancer survivors,101 and 0.52 to 1.25 

(p < 0.001) in an RCT of postmenopausal women without a history of breast cancer.100 

Relaxation

The evidence, based on findings from the 4 RCTs in Saensak et al45 plus one RCT from the 

multiple intervention SR by Rada et al48 along with 6 of the new RCTs we identified,56-61 does 

not support a significant reduction in hot flash frequency with relaxation techniques versus 

comparator interventions or placebo. One new RCT (n = 60)58 noted a significant decrease in hot 

flash frequency among women treated with applied relaxation compared with control at 12 

weeks (5.0 fewer hot flashes/24 hours compared with 1.9 fewer hot flashes/24 hours respectively 

[P<0.001]). 

We conducted a new meta-analysis of 3 new RCTs56,57,60 plus one RCT97 included in the Saensak 

et al SR, all of which examined paced respiration compared with control. This meta-analysis 

supported the prior conclusion that paced respiration as a relaxation technique is not associated 

with a statistically significant decrease in hot flash frequency or severity. While quality of life 

was among the outcomes reported to be measured by some of these RCTs, it was measured less 

often than hot flash frequency or severity, and the results were rarely noted in the SRs. 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

52

Active comparators 

Of the 4 RCTs included in Saensak et al,

45 2 compared applied relaxation with acupuncture and 

were included in a meta-analysis that examined changes in frequency and severity of hot 

flashes.98,99 Of note, follow-up data from these 2 RCTs were combined even though the timing of 

outcome assessments differed between studies (12 weeks and 24 weeks). In one of these, data 

from both the superficial needle insertion and electroacupuncture groups were combined into one 

“acupuncture” group.99 There was no significant difference in the change of number of hot 

flashes per 24 hours between relaxation versus acupuncture (MD 0.05, 95% CI -1.33 to 1.43, I2= 

0%, 2 trials). In a sensitivity analysis that excluded individuals who were in the superficial 

needle insertion group, effects were similar (MD 0.16, 95% CI -1.35 to 1.68, I2= 0%). Similarly, 

no significant difference was found in severity of hot flashes between groups using the 

Kupperman index (MD -1.32, 95% CI -5.06 to 2.43, I2

= 0%, 2 trials). Saensak et al also 

included a 3-arm study (n = 11 per arm) evaluating paced respiration, muscle relaxation, and 

alpha-wave biofeedback (control).97 The paced respiration group experienced a significant 

decrease in frequency of VMS per 24-hour period from the pretest period to the posttest period 

(p<0.02) while the muscle relaxation group did not. The difference between the groups was not 

significant. 

One new RCT (n = 71)59 randomized perimenopausal and postmenopausal women to a 

traditional 12-week applied relaxation training plus daily home practice compared with a 

modified version of applied relaxation that had a single in-person training session followed by 

daily home practice. Authors found similar reductions in hot flash frequency in both groups, 

though hot flash severity decreased more in the modified applied relaxation training group (p = 

0.02). 

Inactive comparators 

Two RCTs96,97 included in Saensak et al compared relaxation to inactive controls; however, they 

were not suitable for meta-analysis due to differences in outcomes reported and large standard 

deviations in one RCT. Neither found a significant difference in VMS frequency between 

groups. The SR by Rada et al48 provided one additional small RCT comparing deep breathing 

and guided imagery with no treatment among women with breast cancer (n = 16),94 finding no 

significant differences in the frequency of daily hot flashes (MD 0.50; 95% CI -1.23 to 2.23) or 

severity (MD 0.64; 95% CI -2.10 to 3.38) between groups. This RCT also found no difference in 

quality of life between groups. 

Two new RCTs also made an inactive comparison.58,61 One randomized healthy postmenopausal 

women (n = 60) to 10 sessions of therapist-led applied relaxation versus a waitlist control 

condition.58 Authors found a significant decrease in hot flash frequency in the applied relaxation 

group compared with the control group at 12 weeks that was sustained at 3 months (5.0 fewer hot 

flashes/24 hours compared with 1.9 fewer hot flashes/24 hours respectively [p < 0.001]). A 

second RCT (n = 46) comparing internet-delivered applied relaxation with control found no 

differences in hot flash frequency between groups at 10 weeks.61 This RCT was limited due to 

early termination in the setting of more than 60-percent dropout rate. Only 3 (13%) of the 

women assigned to internet-delivered applied relaxation completed at least 6 of the 9 planned 

modules. 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

53

We combined the findings from one RCT97 included in Saensak et al with data from 3 new RCTs 

comparing paced respiration with control for 2 new meta-analyses.56,57,60 For these metaanalyses, we combined control groups for the comparison as follows: attention control groups 

from 3 trials56,57,60 were combined with an alpha-wave feedback control group from a fourth 

trial,97 and 2 attention control comparator groups from one RCT60 were combined together. We 

combined data from end-of-treatment across trials (range 4 to 16 weeks). None of these 4 RCTs 

included follow-up after completion of the intervention to assess for duration of treatment 

effects. In each of our 2 meta-analyses, only 3 of the 4 RCTs are included. Freedman et al97

measured only hot flash frequency and although Sood et al60 measured both frequency and 

severity, the data on frequency was not sufficient to be included in the meta-analysis. We found 

that paced respiration was not associated with a statistically significant decrease in hot flash 

frequency (SMD 0.04, 95% CI -0.73 to 0.82, I2= 56.6%, 3 trials) (Figure 14) or in hot flash 

severity (SMD 0.06, 95% CI -0.69 to 0.80, I2= 65.1%, 3 trials) (Figure 15), but 95% CIs were 

wide and do not exclude a small effect. 

Figure 14. Forest Plot of Paced Respiration versus Control on Change in Hot Flash 

Frequency
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

54

Figure 15. Forest Plot of Paced Respiration versus Control on Change in Hot Flash 

Severity at End-of-Treatment

Summary of Findings for Meditation, Mindfulness, Hypnosis, and Relaxation

We found that there is some support for the use of hypnosis to treat menopause-associated VMS, 

but the evidence does not support the use of relaxation techniques to alleviate VMS, and there is 

insufficient data on the role of mindfulness. To make this determination, we drew from 5 

existing SRs (2 good and 3 fair quality)45-49 and 6 new RCTs.56-61 Overall, the quality of data is 

poor to mixed. For relaxation, there were 11 trials including 4 from one good-quality SR by 

Saensak et al,

45 1 from a good-quality SR by Rada et al,48 and 6 new RCTs.56-61 Relaxation 

techniques studied were mostly applied relaxation and paced respiration. We added to the 

existing literature by conducting a new meta-analysis of paced respiration trials by combining 

data from 3 new RCTs and one RCT from the SR.45 Similar to conclusions drawn in the SR, our 

meta-analysis found no significant treatment effect on VMS frequency (SMD 0.04, 95% CI -0.73 

to 0.82; n = 162, I2

= 56.6%) or severity (SMD 0.06, 95% CI -0.69 to 0.80; n = 211; I2= 65.1%). 

One small RCT59 found that severity of hot flashes decreased more in a modified applied 

relaxation training group compared with traditional applied relaxation. One fair-quality SR of 

hypnosis49 included 3 RCTs and found a significant decrease in hot flashes compared with no 

treatment (effect size ranged from 0.479 to 1.25), though no difference when compared to 

treatment with gabapentin. No new hypnosis trials were found. A fair-quality SR46 included the 

only RCT95 of mindfulness-based stress reduction compared with a waitlist control and found no 

difference in VMS frequency or severity. 

SECONDARY OUTCOMES ACROSS ALL INTERVENTIONS

Acupuncture

Adverse effects

Four studies included in the SR by Dodin et al40 reported mild bruising at the site of acupuncture 

needle insertion. Four other studies reported no adverse effects associated with acupuncture. 

Adverse effects, if any, reported in the other 7 RCTs were not discussed by Dodin et al. Adverse 

effects were not reported in the RCT by Avis et al.52 No significant adverse events were reported 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

55

in the RCT by Ee et al,

50 but among the 327 patients allocated to either true or sham acupuncture, 

8 (2%) reported bleeding or bruising, 7 (2%) reported pain, 3 (1%) reported syncope or 

presyncope, 3 (1%) reported worsening of symptoms, 1 reported tingling near an acupuncture 

point, 1 reported swelling around an acupuncture point and itching of the whole arm, 1 reported 

skin sensitivity and feeling hot, 1 reported nervousness, and 1 reported essential tremor. The 

RCT by Mao et al51 reported 5 (17%) adverse effects in the real acupuncture arm, 1 (3%) in the 

sham arm, 8 (27%) in the placebo pill group, and 13 (43%) in the gabapentin arm (p value across 

the 4 groups was 0.005). All of the adverse effects were graded as mild. 

Other secondary outcomes

Secondary outcomes such as sleep quality/quantity and symptoms of depression or anxiety were 

evaluated in some of the RCTs included in the SR by Dodin et al,

40 but the findings were not 

reported. Of the 3 new RCTs, the one by Avis et al52 had the most extensive reporting of 

secondary outcomes. At the 6-month end-of-treatment assessment period in this trial of 209 

perimenopausal or postmenopausal women, acupuncture was associated with significant 

improvement of sleep, when compared with a waitlist control, using the Pittsburgh Sleep Quality 

Index score, the sleep domain of the Women’s Health Questionnaire, and the Patient-Reported 

Outcomes Measurement Information System (PROMIS) Sleep Disturbance short form. No 

between-group differences were found at 6 months by the different study instruments designed to 

assess depressive or anxiety symptoms.

Yoga

Adverse effects

Of the 5 RCTs in the SR by Cramer et al43 plus the 2 new RCTs, only one reported assessing 

adverse events that are possibly associated with yoga, and found none.87

Other secondary outcomes

The SR43 found positive long- and-short term effects of yoga on psychological symptoms, but no 

effect of yoga on sleep symptoms. Among the 2 new RCTs, one55 found positive effects of yoga 

on psychological symptoms, but did not examine sleep outcomes. The other54 was not 

sufficiently powered to detect differences and thus findings were inconsistent. However, 

participants in the yoga intervention did not experience meaningful changes in sleep quality, 

perceived stress, or depression. 

Structured Exercise

Adverse effects

No serious adverse events were reported in the 5 RCTs included in the SR by Daley et al44 for 

any of the outcomes. In one RCT, the proportion of incident adverse events were similar across 

the exercise group (17%) and the usual activity group (18%).91

Other secondary outcomes

One new RCT62 measured menopause-specific quality of life using subscales from the Women’s 

Health Questionnaire. That study found significantly lower sleep problem scores (mean 

difference -0.11, 95% CI -0.21 to -0.01) among the exercise group when compared with control 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

56

at the 6-month follow up. No statistically significant effects were found for anxiety (mean 

difference -1, 95% CI -2.0 to 0.02) at the 12-month follow-up. 

One new RCT63 measured generic quality of life using the SF-36 Short Form Health Survey. 

Moderate effect sizes were found for short (effect size 0.46, p<0.001) and long-term follow-up 

(effect size 0.41, p = 0.002) among the exercise group compared with control for physical 

function. 

Four years after the intervention, Luoto et al90 published a companion paper using the original 

cohort103 examining long-term quality of life measured by the SF-36 Health Survey 

Questionnaire. In the companion study, the exercise group had a significantly higher physical

functioning (OR 1.41, 95% CI 1.00 to 1.99) compared with the control group. No significant 

associations were found for higher good role functioning (OR 1.21, 95% CI 0.88 to 1.67), 

physical health (OR 1.33, 95% CI 0.96 to 1.84), or general health (OR 1.14, 95% CI 0.81 to 

1.62).103 

An additional companion publication to Luoto et al90 focused on sleep quality.104 Outcomes for 

this study were sleep quality and the amount of hot flashes during sleep measured by mobile 

phone with a 1 (poor) to 5 (good) scale response to each question. Sleep quality was significantly 

improved in the exercise intervention group compared with the control (OR 1.02, 95% CI 1.0 to 

1.05, p = 0.043).104 The amount of hot flashes related to sleep diminished (p = 0.004) by the end 

of the intervention. 

Meditation, Mindfulness, Hypnosis, and Relaxation

Adverse effects

Overall, adverse effects were rarely reported and when noted were mild. For interventions of 

hypnosis, the SR by Cramer et al49 found 3 adverse events in the gabapentin control group in one 

included RCT,102 and no dropouts due to adverse events or no adverse events related to the 

intervention in 2 other RCTs.100,101 One new RCT of paced breathing compared with control60

noted that more women in the paced breathing arm reported mild dizziness than in the control 

arm.

Other secondary outcomes

In general, secondary outcomes of interest were rarely reported in the SRs addressing relaxation, 

hypnosis, or mindfulness, and the results were mixed when they were reported. In our 

examination of reported secondary outcomes in the SRs and new RCTs, the findings were 

generally not significant, with a few exceptions. In one RCT included by Cramer et al,

101

hypnosis decreased depression and anxiety compared with no treatment, though no specific 

results were given. In the one RCT of mindfulness included in the SR by Woods et al,

46

mindfulness-based stress reduction significantly improved both anxiety and sleep quality at 9 

weeks compared with a waitlist control group (p<0.01). 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

57

SUMMARY AND DISCUSSION

We evaluated a broad range of nonpharmacologic interventions for perimenopausal and 

postmenopausal women with VMS, evaluating effects on VMS, health-related quality of life, and 

adverse events. Our review identified good- and fair-quality SRs for all of the eligible 

intervention categories. In addition, we identified 14 new RCTs, representing a 42% increase in 

RCTs in the past 4 years. Based on the number of trials, the evidence base is most developed for 

acupuncture, followed by relaxation, then exercise and yoga. Except for acupuncture, most trials 

used waitlist controls as the comparator and reported outcomes at 6 months or earlier. There 

were few comparative effectiveness trials. However, the growing evidence base allowed for 

updated meta-analyses and estimates of effect for most interventions compared with inactive or 

attention controls. Almost all studies reported effects on VMS frequency or severity; fewer 

reported effects on quality of life, insomnia, or psychological symptoms. Adverse effects were 

rare but often not reported systematically. 

LIMITATIONS

Limitations of the Umbrella Review 

The novel approach of supplementing a review of reviews with findings from recently published 

RCTs allowed for assessment of a broad range of interventions. This approach made it possible 

for us to synthesize both quantitatively and qualitatively the most current information for each of 

the 4 categories of nonpharmacologic interventions for VMS. A significant limitation to this 

approach is that we relied on the authors’ judgments about risk of bias for individual trials and 

the appropriateness of their search strategies, eligibility criteria, and synthesis of the evidence. 

We confirmed (and at times corrected) data included in meta-analysis that we updated, but we 

did not confirm all of the study characteristics and outcomes data reported in the SRs. We 

limited our review to English-language publications, which may have excluded potentially 

informative evidence. 

Limitations of the Studies

Most of the RCTs discussed in our report were relatively small, short-term trials. Adverse events 

were often not reported. All of the studies used self-report assessments, and most did not mask 

participants to intervention allocation, thereby introducing the risk that patients allocated to the 

active interventions might exaggerate clinical improvement. Few of the trials compared 2 or 

more active interventions, which could have informed clinical decision-making for patients or 

healthcare providers faced with deciding among various therapeutic options. Several of the trials 

used usual care or waitlist controls, which do not control for nonspecific effects of a given 

intervention, and as such do not provide insights about an intervention’s potential mechanisms of 

action. However, usual care controls serve as an appropriate control for trials that aim to inform 

patients or healthcare providers what to expect from a given course of treatment relative to not 

undergoing that course of treatment.105 Trials that include a usual care arm introduce a risk of 

performance bias, which may either overestimate or underestimate the true effect size of an 

intervention.106 

Approximately half of the acupuncture trials used sham acupuncture controls. The purpose of a 

sham procedure or attention control is to evaluate whether a given intervention’s mechanisms of 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

58

action involve physiological processes that are independent of nonspecific effects that can be 

attributed to health care providers’ care and attention or individual patients’ beliefs and 

expectations. In the case of acupuncture, there is considerable debate about the appropriate 

control.107,108 Some argue that sham procedures may not be physiologically inert, and that a usual 

care arm may be a more appropriate comparison for trials that aim to inform clinical practice, as 

opposed to determining the specific effects of an intervention. 

Clinical interpretation of the findings from this report was also hampered by the use of many 

different outcome measures across trials, thereby requiring us to report standardized mean 

differences, which are difficult to interpret clinically. A more readily interpretable outcome 

would be the proportion of women achieving the minimum clinically important response, but this 

value has not been established for any of the primary outcomes used in these studies. This was 

especially true for quality-of-life measures, with the additional caveat that there is no universally 

accepted quality-of-life assessment instrument specific to menopausal symptoms. Authors of the 

SRs frequently considered symptom inventories or functional status questionnaires as healthrelated or menopausal-specific quality-of-life instruments. We used the same terms reported by 

the authors of the SRs, with the understanding that the underlying constructs measured are not 

likely to be truly health-related or menopausal-specific quality of life. 

Unexplained heterogeneity evident in some of our meta-analyses represents another limitation of 

the existing evidence. The source of this heterogeneity across studies is probably multifactorial, 

with poor study quality, variable patient eligibility criteria, the use of a wide variety of different 

outcome instruments, differing doses and duration of treatments, and other factors all likely 

contributing to statistical heterogeneity.

SUMMARY OF EVIDENCE 

Strength of Evidence (SOE)

We found evidence that acupuncture (moderate SOE) and yoga (low SOE) improve VMS more 

than controls. A trial that compared acupuncture to enhanced self-care in women with hot flashes 

and breast cancer was published after our search date, and also found benefit for hot flashes.109

However, traditional acupuncture was no better than sham acupuncture. Hypnosis was effective 

in women with breast cancer (low SOE). Neither structured exercise (moderate SOE) nor paced 

respiration (low SOE) improved VMS. Evidence was insufficient for applied relaxation and 

mindfulness-based stress reduction. No trials evaluated qigong, tai chi, or meditation. 

Effects of interventions on health-related quality of life were reported less frequently, more 

inconsistently, and using measures that did not always conform to standard definitions for this 

construct. Consistent with effects on VMS, acupuncture improved health-related quality of life 

when compared with a waitlist control (moderate SOE) but not when compared with sham 

acupuncture (moderate SOE). Yoga did not improve health-related quality of life (insufficient 

SOE). The SOE for adverse effects was rated insufficient because of inconsistent reporting.

In Table 12, we summarize the SOE for effects of interventions compared with control on 

VMS—the priority symptom for many perimenopausal and postmenopausal women.110 Few 

trials compared these interventions with active interventions such as hormone therapy or 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

59

gabapentin, and none of the interventions were compared with antidepressants. Because of the 

sparseness of evidence for these comparisons, we did not rate the SOE. 

Table 12. Strength of Evidence for Effects of Interventions on VMS

Comparison # RCTs 

(Patients) Findings Strength of Evidence(Rationale by Domain)

Acupuncture vs waitlist 4 (501) SMD 0.66 lower

(1.06 lower to 0.26 lower)

Moderate

Low ROB, consistent, direct, 

imprecise

Acupuncture vs sham 

acupuncture 8 (644) SMD 0.35 lower

(0.70 lower to 0.01 higher)

Moderate

Low ROB, consistent, direct, 

imprecise

Yoga vs control 4 (157) SMD 0.36 lower

(0.65 lower to 0.07 lower)

Low

Moderate ROB, consistent, 

direct, imprecise

Structured exercise vs 

control 4 (431)

SMD 0.08 lower

(0.33 lower to 0.16 higher)

Moderate

Moderate ROB, consistent, 

direct, precise

Paced respiration vs 

control 3 (161) SMD 0.04 higher

(0.73 lower to 0.82 higher)

Low

Low ROB, inconsistent, direct, 

imprecise

Applied relaxation vs 

control 2 (82) 1 RCT showed small benefit 

and 1 RCT showed no effect

Insufficient

Moderate ROB, inconsistent, 

direct, imprecise

Hypnosis vs control 3 (274)

No pooled estimate. Effect 

size ranged from 0.479 to 

1.25

Low

Moderate ROB, consistent, 

direct, imprecise

Mindfulness-based 

stress reduction vs 

control

1 (110) No reduction in hot flashes Not rated

Abbreviations: RCT = randomized controlled trial; ROB = risk of bias; SMD = standardized mean difference

CLINICAL IMPLICATIONS 

The VA does not have a current guideline that addresses the management of menopause in 

general, and few clinical practice guidelines specifically address nonpharmacologic treatment 

strategies for VMS. One exception is a 2015 position statement from the North American 

Menopause Society.25 This statement recommends cognitive behavioral therapy, hypnosis, and, 

with caution, mindfulness-based stress reduction. Exercise, yoga, paced respiration, relaxation, 

and acupuncture were considered but not recommended. Our updated analysis shows benefit for 

yoga, acupuncture, and hypnosis compared (primarily) with no treatment and only very limited 

evidence for mindfulness-based stress reduction. These updated results should be considered 

when making clinical or policy recommendations. 

RESEARCH GAPS/FUTURE RESEARCH

For some interventions such as acupuncture and yoga, there is evidence of benefit. However, 

SOE is low to moderate, so larger, high-quality trials are needed. Comparative effectiveness 

trials would be more likely to inform policy and clinical decision-making than sham- or placebocontrolled effectiveness trials. This may be especially true in the search for alternatives to 

pharmacologic approaches to managing menopausal symptoms, where clinical effectiveness 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

60

outcomes may need to be counterbalanced by other outcomes of importance to women, 

healthcare providers, and policymakers, such as potential harm, cost, overall utility, and 

women’s preferences. Research is needed, as well, to better understand considerations related to 

treatment options that women with menopausal symptoms consider to be most important. 

The design of some of the RCTs included in our review can inform future research. For example, 

the internet-based, applied relaxation trial by Lindh-Astrand et al61 is innovative in that it 

explored a way to make treatment more readily accessible and affordable. However, this trial had 

an exceptionally high drop-out rate. More research is needed to better understand how to engage 

and retain patients in internet-based interventions. Pragmatic trials such as the one recently 

published by Avis et al52 simulated clinical practice by allowing patients and acupuncturists to 

negotiate the number and frequency of acupuncture treatments and allowing the acupuncturists to 

design and administer treatments as they would outside the context of the clinical trial. 

Nonpharmacologic clinical interventions such as acupuncture, yoga, meditation, and exercise 

lend themselves well to these types of pragmatic trials, with the caveat that pragmatic, 

comparative effectiveness trials are not designed to determine mechanisms of actions or to 

estimate the extent to which observed clinical benefit associated with a given intervention may 

be attributable to specific versus nonspecific effects. 

None of the RCTs included in this umbrella review specifically involved Veterans. Additional 

research is needed to evaluate the acceptability, feasibility, and comparative effectiveness of 

nonpharmacologic approaches to managing menopausal symptoms for women Veterans in VA 

primary care clinics, as well as other settings and patient populations such as medically 

underserved populations. 

CONCLUSIONS 

Compared with waitlist controls, evidence from RCTs support acupuncture and yoga for 

reducing VMS and the impact of such symptoms on women’s activities and health-related 

quality life. The strength of evidence, however, is low to moderate. Moderately good evidence 

shows no benefit from structured exercise for VMS, but engaging in exercise is known to be 

important for other reasons. The evidence in support of the effectiveness of mindfulness or 

relaxation is mixed, with some promising evidence that needs replication for hypnosis. There is 

insufficient evidence to draw conclusions about the effectiveness of these nonpharmacologic 

therapies for improving sleep, depression, or anxiety. The safety of the nonpharmacologic, 

nonhormonal approaches evaluated in this report has not been rigorously examined, but there is 

no clear signal for a significant potential for harm. Overall, most of the data included in this 

report comes from smaller studies with homogenous participant populations. Larger trials of 

populations more reflective of the diversity of women experiencing VMS will be necessary to 

discern the effectiveness of nonpharmacologic interventions in symptomatic menopausal women. 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

61

REFERENCES 

1. Woods NF, Mitchell ES. Symptoms during the perimenopause: prevalence, severity, 

trajectory, and significance in women's lives. Am J Med. 2005;118 Suppl 12B:14-24. 

2. Santoro N. Perimenopause: From Research to Practice. J Womens Health (Larchmt). 

2015. 

3. Avis NE, Crawford SL, Greendale G, et al. Duration of menopausal vasomotor symptoms 

over the menopause transition. JAMA Intern Med. 2015;175(4):531-539. 

4. Thurston RC, Sowers MR, Sternfeld B, et al. Gains in body fat and vasomotor symptom 

reporting over the menopausal transition: the study of women's health across the nation. 

Am J Epidemiol. 2009;170(6):766-774. 

5. Guthrie JR, Dennerstein L, Taffe JR, Donnelly V. Health care-seeking for menopausal 

problems. Climacteric. 2003;6(2):112-117. 

6. Avis NE, Colvin A, Bromberger JT, et al. Change in health-related quality of life over the 

menopausal transition in a multiethnic cohort of middle-aged women: Study of Women's 

Health Across the Nation. Menopause. 2009;16(5):860-869. 

7. Ayers B, Hunter MS. Health-related quality of life of women with menopausal hot 

flushes and night sweats. Climacteric. 2013;16(2):235-239. 

8. Bhattacharya SM, Jha A. A comparison of health-related quality of life (HRQOL) after 

natural and surgical menopause. Maturitas. 2010;66(4):431-434. 

9. Thurston RC, Bromberger JT, Joffe H, et al. Beyond frequency: who is most bothered by 

vasomotor symptoms? Menopause. 2008;15(5):841-847. 

10. North American Menopause Society. 2012 hormone therapy position statement. 

Menopause. 2012;19(3):257-271. 

11. Menopause: diagnosis and management. Vol NICE Guidelines [NG23]. November 2015. 

Available at: https://www.nice.org.uk/guidance/ng23. Accessed January 25, 2016. 

12. The North American Menopause Society Statement on Continuing Use of Systemic 

Hormone Therapy After Age 65. Menopause. 2015;22(7):693. 

13. U.S. Food and Drug Administration. Guidance for Industry: Estrogen and 

Estrogen/Progestin Drug Products to Treat Vasomotor Symptoms and Vulvar and 

Vaginal Atrophy Symptoms—Recommendations for Clinical Evaluation. (Draft guidance 

from the Center for Drug Evaluation and Research (CDER), January 2003). Available at: 

http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/UCM135338

.pdf. Accessed January 27, 2016. 

14. ACOG Practice Bulletin No. 141: management of menopausal symptoms. Obstet 

Gynecol. 2014;123(1):202-216. 

15. Stuenkel CA, Davis SR, Gompel A, et al. Treatment of Symptoms of the Menopause: An 

Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 

2015;100(11):3975-4011. 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

62

16. Das SR, Kinsinger LS, Yancy WS, Jr., et al. Obesity prevalence among veterans at

Veterans Affairs medical facilities. Am J Prev Med. 2005;28(3):291-294. 

17. Farmer MM, Rose DE, Riopelle D, Lanto AB, Yano EM. Gender differences in smoking 

and smoking cessation treatment: an examination of the organizational features related to 

care. Womens Health Issues. 2011;21(4 Suppl):S182-189. 

18. Lehavot K, Hoerster KD, Nelson KM, Jakupcak M, Simpson TL. Health indicators for 

military, veteran, and civilian women. Am J Prev Med. 2012;42(5):473-480. 

19. Gerber MR, King MW, Pineles SL, et al. Hormone therapy use in women veterans 

accessing veterans health administration care: a national cross-sectional study. J Gen 

Intern Med. 2015;30(2):169-175. 

20. Taylor M. Complementary and Alternative Approaches to Menopause. Endocrinol Metab 

Clin North Am. 2015;44(3):619-648. 

21. Gartoulla P, Davis SR, Worsley R, Bell RJ. Use of complementary and alternative 

medicines for menopausal symptoms in Australian women aged 40-65 years. Med J Aust. 

2015;203(3):146, 146e.141-146. 

22. Gentry-Maharaj A, Karpinskyj C, Glazer C, et al. Use and perceived efficacy of 

complementary and alternative medicines after discontinuation of hormone therapy: a 

nested United Kingdom Collaborative Trial of Ovarian Cancer Screening cohort study. 

Menopause. 2015;22(4):384-390. 

23. National Center for Complementary and Integrative Health. Complementary, Alternative, 

or Integrative Health: What’s In a Name? Available at: 

https://nccih.nih.gov/health/integrative-health. Accessed March 10, 2016. 

24. Grant MD, Marbella A, Wang AT, et al. Menopausal Symptoms: Comparative 

Effectiveness of Therapies. Comparative Effectiveness Review No. 147. (Prepared by 

Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-based 

Practice Center under Contract No. 290-2007-10058-I.) AHRQ Publication No. 15-

EHC005-EF. Rockville, MD: Agency for Healthcare Research and Quality; March 2015. 

www.effectivehealthcare.ahrq.gov/reports/final.cfm. 

25. The North American Menopause Society. Nonhormonal management of menopauseassociated vasomotor symptoms: 2015 position statement of The North American 

Menopause Society. Menopause. 2015;22(11):1155-1174. 

26. Becker LA, Oxman AD. Chapter 22: Overviews of reviews. In: Higgins JPT, Green S 

(editors). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 

[updated March 2011]. The Cochrane Collaboration, 2011. Available at: www.cochranehandbook.org. Accessed October 21, 2015. 

27. Agency for Healthcare Research and Quality. Methods Guide for Effectiveness and 

Comparative Effectiveness Reviews: Rockville, MD: Agency for Healthcare Research 

and Quality. Available at: http://www.effectivehealthcare.ahrq.gov/index.cfm/search-forguides-reviews-and-reports/?pageaction = displayproduct&productid = 318. Accessed 

July 16, 2015. 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

63

28. Goldstein KM, McDuffie JR, Shepherd-Banigan M, et al. Nonpharmacologic, nonherbal 

management of menopause-associated vasomotor symptoms: an umbrella systematic 

review (protocol). Syst Rev. 2016;5(1):56. 

29. PROSPERO: International prospective register of systematic reviews. 

#CRD42016029335: Available at: http://www.crd.york.ac.uk/prospero/. Accessed 

January 25, 2016. 

30. Whiting P, Savovic J, Higgins JP, et al. ROBIS: A new tool to assess risk of bias in 

systematic reviews was developed. J Clin Epidemiol. 2015. 

31. Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduction-GRADE 

evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):383-394. 

32. Balshem H, Helfand M, Schunemann HJ, et al. GRADE guidelines: 3. Rating the quality 

of evidence. J Clin Epidemiol. 2011;64(4):401-406. 

33. Higgins JPT, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration’s tool for 

assessing risk of bias in randomised trials. BMJ. 2011;343. 

34. Robinson KA, Chou R, Berkman ND, et al. Twelve recommendations for integrating 

existing systematic reviews into new reviews: EPC guidance. J Clin Epidemiol. 2015. 

35. Engauge Digitizer (software package). Available at: 

http://markummitchell.github.io/engauge-digitizer/. Accessed February 1, 2016. 

36. Viechtbauer W. Conducting Meta-Analyses in R with the metafor Package (2010). 

Available at: https://www.jstatsoft.org/article/view/v036i03. Accessed April 6, 2016. 

37. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 

1986;7(3):177-188. 

38. Knapp G, Hartung J. Improved tests for a random effects meta-regression with a single 

covariate. Stat Med. 2003;22(17):2693-2710. 

39. Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale, N.J.: L. 

Erlbaum Associates; 1988. 

40. Dodin S, Blanchet C, Marc I, et al. Acupuncture for menopausal hot flushes. Cochrane 

Database Syst Rev. 2013;7:CD007410. 

41. Garcia MK, Graham-Getty L, Haddad R, et al. Systematic review of acupuncture to 

control hot flashes in cancer patients. Cancer. 2015;121(22):3948-3958. 

42. Garcia MK, McQuade J, Lee R, Haddad R, Spano M, Cohen L. Acupuncture for 

symptom management in cancer care: an update. Curr Oncol Rep. 2014;16(12):418. 

43. Cramer H, Lauche R, Langhorst J, Dobos G. Effectiveness of yoga for menopausal 

symptoms: a systematic review and meta-analysis of randomized controlled trials. Evid 

Based Complement Alternat Med. 2012;2012:863905. 

44. Daley A, Stokes-Lampard H, Thomas A, MacArthur C. Exercise for vasomotor 

menopausal symptoms. Cochrane Database Syst Rev. 2014;11:Cd006108. 

45. Saensak S, Vutyavanich T, Somboonporn W, Srisurapanont M. Relaxation for 

perimenopausal and postmenopausal symptoms. Cochrane Database Syst Rev. 

2014;7:CD008582. 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

64

46. Woods NF, Mitchell ES, Schnall JG, et al. Effects of mind-body therapies on symptom 

clusters during the menopausal transition. Climacteric. 2014;17(1):10-22. 

47. Innes KE, Selfe TK, Vishnu A. Mind-body therapies for menopausal symptoms: a 

systematic review. Maturitas. 2010;66(2):135-149. 

48. Rada G, Capurro D, Pantoja T, et al. Non-hormonal interventions for hot flushes in 

women with a history of breast cancer. Cochrane Database Syst Rev. 2010(9):Cd004923. 

49. Cramer H, Lauche R, Paul A, Langhorst J, Kummel S, Dobos GJ. Hypnosis in breast 

cancer care: a systematic review of randomized controlled trials. Integr Cancer Ther. 

2015;14(1):5-15. 

50. Ee C, Xue C, Chondros P, et al. Acupuncture for Menopausal Hot Flashes: A 

Randomized Trial. Ann Intern Med. 2016;164(3):146-154. 

51. Mao JJ, Bowman MA, Xie SX, Bruner D, DeMichele A, Farrar JT. Electroacupuncture 

Versus Gabapentin for Hot Flashes Among Breast Cancer Survivors: A Randomized 

Placebo-Controlled Trial. J Clin Oncol. 2015;33(31):3615-3620. 

52. Avis NE, Coeytaux RR, Isom S, Prevette K, Morgan T. Acupuncture in Menopause 

(AIM) study: a pragmatic, randomized controlled trial. Menopause. 2016. 

53. Nedeljkovic M, Tian L, Ji P, et al. Effects of acupuncture and Chinese herbal medicine 

(Zhi Mu 14) on hot flushes and quality of life in postmenopausal women: results of a 

four-arm randomized controlled pilot trial. Menopause. 2014;21(1):15-24. 

54. Avis NE, Legault C, Russell G, Weaver K, Danhauer SC. Pilot study of integral yoga for 

menopausal hot flashes. Menopause. 2014;21(8):846-854. 

55. Ngowsiri K, Tanmahasamut P, Sukonthasab S. Rusie Dutton traditional Thai exercise 

promotes health related physical fitness and quality of life in menopausal women. 

Complement Ther Clin Pract. 2014;20(3):164-171. 

56. Carpenter JS, Burns DS, Wu J, et al. Paced respiration for vasomotor and other 

menopausal symptoms: a randomized, controlled trial. J Gen Intern Med. 

2013;28(2):193-200. 

57. Huang AJ, Phillips S, Schembri M, Vittinghoff E, Grady D. Device-guided slow-paced 

respiration for menopausal hot flushes: a randomized controlled trial. Obstet Gynecol. 

2015;125(5):1130-1138. 

58. Lindh-Astrand L, Nedstrand E. Effects of applied relaxation on vasomotor symptoms in 

postmenopausal women: a randomized controlled trial. Menopause. 2013;20(4):401-408. 

59. Saensak S, Vutyavanich T, Somboonporn W, Srisurapanont M. Effectiveness of a 

modified version of the applied relaxation technique in treatment of perimenopausal and 

postmenopausal symptoms. Int J Womens Health. 2013;5:765-771. 

60. Sood R, Sood A, Wolf SL, et al. Paced breathing compared with usual breathing for hot 

flashes. Menopause. 2013;20(2):179-184. 

61. Lindh-Astrand L, Holm ACS, Sydsjö G, Andersson G, Carlbring P, Nedstrand E. 

Internet-delivered applied relaxation for vasomotor symptoms in postmenopausal 

women: Lessons from a failed trial. Maturitas. 2015;80(4):432-434. 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

65

62. Daley AJ, Thomas A, Roalfe AK, et al. The effectiveness of exercise as treatment for 

vasomotor menopausal symptoms: randomised controlled trial. BJOG. 2015;122(4):565-

575. 

63. Duijts SF, van Beurden M, Oldenburg HS, et al. Efficacy of cognitive behavioral therapy 

and physical exercise in alleviating treatment-induced menopausal symptoms in patients 

with breast cancer: results of a randomized, controlled, multicenter trial. J Clin Oncol. 

2012;30(33):4124-4133. 

64. Garcia MK, McQuade J, Haddad R, et al. Systematic review of acupuncture in cancer 

care: a synthesis of the evidence. J Clin Oncol. 2013;31(7):952-960. 

65. Walker EM, Rodriguez AI, Kohn B, et al. Acupuncture versus venlafaxine for the 

management of vasomotor symptoms in patients with hormone receptor-positive breast 

cancer: a randomized controlled trial. J Clin Oncol. 2010;28(4):634-640. 

66. Liljegren A, Gunnarsson P, Landgren BM, Robeus N, Johansson H, Rotstein S. Reducing 

vasomotor symptoms with acupuncture in breast cancer patients treated with adjuvant 

tamoxifen: a randomized controlled trial. Breast Cancer Res Treat. 2012;135(3):791-798. 

67. Bao T, Cai L, Snyder C, et al. Patient-reported outcomes in women with breast cancer 

enrolled in a dual-center, double-blind, randomized controlled trial assessing the effect of 

acupuncture in reducing aromatase inhibitor-induced musculoskeletal symptoms. Cancer. 

2014;120(3):381-389. 

68. Vincent A, Barton DL, Mandrekar JN, et al. Acupuncture for hot flashes: a randomized, 

sham-controlled clinical study. Menopause. 2007;14(1):45-52. 

69. Venzke L, Calvert JF, Jr., Gilbertson B. A randomized trial of acupuncture for vasomotor 

symptoms in post-menopausal women. Complement Ther Med. 2010;18(2):59-66. 

70. Park JE, Lee MS, Jung S, et al. Moxibustion for treating menopausal hot flashes: a 

randomized clinical trial. Menopause. 2009;16(4):660-665. 

71. Painovich JM, Shufelt CL, Azziz R, et al. A pilot randomized, single-blind, placebocontrolled trial of traditional acupuncture for vasomotor symptoms and mechanistic 

pathways of menopause. Menopause. 2012;19(1):54-61. 

72. Nir Y, Huang MI, Schnyer R, Chen B, Manber R. Acupuncture for postmenopausal hot 

flashes. Maturitas. 2007;56(4):383-395. 

73. Nedstrand E, Wyon Y, Hammar M, Wijma K. Psychological well-being improves in 

women with breast cancer after treatment with applied relaxation or electro-acupuncture 

for vasomotor symptom. J Psychosom Obstet Gynaecol. 2006;27(4):193-199. 

74. Kim DI, Jeong JC, Kim KH, et al. Acupuncture for hot flushes in perimenopausal and 

postmenopausal women: a randomised, sham-controlled trial. Acupunct Med. 

2011;29(4):249-256. 

75. Kim KH, Kang KW, Kim DI, et al. Effects of acupuncture on hot flashes in 

perimenopausal and postmenopausal women--a multicenter randomized clinical trial. 

Menopause. 2010;17(2):269-280. 

76. Hervik J, Mjaland O. Acupuncture for the treatment of hot flashes in breast cancer 

patients, a randomized, controlled trial. Breast Cancer Res Treat. 2009;116(2):311-316. 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

66

77. Deng G, Vickers A, Yeung S, et al. Randomized, controlled trial of acupuncture for the 

treatment of hot flashes in breast cancer patients. J Clin Oncol. 2007;25(35):5584-5590. 

78. Borud EK, Alraek T, White A, et al. The Acupuncture on Hot Flushes Among 

Menopausal Women (ACUFLASH) study, a randomized controlled trial. Menopause. 

2009;16(3):484-493. 

79. Bokmand S, Flyger H. Acupuncture relieves menopausal discomfort in breast cancer 

patients: a prospective, double blinded, randomized study. Breast. 2013;22(3):320-323. 

80. Avis NE, Legault C, Coeytaux RR, et al. A randomized, controlled pilot study of 

acupuncture treatment for menopausal hot flashes. Menopause. 2008;15(6):1070-1078. 

81. Zhou J, Qu F, Sang X, Wang X, Nan R. Acupuncture and auricular acupressure in 

relieving menopausal hot flashes of bilaterally ovariectomized chinese women: a 

randomized controlled trial. Evid Based Complement Alternat Med. 2011;2011:713274. 

82. Frisk J, Carlhall S, Kallstrom AC, Lindh-Astrand L, Malmstrom A, Hammar M. Longterm follow-up of acupuncture and hormone therapy on hot flushes in women with breast 

cancer: a prospective, randomized, controlled multicenter trial. Climacteric. 

2008;11(2):166-174. 

83. Wyon Y, Wijma K, Nedstrand E, Hammar M. A comparison of acupuncture and oral 

estradiol treatment of vasomotor symptoms in postmenopausal women. Climacteric. 

2004;7(2):153-164. 

84. Cornell JE, Mulrow CD, Localio R, et al. Random-effects meta-analysis of inconsistent 

effects: a time for change. Ann Intern Med. 2014;160(4):267-270. 

85. Elavsky S, McAuley E. Physical activity and mental health outcomes during menopause: 

a randomized controlled trial. Ann Behav Med. 2007;33(2):132-142. 

86. Joshi S, Khandwe R, Bapat D, Deshmukh U. Effect of yoga on menopausal symptoms. 

Menopause Int. 2011;17(3):78-81. 

87. Afonso RF, Hachul H, Kozasa EH, et al. Yoga decreases insomnia in postmenopausal 

women: a randomized clinical trial. Menopause. 2012;19(2):186-193. 

88. Carson JW, Carson KM, Porter LS, Keefe FJ, Seewaldt VL. Yoga of Awareness program 

for menopausal symptoms in breast cancer survivors: results from a randomized trial. 

Support Care Cancer. 2009;17(10):1301-1309. 

89. Chattha R, Raghuram N, Venkatram P, Hongasandra NR. Treating the climacteric 

symptoms in Indian women with an integrated approach to yoga therapy: a randomized 

control study. Menopause. 2008;15(5):862-870. 

90. Luoto R, Moilanen J, Heinonen R, et al. Effect of aerobic training on hot flushes and 

quality of life--a randomized controlled trial. Ann Med. 2012;44(6):616-626. 

91. Sternfeld B, Guthrie KA, Ensrud KE, et al. Efficacy of exercise for menopausal 

symptoms: a randomized controlled trial. Menopause. 2014;21(4):330-338. 

92. Lindh-Astrand L, Nedstrand E, Wyon Y, Hammar M. Vasomotor symptoms and quality 

of life in previously sedentary postmenopausal women randomised to physical activity or 

estrogen therapy. Maturitas. 2004;48(2):97-105. 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

67

93. Hanachi P, Golkho S. Assessment of soy phytoestrogens and exercise on lipid profiles 

and menopause symptoms in menopausal women. Journal of Biological Sciences. 

2008;8(4):789-793. 

94. Fenlon D. Relaxation therapy as an intervention for hot flushes in women with breast 

cancer. Eur J Oncol Nurs. 1999;3(4):223-231. 

95. Carmody J, Crawford S, Churchill L. A pilot study of mindfulness-based stress reduction 

for hot flashes. Menopause. 2006;13(5):760-769. 

96. Fenlon DR, Corner JL, Haviland JS. A randomized controlled trial of relaxation training 

to reduce hot flashes in women with primary breast cancer. J Pain Symptom Manage. 

2008;35(4):397-405. 

97. Freedman RR, Woodward S. Behavioral treatment of menopausal hot flushes: evaluation 

by ambulatory monitoring. Am J Obstet Gynecol. 1992;167(2):436-439. 

98. Nedstrand E, Wijma K, Wyon Y, Hammar M. Vasomotor symptoms decrease in women 

with breast cancer randomized to treatment with applied relaxation or electroacupuncture: a preliminary study. Climacteric. 2005;8(3):243-250. 

99. Zaborowska E, Brynhildsen J, Damberg S, et al. Effects of acupuncture, applied 

relaxation, estrogens and placebo on hot flushes in postmenopausal women: an analysis 

of two prospective, parallel, randomized studies. Climacteric. 2007;10(1):38-45. 

100. Elkins GR, Fisher WI, Johnson AK, Carpenter JS, Keith TZ. Clinical hypnosis in the 

treatment of postmenopausal hot flashes: a randomized controlled trial. Menopause. 

2013;20(3):291-298. 

101. Elkins G, Marcus J, Stearns V, et al. Randomized trial of a hypnosis intervention for 

treatment of hot flashes among breast cancer survivors. J Clin Oncol. 2008;26(31):5022-

5026. 

102. Maclaughlan David S, Salzillo S, Bowe P, et al. Randomised controlled trial comparing 

hypnotherapy versus gabapentin for the treatment of hot flashes in breast cancer 

survivors: a pilot study. BMJ Open. 2013;3(9):e003138. 

103. Mansikkamaki K, Raitanen J, Nygard CH, Tomas E, Rutanen R, Luoto R. Long-term 

effect of physical activity on health-related quality of life among menopausal women: a 

4-year follow-up study to a randomised controlled trial. BMJ Open. 2015;5(9):e008232. 

104. Mansikkamaki K, Raitanen J, Nygard CH, et al. Sleep quality and aerobic training among 

menopausal women--a randomized controlled trial. Maturitas. 2012;72(4):339-345. 

105. Kinser PA, Robins JL. Control group design: enhancing rigor in research of mind-body 

therapies for depression. Evid Based Complement Alternat Med. 2013;2013:140467. 

106. McCambridge J, Sorhaindo A, Quirk A, Nanchahal K. Patient preferences and 

performance bias in a weight loss trial with a usual care arm. Patient Educ Couns. 

2014;95(2):243-247. 

107. Chiu HY, Pan CH, Shyu YK, Han BC, Tsai PS. Effects of acupuncture on menopauserelated symptoms and quality of life in women in natural menopause: a meta-analysis of 

randomized controlled trials. Menopause. 2015;22(2):234-244. 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

68

108. Lund I, Lundeberg T. Are minimal, superficial or sham acupuncture procedures 

acceptable as inert placebo controls? Acupunct Med. 2006;24(1):13-15. 

109. Lesi G, Razzini G, Musti MA, et al. Acupuncture as an integrative approach for the 

treatment of hot flashes in women with breast cancer: a prospective multicenter 

randomized controlled trial (AcCliMaT). J Clin Oncol. 2016;34(15):1795-1802. 

110. Carpenter JS, Woods NF, Otte JL, et al. MsFLASH participants' priorities for alleviating 

menopausal symptoms. Climacteric. 2015:1-8. 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

69

APPENDIX A. SEARCH STRATEGY

SYSTEMATIC REVIEWS

PubMed: November 9, 2015

Search Query Items 

found

#1 Search "Menopause"[Mesh] OR menopaus*[tiab] OR "Climacteric"[Mesh:NoExp] OR 

"Hot Flashes"[Mesh] OR peri-menopaus*[tiab] OR perimenopaus*[tiab] OR 

postmenopaus*[tiab] OR post-menopaus*[tiab] OR climacteric*[tiab] OR hotflash*[tiab] OR hot flash*[tiab] OR hot-flush*[tiab] OR hot flush*[tiab] OR night 

sweat*[tiab] OR vasomotor symptom*[tiab]

91908

#2 Search systematic[sb] OR "Systematic Review"[tiab] OR "Umbrella Review"[tiab] OR 

meta-analysis[tiab] OR "meta analysis"[tiab]

280172

#3 Search #1 AND #2 2771

#4 Search "Acupuncture Therapy"[Mesh] OR "Acupuncture"[Mesh] OR 

"Acupressure"[Mesh] OR "acupuncture"[tiab] OR "acupressure"[tiab] OR 

"electroacupuncture"[tiab]

23260

#5 Search #3 AND #4 45

#6 Search "Mind-Body Therapies"[Mesh: NoExp] OR "Mind-Body Therapy"[tiab] OR 

"Mind Body Therapy"[tiab] OR "Mind-Body Therapies"[tiab] OR "Mind Body 

Therapies"[tiab] OR "Mind Body Medicine"[tiab] OR "Breathing Exercises"[Mesh] OR 

"Breathing Exercise"[tiab] OR "Breathing Exercises"[tiab] OR "Respiratory Muscle 

Training"[tiab] OR "Imagery (Psychotherapy)"[Mesh] OR "Guided Imagery"[tiab] OR 

"Meditation"[Mesh] OR "Meditation"[tiab] OR "Relaxation Therapy"[Mesh] OR 

"Relaxation Therapy"[tiab] OR "Relaxation Techniques"[tiab] OR "Relaxation 

Technique"[tiab] OR "Alexander Technique"[tiab] OR "Mind-Body Relations, 

Metaphysical"[Mesh] OR "Mindfulness"[Mesh] OR "Mindfulness-based Stress 

Reduction"[tiab] OR "MBSR"[tiab] OR "paced respiration"[tiab] OR "Hypnosis"[Mesh] 

OR Hypnoses[tiab] OR Hypnotism[tiab] OR Hypnotherapy[tiab] OR 

Hypnotherapies[tiab] OR Mesmerism[tiab]

16823

#7 Search #3 AND #6 16

#8 "Yoga"[Mesh] OR "Yoga"[tiab] OR "Tai Ji"[Mesh] OR "Tai Ji"[tiab] OR "Tai-ji"[tiab] 

OR "Tai Chi"[tiab] OR "T'ai Chi"[tiab] OR "Taiji"[tiab] OR "Taijiquan"[tiab] OR "Qi 

Gong"[tiab] OR "Qigong"[tiab] OR "Ch'I Kung"[tiab]

4440

#9 Search #3 AND #8 22

#10 Search "Exercise"[Mesh:NoExp] OR "Exercise"[Majr] OR "Circuit-Based 

Exercise"[Mesh] OR "Muscle Stretching Exercises"[Mesh] OR "Physical 

Conditioning, Human"[Mesh] OR "Resistance Training"[Mesh] OR "Resistance 

Training"[tiab] OR "Running"[Mesh] OR "Jogging"[Mesh] OR "Swimming"[Mesh] OR 

"Walking"[Mesh] OR "Exercise"[tiab] OR "Exercises"[tiab] OR "physical activity"[tiab] 

OR "aerobic activity"[tiab] OR "Exercise Movement Techniques"[Mesh] OR 

"Sports"[Mesh]

378950

#11 Search #3 AND #10 204

#12 Search #5 OR #7 OR #9 OR #11 247

#13 Search (#12) AND ("2009/01/01"[Date – Publication] : "3000"[Date – Publication]) 132

#14 Search #13 AND "English"[lang] 123
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

70

EMBASE: November 9, 2015

Search Query Items 

found

#1 'menopause and climacterium'/exp OR 'menopause':ti,ab OR 'menopausal':ti,ab OR 

'peri-menopause':ti,ab OR 'peri-menopausal':ti,ab OR 'perimenopause':ti,ab OR 

'perimenopausal':ti,ab OR postmenopause:ti,ab OR postmenopausal:ti,ab OR postmenopause:ti,ab OR post-menopausal:ti,ab OR climacteric:ti,ab OR 'hot flash':ti,ab 

OR 'hot flashes':ti,ab OR 'hot flush':ti,ab OR 'hot flushes':ti,ab OR 'night sweat':ti,ab 

OR 'night sweats':ti,ab OR 'vasomotor symptoms':ti,ab

140,141

#2 'SR'/exp OR 'meta analysis'/exp OR 'Systematic Review':ti,ab OR 'Umbrella 

Review':ti,ab OR 'meta analysis':ti,ab

200,849

#3 #1 AND #2 2,962

#4 'acupuncture'/exp OR 'acupuncture':ab,ti OR 'acupressure':ab,ti OR 

'electroacupuncture':ab,ti

37,866

#5 #3 AND #4 55

#6 'alternative medicine'/exp OR 'Mind Body Therapy':ti,ab OR 'Mind Body 

Therapies':ti,ab OR 'Mind Body Medicine':ti,ab OR 'breathing exercise'/exp OR 

'Breathing Exercise':ti,ab OR 'Breathing Exercises':ti,ab OR 'Respiratory Muscle 

Training':ti,ab OR 'guided imagery'/exp OR 'Guided Imagery':ti,ab OR 

'meditation'/exp OR 'Meditation':ti,ab OR 'transcendental meditation'/exp OR 

'relaxation training'/exp OR 'relaxation training':ti,ab OR 'Relaxation Therapy':ti,ab 

OR 'Relaxation Techniques':ti,ab OR 'Relaxation Technique':ti,ab OR ' Alexander 

Technique':ti,ab OR 'mindfulness'/exp OR 'Mindfulness-based Stress Reduction':ti,ab 

OR 'MBSR':ti,ab OR 'paced respiration':ti,ab OR 'hypnosis'/exp OR 

hypnogenesis:ti,ab OR hypnosis:ti,ab OR hypnotism:ti,ab OR mesmerism:ti

59,899

#7 #3 AND #6 65

#8 'Qi Gong':ti,ab OR 'Qigong':ti,ab OR 'Chi Kung':ti,ab OR 'Tai Chi'/exp OR 'Tai Ji':ti,ab 

OR 'Tai Chi':ti,ab OR 'Taiji':ti,ab OR 'Taijiquan':ti,ab OR 'Yoga':ti,ab OR 

'kinesiotherapy'/exp

56,974

#9 #3 AND #8 60

#10 'exercise'/exp OR 'sport'/exp OR 'Resistance Training':ti,ab OR 'Exercise':ti,ab OR 

'Exercises':ti,ab OR 'physical activity':ti,ab OR 'aerobic activity':ti,ab

510,515

#11 #3 AND #10 249

#12 #5 OR #7 OR #9 OR #11 319

#13 #12 AND [2009-2015]/py 180

#14 #13 AND [english]/lim 173
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

71

Cochrane: November 9, 2015

Search Query Items 

found

#1 menopause OR menopausal OR peri-menopause OR peri-menopausal OR 

perimenopause OR perimenopausal OR postmenopause OR postmenopausal OR 

post-menopause OR post-menopausal OR climacteric OR hot flash OR hot flashes 

OR hot flush OR hot flushes OR night sweat OR night sweats OR vasomotor 

symptoms:ti,ab,kw (Word variations have been searched)

15991

#2 (MH "Acupuncture+") OR (MH "Alternative Therapies+") OR (MH "Mind Body 

Techniques+") OR (MH "Breathing Exercises+") OR (MH "Qigong") OR (MH "Guided 

Imagery") OR (MH "Meditation") OR (MH "Hypnosis+") OR (MH "Relaxation 

Techniques+") OR (MH "Alexander Technique") OR (MH "Tai Chi") OR (MH 

"Mindfulness") OR (MH "Resistance Training") OR (MH "Muscle Strengthening+") OR 

(MH "Therapeutic Exercise+") OR (MH "Exercise+") OR (MH "Sports+") OR (MH 

"Physical Activity") OR TI (acupuncture OR acupressure OR electroacupuncture OR 

"alternative medicine" OR "Mind Body Therapy" OR "Mind Body Therapies" OR "Mind 

Body Medicine" OR "Breathing Exercise" OR "Breathing Exercises" OR "Qi Gong" OR 

Qigong OR "Chi Kung" OR "Respiratory Muscle Training" OR "Guided Imagery" OR 

Meditation OR "relaxation training" OR "Relaxation Therapy" OR "Relaxation 

Techniques" OR "Relaxation Technique" OR hypnosis OR "Alexander Technique" OR 

"Tai Ji" OR "Tai Chi" OR Taiji OR Taijiquan OR Yoga OR "Mindfulness-based Stress 

Reduction" OR MBSR OR "paced respiration" OR sport OR "Resistance Training" OR 

Exercise OR Exercises OR "physical activity" OR "aerobic activity") OR AB 

(acupuncture OR acupressure OR electroacupuncture OR "alternative medicine" OR 

"Mind Body Therapy" OR "Mind Body Therapies" OR "Mind Body Medicine" OR 

"Breathing Exercise" OR "Breathing Exercises" OR "Qi Gong" OR Qigong OR "Chi 

Kung" OR "Respiratory Muscle Training" OR "Guided Imagery" OR Meditation OR 

"relaxation training" OR "Relaxation Therapy" OR "Relaxation Techniques" OR 

"Relaxation Technique" OR hypnosis OR "Alexander Technique" OR "Tai Ji" OR "Tai 

Chi" OR Taiji OR Taijiquan OR Yoga OR "Mindfulness-based Stress Reduction" OR 

MBSR OR "paced respiration" OR sport OR "Resistance Training" OR Exercise OR 

Exercises OR "physical activity" OR "aerobic activity") (Word variations have been 

searched)

72084

#3 #1 AND #2

Publication Year from 2009 to 2015

806

#4 #3

Cochrane Reviews: 15

Other Reviews: 23

38
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

72

RANDOMIZED CONTROLLED TRIALS

PubMed: February 12, 2016

Search Query Items 

found

#1 Search "Menopause"[Mesh] OR menopaus*[tiab] OR "Climacteric"[Mesh:NoExp] OR 

"Hot Flashes"[Mesh] OR peri-menopaus*[tiab] OR perimenopaus*[tiab] OR 

postmenopaus*[tiab] OR post-menopaus*[tiab] OR climacteric*[tiab] OR hotflash*[tiab] OR hot flash*[tiab] OR hot-flush*[tiab] OR hot flush*[tiab] OR night 

sweat*[tiab] OR vasomotor symptom*[tiab]

92983

#2 Search (randomized controlled trial[pt] OR controlled clinical trial[pt] OR 

randomized[tiab] OR randomised[tiab] OR randomization[tiab] OR 

randomisation[tiab] OR placebo[tiab] OR drug therapy[sh] OR randomly[tiab] OR 

trial[tiab] OR groups[tiab]) NOT (animals[mh] NOT humans[mh]) NOT (Editorial[ptyp] 

OR Letter[ptyp] OR Case Reports[ptyp] OR Comment[ptyp])

2838660

#3 Search #1 AND #2 33136

#4 Search "Acupuncture Therapy"[Mesh] OR "Acupuncture"[Mesh] OR 

"Acupressure"[Mesh] OR "acupuncture"[tiab] OR "acupressure"[tiab] OR 

"electroacupuncture"[tiab]

23994

#5 Search #3 AND #4 186

#6 Search "Mind-Body Therapies"[Mesh: NoExp] OR "Mind-Body Therapy"[tiab] OR 

"Mind Body Therapy"[tiab] OR "Mind-Body Therapies"[tiab] OR "Mind Body 

Therapies"[tiab] OR "Mind Body Medicine"[tiab] OR "Breathing Exercises"[Mesh] OR 

"Breathing Exercise"[tiab] OR "Breathing Exercises"[tiab] OR "Respiratory Muscle 

Training"[tiab] OR "Imagery (Psychotherapy)"[Mesh] OR "Guided Imagery"[tiab] OR 

"Meditation"[Mesh] OR "Meditation"[tiab] OR "Relaxation Therapy"[Mesh] OR 

"Relaxation Therapy"[tiab] OR "Relaxation Techniques"[tiab] OR "Relaxation 

Technique"[tiab] OR "Alexander Technique"[tiab] OR "Mind-Body Relations, 

Metaphysical"[Mesh] OR "Mindfulness"[Mesh] OR "Mindfulness-based Stress 

Reduction"[tiab] OR "MBSR"[tiab] OR "paced respiration"[tiab] OR "Hypnosis"[Mesh] 

OR Hypnoses[tiab] OR Hypnotism[tiab] OR Hypnotherapy[tiab] OR 

Hypnotherapies[tiab] OR Mesmerism[tiab]

28100

#7 Search #3 AND #6 79

#8 Search "Yoga"[Mesh] OR "Yoga"[tiab] OR "Tai Ji"[Mesh] OR "Tai Ji"[tiab] OR "Taiji"[tiab] OR "Tai Chi"[tiab] OR "T'ai Chi"[tiab] OR "Taiji"[tiab] OR "Taijiquan"[tiab] OR 

"Qi Gong"[tiab] OR "Qigong"[tiab] OR "Ch'I Kung"[tiab]

4576

#9 Search #3 AND #8 84

#10 Search "Exercise"[Mesh:NoExp] OR "Exercise"[Majr] OR "Circuit-Based 

Exercise"[Mesh] OR "Muscle Stretching Exercises"[Mesh] OR "Physical 

Conditioning, Human"[Mesh] OR "Resistance Training"[Mesh] OR "Resistance 

Training"[tiab] OR "Running"[Mesh] OR "Jogging"[Mesh] OR "Swimming"[Mesh] OR 

"Walking"[Mesh] OR "Exercise"[tiab] OR "Exercises"[tiab] OR "physical activity"[tiab] 

OR "aerobic activity"[tiab] OR "Exercise Movement Techniques"[Mesh] OR 

"Sports"[Mesh]

387613

#11 Search #3 AND #10 2129

#12 Search #5 OR #7 OR #9 OR #11 2338

#13 Search #12 AND ("2012/01/01"[Date – Publication] : "3000"[Date – Publication]) 653

#14 Search #13 AND "English"[lang] Sort by: Author 612
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

73

EMBASE: February 12, 2016

Search Query Items 

found

#1 'menopause and climacterium'/exp OR 'menopause':ti,ab OR 'menopausal':ti,ab OR 

'peri-menopause':ti,ab OR 'peri-menopausal':ti,ab OR 'perimenopause':ti,ab OR 

'perimenopausal':ti,ab OR postmenopause:ti,ab OR postmenopausal:ti,ab OR postmenopause:ti,ab OR post-menopausal:ti,ab OR climacteric:ti,ab OR 'hot flash':ti,ab 

OR 'hot flashes':ti,ab OR 'hot flush':ti,ab OR 'hot flushes':ti,ab OR 'night sweat':ti,ab 

OR 'night sweats':ti,ab OR 'vasomotor symptoms':ti,ab

142,022

#2 (('randomized controlled trial'/exp OR 'crossover procedure'/exp OR 'double blind 

procedure'/exp OR 'single blind procedure'/exp OR random* OR factorial* OR 

crossover* OR cross NEAR/1 over* OR placebo* OR doubl* NEAR/1 blind* OR singl* 

NEAR/1 blind* OR assign* OR allocat* OR volunteer*) NOT ('case report'/exp OR 

'case study'/exp OR 'editorial'/exp OR 'letter'/exp OR 'note'/exp OR 'conference 

paper'/exp)) AND ([humans]/lim AND [english]/lim AND [2012-2016]/py)

428,259

#3 #1 AND #2 6,358

#4 'acupuncture'/exp OR 'acupuncture':ab,ti OR 'acupressure':ab,ti OR 

'electroacupuncture':ab,ti OR 'alternative medicine'/exp OR 'Mind Body Therapy':ti,ab

OR 'Mind Body Therapies':ti,ab OR 'Mind Body Medicine':ti,ab OR 'breathing 

exercise'/exp OR 'Breathing Exercise':ti,ab OR 'Breathing Exercises':ti,ab OR 

'Respiratory Muscle Training':ti,ab OR 'guided imagery'/exp OR 'Guided Imagery':ti,ab 

OR 'meditation'/exp OR 'Meditation':ti,ab OR 'transcendental meditation'/exp OR 

'relaxation training'/exp OR 'relaxation training':ti,ab OR 'Relaxation Therapy':ti,ab OR 

'Relaxation Techniques':ti,ab OR 'Relaxation Technique':ti,ab OR ' Alexander 

Technique':ti,ab OR 'mindfulness'/exp OR 'Mindfulness-based Stress Reduction':ti,ab 

OR 'MBSR':ti,ab OR 'paced respiration':ti,ab OR 'hypnosis'/exp OR 

hypnogenesis:ti,ab OR hypnosis:ti,ab OR hypnotism:ti,ab OR mesmerism:ti,ab OR 'Qi 

Gong':ti,ab OR 'Qigong':ti,ab OR 'Chi Kung':ti,ab OR 'Tai Chi'/exp OR 'Tai Ji':ti,ab OR 

'Tai Chi':ti,ab OR 'Taiji':ti,ab OR 'Taijiquan':ti,ab OR 'Yoga':ti,ab OR 

'kinesiotherapy'/exp OR 'exercise'/exp OR 'sport'/exp OR 'Resistance Training':ti,ab 

OR 'Exercise':ti,ab OR 'Exercises':ti,ab OR 'physical activity':ti,ab OR 'aerobic 

activity':ti,ab

630,791

#4 #3 AND #4 849

CINAHL: February 12, 2016

Search Query Items 

found

S1 (MH "Menopause+") OR TI ( menopause OR menopausal OR "peri-menopause" OR 

"peri-menopausal" OR perimenopause OR perimenopausal OR postmenopause OR 

postmenopausal OR "post-menopause" OR "post-menopausal" OR climacteric OR 

"hot flash" OR "hot flashes" OR "hot flush" OR "hot flushes" OR "night sweat" OR 

"night sweats" OR "vasomotor symptoms" ) OR AB ( menopause OR menopausal OR 

"peri-menopause" OR "peri-menopausal" OR perimenopause OR perimenopausal OR 

postmenopause OR postmenopausal OR "post-menopause" OR "post-menopausal" 

OR climacteric OR "hot flash" OR "hot flashes" OR "hot flush" OR "hot flushes" OR 

"night sweat" OR "night sweats" OR "vasomotor symptoms" )

22,202

S2 (MH "Acupuncture+") OR (MH "Alternative Therapies+") OR (MH "Mind Body 

Techniques+") OR (MH "Breathing Exercises+") OR (MH "Qigong") OR (MH "Guided 

Imagery") OR (MH "Meditation") OR (MH "Hypnosis+") OR (MH "Relaxation 

Techniques+") OR (MH "Alexander Technique") OR (MH "Tai Chi") OR (MH 

"Mindfulness") OR (MH "Resistance Training") OR (MH "Muscle Strengthening+") OR 

(MH "Therapeutic Exercise+") OR (MH "Exercise+") OR (MH "Sports+") OR (MH 

341,974
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

74

Search Query Items 

found

"Physical Activity") OR TI (acupuncture OR acupressure OR electroacupuncture OR 

"alternative medicine" OR "Mind Body Therapy" OR "Mind Body Therapies" OR "Mind 

Body Medicine" OR "Breathing Exercise" OR "Breathing Exercises" OR "Qi Gong" OR 

Qigong OR "Chi Kung" OR "Respiratory Muscle Training" OR "Guided Imagery" OR 

Meditation OR "relaxation training" OR "Relaxation Therapy" OR "Relaxation 

Techniques" OR "Relaxation Technique" OR hypnosis OR "Alexander Technique" OR 

"Tai Ji" OR "Tai Chi" OR Taiji OR Taijiquan OR Yoga OR "Mindfulness-based Stress 

Reduction" OR MBSR OR "paced respiration" OR sport OR "Resistance Training" OR 

Exercise OR Exercises OR "physical activity" OR "aerobic activity") OR AB 

(acupuncture OR acupressure OR electroacupuncture OR "alternative medicine" OR 

"Mind Body Therapy" OR "Mind Body Therapies" OR "Mind Body Medicine" OR 

"Breathing Exercise" OR "Breathing Exercises" OR "Qi Gong" OR Qigong OR "Chi 

Kung" OR "Respiratory Muscle Training" OR "Guided Imagery" OR Meditation OR 

"relaxation training" OR "Relaxation Therapy" OR "Relaxation Techniques" OR 

"Relaxation Technique" OR hypnosis OR "Alexander Technique" OR "Tai Ji" OR "Tai 

Chi" OR Taiji OR Taijiquan OR Yoga OR "Mindfulness-based Stress Reduction" OR 

MBSR OR "paced respiration" OR sport OR "Resistance Training" OR Exercise OR 

Exercises OR "physical activity" OR "aerobic activity")

S3 S1 AND S2

Published Date: 20120101-20160231

1,029

S4 TI ("randomized controlled trial" OR "controlled clinical trial" OR "randomized" OR 

"randomized" OR "randomization" OR "randomization" OR "placebo" OR "randomly" 

OR "trial" OR "groups" OR AB ("randomized controlled trial" OR "controlled clinical 

trial" OR "randomized" OR "randomized" OR "randomization" OR "randomization" OR 

"placebo" OR "randomly" OR "trial" OR "groups") OR (MH "Randomized Controlled 

Trials")

391,791

S5 S3 AND S4 345

S6 S5 NOT PT (Book OR Book Chapter OR Book Review OR Case Study OR 

Commentary OR Doctoral Dissertation OR Editorial OR Letter OR Masters Thesis OR 

Pamphlet OR Pamphlet Chapter OR Poetry)

339
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

75

APPENDIX B. CRITERIA USED IN QUALITY ASSESSMENT

SYSTEMATIC REVIEWS 

General instructions: The purpose of this rating tool is to evaluate the scientific quality of SRs. It is not 

intended to measure the literary quality, importance, relevance, originality, or other attributes of SRs. 

Step 1: First determine whether it is a SR (SR). Systematic reviews are studies that: 1) include an 

explicit and adequate search, 2) apply prespecified eligibility criteria, and 3) consider quality of 

included studies or risk of bias assessment, and/or describe plans to synthesize or attempt to 

synthesize findings quantitatively and/or qualitatively. 

Step 2: For SRs, grade each of the criteria listed below as “Yes,” “No,” “Can’t tell,” or “Not 

Applicable.” Factors to consider when making an assessment are listed under each criterion. For 

each domain, summarize key methods, level of concern overall (low, high, unclear), and rationale 

for concerns.

STUDY ELIGIBILITY CRITERIA

1. Was an ‘a priori’ design provided?

The research question and inclusion criteria should be established before the conduct of the review 

and the review should adhere to pre-defined objectives and eligibility criteria.

Note: Need to refer to a protocol, ethics approval, or pre-determined/a priori published research 

objectives to score a “yes.”

[] Yes [] No [] Can’t tell [] N/A

Comment: No published protocol; however, their approach is reasonable

 

2. Were study eligibility criteria clearly specified? 

Note: Criteria should be sufficiently detailed to allow replication of study

[] Yes [] No [] Can’t tell [] N/A

Comment: 

3. Were restrictions in eligibility criteria appropriate? Restrictions based on study characteristics 

(eg, date, sample size, study quality, outcomes measured) and based on sources of information (eg,

publication status or format, language) should be appropriate?

[] Yes [] No [] Can’t tell [] N/A

Comment: No language or country restrictions given

Summarize key methods related to Eligibility: 

Summarize concerns (low/high/unclear) and your rationale regarding specification of study eligibility 

criteria: 

IDENTIFICATION AND SELECTION OF STUDIES

4. Was a comprehensive literature search performed? 

At least 2 electronic sources should be searched and electronic searches should be supplemented by 

consulting: reference lists from prior reviews, textbooks, or included studies; specialized registries 

(eg, Cochrane registries); or queries to experts in the field. 

Note: If at least 2 sources + one supplementary strategy used, select “yes”; grey literature search 

counts as supplementary
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

76

[] Yes [] No [] Can’t tell [] N/A

Comment: 

5. Were the terms and structure of the search strategy likely to retrieve as many eligible studies 

as possible?

Note: Search methods should describe: search date, databases used, and search terms (Key words 

and/or MESH terms must be stated and where feasible the search strategy should be provided). 

 

[] Yes [] No [] Can’t tell [] N/A

Comment: 

6. Were restrictions based on date, publication format, or language appropriate?

[] Yes [] No [] Can’t tell [] N/A

Comment: 

7. Was selection bias avoided? 

The review reports the number of studies identified through searches, the numbers excluded, and 

gives appropriate reasons for excluding – based on explicit inclusion/exclusion criteria. Two or more 

raters made inclusion/exclusion decisions.

 

[] Yes [] No [] Can’t tell [] N/A

Comment: 

Summarize key methods related to Study Selection: 

Summarize concerns (low, high, unclear) and rationale regarding Study Selection

DATA COLLECTION AND STUDY APPRAISAL

8. Was there duplicate study selection and data extraction?

Did two or more investigators abstract data, and assess study quality – either independently or with 

one rater over-reading the first raters result?

Was an appropriate method used to resolve disagreements (eg, a consensus procedure)?

[] Yes [] No [] Can’t tell [] N/A

Comment: last paragraph, page 136.

9. Were the characteristics of the included studies provided?

In an aggregated form such as a table, data from the original studies should be provided on the 

participants, interventions and outcomes. The ranges of characteristics in all the studies analyzed 

(eg, age, race, sex, relevant socioeconomic data, disease status, duration, severity or other diseases) 

should be reported in sufficient detail to allow the review authors and readers to interpret the results.

Note: Acceptable if not in table format as long as they are described as above.

[] Yes [] No [] Can’t tell [] N/A

Comment: 

10. Was the scientific quality of the included studies assessed and documented?

A priori methods of assessment should be provided and criteria used to assess study quality specified 

in enough detail to permit replication. 

Note: Can include use of a quality scoring tool or checklist, eg, Jadad scale, risk of bias, sensitivity 

analysis, etc., or a description of quality items, with some kind of result for EACH study (“low” or 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

77

“high” is fine, as long as it is clear which studies scored “low” and which scored “high”; a summary 

score/range for all studies is not acceptable).

[] Yes [] No [] Can’t tell [] N/A

Comment: 

Summarize key methods related to data collection/ROB: 

Summarize concerns regarding data collection/ROB: 

SYNTHESIS AND FINDINGS

11. Was the scientific quality of the included studies used appropriately in formulating 

conclusions?

The results of the methodological rigor and scientific quality should be considered in the analysis (eg, 

subgroup analyses) and the conclusions of the review, and explicitly stated in formulating 

recommendations. 

Note: Might say something such as “the results should be interpreted with caution due to poor quality 

of included studies.” Cannot score “yes” for this question if scored “no” for question 10.

[] Yes [] No [] Can’t tell [] N/A

Comment: 

12. Were the methods used to combine the findings of studies appropriate?

For pooled results, the synthesis should be appropriate given the nature and similarity of included 

studies (conceptual homogeneity), and an accepted quantitative method of pooling should be used 

(ie, more than simple addition; eg, random-effects or fixed-effect model). If only qualitative analyses 

are completed, the study should describe the reasons that quantitative analyses were not completed.

[] Yes [] No [] Can’t tell [] N/A@

Comment:.

13. Was between-study variation (heterogeneity) minimal or addressed in the synthesis?

For pooled results, a qualitative and quantitative assessment of homogeneity (Cochran’s Q and/or I2

) 

should be performed.

Note: Indicate “yes” if they explain that they cannot pool because of heterogeneity/variability between 

interventions.

[] Yes [] No [] Can’t tell [] N/A@

Comment: 

14. Was the likelihood of publication bias assessed?

Publication bias tested using funnel plots, test statistics (eg, Egger’s regression test), and/or search of 

trials registry for unpublished studies.

Note: If no test values, clinical trials.gov search, or funnel plot included, score “no”. Score “yes” if 

mentions that publication bias could not be assessed because there were fewer than 10 included 

studies. 

[] Yes [] No [] Can’t tell [] N/A

Comment:

15. Are the stated conclusions supported by the data presented?

Were the conclusions made by the author(s) supported by the data and/or analyses reported in the 

SR? Conclusions should address limitations of the SR and limitations of the primary studies. 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

78

Conclusions should consider relevance of the included studies to the research question. 

[] Yes [] No [] Can’t tell [] N/A

Summarize key methods related to synthesis: 

Summarize concerns regarding synthesis: 

OTHER 

16. Was the conflict of interest stated?

Potential sources of support should be clearly acknowledged in both the SR and the included studies.

Note: To get a “yes,” must indicate source of funding or support for the SR AND for each of the 

included studies

[] Yes [] No [] Can’t tell [] N/A

Comment: Competing interest for SR authors given (none) but not for primary studies

Step 3: Rate the overall quality of the SR as “Good,” “Fair,” or “Poor” using the guidance below 

and summarize major reasons for rating in the comments box. 

Good = After considering items 1-15, item 15 is rated “Yes” with no important limitations. This means 

that few of the items 1-14 are rated “No,” and none of the limitations are thought to decrease the validity 

of the conclusions. If items 3, 4, 7, 9, 10, 11 or 12 are rated “no”, then the review is likely to have major 

flaws

Fair = After considering items 1-15, item 15 is rated “Yes,” but with at least some important limitations. 

This means that enough of the items 1-15 are rated “No” to introduce some uncertainty about the validity 

of the conclusions.

Poor = After considering items 1-15, item 15 is rated “No.” This means that several of items 1-15 are 

rated “No,” introducing serious uncertainty about the validity of the conclusions.

Overall rating comments: 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

79

Concerns regarding specifications of eligibility criteria

Low concern Considerable effort has been made to clearly specify the review question 

and objectives, and to pre-specify and justify appropriate and detailed 

eligibility criteria that have been adhered to during the review 

High concern 

Studies that would have been important and relevant to answering the 

review question are likely to have been excluded from the review, either 

due to the lack of pre-specified objectives and eligibility criteria, or 

because inappropriate restrictions were imposed or studies that are not

appropriate for addressing the review question have been included. 

Unclear concern Insufficient information is reported to make a judgement about risk of bias. 

Concerns regarding methods used to identify and/or select studies

Low concern 

Given the review question and eligibility criteria as assessed in Domain 1, 

a substantial effort has been made to identify as many relevant studies as 

possible through a variety of search methods using a sensitive and 

appropriate search strategy and steps were taken to minimise bias and 

errors when selecting studies for inclusion. 

High concern Some eligible studies are likely to be missing from the review. 

Unclear concern There is insufficient information reported to make a judgement on risk of 

bias. 

Concerns regarding methods used to collect data and appraise studies 

Low concern

Given the studies included in the review as assessed in domain 2, risk of 

bias was assessed using appropriate criteria, data extraction and risk of 

bias assessment involved two reviewers, and relevant study 

characteristics and results were extracted

High concern

Some bias may have been introduced through the data collection or risk 

of bias assessment processes.

Unclear concerns

There is insufficient information reported to inform a judgement on risk of 

bias. 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

80

Concerns regarding methods used to synthesize results 

Low concern

The synthesis is unlikely to produce biased results, because any 

limitations in the data were overcome, or the findings were so convincing 

that the limitations would have little impact 

High concern

The synthesis is likely to produce biased results, because (i) potential 

biases were ignored (within and/or across studies), (ii) important 

between-study variation was not accounted for; (iii) there were important 

inadequacies in the methodology; or (iv) findings are incompletely 

reported in a way that raises concerns.

Unclear concerns

There is insufficient information reported to make a judgement on risk of 

bias. 

References

Marinopoulos SS, Dorman T, Ratanawongsa N, et al. Effectiveness of continuing medical 

education. Evid Rep Technol Assess (Full Rep). 2007(149):1-69. 

Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF. Improving the quality of reports 

of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting 

of Meta-analyses. Lancet. 1999;354(9193):1896-1900.

Shea BJ, Grimshaw JM, Wells GA, et al. Development of AMSTAR: a measurement tool to 

assess the methodological quality of SRs. BMC Medical Research Methodology. 2007;7(1):1-7.

Whiting P, Savovic J, Higgins JP, et al. ROBIS: A new tool to assess risk of bias in SRs was 

developed. J Clin Epidemiol. 2015. 

RANDOMIZED CONTROLLED TRIALS

General instructions: Rate each risk of bias item listed below as “Low,” “High,” or “Unclear.” 

Rating of individual items:

1.Selection bias:

Domain: Random sequence generation

(Support for judgement: Describe the method used to generate the allocation sequence in sufficient 

detail to allow an assessment of whether it should produce comparable groups.)

Was the allocation sequence adequately generated?

Low risk High risk Unclear risk 

Comment
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

81

Domain: Allocation concealment? 

(Support for judgement: Describe the method used to conceal the allocation sequence in sufficient 

detail to determine whether intervention allocations could have been foreseen in advance of, or during, 

enrolment)

Was allocation adequately concealed?

Low risk High risk Unclear risk 

2. Performance bias 

Domain: Blinding of participants and "treating" personnel (ie, the person(s) delivering the 

intervention).

(Support for judgement: Describe all measures used, if any, to blind study participants and personnel 

from knowledge of which intervention a participant received. Provide any information relating to whether 

the intended blinding was effective.)

Was knowledge of the allocated intervention adequately prevented during the study?

Low risk High risk Unclear risk Outcome NR 

3a. Detection bias (VMS symptoms):

Domain: Blinding of outcome assessment

(Support for judgement: Describe all measures used, if any, to blind outcome assessors from 

knowledge of which intervention a participant received. Provide any information relating to whether the 

intended blinding was effective.)

Was knowledge of the allocated intervention adequately prevented from outcome assessors?

Low risk High risk Unclear risk Outcome NR 

Comment

Comment

Comment
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

82

3b. Detection bias (outcomes measured by self-report, ie, depression, anxiety, sleep, QoL, etc):

Domain: Blinding of outcome assessment

(Support for judgement: Describe all measures used, if any, to blind outcome assessors from 

knowledge of which intervention a participant received. Provide any information relating to whether the 

intended blinding was effective.)

Was knowledge of the allocated intervention adequately prevented from outcome assessors?

Low risk High risk Unclear risk Outcome NR 

3c. Detection bias (Adverse effects):

Domain: Blinding of outcome assessment

(Support for judgement: Describe all measures used, if any, to blind outcome assessors from 

knowledge of which intervention a participant received. Provide any information relating to whether the 

intended blinding was effective.)

Was knowledge of the allocated intervention adequately prevented from outcome assessors?

Low risk High risk Unclear risk Outcome NR 

4. Attrition bias:

Domain: Incomplete outcome data 

(Support for judgement: Describe the completeness of outcome data for each main outcome, including 

attrition and exclusions from the analysis. State whether attrition and exclusions were reported, the 

numbers in each intervention group (compared with total randomized participants), reasons for 

attrition/exclusions where reported, and any re-inclusions in analyses performed by the review authors.)

Were incomplete outcome data adequately addressed?

Low risk High risk Unclear risk 

Comment

Comment

Comment
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

83

5. Reporting bias:

Domain: Selective outcomes reporting 

 (Support for judgement: State how the possibility of selective outcome reporting was examined by the 

review authors, and what was found.)

Are reports of the study free of suggestion of selective outcome reporting? (i.e., the author states 

they will measure an outcome but do not report it)

Low risk High risk Unclear risk 

6. Other

Domain: Other sources of bias

(Support for judgement: State any important concerns about bias not addressed in the other domains 

in the tool.

If particular questions/entries were pre-specified in the review’s protocol, responses should be provided 

for each question/entry.)

Are reports of the study free from other bias due to problems not covered above?

Low risk High risk Unclear risk 

Overall risk of bias rating

Low Unclear High

Narrative:

Comment

Comment
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

84

Risk of Bias Interpretation Criteria

Low risk of bias Bias, if present, is unlikely to alter the results 

seriously.

Adequacy of random sequence 

generation, allocation 

concealment, and blinding scored 

as “low risk of bias” and no 

important concerns related to the 

other domains.

Unclear risk of bias

A risk of bias that raises some doubts about 

the results One or two domains are scored 

“not clear” or not done.

High risk of bias Bias may alter the results seriously More than 2 domains are scored 

as “not clear” or not done

* Items contained in Cochrane Risk of Bias Tool
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

85

APPENDIX C. QUALITY ASSESSMENT RATINGS

References cited in this appendix appear in the reference list of the main report. 

SYSTEMATIC REVIEWS

Publication Eligibility 

Criteria

ID/Select

Studies

Data 

Collection Synthesis Overall

Acupuncture

Dodin 201340 Low Low Low Low Good

Garcia 201541 Low High Low Low Fair

Garcia 201364 Low High Low Low Fair

Yoga

Cramer 201243 Low Low Low Low Good

Exercise

Daley 201444 Low Low Low Low Good

Meditation/Mindfulness/

Hypnosis/ 

Relaxation/Mixed

Saensak 201445 Low Low Low Low Good

Woods 201446 Low Low High High Fair

Cramer 201549 Low Low Low High Fair

Innes 201047 Low Low Low High Fair

Rada 201048 Low Low Low Low Good
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

86

RANDOMIZED CONTROLLED TRIALS

Publication 1 2 3 4 5 6 7 8 9 Overall

Acupuncture

Avis 201652 LR LR HR LR LR Outcome NR LR LR UR Low

Ee 201650 LR LR LR LR LR LR LR LR LR Low

Mao 201551 LR LR LR LR LR LR LR LR LR Low

Nedeljkovic 201453 LR LR LR LR LR UR LR LR UR Low

Yoga

Avis 2014 54 UR UR HR LR UR UR LR LR HR High

Ngowsiri 201455 HR HR HR HR HR HR HR HR UR High

Exercise

Daley 201562 LR LR UR UR UR Outcome NR LR LR HR Unclear

Duijts 201263 LR UR HR LR LR Outcome NR LR LR LR Low

Meditation/Mindfulness/

Hypnosis/Relaxation/Mixed

Carpenter 201356 LR LR HR LR LR LR UR LR LR Low

Huang 201557 LR LR LR LR UR UR LR LR LR Low

Lindh-Astrand 201358 LR LR HR UR UR UR LR LR LR Unclear

Lindh-Astrand 201561 LR LR HR LR Outcome NR Outcome NR HR LR HR High

Saensak 201359 LR LR LR LR Outcome NR Outcome NR LR LR HR Low

Sood 201360 HR HR UR LR LR LR UR LR UR Unclear

Risk of bias abbreviations: HR = High risk; LR = Low risk; UR = Unclear risk 

Column headings: 

1. Randomization adequate 

2. Allocation concealment 

3. Performance bias 

4. Detection bias: VMS 

5. Detection bias: Health-related quality of life 

6. Detection bias: Adverse effects 

7. Incomplete outcome 

8. Selective outcomes reporting 

9. Other bias 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms 

87

Risk of Bias Summary for New RCTs
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

88

APPENDIX D. MEASUREMENT SCALES FOR MENOPAUSE

VASOMOTOR SYMPTOMS (VMS)

Daily Hot Flash Diary (Sloan et al, 2001). A measure of self-reported hot flashes, night 

sweats and/or severity of hot flashes typically using a dairy to record the frequency and 

severity of hot flashes using a 4-point scale: mild, moderate, severe, very severe to 

provide a hot flash index (sum of the number of hot flashes multiplied by severity). 

Hot Flush Rating Scale (Hunter et al, 1995). Yields a hot flush frequency score (2 items 

that each have times/day and days/week summed to give number of hot flushes and night 

sweats that have caused waking in the past week) and a hot flush problem rating (3 items, 

each scored 1 to 10). 

Vasomotor subscales. From instruments such as the Green Climacteric Scale, the 

Kupperman Menopausal Index, the Women’s Health Questionnaire (WHQ), and the 

Menopause-specific Quality of Life (MENQOL), Health-related Quality of Life 

(HRQOL) Specific to Perimenopausal Symptoms (ie, measures used to report 

menopause-related HRQOL).

Greene Climacteric Scale. 21 questions covering 5 domains: anxiety, depression, somatic 

symptoms, vasomotor symptoms, and sexual function. Each question is answered on a 4-

point Likert scale. The answers to all 21 questions are summed to give a total quality-oflife measure; a higher score indicates a worse quality of life.

Global quality of life. Not a specific measure but a term used for single-item visual 

analogue scales designed to measure overall quality of life when 0 is the lowest possible 

and 100 is the highest possible quality of life. 

Hot Flush Behavior Scale (or Hunter menopause scale). A measure of behavioral 

reactions to VMS.

Hot Flash Related Daily Interference Scale. A 10-item measure for assessing the impact 

of vasomotor symptoms on daily activities in nine specific domains within the past week 

(work, social activities, leisure activities, sleep, mood, concentration, relation with others, 

sexuality, and enjoyment of life) and overall quality of life. 

Kupperman Menopausal Index. A numerical index that scores 11 menopausal symptoms: 

hot flushes, paresthesia, insomnia, nervousness, melancholia, vertigo, weakness, 

arthralgia or myalgia, headache, palpitations, and formication. Each symptom is rated 

from 0 to 3 according to severity. The scores are weighted and a total sum is calculated 

with a higher score indicating a worse quality of life. 

Menopause-specific quality of life (MENQOL) (Lewis et al, 2005). 29 questions 

covering 4 domains: vasomotor, psychosocial, physical, and sexual. The scoring for each 

question is 1–“No”, 2–“Yes, but not at all bothered” through 8–“Yes, extremely 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

89

bothered.” The scores for each question are summed for a total quality-of-life score 

where a higher score indicates a worse quality of life.

Menopause Rating Scale. Scores 11 menopausal symptoms: hot flushes, heart discomfort,

sleep problems, depressive mood, irritability, anxiety, physical and mental exhaustion,

sexual problems, bladder problems, vaginal dryness, and joint and muscular discomfort.

Each item is scored from 0-4. The scores are summed for a total quality-of-life score, in

which a higher score indicates a worse quality of life.

Women’s Health Questionnaire (WHQ). Contains menopause-specific quality of life

subscales enabling a detailed assessment of dimensions of emotional and physical health,

such as depression, anxiety, sleep problems, somatic symptoms, with optional subscales

for menstrual problems and sexual difficulties.

Utian Quality of Life Scale (UQOL). 23 items scored 1 to 5; 4 subscales (occupational,

health, emotional, sexual) and total score.

GENERAL HEALTH-RELATED QUALITY OF LIFE (HRQOL) 

SF-36 or Rand-36. Consists of 36 questions covering 8 domains: physical functioning,

role limitations caused by physical health problems, role limitations caused by emotional

problems, social functioning, emotional well-being, energy/fatigue, pain, and general

health perceptions. This questionnaire produces outcomes on total quality of life, subscores for each of the domains, a physical health sub-score, or a mental health sub-score.

For this scale, the higher the score, the better the quality of life.

Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES). An 18-item

instrument designed to measure the side effects and benefits of hormonal treatments used

in women with breast cancer.

EQ-5D-3L. Evaluates function in 5 domains: mobility, self-care, usual activities,

pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some

problems, extreme problems.

EQ-5D-5L. Like the EQ-5D-3L but each dimension has 5 levels: no problems, slight

problems, moderate problems, severe problems, and extreme problems.

EQ VAS. Records the respondent’s self-rated health on a 20 cm vertical, visual analogue

scale with endpoints labelled “the best health you can imagine” and “the worst health you

can imagine.”

Functional Assessment of Cancer Therapy-Breast (FACT-B). Measures overall quality of

life and has 5 subscales including physical, social, emotional, functional well-being, and

breast concerns.
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

90

APPENDIX E. PEER REVIEW COMMENTS/AUTHOR RESPONSES

Reviewer Comment Response

Question 1. Are the objectives, scope, and methods for this review clearly described?

1 Yes Acknowledged

2 Yes Acknowledged

3 No: I had difficulty with statements like "judged to be of high 

quality" (p 7, line 48) and "poor quality" (p 7, line 57) that came 

before the detailed Methods explanation and discussion of how 

"quality" was judged. This may just be the ESP format but I found 

it hard to read statements like these w/o knowing more. This is a 

minor point, but may be best to avoid the statement HT "only for 

short-term use" as this doesn't encompass newer 

recommendations to individualize care. These 

alternative/integrative methods are really a move toward 

individualization or personalization of health.

We added a statement in the abstract that briefly defines goodand fair-quality reviews.

We clarified the statement about current recommendations for 

duration of HT use to encompass guidance around 

individualization of care as recommended. 

4 Yes Acknowledged

Question 2. Are there any published or unpublished studies that we may have overlooked?

1 No Acknowledged

2 No Acknowledged

3 No Acknowledged

4 No Acknowledged

Question 3. Is there any indication of bias in our synthesis of the evidence?

1 No Acknowledged

2 No Acknowledged

3 No Acknowledged

4 Yes: Lesi et al. J. Clin Onc, 2016 studied acupuncture vs. usual 

care (included 190 women with breast cancer)

This study was published after our search date and including it in 

the analysis without completing an updated search for other 

recently published studies could introduce bias. However, we 

added a citation to this study in the discussion and note that 

results were consistent with our review findings.
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

91

Reviewer Comment Response

Question 4: Please write additional suggestions or comments below. If applicable, please indicate the page and line numbers from the 

draft report.

1 This is an incredibly extensive and thorough review. It would be 

helpful to indicate if at all possible if the results from the metaanalysis that were statistically significant translated to clinically 

meaningful changes in the outcomes (e.g. frequency of VMS). 

Some of these look quite small and it is difficult to determine 

whether these changes would make a meaningful difference to 

women struggling with VMS.

Thank you for this comment. For daily hot flash frequency, which 

was measured in a consistent manner, we were able to make this 

transformation. For hot flash severity and health-related qualityof-life, there was too much variability in measurement to make a 

reliable transformation back to natural units. Although we wanted 

to add information on the minimum clinically important difference 

for hot flash frequency, there is no consensus on this value.

2 Very thorough review of existing SR's and RCTs on topics related 

to nonpharmacological therapies for VMS. This review was wellwritten, clear, and described each area very well. Two 

suggestions: 1. Please add information on the inclusion/exclusion 

criteria for the SR's and RCTs that were reviewed for this 

synthesis. 2. Please provide information on the strength of 

evidence guidelines that were used by the authors--there is a 

reference to AHRQ's Methods, however, even a short description 

of what good, fair, etc... entails would be helpful for the reader. 

Otherwise, well done, comprehensive review.

Eligibility criteria and definitions of the strength of evidence are 

presented in detail in the Methods section

3 See above, well written, difficult topic to take on. This provides 

important contributions to Women's Health.

Thank you.
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

92

Reviewer Comment Response

4 I had the pleasure reviewing the Non-pharmacological treatment 

of menopause associated vasomotor symptoms prepared for the 

Department of Veterans Affairs (Lead author: John Williams). 

This review is thorough, well-written, with appropriately stated 

conclusions. I think this will have important implications for 

improving VM symptom management. 

A few aspects should be addressed to enhance the quality of this 

manuscript 

One new paper just published is highly relevant to this review. 

Lesi et al. J. Clin Onc, 2016 studied acupuncture vs. usual care 

(included 190 women with breast cancer) 

I am not sure whether there would be enough trials to do a 

meaningful comparison for acupuncture against non-hormonal 

based drugs (Gabapentin, Venlafaxine) for effect size, 

adverse events, and treatment durability. I am aware of at least 

two such studies. This may be a particularly useful comparison 

given that for those women who do not want hormones, these 

are viable options. The authors advocated for comparative 

effectiveness trials so these analyses (even a qualitative review) 

may help the authors to be more explicit on what these 

comparisons should focus on, main effects on hot flashes, 

adverse effects, durability. 

Another aspect is the durability of treatment effect. Currently, this 

is buried in the text. For women, they want to know if they choose 

a therapy (acupuncture, yoga, or drugs), if the reduction of their 

symptoms are durable or they need to get continued treatments. 

It will be great to summarize these findings as it will have impact 

on patient quality of life and health care utilization (getting a 

defined course of acupuncture/drugs will have very different cost 

implications for VA than getting continued treatment for a long 

period of time

Thank you

See response to this comment above.

We considered but did not think it appropriate to compare 

acupuncture with any drug therapy (i.e., drugs from differing 

classes with differing mechanisms of effect). Our a priori

threshold for meta-analysis was 3 trials and comparisons of 

acupuncture to differing drug classes, and so this did not meet 

that threshold.

Thank you for this comment. We have revised the text to more 

clearly identify timing of outcome assessments and whether the 

durability of treatment effect was addressed. 
Nonpharmacologic Treatments for Menopause-Associated Evidence-based Synthesis Program

Vasomotor Symptoms

93

Reviewer Comment Response

4 continued Other minor edits 

Introduction: 

P11line10: change “2” to “two” 

P11line 22: please add “severity” 

In third paragraph of the introduction, please discuss that 

hormonal treatment is contraindicated for breast cancer survivors 

or those with high risk for breast cancer 

Page 45: “though it found no difference due to hypnosis when 

compared to treatment with gabapentin”. I would assume 

gabapentin is an active control since it has been shown to be 

more beneficial than placebo for hot flashes

Per VA report editorial style, all numbers below 10 (except “one”) 

are to use numerals.

This line of the report is in the Data Analysis section of the 

Methods, which is not concerned with frequency or severity of 

VMS. Perhaps the reviewer meant a different line. We have 

carefully reviewed the manuscript to ensure that frequency and 

severity are used properly and are present where necessary. 

Text was added to note that HT is contraindicated in women with 

a history of breast cancer or those at high risk for breast cancer. 

This sentence was adjusted to clarify that gabapentin is an active 

comparator.