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Effects of Acupuncture on Menopause-Related Symptoms in Breast Cancer Survivors: A Meta-analysis of Randomized Controlled Trials

Chiu, Hsiao-Yean PhD, RN; Shyu, Yuh-Kae PhD, RN; Chang, Pi-Chen PhD, RN; Tsai, Pei-Shan PhD, RN

doi: 10.1097/NCC.0000000000000278
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Background: Evidence regarding the effects of acupuncture on hot flashes in breast cancer survivors is conflicting. Little is known about the intermediate-term effects of acupuncture on hot flashes and other menopause-related symptoms in breast cancer survivors.

Objective: The objective of this study was to evaluate the short-term and intermediate-term effects of acupuncture on menopause-related symptoms and particularly on hot flashes in breast cancer survivors.

Methods: Electronic databases including EMBASE, PubMed, PsycINFO, Web of Science, CINAHL, Wanfang Data Chinese Database, and China Knowledge Resource Integrated Database from inception until June 15, 2014, were searched. Randomized controlled trials in which acupuncture was compared with sham controls or other interventions according to the reduction of hot flashes or menopause-related symptoms in breast cancer survivors were included.

Results: We analyzed 7 studies involving 342 participants. Acupuncture significantly reduced the frequency of hot flashes and severity of menopause-related symptoms (g = −0.23 and −0.36, respectively) immediately after the completion of treatment. In comparison with sham acupuncture, effects of true acupuncture on the frequency and severity of hot flashes were not significantly different. At 1 to 3 months’ follow-up, the severity of menopause-related symptoms remained significantly reduced (g = −0.56).

Conclusion: Acupuncture yielded small-size effects on reducing hot-flash frequency and the severity of menopause-related symptoms.

Implications for Practice: Acupuncture may be used as a complementary therapy for breast cancer survivors experiencing hot flashes and other menopause-related symptoms; however, whether acupuncture exerts specific treatment effects other than needling or placebo effects needs to be further evaluated.

Author Affiliations: Graduate Institute of Nursing, College of Nursing, Taipei Medical University (Drs Chiu, Chang, and Tsai); Department of Nursing, Fu-Jen Catholic University, New Taipei City (Dr Shyu); Department of Nursing, Taipei Municipal Wanfang Hospital, Taiwan (Dr Tsai); and Sleep Science Center, Taipei Medical University Hospital (Dr Tsai), Taiwan.

This meta-analysis was supported by a grant from the Ministry of Science and Technology, Taiwan (NSC 102-2628-B-038-004-MY3).

The authors have no conflicts of interest to disclose.

Correspondence: Pei-Shan Tsai, PhD, RN, 250 Wu-Hsing St, Taipei, 110 Taiwan (ptsai@tmu.edu.tw).

Accepted for publication March 17, 2015.

Breast cancer is the most prevalent cancer among women worldwide.1 Nearly two-thirds of breast cancer survivors suffer from hot flashes and other menopause-related symptoms such as sleep difficulty and urogenital atrophy because of spontaneous menopause, ovarian disruption, or artificial menopause caused by the use of adjuvant chemotherapy and antihormone therapies (ie, estrogen receptor antagonist and aromatase inhibitor).2 These factors may explain why breast cancer survivors experience more frequent, more severe, and longer-lasting hot flashes and other menopause-related symptoms than do women with natural menopause.3–5

Menopausal hormone therapy (MHT) is the most effective treatment for reducing menopause-related symptoms in breast cancer survivors.6 However, previous studies on MHT have reported equivocal results on the association between the sustained use of MHT and increased risk of cancer recurrence and mortality after a diagnosis of breast cancer.7–9 Therefore, some breast cancer survivors consider MHT as an unaccepted alternative for managing their menopause-related symptoms.10 Nonhormone therapies such as clonidine,11 gabapentin,12 and antidepressants13,14 have demonstrated effects of alleviating hot flashes. However, the use of these pharmacological therapies can be accompanied by unpleasant symptoms and adverse effects.15 Therefore, many breast cancer survivors use complementary and alternative therapies to alleviate menopause-related symptoms.16

Studies have indicated that acupuncture for the reduction of menopausal vasomotor symptoms (ie, hot flashes) is associated with fewer adverse effects than are pharmacological therapies.17 Acupuncture has been shown to increase central β-endorphin activity,18 which in turn may stabilize the thermoregulation center and thereby reduce vasomotor symptoms.19 Two previous meta-analyses20,21 yielded conflicting findings, with one denying,20 and the other confirming21 the beneficial effect of acupuncture on the frequency of hot flashes in comparison to sham acupuncture. Of note, the causes and severity of menopausal hot flashes are different between women experiencing a natural menopause and breast cancer survivors.3–5 Among these 2 reports, 1 meta-analysis20 involved both perimenopausal women and breast cancer survivors and thus could not answer the question of whether the effects of acupuncture on hot flashes differ between the 2 populations. The other meta-analysis included only 3 randomized controlled trials (RCTs).21 Several studies investigating the effect of acupuncture on hot flashes in women with breast cancer have been published22–26 since these meta-analyses. To date, no meta-analysis has summarized the results of existing studies on the effects of acupuncture on menopause-related symptoms such as sleep problems, vaginal dryness, sweating, palpitation, and depression and the intermediate-term effects (≤3 months) on hot flashes and the severity of menopause-related symptoms in breast cancer survivors. Needed next is a meta-analysis to evaluate the effects of acupuncture on hot flashes and menopause-related symptoms in breast cancer survivors and to determine whether acupuncture exerts specific treatment effects other than needling or placebo effects.

The effects of acupuncture on menopause-related symptoms in women with natural menopause have been reported in a previous meta-analysis.27 The current meta-analysis was performed to examine the short- and intermediate-term effects of acupuncture on the frequency and severity of hot flashes and the severity of menopause-related symptoms in breast cancer survivors. The results from the current meta-analysis could aid the healthcare providers and breast cancer survivors in making an informed decision regarding the use of acupuncture for hot flashes and other menopause-related symptoms.

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Methods

Data Source and Searches

This meta-analysis was conducted according to the statement regarding preferred reporting items for use in systematic reviews and meta-analysis.28 EMBASE, PubMed, PsycINFO, Web of Science, CINAHL, Wanfang Data Chinese Database, and China Knowledge Resource Integrated Database from inception until June 15, 2014, were searched for articles that included the following search terms in their titles, abstracts, or keyword lists: (“breast cancer” OR “breast neoplasm” OR “breast tumor”) AND (“menopause” OR “menopause-related symptoms” OR “hot flash” OR “hot flush”) AND (“acupuncture” OR “acupuncture points” OR “acupressure”) AND (“randomized controlled trials” OR “randomized”).

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Selection Criteria

To be included in the meta-analysis, studies were required to meet the following criteria: (1) used a prospective randomized controlled design; (2) participants were breast cancer survivors; (3) acupuncture (ie, traditional Chinese medicine acupuncture and electroacupuncture) was provided as an intervention; (4) an inactive (ie, sham acupuncture, which is applied a few centimeters away from the true acupuncture points and/or used identical needles placed on top of the skin without penetration) or active (ie, MHT and relaxation therapy) intervention was provided as a control; (5) the frequency and severity of hot flashes or menopause-related symptoms were measured as outcomes; and (6) published in English or Chinese. The frequency and severity of hot flashes were measured using diaries or a visual analog scale; the menopause-related symptoms were assessed by the revised National Surgical Adjuvant Breast and Bowel Project (NSABP) menopausal questionnaire or the Kupperman Index. The revised 42-item NSABP menopausal questionnaire comprising 8 domains (cognitive symptoms, musculoskeletal pain, vasomotor symptoms, nausea, sexual problems, bladder problems, body image, and vaginal symptoms) evaluates the menopause-related symptoms over the past week, with higher scores reflecting worse menopause-related symptom disturbances. Reliability and validity of the NSABP have been previously reported.29,30 The 11-item Kupperman Index measures menopause-related symptoms such as hot flashes, sweating, palpitation, vertigo, headache, sleep disturbances, vaginal dryness, arthralgia, fatigue, nervousness, and depression, with higher scores indicating higher degrees of severity on menopause-related symptoms. Satisfactory reliability and validity of the Kupperman Index have been established.31

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Study Selection

Two investigators (H.-Y.C. and Y.-K.S.) independently evaluated the titles and abstracts of potentially eligible articles. Duplicates were removed, and the full-text articles of the remaining studies were retrieved and reviewed. Studies fulfilling the inclusion criteria were selected for meta-analytic evaluation.

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Data Extraction

Quantitative and narrative data were independently extracted by the same 2 investigators using a standard form. The standard form included the (1) characteristics of the included studies (eg, first author’s name and year of publication); (2) characteristics of the patient population (eg, age, number of participants in each group, and menopause status); (3) characteristics of the intervention (eg, type, frequency, and duration); and (4) outcome measures and instruments. Disagreements were resolved by engaging in discussion with the corresponding author (P.-S.T.) until a consensus was reached.

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Risk of Bias Assessment

The quality of the study reports was assessed using the criteria recommended in the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0.32 Six domains were assessed: (1) random sequence generation, (2) allocation concealment, (3) the blinding of participants and personnel, (4) the blinding of outcome assessment, (5) incomplete outcome data, and (6) selective outcome reporting. Two investigators (H.-Y.C and Y.-K.S) individually evaluated the quality of the studies. Disagreements between the raters were resolved by engaging in discussion with the corresponding author (P.-S.T.) until a consensus was reached.

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Data Analysis

All quantitative data were entered into the Comprehensive Meta Analysis software, version 2.0 (Biostat, Englewood, New Jersey). An inverse variance random-effects model was selected because this model is more conservative than the fixed-effects model.33 Effect size (Hedges g) was calculated using the mean and SD of pre-post differences in the outcomes and sample sizes between the experimental and control groups. We evaluated the magnitude of the effect size, with g > 0.2 to 0.5 = small effect, g > 0.5 to 0.8 = medium effect size, and g > 0.8 = large effect size based on Cohen’s34 categories. Between-study heterogeneity was examined using Q test and I2 statistics,35 in which Q < 0.05 and an I2 ≥ 50% represented substantial heterogeneity. If there were at least 3 studies available, the effect of acupuncture was assessed according to prespecified subgroups: true versus sham acupuncture, and treatment dosage 420 minutes or more (range, 420–450 minutes) versus 200 minutes or less (range, 160–200 minutes). Metaregression was performed using the mixed-effects model to examine the moderating effect. τ2 Variance was estimated by the method of unrestricted maximum likelihood. Because of a higher degree of random variation, studies with smaller samples yield a wider distribution than do studies with large samples, which can cause asymmetry in a funnel plot.36,37 Because this meta-analysis included a limited number of studies, publication bias was examined using the Egger’s36 intercept test.

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Results

Search Results

Figure 1 illustrates the electronic search process. The search initially yielded 121 articles. Among these articles, we excluded 112 duplicate articles or articles unrelated to the inclusion criteria by using Endnote software. We retained 9 articles for further analysis. Among these articles, we excluded 2 studies because we could not obtain sufficient data from 1 study17 even after contacting the authors, and another study that used the same sample as the other study.38 We analyzed 7 studies that met the inclusion criteria.22–26,39,40 Of these, acupuncture treatment was used in 6 studies for the frequency of hot flashes, 3 studies for the severity of hot flashes, and 4 studies for menopause-related symptoms. In terms of the intermediate-term effects of acupuncture (≤3 months), we included 4, 2, and 3 studies for analyzing the frequency and severity of hot flashes and menopause-related symptoms because 2 studies22,24 did not provide sufficient data at the period of 1 to 3 months to compute an effect size, even after contacting the authors.

Figure 1

Figure 1

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Study Descriptions and Risk of Bias

As shown in Table 1, the study sample size ranged from 38 to 72, with a total of 391 randomized participants. The average participant age was 57.5 and 57.2 years in the acupuncture and control groups (ranges, 45–85 and 43–82 years), respectively. The 3 types of control conditions used for comparison were sham acupuncture (5 studies), MHT (1 study), and relaxation (1 study). Among the 7 included studies, 3 studies22,25,39 involved breast cancer survivors with treatment-induced menopause, and others involved both treatment-induced menopause women and women with natural menopause or breast cancer survivors with unspecified menopause status.23,24,26,41 Most commonly used measurement for hot flashes was the diary. Three studies24,26,39 used the Kupperman Index to assess the menopause-related symptoms. The total treatment session ranged from 5 to 15, and the average intervention dose was 283.6 minutes, ranging from 75 to 450 minutes.

Table 1

Table 1

Table 2 lists the results regarding the risk of bias. Most of the studies were at low risk of bias in allocation concealment (6 at low risk), the blinding of assessors (6 at low risk), the blinding of participants and personnel (5 at low risk), incomplete outcome assessments (5 at low risk) and selective reporting (5 at low risk). Only 4 studies were judged to be at low risk of sequence generation bias.

Table 2

Table 2

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Short-term Effects of Acupuncture on the Frequency and Severity of Hot Flashes and Menopause-Related Symptoms

Six studies evaluated the short-term (immediate posttreatment) effects of acupuncture on the frequency of hot flashes in breast cancer survivors (Figure 2). The pooled effect size for the frequency of hot flashes was −0.23 (95% confidence interval [CI], −0.44 to −0.006; P = .04). No evidence of heterogeneity was identified across these studies (Q = 5.02, P = .41, I2 = 0.32).

Figure 2

Figure 2

Three studies evaluated the short-term effects of acupuncture on hot-flash severity in comparison to sham acupuncture. We found that the weighted effect of true acupuncture was not significantly (g = −0.41; 95% CI, −0.95 to 0.12; P = .13) different from that of sham acupuncture. The values of the Q test and I2 statistics (Q = 6.54, P = .04, I2 = 69.42) indicated heterogeneity among the studies.

Four studies evaluated the short-term effects of acupuncture on the severity of menopause-related symptoms in breast cancer survivors (Figure 2). We observed a pooled effect size of −0.36 (95% CI, −0.65 to −0.06; P = .018) with substantial homogeneity among the studies (Q = 3.01, P = .39, I2 = 0.47) (Figure 3).

Figure 3

Figure 3

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Subgroup Analysis and Metaregression

In terms of the subgroup analysis, 4 studies22,25,39,42 including sham acupuncture as the control showed that true acupuncture was not superior to sham acupuncture in alleviating hot-flash frequency (g = −0.24, P = .38). Treatment dosage 420 minutes or more yielded a significantly moderate effect on reducing the frequency of hot flashes (g= −0.45; 95% CI, −0.80 to −0.11), whereas treatment dosage 200 minutes or less did not significantly improve hot-flash frequency (g = −0.08; 95% CI, −0.36 to 0.20). The metaregression outcome was that the effect size was not significantly associated with age (P = .25).

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Intermediate-term Effects of Acupuncture on the Frequency and Severity of Hot Flashes and Menopause-Related Symptoms

Four and 2 studies, respectively, were included to investigate the intermediate-term effects (≤3 months) of acupuncture on the frequency and severity of hot flashes. Both effects were not statistically significant (g = −0.28 and −0.34; 95% CI, −0.59 to 0.05 and −0.85 to 0.18, respectively). The values of the Q test and I2 statistics indicated homogeneity among the studies (hot-flash frequency: Q = 4.18, P = .24, I2 = 28.15; hot-flash severity: Q = 2.24, P = .13, I2 = 55.37).

Three studies investigated the intermediate-term effects (≤3 months) of acupuncture on the severity of menopause-related symptoms. Acupuncture significantly improved the severity of menopause-related symptoms (g = −0.56; 95% CI, −1.040 to −0.09; P = .02). The values of the Q test and I2 statistics indicated homogeneity among the studies (Q = 3.58, P = .17, I2 =44.06).

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Publication Bias

We observed no significant publication bias in the analyzed studies regarding the frequency and severity of hot flashes and menopause-related symptoms (P = .68, .27, and .32, respectively).

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Discussion

The results of the present meta-analysis of 7 RCTs suggest that acupuncture had small-size effects on hot-flash frequency and the severity of menopause-related symptoms immediately after the completion of 5 to 15 sessions of acupuncture in breast cancer survivors. The subgroup analysis revealed that the effects of true acupuncture compared with sham acupuncture on the frequency and severity of hot flashes were not significant. Moreover, acupuncture could reduce the severity of menopause-related symptoms as a whole, but not the frequency and severity of hot flashes at a 1 to 3 months’ follow-up.

The pathophysiological mechanisms underlying the vasomotor symptoms experienced by breast cancer survivors are multifactorial and might involve the disturbance of the thermoregulation center in the hypothalamus.42 A previous study43 reported that the expression of the vasodilator calcitonin gene-related peptide (CGRP) is associated with the manifestation of hot flashes. Therefore, a hypothesis for the mechanism underlying the beneficial effects of acupuncture on vasomotor symptoms is that acupuncture causes the release of β-endorphins in the hypothalamus, which exerts inhibitory effects on CGRP19,42,44 and thus reduces vasomotor symptoms. However, previous studies examining urine CGRP levels after acupuncture43,45,46 yielded mixed findings, with 1 study supporting43 and 2 studies rejecting45,46 the hypothesis. Therefore, further investigation is required to determine the exact mechanisms underlying the effects of acupuncture on vasomotor symptoms. Although the present results indicate that acupuncture significantly reduces the frequency of hot flashes, a wide CI suggests a high degree of variation across the included studies. Therefore, the present results must be interpreted with caution.

Coincidently, both the subgroup analysis of the comparison group regarding the frequency of hot flashes as well as the results from the overall effect on the severity of hot flashes showed that sham acupuncture could induce a treatment effect that is not inferior to that of true acupuncture. Previous studies on the effects of acupuncture on pain relief have demonstrated that touching the skin lightly can induce mechanoreceptors that stimulate emotional and hormonal reactions, which relieve the affective component of pain.47,48 The hormonal reactions include the release of β-endorphin.49 Increased β-endorphin is associated with the secretion of CGRP, which reduces vasomotor symptoms. This might provide a possible explanation for the apparent lack of differences between the effects of true acupuncture and sham acupuncture on the frequency and severity of hot flashes and raise doubts concerning whether acupuncture exerts a specific treatment effect for managing hot flashes.

Of note, we found that the effects of acupuncture on the frequency of hot flashes were short-term in nature and did not persist at 1 to 3 months’ follow-up in breast cancer survivors. A possible reason for the nonsignificant effects on the frequency of hot flashes at the 1 to 3 months’ follow up could be attributed to insufficient treatment dosages as we found in the subgroup analyses that the effect size for treatment dosage 420 minutes or more was significant, whereas that of the treatment dosage 200 minutes or less was not. Findings from a previous meta-analysis revealed that acupuncture with average treatment dosage of 391.1 minutes significantly relieves the frequency and severity of hot flashes at 3 months after the final treatment in women with natural menopause.27 In the present study, the mean treatment dosage was 283.6 minutes for breast cancer survivors, which is much lower than the previous report.27 However, because the present meta-analysis included only a small number of studies, additional RCTs are required to further elucidate the intermediate-term effects of acupuncture on vasomotor symptoms.

The present results support that acupuncture yielded significant short- and intermediate-term effects on reducing the severity of menopause-related symptoms. Hot flashes and other menopause-related symptoms such as sleep problems, fatigue, and mood disturbances often coexist and can interact with each other. When the frequency of hot flashes is relieved by acupuncture, other menopause-related symptoms are likely to be mitigated. Nevertheless, the interaction effects could not explain why the severity of menopause-related symptoms as a whole was significantly reduced at 1 to 3 months after the completion of the treatment course when the frequency and severity of hot flashes in particular were not. Therefore, further studies are required to identify the mechanisms underlying the effects of acupuncture on menopause-related symptoms.

To achieve high internal validity, this meta-analysis included only RCTs to evaluate the effects of acupuncture on hot flashes and menopause-related symptoms in breast cancer survivors. However, several limitations must be considered. First, this meta-analysis included only a small number of studies containing small samples. Second, variations in patient population, menopause status, acupoints, treatment duration, and treatment doses existed among the included studies, which might lead to inconsistent results. Unfortunately, the small number of included studies precluded valid and meaningful subgroup analyses. Third, although all 7 studies reported randomization, only 4 studies adopted adequate randomization methods. Lastly, the exclusion of studies based on language might have limited the external validity of our findings.

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Conclusion

The results of this meta-analysis indicate that acupuncture yield a small-size effect on reducing hot-flash frequency and the severity of menopause-related symptoms immediately after the completion of treatment. The effects of acupuncture on the severity of menopause-related symptoms, but not hot-flash frequency and severity, could persist at a 1 to 3 months’ follow-up. The implication of this meta-analysis is that acupuncture can be used as a complementary therapy for breast cancer survivors experiencing hot flashes and menopause-related symptoms in addition to the conventional therapies. Although the optimal treatment dose remains unclear, our findings give evidence to support that acupuncture with a larger treatment dosage (ie, ≥420 minutes) shows a significantly moderate effect for reducing hot-flash frequency. Additional studies that used adequate randomization methods and include homogenous participants are required to evaluate the effects of acupuncture on hot flashes and other menopause-related symptoms in breast cancer survivors.

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References

1. Igene H. Global health inequalities and breast cancer: an impending public health problem for developing countries. Breast J. 2008; 14(5): 428–434.
2. Goodwin PJ, Ennis M, Pritchard KI, Trudeau M, Hood N. Risk of menopause during the first year after breast cancer diagnosis. J Clin Oncol. 1999; 17(8): 2365–2370.
3. Carpenter JS, Elam JL, Ridner SH, Carney PH, Cherry GJ, Cucullu HL. Sleep, fatigue, and depressive symptoms in breast cancer survivors and matched healthy women experiencing hot flashes. Oncol Nurs Forum. 2004; 31(3): 591–5598.
4. Carpenter JS, Johnson D, Wagner L, Andrykowski M. Hot flashes and related outcomes in breast cancer survivors and matched comparison women. Oncol Nurs Forum. 2002; 29(3): E16–E25.
5. Carpenter JS, Andrykowski MA, Cordova M, et al. Hot flashes in postmenopausal women treated for breast carcinoma: prevalence, severity, correlates, management, and relation to quality of life. Cancer. 1998; 82(9): 1682–1691.
6. Beckmann MW, Jap D, Djahansouzi S, et al. Hormone replacement therapy after treatment of breast cancer: effects on postmenopausal symptoms, bone mineral density and recurrence rates. Oncology. 2001; 60(3): 199–206.
7. Meurer LN, Lena S. Cancer recurrence and mortality in women using hormone replacement therapy: meta-analysis. J Fam Pract. 2002; 51(12): 1056–1062.
8. O’Meara ES, Rossing MA, Daling JR, Elmore JG, Barlow WE, Weiss NS. Hormone replacement therapy after a diagnosis of breast cancer in relation to recurrence and mortality. J Natl Cancer Inst. 2001; 93(10): 754–762.
9. National Center for Complementary and Alternative Medicine (NCCAM). Complementary, Alternative, or Integrative Health: What’s in a Name? Bethesda, MD: National Center for Complementary and Alternative Medicine; 2013.
10. Vassilopoulou-Sellin R, Zolinski C. Estrogen replacement therapy in women with breast cancer: a survey of patient attitudes. Am J Med Sci. 1992; 304(3): 145–149.
11. Pandya KJ, Raubertas RF, Flynn PJ, et al. Oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifen-induced hot flashes: a University of Rochester Cancer Center Community Clinical Oncology Program study. Ann Intern Med. 2000; 132(10): 788–793.
12. Pandya KJ, Morrow GR, Roscoe JA, et al. Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial. Lancet. 2005; 366(9488): 818–824.
13. Loprinzi CL, Kugler JW, Sloan JA, et al. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet. 2000; 356(9247): 2059–2063.
14. Stearns V, Slack R, Greep N, et al. Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial. J Clin Oncol. 2005; 23(28): 6919–6930.
15. Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA. 2006; 295(17): 2057–2071.
16. Harris PF, Remington PL, Trentham-Dietz A, Allen CI, Newcomb PA. Prevalence and treatment of menopausal symptoms among breast cancer survivors. J Pain Symptom Manage. 2002; 23(6): 501–509.
17. 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.
18. Andersson S, Lundeberg T. Acupuncture—from empiricism to science: functional background to acupuncture effects in pain and disease. Med Hypotheses. 1995; 45(3): 271–281.
19. Filshie J, Bolton T, Browne D, Ashley S. Acupuncture and self acupuncture for long-term treatment of vasomotor symptoms in cancer patients—audit and treatment algorithm. Acupunct Med. 2005; 23(4): 171–180.
20. Dodin S, Blanchet C, Marc I, et al. Acupuncture for menopausal hot flushes. Cochrane Database Syst Rev. 2013; 7: CD007410.
21. Lee MS, Kim KH, Choi SM, Ernst E. Acupuncture for treating hot flashes in breast cancer patients: a systematic review. Breast Cancer Res Treat. 2009; 115(3): 497–503.
22. 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.
23. Bokmand S, Flyger H. Acupuncture relieves menopausal discomfort in breast cancer patients: a prospective, double blinded, randomized study. Breast. 2013; 22(3): 320–323.
24. Frisk J, Carlhall S, Kallstrom AC, Lindh-Astrand L, Malmstrom A, Hammar M. Long-term 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.
25. 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.
26. Nedstrand E, Wijma K, Wyon Y, Hammar M. Vasomotor symptoms decrease in women with breast cancer randomized to treatment with applied relaxation or electro-acupuncture: a preliminary study. Climacteric. 2005; 8(3): 243–250.
27. Chiu HY, Pan CH, Shyu YK, Han BC, Tsai PS. The effects of acupuncture on menopause-related symptoms and quality of life in women with natural menopause: a meta-analysis of randomized controlled trials. Menopause. 2015; 22(2): 234–244.
28. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009; 151(4): 264–269, W264.
29. Stanton AL, Bernaards CA, Ganz PA. The BCPT symptom scales: a measure of physical symptoms for women diagnosed with or at risk for breast cancer. J Natl Cancer Inst. 2005; 97(6): 448–456.
30. Terhorst L, Blair-Belansky H, Moore PJ, Bender C. Evaluation of the psychometric properties of the BCPT Symptom Checklist with a sample of breast cancer patients before and after adjuvant therapy. Psychooncology. 2011; 20(9): 961–968.
31. Schneider HP, Heinemann LA, Rosemeier HP, Potthoff P, Behre HM. The Menopause Rating Scale (MRS): comparison with Kupperman Index and quality-of-life scale SF-36. Climacteric. 2000; 3(1): 50–58.
32. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. 2011. www.cochrane-handbook.org. Accessed December 31, 2014.
33. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986; 7(3): 177–188.
34. Cohen J. Statistical Power Analysis for the Behaviral Sciences. Hillsdale, NJ: Lawrence Erlbaum; 1988.
35. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003; 327(7414): 557–560.
36. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997; 315(7109): 629–634.
37. Song F, Khan KS, Dinnes J, Sutton AJ. Asymmetric funnel plots and publication bias in meta-analyses of diagnostic accuracy. Int J Epidemiol. 2002; 31(1): 88–95.
38. Frisk J, Kallstrom AC, Wall N, Fredrikson M, Hammar M. Acupuncture improves health-related quality-of-life (HRQoL) and sleep in women with breast cancer and hot flushes. Support Care Cancer. 2012; 20(4): 715–724.
39. 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.
40. Dong H, Ludicke F, Comte I, Campana A, Graff P, Bischof P. An exploratory pilot study of acupuncture on the quality of life and reproductive hormone secretion in menopausal women. J Altern Complement Med. 2001; 7(6): 651–658.
41. 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.
42. Andrikoula M, Prelevic G. Menopausal hot flushes revisited. Climacteric. 2009; 12(1): 3–15.
43. Wyon Y, Lindgren R, Lundeberg T, Hammar M. Effects of acupuncture on climacteric vasomotor symptoms, quality of life, and urinary excretion of neuropeptides among post menopausal women. Menopause. 1995; 2(1): 3–12.
44. Tukmachi E. Treatment of hot flushes in breast cancer patients with acupuncture. Acupunct Med. 2000; 18(1): 22–27.
45. 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.
46. Frisk J, Spetz AC, Hjertberg H, Petersson B, Hammar M. Two modes of acupuncture as a treatment for hot flushes in men with prostate cancer—a prospective multicenter study with long-term follow-up. Eur Urol. 2009; 55(1): 156–163.
47. Lund I, Lundeberg T. Are minimal, superficial or sham acupuncture procedures acceptable as inert placebo controls? Acupunct Med. 2006; 24(1): 13–15.
48. Olausson H, Lamarre Y, Backlund H, et al. Unmyelinated tactile afferents signal touch and project to insular cortex. Nat Neurosci. 2002;r 5(9): 900–904.
49. Benedetti F, Arduino C, Amanzio M. Somatotopic activation of opioid systems by target-directed expectations of analgesia. J Neurosci. 1999; 19(9): 3639–3648.
Keywords:

Acupuncture; Breast cancer; Hot flash; Menopause-related symptoms; Meta-analysis

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